FORTY-EIGHTH NATIONAL MEETING

OF THE CHILD NEUROLOGY SOCIETY

PLANNING COMMITTEE
Child Neurology Society Executive Board

Jonathan Mink, President Rochester, NY

Phillip Pearl, President- Elect Boston, MA
Bruce H. Cohen, Secretary-Treasurer Akron, OH
Donald Gilbert, Councillor Cincinnati, OH
Lori Jordan, Councillor Nashville, TN
Michael Shevell, Councillor Montreal, QC, Canada
Mark Wainwright, Councillor Seattle, WA

CNS Scientific Selection and Program Planning Committee

Erika Augustine, Chair Rochester, NY Sucheta Joshi Ann Arbor, MI

Gyula Acsadi Farmington, CT Yasmin Khakoo New York, NY
Nigel Bamford New Haven, CT Karl Kuban Boston, MA
Alexander Bassuk Iowa City, IA Laura Lehman Boston, MA
Joanna Blackburn Chicago, IL Ariel Lyons-Warren Houston, TX
Clari Borrero-Mejias Phoenix, AZ Ganeshwaran Mochida Boston, MA
Audrey Brumback Austin, TX Marc Patterson Rochester, MN
Keith Coffman Kansas City, MO Toni Pearson St. Louis, MO
Alexander Cohen Boston, MA Eugene Schnitzler Maywood, IL
David Dredge Boston, MA Chris Smyser St. Louis, MO
Leon Dure Birmingham, AL Liu Lin Thio St. Louis, MO
Donald Gilbert Cincinnati, OH Laura Tochen Washington, DC
Howard Goodkin Charlottesville, VA Keith Van Haren Palo Alto, CA
Ajay Gupta Cleveland, OH Yvonne Wu San Francisco, CA
Shafali Jeste Los Angeles, CA

National Office
Roger Larson, Executive Director
Sue Hussman, Associate Director
Kathy Pavel, Office Administrator
Emily McConnell, Professional Development Manager

Presented at The Charlotte Convention Center

Charlotte, NC
October 23-26, 2019

ACCREDITATION
This activity has been planned and implemented in accordance with the accreditation requirements and policies of
the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the
Minnesota Medical Association and Child Neurology Society. The Minnesota Medical Association (MMA) is
accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical
education for physicians.

The Minnesota Medical Association designates this live activity for a maximum of 28.5 AMA PRA Category 1
Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the
activity.

To receive CME credits, physicians must complete the on-line CME survey accessed via the CNS website
(www.childneurologysociety.org) on or before November 20, 2019

© 2019 Child Neurology Society S1

 PAST OFFICERS
President Karin Nelson 1973-74 E. Steve Roach 1998-2000
Kenneth Swaiman 1972-73 Raymond Chun 1973-75 Faye Silverstein 1999-2001
Gerald Fenichel 1973-74 Bruce Berg 1974-76 Michael Johnston 1999-2001
Manuel Gomez 1974-75 Paul Dyken 1974-76 Carmela Tardo 2000-02
James Schwartz 1975-76 Arthur Prensky 1975-77 Pauline Filipek 2000-02
Richard Allen 1976-77 N. Paul Rosman 1975-77 Michael Noetzel 2001-03
Bruce Berg 1977-78 Jack Madsen 1976-78 Carl Crosley 2001-03
N. Paul Rosman 1978-79 Peggy Copple (Ferry) 1976-78 Julie Parke 2002-04
Arthur Prensky 1979-80 Joseph French 1977-79 Roy Elterman 2002-04
Paul Dyken 1980-81 Francis Wright 1977-79 Marc Patterson 2003-05
Mary Anne Guggenheim 1981-82 Mary Anne Guggenheim 1978-80 Douglas Nordli 2003-05
Raymond Chun 1982-83 Gerald Golden 1978-80 Donna Ferriero 2004-06
Robert Eiben 1983-85 Gerald Erenberg 1979-81 Leon Dure 2004-06
David Stumpf 1985-87 John Freeman 1979-81 Kenneth Mack 2005-07
Marvin Fishman 1987-89 Marvin Weil 1980-82 Laura Ment 2005-07
Darryl C. De Vivo 1989-91 Marvin Fishman 1980-82 Leslie Morrison 2006-08
Peter H. Berman 1991-93 Peter Huttenlocher 1981-83 Anne Anderson 2006-08
Joseph J. Volpe 1993-95 Michael Bresnan 1981-83 Steven Leber 2007-09
Michael E. Cohen 1995-97 David Stumpf 1982-84 Jonathan Mink 2007-09
Alan K. Percy 1997-99 Gwendolyn Hogan 1982-84 Robert Rust 2008-10
Michael J. Painter 1999-2001 Joseph Volpe 1983-85 Wendy Mitchell 2008-10
Stephen Ashwal 2001-2003 Barry Russman 1983-85 Warren Lo 2009-11
James Bale 2003-2005 Russell Snyder 1984-86 Sakkubai Naidu 2009-11
Ann Tilton 2005-2007 Ian Butler 1984-86 Gary Clark 2010-12
John Bodensteiner 2007-2009 W. Edwin Dodson 1985-87 Sidney Gospe 2010-12
Donna Ferriero 2009-2011 Michael Painter 1985-87 Barry Kosofsky 2011-13
E. Steve Roach 2011-2013 Robert Zeller 1986-88 Suresh Kotagal 2011-13
Nina F. Schor 2013-2015 Doris Trauner 1986-88 Vinodh Narayanan 2012-14
Kenneth Mack 2015-2017 Darryl De Vivo 1987-88 Jayne Ness 2012-14
Jonathan Mink 2017-2019 Gary Goldstein 1987-89 Bruce Cohen 2013-15
Phillip Pearl 2019- Robert Vannucci 1988-89 Roger Packer 2013-15
Stephen Ashwal 1988-90 Kevin Ess 2014-16
Secretary-Treasurer Jack Pellock 1988-90 Kara Lewis 2014-16
Richard Allen 1972-75 Joseph Pasternak 1989-91 Phillip Pearl 2015-17
Raymond Chun 1975-78 Patricia Duffner 1989-91 Renee Shellhaas 2015-17
Robert Eiben 1978-81 O. Carter Snead 1990-92 Peter B. Kang 2016-18
Lawrence Lockman 1981-84 Edwin Meyer 1990-92 Mary Zupanc 2016-18
Marvin Fishman 1984-86 Israel Abroms 1991-93 Donald Gilbert 2017-2019
Ira Lott 1986-89 William Logan 1991-93 Michael Shevell 2017-2019
Peggy Copple (Ferry) 1989-93 Mary Johnson 1992-94 Lori Jordan 2018-
Stephen Ashwal 1993-97 Alan Percy 1992-94 Mark Wainwright 2018-
Patricia Crumrine 1997-2002 Phyllis Sher 1993-95
Ann Tilton 2003-2004 Gregory Holmes 1993-95
Nina Schor 2004-2010 W. Donald Shields 1994-96
Harvey Singer 2010-2015 John Bodensteiner 1994-96
Bruce Cohen 2015- Patricia Crumrine 1995-97
James Bale 1995-97
Councillor Alan Hill 1996-98
Isabelle Rapin 1972-73 Ann Tilton 1996-98
Manuel Gomez 1972-73 Edward Kovnar 1997-99
John Menkes 1972-74 Richard Nordgren 1997-99
James Schwartz 1972-74 Michael Goldstein 1998-2000

S2 Annals of Neurology Vol 86 (suppl 23) 2019

 NATIONAL MEETINGS
Ann Arbor, Michigan 1972
Nashville, Tennessee 1973
Madison, Wisconsin 1974
Hamilton, Ontario, Canada 1975
Monterey, California 1976
Charlottesville, Virginia 1977
Keystone, Colorado 1978
Hanover, New Hampshire 1979
Savannah, Georgia 1980
Minneapolis, Minnesota 1981
Salt Lake City, Utah 1982
Williamsburg, Virginia 1983
Phoenix, Arizona 1984
Memphis, Tennessee 1985
Boston, Massachusetts 1986
San Diego, California 1987
Halifax, Nova Scotia, Canada 1988
San Antonio, Texas 1989
Atlanta, Georgia 1990
Portland, Oregon 1991
New Orleans, Louisiana 1992
Orlando, Florida 1993
San Francisco, California 1994
Baltimore, Maryland 1995
Minneapolis, Minnesota 1996
Phoenix, Arizona 1997
Montreal, Quebec, Canada 1998
Nashville, Tennessee 1999
St. Louis, Missouri 2000
Victoria, British Columbia, Canada 2001
Washington, DC 2002
Miami Beach, FL 2003
Ottawa, Ontario, Canada 2004
Los Angeles, CA 2005
Pittsburgh, PA 2006
Quebec City, PQ, Canada 2007
Santa Clara, CA 2008
Louisville, KY 2009
Providence, RI 2010
Savannah, GA 2011
Huntington Beach, CA 2012
Hilton Austin, Austin, TX 2013
Columbus, OH 2014
Washington, DC 2015
Vancouver, BC, Canada 2016
Kansas City, MO 2017
Chicago, IL Oct 15-18, 2018
Charlotte, NC Oct 23-26, 2019
San Diego, CA Oct 19-23, 2020
Boston, MA Sep 29-Oct 2, 2021

Program and Abstracts, Child Neurology Society S3

 HOWER AWARD

1974 Douglas Buchanan 1991 Karin B. Nelson 2008 Stephen Ashwal

Chicago Bethesda Loma Linda

1975 Randolph K. Byers 1992 Darryl C. De Vivo 2009 Peter Camfield

Boston New York Halifax

1976 Sidney Carter 1993 Bengt D. Hagberg 2010 Sakkubai Naidu

New York Goteborg Baltimore

1977 David B. Clark 1994 Hugo Moser 2011 Deborah Hirtz

Lexington Baltimore Bethesda

1978 Philip R. Dodge 1995 Salvatore DiMauro 2012 Ann Tilton

St. Louis New York New Orleans

1979 Paul I. Yakovlev 1996 William Bell 2013 John Bodensteiner

Boston Iowa City Rochester, MN

1980 John H. Menkes 1997 Gerald Fenichel 2014 Michael Shevell

Beverly Hills Nashville Montreal

1981 Kenneth F.Swaiman 1998 N. Paul Rosman 2015 E. Steve Roach

Minneapolis Boston Columbus

1982 Patrick F. Bray 1999 Marvin Fishman 2016 Harvey Singer

Salt Lake City Houston Baltimore

1983 Betty Q. Banker 2000 Arthur Prensky 2017 Nina F. Schor

Cleveland St. Louis Rochester, NY

1984 Peter Huttenlocher 2001 Charles Barlow 2018 Bernard L. Maria

Chicago Boston Morristown, NJ

1985 RaymondD.Adams 2002 Peter H. Berman 2019 James F. Bale, Jr.

Boston Philadelphia Salt Lake City

1986 Jean Aicardi 2003 Michael E. Cohen

Paris Buffalo

1987 Isabelle Rapin 2004 John Freeman

Bronx Baltimore

1988 Bruce Berg 2005 Alan Percy

San Francisco Birmingham

1989 Manuel Gomez 2006 Michael Painter

Rochester Pittsburgh

1990 Joseph J. Volpe 2007 Robert S. Rust

Boston Charlottesville

S4 Annals of Neurology Vol 86 (suppl 23) 2019

 BERNARD SACHS AWARD

1977 George Cahill 1994 David Prince 2011 Laura Ment

Boston Stanford New Haven

1978 W. Maxwell Cowan 1995 Gerald D. Fischbach 2012 Roger Packer

St. Louis Boston Washington, DC

1979 Fred Plum 1996 Verne S. Caviness 2013 Tallie Z. Baram

New York Boston Irvine

1980 Dominick Purpura 1997 Martha Bridge Denckla 2014 Gabrielle deVeber
New York Baltimore Toronto

1981 Pasko Rakic 1998 Andrew Engel 2015 Harry T. Chugani

New Haven Rochester Detroit

1982 John O’Brien 1999 Carla Shatz 2016 Harvey Sarnat

La Jolla Berkeley Calgary

1983 Roger N. Rosenberg 2000 Joseph Volpe 2017 Solomon Moshé

Dallas Boston Bronx, NY

1984 William L. Nyhan 2001 Huda Zoghbi 2018 William B. Dobyns

La Jolla Houston Seattle

1985 Patricia Goldman-Rakic 2002 Francis Collins 2019 Scott Pomeroy

New Haven Bethesda Boston

1986 Louis Sokoloff 2003 Darryl C. De Vivo

Bethesda New York

1987 Hugo Moser 2004 Karin Nelson

Baltimore Bethesda

1988 Victor Dubowitz 2005 O. Carter Snead III

London Toronto

1989 Salvatore DiMauro 2006 Donna Ferriero

New York San Francisco

1990 Roscoe O. Brady 2007 Frederick Andermann

Bethesda Montreal

1991 Marcus E.Raichle 2008 Michael Johnston

St. Louis Baltimore

1992 Louis M. Kunkel 2009 Gregory Holmes

Boston Lebanon, NH

1993 C. Thomas Caskey 2010 Thomas Jessell

Houston New York

Program and Abstracts, Child Neurology Society S5

 PHILIP R. DODGE
YOUNG INVESTIGATOR AWARD

1983 Michael Pranzatelli 2000 Stephen Back 2017 Audrey C. Brumback

Washington Portland Austin

1985 Richard J. Konkol 2001 Daniel J. Bonthius 2018 Christopher Elitt

Milwaukee Iowa City Boston

1986 Faye S. Silverstein 2002 Nigel Bamford 2019 Louis Dang

Ann Arbor New York Ann Arbor

1987 Vinodh Narayanan 2003 Bradley Schlaggar

Pittsburgh St, Louis

1988 Huda Zoghbi 2004 Terri Inder

Houston Melbourne

1989 Scott L. Pomeroy 2005 Mustafa Sahin

St. Louis Boston

1990 Harris Gelbard 2006 Elliott Sherr

Rochester, NY San Francisco

Evan Y. Snyder 2007 Mirjana Maletic-Savatic

Boston Stony Brook

1991 Kenneth J. Mack 2008 Laura Jansen

Madison Seattle

1992 Kelvin A. Yamada 2009 Jeffrey Neul

St. Louis Houston

1993 Jeffrey J. Neil 2010 Stephen Maricich

St. Louis Cleveland

1994 Mia MacCollin 2011 James Dowling

Boston Ann Arbor

1995 Adre J. du Plessis 2012 Yoon Jae-Cho

Boston Stanford

1996 Michael Rivkin 2013 Peter Tsai

Boston Boston

1997 William A. Weiss 2014 Christopher Smyser

San Francisco St. Louis

1998 Joseph Gleeson 2015 Jimmy Holder, Jr.

Boston Houston

1999 Amy Brooks-Kayal 2016 Diana Bharucha-Goebel

Philadelphia Bethesda

S6 Annals of Neurology Vol 86 (suppl 23) 2019

 ROGER & MARY BRUMBACK
LIFETIME ACHIEVEMENT AWARD
2004 2013
Jean Holowach Thurston Arthur Rose
St. Louis, MO Brooklyn, NY

2005 A. David Rothner

Robert Eiben Cleveland, OH
Cleveland, OH
2014
Arnold Gold G. Robert De Long
New York, NY Durham, NC

2006 2015
Raymond Chun Pat Crumrine
Madison, WI Pittsburgh, PA

Barry Russman Suresh Kotagal

Portland, OR Rochester, MN

2007 2016
William Kennedy Kalpathy Krishnamoorthy
Watertown, ME Boston, MA

Gordon Watters Doris Trauner

Montreal, Quebec La Jolla, CA

2008 2017
Cesare Lombroso Abe Chutorian
Boston, MA New York, NY

Niels Lowe W. Donald Shields

Tenafly, NJ Los Angeles, CA

2009 2018
Mary Anne Guggenheim Gerald Erenberg
Helena, MT Cleveland, OH

G Dean Timmons William Logan

Akron, OH Toronto, Ontario

2010 Alfred Spiro

Russell Snyder Bronx, NY
Albuquerque, NM
2019
2011 Carol Camfield
Warren Grover Halifax, Nova Scotia
Philadelphia, PA
W. Edwin Dodson
2012 St. Louis, MO
Bhuwan Garg
Indianapolis, IN

M. Richard Koenigsberger
Demarest, NJ

Program and Abstracts, Child Neurology Society S7

 ARNOLD P. GOLD FOUNDATION
HUMANISM IN MEDICINE AWARD
AT THE CHILD NEUROLOGY SOCIETY

2010 2014 2018

Ruth Ness Kenton Holden Audrey Foster-Barber
New York, NY Mt. Pleasant, SC San Francisco, CA

2011 2015 2019

Shaul Harel Robert Zeller H. Terry Hutchison
Tel Aviv, Israel Houston, TX Fresno, CA

2012 2016
Marvin Fishman Oscar Papazian
Houston, TX Miami, FL

2013 2017
Douglas Postels David Coulter
East Lansing, MI Boston, MA

BERNARD D'SOUZA
INTERNATIONAL FELLOWSHIP AWARD

1989 Meral Ozmen 2001 Dimitrios Zafeiriou 2013 Samson Gwer

Istanbul, Turkey Thessalonikki, Greece Nairobi, Kenya

1990 Najoua Miladi 2002 Vedrana Milic Rasic 2014 Jithangi Wanigasinghe
Tunis, Tunisia Belgrade, Serbia Dehiwela, Sri Lanka

1991 Sergio A. Antoniuk 2003 David Chkhartishvili 2015 Edward Kija

Curitiba, Brazil Tbilisi, Georgia Tanzania

1992 Qin Jiong 2004 Natalia A. Yermolenko 2016 Arushi Gahlot Saini
Beijing, China Voronezh, Russia Chandigarh, India

1993 Anu Soot 2005 Lusine Kirakosyan Tipu Sultan

Tartu, Estonia Yerevan, Armenia Lahore, Pakistan

1994 Lai Choo Ong 2006 Gia Melikoshvili 2017 Charles Hammond
Kuala Lampur, Malaysia Tbilisi, Georgia Kumasi, Ghana

1995 Nina Barisic 2007 David E. Kombo Aye Mya Min Aye
Zagreb, Croatia Dars Es Salaam, Tanzania Yangon, Myanmar

1996 Shan Wei Song 2008 Ikeolu Lagunju 2018 Suvasini Sharma
Beijing, China Ibadan, Nigeria New Delhi, India

1997 Aleksandra Djukic 2009 Uduak Mayen Offiong 2019 Nicolás Garófalo Gómez
Belgrade, Yugoslavia Abuja, Nigeria Havana, Cuba

1998 Ana Keleme 2010 Parayil S. Bindu Jitendra Kumar Sahu

Novi Sad, Yugoslavia Bangalor, India Chandigarh, India

1999 Magda L Nunes 2011 Kyaw Linn

Porto Alegre, Brazil Myanmar

2000 Brahim Tabarki-Melaiki 2012 Inga Talvik

Brussels, Belgium Tartu, Estonia

S8 Annals of Neurology Vol 86 (suppl 23) 2019

 OUTSTANDING JUNIOR MEMBER AWARD

1996 2000
Gyula Acsadi Sucheta Joshi
Children’s Hospital of Detroit Stanford University Medical Center

Lauren Plawner
Joseph Gleeson
Stanford University Medical Center
Boston Children’s Hospital
Monique Ryan
Andrea Gropman Boston Children’s Hospital
Children’s National Medical Center
Mustafa Sahin
Mary Sutton Boston Children’s Hospital
Boston Children’s Hospital

1997 2001
Gyula Acsadi Maria Acosta
Children’s Hospital of Detroit Children’s National Medical Center

Ann Bergin Randa Jarrar

Johns Hopkins University Mayo Clinic

Edwin Demeritte Steven Miller

Children’s Hospital of Detroit UC San Francisco

Jayne Ness
Sanford Shu
Loma Linda University Children’s Hospital of Alabama

1998 2002
June Caruso Taeun Chang
Rhode Island Children’s Hospital Children’s National Medical Center

Andrea Gropman Mirjana Maletic-Savatic

Children’s National Medical Center SUNY Stony Brook

Lauren Plawner
Alyssa Reddy
Stanford University Medical Center
Children’s Hospital of Alabama
Michael Seyffert
Janet Soul University of Washington Medical Center
Boston Children’s Hospital

1999 2003
June Caruso Taeun Chang
Rhode Island Children’s Hospital Children’s National Medical Center

Debra Holder Yoshimi Sogawa

Texas Children’s Hospital Schneider Children’s Hospital

Carolyn Menache Ignacio Valencia

Boston Children’s Hospital St. Christopher’s Hospital

Adeline Vanderver
Children’s National Medical Center

Program and Abstracts, Child Neurology Society S9

 2004 2008
Ignacio Valencia Gregory Aaen
St. Christopher’s Hospital Loma Linda University

Robert Avery
Brannon Morris
Mayo Clinic Children’s Hospital of Philadelphia

Haim Bassan Joseph Scafidi

Boston Children’s Hospital Children’s National Medical Center

William Benko Karen Powers

Children’s National Medical Center Virginia Commonwealth University

2009
2005
Bennett Gertz
William Benko
Children’s National Medical Center
Children’s National Medical Center
Ryan Lee
Alexander Bassuk
Kennedy Krieger Institute
Children’s Memorial Hospital Chicago
John Mytinger
Josh Bonkowsky University of Virginia
University of Utah Medical Center
Brandon Zielinski
Robert Safier University of California San Francisco
Children’s Hospital of Pittsburgh
2010
Dawn Gano
Renée Shellhaas University of British Columbia
Children’s Hospital of Philadelphia
Radhika Dhamija
2006 Mayo Clinic
Nicholas Abend
Children’s Hospital of Philadelphia Patricia Musolino
Massachusetts General Hospital
Lori Billinghurst Thitiwan Simasathien
University of Alberta University of Alabama-Birmingham
Holly Dudley-Harrell
2011
Children’s Hospital of Cincinnati Partha Ghosh
Cleveland Clinic Foundation
Jena Khera
The Cleveland Clinic Andrea Pardo
Cincinnati Children’s Hospital Medical Center
2007
Keith Abe
Thitiwan Simasathien
Stanford University Medical Center University of Alabama-Birmingham
Tarannum Lateef Syndi Seinfeld
Children’s National Medical Center Virginia Commonwealth University

Joseph Scafidi
Children’s National Medical Center

Marie-Pierre Thibeault-Eybalin
McGill University

S10 Annals of Neurology Vol 86 (suppl 23) 2019

2012 2016
Partha Ghosh Sonika Agarwal
Clevland Clinic Foundation Baylor College of Medicine

J.J. Gold Darius Ebrahimi-Fakhari

University of California San Diego Boston Children’s Hospital
Gayatri Mainali
Juliane Gust
Cleveland Clinic Foundation
Seattle Children’s Hospital
Christopher B. Oakley
Johns Hopkins Medical Institute Manisha Malik
Emory University

2013 2017
Anuja Jindal Ka Ye Clara Chan
Pittsburgh Children’s Hospital Loma Linda University Children’s Hospital

Archana Patel Hsaio-Tuan Chao

Boston Children’s Hospital Baylor College of Medicine

Rachel Goldstein Hirschberg

Pilar Pichon
Loma Linda University Boston Children’s Hospital

Mark Schomer Carla Watson

Boston Children’s Hospital Children’s Hospital of Michigan

Mitchell Williams 2018

Children’s Hospital of Michigan Adrienne Bruce
Cincinnati Children’s Hospital Medical Center

2014 Sara Fridinger

Jonathan Kurz Children’s Hospital of Philadelphia
Children’s National Medical Center
Melissa Hutchinson
Neggy Rismanchi Children’s Hospital of Philadelphia
University of California San Diego
Jeffrey A. Strelzik
Siddharth Srivastava
Kennedy Krieger Institute Children’s National Health System

Kavita Thakkar Elizabeth Troy

Pittsburgh Children’s Hospital University of Colorado

2019
2015
Lauren Chamberlain
Robert Blake
Duke University Medical Center
Cincinnati Children’s Hospital Medical Center
Darius Ebrahimi-Fakhari
Dana Marafie Boston Children’s Hospital
Texas Children’s Hospital
Aram Kim
Davut Pehlivan Children’s Hospital of Pittsburgh
Texas Children’s Hospital
Youssef Ayoub Kousa
Siddharth Srivastava Children’s Hospital National Medical Center
Kennedy Krieger Institute

Program and Abstracts, Child Neurology Society S11

 OUTSTANDING JUNIOR MEMBER POST GRADUATE AWARD

2018 2019
Bhooma Aravamuthan Giulia Benedetti
Boston Children’s Hospital
Boston Children’s Hospital Seattle
Seattle Children’s Hospital
Children’s Hospital

Elana Pinchefsky
The Hospital for Sick Children

M. RICHARD KOENIGSBERGER SCHOLARSHIP

Awarded in memory of M. Richard Koenigsberger, MD to the CNS Junior Member
submitting the best abstract in genetics, neonatal neurology, HIV or metabolic disorders
disorders

2013 2017
Louis Dang Davut Pehlivan
Children’s Hospital of Michigan Baylor College of Medicine

2014 2018
Joshua Bear Tayyba Anwar
University of California San Francisco Children’s National Medical Center

2015 2019
Vincent Carson David Ritter
Pittsburg Children’s Hospital Cincinnati Children’s Hospital Medical Center
2016
Ann McCarthy
Children’s Hospital Philadelphia

AAP SECTION ON NEUROLOGY TRAINEE TRAVEL AWARD

2015 2018
Jennifer Jaskiewicz Kerri Neville
Walter Reed National Military Medical Center Michigan Medicine

2016 2019
Sharoon Qaiser E. Justine Record
University of Kentucky Children’s National Medical Center

2017
Audie Espinoza
University of Utah

S12 Annals of Neurology Vol 86 (suppl 23) 2019

 BLUE BIRD CIRCLE
TRAINING PROGRAM DIRECTOR AWARD

2013 2016 2019

Harvey Singer David K. Urion Karen Ballaban-Gil
Baltimore, MD Boston, MA Bronx, NY

2014 2017
Steve Leber Sidney M. Gospe Jr.
Ann Arbor, MI Seattle, WA

2015 2018
Robert Rust Bruce K. Shapiro
Charlottesville, VA Baltimore, MD

BHUWAN GARG HIGH SCHOOL STUDENT NEUROSCIENCE

PRIZE

1998 2006 2014

Karla Malloy Shoshana Tell Laura Mariah Herman
Richmond, VA Coral Springs, FL Ft. Lauderdale, FL

1999 2007 2015

Nihar Gupta David Shiovitz Amrita Mohanty
New York, NY Briarcliff Manor, NY Woodbury, MN

2000 2008 2016

Rishikesh Dalal Lauren Lisann Ryan Infante
Lenexa, KS Dix Hills, NY Armonk, NY

2001 2009 2017

Melanie Napier Inar Zhang Lauren Singer
Laurelton, NY Mercer Island, WA Scarsdale, NY

2002 2010 2018

Corinna Zygourakis Pragya Kakani Amy Shteyman
Houston, TX Jericho, NY Great Neck, NY

2003 2011 2019

Henry Marr Spencer Chan Shan Lateef
Alhambra, CA Forest Hills, NY Manassas, VA

2004 2012
Debashish Zircar Vincent Shieh
Bronx, NY Bronx, NY

2005 2013
Max Christie Anna Thomas
Briarcliff Manor, NY San Jose, CA

Program and Abstracts, Child Neurology Society S13

 ASSOCIATION OF CHILD NEUROLOGY NURSES
CLAIRE CHEE AWARD FOR EXCELLENCE

2000 2008 2015

Jan Mims Irene M. Elliott Nancy Elling
Minneapolis, MN Toronto, ON Washington, DC

2001 2009 2016

Claire Chee Christine O’Dell Kathryn O’Hara
Philadelphia, PA Bronx, NY Richmond, VA

2002 2010 2017

Rhonda Roell Werner Julie Sprague-McRae Jennifer Boyd
New Berlin, WI Fremont, CA Toronto, ON

2003 2011 2018

Elizabeth F. Hobdell Yolanda Harris Cheryl Cahill
Chester Brook, PA Birmingham, AL Boston, MA

2004 2012 2019

Jane Meyer Jane Lane Courtney Wellman
Cottage Grove, WI Birmingham, AL Kansas City, MO

2006 2013
Amy Vierhile Cheryl Fischer
Rochester, NY New York, NY

2007 2014
Elizabeth Tate Jo Ellen Lee
Springfield, IL Columbus, OH

ASSOCIATION OF CHILD NEUROLOGY NURSES

NURSE PRACTITIONER EXCELLENCE AWARD

2015 2017 2019

Regina Laine Rebecca Schultz Erin Fecske
Boston, MA Houston, TX Kansas City, MO

2016 2018
Sue Yudovin Scott B. Turner
Los Angeles, CA Birmingham, AL

S14 Annals of Neurology Vol 86 (suppl 23) 2019

 THE
CHILD NEUROLOGY SOCIETY
GRATEFULLY ACKNOWLEDGES THE
FINANCIAL SUPPORT
OF

 Akron Children’s Hospital

 Atrium Health Levine Children’s

 AveXis, Inc.

 bluebirdbio

 Blue Bird Circle of Texas Children’s Hospital

 Child Neurology Foundation

 Eisai, Inc.

 Genentech

 Greenwich Biosciences

 Ipsen Biopharmaceuticals, Inc.

 Pediatric Epilepsy Research Foundation (PERF)

 PTC Therapeutics

 Recordati Rare Diseases

 Sanofi Genzyme

 Sarepta Therapeutics

 Zogenix, Inc.

Program and Abstracts, Child Neurology Society S15

 48th Annual Meeting of the Child Neurology Society
Scientific Program
Charlotte, NC

October 23 – October 26, 2019

Jonathan W. Mink, MD, PhD, President, CNS

Erika Fullwood Augustine, MD, Chair, CNS Scientific Selection and Program Planning Committee

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the
Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Minnesota
Medical Association and Child Neurology Society. The Minnesota Medical Association (MMA) is accredited by the
Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Minnesota Medical Association designates this live activity for a maximum of 28.5 AMA PRA Category 1 Credit(s)™.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.

PROGRAM

Wednesday, October 23 8:00 AM- Overview of Clinical Aspects

8:20 AM Nada Jabado, MD, PhD
7:45 AM- SYMPOSIUM I: Neurobiology of
5:00 PM Disease in Children (NDC): Childhood 8:20 AM- Neuroimaging: Novel Investigations and
Brain Tumors 8:50 AM Limitations
Organizer: Bernard L. Maria, MD, MBA, Kristen Yeom, MD; Lucile Packard
Goryeb Children’s Hospital, Morristown, Children’s Hospital at Stanford University,
NJ Palo Alto, CA

8:50 AM- Neuropathology and Molecular (Re-)

9:20 AM Classification
Brent Orr, MD, PhD; St. Jude Children’s
Supported by the National Institutes of Health
Research Hospital, Memphis, TN
(NIH grant 5R13NS040925-21), the Child
Neurology Society, the Pediatric Brain Tumor
Foundation, and Children’s National Medical 9:20 AM- Significance and Limitations of Molecular
Center 9:50 AM Data
Scott Pomeroy, MD, PhD; Harvard
7:45 AM- Opening Comments/Introduction Medical School, Boston Children’s
8:00 AM Bernard L. Maria, MD, MBA Hospital, Boston, MA

8:00 AM- SESSION I: CLINICAL ASPECTS 9:50 AM- Molecular Diagnosis in Embryonal, Glial and
10:20 AM Co-Director & Moderator: Nada Jabado, 10:20 AM Ependymal Tumors
MD, PhD; McGill University, Montreal, David T.W. Jones, PhD; Cancer Research
QC, Canada Center, Heidelberg, Germany

S16 Annals of Neurology Vol 86 (suppl 23) 2019

10:20 AM- Question and Answer Session 4:05 PM- Executive Summary of the Day
10:30 AM 4:20 PM Nada Jabado, MD, PhD
Roger Packer, MD
10:30 AM- Coffee Break Robert Wechsler-Reya, PhD
10:45 AM
10:45 AM- SESSION II: PATHOGENESIS 4:20 PM- SESSION IV: FUTURE DIRECTIONS
12:35 PM Co-Director and Moderator: Robert 4:55 PM PANEL DISCUSSION & QUESTION
Wechsler-Reya, PhD, Sanford Burnham AND ANSWER SESSION
Prebys Medical Discovery Institute, Moderator: Bernard L. Maria, MD, MBA
La Jolla, CA
PANELISTS:
10:45 AM- Overview of Pathogenesis and Mouse Modeling • Roger Packer, MD
11:05 AM Robert Wechsler-Reya, PhD • Nada Jabado, MD, PhD
• Robert Wechsler-Reya, PhD
11:05 AM- Neoplastic Transformation • Nina F. Schor, MD, PhD; National
11:35 AM David H. Gutmann, MD, PhD, FAAN;
Institute of Neurological Disorders and
Washington University School of
Medicine, St. Louis, MO Stroke, Bethesda, MD

11:35 AM- Genetic Predisposition Syndromes and 4:55 PM- Closing Comments and Thanks
12:05 PM Epigenetics 5:00 PM Bernard L. Maria, MD, MBA
Nada Jabado, MD, PhD

12:05 PM- Inter- and Intra-Tumoral Heterogeneity Additional Wednesday Meetings/

12:35 PM Underlying Medulloblastoma and Other Sessions
Embryonal Tumors
Paul Northcott, PhD; St. Jude Children’s 8:30 AM- Association of Child Neurology Nurses
Research Hospital, Memphis, TN 4:00 PM

12:35 PM- Question and Answer Session 8:00 AM- Pellock Resident Seminar on Epilepsy (Closed
12:45 PM 4:30 PM Session)

12:45 PM- Lunch with Foundation/Association (e.g. 8:00 AM- Program Coordinators of Child Neurology
1:45 PM PBTF) Presentation 5:00 PM (PCCN)

1:45 PM- SESSION III: THERAPY 2:00 PM- Professors of Child Neurology (Closed Session)
4:05 PM Co-Director and Moderator: Roger Packer, 5:00 PM
MD; Brain Tumor Institute; Children’s
National Medical Center, Washington, DC 6:00 PM- WELCOME RECEPTION
7:30 PM Sponsored by Atrium Health Levine
1:45 PM- Overview of Clinical and Translational Trials Children’s, Charlotte, NC
2:05 PM Nicole Ullrich, MD, PhD; Boston
Children’s Hospital, Boston, MA 7:45 PM- CNS LEGACY RECEPTION
9:30 PM PresentationofArnoldP.GoldFoundation
2:05 PM- Targeted Therapies Humanism in Medicine Award
2:35 PM Roger Packer, MD
• H. Terry Hutchison, MD, PhD;
2:35 PM- Radiotherapy
University of California San Francisco-
3:05 PM Tom Merchant, DO, PhD; St. Jude
Children’s Research Hospital, Memphis, Fresno Medical Education Program,
TN Fresno, CA
Presentation of Roger & Mary Brumback
3:05 PM- Immunotherapy
Lifetime Achievement Awards
3:35 PM EugeneHwang, MD; Center for Cancer and
Blood Disorders, Children’s National • Carol Camfield, MD; Professor Emerita,
Medical Center, Washington, DC Dalhousie University, IWK Health
Centre, Halifax, Nova Scotia, Canada
3:35 PM- Late Effects: Prevention and Management
4:05 PM Elizabeth Wells, MD, MHS; Brain Tumor • W. Edwin Dodson, MD; Washington
Institute, Children’s National Medical University School of Medicine, St.
Center, Washington, DC Louis, MO

Program and Abstracts, Child Neurology Society S17

 CNS/PCN Blue Bird Circle Training Therapeutic Studies in Autism Spectrum
Program Director Awards Disorder: The Future
Evdokia Anagnostou, MD; Bloorview
• Karen Ballaban-Gil, MD; Albert Research Institute, Toronto, Ontario,
Einstein College of Medicine, Canada
Montefiore Medical Center, Bronx, NY
Breakfast Seminar 3: Trauma
8:00 PM- Movement Disorders SIG Bay-to-Classroom: Barriers to School
10:00 PM Re-entry After Acquired Brain Injury
Organizer: John Taylor, MD; Cincinnati
Thursday, October 24 Children’s Hospital Medical Center,
Cincinnati, OH
7:00 AM- CONTINENTAL BREAKFAST AND Acute Brain Injury Pathophysiology and
8:15 AM SEMINARS Potential Relationship to Neurobehavioral
Seminars Supported by an Unrestricted Sequela
Educational Grant from Greenwich Biosciences Jonathan Kurz, MD, PhD; Ann &
Robert H. Lurie Children’s Hospital,
Breakfast Seminar 1: Antiepileptic vs Chicago, IL
Artisanal Cannabidiol: Ethical
Considerations Learning and Behavioral Challenges
Organizer & Moderator: Kathryn McVicar, Following ABI: Supporting Parents &
MD; Yale New Haven Children’s Hospital, Teachers
New Haven, CT Jennifer Frey, PhD, BCBA-D; Special
Antiepileptic vs. Artisanal Cannabidiol: Education & Disability Studies, Washington,
Ethical Considerations DC
Kathryn McVicar, MD Promoting Hope through Strategic School
Marijuana Legality: A Moving Target Supports: A Model for Overcoming the Barriers
Bennett Lavenstein, MD; National Children’s Patricia Dillhoff, MAT; Cincinnati
Medical Center, Washington, DC Children’s Hospital Medical Center,
Cincinnati, OH
Antiepileptic Cannabidiol in Epilepsy
Amy Brooks-Kayal, MD; Children’s
Hospital Colorado, Aurora, CO
WELCOME
Artisanal Cannabidiol in the Community
Anup Patel, MD; Nationwide Children’s
8:45 AM- Association of Child Neurology Nurses
Hospital, Columbus, OH
9:00 AM Claire Chee Award for Excellence
Case Presentations • Courtney Wellman, MSN, RN, CPN;
Kathryn McVicar, MD
Children’s Mercy Hospital and Clinics,
Breakfast Seminar 2: Clinical Research in Kansas City, MO
Autism: Trials and Tribulations
Organizer: Ann Neumeyer, MD; Association of Child Neurology Nurses
Massachusetts General Hospital for Nurse Practitioner Award
Children, Lexington, MA
• Erin Fecske, DNP, APRN, CNRN,
CPNP-PC; Children’s Mercy Hospital
Biomarkers for Clincial Trials in Autism
Spectrum Disorder and Clinics, Kansas City, MO
Shafali Jeste, MD; UCLA David Geffen
School of Medicine, Los Angeles, CA CNS Bernard D’Souza International
Fellowship Award
Measuring Meaningful Change in Individuals • Nicolás Garófalo Gómez, MD, PhD;
with Autism Spectrum Disorder Institute of Neurology and
Audrey Thurm, PhD; National Institute of Neurosurgery of Cuba, Havana, Cuba
Mental Health, Bethesda, MD • Jitendra Kumar Sahu, MD, DM;
Postgraduate Institute of Medical
Therapeutic Studies in Autism Spectrum: The
Past Education and Research, Chandigarh,
Ann Neumeyer, MD India

S18 Annals of Neurology Vol 86 (suppl 23) 2019

9:00 AM- SYMPOSIUM II: PRESIDENTIAL 12:00 PM- MEET THE EXPERTS: TBI
11:45 AM SYMPOSIUM: GENETIC 12:45 PM Moderator: Rachel Pearson, MD; UCLA,
HETEROGENEITY & PHENOTYPIC Los Angeles, CA
PLEIOTROPY IN THE NEXTGEN
SEQUENCING ERA Introduction
Organizers: Jonathan Mink, MD, PhD and Rachel Pearson, MD
Erika Fullwood Augustine, MD; University
of Rochester, Rochester, NY
Case #1: What a Pain: Persistent
Post-traumatic Headache in an Adolescent
Genetic Diagnostics for our Child Neurology Hockey Player
Patients: Where Are We Today? Raquel Langdon, MD; Children’s National,
Alexander Paciorkowski, MD; University Washington, DC
of Rochester Medical Center,
Rochester, NY Case #2: Going Back for More: Complex
Decision-making for a Young Football Player
Big Data Solutions to Variants of Uncertain Christopher Giza, MD; UCLA, Los Angeles,
Significance CA
Christina Gurnett, MD, PhD; Washington
University School of Medicine, St. Louis, PANELISTS:
MO • Raquel Langdon, MD
• Christopher Giza, MD
ATP1A3 Disorders, from Gene Discovery to • Meeryo Choe, MD; UCLA, Los Angeles, CA
Expanding Phenotypic Spectrum
• Sharief Taraman, MD; Children’s
Allison Brashear, MD, MBA; University of
California Davis, Sacramento, CA Hospital of Orange County,
Orange, CA
Pathophysiology and Treatment Implications
of Pleiotropy and Heterogeneity in 12:45 PM- CHILD NEURO NEWS FORUM:
Neuromuscular Diseases 2:00 PM GUIDED POSTER TOURS
Carsten Bönnemann, MD; National Supported by an Unrestricted Educational
Institute of Neurological Disorders and Grant from Greenwich Biosciences
Stroke, Bethesda, MD
12:45 PM- EXHIBITS & POSTER REVIEW
2:00 PM (Lunch served)
12:00 PM- MEET THE EXPERTS: EPILEPSY
12:45 PM Moderator & Expert: Elaine Wyllie, MD; 1:00 PM- Committee Meetings
Cleveland Clinic Lerner College of 2:00 PM
Medicine, Cleveland, OH
2:00 PM- SYMPOSIUM III: INFANTILE SPASMS:
Emerging Opportunities for Epilepsy Surgery 4:00 PM MAKING PROGRESS
in Complex Cases Organizer: Kelly Knupp, MD, MSCS;
University of Colorado, Aurora, CO
Case Study 1, 2, & 3
Elaine Wyllie, MD Co-Organizer & Moderator: Renée
Shellhaas, MD, MS; University of
PANELISTS: Michigan, Ann Arbor, MI
• Elia Pestana-Knight, MD; Cleveland
Clinic Epilepsy Center, Cleveland, OH Introduction
• Dave Clarke, MD; Dell Medical School, Kelly Knupp, MD, MSCS
University of Texas at Austin,
Austin, TX What is West Syndrome?
• Sucheta Joshi, MD, MS, FAES, FAAP; Katherine Nickels, MD; Mayo Clinic,
Rochester, MN
Michigan Medicine, Ann Arbor, MI
• William Gaillard, MD; Children’s The H Word
National Medical Center, Courtney Wusthoff, MD, MS; Stanford
Washington, DC University, Palo Alto, CA

Program and Abstracts, Child Neurology Society S19

 Mythbusters – Debunking Common 7:00 AM- CHILD NEURO NEWS FORUM:
Misperceptions about Infantile Spasms 8:15 AM GUIDED POSTER TOURS, POSTER
Scott Demarest, MD; University of REVIEW & EXHIBITS (Breakfast
Colorado, Aurora, CO Served)
Supported by an Unrestricted Educational
Debate: Early vs Later Surgery Grant from Greenwich Biosciences
Elaine Wyllie, MD; Cleveland Clinic,
Cleveland, OH 8:30 AM- PLATFORM SESSIONS I, II & III
10:15 AM
Sarah Kelley, MD; Johns Hopkins,
Baltimore, MD PLATFORM SESSION 1

What is the Evidence for Treatment of

8:30 AM- PL1-1 : Withdrawn
Infantile Spasms?
8:45 AM
Kelly Knupp, MD, MSCS
Conclusions & Questions 8:45 AM- PL1-2: Ochoa-Lubinoff et al
Renée Shellhaas, MD, MS 9:00 AM STARS: Results from a Safety and
Efficacy Study of OV101 (gaboxadol) in
4:00 PM- CHILD NEURO NEWS FORUM: Adults and Adolescents with Angelman
5:30 PM GUIDED POSTER TOURS Syndrome
Supported by an Unrestricted Educational Grant
from Greenwich Biosciences 9:00 AM- PL1-3: Finkel et al
9:15 AM Treatment of Young Boys with Duchenne
4:00 PM- EXHIBITS & POSTER REVIEW Muscular Dystrophy with the NF-B
5:30 PM (Wine & Cheese Served) Inhibitor Edasalonexent Showed a Slowing of
Disease Progression as Assessed by MRI and
Functional Measures
Additional Thursday Meetings/
Sessions 9:15 AM- PL1-4: Schulz et al
9:30 AM Persistent Treatment Effect of Cerliponase Alfa
in Children with CLN2 Disease: A 3 Year
8:00 AM- Program Coordinators of Child Neurology
Update from an Ongoing Multicenter
3:00 PM (PCCN)
Extension Study
9:00 AM- Association of Child Neurology Nurses
2:00 PM (ACNN) 9:30 AM- PL1-5 : Finkel et al
9:45 AM Intrathecal Administration of Onasemnogene
Abeparvovec Gene-Replacement Therapy (GRT)
Friday, October 25 for Spinal Muscular Atrophy Type 2 (SMA2):
Phase 1/2a Study (STRONG)
7:00 AM- CNS Arnold P. Gold Humanism in
8:15 AM Medicine Workshop 2019: Using 9:45 AM- PL 1-6: Vanderver et al
Humanism to Improve Patient Care in 10:00 AM Open Label use of the Janus Kinase Inhibitor
Child Neurology (Pre-Registration Baricitinib in a Genetic Interferonopathy,
Required) Aicardi Goutières Syndrome

Organizer and Moderator: 10:00 AM- PL 1-7: Raju et al

Nigel Bamford, MD; New Haven 10:15 AM Nanotherapeutic Targeting of Tumor
Children’s Hospital, New Haven, CT Endothelium Enhances Drug Delivery Past the
Blood-Brain-Barrier in Pediatric
Being Good at Breaking Bad News to Patients Medulloblastoma
and Parents

PANELISTS: PLATFORM SESSION 2

• Audrey Foster Barber, MD, PhD; Benioff
Children’s Hospital, UCSF Medical 8:30 AM- PL 2-1: Yun et al
Center, San Francisco, CA 8:45 AM Effect of Anti-Epileptic Drug Prophylaxis on
• Sonia Partap, MD, MS; Lucile Packard Time to First Seizure Diagnosis in Children
with Brain Tumors, Using National Medicaid
Children’s Hospital at Stanford,
Claims from 2009 to 2012
Stanford University, Palo Alto, CA

S20 Annals of Neurology Vol 86 (suppl 23) 2019

8:45 AM- PL 2-2: Tchapyjnikov et al 9:45 AM- PL 3-6: Stasheff et al
9:00 AM Delayed Time to EEG Placement is Associated 10:00 AM Physiologic Dysfunction, Demyelination, and
with Longer Seizure Duration in Refractory Retinal Ganglion Cell Loss in Mice with
Pediatric Status Epilepticus (the pSERG Neurofibromatosis and Optic Pathway
Cohort) Gliomas

9:00 AM- PL 2-3: Lemmon et al 10:00 AM- PL 3-7: Ciftci-Kavaklioglu et al

9:15 AM Parent Experience of Caring for Neonates with 10:15 AM Relevance of Timing of Mog Serum
Seizures Testing: Does Positivity Always Signal
Recurrence?
9:15 AM- PL 2-4: Joshi et al
9:30 AM Integrating Quality Improvement into the
ECHO Model to Improve Care for Children
and Youth with Epilepsy AWARD PRESENTATIONS

9:30 AM- PL 2-5: Ritter et al

10:45 AM- Outstanding Junior Member Awards
9:45 AM In Silico Predictions of KCNQ Channel
11:00 AM
Variant Pathogenicity in Epilepsy
• Lauren Chamberlain, DO; Duke
9:45 AM- PL 2-6: Mithal et al University Medical Center, Durham, NC
10:00 AM A Text-based Search of Electronic • Darius Ebrahimi-Fakhari, MD, PhD;
Medical Records Accurately Identifies Patients Boston Children’s Hospital, Harvard
with Mitochondrial Disease and Enables Medical School, Boston, MA
Analysis of Clinical and Genetic Data
• Aram Kim, MD; Children’s Hospital
10:00 AM- PL 2-7: Kruk et al of Pittsburgh, Pittsburgh, PA
10:15 AM Vulnerability of Pediatric Patients with • Youssef Ayoub Kousa, MS, DO, PhD;
Mitochondrial Disease to Vaccine Preventable Children’s National Health System,
Diseases Washington, DC
Outstanding Junior Member Award-Post
Graduate
PLATFORM SESSION 3
• Giulia Benedetti, MD; Seattle Children’s
Hospital, University of Washington,
8:30 AM- PL 3-1: Pulcine et al
Seattle, WA
8:45 AM The Safety of Antithrombotic Therapy in
Pediatric Cardioembolic Arterial Ischemic AAP Award
Stroke • E. Justine Record, MD; Children’s
National Medical Center, Washington,
8:45 AM- PL 3-2: Slim et al DC
9:00 AM Long Term Neuropsychological Outcomes
Following Cerebral Sinovenous Thrombosis in M. Richard Koenigsberger Scholarship
Childhood Award
• David Ritter, MD, PhD; Cincinnati
9:00 AM- PL 3-3: Hashmi et al Children’s Hospital Medical Center,
9:15 AM Delayed Initiation of Therapeutic Hypothermia Cincinnati, OH
for Outborn Infants is Associated with Adverse
Outcomes
Bhuwan Garg High School Student
Neuroscience Award
9:15 AM- PL 3-4: Benedetti et al
• Shan Lateef, Manassas, VA
9:30 AM EEG Background Could Inform Optimal
Duration of Monitoring for Neonatal Child Neurology Foundation Scientific
Encephalopathy Treated with Therapeutic Grant & Award Announcements
Hypothermia
11:00 AM- Philip R. Dodge Young Investigator
9:30 AM- PL 3-5: Ebrahimi-Fakhari et al 11:30 AM Award Lecture:
9:45 AM Adaptor Protein Complex 4 Deficiency: A Human Stem Cell Models of Genetic
Paradigm of Childhood-onset Hereditary Epilepsies
Spastic Paraplegia Associated with Defective • Louis Dang, MD; University of
Protein Trafficking Michigan, Ann Arbor, MI

Program and Abstracts, Child Neurology Society S21

11:30 AM- Bernard Sachs Award Lecture: Junior Member Seminar 3: Residents &
12:15 PM Neurodevelopmental Origin of Childhood Fellows: Getting your First Job
Central Nervous System Tumors
• Scott Pomeroy, MD, PhD; Harvard 5:30 PM- Meet the Editors
Medical School, Boston Children’s 6:15 PM
Hospital, Boston, MA 7:00 PM- GALA CLOSING RECEPTION
12:30 AM- CHILD NEURO NEWS FORUM: 9:00 PM
1:45 PM BEST OF SHOW (Top-Ranked Posters) Additional Friday Meetings/Sessions
Supported by an Unrestricted Educational
Grant from Greenwich Biosciences 8:00 AM- Program Coordinators of Child Neurology
5:30 PM (PCCN)
12:30 AM- LUNCH & SIG MEETINGS
1:45 PM 9:00 AM- Association of Child Neurology Nurses
2:15 PM- SYMPOSIUM IV: CURRENT 2:00 PM (ACNN)
4:15 PM CONCEPTS IN PEDIATRIC
NEUROLOGICAL INFECTIONS
Organizer: Daniel Bonthius, MD, PhD; Saturday, October 26
Levine Children’s Hospital – Atrium Health,
Charlotte, NC
7:00 AM- CONTINENTAL BREAKFAST AND
LCMV and Zika Virus: How Viruses Damage 8:15 AM SEMINARS
the Fetal Brain
Daniel Bonthius, MD, PhD Breakfast Seminar 4: Treatable Brain
CMV and Sensorineural Hearing Loss: Metabolic Disorders
Diagnosis and Management Organizer: Barry Kosofsky, MD, PhD;
James F. Bale, Jr., MD; University of Utah, Weill-Cornell Medical College, New York,
Salt Lake City, UT NY

Acute Flaccid Myelitis Moderator: Devorah Segal, MD, PhD;

Gary Nelson, MD; University of Utah, Salt Weill Cornell Medicine, New York, NY
Lake City, UT
Biomarkers of Rare Disease: What Can Brains
Encephalitis: Infectious and Immune- and Genes Tell Us?
Mediated Andrea Gropman, MD; Children’s
Carol Glaser, DVM, MPVM, MD; Kaiser National Health System, Washington, DC
Oakland Medical Center, Oakland, CA
Expanding Horizons in "Treatable" Epileptic
4:30 PM- CNS BUSINESS MEETING Encephalopathies
5:00 PM John M. Schreiber, MD; Children’s
National Medical Center, Washington, DC
4:30 PM- Education SIG
5:30 PM Organizer: Tarif Bakdash, MD, MHSc, Approach to Treatment in Neurometabolic
MEHP; Professor, Oakland University Disorders with Updates on Novel Therapeutics
William Beaumont Children’s Hospital, Gabriella Horvath, MD, PhD; BC
Royal Oak, MI Children’s Hospital, Vancouver, BC,
Canada
Are we Educating our Medical Students
and Child Neurology Residents for the Future? Breakfast Seminar 5: NF1: Updated
Tarif Bakdash, MD, MHSc, MEHP Diagnostic Criteria, New Guidelines and
Case-based Learning and Systems-based Targeted Therapies – The First-Hand
Curriculum for First-year Medical Students: Scene in 2019
Neuroscience and Behavior Organizer: Kaleb Yohay, MD; NYU
Riddhiben Patel, MD; University of Langone Health, New York, NY
Mississippi Medical Center, Jackson, MS
Diagnosing NF1 in 2019: GeneticTesting and
new Diagnostic Criteria
4:30 PM- JUNIOR MEMBER SEMINARS
Kaleb Yohay, MD
5:15 PM
Junior Member Seminar 1: Medical Clinical Management of Children with NF1:
Students: Finding a Residency New Practice Guidelines
Junior Member Seminar 2: Residents: Tena Rosser, MD; Children’s Hospital Los
Finding a Fellowship Angeles, Los Angeles, CA

S22 Annals of Neurology Vol 86 (suppl 23) 2019

 Emerging Treatments for NF1: MEK 1:00 PM – SYMPOSIUM VI: CHILD
Inhibitors and Beyond 4:30 PM NEUROLOGY FOUNDATION:
Nicole Ullrich, MD, PhD; Boston MANAGEMENT OF DISRUPTIVE
Children’s Hospital, Boston, MA AND HARMFUL BEHAVIOR IN
CHILDREN WITH EPILEPSY AND
Breakfast Seminar 6: Biomarkers, AUTISM SPECTRUM DISORDER
Mimics, and Treatment of Pediatric Organizer: Child Neurology Foundation
Demyelinating Diseases
Organizer: Soe Mar, MD; St. Louis Supported by an Unrestricted Education
Children’s Hospital, St. Louis, Grant from Child Neurology Foundation
MO Welcome
Ann Tilton, MD; President of the Child
Acute Flaccid Myelitis and other Mimics of Neurology Foundation, Louisiana State
Transverse Myelitis University Health Science Center New
Teri Schreiner, MD, MPH; Children’s Orleans, Children’s Hospital of New
Hospital Colorado, Aurora, CO Orleans, New Orleans, LA

Mimics of Supratentorial Demyelinating Current Clinical and Family Perspectives on

Diseases Disruptive and Harmful Behaviors
Jayne Ness, MD, PhD; University of Shafali Jeste, MD; UCLA David Geffen
Alabama at Birmingham, Birmingham, AL School of Medicine, Los Angeles, CA
Tanjala Gipson, MD; Le Bonheur
Biomarkers of Pediatric CNS Demyelinating Children’s Hospital, Boling Center for
Diseases Developmental Disabilities, Memphis, TN
Soe Mar, MD; St. Louis Children’s
Hospital, St. Louis, MO Victoria Maxwell-Kellam, Parent, Santa
Rosa, CA
Next Generation Treatment of MS and Other Leslie Russell, Parent, Dallas, TX
Neuroimmune Diseases of the CNS
Tim Lotze, MD; Baylor College of Assessment and Treatment of Problem
Medicine, Houston, TX Behaviors
Nathan Call, PhD, BCAB-D; Emory
University School of Medicine, Atlanta, GA
8:45 AM – Hower Award Lecture:
9:45 AM Assessing and Enhancing Clinical Competence Pharmalogic Approaches to Behavior
• James F. Bale Jr., MD; University of Management
David Dunn, MD; Indiana University
Utah, Salt Lake City, UT School of Medicine, Indianapolis, IN
10:00 AM – SYMPOSIUM V: FETAL Tabletop Case Study Discussions
12:00 PM NEUROLOGY: AT THE ORIGIN OF Paul Cooper, Child Neurology Foundation
NEUROLOGIC DISEASE
Organizer: Sarah Mulkey, MD, PhD; Panel Discussion
Children’s National Health Center, Q&A and Closing Remarks
Washington, DC 1:00 PM– Biomedical Writing Workshop
5:00 PM Organizer & Presenter: E. Steve Roach,
Fetal Neurology in Practice, Part 1
MD; University of Texas Dell Medical
Sarah Mulkey, MD, PhD
School, Austin, TX
Fetal Neuroimaging Introduction: Why Manuscripts are Rejected
Orit Glenn, MD; University of California
Shortcuts to Better Papers
San Francisco, San Francisco, CA
Keeping Things Moving: Combating Writer’s
Advances in Genetic Evaluation and Related Block
Outcomes of Structural Brain Disorders
Break
Elliott Sherr, MD, PhD; University of
California San Francisco, San Francisco, Responding to Reviews and Revising your
CA Manuscript
Rules of the Road: Permissions, Consents, and
Fetal Neurology in Practice, Part 2
Other Potholes
Taeun Chang, MD; Children’s National
Medical Center, Washington, DC Meet the Editors Q & A

Program and Abstracts, Child Neurology Society S23

 Agenda for 2019 ACNN Conference Program
Charlotte, NC
October 23-25, 2019

PROGRAM

Wednesday, October 23 1:30 PM- Updates in Vagal Nerve Stimulation

2:00 PM (VNS) for Patients with Intractable
Epilepsy
8:30 AM- WELCOME Julie Socha, RN, PPCNP-BC; University of
8:45 AM Rochester Medical Center, Rochester, NY
8:45 AM- Janet Brucker Keynote Address: Issues 2:00 PM- Progress is Progress, No Matter
9:30 AM and Trends in Nursing Regulation 2:30 PM How Small . . . the Infantile Spasm
Valerie Fuller, DNP, PhD; University of Journey
Southern Maine, Portland, ME Jennifer Coffman, JD, BSN, RN, CNRN;
Children’s Hospital Colorado, Aurora, CO
9:30 AM- Neurogenetics: Looking Toward the
10:00 AM Future 2:30 PM- Q & A/Break
Sarah Hansen, MSN-ED, RN, CNL; Helen 3:00 PM
DeVos Children’s Hospital, Grand Rapids,
MI 3:00 PM- Seize the Day: A Standardized
10:00 AM- Business Meeting 3:30 PM Educational Pathway to Reduce
10:30 AM Readmission Rates
Jenna Klareich, MSN, RN, CPN; Nicklaus
Children’s Hospital , Miami, FL
10:30 AM- Seizure Medications: A Primer for
11:15 AM Neurology Advanced Practice Providers Jeannie Perez, RN, CPN; Nicklaus
and Nurses Children’s Hospital, Miami, FL
Mona Jacobson, MSN, CPNP; Children’s
Hospital Colorado, Aurora, CO
3:30 PM- Treatment of Cluster Seizures: New
11:15 AM- Talking to your Patients and their 4:00 PM Treatment Options and Model of Care
11:45 AM Families about Cannabidiol for Epilepsy Nancy Santilli, RN, PNP, MN, FAAN;
Patricia Dean, APRN, MSN, CNRN; Human Care Systems and Consultant,
Nicklaus Children’s Hospital, Miami, FL Sunnyvale, CA
Kathy O’Hara, RN; Virginia
Mary Holmay, PhD, RN; Greenwich
Commonwealth University, Richmond, VA
Biosciences, St. Paul, MN

11:45 AM- Q&A

12:00 PM Thursday, October 24

12:00 PM- Lunch 9:00 AM- The Headache Champion Program

1:00 PM 9:30 AM Courtney Wellman, MSN,
RN, CPN; Children’s Mercy Hospital and
1:00 PM- SUDEP - What is Our Current
Clinics, Kansas City, MO
1:30 PM Understanding
Rhonda Roell Werner, MS, APNP; Allison Liles, BSN, RN, CPN; Children’s
Children’s Hospital of Wisconsin, Mercy Hospital and Clinics, Kansas City,
Milwaukee, WI MO

S24 Annals of Neurology Vol 86 (suppl 23) 2019

9:30 AM- Development of a Pediatric Migraine Friday, October 25
10:00 AM Action Plan
Scott Turner, DNP; University of Alabama
Birmingham, Birmingham, AL 9:00 AM- Tic Disorders: Diagnosis and
9:30 AM Management in Outpatient Settings
10:00 AM- Cefaly Device for Pediatric Acute Jocelyn Pedrick, MSN, CPNP, CNRN;
10:30 AM Migraine? Boston Children’s Hospital, Boston, MA
Tara Pezzuto, DNP; Nemours, Wilmington,
DE 9:30 AM- Reflex Epilepsy- What We Know
10:30 AM- What’s UP with ICP-Related Headaches? 10:00 AM Dianne Kulasa-Luke, MS, APRN-CNP,
11:00 AM PPNP-BC; Akron Children’s Hospital,
Elizabeth K. Rende DNP, APRN, CPNP- Akron, OH
PC, PMHS-BC, FAANP; CentraCare
Health, St. Cloud, MN 10:00 AM- Acute Flaccid Myelitis: Case Presentation
10:30 AM and Approach to Management
11:00 AM- Awards Erica Prendergast, RN, DNP, CPNP-AC;
11:30 AM Ann & Robert H. Lurie Children’s Hospital
of Chicago, Chicago, IL
11:30 AM- Innovative Clinical Practice Award
12:00 PM Presentation: Status Epilepticus Clinical 10:30 AM- Q&A
Care Guideline 11:00 AM
Michele Mills, RN, MSN, FNP-BC, PNP-
AC; Ann & Robert H. Lurie Children’s 11:00 AM- An Interdisciplinary Transition Clinic for
Hospital, Chicago, IL 11:30 AM Adolescents with Epilepsy: A Model for
12:00 PM- Lunch – Abstract & Grant Writing Mental Health Integration
1:00 PM Beck Reyes, MSN, RN, CPNP; University
of California, Los Angeles, CA
1:00 PM- Pediatric Neurology Nurse Practitioner
1:20 PM Transition to Practice 11:30 AM- Standardized Screening for Depression in
12:00 PM Pediatric Epilepsy
Tara Pezzuto, DNP; Nemours, Wilmington,
Erin Fecske, DNP, APRN, CNRN, CPNP-
DE
PC; Children’s Mercy Hospital and Clinics,
Kansas City, MO
1:20 PM- Design and Implementation of a
1:40 PM Certification Program Curriculum 12:00 PM- Lunch
Beck Reyes, MSN, RN, CPNP; 1:00 PM
University of California, Los Angeles,
CA 1:00 PM- Assessment of Awareness of the Early
1:30 PM Clinical Features of Spinal Muscular
RJDave H.Soliven,MSN,RN-BC, CCRN, Atrophy (SMA) Amongst Pediatricians in
ACCNS-P; Mattel Children’s Hospital at the Current Treatment Landscape
UCLA, Los Angeles, CA Mary Curry, ND; Cure SMA; Chicago, IL

1:40 PM- An Introduction and Evaluation of 1:30 PM- A Health Policy Analysis of Spinraza:
2:00 PM Advanced Practice Nurse-Run Clinics 2:00 PM Orphan Drug for Spinal Muscular
(APNRCs) in a Subspecialty Setting Atrophy
Jacqueline Wolak, DNP, APN, FNP-C; Brenda Cowan, DNP, APRN CNS, CPNP-
Ann & Robert H. Lurie Children’s Hospital PC; Baylor College of Medicine, Houston,
of Chicago, Chicago, IL TX

Program and Abstracts, Child Neurology Society S25

 PROGRAM COORDINATORS OF CHILD NEUROLOGY
ANNUAL EDUCATIONAL CONFERENCE AGENDA
OCTOBER 23-25, 2019

PROGRAM

Tuesday, October 22 12:00 PM- Networking Lunch - Lunch Provided

1:00 PM
Program Coordinators Networking 2:00 PM- Professors of Child Neurology (PCN)
Excursion 5:00 PM Meeting

Wednesday, October 23 6:00 PM- Child Neurology Society Welcome

7:30 PM Reception
NEW: Coordinator Bootcamp
The information covered this day is targeted to Thursday, October 24
those in the position up to two years.

8:00 AM- Continental Breakfast 8:00 AM- Continental Breakfast

8:50 AM 8:30 AM

8:50 AM- Opening Remarks 8:30 AM- Welcome – Day 1

9:00 AM Terri Feist, BBA, C-TAGME; President, 9:00 AM
Program Coordinators of Child Neurology, 9:00 AM- Coordinator Coalition
Cincinnati Children’s Hospital Medical 10:00 AM Jennifer Rew, M. Ed, Virginia
Center, Cincinnati, OH Commonwealth University, Richmond, VA
9:00 AM- Annual Program Calendar 10:00 AM- Break
9:30 AM Cathy Winter, Loma Linda University 10:15 AM
Health, Loma Linda, CA
10:15 AM- ACGME Updates
9:30 AM- PEC/APE 12:00 PM Laurie Gutmann, MD; Chair, Neurology
10:00 AM Kellie Shaw, UT Southwestern Medical RC Professor, University of Iowa, Iowa City,
Center, Dallas, TX IA
10:00 AM- Break Tiffany Hewitt, Senior Accreditation
10:15 AM Administrator; ACGME, Chicago, IL

10:15 AM- Child Neurology Program 12:00 PM- Networking Lunch - Lunch Provided
10:45 AM Requirements/Milestones/Being a Core 1:00 PM
Program
Adam Finney, BS, MS; University of 1:00 PM- Surviving the 10-Year Accreditation Site
Colorado, Aurora, CO 2:00 PM Visit
Terri Feist, BBA, C-TAGME; President,
10:45 AM- ABPN preCERT Program Coordinators of Child Neurology,
11:15 AM Terri Feist, BBA, C-TAGME Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH
11:15 AM- Break
11:30 AM 2:00 PM- Parking Lot
3:00 PM
11:30 AM- CCC
12:00 PM Teri Behnke, University of Michigan, Ann 5:00 PM- Program Coordinator Social
Arbor, MI 7:00 PM

S26 Annals of Neurology Vol 86 (suppl 23) 2019

 Friday, October 25 1:00 PM- Post Recruitment – Survey Results
2:00 PM Adam Finney, BS, MS; University of
Colorado, Aurora, CO
8:00 AM- Continental Breakfast
8:45 AM Danielle Taylor, MHA
8:45 AM- Welcome – Day 2
9:00 AM 2:00 PM- Break
2:15 PM
9:00 AM- Recruitment
10:00 AM Amy Orthaus, BBA; Mayo Clinic, 2:15 PM- Legal Responsibilities of the Coordinator
Rochester, MN 3:00 PM Adam Finney, BS, MS
10:00 AM- Resident/Fellow Wellness
11:00 AM Danielle Taylor, MHA; The University of 3:00 PM- Coordinator Market Title
Chicago, Cormer Children’s Hospital, 4:00 PM Teri Behnke, University of Michigan, Ann
Chicago, IL Arbor, MI

11:00 AM- Break 4:00 PM- Break

11:15 AM 4:30 PM

11:15 AM- Faculty Evaluations 4:30 PM- Education SIG

12:00 PM Amy Orthaus, BBA 5:30 PM

12:00 PM- Networking Lunch - Lunch Provided 7:00 PM- CNS Gala Closing Reception
1:00 PM 9:00 PM

Program and Abstracts, Child Neurology Society S27

 PLATFORM PRESENTATIONS

Platform Session 1
Friday, October 25
(8:30 am - 10:15 am)

PL1-1. Withdrawn

S28 Annals of Neurology Vol 86 (suppl 23) 2019

PL1-2. STARS: Results from a Safety and Efficacy Study Methods: MoveDMD was a Phase 2 randomized, placebo-
of OV101 (gaboxadol) in Adults and Adolescents with controlled trial with open-label-extension enrolling steroid-
Angelman Syndrome naïve 4-7 year old boys with DMD. In patients dosed at
Ochoa-Lubinoff C (Chicago, IL), Bird L, Tan W-H, 100 mg/kg/day, functional and MRI assessments were
Heimer G, Melmed R, Visootsak J, During M, Burdine R, compared to an off-treatment control period. Safety
Kolevzon A, Thibert R measures included assessments of growth and adrenal
Objective: To evaluate safety, tolerability, and efficacy of function.
OV101 (gaboxadol) in adult and adolescent patients with Results: Disease progression in the off-treatment control
Angelman syndrome (AS). period corresponded with off-steroid natural history in this
Methods: STARS was a phase 2, randomized, double-blind, age range. With edasa, there was slowing of disease progres-
placebo-controlled trial of OV101 QD (15 mg) and BID sion compared to off-treatment control period as assessed
(10 mg, 15 mg) vs placebo. The primary objective was safety by timed function tests (10-meter-walk/run, time-to-stand
and tolerability of OV101 over 12 weeks. Exploratory objec- and 4-stair-climb) and the North Star Ambulatory Assess-
tives included efficacy on motor function, sleep, and behav- ment (NSAA). Muscle enzymes decreased >12 weeks.
ior, assessed using Clinical Global Impressions – Lower leg muscle MRI-T2 changes up to 72 weeks were
Improvement scale (CGI-I) and various domain specific consistent with slowing of disease progression in contrast to
instruments. off-treatment progression. Edasa was well tolerated. There
Results: Seventy-eight participants completed the study. were no adverse trends in cortisol nor ACTH. BMI
Most AEs were mild with similar frequencies observed decreased to the 55thpercentile of expected on treatment,
across groups. Global improvement, captured by the reflecting maintenance of height percentile while weight
clinician-completed CGI-I, was observed at Week 12 with percentile decreased. Heart rate declined toward age-
OV101 QD vs placebo (P=0.0006). Additional post- normative values.
hocanalyses showed improvements in sleep onset latency and Conclusions: In the MoveDMD trial, edasa treatment was
overall sleep/motor function using actigraphy, Bayley-III associated with slowing of disease progression compared to
and PEDI-CAT scales. The Parent Global Impressions sug- an off-treatment control period with favorable growth pat-
gests patients who show a clinically meaningful improve- terns without negative impact on adrenal function. These
ment on the clinician-rated CGI-I (<2), also demonstrate results support potential for edasa to be disease-modifying in
improvements in communication, challenging behavior, and DMD alone or in combination. The Phase 3 PolarisDMD
anxiety. study of edasalonexent is ongoing.
Conclusions: STARS is the first trial to demonstrate clini- Keywords: Neuromuscular Disorders, Rare Diseases, Trans-
cal benefit of OV101 in participants with AS, with overall lational/Experimental Therapeutics
improvement based on CGI-I. The CGI-I offers the
opportunity to assess each individual as his/her own con- PL1-4. Persistent Treatment Effect of Cerliponase Alfa in
trol, and measures improvement across multiple symptom Children with CLN2 Disease: A 3 Year Update from an
domains. These data suggest that CGI-I may be suitable as Ongoing Multicenter Extension Study
a primary endpoint for assessing disorders with symptoms Schulz A (Hamburg, Germany), Specchio N, Gissen P, de los
in multiple domains, particularly in the setting of pheno- Reyes E, Cahan H, Slasor P, Jacoby D, Ajayi T
typic heterogeneity. The results support further develop- Objective: An open-label study demonstrated that intra-
ment of OV101 for treatment of individuals with AS and cerebroventricular (ICV) infusion of 300 mg cerliponase alfa
continued exploration of CGI-I as an endpoint in clinical (rhTPP1 enzyme) every other week for 48 weeks slowed
trials. deterioration in motor and language function in patients with
Keywords: Rare Diseases, Cognitive/Behavioral Disorders, CLN2 disease, a neurodegenerative lysosomal storage disor-
Translational/Experimental Therapeutics der. We report additional safety and efficacy data for at least
160 weeks.
Methods: Subjects who completed the initial study contin-
PL1-3. Treatment of Young Boys with Duchenne ued receiving 300 mg cerliponase alfa q.o.w. in an exten-
Muscular Dystrophy with the NF-κB Inhibitor sion study. Cumulative data from both studies were used
Edasalonexent Showed a Slowing of Disease Progression to evaluate long-term safety (assessed by adverse events
as Assessed by MRI and Functional Measures (AEs)) and efficacy (assessed by changes in the CLN2 clin-
Finkel R (Orlando, FL), Vandenborne K, Sweeney H, ical rating scale motor and language (ML) domains).
Finanger E, Tennekoon G, Shieh P, Willcocks R, Walter G, Results: 24 subjects were treated in the open-label study
Rooney W, Forbes S, Triplett W, Yum S, Mancini M, (9 male, 15 female, mean (SD) age 4.3 years (1.24));
MacDougall J, Donovan J 23 enrolled in the extension study and 22 remained on
Objective: Edasalonexent (edasa, CAT-1004), an oral NF-κB study for at least 168 weeks. Common AEs included
inhibitor, is being investigated as a potential foundational pyrexia, vomiting, and convulsion. Fewer subjects reported
therapy for patients with any DMDmutation not on cortico- convulsions over time (21 (88%) during the first 24 weeks
steroids. NF-kB is a central mediator of DMD disease pro- of therapy vs 6 (26%) during the last 24 weeks). Twenty
gression in both skeletal and cardiac muscle. (83%) subjects experienced serious AEs including

Program and Abstracts, Child Neurology Society S29

hypersensitivity and device-related infections. The PL1-6. Open Label use of the Janus Kinase Inhibitor
responder (<2 point loss per 48 weeks) rate at 160 weeks Baricitinib in a Genetic Interferonopathy, Aicardi
was 83% (p=0.0013). The rate of decline in ML score Goutières Syndrome
(mean (95% CI): 0.20 (0.10, 0.30) points/48 weeks, Vanderver A (Philadelphia, PA), Adang L, Gavazzi F,
p<0.0001) was significantly attenuated compared with a Ulrick N, Koh J, McDonald K, Peer K, Besnier C, Cross Z,
rate of decline of 2.0 points/48 weeks in untreated Helman G, Rhee J, Takanohashi A, Armangue T, Goldback-
patients, and has improved since prior analysis at 48 weeks Mansky R, Shults J
(0.40 points/48 weeks). Objective: Aicardi Goutières Syndrome (AGS) is a neurologi-
Conclusions: Cerliponase alfa has an acceptable safety profile cally devastating leukodystrophy. All known AGS genotypes
and a sustained treatment effect. activate a common pathway: interferon (IFN) production
Keywords: Rare Diseases leading to Janus-kinase (JAK) activation and transcription of
IFN-stimulated genes (ISG). We aimed to assess the safety of
PL1-5. Intrathecal Administration of Onasemnogene JAK-inhibitors in AGS children.
Abeparvovec Gene-Replacement Therapy (GRT) for Methods: We launched an unblinded, expanded access
Spinal Muscular Atrophy Type 2 (SMA2): Phase 1/2a program using Baricitinib, a JAK-inhibitor, in 36 children
Study (STRONG) with molecularly confirmed AGS. Baricitinib was weight
Finkel R (Orlando, FL), Day J, Darras B, Kuntz N, and eGFR dosed according to our protocol. We collected
Connolly A, Crawford T, Butterfield R, Shieh P, Tennekoon G, a minimum of 6 months of data for participants, includ-
Iannaccone S, Ogrinc F, Kavanagh S, Kernbauer E, Whittle J, ing safety laboratories, pharmacokinetic data, and daily
L’Italien J, Kaspar B, Sproule D, Spector S, Feltner D, AGS clinical diary scores. In parallel, all participants had
Mendell J neurologic outcome measure assessments: Peabody Devel-
Objective: The survival motor neuron (SMN) GRT opmental Motor Scales and Gross-Motor Function
onasemnogene abeparvovec (AVXS-101) treats the genetic Measure-88 used to evaluate efficacy in post-hoc analysis.
root cause of SMA. In a phase 1/2a study (CL-101; IFN signaling indirectly measured through mRNA levels
NCT02122952), one-time intravenous AVXS-101 adminis- of interferon-stimulated genes (ISG expression scores). As
tration improved outcomes in SMA type 1 patients. an exploratory endpoint, we created a novel AGS-specific
STRONG is a multicenter, open-label phase 1/2a study neurologic scale, retrospectively applied to assess neurologic
(NCT03381729) assessing intrathecal AVXS-101 in SMA2 function.
patients. Results: All serious adverse events were secondary to the
Methods: SMA2 patients (biallelic SMN1loss, 3xSMN2) underlying disease. There were variable laboratory
aged ≥6–<60 months who could sit but not stand/walk abnormalites at baseline and on study. Baricitinib decreased
receive a one-time intrathecal AVXS-101 dose (dose A: IFN-stimulated gene expression and improved symptoms (e.g
6.0x10e13; B: 1.2x10e14; C: 2.4x10e14 vg). Enrollment in irritability, skin inflammation) as recorded by the daily AGS
dose B was complete following demonstration of acceptable symptom diary. While traditional outcome measures were
safety in dose A and B. Primary endpoints are safety/ inconsistent over time, our exploratory AGS scale demon-
tolerability, optimal dose, unsupported standing ≥3 seconds strated improvement in neurologic function in a significant
(≥6–<24 months), and change in Hammersmith Functional subset of individuals.
Motor Scale-Expanded (HFMSE) score from baseline (≥24– Conclusions: Barictinib was safely administered to AGS indi-
<60 months) at 12 months post-dose. viduals. We found floor effects in traditional outcome mea-
Results: As of 3/24/2019, 31 patients were enrolled at sures, but our AGS scale demonstrated promise. This study
11 sites. Enrollment is complete for dose A (N=3, ≥6– establishes the foundation for safety and possible efficacy of
<24 months) and B (N=25; n=13, ≥6–<24 months; JAK-inhibitors in children with genetic interferonopathies
n=12, ≥24–<60 months), and ongoing for dose C such as AGS.
(3 patients dosed [≥6–<24 months]; 12 planned each ≥6– Keywords: Genetics, Rare Diseases
<24 and ≥24–<60 months). As of 9/27/2018, no
safety/tolerability concerns have been identified; 1 patient
PL1-7. Nanotherapeutic Targeting of Tumor
(4.0%) experienced 2 serious adverse events (elevated alka-
Endothelium Enhances Drug Delivery
line phosphatase, respiratory failure). 4/10 patients
Past the Blood-brain-barrier in Pediatric
(≥24 months) with available HFMSE data 1-month post-
Medulloblastoma
dose had ≥3-point score increase from baseline. Three
Raju P (New York, NY), Kiguchi H, Manzari M,
patients achieved 4 additional milestones. A study update
Vaynshteyn J, Gerwin J, Li N, Greenblatt M, Heller D
will be presented.
Conclusions: Results from STRONG show intrathecal Objective: The Sonic Hedgehog (SHH) medulloblastoma
AVXS-101 delivery is feasible and well tolerated, with no subgroup accounts for ~25% of all cases and has an inter-
safety concerns to date. mediate prognosis. Current conventional therapies result in
Keywords: Neuromuscular Disorders, Translational/Experi- devastating morbidities including intellectual disability and
mental Therapeutics, Rare Diseases secondary malignancies. Although molecularly targeted

S30 Annals of Neurology Vol 86 (suppl 23) 2019

agents that inhibit the SHH pathway (Vismodegib) have Conclusions: These data suggest applicability of combined
demonstrated clinical efficacy, recent studies have XRT and tumor vasculature-targeted nanotherapeutic dose
shown significant on-target secondary toxicities on bone de-escalation strategies for SHH medulloblastoma with
development suggesting new therapeutic approaches are potential implications for other pediatric brain tumors.
needed. Keywords: Brain Tumors/Oncology, Translational/Experi-
Methods: We investigated the efficacy of the SHH pathway mental Therapeutics
inhibitor, Vismodegib packaged in a fucoidan-based nanopar-
ticle (Fi-Vis) that targets P-selectin, a protein overexpressed
on vascular endothelial cells and induced by low-dose ioniz-
ing radiation (XRT) in a time- and dose-dependent manner. Platform Session 2
This P-selectin targeting nanoparticle drug delivery system Friday, October 25
shows selectivity toward tumor vasculature and not normal
brain vasculature in a genetic SHH medulloblastoma mouse (8:30 am - 10:15 am)
model as assessed by ex vivo infrared imaging and two-photon
intravital imaging.
>Results: Quantitative RT-PCR analysis of SHH medullo- PL2-1. Effect of Anti-Epileptic Drug Prophylaxis on Time
blastoma tissue following single dose XRT and Fi-Vis treat- to First Seizure Diagnosis in Children with Brain
ment (10mg/kg) showed a synergistic inhibition of Gli1 Tumors, Using National Medicaid Claims from 2009
expression (>90% target inhibition). Furthermore, we dem- to 2012
onstrate that very low dose XRT (0.25Gy) can induce P- Yun M (New York, NY), Zhang M, Basma N, Khakoo Y,
selectin expression specifically within MB tumor vasculature Grinspan Z
and synergize with low dose Fi-Vis (10mg/kg) to signifi- Objective: There is a high incidence of seizures among chil-
cantly enhance medulloblastoma mouse survival (p<0.01) dren with brain tumors. Though seizure prophylaxis with anti-
when compared to radiation or Fi-Vis alone. Finally, assess- epileptic seizure drugs (AEDs) is discouraged in adults with
ment of bone toxicity using micro-CT and histological brain tumors, there is limited data on its efficacy in children.
analysis following Fi-Vis administration in postnatal (P10) Methods: We performed a case-control study using
mice shows no bone toxicity when compared to free national Medicaid claims data between 2009 and 2012.
Vismodegib. We included children with brain tumor diagnosis (ICD9

FIGURE 1: Abstract PL 2-1 [Color figure can be viewed at www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S31

TABLE 1: Demographics. Abstract PL 2-1

191.x) at age 0-20 years old; seizure diagnosis (ICD9 4 of the 66 cases (6.1%) had their first seizure diagnosis after
345.x or 780.39) within 6 months after brain tumor prophylactic AED discontinuation.
diagnosis; AED prescription; 12 continuous months of Conclusions: Levetiracetam, oxcarbazepine, and phenytoin
Medicaid. We defined seizure prophylaxis as AED pre- were the most common initial prophylactic AEDs. AED pro-
scription within 30 days after brain tumor diagnosis but phylaxis was associated with a longer gap between brain
before first seizure diagnosis. We examined the following: tumor diagnosis and first seizure diagnosis (Figure 1b).
most common initial prophylactic AEDs; time to first sei- Keywords: Brain Tumors/Oncology, Epilepsy
zure diagnosis; proportion of cases with first seizure diag-
nosis after prophylactic AED discontinuation, defined as a PL2-2. Delayed Time to EEG Placement is Associated
treatment gap >30 days. with Longer Seizure Duration in Refractory Pediatric
Results: 176 children (66 cases, 110 controls) were included Status Epilepticus (the pSERG Cohort)
(Figure 1a). Children on prophylactic AED (cases) were older Tchapyjnikov D (Durham, NC), Feinstein L, Morgan L,
and less likely to be white than controls (Table 1). The most Abend N, Anderson A, Arya R, Brenton N, Carpenter J,
common initial prophylactic AEDs were levetiracetam Chapman K, Gaillard W, Gainza-Lein M, Glauser T,
(65.9%), oxcarbazepine (9.1%), and phenytoin (9.1%). Chil- Goldstein J, Goodkin H, Lai Y-C, McDonough T, Peariso K,
dren on AED prophylaxis had a longer median gap of Riviello J, Sanchez-Fernandez I, Sands T, Tasker R, Topjian A,
61.5 days (30.25-109.5) before their first seizure diagnosis, Wainwright M, Wilfong A, Williams K, Loddenkemper T,
compared to 22.5 days (6.25-57.75) for controls (p<0.001). Mikati M

FIGURE 1: Cumulative seizure resolution within 24-hours of seizure onset by EEG placement time among children with seizure
durations of ≥3 hours. Abstract PL 2-2

S32 Annals of Neurology Vol 86 (suppl 23) 2019

Objective: Rapid initiation of continuous EEG (cEEG) routine. Many parents anticipated financial and work chal-
monitoring is indicated in all cases of pediatric refractory sta- lenges. Emotional and physical toll (62%): Parents reported
tus epilepticus (RSE). The relationship between delays in feelings of worry, fear, and stress; many felt helpless in the
cEEG initiation and outcomes in RSE remains unknown. setting of their child’s complex early course.
We assessed trends in time to cEEG initiation and whether Conclusions: Parents of neonates with seizures face unique
delays are associated with longer seizure duration. challenges as they adapt to their role as a parent of a child
Methods: We analyzed data from 11 hospitals in the Pediatric with medical complexity. Future interventions should target
Status Epilepticus Research Group (pSERG), a prospective improving team consensus, reducing the burden associated
observational cohort of pediatric patients admitted from with prognostic uncertainty, and facilitating parent involve-
2011-2017 with RSE (seizure persisted after ≥2 anti-seizure med- ment in caregiving.
ications [ASM], one of which one had to be a non- Keywords: Neonatal Neurology, Epilepsy
benzodiazepine ASM or a continuous infusion). We included
121 patients who had seizure durations ≥3 hours. Delay was PL2-4. Integrating Quality Improvement into the ECHO
defined as cEEG placement >5 hours after seizure onset based Model to Improve Care for Children and Youth with
on an exploratory analysis of different time-point cut-offs. The Epilepsy
Kaplan Meier estimator was used to assess time to cEEG and Joshi S (Ann Arbor, MI), Gali K, Radecki L, Sachdeva R,
covariate-adjusted proportional hazards models to assess the asso- Calabrese T, Shah A, Hueneke S, Brown L, Kimball E,
ciation between cEEG placement delay and seizure duration. White P, Wood D, McManus M, Nelson E-L, Archuleta P
Results: Median time to cEEG after seizure onset was 9 hours,
Objective: Telementoring programs like Project ECHO®
4% of children had cEEG placed within 1 hour and 74%
(Extension for Community Healthcare Outcomes) employ
within 24 hours. 68% of children were having seizures at time
didactics, case-based learning and an “all teach-all learn”
of cEEG placement. The 24-hour cumulative probability of
approach to increase PCP knowledge/confidence in managing
seizure resolution was lower among those who did not have
chronic health conditions. The AAP Epilepsy and Com-
cEEG initiation within 5 hours (56% vs 70%; p=0.0360).
orbidities ECHO aimed to incorporate Quality Improvement
The association remained significant after adjusting for
(QI) methodology to create sustainable practice change, while
covariates (hazard ratio: 0.31; 95% CI: 0.16, 0.59; p=0.0004).
increasing PCP knowledge/confidence/self-efficacy in epilepsy
Conclusions: Results from this multicenter study show that
management using the ECHO model™.
cEEG initiation is delayed among children with RSE. These
Methods: ECHO sessions occurred monthly (5/2018-12/2018).
delays are associated with longer seizure duration.
Sessions included lectures, case presentations/discussion and QI
Keywords: Epilepsy, Critical Care
review. Practices, recruited through the AAP, implemented
monthly PDSA cycles using team huddles, chart reviews, QI
coaching calls and discussion. Measures for improvement were
PL2-3. Parent Experience of Caring for Neonates with selected from the American Academy of Neurology Epilepsy
Seizures Measures set. The AAP Quality Improvement Data Aggregator
Lemmon M (Durham, NC), Glass H, Shellhaas R, Barks M, was used for data entry, run chart development, tracking out-
Bailey B, Grant K, Grossbauer L, Pawlowski K, Wusthoff C, comes. Participants completed pre and post-surveys and received
Chang T, Soul J, Chu C, Thomas C, Massey S, Franck L Maintenance of Certification Part 4 credits.
Objective: We aimed to characterize the parent experience of Results: Average session attendance was 14 (13-17), across
caring for neonates with seizures at hospital discharge. 7 practices in 5 states. QI coaching facilitated practice
Methods: This prospective, observational study enrolled neonates change and development of resource toolkits with documen-
with acute symptomatic seizures and their parents, cared for at tation templates, safety handouts, medication side effects
the nine sites of the Neonatal Seizure Registry. At hospital dis- sheets. Individual and aggregate run charts with data analy-
charge, parents answered six open-ended questions that targeted sis augmented workflow changes. 479 chart reviews demon-
their experience. Responses were analyzed using a directed con- strated improvement in 6/7 measures (Table1):
tent analysis approach, with kappa > 0.7 for all themes. documenting seizure frequency (7.1% increase), anti-seizure
Results: 144 parents completed the open-ended questions therapy side effects (23%), safety education(41.6%,
(732 total comments). Four themes were identified: Sources p=0.036); Mental/behavioral health screening(32.2%
of strength (91% of respondents): Families valued medical p=0.027); Tertiary Center referral(26.7%); Health Care
team consensus, opportunities to contribute to their child’s transition(45.3%, p=0.005). Counseling for women of
care, and watching their child’s progress. Uncertainty (72%): childbearing age decreased by 7.8%. Participants reported
Three types of uncertainty caused distress: 1) the daily uncer- gains in knowledge/confidence/self-efficacy regarding epi-
tainty of the intensive care experience, 2) concerns about lepsy management (p< 0.02)
their child’s uncertain future, and 3) lack of consensus Conclusions: This project demonstrated that integrating QI
between members of the medical team. Adapting family life into an ECHO model results in sustainable practice change
(67%): Parents described the ways their infant’s condition and increases PCP knowledge/confidence/self-efficacy in
may necessitate adaptations in their family life, including managing epilepsy.
adjusting their family’s lifestyle, parenting approach, and Keywords: Epilepsy, Teaching of Child Neurology

Program and Abstracts, Child Neurology Society S33

 TABLE 1. Epilepsy Measures at baseline and after completion of eight ECHO sessions. Abstract PL 2-4
% % at ECHO Target
Epilepsy Measure Baseline conclusion Difference change df F Statistic p-value

Documentation of Seizure 77.9 85 7.1 5% 42 1.95708523 0.08

Frequency
Documentation of Anti-seizure 44.1 67.5 23.4 20% 42 2.1835047 0.05
therapy side effects
Safety Education documentation 30.9 72.5 30% 42 2.40054532 0.03
Screening for Mental/Behavioral 25.2 67.5 42.3 5% 42 2.55402735 0.02
Health
Counseling women during 36.4 28.6 -7.8 5% 42 0.71401269 0.66
childbearing age
Referral to Epilepsy Center 73.3 100 26.7 5% 42 0.88087066 0.53
Implementation of Transition 33.3 78.6 45.3 20% 42 3.45366474 0.005
Readiness Plan

PL2-5. In Silico Predictions of KCNQ Channel Variant PL2-6. A Text-based Search of Electronic Medical
Pathogenicity in Epilepsy Records Accurately Identifies Patients with Mitochondrial
Ritter D (Cincinnati, OH), Horn P, Holland K Disease and Enables Analysis of Clinical and
Objective: Variants in KCNQ channels have been associated Genetic Data
with early infantile epileptic encephalopathy and benign famil- Mithal D (Chicago, IL), Reilly S, Hitchins L, Epstein L
ial neonatal seizures. With the increase in genetic testing, more Objective: Mitochondrial diseases are a genetically heteroge-
variants of unknown significance are being reported in KCNQ nous group of disorders with predilection for the nervous sys-
channels. We set out to identify a prediction model that deter- tem. Retrospective identification of patients with confirmed
mines if KCNQ channel variants in infantile epilepsy are path- disease is appealing but challenging. We developed a text-
ogenic and to predict the severity of the phenotype. based search of the electronic medical records (EMR) to iden-
Methods: Databases of reported KCNQ2 and KCNQ3 vari- tify patients with mitochondrial disease.
ants in patients with neonatal epilepsy were accessed. The Methods: EMR were searched through a Lurie Children’s
variants were plugged into eight available prediction pro- internal review board approved study. A list of mitochondrial
grams. Sensitivity, specificity, percent correct decision, and metabolism search terms was used to query Lurie Children’s
the classification accuracy were determined and compared for EMR system from 1986 to 2018. Terms specific to mito-
each program. Mathematical models of the pathogenic vari- chondria resulted in a “positive” group and a “negative”
ants were then created using their amino acid location and derived from words generally associated with metabolism.
prediction program scores to predict the phenotype. The patients were then stratified by the degree of certainty
Results: In patients with epilepsy, PROVEAN prediction for diagnosis (“confirmed,” “likely,” “unlikely” and “not
algorithm was accurate 93% of the time (sensitivity 0.91 and mitochondrial”) using clinical and testing information from
specificity 0.94) and the next best algorithm was correct 86% the patient charts. The groups are compared using a variety
of the time. PROVEAN met the American College of Medi- of clinical characteristics including presence of epilepsy, dura-
cal Genetics standard for determining pathogenicity in tion of ICU stay and other co-morbidities.
KCNQ channels. The pathological KCNQ channel variants Results: 548 patient charts resulted from the initial text-
show no model that predicts the epilepsy phenotype with based search. The “positive” group consisted of 332 charts
>90% accuracy but regulatory domains of the channel are (61%), of which 32% had a high suspicion for mitochondrial
more likely to have pathogenic variants causing early infantile disease (113/548, 20.6%). The “negative” control population
epileptic encephalopathy. consisted of 216 charts (39%) of which only 3% were identi-
Conclusions: These results show that the clinician can use a fied as mitochondrial disease (6/548, 1%). 64% had a con-
free online tool to predict whether a variant of unknown sig- firmed genetic diagnosis (“confirmed”) and 25% were
nificance in KCNQ channels is likely to be pathogenic in “likely” based on chart review. Over 10% of the patients
infantile epilepsy. However, more work is needed to be able identified had a novel genetic variant.
to predict the phenotype of the disease. Conclusions: We identified a new patient cohort with mito-
Keywords: Epilepsy, Genetics, Neonatal Neurology chondrial disease using a text-based algorithm. We

S34 Annals of Neurology Vol 86 (suppl 23) 2019

demonstrate feasibility for broadening genotype-phenotype determine the safety of anticoagulant treatment in infants
correlations, particularly concerning neurologic morbidity. and children with CE-AIS.
Keywords: Rare Diseases, Genetics, Critical Care Methods: Single-center, retrospective analysis of a prospec-
tively enrolled cohort of neonates and children with
PL2-7. Vulnerability of Pediatric Patients with radiologically-confirmed CE-AIS from 2003 – 2017. Clinical
Mitochondrial Disease to Vaccine Preventable Diseases features examined included details of cardiac anatomy, type,
Kruk S (Bethesda, MD), Gordon-Lipkin E, McGuire P dose, intensity and duration of antithrombotic therapy.
Radiological features examined included CE-AIS location,
Objective: Infection is the most common cause of death
size and number of infarcts and hemorrhagic transformation
in patients with mitochondrial disease (MD). Given the
subtype according to the European Cooperative Acute Stroke
recent outbreaks of vaccine preventable diseases
Study (ECASS). Clinical outcome was measured by the pae-
(e.g. measles, varicella), and the morbidity and mortality
diatric stroke outcome measure (PSOM).
associated with infection in patients with MD, we exam-
Results: Ninty-three children met inclusion criteria [male
ined the serum titer status for most of the childhood vac-
52 (55.9%); neonates 24 (25.8%); median age 0.44 (0.10 –
cines in patients with MD.
4.22)]. Cardiac diagnosis included 57 (61.3%) cyanotic heart
Methods: Children ages 0-18y with “probable” or “definite”
disease, 14 (15.1%) acyanotic heart disease, 14 (15.1%) car-
MD by revised Walker criteria were included. Serum titers
diomyopathy and 8 (8.6%) other. HT occurred in 30 of
were determined by clinical testing at the NIH Clinical Cen-
93 children (32.3%), 6 (20.0%) of whom were symptomatic.
ter and Mayo Medical Laboratories.
Hemorrhage classification was HI1 in 11, HI2 in 12, PH1 in
Results: 26 children with MD were identified; 18 males and
6 and PH2 in 1. Our preliminary analysis suggests that HT
8 females with mean age of 10.8
3.6 years. MD phenotypes
is not associated with monotherapy vs. combination therapy
were Kearns Sayre Syndrome (N = 3), Leigh Syndrome (N =
nor antiplatelet vs. anticoagulant therapy. Mean total PSOM
5), and MD, not otherwise specified (N = 18). Medical record
scores were different in those with and without HT (2.2

review showed 73% were identified with immune abnormali-
2.3 vs. 1.2
1.7; p=0.0463) at follow-up.
ties, which included recurrent/delayed recovery from infection
Conclusions: This study will provide crucial safety data that
(58%) and hypogammaglobulinemia (19%). Patients with
will translate into better care for infants and children with
MD displayed vulnerability to Hib (33% seronegative) measles
CE-AIS.
(20% seronegative), and varicella (60% seronegative). Up to
Keywords: Stroke, Neuroimaging
56% of our patients with were found to be seronegative for
2 or more titers. Three patients treated with IVIG had normal
titers for all childhood vaccinations examined. PL3-2. Long Term Neuropsychological Outcomes
Conclusions: A considerable number of patients with MD following Cerebral Sinovenous Thrombosis in Childhood
are susceptible to vaccine preventable diseases. Monitoring Slim M (Toronto, Ontario, Canada), Aziz A, Westmacott R,
serum titers of patients with MD may be indicated, especially Dlamini N, deVeber G, MacGregor D, Yau I, Moharir M
in areas with increased risk of exposure due to reduced adher- Objective: To evaluate long-term neuropsychological impair-
ence to vaccination recommendations in the community. ments in children following cerebral sinovenous thrombo-
Understanding the immune status of patients with MD is an sis (CSVT).
important part of maintaining the health of this vulnerable Methods: Children with CSVT from 1993-2015, who had
population. neuropsychological testing, were included. Demographic,
Keywords: Genetics, Infections/Neuroimmunology clinical and radiographic features at diagnosis were obtained.
Neuropsychological testing assessed intellectual ability, execu-
tive function, attention, language and behavior. Outcomes
were compared to population-based normative mean using
Platform Session 3 one-sample t-test. Scores≥ one standard deviation away from
Friday, October 25 the mean (toward the abnormal end of each scale) were classi-
fied as impaired. Predictors of impaired function were
(8:30 am - 10:15 am) assessed using logistic regression.
Results: Fifty children with CSVT were included (median
age-diagnosis 2.8 years, 70% males). Seizure at diagnosis was
PL3-1. The Safety of Antithrombotic Therapy in present in 16%, 60% had superficial venous system involve-
Pediatric Cardioembolic Arterial Ischemic Stroke ment, 50% had infarcts, 30% had intracranial hemorrhage
Pulcine E (Toronto, Ontario, Canada), Seed M, Brandao L, and 80% received anticoagulants. Neuropsychological testing
Slim M, Shroff M, Palasamudram S, Moharir M, deVeber G, was performed at a median of 4 years post-diagnosis.
Dlamini N Children with CSVT demonstrated significantly impaired
Objective: Congenital heart disease is a major cause of car- intellectual function outcomes on the full scale intelligence-
dioembolic arterial ischemic stroke (CE-AIS) occurring in quotient, working memory and processing speed domains
25% of neonates and children. Hemorrhagic transformation (93.3
16, p=0.01; 93.6
16, p=0.04; 93.7
15.3, p=0.02,
(HT) rates in pediatric CE-AIS are largely unknown and respectively). Children with CSVT showed significant impair-
adult safety data are of limited applicability. We aim to ments in executive function, attention and language domains.

Program and Abstracts, Child Neurology Society S35

 TABLE 1. Clinical and radiological features of cardioembolic arterial ischemic stroke. Abstract PL 3-1
Total (n=93) HT (n=30) No HT (n=63) P-value

CE-AIS Number of Visible Infarcts, n (%)

Single 48 (51.6%) 17 (56.7%) 31 (49.2%) 0.66
Multiple – Concurrent 35 (37.6%) 11 (36.7%) 24 (38.1%)
Multiple – Different Ages 10 (10.8%) 2 (6.7%) 8 (12.7%)
CE-AIS Laterality, n (%)
Unilateral 59 (63.4%) 20 (66.7%) 39 (61.9%) 0.96
Bilateral 17 (18.3%) 5 (16.7%) 12 (19.0%)
Multifocal 17 (18.3%) 5 (16.7%) 12 (19.0%)
Modified Pediatric ASPECTS 4.5
2.9 [0 – 13] 5.2
3.4 [0 – 13] 4.1
2.6[0 – 12] 0.22
(mean
SD [range])
Hemorrhagic Transformation 30 (32.3%)
Subtype, n (%)
HI1 11 (36.7%)
HI2 12 (40.0%)
PH1 6 (20.0%)
PH2 1 (%)
Symptomatic HT, n (%) 6 (20.0%)
HT Change Over Time, n (%) 5 (16.7%)
Mean Time to HT (days
SD 3.5
4.2 [0 – 15]
[range])
Median Time to HT (days [IQR]) 2.5 [0 – 5]
Other Types of Intracranial Hemorrhage, n (%)
Subdural 20 (21.5%) 4 (13.3%) 16 (25.4%) 0.28
Subarachnoid 3 (3.2%) 2 (6.7%) 1 (1.6%) 0.24
Intraventricular 3 (3.2%) 1 (3.3%) 2 (6.3%) 1.00
Systemic Hemorrhage, n (%) 5 (5.4%) 3 (10.0%) 2 (3.2%) 0.32
Cortical Laminar Necrosis, n (%) 12 (12.9%) 2 (6.7%) 10 (15.9%) 0.33
SWI+ Microhemorrhages, n (%) 16 (17.2%) 4 (13.3%) 12 (19.0%) 0.57
Mean Creatinine at Stroke Ictus 43.8
24.3 49.4
30.4 41.1
20.5 0.30
(μmol/L
SD [range]) [18 – 153] [22 – 153] [18 – 130]
Mean Total PSOM Score
SD 1.5
1.9 2.2
2.3 1.2
1.7 0.05

Seizure at presentation was associated with a trend for long- Conclusions: Children with CSVT have residual neuropsy-
term behavioral impairment (odd ratio [OR]=6.3, 95% confi- chological impairments as a group compared to the general
dence interval [CI]:0.9-46, p=0.07) and females were less pediatric population. Further studies of larger cohorts
likely to experience impaired processing speed (OR=0.22, aimed at evaluating potential predictors of neuropsychologi-
95% CI:0.04-1.3, p=0.09). Incomplete recanalization was cal deficits in individual children with CSVT are
associated with impaired verbal comprehension (OR=5.3, warranted.
95% CI:0.93-30.5, p=0.059). Keywords: Stroke, Cognitive/Behavioral Disorders

S36 Annals of Neurology Vol 86 (suppl 23) 2019

 TABLE 2. Details of antithrombotic treatment. Abstract PL 3-1
Total (n=93) HT (n=30) No HT (n=63) P-value

Remained on No Treatment Following Stroke Ictus, n (%) 8 (8.6%) 4 (13.3%) 4 (6.3%) 0.27
No Change in Antithrombotic Treatment, n (%) 18 (20.5%) 6 (22.2%) 12 (19.0%) 0.78
Commenced Treatment or Antithrombotic Regimen Was 67 (76.1%) 20 (74.1%) 47 (74.6%) 0.76
Escalated, n (%)
Monotherapy, n (%) 68 (73.1%) 19 (63.3%) 49 (77.8%) 0.14
Combination Therapy, n (%) 16 (17.2%) 6 (20%) 10 (15.9%) 0.62
Antiplatelet, n (%) 3 (3.2%) 0 3 (4.8%) 0.55
Anticoagulant, n (%) 71 (76.3%) 24 (80%) 47 (74.6%) 0.57
Antiplatelet + Anticoagulant, n (%) 12 (12.9%) 1 (3.3%) 11 (17.4%) 0.10
tPA, n (%) 2 (2.2%) 0 2 (31.7%) 1.00
Days from Stroke Ictus to Initiation of Antithrombotic 1.6
5.4 [0 – 41] 1.3
2.9 [0 – 11] 1.7
6.3 [0 – 41] 0.43
Treatment (mean
SD [range])
Arterial Ischemic Stroke Recurrence, n (%) 18 (19.4%) 5 (16.7%) 13 (%) 0.78

TABLE 1. Clinical and demographic characteristics of 222 infants treated with TH*. Abstract PL 3-3
Inborn n = 69 Outborn n = 153 p-value

Maternal Characteristics
Gestational Diabetes (n, %) 14 (20%) 15 (10%) 0.05
Mean Maternal Age (SD) 30.4 (5.9) 27.6 (5.9) 0.001
Delivery Characteristics
Cesarean section (n, %) 41 (59%) 79 (52%) 0.35
Chest compression administration 10 (15%) 56 (37%) 0.001
Infant Characteristics
Female Sex (n, %) 31 (45%) 70 (46%) 0.99
Mean birth weight in kg (SD) 3.3 (0.7) 3.4 (0.6) 0.19
Mean Gestational Age in Weeks (SD) 38.5 (2.0) 39.6 (1.7) <0.001
Median Apgar Score 1 min (# obtained, IQR) 1 [69, 1, 2] 2 [151, 1, 3] 0.06
Median Apgar Score 5 min (# obtained, IQR) 4 [69, 3, 6] 4 [150, 3, 5] 0.70
Median Apgar Score 10 min (# obtained, IQR) 6 [55, 4, 7] 6 [135, 4, 7] 0.53
Cord Gases
Number of arterial gases obtained (n, %) 55 (80%) 88 (58%) 0.002
Mean arterial pH (SD) 7.04 (0.16) 7.06 (0.18) 0.48
Number of venous gases obtained (n, %) 52 (75%) 82 (54%) 0.003
Mean venous pH (SD) 7.10 (0.17) 7.13 (0.20) 0.47

*Statistically insignificant differences in characteristics not shown here include maternal fever, GBS positive mothers, pre-eclampsia/eclampsia, vacuum
assistance, shoulder dystocia, nuchal cord, cord prolapse, placental abruption, uterine rupture, late decelerations on fetal heart monitoring,
chorioamnionitis, and prolonged rupture of membrane

PL3-3. Delayed Initiation of Therapeutic Hypothermia versus community hospitals (outborn). Determine if delayed
for Outborn Infants is Associated with Adverse Outcomes initiation is associated with adverse short-term outcomes.
Hashmi N (Portland, OR), Sale M, Fox L, Kerecman J, Methods: A retrospective study of infants treated with TH in
McAllister L, Melendi M, Lucas F, Craig A Maine was performed excluding infants >6 hours old at TH initi-
Objective: Characterize the time to initiation of therapeutic ation and <35 weeks gestation. Outcomes included time to TH
hypothermia (TH) for infants born in tertiary centers (inborn) initiation, in-hospital mortality, presence of severe seizures

Program and Abstracts, Child Neurology Society S37

 TABLE 2. Short-term outcomes of 222 infants treated with TH. Abstract PL 3-3
All Infants Inborn n = 69 Outborn n = 153 p-value

Median Hour of Life TH Initiated (IQR) 1 (1,3) 4 (3,5) <0.001

Mortality (n, %) 3 (4.3%) 21 (13.7%) 0.038
Any seizure (n, %) 16 (23.2%) 57 (37.5%) 0.045
Severe seizure (n, %) 3 (4.3%) 14 (9.2%) 0.28
Severe GM injury on MRI (n, %)* 2 (3%) 8 (5.7%) 0.62
Mortality, severe seizure, and/or severe GM injury 7 (10.1%) 34 (22.2%) 0.039
on MRI (n, %)
Mild Encephalopathy n=9 n = 32
Median Hour of Life TH Initiated (IQR) 4 (1.5, 4.5) 4.1 (3.5, 5) 0.57
Mortality, severe seizure, and/or severe GM injury 0 (0%) 1 (3.1%) 1.00
on MRI (n, %)
Moderate Encephalopathy n = 52 n = 101
Median Hour of Life TH Initiated (IQR) 1 (1, 2.5) 3.5 (3, 4.5) <0.001
Mortality, severe seizure, and/or severe GM injury 3 (5.8%) 14 (13.9%) 0.18
on MRI (n, %)
Severe Encephalopathy n=8 n = 20
Median Hour of Life TH Initiated (IQR) 1 (0.9, 1.6) 3 (2.4, 5) 0.002
Mortality, severe seizure, and/or severe GM injury 4 (50%) 19 (95%) 0.015
on MRI (n, %)

*MRI scores were assigned by a neuroradiologist using scoring guidelines as detailed in Weeke, L. C., et al. (2018). "A Novel Magnetic Resonance
Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia." J Pediatr 192: 33-40 e32.

(requiring phenobarbital, fosphenytoin and midazolam infusion) encephalopathy (HIE) have acute symptomatic seizures.
and magnetic resonance imaging (MRI) grey matter (GM) injury Many centers provide continuous electroencephalography
score >9.5 as assigned by a blinded neuroradiologist. (cEEG) monitoring throughout cooling and rewarming,
Results: From 2008-2018, 255 infants were treated with TH and even though most seizures emerge during the first 24h of
222 were included; 31% were inborn and 69% were outborn monitoring. We hypothesized that early cEEG background
(Table 1). Mothers of inborn infants were older and gave birth features could inform optimal duration of cEEG monitor-
approximately one week earlier. Chest compression use, a proxy ing for seizure detection in neonates treated with TH
for resuscitation, was significantly lower for inborn infants. for HIE.
Median time to TH initiation and rate of mortality, severe seizure, Methods: Retrospective cohort study of consecutive neonates
and/or severe GM injury on MRI were significantly higher in out- treated with TH for moderate or severe HIE at a Level IV
born infants (Table 2). In uncontrolled logistic regression analysis, NICU between 2012-2018. All had cEEG throughout
the odds of in-hospital mortality, severe seizures or severe GM cooling and rewarming. Archived samples of the first 24h of
injury were 2.5-fold higher for outborn infants (95% CI 1.1-6.5) cEEG were reviewed systematically for background classifica-
and 5-fold higher after controlling for sex, gestational age, gesta- tion (Table 1).
tional diabetes and encephalopathy severity (95% CI 1.6-20.0). Results: Electrographic seizures occurred in 56/114 neonates
Conclusions: There is a significant delay in TH initiation for (49%). Seizure onset was usually within the first 24h of
outborn infants and a striking association between being out- cEEG (49/56, 88%), with only four (7%) between 24-48h,
born and increased mortality, severe seizures, or severe grey zero between 48-72h, and just three (5%) >72h after EEG
matter injury that is most elevated for infants with severe initiation (Figure 1). Infants with normal or mildly abnormal
encephalopathy. Investigation into factors contributing to EEG background either had seizure onset within 24h or
severe encephalopathy is urgently needed. never developed seizures. The four patients with seizure onset
Keywords: Neonatal Neurology, Neuroimaging between 24-48h had markedly abnormal EEG backgrounds.
Seizure onset beyond 72h occurred in three patients, all of
PL3-4. EEG Background Could Inform Optimal whom had moderately or severely abnormal backgrounds and
Duration of Monitoring for Neonatal Encephalopathy atypical clinical courses.
Treated With Therapeutic Hypothermia Conclusions: It may be appropriate to use early cEEG back-
Benedetti G (Ann Arbor, MI), Vartanian R, Pace R, ground categorization to guide duration of cEEG for neo-
McCaffery H, Shellhaas R nates treated with TH for HIE. Some neonates may
Objective: About half of all neonates who require thera- reasonably be monitored for 24h-48h, rather than through-
peutic hypothermia (TH) for suspected hypoxic-ischemic out cooling and rewarming, without significant risk of missed

S38 Annals of Neurology Vol 86 (suppl 23) 2019

 TABLE 1. Classification of EEG background for term and near-term neonates treated with therapeutic
hypothermia. Abstract PL 3-4
EEG Features Normal-Mildly Abnormal Moderately Abnormal Markedly Abnormal

Continuity Wakefulness (W) and active sleep (AS): QS: IBIs 7-15 sec Discontinuous with
continuous IBIs >15 sec
Quiet sleep (QS): IBIs <7 sec
Amplitude W and AS: 25-50 μV W/AS: 5-15 μV <10 μV
QS: some <25 μV but often ≥25 μV QS: 10-25 μV, some IBIs <10 μV IBIs <10 μV
Symmetry Symmetric May be asymmetrica May be asymmetric
b
Synchrony Synchronous with no more than rare Persistent asynchrony during Persistent asynchrony
asynchronous bursts in quiet sleep discontinuous segments
State cycling Spontaneous state cycling Poor state modulation No state cycling
c
Reactivity Reactive to external stimulation Inconsistent response to external Nonreactive
stimulation
Normal Contains an age-appropriate admixture of Paucity of normal graphoelements No normal graphoelements
graphoelements frequencies and normal graphoelementsd
Epileptiform None Excessive negative sharps and/or BRDs Excessive negative sharps
abnormalities and/or BRDs
a
W = wakefulness Asymmetry is present if the amplitude over one hemisphere is >50% that
AS = active sleep of the other
b
QS = quiet sleep Asynchrony is present if >1.5 seconds separae the onset of bursts between
IBI = interburst interval the right and left hemispheres
c
BRD = brief rhythmic discharges Reactivity defined electrographically as brief diffuse background
attenuation in response to external stimulation
d
Includes synchronous and symmetric delta brushes, anterior dysrhythmia,
encoches frontales

FIGURE 1: Electrographic seizure onset for neonates with normal or mildly abnormal EEG background was consistently within
the first 24h of cEEG monitoring. Seizures were more common in neonates with markedly abnormal background EEG (28/37
(76%)) compared to those with moderately abnormal background (13/33 (39%)) and normal or mildly abnormal backgrounds
(15/47 (32%), p<0.001, Fisher’s Exact Test). Abstract PL 3-4

Program and Abstracts, Child Neurology Society S39

seizures. This could have significant implications for cEEG Methods: In mice with neurofibromin (Nf1) deletions in glial
resource utilization. precursor cells (NF1-OPG) and littermate controls, we com-
Keywords: Neonatal Neurology, Critical Care, Epilepsy pared visual behavior (optomotor responses [OMR]), in vivo
anatomy (optical coherence tomography [OCT]), in vitro
PL3-5. Adaptor Protein Complex 4 Deficiency: A multielectrode recording of spontaneous and light-evoked
Paradigm of Childhood-onset Hereditary Spastic RGC activity, and histologic analysis of RGCs, optic nerves
Paraplegia Associated with Defective Protein Trafficking and chiasms.
Ebrahimi-Fakhari D (Boston, MA), Behne R, Teinert J, Results: NF1-OPG mice proliferate atypical glial cells by post-
Wimmer M, D’Amore A, Carmody E, Dies K, Chen I, natal day 15-21 (P15-21). Between 1-7 months they lose sub-
Buttermore E, Sahin M stantial vision (OMR sensitivity), central retina thickness
(on OCT) and RGCs, in diffuse or focal patterns. However,
Objective: Bi-allelic variants in subunits of the adaptor pro-
regions with normal RGC density have many cells with no
tein complex 4 (AP-4) lead to childhood-onset hereditary
recordable activity or higher spontaneous activity and weaker or
spastic paraplegia (AP-4-HSP). Aims: 1) to develop a natural
suppressive light responses. Retrobulbar optic nerves are unmy-
history; 2) to generate AP-4-HSP induced pluripotent stem
elinated, even in mice without optic nerve or chiasmal injury.
cell (iPSC)-derived neurons; 3) to characterize these neurons
Conclusions: We demonstrate novel abnormalities in RGC
with respect to AP-4-related cellular phenotypes.
structure and function in NF1-OPG mice, and that early dis-
Methods: A cross-sectional analysis of clinical data, cell biol-
ruption in the retina’s “message” to the brain can precede
ogy and high-content imaging.
anatomic defects. These findings may explain disparities
Results: We report a detailed characterization of 147 patients
between visual loss and tumor characteristics among NF1
of 93 families enrolled in the AP-4-HSP International Regis-
patients. We propose clinical tests based on these mecha-
try. We define a core set of symptoms: Early-onset develop-
nisms, to translate our findings to earlier detection of patients
mental delay with significant speech delay (54% non-verbal);
at risk for visual loss, and improved treatment.
intellectual disability (moderate to severe); mild hypotonia in
infancy followed by spastic diplegia and later tetraplegia; Keywords: Brain Tumors/Oncology, Translational/Experi-
microcephaly; foot deformities; and epilepsy that is refractory mental Therapeutics, Genetics
in a subset. At last follow up 28% of patients ambulated with
assistance and 69% were wheelchair-dependent. Key features PL3-7. Relevance of Timing of Mog Serum Testing: Does
on neuroimaging include a thin corpus callosum (91%), Positivity Always Signal Recurrence?
ventriculomegaly (71%), and periventricular white-matter Ciftci-Kavaklioglu B (Toronto, Ontario, Canada), Longoni G,
signal abnormalities (66%). Iron deposition and poly- Yea C, Grover S, Albassam F, Iruthayanathan R, Yeh EA
microgyria are found in a small subset. Variants in AP4B1and Objective: To evaluate the relevance of timing of MOG test-
AP4M1 account for the majority of cases. More than ing for predicting recurrence in pediatric demyelinating
70 unique variants were present, the majority of which are
syndromes.
frameshift or non-sense mutations. In 15 patient-derived
Methods: Analysis of prospectively collected data from con-
fibroblast lines and six lines of iPSC-derived neurons, we find
secutive patients. MOG serostatus was tested using a cell
that the AP-4 cargo and autophagy-related protein ATG9A
based commercial assay (Oxford, UK) at variable intervals
accumulates in the trans-Golgi network and is depleted from
from disease onset.
other compartments. This provides evidence for ATG9A mis-
Results: Results from 360 specimens from 214 patients
localization as a key disease mechanism and marker of AP-4
(121 F, median (IQR) age at onset [y] 11(8.4), 74 (34%)
deficiency.
with recurrent disease, 22 with multiple sclerosis
Conclusions: We define the clinical, molecular and radio-
(MS) (10%)) were analyzed. 34/103 tested (33%) resulted
graphic spectrum of AP-4-HSP and identify cellular pheno-
positive within 3 months from onset (MOG 12 months
types of AP-4 deficiency.
(MOG>12). None of the patients with MS were MOG-
Keywords: Rare Diseases, Movement Disorders, Genetics
positive at any timepoint. Four Chi-Square Independence
tests (Bonferroni corrected α: .013) did not show any signifi-
PL3-6. Physiologic Dysfunction, Demyelination, and cant association between MOG12 serostatus were associated
Retinal Ganglion Cell Loss in Mice with with recurrent disease (Phi .48, p .003, and Phi .25, p .013,
Neurofibromatosis and Optic Pathway Gliomas respectively), with MOG6-12 showing the highest predictive
Stasheff S (Washington, DC), Nadal-Nicolas F, Jecrois E, Li W, accuracy (sensitivity 61.1%, specificity 85%, PPV 78.6%,
Bornhorst M, Zheng W, Zhu Y NPV 70.8%). Survival analysis (Kaplan-Meier) conducted on
Objective: Using an animal model, we identify novel mecha- participants with at least 1 positive MOG test and who were
nisms that help explain a striking disparity in children with off of any immunosuppressant treatment (45/121 (37%))
neurofibromatosis type 1 (NF1) and optic pathway gliomas estimated a median conversion time of 60 (Std. error 48)
(OPGs): In many patients the degree of visual loss is inade- months to MOG seronegative status. Only 7 patients were
quately predicted by tumor characteristics or treatment on active immunosuppressant therapy at the time of their last
response. In transgenic mice with NF1, OPGs and visual evaluation (13%), all but one showing persisting MOG anti-
loss, we identify previously unknown abnormalities of retinal body. MOG serostatus fluctuated in 6 patients (in one case
ganglion cell (RGC) anatomy and physiology. during rituximab-induced B-cell suppression).

S40 Annals of Neurology Vol 86 (suppl 23) 2019

Conclusions: MOG positivity at 6 to 12 months after symp- Objective: To review the treatment and revaccination of
toms can predict recurrent disease. MOG antibodies seem to neuroblastoma-associated OMS patients at MSK.
decline over longer periods of time than previously reported. Methods: Institutional Review Board approval was obtained
Keywords: Demyelinating Disorders for this retrospective study of patients with neuroblastoma-
associated OMS followed at MSK from 2000-2016.
Results: The 15 patients (10 female) were 4-21 (median
16) months old at diagnosis of neuroblastoma and OMS.
POSTER PRESENTATIONS They had stage 1 (n=12), 2B, intermediate-risk stage 4, or
4S disease. Tumor histology was favorable in 12 patients,
unfavorable in 2, and unknown in 1 patient. No patient
had amplified-MYCN. All patients underwent tumor re-
BRAIN TUMORS/ONCOLOGY section at diagnosis. Anti-neuroblastoma treatment was
limited to chemotherapy in 1 patient. Overall survival is
100% at 3-16 (median 10) years. For OMS, 13 patients
1. Imaging and Neurologic Symptoms after received IVIg, ACTH, and rituximab; 1 received ACTH
Hematopoietic Stem Cell Transplant in Children and IVIg; and 1 patient required no therapy. Seven patients
Duke E (Boston, MA), Ullrich N, Lehmann L developed OMS relapse for these relapses, 5 patients
received low-dose cyclophosphamide and 2 received
Objective: Neurologic complications after hematopoietic
rituximab. The mean total OMS treatment was 47 months
stem cell transplant (HSCT) in children are poorly defined
(range: 1-96 months). Seven of 13 patients received
but may contribute to morbidity and mortality. We identi-
rituximab ≤3 months from diagnosis without relapse. The
fied HSCT patients with brain MRIs after transplant, identi-
remaining 6 experienced OMS relapse requiring longer
fied indications for imaging and determined correlation of
treatment. To date, 7 patients have been revaccinated at a
imaging with neurologic symptoms.
minimum of two years after completion of OMS therapy
Methods: We retrospectively reviewed patients after HSCT
without OMS recurrence.
at Boston Children’s Hospital between October
Conclusions: Patients with neuroblastoma-associated OMS
2013-September 2016 and characterized subset with brain
had excellent overall survival. Early initiation of rituximab,
MRIs post-transplant. Clinical data included demographics,
IVIg and ACTH may reduce risks of OMS relapse.
transplant details, MRI findings and neurologic symptoms.
Revaccination can be resumed without exacerbation of OMS.
Results: 261 patients (158 males; mean transplant age
Further investigation with a larger cohort of patients is
8.5
6.5yrs); 57/261 (22%) had at least one MR brain after
needed.
transplant. 93 total MRIs completed post-transplant (range
Keywords: Brain Tumors/Oncology, Rare Diseases
1-7 per patient) within 3 years. Acute symptoms prompted
imaging for 42/93 (45%): altered mental status (n=15), focal
neurologic symptoms (n=13), headache (n=9), seizure (n=5). 3. Significant Response of a TSC-associated Pediatric
An additional 51 (55%) performed for known systemic infec- Clival Chordoma Treated with Everolimus
tion (n=18), follow-up of previously identified process (n=18), Malbari F (Houston, TX), Aldave G, Whitehead W,
or screening (n=15). Only 14/93 (15%) had acute findings (all Kukreja M, Glinton K, Chintagumpala M, Rednam S,
had acute symptoms) which changed clinical management. Adesina A, Robak L, Lin F
Other MR findings not associated with clinical symptoms Objective: Chordomas are rare cancers thought to arise from
(n=69, 74%) included non-specific T2 hyperintensities, vol- notochordal remnants along the axial skeleton. Chordomas
ume loss, sinus disease, stable or improved known lesions, have occasionally been reported in patients with tuberous
chronic microhemorrhage. Only 10 scans (11%) were normal. sclerosis complex (TSC), an autosomal dominant
Conclusions: 1/5 of patients in this pediatric HSCT popula- neurocutaneous disorder caused by pathogenic variants in
tion had at least one brain MRI after transplant, nearly half TSC1or TSC2 that result in aberrant mTOR-pathway
performed to investigate new neurologic symptoms. Of these, signaling.
1/3 had MR findings correlating with symptoms; 3/4 had Methods: We report a child with clival chordoma, with
subacute findings. It will be important to further characterize TSC, treated with everolimus upfront due to concern for
MR findings in symptomatic and asymptomatic patients, ide- morbidity and anticipated poor response to conventional
ally with neuropsychological testing, to better understand therapy.
long-term impact of transplant in children. Results: A 2 year-old male presented with regression of
Keywords: Brain Tumors/Oncology, Neuroimaging milestones, left hemiparesis, and dysphagia. Physical exami-
nation revealed hypopigmented macules. MRI brain dem-
2. Treatment and Revaccination of Children with onstrated an extensive T2-hyperintense, infiltrative tumor of
Paraneoplastic Opsoclonus-myoclonus Syndrome (OMS) the skull base with intraspinal extension to C2-3 and com-
and Neuroblastoma: The Memorial Sloan Kettering pression of brainstem as well as subependymal nodules.
(MSK) Experience Echocardiogram revealed rhabdomyomas. Staged neurosur-
Patel A (New York, NY), Fischer C, Lin Y-C, Basu E, gical resection was planned, however, after 25% removal of
Kushner B, DeBraganca K, Khakoo Y the mass, imaging revealed absence of flow in right vertebral

Program and Abstracts, Child Neurology Society S41

artery without ischemia. Histopathologic examination was
consistent with chordoma –epithelioid, vacuolated, and
COGNITIVE/BEHAVIORAL
physaliphorous cells within a myxoid matrix, immunohisto- DISORDERS
chemical staining positive for S-100, CK-Pan, and EMA.
Germline sequencing of blood (TSC Panel, Invitae) identi- 5. A Ball, a Stick, a Stopwatch, and a Sharpened Romberg
fied a heterozygous known pathogenic variant in TSC1 Can be used for the Assessment and Management of
(c.1715_1722dupGCCAGACT, p.Ser575AlafsTer57). Due Concussion in Pediatric Patients within 8 Weeks of Injury
to patient’s young age and potential morbidity from addi- Brown W (Providence, RI), Baird J, Kriz P
tional surgery, chemotherapy or radiotherapy, treatment was Objective: To describe age dependent normal values for four
initiated with everolimus. After 6 months of therapy, mini- bedside analog tests of neurological functioning in children
mal toxicity is noted and exam shows improved strength, 10-18 years of age both with and without a recent concus-
re-attainment of milestones. MRI revealed ~30% reduction sion, and to determine whether these tests provide guidance
in tumor size. information useful to the assessing clinician.
Conclusions: Treatment with everolimus is beneficial in Methods: Four tests: (stick drop (SD), sharpened Romberg
patients with TSC-associated tumors such as SEGA and (SR), timed alternating hand wall bounce (WB), and an oral,
angiomyolipoma. Our report suggests everolimus may also timed animal name list production (AN) were administered
benefit patients with TSC-associated chordoma. to children both without and with a recent concussion
Keywords: Brain Tumors/Oncology, Translational/Experi- (within preceding 8 weeks) and at subsequent clinical visits
mental Therapeutics following initial assessment.
Results: Across 748 total office visits, performance on SD,
SR, and WB but not AN in 90 children with recent (<8wks)
4. Provider Views on Perioperative Steroid use in Newly
but not remote (>8wks) concussion were statistically distinct
Diagnosed Pediatric Brain Tumors
from the performances on identical tests of 316 never-
Malbari F (Houston, TX), Weiner H, Staggers K, Minard C,
concussed children and 252 ever-concussed children of simi-
Chintagumpala M, Levy A
lar age, gender, and handedness.
Objective: Cerebral edema from brain tumors can cause neu- Conclusions: We demonstrate that 3 of 4 in-office tests (SD,
rological impairment. Steroids treat edema but with possible SR, WB) that require only a ball, stopwatch, and a stick to per-
adverse effects. We surveyed providers about steroid use in form show evidence of derangement in recently (<8wks) but
newly diagnosed patients with brain tumors, to potentially not ever or never concussed children ages 10-18 years. Serial
develop a standardized practice. testing shows regression of the abnormal findings to baseline.
Methods: An anonymous voluntary online survey was sent We describe normal values in never concussed children for each
to members of the Children’s Oncology Group. Four clinical assessment and consider that in-office testing with actual objects
scenarios were provided and questions regarding initiation of as opposed to computerized or pen and paper assessments are
steroids, type, dose, formulation, and duration were asked. intrinsically motivating; immediately demonstrative of physical,
Demographic information was collected. concussion related deficits to the child-parent dyad; supplement
Results: 369 providers received the survey, 76 responded the routine neurological examination; and are a useful addition
(20.6% response rate). The proportion of providers who to the expanding list of assessment tools in pediatric concussion.
would start steroids significantly differed among scenarios Keywords: Cognitive/Behavioral Disorders
(scenario 1 vs 2, p<0.001; 2 vs 3, p<0.001; 1 vs
3, p<0.001). 75 (98.7%) providers would start steroids for
vasogenic edema (scenario 1) and 55 (72.4%) for obstruc-
tive hydrocephalus (scenario 2). 73 (96%) would not start
steroids for an incidental tumor (scenario 3). 16 (21.1%)
would start steroids for vasogenic edema but not obstructive
hydrocephalus (p<0.001). The odds of choosing to start ste-
roids in patients with obstructive hydrocephalus were 7.59
times more (95% CI: 2.29, 25.13) if providers felt symp-
toms would improve within 24 hours. All would use dexa-
methasone. 11 (14.5%) would give a loading dose if
neurological deficits were noted, not the presence of
vasogenic edema (p=0.002).
Conclusions: These results suggest that providers recom-
mend dexamethasone for patients with vasogenic edema and
obstructive hydrocephalus. Steroids are more likely to be ini-
tiated sooner and with a loading dose if neurological deficits
are present. Variability remains with dosing schedule of dexa-
methasone. Steroid management guidelines need to be
created. FIGURE 1: Symptoms and Behavior Changes during
Keywords: Brain Tumors/Oncology Menstrual Cycle. Abstract 5

S42 Annals of Neurology Vol 86 (suppl 23) 2019

 7. Clinical Characteristics of Dyslexia in Children
Kim SK (Seoul, Korea), Kim SH
Objective: Developmental dyslexia (or specific reading disability)
is defined as an unexpected difficulty in accuracy or fluency of
reading for an individual chronological age, intelligence, level of
education or professional status. In Korea, there is a lack of sys-
tematic research on dyslexia but some pediatric psychiatrist and
special educator are concerned in dyslexia. The purpose of this
study was to investigate the clinical characteristics of patients
diagnosed with dyslexia in the developmental disorders clinic.
Methods: From January 2017 to January 2018, of the
patients who visited the developmental clinic in Dongtan
Sacred Heart Hospital, Hallym University, 8 patients who
met the DSM-5 diagnostic criteria of dyslexia were included.
Patients’ intelligence test, psychological test, learning disabil-
ity test, reading analyzer test were analyzed.
Results: The mean age was 11.0
3.3 years and the male to
female ratio was 2.36: 1. Patients with dyslexia were visited for
FIGURE 2: Women’s Health-Related Examinations in difficulty in learning difficulties and ADHD symptoms. Intelli-
participants for whom exam was indicated by the American gence was the average point. In the evaluation of learning disabil-
College of Obstetricians and Gynecologists. Abstract 5 ity with the test, the average number of learning score was lower
than the standard value, and the reading and writing index was
6. Characterization of Women’s Healthcare and the lowest score. In the reading analyzer test, slow reading speed,
Parameters in Patients with Rett Syndrome low comprehension, number of eye fixation and number of eye
Humphrey K (Cincinnati, OH), Standridge S, Reebals L, regression were compared with normal reference point.
Horn P, Olshavsky L Conclusions: When patients with learning difficulty visit the
Objective: Rett syndrome (RTT) is a neurodevelopmental dis- developmental disability clinic, dyslexia should be evaluated
order that affects females and is characterized by neurological and interested.
regression. Few studies have consolidated data on the impact Keywords: Cognitive/Behavioral Disorders
of hormonal changes and gynecologic maturation on women’s
health in RTT, which poses clinical challenges in treating 8. Spontaneous Third Ventriculostomy in Krabbe Disease
patients according to the recommendations of the American Kim A (Pittsburgh, PA), Zuccoli G, Wu J, Poe M, Escolar M
College of Obstetricians and Gynecologists (ACOG). The goal Objective: Spontaneous third ventriculostomies (STV) have
of the study was to collect data on menstruation management only been reported in relation to obstructive hydrocephalus
and women’s health examinations/interventions to help and increased intracranial pressure (ICP). Hydrocephalus has
develop a clinical approach to these parameters in RTT. been reported in very few case studies of patients with
Methods: A chart review of 77 patients with a diagnosis of Krabbe disease, a rare progressive neurodegenerative disease.
RTT was conducted to collect data on menstrual patterns, However, monitoring for hydrocephalus or increased ICP is
women’s health examinations (breast and pelvic exams), and challenging in patients with Krabbe disease as patients with
women’s health interventions (contraception, HPV vaccina- Krabbe disease have symptoms commonly seen in patients
tion, mammograms). Primary outcome measures are descrip- with increased ICP and hydrocephalus – irritability, poor
tive data on menstruation management and women’s health feeding, lethargy, and upward gaze weakness. We describe a
examinations/interventions. Secondary outcome measure is series of cases of STV in patients with Krabbe disease.
the proportion of patients that have received well-woman Methods: Brain magnetic resonance images (MRI) of
examinations according to recommendations of the ACOG. patients with Krabbe disease were retrospectively analyzed
Results: 38% of patients report an irregular monthly cycle. assessing for ventricular size and presence of STV. A brain
Cycle related behavior changes are shown in Figure 1. 67.5% atlas was used to standardize calculation of ventricular size.
of patients have a history of menstrual manipulation. Per- Mid-sagittal, T2-weighted images around the third ventricle
centages of patients who have met the recommendations of were assessed for STV. Developmental outcomes were mea-
the ACOG for women’s health examinations are shown in sured with a series of standardized tests.
Figure 2. 22.9% of patients who were eligible for the HPV Results: MRI of 75 early and late infantile patients with
vaccine have received it. Krabbe disease were evaluated. Twelve cases of STV were
Conclusions: Patients with RTT experience abnormal hor- identified. Head circumference (SE=8.07; p<0.001) and the
monal cycles that are characterized by irregular menstrual cycles, average ventricular volume (Left: SE=1.47, p<0.001, Right:
dysmenorrhea, behavior changes, and catamenial seizures. Many SE=1.49, p<0.001) were greater in patients with STV.
patients with RTT do not receive well-women examinations Patients with STV had more delayed development in adap-
and HPV vaccinations as recommended by the ACOG. tive (diff=0.2, p<0.01), gross motor (diff=0.0, p<0.01), and
Keywords: Cognitive/Behavioral Disorders fine motor (diff=0.1, p<0.001).

Program and Abstracts, Child Neurology Society S43

FIGURE 1: Head circumference over time among male patients with Krabbe disease, stratified by the presence and absence of STV.
Each point depicts an individual measurement; lines connecting points show multiple measurements for an individual child. The black
line represents the mean curve for typical developing children. Abstract 8 [Color figure can be viewed at www.wileyonlinelibrary.com]

FIGURE 2: Right ventricular volume over time stratified based on the presence and absence of STV. Each point depicts an
individual measurement; lines connecting points show multiple measurements for an individual child. Abstract 8 [Color figure can
be viewed at www.wileyonlinelibrary.com]

Conclusions: STV, likely in the context of increased and resultant STV in patients with leukodystrophies
ICP, were identified in patients with infantile Krabbe such as Krabbe disease where symptoms may be difficult
disease. Though difficult to assess for, our study high- to detect.
lights the importance of monitoring for increased ICP Keywords: Cognitive/Behavioral Disorders

S44 Annals of Neurology Vol 86 (suppl 23) 2019

9. Dissecting the Role of GABAergic Inhibition variation of hospital area in which the patients were evaluated,
from Co-transmitting Inhibitory Interneurons in the i.e., epilepsy monitoring unit versus the emergency department.
Olfactory Bulb The majority of patients (73.5%) returned to the hospital due
Lyons-Warren A (Houston, TX), Hanson E, Arenkiel B to the lack of adequate follow up care.
Objective: Inhibitory interneuron function is disrupted in Conclusions: Our study indicates that patients with FND
many neurodevelopmental disorders including Fragile X, pose a significant healthcare burden primarily due to lack of
Autism spectrum disorder, and Rett syndrome. In order to adequate follow up care. This study reveals a need for devel-
understand how inhibitory interneuron dysfunction contrib- opment of a standardized protocol to be used in the evalua-
utes to neurodevelopmental diseases, it is important to tion, management, and follow-up of patients with functional
elucidate the specific mechanisms by which inhibitory inter- symptoms. Further investigation in this area is needed in
neurons contribute to the encoding of information in the order to facilitate development of such protocols and to
brain. The olfactory bulb is an ideal model system in which address the need for adequate follow up care.
to study the role of inhibitory interneurons. One important Keywords: Cognitive/Behavioral Disorders, Epilepsy
yet poorly understood subgroup of inhibitory interneurons in
the olfactory bulb are short axon cells which release both 11. Expanding the Spectrum of TBCK Mutation in
GABA and dopamine. The objective of this study was to Infantile Hypotonia with Psychomotor Retardation
identify how these co-transmitting inhibitory interneurons in Spivey T (Washington, DC), Moroni I, Cauley E, Saredi S,
the olfactory bulb modulate olfactory coding. Mora M, Manzini M
Methods: We investigated the role of GABAergic inhibition
Objective: Infantile hypotonia with psychomotor retardation
from short axon cells towards olfactory coding using
and characteristics facies 3 (IHPRF3, MIM 616900) is a neu-
optogenetic slice electrophysiology, in-vivo calcium imaging
rodevelopmental disorder with autosomal recessive inheri-
and behavioral measures of olfaction.
tance that often presents in infancy and caused by mutations
Results: Short axon cells make monosynaptic connections onto
in TBC1-domain-containing kinase (TBCK, MIM 616899).
excitatory interneurons but not directly onto projection cells or
IHPRF3 is characterized by global developmental delay with
other short axon cells. Projection cells have mono- and poly-
synaptic feedback connections onto short axon cells. Inhibition severe cognitive and motor deficits, hypotonia, variable dys-
from short axon cells does not significantly alter the spatial morphic facial features, and brain abnormalities. It remained
dynamics of population level olfactory coding. Finally, inhibi- unclear whether the hypotonia in these individuals was purely
tion from short axon cells is not necessary for odor detection or neurogenic, or also caused by muscle disease.
odor preference but may contribute to odor discrimination. Methods: This report discusses two sisters with a novel homozy-
Conclusions: This study identifies novel circuit connections gous truncation in TBCK. Both present with hypotonia, areflexia,
that expand our previous understanding of the inhibitory severe developmental delay, brain malformations, and epileptic
interneuron network in the glomerular layer of the olfactory seizures. Clinical exam was performed on the patients including
bulb and suggests new mechanisms by which inhibitory Brain MRI, muscle biopsy, and TBCK molecular analysis.
interneuron disruption could cause cognitive dysfunction in Results: Brain MRI was performed on each child and
neurodevelopmental disorders. showed abnormalities consistent with TBCK-
Keywords: Cognitive/Behavioral Disorders encephaloneuropathy (TBCKE). Muscle biopsies showed
fiber size variability, and a few degenerating and regenerating
10. Functional Disorders Present an Excessive Burden to fibers in P1. A less severe presentation was seen in P2. TBCK
Healthcare Resources expression analysis was performed by Western blot which
Rao M (Memphis, TN), Jack R, McCoy E, Ledet D, Wheless J showed almost complete protein loss.
Conclusions: This study identifies a novel early truncation in
Objective: To assess healthcare burden created by patients
TBCK that leads to a complete loss of the protein in patient
with functional neurologic disorders (FND).
cell lines and muscle, and to a phenotype consistent with
Methods: Single center, retrospective chart review of
IHPRF3 and TBCKE. A progressive skeletal muscle pheno-
103 patients, ages 8-18 years, who presented with functional
type had been suspected in other cases, and we found myo-
symptoms, filed under the ICD-9 Code R300.1 and the
pathic changes in one of the affected individuals. Our findings
ICD-10 Code F44.5, between the years of 2015-2017. The
add to the variability of phenotypes associated with TBCK
length of a patient’s stay was used as a measure of minimal
mutations, which can be ascribed to the multiple roles of this
resource use during hospital stay.
protein in intracellular signaling and endolysosomal function.
Results: Out of 103 patients (75 females, 28 males, mean age:
Keywords: Cognitive/Behavioral Disorders
14.6 years, and mean length of hospital stay: 31.7 hours)
patients presented most commonly with seizure-like episodes
(n=63), syncopal-like episodes (n=14), or limb 12. Role of Serotonin in Synaptic Signaling and Plasticity
weakness/paralysis (n=9). Length of stay was likely to be shortest in Tuberous Sclerosis
in patients that presented with seizure-like episodes (p= 0.040). Srinivasan R (Chicago, IL), Francesconi W, Berton F, Koster K,
Most children who presented with functional symptoms were Yoshii A
females (72.8%) and presented with seizure-like symptoms. The Objective: Tuberous sclerosis complex (TSC) is a multi-
length of hospital stay had a wide standard deviation due to the organ disease and its neurological symptoms include

Program and Abstracts, Child Neurology Society S45

epilepsy, intellectual disabilities, and autistic behaviors. Sup- Results: Furthermore, daily injection of the serotonin path-
pression of mTOR by rapamycin or its derivatives is one way antagonist rescued the premature death of the mutant
way to correct the pathophysiology of TSC. However, pups. Our results indicate synaptic dysregulation in TSC can
mTOR pathway has multiple roles and rapamycin neither be corrected by modulating serotonergic pathway and set the
specifically nor completely cures all neurological symptoms. stage for developing a new therapeutic approach.
A greater understanding of dysregulated synaptic function Conclusions: TSC- Associated Neuropsychiatric Disorders
will enable identification of specific therapeutic targets for (TAND) is often treated with risperidone, the first FDA-
epilepsy and cognitive disabilities in TSC. approved drug indicated for behavioral problems in autistic
Methods: To identify the cause of these abnormal synaptic patients. Risperidone possesses anti-serotonergic properties.
activities, we conducted an RNA-seq analysis and immuno- Thus, 5HT2C inhibition as a novel, specific therapeutic
blots found an excess of transcripts associated with the seroto- strategy for neurological symptoms of TSC.
nin signaling pathway. The amount of protein was also Keywords: Cognitive/Behavioral Disorders, Genetics, Epilepsy
higher and its intracellular distribution was altered in pyrami-
dal cells of the TSC1 - /- cortex. We used calcium imaging
and found that TSC1 - /- cultured cortical neurons had fre- 13. Cannabidiol use in Autism Spectrum Disorder:
quent Ca 2+ bursts throughout the soma and dendrites that Lessons from the Literature
depended on a specific serotonin pathway while wildtype Yang Brown J (Palo Alto, CA), Fung L, Baumer F
neurons showed random and scattered transients mostly Objective: Cannabis sativa, commonly known as marijuana,
within dendritic spines. contains cannabidiol (CBD) a compound with therapeutic

TABLE 1. Abstract 13
Author,
year Participants CBD Dosing Outcome measure(s) Result(s)

Clinical Schleider, N=188, Mean OCE 1THC:20CBD Symptoms inventory 30% significant improvement
Research 2019 age 12.9 Average dose: 79.5 (sleep, appetite, 54% moderate improvement
mg
61.5 mg concentration) 6.4% slight improvement
Patient global
assessment (quality of
life)
Aran, N=60, Mean OCE 1THC:20CBD Caregiver Global Behavior, anxiety, and communication
2019 age: 11.8 yrs Mean dose: 3.8 Impression of Change (core symptom) showed improvements
(range 5-18) mg/kg/day for TID Home situations Parenting stress improved in 33%
dosing, 1.8 questionnaire-ASD 1 case of psychosis
mg/kg/day for BID Autism Parenting
dosing Stress Index
Barchel, N=53, Median OCE 1THC:20CBD Parental survey of Hyperactivity: 68% improved
2019 age: 11 years Median CBD dose: hyperactivity, sleep, Self injurious behaviors: 67% improved
(4-22) 90 mg (IQR 45-143 self-injurious Sleep: 71% improved
mg) behavior, anxiety
Kuester, N = 20 children, OCE Clinical Global 67% significant improvement on CGI-I
2017 1 adult 1CBD:1THC (71%) Impression of (core symptoms of social
Mean age: 9 yrs High CBD (19%) Improvement communication, language, repetitive
(26 months- High THC (9.5%) Autism Parenting behaviors) and APSI
22 years) Stress Index
Kurz, 1 child with Dronabinol (synthetic Parental report Improvement in hyperactivity, lethargy,
2010 ASD THC) irritability, stereotypy and inappropriate
speech
Animal Kaplan, Murine model of CBD 3 chamber test: DS mice interact with stranger mice less
model 2017 Dravet syndrome 10-100 mg/kg/day measures time spent than WT (DS PR 0.49
0.03, WT PR
(SCN1A+/- mice) interacting in a 0.59
0.02).
N=53 chamber with stranger CBD 20 mg/kg administered 1 hr before
Control: WT mouse (PR) testing increased PR (0.60
0.03, p =
mice N=47 0.0.006) in DS mice, suggesting reversal
of autism-like behavioral deficit.
CBD 50-100 mg/kg did not increase PR
as at lower doses.

CBD = Cannabidiol, THC = tetrahydrocannabinol, OCE = Oral cannabis extract, WT = Wild type, PR = Preference Ratio

S46 Annals of Neurology Vol 86 (suppl 23) 2019

indication for multiple neurologic disorders. There is great
interest in CBD as a therapy for behavioral comorbidities
associated with autism spectrum disorder (ASD). We review
the existing literature of CBD in ASD.
Methods: PubMed, EMBASE, Web of Science, and
Cochrane databases were searched from inception through
March 31, 2019. Search terms included cannabinoids,
cannabidiol, marijuana, autism, autism spectrum disorder,
and Asperger. We reviewed studies of CBD as a treatment
for core symptoms of ASD or behavioral comorbidities. We
excluded editorials, ethics pieces, and investigations of mech-
anism of action or endocannabinoid physiology.
Results: Six studies met inclusion criteria. Studies in humans
included 1 case report and 4 large descriptive studies. Only
the animal study had a control arm. Results summarized in
Table 1. The animal study showed improved social interac-
tions with CBD 20 mg/kg but not sustained at the higher
dose 100 mg/kg to treat seizures. The human studies report
descriptive statistics of improvement in a variety of associated
symptoms, quality of life, and parental stress. 2 studies
FIGURE 1: Abstract 14 [Color figure can be viewed at www.
reported improvements in core symptoms of ASD: communi-
wileyonlinelibrary.com]
cation and repetitive behaviors. Most common side effects
included somnolence, appetite loss, and 1 case of psychosis.
Conclusions: Several small, descriptive studies of CBD in Conclusions: Although children with ASD make similar
ASD have found improved behavioral symptomatology at practice-related gains in imitation over the course of 4 repeti-
lower doses than needed for epilepsy management; the side tions of novel gesture imitation, the internal shape of the
effect profile at these doses has been relatively favorable. Of learning curves differ in a way that relates to both to social
note, studies rarely focus on the core symptoms of ASD. and motor skill.
Randomized clinical trials are ongoing. Keywords: Cognitive/Behavioral Disorders, Movement
Keywords: Cognitive/Behavioral Disorders Disorders

14. Altered Learning Via Imitation in Autism 15. Epilepsy, Autism Severity and Regression
Zhao Y (Baltimore, MD), Caffo B, Mostofsky S, Ewen J Ewen J (Baltimore, MD), Lipkin P
Objective: Autism spectrum disorder (ASD) is considered a Objective: Epilepsy is known to occur more often than
neurodevelopmental disorder, yet it is not clear how devel- expected in individuals with autism spectrum disorders
opmental processes affect the trajectory of the disorder. We (ASD). Prior studies have suggested that IQ may drive this
have hypothesized that both core social and highly preva- relationship. Because intellectual disability (ID) is an inde-
lent motor deficits in the disorder reflect impaired skill pendent risk factor for epilepsy, there is controversy about
learning. the long-understood unique relationship between ASD and
Methods: 18 participants with high-functioning ASD and epilepsy. Additionally, decades of results have failed to clarify
19 typically developing (TD) controls, aged 8-12, watched a the relationship between developmental regression in ASD
video of a unimanual, meaningless gesture and then copied and the risk for epilepsy.
it. The video and imitation were repeated a total of 4-6 times Methods: From 6,975 participants with ASD in two cohorts
per gesture. 8 gestures were scored. Dependent variables were from an online research registry, we examined the indepen-
% gestures performed correctly at repetitions 1-4. dent role of four different measures of ASD severity measures
Results: Children with ASD had a downward translation of imi- in driving the relationship with epilepsy: ID, language
tation performance curve, but similar trajectories (Fig. 1). Mar- impairment, core ASD symptom severity, and motor dys-
kov models assessing learning from one repetition to the next function, adjusting for two factors known to be relevant to
showed greater learning in TDs from repetition 2 to 3, but chil- the ASD-epilepsy relationship (age, sex). We also examined
dren with ASD began to "catch up" by repetition 4. Learning whether developmental regression and epilepsy have an inde-
curve shape was a strong predictor of tool use and communica- pendent statistical relationship.
tive gesture praxis (via the Florida Apraxia Battery, modified for Results: While ID showed the largest relative risk (RR) for
children; Cohen’s d=.90;p=.010); and was a moderate predictor epilepsy in both cohorts, all other ASD severity markers
of ASD severity (Autism Diagnostic Observation Schedule; d=- showed statistical associations in one cohort and all but one
.67;p=.038) within participants with ASD. The effect of learning in the other. These results demonstrate that the ASD-epilepsy
curve shape on praxis was large (d=1.24;p<.001); the effect on association is not reducible to the effect of ID. Effect sizes
diagnosis (binary) was moderate (d=-.68;p=.001) in the pooled were modest. Regression similarly showed an independent
sample. statistical association with epilepsy, but with small effect size.

Program and Abstracts, Child Neurology Society S47

Conclusions: Prior inconsistencies in the literature may be Further, there was an effect of diagnosis on the association of
due to underpowered studies, yet moving forward with alpha ERD with MEP up-modulation: for TD, less ERD was
larger-n studies, clinical significance and scientific relevance associated with greater MEP up-modulation (p<0.0001),
may be dictated by effect size and not merely statistical whereas for ADHD less ERD was associated with less up-
significance. modulation (p<0.0001) (Fig. 1).
Keywords: Cognitive/Behavioral Disorders, Epilepsy Conclusions: The findings reveal that children with ADHD
show a fundamentally different relationship between alpha-
16. Differing Relationship Between Task-Related TMS ERD-measured M1-cortical activation and cortical activation
and EEG Measures of Cortical Activation in ADHD and as measured by task-related MEP up-regulation. Unexpect-
Controls edly, TDs showed an apparently inverse relationship between
Ewen J (Baltimore, MD), Mostofsky S, Horn P, Gilbert D task-related changes as assessed with ERD and TMS.
Keywords: Cognitive/Behavioral Disorders, Movement
Objective: Children with ADHD show developmentally
Disorders
abnormal motor function as well as primary motor cortex
(M1) physiology measured using Transcranial Magnetic
Stimulation (TMS) and EEG. Central alpha-band
(mu) event-related desynchronization (ERD) reflects motor
cortical activation. Task-related modulation of motor-evoked
potentials (MEPs) during TMS is understood to reflect a CRITICAL CARE
shift in the balance of inhibitory and excitatory inputs
into M1.
Methods: EEG was acquired during right-hand sequential 17. Critical Role for the Thalamus, Corpus Callosum and
finger-tapping; left-central alpha-ERD was calculated. During Basal Ganglia in Pediatric TBI: Results of a Longitudinal
a stop-signal reaction-time task, TMS was applied to left M1 Imaging Study
with MEP amplitudes measured in the right hand at rest and Ashwal S (Loma Linda, CA), Pivonka-James J, Nichols J,
during task (action selection) states. Mixed model regression Oyoyo U, Barnik-Olson B, Tong K, Holshouser B
was used with MEP amplitudes as the outcome and diagno- Objective: MR spectroscopic imaging (MRSI) and Diffusion
sis, task-state, pulse type, and ERD as factors. Tensor Imaging (DTI) are useful in assessing injury
Results: 14 children with ADHD (8M, mean age=10.7y) location/severity after TBI to predict neuropsychological out-
and 17 typically developing (TD) controls (13M, mean comes. Attention has focused on the thalamus, corpus cal-
age=10.9y) participated. TD children showed greater alpha- losum and basal ganglia as mediators of cognitive
ERD (p=0.03) and greater MEP up-modulation from rest to impairments because of their role in brain connectivity. We
task states (p<0.0001) than did children with ADHD. correlated acute/long-term imaging with 12mo. NP data.

FIGURE 1: Abstract 16 [Color figure can be viewed at www.wileyonlinelibrary.com]

S48 Annals of Neurology Vol 86 (suppl 23) 2019

Methods: We examined 63 mod/sev TBI (6-17d and 1yr) time as compared to outpatient studies suggests that patients
and 64 controls with 3D-proton MRSI (NAA/Cr etc) from admitted to a pediatric trauma service are also at risk for pro-
7 regions (BG, ant/post CC, frontal/parietal/temporal-white longed recovery. These findings suggest additional criteria
matter, thal). A subset (30 mod/sev TBI; 38 controls) under- need to be included in anticipatory guidelines for pediatric
went DTI (FA/MD/AD/RD). Memory, attention, patients recovering from TBI.
FSIQ/PIQ were assessed at 3mo/1yr. Keywords: Critical Care, Headache/Migraine
Results: In mod-TBI, metabolite ratios normalized to control
levels at 12mo. In mod-TBI, DTI initially showed decreased 19. Association Between Glasgow Coma Scale Scores with
FA and increased MD/AD/RD that further increased region- and without the Verbal Component and Intubation in
ally at 12mo. In sev-TBI, early reduced NAA/Cr was seen in Critically-Ill Children
most regions and remained reduced subcortically Girkar U (Sunnyvale, CA), Palacios R, Gupta A
(TH/BG/CC) at 12mo. FA/MD/AD/RD showed changes in
Objective: Studies have shown that the verbal component of
sev-TBI in most regions at 12mo. with few changes initially.
the Glasgow Coma Scale (GCS), used to assess consciousness,
Acutely, in sev-TBI, reductions in NAA/Cr, FA/AD from all
cannot often be assessed properly if the patient is intubated.
regions correlated with 12mo. memory deficits, FSIQ, and
We sought to understand if poor neurological function with
PIQ; only a reduction in BG NAA/Cr correlated with 12mo.
and without the verbal score differs in correlation to intuba-
memory in mod-TBI. Early reduced NAA/Cr from
tion in critically ill children.
BG/TH/CC strongly correlated with 12mo. DTI in multiple
Methods: We obtained our data from the large, multi-center
white matter regions.
telehealth Philips eICU-Collaborative database. We defined
Conclusions: rly NAA reductions (TH/CC/BG) that persist
vitals as abnormal if the values of temperature, mean blood
suggest that early prolonged metabolic dysfunction contrib-
pressure, or heart rate deviated from the APACHE-defined
utes to long-term white matter abnormalities. As mitochon-
midpoint by 2, 40, and 25 respectively. We defined poor neu-
dria play a role in NAA synthesis and neuronal metabolism,
rologic function as a GCS score less than 8 and less than 6 if
our findings suggest that mitochondrial dysfunction in cen-
the verbal component was excluded. We computed intubation
tral brain structures may be pivotal as they are major hubs
rates for children younger than 18 demonstrating poor neuro-
for brain networks.
logic function with and without the verbal component consid-
Keywords: Critical Care, Neuroimaging
ering all patients and just patients with abnormal vitals.
Results: When all the patients were considered, intubation
18. Factors Influencing Pediatric Recovery from rates were 0.60 and 0.605 with and without the verbal com-
Traumatic Brain Injury ponent respectively. When only patients with abnormal vitals
Feldman A (Hershey, PA), Thomas S, Hess J, Lewis M, were considered, intubation rates were 0.605 and 0.595 with
Engbrecht B, Shirk B, Bramley H and without the verbal component respectively.
Objective: Many factors have been linked to prolonged Conclusions: Despite studies demonstrating difficulties in
recovery from traumatic brain injury (TBI) in the pediatric verbal score assessment due to intubation, these results pro-
population, such as female gender, multiple previous head vide evidence that the correlation between intubation rates
injuries, concurrent mood disorders, post-concussive sleep and poor neurologic function does not differ based on con-
disturbance, and presentation at initial injury. The goal of sideration of the GCS score with and without the verbal
this study was to investigate these risk factors to aid anticipa- component. Future work can further investigate the integrity
tory guidance and treatment strategies. of the verbal component for use in statistics-based clinical
Methods: A retrospective chart review was conducted utiliz- decision making.
ing patients admitted to a pediatric trauma service at a Level Keywords: Critical Care
1 Pediatric Trauma Center. 133 patients met the inclusion
criteria consisting of patient demographics, mechanism of
injury, Glasgow Coma Score (GCS), past medical history, 20. Continuous EEG for Seizure Detection in Neonates
long term sequelae, and recovery time. after Cardiac Bypass without Deep Hypothermic Cardiac
Results: No significant difference in recovery time was found Arrest
based on acute injury severity as graded by initial GCS and Levy R (Palo Alto, CA), Purington N, Kaimal R, Iqbal M,
presence of intracranial hemorrhage (ICH). Patients with Mayne E, Sandoval Karamian A, Ryan K, Wusthoff C
post-concussive sleep disturbances and comorbid mood disor- Objective: The American Clinical Neurophysiology Society
ders showed an increased median recovery length. The overall suggests continuous EEG (cEEG) for seizure detection after
median recovery time was longer as compared to outpatient neonatal surgery involving cardiopulmonary bypass (CPB).
studies. Early reports described seizures in >20% of children after
Conclusions: This study verified that GCS and ICH are not CPB, with recent estimates ranging 3-12%. Seizures have
good prognostic markers for recovery time for pediatric been associated with deep hypothermic cardiac arrest
patients with a TBI who are discharged from the hospital to (DHCA), bypass duration, and age. This study characterizes
home, whereas sleep disturbances and comorbid mood disor- seizure prevalence in a neonatal cohort after CPB without
ders are strong prognostic factors. A longer median recovery standard DHCA.

Program and Abstracts, Child Neurology Society S49

Methods: Single-center chart review of all infants from July 22. Too Much of a Good Thing? Cerebral Venous Sinus
2017 through February 2019 monitored with cEEG for Thrombosis Due to Excessive Milk Intake-Associated
48 hours after CPB, as per institutional guideline. Clinical Anemia
and EEG variables were recorded for univariate and multivar- Siddiqui S (Milwaukee, WI), Mondok L, Farias-Moeller R
iate analyses. Objective: To review a case series of toddlers presenting with
Results: 10 of 91 (11%) patients had seizures on cEEG; cerebral venous sinus thrombosis (CVST) in the setting of
4 (40%) had status epilepticus. All 10 had subclinical sei- acute dehydration and iron-deficiency anemia (IDA) from
zures; 2 (20%) also had electroclinical seizures. Median time excessive milk consumption.
from bypass end to first seizure was 30.9 hours [IQR 22-34 Methods: This was an observational retrospective case series
hours, range 8-52 hours]. Only 2 patients underwent of 3 patients collected between 2017-2019 selected for pres-
DHCA; neither had seizures. Bypass time was significantly ence of CVST, IDA (Hgb < 7, MCV <60, iron <20, ferritin
longer in patients with seizures than those without < 4), and excessive milk consumption.
(178.5 min vs. 148 min, p=0.038).
Conclusions: Seizure prevalence in our cohort was analogous
to other reports, despite minimal DHCA in our group.
Among infants with seizures, time to first seizure ranged from
8-52 hours after end of CBP, suggesting a window of highest
yield for cEEG. Longer bypass time was associated with
increased risk of seizure.
Keywords: Critical Care, Epilepsy, Neonatal Neurology

21. Acute Fulminant Cerebral Edema: A Profile of

5 Pediatric Cases from a Tertiary Care Center
Patterson Gentile C (Philadelphia, PA), Hardy D, Agarwal S
Objective: Fulminant cerebral edema is a poorly understood
serious neurologic condition with a high fatality rate. The
objective of this case series is to compare the presenting fea-
tures, time course, underlying etiology, and management of
5 pediatric patients presenting with fulminant cerebral
edema.
Methods: We review a case series of five pediatric patients
who presented with fulminant cerebral edema at Children’s
Hospital of Philadelphia between 2018 and 2019. Patients
were included if they presented with acute encephalopathy FIGURE 1: Abstract 22
defined as rapid deterioration in mental status, and had neu-
roimaging evidence of fulminant cerebral edema.
Results: Five patients, two females and three males between
2 to 7 years old, were included in this case series. All patients
had prodromal symptoms. Two patients were positive for
influenza, and one patient had neuropathology consistent
with acute hemorrhagic leukoencephalitis on autopsy. In two
cases, no cause was identified. Treatments included broad
spectrum antibiotics, hyperosmolar agents, IV steroids, man-
agement of seizures with anti-convulsive agents, and
decompressive craniectomy. Four patients died, and one
patient had a good outcome.
Conclusions: Acute encephalopathy complicated by fulmi-
nant cerebral edema is a rapidly evolving, and often fatal neu-
rologic condition. While flu was the most common etiology,
more than one etiology was present in the case series consis-
tent with previous assertions that fulminant cerebral edema is
a common pathophysiologic endpoint to multiple disease
processes. Early identification with neuroimaging and inter-
vention may improve outcomes, and steroids may have pro-
vided benefit in the patient who survived. However, the
rapid course of the disease poses continued challenges.
Keywords: Critical Care, Epilepsy, Neuroimaging, Rare
Diseases FIGURE 2 Abstract 22

S50 Annals of Neurology Vol 86 (suppl 23) 2019

Results: 3 cases are reviewed. Patient 1: 17-month female pre- Conclusions: Cosyntropin-treated CCI animals showed
senting with acute right sided weakness and decreased oral reduced morphological changes in microglia suggesting a
intake. Extensive thrombus of the superior sagittal sinus, bilat- reduced activation state. Cosyntropin may decrease microglial
eral cortical veins, and proximal left transverse sinus was identi- activation and neuroinflammation through melanocortin
fied. Severe IDA was identified. Milk intake was 35-40 oz receptor signaling and result in improved functional outcome.
daily. Patient 2: 24-month healthy female presenting with Keywords: Critical Care, Infections/Neuroimmunology,
1 day of aphasia and headache. Occlusive thrombus of bilateral Translational/Experimental Therapeutics
internal cerebral veins, vein of Galen and straight sinus and
ischemic infarcts of bilateral thalami, left caudate, and bilateral
centrum semiovale were identified. Severe IDA was identified.
Milk intake was 1 gallon every 3 days (~43oz daily). Patient 3: DEMYELINATING DISORDERS
24-month female presenting with 1 day of emesis and aphasia.
Partially occlusive thrombus of the inferior sagittal sinus, bilat-
eral internal cerebral veins, vein of Galen, straight sinus, tor- 24. Characteristics of Children with Demyelinating
cula, bilateral medial transverse sinuses and bithalamic Disorders with Myelin Oligodendrocyte Glycoprotein
ischemic infarcts were identified. IDA was identified. Milk (MOG) Antibodies
intake was 40-60 oz daily. All patients received standard anti- Chong J (San Francisco, CA), Wiltrout K, Lui A,
coagulation; patients 2 and 3 also received intravenous iron. Rutatangwa A, Krysko K, Waubant E, Mar S
All patients had a return to baseline by discharge. Objective: The relevance of MOG antibody to pediatric
Conclusions: This study highlights the risk of CVST in tod- demyelinating disorders and its role as a discrete syndrome is
dlers with IDA from excessive milk consumption. debated, and subsequently, so are the optimal treatment strat-
Keywords: Critical Care, Epilepsy, Neuroimaging, Stroke egies for MOG antibody patients. We aim to characterize
children with CNS demyelinating disorders who tested posi-
23. Melanocortin Agonist Reduces Microglial Activation tive for MOG antibody.
and Neuroinflammation Following Experimental Methods: This descriptive study evaluated children with
Traumatic Brain Injury demyelinating disorders seen at UCSF and Washington Uni-
Siebold L (Loma Linda, CA), Wilson C, Abdala J, Bartnik- versity who were systematically tested for MOG antibodies in
Olson B, Figueroa J, Holshouser B, Vega-Torres J, Tone B, the past 23 months. Demographic data, clinical course, and
Ashwal S treatment were collected.
Results: 24 MOG antibody positive children were identified
Objective: Traumatic brain injury (TBI) is a leading cause of
(58% female). Median age at onset was 7.8 years (range
mortality/morbidity and is associated with chronic neu-
1.7-16.5). 11 children had high titers (1:1000), 10 had medium
roinflammation. Melanocortin receptor (MCR) agonists
titers (1:100), and three had low titers (1:40). Nine had repeat
(e.g., ACTH or adrenocorticotropic hormone) that target
testing: seven remained positive, while two became MOG anti-
MC3R/4R ameliorate inflammation and provide a novel thera-
body negative. Upon re-testing, all initial high titers decreased,
peutic approach. Following TBI, quiescent microglia become
and one with a moderate titer remained unchanged. Clinical
activated resulting in anti and pro-inflammatory responses and
presentation at onset included isolated optic neuritis (n=10),
morphological changes. We examined the effect of Cos-
none had isolated transverse myelitis, and 14 had other initial
yntropin (synthetic ACTH) administration on microglial acti-
presentations, including eight with encephalopathy. 19 children
vation in a rodent TBI model. We hypothesized that
had abnormal brain MRI at onset. For the first event, 21 were
Cosyntropin administration would reduce inflammation and
treated with at least three days of pulse high dose steroids, and
microglial activation following experimental TBI in rats.
one was treated with IVIG. At least 10 patients with recurrent
Methods: We used a rodent model of CCI randomized to
events and varying final diagnoses initiated disease-modifying
4 groups: sham-vehicle, sham-cosyntropin, CCI-vehicle, and
therapy. During follow-up, 12 of the 24 children relapsed.
CCI-Cosyntropin. Subcutaneous injections of Cosyntropin
Conclusions: Varying pediatric demyelinating presentations
(West Therapeutic Development; Grayslake, IL) were given
can have positive MOG antibodies. MOG antibody titers
for 7 days following injury. Microglia activation was quantified
can decrease or revert to negative.
based on morphology. Sectioned brains were immunostained
Keywords: Demyelinating Disorders
(Iba1) and imaged followed by morphological quantification
with FIJI and FracLac for ImageJ. Parameters included cell
area, fractal dimension, circularity, cell perimeter and density. 25. Anxiety, Depression and Fatigue in Youth with Mog-
Cytokine expression was compared between groups. Associated Neuroinflammation: A Preliminary Report
Results: CCI animals exhibited increased microglia in the Ciftci-Kavaklioglu B (Toronto, Ontario, Canada), Longoni G,
lesion site with no difference in cell count between vehicle Grover S, Yea C, Yeh EA
and treated. Microglia from CCI animals exhibited no Objective: To report the prevalence of anxiety, depression
change in cell area, decreased cell perimeter and increased and fatigue in youth with MOG-positive compared to those
density and circularity compared to sham animals. Cos- with MOG-negative demyelinating syndromes.
yntropin treatment altered CCI-induced microglia changes in Methods: This was a cross sectional analysis of prospectively col-
cell area, cell perimeter, and cell density. lected data. Cell based assay was used to test for MOG-IgG and

Program and Abstracts, Child Neurology Society S51

persistent positivity was defined as a positive result >6 mo from Methods: NeuroQL and PROMIS questionnaires were given pro-
onset and negative serostatus was defined as a negative result at a sin- spectively to parent proxy or patients with pediatric-onset RRMS
gle timepoint. Participants completed the SCARED questionnaire during routine follow-up care from July 2017 – April 2019.
for anxiety, CES-DC for depression, PedsQL MFS for fatigue. Results: 16 participants (9 female) completed 28 questionnaires.
Results: Twenty-seven (F=18) patients with MOG+ and Average length of treatment on study was 6.4 months (SD 5.9,
45 (F=25) patients with MOG- demyelination were included in median 5.5). 7/16(43%) started an injectable or oral therapy and
the analysis. There was no statistically significant difference escalated to an infusion. 4/7 (57%) completed questionnaires
between the groups in terms of gender, median age at question- before and after the switch. 5/16(31%) started with an infusion
naire completion, or median time since first event. Total anxiety and did not switch medications. 2/16(12.5%) received injectable
score was a median of 13 (IQR 17.5) in the MOG+ and or oral therapy only. 2/16(12.5%) had no DMT. Participants
15(IQR 16) in the MOG- group (p=0.56). Total depression starting oral or injectable treatment who did not escalate therapy
score was a median of 8(IQR 13) in MOG+ and 11(IQR 15) in reported above average QoL in all domains that remained stable.
MOG- group (p=0.15). Total fatigue score was lower in the Participants who started with infusions reported below average
MOG+ group with a median of 17(IQR 15.5) compared to the psychological and cognitive function, with physical domains
MOG- group with a median of 27(IQR 16, p=0.01). Bivariate above average; in one case QoL decreased over time. When par-
correlation analyses revealed a moderate positive monotonic ticipants escalated therapy to infusion, there was usually physical
association between anxiety and depression scores (r=0.55, improvement but not psychological improvement. 2 participants
p=0.01 in MOG+ and r=0.66, p=1.02x10-6 in MOG- group), with scores at 8 and 10 months, respectively, after escalation
and anxiety and fatigue scores (r=0.67, p<0.001 in MOG+ and reported worse pain, fatigue, anger, anxiety, depression, and
r=0.64, p=2.06x10-6 in MOG- group). emotional and behavioral dysfunction. In one participant with
Conclusions: Persistent MOG-IgG positivity is not associ- 18 month follow-up all domains improved.
ated with an increased prevalence of anxiety or depression Conclusions: MS patients are motivated to complete Neu-
compared to MOG-IgG negative participants. Fatigue how- roQL and PROMIS questionnaires. Patient-reported QoL
ever is less severe among MOG-positives. does not necessarily correlate with DMT choice or physical
Keywords: Demyelinating Disorders function. Larger numbers of participants, more attention to
psychological QoL and longer follow-ups are needed.
26. Impact of Disease Modifying Therapy on Quality of Keywords: Demyelinating Disorders
Life in Pediatric Multiple Sclerosis
Doslea A (Washington, DC), Parker M, Suslovic W, Ball L, 27. Imaging Negative bilateral Internuclear
Fleming M, Sady M, Wells E, Khan I Ophthalmoplegia (INO) in a 14-year old female
Objective: Evaluate the impact choice of disease modifying Osman M (Boston, MA), Ejaz L, Santoro J, Waite S
therapy (DMT) has on quality of life (QoL) in pediatric- Objective: Internuclear ophthalmoplegia (INO) is the most
onset Relapsing Remitting Multiple Sclerosis (RRMS). common eye abnormality observed in multiple sclerosis

FIGURE 1: MRI Images. Abstract 27 [Color figure can be viewed at www.wileyonlinelibrary.com]

S52 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 2: Eye Movements. I Written consent was obtained from the family to be published. Abstract 27 [Color figure can be
viewed at www.wileyonlinelibrary.com]

(MS). One-third of the cases of INO are caused by MS and findings. Surveillance imaging will be needed moving forward
it is the most common cause in a young person. The deficit to determine if this indeed is consistent with early MS, par-
is bilateral in 73 percent of cases1. Insults localize to the ticularly in light of negative workup.
medial longitudinal fasciculus (MLF). Keywords: Demyelinating Disorders, Infections/
Methods: We report a case of a 14 yo female who presented Neuroimmunology, Neuroimaging
with one day of horizontal diplopia, found to have a bilateral
INO on evaluation.
Results: On exam, bilateral INO was present in association 28. A Stroke Mimic: MOG Antibody Encephalomyelitis
with a LMN pattern right facial droop and improvement of Presenting as Acute Hemiparesis
the eye adduction bilaterally with convergence, localizing the Tutmaher M (Boston, MA), Chen D, Hallman-Cooper J,
lesion to the MLF. An extensive work up for central and Holt P, Philbrook B, Gombolay G
peripheral causes including two neuroaxis MRIs, EMG/NCS, Objective: Myelin oligodendrocyte glycoprotein (MOG) is a
CSF and serum studies were negative. Slow improvement protein expressed as part of the myelin sheath. Anti-MOG
was noted on hospital day 3, examination consistent with antibodies (MOG-ab) can be seen in CNS demyelination,
eight and half syndrome. She was started on empiric IV and has been proposed as a distinct entity with varying clini-
methylprednisolone for presumed inflammatory etiology and cal manifestations. We aim to expand our knowledge of the
had continued improvement and eventual resolution of clinical presentations of MOG-ab by describing a case report
symptoms after 7 days. of MOG-ab encephalomyelitis presenting as a stroke mimic
Conclusions: Our patient was diagnosed with MRI negative with acute onset hemiparesis and respiratory failure.
clinically isolated syndrome presenting with a bilateral INO. Methods: Retrospective review of the clinical history, neuro-
While a central lesion was expected with the degree of defi- logical exam, laboratory studies, neuroimaging, and electroen-
cits, neuro-diagnostic evaluation was negative. Adult cases cephalogram (EEG) was performed.
report 4% recurrence risk in MRI negative CIS in the Results: 11-year-old girl presented with sudden worsening of
absence of oligoclonal bands. The authors are not aware of headache, dysarthria, acute right facial droop, right
similar cases in pediatric patients with these brainstem hemiparesis, and respiratory failure requiring intubation

Program and Abstracts, Child Neurology Society S53

FIGURE 1: T2 FLAIR post contrast. Abnormal leptomeningeal enhancement predominately in the frontal and parietal regions of
the left cerebral hemisphere with associated mild cortical edema. Abstract 28

FIGURE 2: EEG showing continuous, diffuse, delta slowing of the background with focal slowing over the left hemisphere.
Continuous, diffuse, delta slowing of the background with superimposed faster frequencies, with superimposed focal slowing
over the left hemisphere. Abstract 28 [Color figure can be viewed at www.wileyonlinelibrary.com]

preceded by 2 days of intermittent headache and dizziness. Conclusions: There is wide variability among clinical presen-
NIHSS was 31. Toxicology screening negative. CBC and tations of MOG-ab encephalomyelitis, which should be
chemistries unremarkable. MRI brain with and without considered when evaluating for stroke mimics.
contrast was negative for stroke but demonstrated Keywords: Demyelinating Disorders, Infections/
leptomeningeal enhancement in the left frontal and parietal Neuroimmunology
regions with associated mild cortical edema (Figure 1). EEG
demonstrated focal slowingover the left hemisphere (Figure 2). 29. Clinical Presentation of Metachromatic
Lumbar puncture with CSF WBC 8 (56% segs), protein 28. Leukodystrophy
Her strength recovered within 24 hours with residual confu- Adang L (Philadelphia, PA), Groeschel S, Patel K, Cross Z,
sion and mild aphasia. She also was intermittently febrile Elguen S, Kehrer C, Kraegeloh-Mann I, Sherbini O, Kramer-
(Tmax 39 C). Infectious studies including HSV PCR and Golinkoff K, Stutterd C, Shults J, Vanderver A
Mayo encephalopathy panels (serum and CSF) returned nega- Objective: Metachromatic leukodystrophy (MLD) is a rare,
tive. However, MOG-ab was positive at 1:40 in the serum lysosomal storage disorder caused by decreased enzymatic
(nl <1:20). She was treated with IVIG with improvement. activity of arylsulfatase A. This can be the result of

S54 Annals of Neurology Vol 86 (suppl 23) 2019

mutations in the ASA gene. Historically, MLD has been cause disease with contrast enhancement on MRI. The
subdivided into 3 forms based on age of onset: late infantile, most common biological function of the genes was
juvenile, and adult. The age-based historical definitions do involvement in metabolic processes. Pathway analysis
not fully account for the spectrum of disease and are not showed involvement of 23 major pathways, with a large
founded in evidence-based analysis of phenotypic cohorts. number of genes involved in immune system and meta-
Additionally, the antiquated definitions do not fully predict bolic pathways.
presenting features or disease course, and they fail to stratify Conclusions: We uncovered hundreds of genes, previously
outcomes in the few therapies currently available to treat underrecognized to the leukodystrophy community, associ-
this disease. As novel targeted therapeutics are developed, it ated with white matter changes on MRI. Previously, only
is essential to have a clear understanding of the clinical pre- ~30-60 genes were considered as leukodystrophies. We also
sentation and natural history of MLD. Without properly identified shared pathways and mechanisms potentially impli-
defined sub-populations, it is difficult to design a therapeu- cating directions for future treatment.
tic clinical trial that can demonstrate efficacy in a heteroge- Keywords: Demyelinating Disorders, Rare Diseases
neous group.
Methods: We collected the retrospective natural history of 31. High Leukodystrophy Incidence Discovered Using
over 100 individuals from around the world. We created an Genomics Database Allele Frequency Determinations
electronic database in REDCap to able to longitudinally col- Soderholm H (Salt Lake City, UT), Chapin A, Bayrak-
lect clinical information. Toydemir P, Bonkowsky J
Results: Using this retrospective natural history approach to Objective: Leukodystrophies are rare neurological diseases
understanding the disease course of individuals affected by and the incidence has been difficult to determine. An esti-
MLD, we were able to characterize age of onset, delay to mate of 1:7,663 live births was calculated in 2010 from a
diagnosis, and common presenting features. Our results sug- Utah-based clinical population. Our purpose was to obtain
gest distinct clinical phenotypic subgroups. an improved estimate using whole-genome and exome
Conclusions: With a better understanding of the natural his- sequencing data to find the allele frequencies of
tory of MLD, we will be able to better counsel families and leukodystrophy-causing mutations in the population.
to design clinical trials with more coherent cohorts and more Methods: Using 30 previously defined canonical leukodys-
appropriate clinical endpoints. trophy causing genes, we used the Human Genetic Mutation
Keywords: Demyelinating Disorders, Genetics, Rare Database of previously published pathogenic mutations seen
Diseases in publications, together with loss of function truncating vari-
ants from the gnomAD database. We filtered the mutations
30. Revised Identifications Reveals Hundreds of to incorporate only high-confidence pathogenic variants and
Leukodystrophy Genes gathered the accompanying allele frequency data from
Soderholm H (Salt Lake City, UT), Urbik V, Schmiedel M, gnomAD. We then used the Hardy-Weinberg equation to
Bonkowsky J calculate a recessive allele frequency.
Objective: Definitions of leukodystrophies have been a con- Results: We obtained an estimate of approximately 1:1,800
tentious issue, which may limit progress on utilizing next- live births. Further examination of the subgroups revealed a
generation sequencing approaches for diagnosis. The pur- potential under-diagnosis within specific leukodystrophies,
pose of this study was to use a broad review of available such as Krabbe Disease and an increase in prevalence within
sources to provide an updated and expanded understanding certain racial subgroups.
of the different genes involved in leukodystrophies. A sec- Conclusions: Using the allele counts of pathogenic variants
ondary objective was to identify shared pathways and mech- of leukodystrophies in the population, we have determined a
anisms that might reveal novel genes that could be conservative incidence of leukodystrophies of 1:1,800 live
implicated in leukodystrophies with the goal of identifying births. This is a dramatic increase compared to previous
common mechanisms of disease with implications for determinations. This suggests significant underdiagnosis,
treatment. altered phenotypic presentations, or the presence of disease-
Methods: We conducted a search using keywords “leukodys- modifying genes.
trophy” or “leukoencephalopathy,” including of PubMed, Keywords: Demyelinating Disorders, Genetics, Rare
Google, published literature reviews, and commercial gene Diseases
panels. Inclusion required a published report of abnormal T2
white matter signal abnormality on brain MRI. Exclusion 32. A Zebrafish Model of Vanishing White Matter
criteria included any white matter change secondary to non- Disease Reveals Novel Pathology Involving Intron
genetic cause, including traumatic and autoimmune etiolo- Retention, and a Downstream Role for HSPD1 in Myelin
gies. Following review and manual curation, genes were char- Maintenance
acterized and grouped. Soderholm H (Salt Lake City, UT), Keefe M, Stevenson T,
Results: We identified 409 unique genes with white Stephenson D, Glaittli K, Scholl E, Bonkowsky J
matter MRI pathology in humans. 21% of these genes Objective: Vanishing White Matter (VWM) is an autosomal
were hypomyelinating. Only 2 genes were reported to recessive form of leukodystrophy for which there is currently

Program and Abstracts, Child Neurology Society S55

no treatment. VWM is caused by genetic mutations in the
five subunits of the eukaryotic translation initiation factor 2B
(eIF2B). The overall purpose of our study was to develop a
zebrafish model of VWM.
Methods: We used CRISPR to generate mutations in the
eif2B subunits. We characterized the phenotypes through
immunohistochemistry, in-situ hybridization, qRT-PCR,
behavior analysis, and developed a new technique to measure
myelin levels, a zebrafish MRI. We generated a rescue with
the human version of the mutated gene. Lastly, we tested var-
ious drug compounds for treatment.
Results: We show a conservation of function between
zebrafish and humans for the eif2B complex and recapitulate
the clinical phenotypes of VWM with an increase in apopto- TABLE 1: Clinical Characteristics. DD/ID: Developmental
tic oligodendrocytes. We see behavioral deficits and a loss of Delay/Intellectual Disability. HS: Hypsarrythmia, GS:
white matter in the brain. Additionally, we see an increase in Generalized Spikes , SAS: Subarachnoid spaces. Abstract 33
the expression of the gene hspd1, a known leukodystrophy [Color figure can be viewed at www.wileyonlinelibrary.com]
causing gene, and a retention of intron 12 in the eif2B5 sub-
unit, indicative of a stress response further inhibiting transla-
tion creating a potential mechanism for disease progression.
We also found a compound that alleviates apoptosis seen in Conclusions: A founder effect in a specific population in
VWM in zebrafish. southern Puerto Rico is a probable explanation for a higher
Conclusions: We have created a VWM zebrafish model incidence of EEIE-37, in our patients with a very homoge-
accurately recapitulating the human disease. We discovered a nous phenotype of severe developmental delay, intractable
potential drug therapy for VWM. Lastly, we propose a model epilepsy, and movement disorders.
for how VWM mutations in the eIF2B complex specifically Keywords: Epilepsy, Genetics, Rare Diseases
affect white matter.
Keywords: Demyelinating Disorders, Translational/Experi- 34. Retrospective Review of EEG Monitoring, Seizure
mental Therapeutics Management, and Outcomes in a Neonatal ICU Over a
2-year Period
Abreu Molnar D (Miami, FL), Frade-Garcia A, Jayakar A
Objective: Seizures are common in neonates and can be diffi-
EPILEPSY cult to treat, often resulting in significant morbidity. Pheno-
barbital is most often used as the first line agent, but overall
there is no established consensus on which antiepileptic
33. FRRS1L Gene Homozygous Mutation (p.Gly246del) should be used, especially with second line agents.
in Puerto Rican Families With Epileptic Encephalopathy Methods: We conducted a retrospective chart review of
and Dyskinetic Movements patients admitted to our Level IV NICU who underwent
Abdelmoumen I (Philadelphia, PA), Jimenez S, Valencia I, video EEG (vEEG) over a 2 year period. Patients were ana-
Schneider M, Melvin J, Legido A lyzed by presence of seizures on EEG, utilization of anti-
Objective: To describe the clinical presentation of Early epileptic drugs (AEDs), and clinical outcomes of interest
Infantile Epileptic Encephalopathy-37 (EIEE-37) in six included seizures at discharge, AEDs at discharge, and need
patients with Southern Puerto Rican ancestry that are homo- for gastrostomy tube or tracheostomy.
zygous for the same FRRS1L mutation. Results: A total of 133 patients were reviewed. One third of
Methods: A retrospective chart review of patients with the patients had clinical seizures prior to vEEG and were
FRRS1L mutation, followed at neurology clinic was per- treated. Once on vEEG, 28% of the patients had recorded
formed. Clinical variables included age of onset, presence of seizures. Most patients first received Phenobarbital, which
developmental delay, EEG and brain MRI findings, genetic stopped 47% of seizures. Second-line antiepileptic therapy
testing and ancestry information. included Levetiracetam in 75% of patients, and stopped 45%
Results: Six patients from four different families were homo- of the seizures. Topiramate, Midazolam, and Fosphenytoin
zygous for the (p.Gly246del) FRRS1L mutation detected via were used as third line agents, stopping one third of the sei-
Whole Exome Sequencing or an epilepsy panel. The age of zures. About 40% of patients discharged on AEDs required a
onset of symptoms was eight to fifteen months. All had tracheostomy and/or G tube. Only ~20% of patients who
severe global developmental delay. EEG showed did not require AEDs at discharge required tracheostomy
hypsarrhythmia in three out of six patients; the remainder and/or G tube (p=0.0317).
had slow backgrounds and epileptiform activity. All had Conclusions: Phenobarbital alone was able to stop about half
refractory epilepsy. Two patients demonstrated progressive of seizures. Our results demonstrated that Levetiracetam is an
cerebellar atrophy on brain MRI. appropriate additional AED if seizures continue. In addition,

S56 Annals of Neurology Vol 86 (suppl 23) 2019

patients with poorly controlled seizures were more likely to correlated with change in PedsQL Total scores, sharing from
require a gastrostomy tube and/or tracheostomy. 11% to 40% of variance (P<0.05). More problematic self-
Keywords: Epilepsy, Neonatal Neurology regulation scores on the BRIEF2 were associated with worse
scores on the Social, School, Psychosocial, and Total Func-
35. A Complicated Case of Gastroesophageal Reflux tioning scales of the PedsQL. The strongest relationships
Berry M (Milton, WA), Wheeler M, Guenther E were seen between changes in BRIEF2 ratings and overall
functioning (Total score) on the PedsQL. Increasing ZX008
Objective: The purpose of this case study was to determine
dose was associated with greater improvements in self-
the best course of diagnosis, treatment, and prognosis for an
regulation and QOL in most domains.
infant with refractory epilepsy. This case was chosen due to
Conclusions: Improvement in self-regulation was associated
the complicated and unique nature of our patient’s diagnostic
with better Physical, Social, School, and Psychosocial scores
and prognostic features.
and a better overall QOL score. The apparent dose-response
Methods: The case was reviewed in detail. A literature review of
effect observed with regard to the number of significant asso-
the most up to date information on refractory seizure disorders
ciations between changes in BRIEF2 and PedsQL scores
was conducted. This information was used to examine the care
could suggest an important contribution of seizure control
given to our patient and the likely outcomes of her disorder.
and/or an independent drug effect on self-regulation.
Results: An infant presented with a complicated history of
Keywords: Epilepsy
gastroesophageal reflux, failure to thrive, and episodic spasms.
After a complicated hospital course the patient was diagnosed
with a rare genetic mutation, STXBP1, and Ohtahara Syn- 37. One Hundred Consecutive Cases: Lessons Learned
drome, a type of early onset epileptic encephalopathy with a Over One Year in a First Time Seizure Clinic
characteristic suppression-burst pattern on EEG. Ohtahara Ananth A (Birmingham, AL), Borasino P, Novara S, Dure L
syndrome comprises less than 1% of childhood epilepsies,
Objective: Understand the incidence of epilepsy and the tra-
and about 25% of children diagnosed with Ohtahara have
jectory of patients following a single unprovoked seizure in a
the identified mutation in STXBP1. Treatment is difficult.
dedicated pediatric neurology clinic.
Recommendations include a combination of antiepileptic
Methods: We retrospectively reviewed the charts of the first one
drugs, but refractory epilepsy may also benefit from a keto-
hundred patients seen in our first time seizure clinic (February
genic diet or other alternatives. Ohtahara can improve over
2018-March 2019). All patients were referred from the emer-
the first year of life, or it can progress into other syndromes.
gency room (ER) at our tertiary children’s hospital. Criteria for
It always results in some level of developmental delay.
referral included: age between six months to eighteen years, clini-
Conclusions: Ohtahara Syndrome is a rare but important form
cian suspicion for seizure, return to baseline, and discharge to
of infantile epilepsy, with ongoing research into the best treat-
home from the ER. Exclusion criteria included: febrile seizures,
ment options. It has a characteristic EEG change which should
concern for infantile spasms, admission, or previous care from a
be recognized by neurologists in order to provide the best infor-
neurologist. The primary outcome of interest was epilepsy as
mation for patients. Treatment is an ongoing challenge.
defined by International League Against Epilepsy 2014 Guide-
Keywords: Epilepsy, Neonatal Neurology
lines. A diagnosis of transient alteration of awareness was given
when a clinical diagnosis for the event could not be made.
36. Relationships Between Self-Regulation and Quality of Results: Seventy-four patients were diagnosed with seizures. Of
Life: Results From a Phase 3 Study of ZX008 these, forty-five (61%) were ultimately diagnosed with epilepsy.
(Fenfluramine HCl Oral Solution) in Children and Young Twelve patients had a transient alteration in awareness, four had
Adults With Dravet Syndrome a psychogenic non-epileptic event, and four had syncope. The
Bishop K (Muncy, PA), Gioia G, Isquith P, Gammaitoni A, diagnosis of complex migraine, spasmus nutans, breath holding
Farfel G, Galer B, Mistry A, Lock M, Morrison G spell, paroxysmal kinesiogenic dyskinesia, shuddering spell, and
sleep myoclonus were made in one patient each.
Objective: To explore the relationships between caregiver- Conclusions: Our study illustrates that ER referral to our
reported self-regulation and quality-of-life (QOL) ratings in first time seizure clinic resulted in the diagnosis of epilepsy in
children and young adults with Dravet Syndrome nearly half of all the patients seen. A first time seizure clinic
(DS) participating in a phase 3 study. can be used to triage and streamline care for pediatric patients
Methods: Patients with DS were randomized to 1 of 2 doses presenting with seizure-like events.
of ZX008 (fenfluramine HCl oral solution) (0.8 or 0.2 Keywords: Epilepsy
mg/kg/day) or placebo for 14 weeks. Behavior Rating Inven-
tory for Executive Function (BRIEF®2) and Pediatric Quality
38. A Phase 1, Single-Dose, Open-Label Pharmacokinetic
of Life Inventory (PedsQL) ratings were administered to care-
Study to Investigate the Drug-Drug Interaction Potential
givers at baseline and at end of study. Correlations for change
of ZX008 (Fenfluramine HCl Oral Solution) and
from baseline scores between the BRIEF2 and PedsQL scores
Cannabidiol
were examined overall and by treatment group.
Boyd B (Emeryville, CA), Smith S, Farfel G, Morrison G
Results: Ratings were available from caregivers of 77 of
119 patients (mean patient age, 10.7 years). Change in care- Objective: Cannabidiol (CBD) was recently approved for
giver BRIEF2 index ratings from baseline to the end of study Dravet syndrome (DS); a New Drug Application for ZX008

Program and Abstracts, Child Neurology Society S57

FIGURE 1: Mean (
SD) Fenfluramine and Norfenfluramine Plasma Concentrations Before (Day 1) and Concomitant with (Day 22)
Cannabidiol. Abstract 38

(fenfluramine HCl oral solution) for DS was submitted. In 39. Benign Epilepsy with Centrotemporal Spikes vs
vitro, fenfluramine (FFA) and its major metabolite Childhood Absence Epilepsy: Differences in Resting State
norfenfluramine (norFFA) did not affect CBD metabolism. Language Network Functional Connectivity
This study analyzed the effects of CBD on FFA and norFFA Calley C (Cincinnati, OH), Vannest J, Tenney J
pharmacokinetics (PK). Objective: Benign Epilepsy with Centrotemporal Spikes
Methods: Healthy adult recreational drug users with recent (BECTS) and Childhood Absence Epilepsy (CAE) are the
cannabis product experience (BMI 18-31 kg/m2) were two most common benign epilepsy syndromes, and represent
administered ZX008 (0.4 mg/kg orally with food) on Day focal and generalized epilepsy respectively. Previous studies
1. Oral CBD (CanniMed® Oil 20:1 [20 mg/mL CBD + suggest both are associated with cognitive impairments
1 mg/mL tetrahydrocannabidiol (THC)] dosing was started including language, however it is unknown whether these are
the product of epilepsy in general or syndrome-specific
at 100 mg BID on Day 14, titrated through Day 18 to
effects. This study aims to directly compare the resting state
400 mg BID, and maintained through Day 31. ZX008 was
connectivity of the language network between BECTS and
again dosed on Day 22. PK blood sampling was done after CAE to better understand how differences in network con-
dosing on Days 1, 21, and 22. nectivity may contribute to language dysfunction.
Results: Fourteen participants completed the study (mean Methods: Concurrent resting state fMRI and EEG data were
age, 30.4
10.1 [SD] years). CBD co-administration collected on newly-diagnosed and drug naïve children with
increased FFA Cmaxand AUC(0-t)by 10% and 60%, respec- BECTS (n=23) and CAE (n=18). EEG was used to identify
tively; Cmaxand AUC(0-t)of norFFA decreased by 33% and seizure activity, which was subsequently removed from fMRI
22% (Figure). The effect on FFA was attributed to CBD; analyses. fMRI resting state data was preprocessed in standard
based on THC’s significantly lower dose and reported lower fashion via SPM12, and subsequent connectivity analyses were
processed using CONN. Language network connectivity was
inhibitory potency, THC was not expected to interfere with
measured by placing 20mm spherical seeds into bilateral infe-
PK study objectives. CBD steady-state mean AUC(0-12h) rior temporal gyri and posterior superior temporal gyri.
(1865 ng•h/mL) was unaffected by ZX008 coadministration. Results: The BECTS group showed significantly decreased
The most common adverse events included headache, nausea, connectivity among the language network seeds and other
and vertigo. regions of interest compared to CAE. The most notable
Conclusions: Co-administration of CBD with ZX008 did decreased connectivity was seen in pairs containing the left
not result in any clinically relevant effects on FFA and superior temporal gyrus including: bilateral accumbens p-
norFFA exposure. These data support co-administration of FDR<0.01, right inferior temporal gyrus p-FDR<0.01, right
ZX008 with CBD in DS without dose adjustment. lateral frontoparietal cortex p-FDR<0.02, and right sup-
Keywords: Epilepsy ramarginal gyrus p-FDR<0.03.

S58 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 1: Abstract 39 [Color figure can be viewed at www.wileyonlinelibrary.com]

Conclusions: This study is the first to directly compare rest- hemorrhage). Three were later treated with anatomic (2) or
ing state language network connectivity between BECTS and functional (1) hemispherectomy when seizures re-emerged
CAE. Decreased connectivity in BECTS group likely repre- from brain remnants. All survivors remain seizure-controlled
sents a syndrome-specific effect which may contribute to lan- on 2-3 anti-seizure medications. Both newborns who subse-
guage dysfunction. quently received anatomic hemispherectomy developed
Keywords: Epilepsy, Neuroimaging, Cognitive/Behavioral hydrocephalus requiring shunt placement.
Disorders Conclusions: Staged transarterial hemispheric embolization for
hemimegalencephaly is an effective alternate treatment option
40. Staged Transarterial Hemispheric Embolization: An for the management of intractable seizures in the newborn.
Innovative and Effective Treatment Option for Keywords: Epilepsy, Neonatal Neurology, Critical Care
Intractable Seizures in Newborns with
Hemimegalencephaly 41. ZX008 (Fenfluramine HCl Oral Solution)
Chang T (Washington, DC), Tsuchida T, Oluigbo C, Significantly Reduces Frequency of Generalized Tonic-
Kratimenos P, Vezina G, Gaillard W, Pearl M Clonic Seizures in Dravet Syndrome: Pooled Analysis
Objective: Anatomic or functional hemispherectomy is the from Two Phase 3 Clinical Trials
established treatment for intractable seizures in patients with Devinsky O (Livingston, NJ), Cross JH, Gil-Nagel A,
hemimegalencephaly; however, in infants <3 months of age, Gunning B, Battaglia D, Riney K, Gammaitoni A, Farfel G,
surgery can be life threatening from intraoperative blood loss. Mistry A, Galer B, Morrison G
We present our experience with 5 newborns with Objective: ZX008 (fenfluramine HCl oral solution) signifi-
hemimegalencephaly and intractable seizures who underwent cantly reduced the frequency of convulsive seizures in
staged transarterial glue embolization. patients with Dravet syndrome in two Phase 3 clinical trials.
Methods: A multidisciplinary team including a Level 4 Pediat- We conducted a pooled analysis of these trials to analyze the
ric Epilepsy Program, Neonatal ICU, Neonatal Neurocritical effect of ZX008 on the frequency of tonic-clonic seizures
Care Service, and an interventional neuroradiology program (TCs), recently identified as a major risk factor for sudden
instituted a staged transarterial glue embolization as the best unexpected death in epilepsy.
approach in 5 newborns presenting with hemimegalencephaly Methods: The frequency of generalized TCs and focal-to-
and intractable seizures between 2013-2018. The region of bilateral TCs in patients with DS enrolled in one of two
highest seizure burden was selected for initial and subsequent phase 3 clinical trials of ZX008 added to current antiepileptic
embolization. During and between embolization, seizure con- drug regimens were analyzed.
trol was maximized with continuous EEG monitoring. Preven- Results: 206 patients (55% male, mean age=9 years) enrolled
tive measures to minimize cerebral edema, intracranial and were randomized to placebo (n=84), or ZX008 0.8 (n=40),
bleeding and vasospasm were established. 0.5 (n=43), or 0.2 (n=39) mg/kg/day. The median baseline
Results: 1 boy and 4 girls (ages 6-51 days old) with monthly frequency of generalized TCs ranged from 8.0 to 12.3/
hemimegalencephaly and intractable seizures underwent 1-3 month in the four dose groups, and decreased by 80%, 64%,
staged transarterial glue embolizations (per stage mean and 48% in the ZX008 0.8, 0.5, and 0.2 mg/kg/day groups,
3 embolizations, range 1-5). Seizure burden improved with respectively, and by 10% in the placebo group. Focal-to-bilateral
each stage; complete seizure resolution was achieved in all TCs were experienced by fewer patients and had a median base-
4 survivors. Two patients experienced micro-perforation line frequency of 2.0 to 4.7/month. During treatment, median
(1 asymptomatic, 1 fatality from an arteriovenous fistula percent reductions in focal-to-bilateral TC frequency were 97%,

Program and Abstracts, Child Neurology Society S59

33%, and 69% in the ZX008 0.8, 0.5, and 0.2 mg/kg/day Mean time from IS diagnosis to KD initiation was
groups, respectively, and 39% in the placebo group. Most com- 6.7
4.8 months. Upon KD initiation, 16 were taking
mon adverse events included decreased appetite, diarrhea, and vigabatrin and 16 were taking other anti-seizure medications
fatigue. No valvular heart disease or pulmonary arterial hyperten- (median 2 medications); 16 completed ACTH and 10 pred-
sion was seen in any subject at any time. nisolone. Before KD, 16/23 had hypsarrhythmia; after
Conclusions: ZX008 substantially reduced the frequency of 6 months, 3/14 had persistent hypsarrhythmia; after
TCs. ZX008 may be an important, effective new treatment 12 months 2/11 had continued hypsarrhythmia. One month
option for DS patients. after KD initiation, 1 child was spasm-free (none seizure-
Keywords: Epilepsy free); by 6 months, 5/14 children were spasm-free and 1 was
completely seizure-free; by 12 months, 4/11 were spasm-free
42. Ketogenic Diet for Pharmacoresistent Infantile and 3 were completely seizure-free. All children continued at
Spasms least one anti-seizure medication. Reasons for KD discontinu-
Fedak Romanowski E (Ann Arbor, MI), McNamara N, Rau S, ation included adherence difficulty (4), treatment failure (3),
Lester-Pelham S, Choi S, Thorwall R, Joshi S, Shellhaas R death (1). Every child who stopped KD had persistent IS.
Conclusions: Among children with pharmacoresistent IS,
Objective: While first-line therapy for infantile spasms (IS) is
the KD may be an effective third line therapy when com-
established (ACTH, prednisolone, vigabatrin), there is little evi-
bined with anti-seizure medications.
dence to guide treatment for pharmacoresistent IS. We evaluated
Keywords: Epilepsy
efficacy of the ketogenic diet (KD) for pharmacoresistent IS.
Methods: Every child who received dietary therapy for epilepsy
was enrolled in a prospective observational study at a Level IV 43. Characteristics of Individuals with Cortical Visual
Epilepsy Center from 2014-2019. Data were abstracted system- Impairment of Pediatric Onset: An Interim Analysis of a
atically at baseline and after 1, 3, 6, 9, and 12 months of Longitudinal Study
KD. Children with IS received classic KD (ratios 2:1-4:1); treat- Fisher K (Houston, TX), Jimenez-Gomez A, Shah V
ment was at the clinicians’ discretion and guided by an institu- Objective: Cortical visual impairment (CVI) is the commonest
tional pathway that followed contemporary KD guidelines. cause of severe visual impairment in developed countries, with
Results: Twenty-three children had IS upon KD initiation a high burden of disability. There is limited information on
(age 15.6
7.8 months); 11 had concurrent non-IS seizures. factors for severity, and outcome predictors in CVI.
Methods: Retrospective review of pediatric CVI patients seen at
Texas Children’s Neuro-ophthalmology 2013-2017. Data col-
lected included perinatal history, genetic, developmental and neu-
rologic diagnoses. Serial ophthalmologic examinations paired with
development, neuroimaging and seizure control was collected.
Descriptive statistics and select inferential statistics were calculated.
Results: 246 individuals were identified (mean age at diagnosis
19 months, range 2-108 months). 64% were term at birth.
Perinatal history revealed Hypoxic ischemic encephalopathy
(HIE) in 16%, intraventricular hemorrhage in 12%, and sei-
zures in 22%. At diagnosis, 82% had Global delay, 60% had
CP; 61% had epilepsy, 8% patients suffered a traumatic brain
injury and 7% had post-neonatal HIE. Among epileptics, 24%
TABLE 1: Demographics and clinical data for 23 children with had an epileptic encephalopathy; 85% had with
pharmacoresistent infantile spasms. Abstract 42 [Color figure spasms/hypsarrhythmia. Imaging suggested a genetic/metabolic
can be viewed at www.wileyonlinelibrary.com] etiology in 28%. Confirmed pathogenic mutations were present

TABLE 2: Infantile spasm burden before and during ketogenic diet. Abstract 42 [Color figure can be viewed at www.
wileyonlinelibrary.com]

S60 Annals of Neurology Vol 86 (suppl 23) 2019

in 61% of total. Baseline visual examination revealed no blink
to light (BTL) in 24%; only BTL (35%), fixation/tracking
(27%), or optokinetic drum follow or better (14%). When
comparing groups, epilepsy diagnosis and poor seizure control
were associated with worse baseline visual acuity (p<.05). At
12 months, epilepsy/epileptic encephalopathy (p<0.05) but not
seizure control (p=0.34) were associated with improved vision.
Conclusions: In pediatric CVI patients, epilepsy and poor
seizure control may be a factor for worse baseline disease;
Longitudinal followup suggests seizure control may not be
associated with improved outcomes.
Keywords: Epilepsy, Genetics
FIGURE 1: Response Analysis Applying the ROC-Derived
MCID Threshold (≥37.5%) P values are vs placebo. MCID,
44. Defining a Minimal Clinically Important Difference minimal clinically important difference; MCSF, monthly
in Seizure Frequency Using Data from a Phase 3 Clinical convulsive seizure frequency; OR, odds ratio vs placebo;
Study of Add-On, Low-Dose ZX008 (Fenfluramine HCl ROC, receiver operating characteristic. Abstract 44 [Color
Oral Solution) in Dravet Syndrome Patients Receiving an figure can be viewed at www.wileyonlinelibrary.com]
Antiepileptic Drug Regimen Containing Stiripentol
Gammaitoni A (Emeryville, CA), Sullivan J, Dlugos D,
Farfel G, Galer B, Morrison G, Haney D, Nabbout R Results: Reduction in MCSF was positively associated with
Objective: To define a minimal clinically important difference improved caregiver and investigator CGI-I scores. ROC analysis
(MCID) in monthly convulsive seizure frequency (MCSF) vs of both clinically meaningful caregiver and investigator CGI-I
baseline using data from a clinical study in patients with ratings identified MCIDs of ≥37.5% (Table). Using this
treatment-refractory Dravet syndrome (DS) receiving ZX008 threshold, 67.4% of ZX008-treated and 13.6% of placebo-
(fenfluramine HCl oral solution) added to an antiepileptic treated patients achieved a clinically meaningful MCSF reduc-
drug (AED) regimen containing stiripentol (STP). tion (Figure). Higher levels of reduction in MCSF (40% and
Methods: This post-hoc analysis used data from Study 1504 50%) were associated with “Very Much Improved” CGI-I rat-
(NCT02926898), a phase 3 study of 87 DS patients 2-18 ings by investigators and caregivers, respectively.
years old receiving oral add-on ZX008 (0.5 mg/kg/day; maxi- Conclusions: Using CGI-I ratings, we identified an MCID
mum: 20 mg/day) or placebo in STP-inclusive AED regi- of ≥37.5% reduction in MCSF in the current study of
mens. Receiver operating characteristic (ROC) analysis ZX008 treatment of seizures in a DS population. This cut-
compared change in MCSF with binary categorizations of point is lower than the threshold of 50% improvement used
investigator and caregiver Clinical Global Impression of by regulators and widely used as the threshold of meaningful
Improvement (CGI-I) ratings (clinically meaningful range: seizure improvement, and may reflect the dramatic need for
≥“Much Improved”). MCID cut-off for change in MCSF seizure control in this population.
was chosen to ensure that sensitivity≈specificity. Keywords: Epilepsy

TABLE 1. Receiver Operator Characteristic Analysis. Abstract 44

Change in MCSF Sensitivity Specificity
CGI-I Category Cut-point (%) (%) (%) % Correct

Caregiver Assessment of CGI-I

Very Much Improved -50 67 74 73
Much Improved or Better (Clinically -37.5 70 71 71
Meaningful)
Minimally Improved or Better -19.5 79 78 78
Investigator Assessment of CGI-I
Very Much Improved -40 64 63 63
Much Improved or Better (Clinically -37.5 77 75 76
Meaningful)
Minimally Improved or Better -20 76 76 76
CGI-I, Clinical Global Impression of Improvement; MCSF, monthly convulsive seizure frequency.

Program and Abstracts, Child Neurology Society S61

45. Drug-Drug Interaction (DDI) Studies with CLB in HVTs (3.4 fold) and patients (2.6 fold). Concomitant
Coadministration of Cannabidiol (CBD) and Clobazam (CLB), CLB increased CBD by 30% and its active metabolite, 7-OH-
Valproate (VPA), Stiripentol (STP) or Midazolam (MDZ) in CBD by 47%. Concomitant CBD had no effect on VPA or
Healthy Volunteers (HVTs) and Adults with Epilepsy 4-ene-VPA, and increased exposure to STP by 55%. Concom-
Gidal B (Madison, WI), Patsalos P, Szaflarski J, Critchley D, itant VPA or STP did not alter CBD or its metabolites. CBD
Morrison G had no effect on MDZ clearance. CBD safety profile was con-
Objective: Summarize current understanding of DDIs when sistent with previous randomized placebo-controlled trials.
CBD is coadministered with CLB, VPA, STP, or CYP3A4 Conclusions: Combination of CBD with CLB resulted in a
substrate. bidirectional DDI that increased levels of active metabolites
Methods: Effects of multiple-dose CBD on steady-state phar- of both compounds. There was no effect of CBD on VPA
macokinetics (PK) of CLB, N-desmethyl clobazam (N-CLB), exposure or MDZ clearance. The slight increase of exposure
VPA, 4-ene-VPA, and STP, and multiple-dose CLB, VPA, to STP when coadministered with CBD is not expected to
and STP on steady-state PK of CBD and metabolites were be clinically important. Funding: GW Research Ltd
evaluated in HVTs. Effects of multiple-dose CBD on steady- Keywords: Epilepsy, Rare Diseases, Critical Care
state PK of CLB, N-CLB, VPA, and 4-ene-VPA were evalu-
ated in patients with epilepsy. Effect of CBD on CYP3A4 46. Corticosteroids Reduce Seizures and Improve Diffuse
activity was evaluated in HVTs using MDZ as a probe. In all Slowing and Organization Amongst Pediatric Patients
studies, plant-derived highly purified CBD in oral solution with Refractory Epilepsy
(Epidiolex®in U.S.; 100 mg/mL) was uptitrated over 10 days Gofshteyn J (New York, NY), Gurcharran K, Marquis B,
to 750 mg twice-daily in HVTs or 20 mg/kg/day in patients. LaMothe J, Gourley D, Grinspan Z, Nangia S
Results: Concomitant CBD had no relevant effect on CLB Objective: Corticosteroids are sometimes used in refractory
exposure but increased exposure to its active metabolite, N- epilepsy, but the benefits are understudied. Here, we

TABLE 1. Presence and description of slowing, epileptiform activity and organization. Abstract 46
Pre-steroid Post-steroid P Pre vs. Post-steroid P Pre vs.
Slowing Description N (%) EEG 1 N (%) EEG 1† EEG #2 N (%) EEG #2†

Diffuse excessive theta activity 8 (22) 9 (25) 1 6 (33) 0.39

Diffuse excessive delta activity 23 (64) 22 (61) 0.29 8 (44) <0.01
Focal slowing, unilateral, single focus 8 (22) 9 (25) 0.63 3 (17) 0.02
Focal slowing bilateral or multiple 4 (11) 4 (11) 1 1 (6) 0.13
foci
Slow posterior dominant rhythm 4 (11) 2 (6) 0.5 3 (17) 0.63
No slowing 2 (6) 1 (3) 0.5 1 (6) 0.5

EEG organization 0.74 0.02

0 8 (19) 7 (21) 3 (21)
1 11 (26) 5 (15) 4 (29)
2 22 (51) 21 (64) 7 (50)
3 2 (5) 0 0

EEG epileptiform scale 0.28 0.63

0 0 1 (3) 0
1 3 (7) 3 (8) 1 (7)
2 19 (45) 18 (47) 7 (50)
3 20 (48) 16 (42) 6 (43)
† Wilcoxon rank sum

S62 Annals of Neurology Vol 86 (suppl 23) 2019

 effect on thalamo-cortical and/or brainstem networks, which
TABLE 2. Parental assessment (n=39). Abstract 46 warrants additional investigation.
Dex Methyl P value Keywords: Epilepsy, Translational/Experimental Therapeutics
Yes (n = 16) (n = 18) dex vs.
47. A Learning Healthcare System for Pediatric Epilepsy:
Assessment (%) improved improved methyl*
Preliminary Counts
Grinspan Z (New York City, NY), Shellhaas R, Patel A,
Overall 25 12 (75) 10 (56) 0.18 Berg A, Buchhalter J, Yozawitz E, Loddenkemper T, Singhal N,
improved (64) McGoldrick P, Wolf S, Koh S, Dlugos D, Morgan L,
Improved 22 10 (63) 9 (50) 0.30 Gaillard W, Goodkin H
seizure (56) Objective: A learning healthcare system (LHS) collects elec-
frequency tronic health information from multiple sites and dissemi-
nates analyses to change practice and continuously improve
Improved 4 2 (13) 1 (6) 0.33
outcomes. To demonstrate feasibility of an LHS for children
motor skills (10)
with epilepsy, we report a strategy for ethical oversight, pri-
Improved 0 0 0 1 vacy, and data sharing, as well as preliminary counts.
sleep (0) Methods: The Pediatric Epilepsy Learning Healthcare Sys-
tem (PELHS) obtained central IRB approval using the lim-
Improved 9 4 (25) 4 (22) 0.54 ited personal health information framework for privacy. This
behavior (23) allowed data sharing via data use agreements, rather than
Improved 9 4 (25) 5 (28) 0.67 business associate agreements, facilitating legal negotiations.
seizure (23) Sites extracted administrative data for children with any
duration ICD9/10 code for epilepsy or convulsions, from 2010-2018,
including demographics, diagnosis codes, encounters, medica-
Improved 17 10 (63) 5 (28) 0.04 tions, and procedures. Data were securely transferred to a
cognition (44) data coordinating center (DCC) at Weil Cornell Medicine.
*Fisher’s exact t-test
Results: Twelve centers approved the IRB protocol, 13 exe-
cuted data use agreements, and 8 transferred data to the DCC.
From these 8, there were 118,943 individuals, including
examined children with refractory epilepsy treated with one 11,223 with a visit in the neonatal period, 24,154 in infancy,
of two corticosteroid regiments: methylprednisolone and 47,981 early childhood, 55,204 school age, and 38,805 adoles-
dexamethasone, to determine clinical and electrographic cence. The cohort is 47% female, 49% White, 10% Black,
response. 11% Hispanic, and 40% mixed race/other/unknown. The
Methods: This was a retrospective cohort study of children data include 12,663,105 diagnoses, 2,988,605 outpatient
seen in the refractory epilepsy clinic at Weill Cornell Medi- encounters, 240,837 inpatient admissions, 130,146 emergency
cine and treated with corticosteroids. Video long term elec- department visits, 17,273,760 medication administrations and
troencephalography (EEG) were assessed utilizing ordinal prescriptions, and 8,886,634 procedures.
scales for five features: seizures, epileptiform activity, slowing, Conclusions: Multisite administrative data collection to sup-
organization, and sleep architecture. We abstracted parental port a pediatric epilepsy LHS is feasible. Race and ethnicity
assessment of functional domains (i.e., cognition) from the figures differ from US census estimates, possibly due to
medical records. We compared pre-treatment to post-treat- under-reporting in some groups. We are currently validating
ment, and we compared treatment with dexamethasone ver- the extracted data to support a series of demonstration
sus methylprednisolone. projects.
Results: There was a significant decrease in overall seizure fre- Keywords: Epilepsy, Critical Care, Genetics
quency (median 10 IQR [1-26] to 2[0-10], p=0.01), 76% of
which were tonic seizures. Electrographic findings included an 48. The Case for Integrated Behavioral Health in the
improvement in organization of background (p=0.02), delta Management of Adolescent Epilepsy
slowing (p<0.01) and sleep spindles (p=0.04) (Table 1). There Harris M (Los Angeles, CA), Reyes B, Lerner J, Gavi N,
were no significant differences between the methylprednisolone Slavin A, Emerson N
and dexamethasone-treated cohorts. Parental report suggested Objective: Despite the high prevalence of psychiatric co-
cognition often improved after corticosteroid treatment (n=17/39, morbidities in adolescent epilepsy, interdisciplinary epilepsy
44%) observed more frequently in the dexamethasone treated teams have historically operated without a dedicated behavioral
group (n=10/16, 63% vs. n=5/18, 28%, p=0.04) (Table 2). Both health team. This study identified the need for such a service by
modalities were well tolerated without significant adverse events. examining the prevalence of psychiatric disorders and occupa-
Conclusions: Corticosteroids may reduce tonic seizures, tional impairment in a sample of adolescent epilepsy patients.
improve slowing and sleep architecture, and improve cogni- Methods: Data derived from 88 patients treated in an inter-
tion in children with refractory epilepsy. The improvement disciplinary adolescent epilepsy clinic were retrospectively
in slowing, sleep architecture and tonic seizures suggest an analyzed between September 2018 and March 2019. The

Program and Abstracts, Child Neurology Society S63

integrated pediatric psychologist evaluated patients for mental Conclusions: Our preliminary findings highlight the impor-
health concerns. The mental-health specialized occupational tance of integrating behavioral health specialists in an adoles-
therapist (OT), experienced in addressing functional and cent epilepsy team, in order to accurately identify and
occupational engagement in adolescent health, also evaluated address mental health concerns. Future studies will seek to
patients. demonstrate how the inclusion of such team members
Results: Patients were aged 10-24 years (Mage= 15.88, SDage= improves patient outcomes and provides cost-effective care.
3.38; 46.6% female). Of the 55 patients seen by the psychol- Keywords: Epilepsy, Translational/Experimental Therapeutics
ogist, 80% of patients met criteria for a mental health disor-
der according to the Diagnostic and Statistical Manual of
Mental Disorders, 5thedition (DSM 5), most predominantly 49. Digital and Technological Opportunities in Epilepsy:
Autism Spectrum Disorder (27%), other intellectual impair- A Future Self-Management Ecosystem
ment or developmental disability (29%), and anxiety (24%). Hixson J (San Francisco, CA), Braverman L
Of the 69 patients evaluated by the OT, 85% reported diffi- Objective: There are many supportive digital services for
culty engaging in meaningful activities, including education children and adolescents with epilepsy that have been stud-
(61%), instrumental activities of daily living (46%), social ied. The aim was to identify digital tools tailored for this
participation (39%), and activities of daily living (38%). audience including their parents and caregivers. Discuss the

TABLE 1. Potential Barriers to Implementation and Solutions. Abstract 49

Barrier Audience Suggested Solutions

Lack of awareness of available tools Patients/Parents -Marketing campaigns

Caregivers -Managing Epilepsy Well Network
Providers
Lack of perceived benefit of tools Patients/Parents -Improved usability
Caregivers -Next generation versions
Nonadherence with digital tools Patients/Parents -Improved usability
Caregivers -Time-sensitive interfaces
-Automated sensors/mobile devices
Confidentiality and data risk concerns Patients/Parents -Adoption of formal data standards
Caregivers -Potential FDA approval process
Providers
Data accuracy concerns Patients/Parents -Adoption of formal data standards
Caregivers
Providers
Stigma associated with use of digital tools Patients/Parents -Education campaigns
Caregivers -Encourage use of mobile diaries
-Low-profile wearables
Lack of HCP communication and education Patients/Parents -Staff to perform education after formal clinic visit
about available tools Caregivers -Take-away educational materials
Providers -Digital prescription pad
Lack of time for patient education Providers -Staff to perform education after formal clinic visit
-Take-away educational materials
-Digital prescription pad
Historical ‘inertia’ against alternative Providers -Physician ‘championing’
prescribing approaches -Use of digital ‘prescription pad’
Lack of evidence-based effectiveness (or Providers -Physician marketing campaigns
physician comfort with data) -CME courses or training
-Seminars at national conferences
Lack of regulatory approval or evaluation path Providers -Precedent of recent digital wearables
-Encourage use in traditional clinical trials
Lack of an efficient prescribing infrastructure Providers -Use of a digital ‘prescription pad’
-Integration into EMR prescribing
Lack of financial incentives to prescribe Providers -Physician marketing campaigns
-Use of a digital ‘prescription pad’
-Integration into EMR prescribing

S64 Annals of Neurology Vol 86 (suppl 23) 2019

various barriers preventing greater utilization of these inter- frequency, epilepsy type, impact on school/work/activities,
ventions. Finally, identify tactics that can be used by and reproductive health counseling for females. The 302 com-
healthcare teams to advance awareness and usage of these pleted forms had an overall average score across all items of
tools. 3.73 for Epi-TRAQ vs for TRAQ 3.86. The internal consis-
Methods: A literature review of the existing studies tency was high for both Epi-TRAQ (CA 0.95) and the origi-
supporting the use of digital interventions for epilepsy nal TRAQ (0.94). The internal consistency of domains with
patients was completed. We categorized the resulting searches additional Epi-TRAQ questions was good for managing med-
into three primary tools: self-management programs, elec- ications (CA 0.78), and very good for tracking health issues
tronic seizure diaries, and wearable devices for seizure (CA 0.82) and managing daily activities (CA 0.85).
detection. Conclusions: Epi-TRAQ shows high internal validity (overall
Results: Overall, a number of digital resources have been cre- and domain) of the questionnaire. Epi-TRAQ can be a useful
ated and studied to support the needs of patients with epi- tool for transition readiness screening for AYE.
lepsy. Only a portion are available digitally, and a smaller Keywords: Epilepsy
subset have been tailored for children and adolescents. None-
theless, even generic tools could prove beneficial for younger
patients and their parents. For all three categories, there 51. Impact of Epilepsy Surgery on Behavioral and
remain significant barriers to awareness, dissemination, and Cognitive Outcomes
real-world use. These barriers include patient-facing concerns, Kantamneni T (Sacramento, CA), Lapin B, Jehi L, Pestana
provider- or healthcare team challenges, and informatics Knight E
infrastructure gaps (Table 1). Objective: Report the behavioral and cognitive outcomes fol-
Conclusions: Many supportive digital tools exist for epilepsy lowing epilepsy surgery in children and identify the predictive
patients, although a minority are tailored for children or ado- factors that determine these outcomes.
lescents. These tools include self-management programs, dia- Methods: We retrospectively reviewed 126 patients below
ries, and wearable technologies, each with varying levels of 18 years who underwent epilepsy surgery for medically refrac-
supportive evidence. Many addressable barriers are currently tory epilepsy between January 2009 to December 2016. The
contributing to implementation difficulties, including primary outcome measure was the Impact of Childhood Neu-
patient-facing, provider-centric, and infrastructure-based rologic Disability scale scores (ICNDS, parent reported scale
issues. Epilepsy care providers are positioned to take a leading of children with epilepsy assessing behavior, cognition and
role in directly addressing these issues to increase the aware- physical/neurological disability), which were measured preoper-
ness and utilization of these tools. atively, at 6, 12, and 24 months post-surgery. Separate linear
Keywords: Epilepsy mixed effects models were constructed to identify predictors of
post-operative ICND total score and sub scores over time.
Results: Of the 126 patients, 88 patients (69.8%) were
50. Developing an Instrument for Screening of Transition seizure-free by the two year follow-up. The average preoperative
Readiness for Adolescents with Epilepsy total ICNDS score was 55.7
28.3. There was a significant
Joshi S (Ann Arbor, MI), Clark S, Beimer N, Patel A, improvement (reflected by a reduction in the ICNDS score) at
Fletcher L, Guyot J, Gebremarium A, Carbone L, Tang R, 6 months post-operatively (total score: 34.6
25.8, p<0.001)
Alam J and 24 months (32.1
23.4, p<0.001). Sub scores for behav-
Objective: Assessment of transition readiness is an essential ior, cognition and epilepsy also improved from pre- to 6 months
step of an organized transition program. Validated tools such post-operatively (p<0.001) and remained consistent through
as the Transition Readiness Assessment Questionnaire 24 months post–operatively. Improvement was observed even
(TRAQ), do not address epilepsy-specific needs. We aimed in patients who were not seizure-free after surgery (p<0.001 for
to design and validate an epilepsy-specific transition instru- both). Significant predictors of improved ICNDS scores
ment for adolescents and young adults with epilepsy (AYE). included absence of associated comorbidities or mood diagno-
Methods: The original 20 questions, Likert scale-style ses, tumor pathology, and seizure-freedom at 2 years.
response options and scoring in TRAQ were maintained. Conclusions: After pediatric epilepsy surgery, there is a
Epilepsy-specific questions were added, based on AAN Epi- sustained improvement in behavior and cognition, as per-
lepsy Quality Measures for 3 of 5 TRAQ domains (managing ceived by the families, regardless of seizure freedom status
medications, tracking health issues, managing daily activities). after surgery.
The new Transition Readiness Assessment Questionnaire for Keywords: Epilepsy, Cognitive/Behavioral Disorders
Epilepsy (Epi-TRAQ) was pilot tested with patients with epi-
lepsy age 16-26 during visits to pediatric and adult neurology
clinics at a tertiary care center. Validation of Epi-TRAQ was 52. Incidence and Prognosis of Seizures in Patients with
performed for the initial 302 completed forms. Internal con- Myelomeningocele Over 38 Year Follow Up
sistency was assessed using Cronbach’s Alpha(CA). Karakas C (Houston, TX), Chen D, Cracco J
Results: Epi-TRAQ included 15 additional questions Objective: To determine the incidence and prognosis of
addressing knowledge of rescue medications, tracking seizure seizures in patients with myelomeningocele (MMC) and

Program and Abstracts, Child Neurology Society S65

examine at the different factors associated with seizures, thus Conclusions: An immune-mediated inflammatory process is
long-term outcome in patients with MMC. suspected as the etiology for NORSE, possibly triggered by
Methods: This was a retrospective study analyzing the data infection. In our patient, CSF levels of IL-1 were significantly
from patients with diagnosis of MMC evaluated at Spina elevated. Along with targeted antibiotics, our patient was ini-
Bifida Clinic at SUNY Downstate Medical Center, NY, USA tiated on anakinra, a recombinant human interleukin-1
from 1975 to 2013. Chi-square was used for statistical differ- receptor antagonist, based on evidence supporting improved
ences. P<0.05 was considered statistically significant. outcomes with blockade of such proinflammatory cytokine
Results: 122 patients with MMC were included in this pathways. Due to the refractory nature of the patient’s pre-
study. There were total of 74 females (60%). Average follow sentation, several interventions were enacted simultaneously,
up duration was 133.6
105.8 months. 108(88%) patients however, targeted antibiotics and anakinra were the most
had hydrocephalus and 98(80%) required shunt procedure. temporally associated with improvement. It is important to
24(19.6 %) patients manifested with seizure, 23/24 patients search for these etiologies and treat based on clinical
with hydrocephalus and 1/24 patient without hydrocephalus. response.
Complicated shunting was a significant risk factor for seizures Keywords: Epilepsy, Infections/Neuroimmunology, Rare
development (P=0.027). 12/24 patients with seizure had Diseases
lumbar MMC. However, MMC level and presence of hydro-
cephalus were not found to be significant risk factor for sei- 54. Behavioral and Cognitive Effects of Long-term
zure development. 14/24 patients had focal seizures and 7/24 Adjunctive Brivaracetam in Children with Epilepsy: A
had generalized seizures. Seizure type was not reported for Pooled Interim Analysis of Two Open-label Trials
3 patients. Average number of AED use was 1.2 (range 0-2). Lagae L (Leuven, Belgium), Gasalla T, Borghs S, Martin M,
Average seizure free period was 9.4
(SD=10.4) years in Cleveland J, Badalamenti V, Elshoff J-P, Pina-Garza J
patients with uncomplicated shunt vs 7.8
(SD=8.6) years
Objective: Investigate behavioral and cognitive effects of
in patients with complicated shunt.
long-term adjunctive brivaracetam (BRV) in children with
Conclusions: Only one patient without hydrocephalus expe-
epilepsy.
rienced seizure activity. Among patients who had seizures,
Methods: N01263 (NCT00422422) was an open-label trial
the presence of complicated shunting was significantly associ-
of adjunctive BRV in children (≥1 month to <16 years) with
ated with seizure activity. This study has addressed a critical
epilepsy uncontrolled by 1-3 concomitant AEDs; patients
gap in the literature “the nature, prognosis and outcome of
completing dose-escalation could continue to an open-label
seizures in patients with MMC”.
extension (N01266; NCT01364597). This pooled interim
Keywords: Epilepsy, Cognitive/Behavioral Disorders
analysis (cut-off: 15 March 2017) investigated changes from
N01266 Baseline in the Behavior Rating Inventory of Execu-
53. Case Report: "The Cat’s Out of the Bag", A Rare tive Function (BRIEF; 5-16 years) and Achenbach Child
Case of New-onset Refractory Status Epilepticus Due to Behavior Checklist (CBCL; 6-18 years) at 2,12, and
Bartonella Henselae 24 months. Treatment-emergent adverse events (TEAEs)
Kern-Smith E (Atlanta, GA), Chen D, Dutt M potentially related to behavior and cognition were assessed
Objective: Cases of new-onset refractory status epilepticus for the overall population and patients aged ≥4 to <16 years
(NORSE) are attributed to autoimmune causes; however, with focal seizures (focal 4-16).
infectious etiologies represent an important cause of this Results: Data were obtained from 219 patients (focal 4-16:
potentially devastating syndrome. We describe a case of n=149; Table 1). Small decreases (improvements) were
NORSE due to Bartonella henselae infection and the observed in all BRIEF (n=104), and most CBCL (n=129) T-
approach to treatment. score subscales (except withdrawn/depressed) from Baseline
Methods: A five year-old previously healthy boy presented in to 2, 12, and 24 months; most patients were stable
status epilepticus not responding to benzodiazepines. EEG (Table 2). TEAE incidences were similar overall and in the
showed continuous electrographic seizures, which remained focal 4-16 group (Table 1). Overall, 59 (26.9%) patients had
refractory to several antiepileptics, and required escalation to a behavioral TEAE, mostly irritability (11.9%) and aggres-
pentobarbital to maintain burst suppression. Imaging, initial sion (5.9%) and mostly occurring during the first 3 treatment
serum labs, and CSF analysis were unremarkable. With auto- months. Overall, 14 (6.4%) patients reported potentially
immune encephalopathy panels pending, he was empirically cognition-related TEAEs, mostly ADHD (1.8%) and confu-
treated with immunosuppressive therapies, including steroids, sional state (1.4%).
plasmapheresis, and rituximab (one dose). Conclusions: In children on long-term adjunctive BRV,
Results: On day 11, his Bartonella Henselae serology indi- behavior and cognition measures were generally stable over
cated a recent infection. Doxycycline and rifampin were time suggesting a limited impact on behavior and no
started. Due to significantly elevated IL-1 in CSF, he was impact on cognition. Behavioral TEAEs occurred mostly
started on anakinra. Pentobarbital was weaned and he trans- early in therapy; few patients reported cognitive TEAEs.
itioned to scheduled antiepileptic medications. At discharge, Further investigations are needed. Funding: UCB Pharma-
he was regaining developmental milestones and remained sponsored
seizure free. Keywords: Epilepsy, Cognitive/Behavioral Disorders

S66 Annals of Neurology Vol 86 (suppl 23) 2019

TABLE 1. Patient characteristics and treatment emergent adverse events (TEAEs). Abstract 54
Patients with focal seizures aged
All patients (n=219) ≥4 to <16 years (n=149)a

Age, median (range), years 8.0 (0, 16) 9.0 (4, 15)
Male, n (%) 120 (54.8) 84 (56.4)
Time since diagnosis, mean (SD), years 4.8 (3.8) 5.6 (3.6)
Exposure to brivaracetam, patient-years 464.6 299.4
a
Seizure type history , n (%)
Focal seizures 186 (84.9) 149 (100)
Generalized seizures 49 (22.4) 1 (0.7)b
Unclassified 7 (3.2) 1 (0.7)
TEAEs, n (%)
Any TEAE 207 (94.5) 140 (94.0)
Drug-related TEAEs 87 (39.7) 56 (37.6)
Discontinuations due to TEAEs 27 (12.3) 12 (8.1)
TEAEs potentially associated with behavioral disorders, n (%)
At least one TEAE 59 (26.9) 37 (24.8)
Irritability 26 (11.9) 16 (10.7)
Aggression 13 (5.9) 7 (4.7)
Psychomotor hyperactivity 7 (3.2) 7 (4.7)
Laceration 7 (3.2) 4 (2.7)
Abnormal behaviour 6 (2.7) 3 (2.0)
Affect lability 3 (1.4) 3 (2.0)
Mood swings 3 (1.4) 1 (0.7)
Oppositional defiant disorder 2 (0.9) 2(1.3)
Anger 1 (0.5) 1 (0.7)
Conduct disorder 1 (0.5) 1 (0.7)
Homicidal ideation 1 (0.5) 0
Hypersexuality 1 (0.5) 1 (0.7)
Mood altered 1 (0.5) 1 (0.7)
TEAEs potentially associated with cognitive impairment, n (%)
At least one TEAE 14 (6.4) 10 (6.7)
ADHD 4 (1.8) 3 (2.0)
Confusional state 3 (1.4) 3 (2.0)
Oppositional defiant disorder 2 (0.9) 2 (1.3)
Disturbance in attention 2 (0.9) 1 (0.7)
Autism spectrum disorder 1 (0.5) 1 (0.7)
Conduct disorder 1 (0.5) 1 (0.7)
Speech disorder developmental 1 (0.5) 0
Neuro-development disorder 1 (0.5) 0

ADHD, attention-deficit hyperactivity disorder; TEAE, treatment-emergent adverse event.

a
At the cut-off date, 118 (53.9%) patients were ongoing in N01266, 97 (44.3%) had discontinued the trial, and 4 (1.8%) had chosen not to enter
N01266.
a
Patients may have experienced more than one seizure type.
b
One patient with a history of focal seizures but not primary generalized seizures was recorded as having a history of generalized (myoclonic) seizures.

Program and Abstracts, Child Neurology Society S67

 TABLE 2. Shift in T-scoresa of Behavior Rating Inventory of Executive Function (BRIEF; 5-16 years) and
Achenbach Child Behavior Checklist (CBCL; 6-18 years) between Baseline and follow-up. Abstract 54
Change in T-score (age-standardized) from Baseline
2 12 24 Last
months months months valueb Shift in T-score categoryc, Baseline to Last Value
Mean Mean Mean Mean
(SD) (SD) (SD) (SD) Improved, Unchanged, Worsened, Missing
(n) (n) (n) (n) n (%) n (%) n (%) n (%)

Behavior Rating of Executive Function (BRIEF)

Global Executive -2.0 -2.7 -3.0 -2.3 19 (18.3) 61 (58.7) 12 (11.5) 12
Composite score (7.3) (9.2) (11.2) (10.3) (11.5)
(n=104) (73) (69) (50) (92)
Behavioral Regulation -1.7 -2.7 -3.0 -2.7 24 (23.1) 61 (58.7) 12 (11.5) 7 (6.7)
Index score (n=104) (9.1) (9.5) (11.7) (10.9)
(79) (74) (53) (97)
Metacognition Index -2.0 -2.1 -2.8 -2.0 20 (19.2) 64 (61.5) 11 (10.6) 9 (8.7)
score (n=104) (6.4) (9.2) (10.4) (9.8)
(77) (73) (53) (95)
Achenbach Child Behavior Checklist (CBCL)
Aggressive Behavior -0.6 -1.8 -2.5 -2.4 28 (21.7) 85 (65.9) 14 (10.9) 2 (1.6)
(n=129) (6.4) (6.5) (7.6) (7.3)
(107) (94) (72) (127)
Anxious/Depressed -1.6 -2.5 -3.1 -1.8 26 (20.2) 92 (71.3) 9 (7.0) 2 (1.6)
(n=129) (6.4) (7.2) (8.0) (7.6)
(107) (94) (72) (127)
Attention Problems -1.8 -1.6 -5.3 -3.2 26 (20.2) 90 (69.8) 11 (8.5) 2 (1.6)
(n=129) (7.7) (8.3) (9.5) (8.8)
(107) (94) (72) (127)
Rule-Breaking Behavior -0.1 -1.6 -2.7 -1.8 18 (14.0) 100 (77.5) 9 (7.0) 2 (1.6)
(n=129) (5.6) (6.8) (6.4) (6.3)
(107) (94) (72) (127)
Social Problems -1.6 -1.8 -2.8 -2.2 32 (24.8) 86 (66.7) 9 (7.0) 2 (1.6)
(n=129) (5.8) (6.3) (6.9) (6.0)
(107) (94) (72) (127)
Somatic Complaints -2.5 -3.0 -3.5 -3.8 30 (23.3) 85 (65.9) 12 (9.3) 2 (1.6)
(n=129) (6.8) (8.0) (6.8) (7.3)
(107) (94) (72) (127)
Thought Problems -1.8 -2.1 -2.6 -2.4 28 (21.7) 86 (66.7) 13 (10.1) 2 (1.6)
(n=129) (8.6) (8.1) (7.6) (8.7)
(107) (94) (72) (127)
Withdrawn/Depressed 0.1 0.6 0.1 0.3 16 (12.4) 89 (69.0) 22 (17.1) 2 (1.6)
(n=129) (6.6) (6.6) (8.4) (7.3)
(107) (94) (72) (127)
a
T-scores relate to a reference population with mean 50, SD 10; higher scores indicate greater problems, hence reductions in scores indicate
improvements.
b
Last value is the last assessment while the patient was receiving BRV.
c
Categories: normal, borderline, clinically significant.

S68 Annals of Neurology Vol 86 (suppl 23) 2019

55. Analysis of a Database of Children with Infantile system. We identified all users with infantile spasms from
Spasms in Seizure Tracker (TM) 2010 to 2017 and analyzed the number of users, the types of
LaGrant B (New York, NY), Goldenholz D, Moss R, users (by frequency of events), patterns in reporting, and sei-
Grinspan Z zure cluster characteristics.
Objective: To describe the demographic and seizure cluster Results: We identified 314 unique infants (51.6% female)
characteristics of infantile spasms as reported by families with infantile spasms. Their parents/guardians reported
using an electronic seizure diary. 24,675 infantile spasm cluster events. 47 (15%) users were
Methods: Seizure TrackerTM is a seizure diary system that frequent reporters (over 100 events), 123 (39%) were moder-
allows users to track seizure events for him/herself or for a ate reporters (between 5 and 100 events), and 144 (46%)
child via website, mobile, and voice interactions with the were infrequent reporters (fewer than 5 events). There were
fewer spasms events at night than expected--21.6% of events
were reported between 11pm and 7am (p< 0.001). The
median duration of a seizure cluster was 149 seconds and the
median number of spasms per cluster was 10. There was a
significant positive association between the number of spasms
and the reported severity of spasms (r= 0.22; p< 0.001).
Conclusions: There is wide variation in the extent to which
individuals use Seizure Tracker. In addition, there may be a
daytime reporting bias of infantile spasms. Future studies will
compare this cohort to a sample of patients with infantile
spasms to determine whether the reported seizure cluster
characteristics from Seizure Tracker are consistent with
clinical data.
Keywords: Epilepsy

56. Time to Onset of Efficacy of Cannabidiol (CBD)

During Titration in Patients with Lennox-Gastaut
Syndrome (LGS) or Dravet Syndrome (DS) Enrolled in
Three Randomized Controlled Trials
FIGURE 1: Histogram of Spasm Cluster Duration – Marsh E (Philadelphia, PA), Privitera M, Mazurkiewicz-
Logarithmically Transformed (excluding reports of Bełdzi
nska M, Villanueva V, Checketts D, Knappertz V
0 seconds). Abstract 55 [Color figure can be viewed at www.
wileyonlinelibrary.com] Objective: To determine time to onset of efficacy of add-on
CBD treatment using a post-hoc analysis of efficacy by cumu-
lative day during titration in three Phase 3 randomized con-
trolled trials in patients with DS (GWPCARE1/
NCT02091375) and LGS (GWPCARE3/NCT02224560;
GWPCARE4/NCT02224690).
Methods: Patients received plant-derived pharmaceutical
formulation of highly purified CBD (Epidiolex®;
100 mg/mL) at 10 mg/kg/day (GWPCARE3) or
20 mg/kg/day (all trials), or placebo. CBD treatment started
at 2.5 mg/kg/day and reached 10 mg/kg/day on Days 7/8
and 20 mg/kg/day by Day 11 in higher dose groups. Cumu-
lative frequencies of convulsive (DS) and drop seizures
(LGS) were calculated as 28-day averages for each titration
day (including previous treatment days). Adverse events
(AEs) were assessed.
Results: Overall, 296 patients were randomized to CBD and
220 to placebo. Mean age was 10 years (DS; GWPCARE1)
and 15 years (LGS; GWPCARE3/GWPCARE4). Nominal
significance for median percentage reductions in primary sei-
zure type frequency for CBD versus placebo emerged by Day
10 in GWPCARE1 (P=0.026) and Day 8 (10 mg/kg/day
group; P=0.0368) or Day 6 (20 mg/kg/day group; P=0.0061)
in GWPCARE3/GWPCARE4 (pooled data). Of patients with
FIGURE 2: Histogram of the Number of Spasms per Cluster AEs, 60% had their first during titration. Differences for CBD
(excluding reports fewer than two). Abstract 55 [Color figure versus placebo in overall AEs and some common AEs were evi-
can be viewed at www.wileyonlinelibrary.com] dent during titration but generally to a lesser degree than

Program and Abstracts, Child Neurology Society S69

during the treatment period. Most common (≥10%) AEs:
somnolence, decreased appetite, fatigue, and diarrhea.
Conclusions: Findings suggest that the titration schedule
used in the GWPCARE trials led to a significant treatment
effect for CBD within 6–10 days during up titration.
Funding: GW Research Ltd
Keywords: Epilepsy, Rare Diseases, Critical Care

57. Cannabidiol as a Novel Treatment for Lafora Body

Disease – A Case Report
Nayak A (Houston, TX), Riviello J
FIGURE 1: Abstract 58 [Color figure can be viewed at www.
Objective: Lafora body disease is an intractable progressive
wileyonlinelibrary.com]
myoclonic epilepsy that is autosomal recessive disorder second-
ary to a mutation in EPM2A gene. Although usually refractory
to antiseizure medications- more recently, valproic acid and showed that 4 of 6 patients (67%) in music effective group,
perampanel have been shown to have efficacy. We report a sin- during listening to the music demonstrated decreased LF/HF
gle case showing a response to Epidiolex (Cannabidiol). ratio (67%). All of them also showed increased in HF nu.
Methods: Our patient is a 17 year old female who started hav- Conclusions: Listening to Mozart K.448 music decreases
ing seizures at age 14 years. The seizure semiology was multi- epileptiform discharges in our epilepsy patients. HRVduring
ple: including absence, generalized tonic clonic and most listening to music showed increased parasympathetic activity.
disabling, myoclonic and atonic seizures. She was tried on Keywords: Epilepsy, Teaching of Child Neurology
clobazam, valproic acid, zonisamide, and levetiracetam with a
poor or transient response, and there was actual worsening with 59. Risk Factors and Comorbidities in Pediatric Epilepsy
lamotrigine. She also had VNS implantation. WES showed in the Seizures and Outcomes Study
two pathogenic variants in the gene for EPM2A. She was then Record E (Washington, DC), Bumbut A, Kroner B, Gaillard W
started on felbamate and Clonazepam, also without success. Objective: To characterize risk factors and comorbidities in a
Epidiolex was subsequently started at 10 mg /kg/day dose. pediatric epilepsy population, in a major city with diversity
Results: Favorable response was noted per parental seizure and differences in socioeconomic levels.
report at follow up appointment with reduction in the num- Methods: SOS-KIDS is a cross-sectional cohort study of pedi-
ber of myoclonic and atonic drop seizures, with increased atric epilepsy patients who live in Washington DC and are
alertness and improvement in cognition. The mechanism of evaluated at Children’s National. Families were recruited at
action of Cannabidiol in this case is unknown at this time. their child’s routine clinic appointment or inpatient visit.
Conclusions: To our knowledge this is the first case Information was extracted from participants’ EMR including
described to show the efficacy of cannabidiol in a progressive seizure risk factors, etiology, characteristics, and comorbidities.
myoclonic epilepsy. Results: Data were collected from 289 participants (47% female,
Keywords: Epilepsy, Translational/Experimental Therapeu- 53% male) and mean age was 7.8 years (2 months to 17 years).
tics, Genetics 80% were African American, 11% Caucasian, and 9% Hispanic.
There are several perinatal risk factors for epilepsy: extreme pre-
58. The Effect of Mozart K. 448 Music on Interictal maturity (10%), IVH (6.9%), and neonatal seizures (6.9%).
Epileptiform Discharges in Children with Epilepsy: A Other risk factors include febrile seizures (16.3%), malformation
Randomized Controlled Trial: A Pilot Study of cortical development (13.5%), known genetic disorders
Paprad T (Bangkok, Thailand), Veeravigrom M (8.6%), presumed genetic disorders (10.7%), head injury
Objective: We aim to study the effect of Mozart K.448 for (5.2%), and CNS infections (1.7%). Numerous participants had
2 pianos music on interictal epileptiform discharges and documented comorbidities including headaches (14.9%),
quantitative EEG in epilepsy patients. The second objective ADHD (14.2%), intellectual disability (12.8%), autism (8.0%),
is to study heart rate variability (HRV) during listening to depression (1.7%), and anxiety (3.5%).
Mozart K.448 which represents parasympathetic activity. Conclusions: We identified a wide variety of risk factors and
Methods: The study design is a blinded randomized control etiologies among pediatric epilepsy patients; genetic, structural,
trial with placebo controlled. The treatment group listened to or acquired components were similar to previous studies. The
the 8 minutes of Mozart K. 448 for 2 pianos during the documented comorbid medical/psychiatric conditions appear
EEG recording. The control group was in quiet environment. underreported compared to other studies. This may in part
The EEG readers counted IEDs for 8 minutes before, during derive from underreporting by patients and under-diagnosis by
and after listening to the song. Quantitative EEG (qEEG) clinicians (especially depression). Future studies will compare
and HRV were analyzed in each period. EMR documentation and active parental and patient screen-
Results: A total of 28 patients aged 0-18 years were enrolled, ing. Identification and documentation of comorbidities may
9 in music group and 13 in controlled. 55% in music group be important for improved overall care. This study is
compared had significantly decreased IEDs during listening supported by the Centers for Disease Control and Prevention.
to the music (RR 0.68, 95% CI 0.65-0.71). HRV analyses Keywords: Epilepsy, Cognitive/Behavioral Disorders

S70 Annals of Neurology Vol 86 (suppl 23) 2019

60. Safety of Valtoco™ (NRL-1; Diazepam Nasal Spray) Objective: To evaluate safety/tolerability of NRL-1 (intrana-
in Children and Adolescents with Epilepsy: Interim sal diazepam) over 12-months in a pediatric (aged 6-17 years)
Subgroup Results from a Phase 3, Open-Label, 12-Month subgroup treated for cluster or acute repetitive seizures.
Repeat Dose Study Methods: Enrolled patients were adults and children/adoles-
Segal E (Hackensack, NJ), Tarquinio D, Miller I, Dlugos D, cents with epilepsy having seizures despite a stable anti-
Wheless J, Carrazana E, for the DIAZ 001.04 Study Group epileptic regimen. Patients/caregivers administered 5, 10,
15, or 20 mg of NRL-1 (weight-based), with a second dose
administered, if needed, 4-12 hours later. Investigators could
adjust doses for efficacy/safety. Safety measures included
TABLE 1. Abstract 60 treatment-emergent adverse events (TEAEs),
TEAE Incidence, n (%) physical/neurological examination, vital signs, laboratory
tests, nasal irritation, and smell tests.
6-11 years 12-17 years Results: This interim analysis evaluated 28 children 6-11
(n = 28) (n = 21) years old (57.1% female, 89.3% white) and 21 adolescents
12-17 years old (28.6% female, 66.7% white). Among these
≥1 TEAE 22 (78.6) 12 (57.1) patients, 19 (38.8%) had exposure ≥6 months and
16 (32.7%) ≥12 months; 29 patients (59.2%) averaged ≥2
TEAE leading to study 0 0
doses/month. Twenty-two children (78.6%) and 12 adoles-
discontinuation
cents (57.1%) had ≥1 TEAE. Eleven (39.3%) children and
Serious TEAE 11 (39.3) 6 (28.6) 6 adolescents (28.6%) had serious TEAEs; none was deemed
related to study drug. No trends were observed in the inci-
Treatment-related TEAE 2 (7.1) 5 (23.8) dence of the most frequent TEAEs (Table). Treatment-
Eye irritation 1 (3.6) 0 related TEAEs (Table) included irritation and epistaxis in
children (1 patient each), and epistaxis, somnolence, seda-
Epistaxis 1 (3.6) 1 (4.8) tion, rash, nasal mucosal disorder, and sleep disorder in ado-
Sedation 0 1 (4.8) lescents (all 1 patient each). Few children/adolescents
reported nasal irritation; smell tests showed no clinically rele-
Somnolence 0 1 (4.8) vant olfactory changes. There were no trends in effects on
Nasal mucosal disorder 0 1 (4.8) hematology, chemistry/urinalysis values; no electrocardio-
graphic abnormalities were observed.
Rash 0 1 (4.8) Conclusions: In this interim analysis of long-term safety,
Sleep disorder 0 1 (4.8) repeated dosing of NRL-1 demonstrated a favorable
safety/tolerability profile in children and adolescents with
Most common TEAE (≥2 epilepsy.
patients in either age Keywords: Epilepsy
group)
Seizure 5 (17.9) 4 (19.0) 61. Long-Term Safety and Efficacy of Add-on
Cannabidiol (CBD) Treatment in Patients with Dravet
Constipation 4 (14.3) 0
Syndrome (DS) in an Open-Label Extension (OLE) Trial
Influenza 4 (14.3) 0 Shiloh-Malawsky Y (Chapel Hill, NC), Scheffer I, Halford J,
Nabbout R, Sanchez-Carpintero R, Wong M, Checketts D,
Nasopharyngitis 4 (14.3) 0 VanLandingham K
Upper respiratory tract 4 (14.3) 0 Objective: Efficacy and safety of add-on CBD treatment for
infection patients with DS were studied in 2 randomized, placebo-
Vomiting 4 (14.3) 0
controlled trials (GWPCARE1&2). Results of the second
interim analysis of the OLE (GWPCARE5
Laceration 3 (10.7) 0 [NCT02224573]) of these studies are reported.
Methods: Patients received plant-derived highly purified
Pneumonia 3 (10.7) 2 (9.5)
CBD in oral solution (Epidiolex®; 100 mg/mL). The pri-
Pyrexia 3 (10.7) 1 (4.8) mary endpoint was safety. Secondary endpoints were change
from baseline in convulsive and total seizure frequency and
Epistaxis 2 (7.1) 1 (4.8)
Subject/Caregiver Global Impression of Change.
Fatigue 2 (7.1) 0 Results: Of 289 patients who completed the randomized
controlled trials, 278 enrolled in GWPCARE5. At data cut-
Sinusitis 2 (7.1) 0
off, 14% of patients had completed, 52% were ongoing, and
Somnolence 2 (7.1) 1 (4.8) 34% had withdrawn. Mean patient age was 9.8 years; 97%
were <18 years. Patients were taking a median of 3 concurrent

Program and Abstracts, Child Neurology Society S71

antiepileptic drugs with 68% taking clobazam, 63% val- neurodevelopmental outcomes reported to be associated with
proate, and 39% stiripentol. The mean of patients’ modal treatment-refractory seizures.
CBD dose was 22 mg/kg/d. Adverse events (AEs) and serious Keywords: Epilepsy
AEs were reported by 96% and 32% of patients, respectively;
7% discontinued due to AEs. Elevated liver transaminases 63. Epilepsy Characterization in a Pediatric Population
>3× upper limit of normal were reported in 26/129 patients; with Celiac Disease
none had severe liver injury (Hy’s Law); at time of analysis, Swartwood S (Salt Lake City, UT), Trandafir C
19/26 had resolved. Two nontreatment-related deaths were Objective: This retrospective study aims to characterize dis-
reported. Median percentage reductions from baseline tinctive features of epilepsy in a pediatric population with
assessed in 12-week intervals were 44%–57% for convulsive celiac disease (CD) and epilepsy, and determine the effect of
and 49%–67% for total seizures through 72 weeks. Over gluten-free diet on seizure burden.
80% of patients/caregivers reported improvements in overall Methods: Retrospective chart review of patients treated at
condition. Primary Children’s Hospital in Salt Lake City, Utah, dating
Conclusions: Long-term treatment with add-on CBD in back to 2002 with ICD-10 codes for both seizure/epilepsy
patients with DS produced sustained seizure reductions, and CD.
with no new safety concerns emerging.Funding: GW Results: Of 190 charts reviewed, 23% had biopsy proven
Research Ltd CD and 12% had only positive serologic markers. In patients
Keywords: Epilepsy, Rare Diseases, Critical Care with CD or positive serologic markers for CD, 22% had
intractable epilepsy. Focal seizures with secondary generaliza-
62. ZX008 (Fenfluramine HCl Oral Solution) Provides tion and generalized tonic-clonic seizures were the most fre-
Long-Term, Clinically Meaningful Reduction of quent seizure types seen in these patients. Interictal temporal
Convulsive Seizure Frequency in Young (<6 years old) lobe epileptiform discharges were common. Brain imaging
Dravet Syndrome Subjects: Analysis From Long-Term studies were abnormal in 20% of patients, however cerebral
Open-Label Study calcifications were not reported. In patients with intractable
Sullivan J (San Francisco, CA), Nabbout R, Knupp K, Laux L, epilepsy and CD or positive serologic markers for CD, adher-
Wirrell E, Thiele E, Schoonjans A-S, Farfel G, Morrison G, ing to a gluten-free diet either reduced seizure frequency or
Gammaitoni A, Mistry A, Agarwal A, Galer B resulted in weaning dosage or weaning off of one or more
Objective: A recent study examining epilepsy onset before antiepileptic drugs in 57% of patients.
2 years of age identified uncontrolled seizures as a predictor Conclusions: Patients with intractable epilepsy and chronic
of poor developmental outcome. We conducted a post-hoc gastrointestinal symptoms should be evaluated for CD, since
analysis of the efficacy and safety of ZX008 (fenfluramine a reduction in seizure burden may be achieved from adhering
HCl oral solution) in patients with Dravet syndrome to a gluten-free diet. Furthermore, patients with particular
(DS) <6 years old. epileptic presentations, specifically temporal or occipital sei-
Methods: Patients (2-18 years old) with DS entered an zures, and with gastrointestinal symptoms may benefit from
open-label extension (OLE) study after completing one of evaluation for possible CD.
two phase 3 studies. In the OLE, all subjects initially received Keywords: Epilepsy
0.2 mg/kg/day ZX008 for 1 month; dosing was then titrated
to optimal effect (maximum dose=0.8 mg/kg/day (maximum 64. Pharmacokinetics and Safety of Valtoco™ (NRL-1;
30 mg/day) or in patients also receiving stiripentol, 0.5 Diazepam Nasal Spray) in Children with Epilepsy During
mg/kg/day (maximum 20 mg/day). Seizure (Ictal/peri-ictal) and Non-seizure (Inter-ictal)
Results: A total of 42 of 158 (26.6%) subjects who Conditions: Results from a Phase 1, Open-Label Study
enrolled in the OLE were <6 years old upon entry into the Tarquinio D (Atlanta, GA), Segal E, Wheless J, Rabinowicz A,
phase 3 studies. The median baseline monthly convulsive Carrazana E, for the DIAZ 001.04 Study Group
seizure frequency (MCSF) prior to double-blind treatment Objective: To evaluate the relative comparability of pharma-
was 10.7 seizures/month (range, 4.0 to 147.3). At the time cokinetics and safety of NRL-1 (intranasal diazepam) in chil-
of the OLE interim analysis, the median decrease in MCSF dren with epilepsy during ictal/peri-ictal and inter-ictal
over the entire observation period compared to baseline periods.
was -75% (P<0.001) compared with -64% in the overall Methods: Patients were diagnosed with partial or generalized
study population (2-18 years of age). The most frequently epilepsy with motor seizures or seizures with clear alteration
reported AEs included pyrexia, upper respiratory tract of awareness. Open-label intranasal NRL-1 was administered
infections, decreased appetite, and diarrhea. No valvular during two periods (ictal/peri-ictal, inter-ictal) ≥14 days
heart disease or pulmonary arterial hypertension was apart. In both periods, one dose was administered (5, 10,
observed. 15, or 20 mg; based on weight), with a second dose permit-
Conclusions: Treatment with ZX008 provided sustained, ted if seizures persisted. Blood samples were taken at
clinically meaningful reduction in MCSF in DS subjects pre-specified timepoints after dosing, analyzed for diazepam,
<6 years old. Importantly, effective control of seizures in this and pharmacokinetic measures were calculated. Safety was
young age group might be expected to mitigate the negative assessed.

S72 Annals of Neurology Vol 86 (suppl 23) 2019

 similar under ictal/peri-ictal and inter-ictal conditions for
TABLE 1. Abstract 64 both age groups (Table). Among all 58 patients,
tmax, hr, 17 (29.3%) had ≥1 treatment-emergent adverse event
AUC0-6, Cmax, median (TEAE). Of these, 8 patients had treatment-related TEAEs
with those reported in ≥2 patients being dysgeusia (n=3;
hr•ng/mL, ng/mL, (min,
5.2%) and nasal discomfort (n=2; 3.4%); no local toxicity
Age group mean
SD mean
SD max)
was observed. There were no serious TEAEs in children,
and overall, only 1 patient had serious TEAEs (recurrent
6 to 11 years seizures, toxic encephalopathy), which were deemed
Inter-ictal (n 739
542 223
148 2.1 (0.8, unrelated to study treatment. No patient required a second
= 10) 6.0) dose for persistent seizures.
Conclusions: The epileptic condition (ictal/peri-ictal, inter-
Ictal/peri-ictal 532
363 148
83 2.0 (1.0, ictal) appeared to have minimal impact on intranasal NRL-1
(n = 10) 4.2) diazepam pharmacokinetics in children with epilepsy. Similar
12 to 16 years to findings in adults. NRL-1 demonstrated a good safety
profile.
Inter-ictal 314
134 103
46 1.8 (1.0, Keywords: Epilepsy
(n = 3) 2.0)
Ictal/peri-ictal 536
188 201
62 1.9 (1.5, 65. Ictal "Squeaks": A Newly Described Semiology of
(n = 4) 6.0) Generalized Seizures
Tsuboyama M (Miami, FL), Fajardo M, Rodriguez A,
AUC, area under the plasma concentration time curve; Cmax, maxi- Resnick T
mum plasma concentration; tmax, time to maximum plasma
concentration
Objective: We describe two patients who presented with a
high-pitched vocalization found to be an ictal phenomenon
not well-described in current literature.
Methods: Two patients were admitted to our epilepsy moni-
Results: The study enrolled 58 patients aged 6-59 years. toring unit with spells characterized by brief, high-pitched
Pharmacokinetic data were available from 10 children 6-11 vocalizations lasting less than one second previously diag-
years old (60% female, 80% white), and 4, 12-16 years old nosed as tics. Case A is a 14-year-old female with history of
(75% female, 75% white). Pharmacokinetic values were generalized tonic-clonic and absence seizures who presented

FIGURE 1: Ictal EEG for patients A and B was characterized by a generalized, high amplitude spike and slow wave discharge
followed by diffuse quasi-rhythmic delta. The vocalization was time-locked with the slow wave following the more prominent
generalized, high amplitude spike. At times, this ictal pattern was preceded by 1-2 second buildup of generalized spike and
wave discharges. A) Patient A’s ictal EEG in a longitudinal bipolar montage (top) and average montage (bottom). B) Patient B’s
ictal EEG in a longitudinal bipolar montage (top) and average montage (bottom). Abstract 65 [Color figure can be viewed at
www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S73

with a “squeak” which was at times accompanied by truncal 67. Yield of Video EEG Monitoring for Patients Admitted
flexion occurring up to 40 times daily. Case B is a 3-year-old to a Primary Pediatric Neurology Inpatient Service
male with history of recent onset generalized convulsions Wood E (Aurora, CO), Park K, Messer R
treated with levetiracetam who presented with brief muscle Objective: Children experiencing spells that cannot safely
jerks and vocalizations occurring multiple times daily. wait for outpatient evaluation are often admitted for urgent
Results: Seizures manifesting as squeaks in both patients inpatient video electroencephalogram (EEG) monitoring.
were generalized in onset (Figure 1). In Case A, these were Our hospital’s pediatric neurohospitalist program recently
seen as part of subtle tonic seizures with neck flexion and launched a primary inpatient service, separate from our Epi-
bilateral arm abduction. In Case B, the events were shorter in lepsy Monitoring Unit and consult service. We evaluated the
duration and more consistent with myoclonic seizures. Both yield of inpatient EEG monitoring as an important quality
of the patients had frequent generalized epileptiform abnor- improvement metric.
malities interictally and did not have other seizure types Methods: We performed retrospective chart review of
found in the remainder of the EEG recordings. 74 inpatients (Sep 2018-Jan 2019) to determine reason for
Conclusions: Although brief vocalizations are often associ- admission, time to first spell captured on EEG, EEG dura-
ated with tics, they can also be seen as an ictal manifestation. tion, and length of stay. We compared our center to publi-
Ictal vocalizations in generalized seizures typically are charac- shed literature (Tables 1 and 2).
terized by a sustained, low-pitch groan. Additionally, ictal Results: Half (38/74) of our inpatients underwent EEG for
vocalizations have been described in association with frontal spell capture, which provided information that changed man-
lobe seizures. We demonstrate, however, that ictal “squeak” agement in most cases. Successful spell capture occurred in
may be a feature seen in generalized or rapidly generalizing 65.8% (25/38), similar to the literature, but EEG duration
seizures. (18.9 vs. 25 hrs) and time to first spell (2.0 vs. 4.5 hrs) were
Keywords: Epilepsy shorter. Spells were nonepileptic in 44% (14/25). Interest-
ingly, 17% of EEGs were less than 12 hours, but EEG was
66. Targeted Therapy with Sirolimus for NPRL3 Epilepsy continued for a median of 15.3 hours after the first spell.
Vawter-Lee M (Cincinnati, OH), Franz D, Greiner H Most patients were under 6 years of age (50%), and only
Objective: We describe our experience using sirolimus as 29.7% had a prior diagnosis of epilepsy.
targeted therapy for epilepsy due to a NPRL3 (nitrogen per-
mease regulator-like 3) mutation.
Methods: NPRL3, NPRL2, and DEPDC5 (disheveled, Egl-
10, and pleckstrin (DEP) domain-containing 5) form the
GATOR1 complex (GTPase-activating protein (GAP) activ- TABLE 1. Patient population comparison.
ity toward RAG complex 1)[1]. GATOR1 negatively regu- Abstract 67
lates mammalian target of rapamycin (mTOR), and Our Literature
mutations in it have been associated with epilepsy and corti- Institution Estimate
cal malformations[2]. We hypothesized that an mTOR
inhibitor could be used to treat epilepsy due to a NPRL3
Age Range 0.31-17.5 0.08-18
mutation.
yrs yrs1-3
Results: A neonate had muscle twitches that electroencepha-
logram (EEG) confirmed to be seizures. Seizures were intrac- Age Breakdown Under 2 yrs 0.1-5.9 yrs =
table to many medications. At one month old EEG showed = 42.1% 41.6%
burst suppression and infantile spasms. Brain imaging 2-6 yrs = 6-11.9 yrs =
showed a left hemisphere cortical malformation. ACTH and 7.9% 39.9%
vigabatrin were started which led to cessation of spasms, but 6-10 yrs = 12-17.9 yrs =
focal seizures were intractable and 20-60 occurred per day. 5.3% 18.5%3
An epilepsy panel (EpiXpanded panel, GeneDx, Gaithers- 10-14 yrs =
burg, MD) revealed a heterozygous deletion within 16p13.3,
21.1%
which includes NPRL3. At 3 months old sirolimus was
>14 yrs =
started. After one week seizures began to improve, and after
23.7%
three weeks seizures were completely controlled. At seven
months old seizures returned when sirolimus was held for an Median Age 6.54 yrs 7 yrs1,3
infection, and seizure control was not regained until a left
Average Age 7.45 yrs 7.4 yrs2
functional hemispherotomy was performed.
Conclusions: To our knowledge this is the first report of Proportion of patients 29.7% 48%1
treatment with an mTOR inhibitor for NPRL3-related epi- with prior epilepsy
lepsy. mTOR inhibitor medications such as sirolimus should diagnosis:
be considered as a targeted treatment option in patients with
*Literature ranges had some variation (2.0-13.51, 0.08-182,
intractable epilepsy and GATOR mutations such as NPRL3.
0.08-17 yrs3)
Keywords: Epilepsy, Genetics

S74 Annals of Neurology Vol 86 (suppl 23) 2019

 TABLE 2. EEG yield comparison. Abstract 67
Our Interquartile Range Literature Interquartile Range
Institution (25%-75%) Estimate (25%-75%)

Duration of EEG 18.9 hrs 15.6-28.7 hrs 25 hrs1 22-48.5 hrs1

(median)
Rate of Spell Capture 65.8% 47-66%1-3
Time to first spell 2.0 hrs 0.7-5.88 hrs 4.5 hrs1 1.4-18.8 hrs1
(median)

Conclusions: Our primary service provided successful EEG and treatment may improve recovery and long-term out-
spell capture in most cases, often in less time than the litera- comes in this poorly understood subset of pediatric epilepsy.
ture. Next steps will evaluate factors that influence these key Keywords: Epilepsy, Infections/Neuroimmunology, Rare
metrics, such as frequency of spells, and determine interven- Diseases
tions, such as early EEG review and discussion with family,
to improve the resource utilization, yield, and cost of urgent 69. Collaborating to Improve Epilepsy Surgical Care in
inpatient EEGs. Children: The Pediatric Epilepsy Research Consortium
Keywords: Epilepsy, Teaching of Child Neurology (PERC) Surgery Subgroup
Perry M (Fort Worth, TX), Wong-Kisiel L, Grinspan Z,
Marashly A, Bolton J, Chapman K, Mohamed I, Wolf S,
68. FIRES: A Case of Immunological Dysregulation? McGoldrick P, Alfarano A, May A, Shrey D, Fedak E, Singh R,
Yang J (San Diego, CA), Nataraj S, Sattar S Clarke D
Background: Febrile infection-related epilepsy syndrome Objective: The Pediatric Epilepsy Research Consortium
(FIRES) is a rare epileptic syndrome characterized by new (PERC) is a network of US pediatric epilepsy centers provid-
onset refractory status epilepticus that is preceded by a febrile ing infrastructure to facilitate collegial, collaborative, practice-
illness. Studies have shown that elevated levels of pro- changing research that delivers answers needed to improve
inflammatory cytokines may contribute to its pathophysiol- the care of children with epilepsy. The Epilepsy Surgery Sub-
ogy. There is evidence supporting the safety and efficacy of group was formed in 2018 to characterize the use of pediatric
Anakinra, an IL-1 recombinant receptor antagonist, to reduce epilepsy surgery in the US and define current practices for
seizure burden in children with FIRES although the literature candidate selection and treatment. We describe the program
on clinical outcomes are limited. characteristics of the participating member institutions.
Case Presentation: A 6-year-old previously healthy girl pre- Methods: This is a cross sectional survey of pediatric surgery
sents with seizures, dyskinesias, behavioral changes and experience at epilepsy centers participating in the PERC Epi-
encephalopathy several days following a upper respiratory lepsy Surgery Subgroup. The survey included questions
infection. related to program participants, technologies, and evaluation
Results: The patient had an extended intensive care admission methods. We disseminated the survey via Qualtrics. We pre-
due to clinical and subclinical seizures. Infectious work up was sent results using descriptive statistics.
significant for positive rhinovirus/enterovirus respiratory PCR. Results: Fifteen of the eighteen (83%) centers provided pro-
Otherwise, cerebrospinal fluid studies, neuroimaging, autoim- gram characteristics (table) demonstrating commonalities in
mune encephalitis panel, metabolic work up, and whole baseline technology, participating professionals, and accredita-
genome sequencing were unrevealing. A brain biopsy did not tion (National Association of Epilepsy Centers Level 4:
show any pathological findings. Seizures were treated with 14, 93%). Differences arose in size of faculty, years of experi-
multiple antiepileptic medications (levetiracetam, fosphenytoin, ence, and additional technologies. In the first year of operation,
phenobarbital, topiramate, lacosamide, CBD oil), anesthetic 183 patients have been enrolled from 7 sites and the remaining
infusions (midazolam, pentobarbital, lidocaine), and ketogenic 11 sites are expected to begin contributing data this year.
diet. High dose steroids and IV immunoglobulin were admin- Conclusions: The PERC Epilepsy Surgery Subgroup repre-
istered without improvement. Four weeks into her course, sents a unique opportunity to collect significant data on mul-
Anakinra was added to her regimen with resolution of seizures tiple aspects of epilepsy surgery in the US. Participating
and improvement in mental status. The patient was discharged programs differ in size, years of experience, and methods of
home seizure-free albeit with residual impulsivity, gross/fine evaluation. Meaningful comparisons between centers will bet-
motor and cognitive impairment. ter define best practices for candidate selection, evaluation,
Discussion: We present a case of FIRES with a robust and treatment.
response to IL-1 blockade, illustrating that early recognition Keywords: Epilepsy

Program and Abstracts, Child Neurology Society S75

 TABLE 1. Abstract 69
Size n (%) Experience n (%) Invasive Monitoring n (%)

Participating Faculty* <10 yrs 2 (13) ECOG used routinely

≤11 1 (7) 10-30 yrs 8 (53) Yes 11 (73)
12-17 10 (67) >30 yrs 5 (33) No 4 (27)
>18 4 (27) Invasive EEG 13 (87)
Technology
EMU Beds 7 (47) Strips 14 (93)
≤8 5 (33) VEEG, 3T MRI, PET, SPECT 15 (100) Grids 13 (87)
9-15 3 (20) Additional Technologies 13 (87) SEEG 14 (93)
≥16 7 (47) MEG 4 (27) Combined
EEG Staff 4 (27) TMS 9 (60)
≤15 2 (13) Intra-op MRI 12 (80)
16-25 Image post-processing 7 (47)
≥25 EEG Source Localization 12 (80)
Surgical robotics
*Epileptologists, Neurosurgeons, Neuropsychologists, Neuroradiologists
Abbreviations: VEEG=video electroencephalogram; EMU=epilepsy monitoring unit; MRI=magnetic resonance imaging; PET=positron emission
tomography; SPECT=single photon emission computed tomography; ECOG=electrocorticography; MEG=magnetoencephalogram; TMS=transcranial
magnetic stimulation; SEEG=stereo-electroencephalography

70. Cannabidiol (CBD) Significantly Reduces Convulsive and discontinuations due to AEs occurred more frequently
Seizure Frequency in Dravet Syndrome: Results of a for CBD20 than CBD10 or placebo. Dose increases above
Dose-Ranging, Multicenter, Randomized, Double-Blind, 10 mg/kg/day should be tailored to individual efficacy/safety.
Placebo-controlled Trial Funded by GW Research Ltd.
Perry M (Fort Worth, TX), Miller I, Scheffer I, Gunning B, Keywords: Epilepsy, Rare Diseases, Critical Care
Sánchez-Carpintero R, Gil-Nagel A, Saneto R, Checketts D,
Dunayevich E, Knappertz V 71. Long-term Safety and Efficacy of Add-on Cannabidiol
Objective: Assess the efficacy and safety of 2 doses of add-on (CBD) Treatment in Patients with Lennox-Gastaut
CBD for seizures in Dravet syndrome (GWPCARE2/ Syndrome (LGS) in an Open-Label Extension (OLE)
NCT02224703). Trial (GWPCARE5)
Methods: 199 patients were randomized to receive highly Perry M (Fort Worth, TX), Patel A, Gil-Nagel A, Chin R,
purified CBD (approved as Epidiolex®in the U.S.) at Mitchell W, Weinstock A, VanLandingham K
20 mg/kg/day (CBD20; n=67), 10 mg/kg/day (CBD10; Objective: To assess long-term safety and efficacy of add-on
n=67), or placebo (pbo; n=65). The primary endpoint was CBD treatment in patients with LGS in a second interim
change from baseline in convulsive seizure frequency over the analysis of an OLE trial.
14-week treatment period. Methods: Patients who completed a 14-week, double-blind,
Results: Mean age was 9 years. Patients had discontinued a randomized controlled trial (GWPCARE3/NCT02224560;
median of 4 AEDs, and were on a median of 3. Percentage GWPCARE4/NCT02224690) could enter this OLE
reduction in convulsive seizures was higher for CBD20 (46%) (GWPCARE5/NCT02224573). Patients received a plant-
and CBD10 (49%) vs. pbo (27%; p=0.0299 and p=0.0095), derived pharmaceutical formulation of highly purified CBD
as were ≥50% responder rates (49% and 44% vs. 26%; (Epidiolex®; 100 mg/mL) for ≤3 years. Primary endpoint:
p=0.0069 and p=0.0332) and % reduction in total seizures safety. Secondary endpoints: drop and total seizure frequency;
(47% and 56% vs. 30%; p=0.0255 and p=0.0003). Incidence Subject/Caregiver Global Impression of Change (S/CGIC).
of adverse events (AEs) was similar across groups (90% Results: 366 of 368 patients who completed GPWCARE3/
CBD20, 88% CBD10, 89% pbo); 5 most common were GWPCARE4 entered the OLE. Median (range) follow-up:
decreased appetite, diarrhoea, somnolence, pyrexia, and fatigue. 61 weeks (3 days to 87 weeks); 88 (24%) withdrew. Mean age:
Serious AEs occurred in 25% CBD20, 20% CBD10, and 16 years; 33% ≥18 years. Baseline median seizure
15% pbo patients. Discontinuations due to AEs occurred only frequency/28 days: 80 drop and 168 total seizures. During the
for CBD20 patients (7%). Elevated transaminases exceeding extended follow-up, adverse event (AE) incidence: 94%; serious
3× upper limit of normal (ULN) occurred in 19% CBD20 AE incidence: 33%; 11% discontinued due to AEs. Most com-
and 5% CBD10 patients, all on valproate; none had elevations mon AEs (≥20%): diarrhea, convulsion, somnolence, pyrexia,
in bilirubin; all elevations resolved. There were no deaths. vomiting, and decreased appetite. Forty-seven patients (13%)
Conclusions: CBD20 and CBD10 significantly reduced sei- had elevations in liver transaminases >3x upper limit of normal;
zure frequency vs. pbo. Elevated transaminases, certain AEs, 35 (74%) were taking valproate; none had severe liver injury

S76 Annals of Neurology Vol 86 (suppl 23) 2019

(Hy’s law). Five deaths occurred, none deemed treatment- postulate the reason for these differences and also described
related by the investigator. Median percentage reductions in sei- cannabidiol (CBD) use for the first time in FIRES.
zure frequency (12-week windows over 72 weeks): 48–70% for Methods: Case report of two patients, who presented to our
drop seizures; 48–63% for total seizures. Approximately 88% of hospital and were diagnosis with FIRES.
patients/caregivers reported an improvement in overall condi- Results: Patient 1: 7 YOF presented with FIRES and recurrent
tion on the S/CGIC at weeks 24 and 48. seizures. In addition to multiple antiepileptic drugs (AEDs)
Conclusions: Long-term add-on CBD treatment had a similar and prolonged pentobarbital coma, the patient was treated
AE profile to that observed previously. Reductions in drop and with high dose IV methylprednisolone, IVIG, plasmapheresis
total seizure frequency and improvements in overall condition and VNS. Ketogenic diet was initiated with achieved ketosis at
were maintainedthrough 72 weeks.Funding: GW Research Ltd day 47 without cessation of seizures, but discontinued for elec-
Keywords: Epilepsy, Rare Diseases, Critical Care trolyte abnormalities. The seizures continued to recur, but
supra-refractory status resolved. Eventually CBD was started
72. Prescribing Practices and Antiepileptic Drug Choice and while the patient continued to have seizures they decreased
in Benign Epilepsy with Centrotemporal Spikes in frequency. Patient 2: 5 YOF, who presented with FIRES.
Hull M (Houston, TX), Stowe R, Cokley J, Jarjour I This patient was also treated with pentobarbital coma, multiple
AEDs, high dose IV steroids and IVIG. The ketogenic diet
Objective: Benign Epilepsy with Centrotemporal Spikes
was started on day 23 with ketosis achieved in a few days.
(BECTS) is one of the most common epilepsies in child- Scheduled lorazepam and pyridoxine were subsequently started.
hood. Much debate exists regarding appropriate treatment; The EEG improved, with no seizure recurrence.
literature varies between choices of antiepileptic drug (AED) Conclusions: FIRES is rare disease, treatment is very chal-
or not using AEDs. We evaluated choice of AED therapy lenging because of the lack of large studies given the limited
and side effect profiles. cases of this disease. We hypothesize that expeditious achieve-
Methods: A retrospective cohort study included patients ment of ketosis was helpful for earlier and complete seizure
≤18 years of age with a diagnosis of BECTS (based on cessation. We also describe CBD use in FIRES.
ICD9/10 codes, documentation of history, and EEG) who Keywords: Epilepsy, Rare Diseases
were evaluated at tertiary care hospital from 2011-2015.
Demographics, AEDs, medical history, examination, and
reports of electroencephalograms were reviewed.
Results: A total of 298 charts were queried, with 159 patients
(51.6% male) meeting inclusion criteria. Mean age of seizure GENETICS
onset was 6.7 years. When diagnosis was established, AEDs
were started in 102 (64.2%), not started in 44 (27.7%), and
stopped in 13 (8.2%). Patients started on AEDs were more 74. MELAS (Mitochondrial Myopathy, Encephalopathy,
Lactic Acidosis and Stroke-like Episodes) – Case Report
likely to have experienced status epilepticus (18.26% vs 2%
and Review of Literature
p = 0.009) and had a higher seizure burden (7.5 +/- 9 vs 3.7
Kerashvili N (Columbia, SC), Venkatesh Y
+/- 3.3 p=0.012) than patients not started on AEDs. The
most commonly prescribed AEDs were oxcarbazepine Objective: We describe a patient with juvenile onset MELAS
(66.7%), levetiracetam (18.6%), carbamazepine (7.8%), (Mitochondrial myopathy, Encephalopathy, Lactic acidosis
zonisamide (6.9 %), topiramate (2.9%) and lamotrigine and Stroke-like episodes), progression of disease through
(2.9%). Incidence of side effects was least using levetiracetam 5 years of follow up and use of L-arginine for treatment.
(21.7%) and highest using lamotrigine (71.4%). Thirty-five Methods: Case report, Patient seen as an inpatient and then
patients were weaned off their AED subsequent to outpatient follow up.
25.4
14.6 months of seizure freedom. Results: Our patient presented to hospital at age 18. Initially
Conclusions: Substantial practice variation exists at a single she was diagnosed with non-alcoholic Wernicke’s encephalopa-
institution regarding AED prescribing in treatment of thy. After one year she was readmitted for seizures with MRI
BECTS. Oxcarbazepine was the most commonly prescribed showing right temporooccipital stroke-like lesions. Patient was
referred for genetic testing, but did not go through with
AED. Side effects were commonly reported in this cohort to
it. After one year, she was readmitted again for seizures and
all AEDs.
altered mental status. MRI showed new left temporoparietal
Keywords: Epilepsy
and occipital lesions and resolution of the right sided lesion
seen on previous MRI. For suspected MELAS, treatment was
73. Febrile Infectious Related Epilepsy Syndrome (FIRES) initiated with L-Arginine, carnitine and Coenzyme Q10 for
a Description of Two Patients one week. Follow up CT head and MR brain did not show
Kerashvili N (Columbia, SC), Peters W improvement in stroke like lesions. Treatment was discon-
Objective: There is no defined treatment protocol for FIRES tinued. She underwent genetic testing, showing A3243G
(febrile infectious related epilepsy), other than initial treatment tRNA mutation which is seen in 80% of MELAS cases. She
for status epilepticus. Our objective is to discuss two medically was restarted on L-arginine and has been stable in follow up.
refractory patients with FIRES, who had different disease pro- Conclusions: MELAS is one of the most frequent maternally
gression, outcome and treatment course. In addition, we inherited mitochondrial disorders. Diagnosis is based on

Program and Abstracts, Child Neurology Society S77

clinical symptoms, abnormal laboratory results, genetic test- hospitals in Riyadh, which is the main referral city and repre-
ing and imaging. If clinical suspicion for juvenile MELAS is sentative of the population in Saudi Arabia. Diagnosis was con-
high, initiating treatment with L-Arginine early should be firmed by high performance liquid chromatography analysis of
considered even in the absence of confirmation by genetic serum transferrin and genetic testing (whole exome sequencing
tests, as juvenile form of MELAS typically has bad sequelae or a CDG gene panel). After finding a mutation, parents and
and high mortality. siblings of the patients were tested for heterozygosity.
Keywords: Genetics, Rare Diseases, Neuroimaging Results: Twenty-seven Saudi patients (14 males, 13 females)
from 13 unrelated families were identified. Based on the
75. Truncating Biallelic Variant in DNAJA1 is Associated molecular studies, the following CDG were identified:
with Intellectual Disability and Seizures ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients,
Alsahli S (Houston, TX) 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG
(3 patients, 11%), SLC35A2-CDG (1 patient, 3.7%), and
Objective: Solve a negative clinical exome in a multiplex
PMM2-CDG (1 patient, 3.7%). All patients had homozy-
consanguineous family.
gous gene mutations; five mutations were novel, and three
Methods: Trio exome sequencing with inhouse interpreta-
mutations were already described.
tion as well as segregation analysis.
Conclusions: This study highlights the clinical and genetic
Results: We identified a novel biallelic truncating variant in
data of Saudi Arabian patients with CDG, and identifies sev-
DNAJA1 gene in a multiplex Saudi consanguineous family.
eral differences from patients with CDG in Western coun-
Three siblings were affected and included in the study. The
tries. Development of a national registry will help both
main phenotype shared between the siblings was intellectual
clinicians and families to ascertain the prevalence of this con-
disability and tonic clonic seizure disorder.
dition and facilitate further research in this field.
Conclusions: DNAJA1 is a strong candidate gene for autosomal
Keywords: Genetics, Rare Diseases, Neuroimaging
recessive intellectual disability and seizure disorder. However,
given the lack of functional studies or a second hit in another
family, further research in this area is needed as the current liter- 77. Sepiapterin Reductase Deficiency: Report of 5 New
ature is relatively deficient in defining the role of chaperones in Cases
human disease overall and in the CNS particularly. Alsubhi S (Montreal, Quebec), Tabarki B, Alshahwan S,
Keywords: Genetics, Epilepsy, Cognitive/Behavioral Disorders Almuhaizae M, Alzaidan H
Objective: Sepiapterin reductase deficiency is a rare, under-rec-
76. Congenital Disorders of Glycosylation : The Saudi ognized, autosomal recessively inherited disorder of neurotrans-
Experience mitter metabolism.Our cases illustrate the difficulties in the
Tabarki B (Riyadh, Saudi Arabia), Alsubhi S, Alhashem A, diagnosis of sepiapterin reductase deficiency in infancy, and
Faqeih E, Alfadhel M, Alfaifi A, Altuwaijri W, Alsahli S, the importance of early recognition and management.
Aldhalaan H, Alkuraya F, Hundallah K, Mahmoud A, Methods: Five new patients from 3 unrelated Saudi consan-
Alasmari A, Almutairi F, Alshahwan S guineous families are reported. We recorded of the main clinical
cardinal features, biochemical testing by cerebrospinal fluid anal-
Objective: To describe and better delineate the different
ysis of neurotransmitters, EEG, MRI brain and genetic testing.
types of CDG in Saudi Arabia and to correlate the phenotype
All 5 patients were treated with L-dopa/carbidopa (dose ranging
and genotype.
from 1 mg/kg/day to 13 mg/kg/day) and 2 patients received a
Methods: We retrospectively reviewed the clinical, biochemical,
combination of L-dopa and 5-hydroxytryptophan.
and genetic data of Saudi patients with CDG using a specific
Results: Symptoms began at 6 months, with delay to diag-
questionnaire. This questionnaire was sent to five major
nosis averaging 8 years. All 5 patients presented with
severe symptoms including axial hypotonia, dystonia, and
cognitive impairment, associated with hyper-reflexia
(4 patients), spasticity (4 patients), bulbar dysfunction
(4 patients), and oculogyric crisis (2 patients) with diurnal
fluctuation and sleep benefit. Cerebrospinal fluid neuro-
transmitters analysis showed a typical pattern with
increased sepiapterin and increased 7,8-dihydrobiopterin.
Analysis of the SPR gene identified 3 novel mutations:
c.1A > G, c.370T > C, and c.527C > T. Patient one, with
early diagnosis, is currently developing within the normal
range. The 4 other patients showed significant improve-
ment in their motor function, but only mild improvement
in their cognitive dysfunction.
Conclusions: Increased awareness of SRD, will improve the
early recognition and treatment of this under-recognized
FIGURE 1: Abstract 76 [Color figure can be viewed at www.
treatable condition.
wileyonlinelibrary.com] Keywords: Genetics, Movement Disorders, Rare Diseases

S78 Annals of Neurology Vol 86 (suppl 23) 2019

78. Lessons from Fetal Medicine: Early Recognition of KD was initiated by 3 months of age. She remains seizure
Pyruvate Dehydrogenase Complex Deficiency free at 4 months of age.
Amin H (Houston, TX), Emrick L Conclusions: 1. Corpus callosal and migrational abnormali-
Objective: Pyruvate Dehydrogenase Complex (PDHc) defi- ties can occur in PDHc deficiency. 2. Lactate should be
ciency is an inborn error of pyruvate metabolism. Clinical checked in female infants with structural abnormalities, even
features range from neonatal encephalopathy, brain mal- without encephalopathy. 3. Early identification of PDHc
formations and epilepsy to later onset intermittent ataxia and deficiency can prompt early treatment and prevention of poor
movement disorders. Most common mutation is X-linked, outcomes.
involving the PDHA1gene, which can affect males and Keywords: Genetics, Neonatal Neurology, Rare Diseases
females. We describe the appearance of PDHc deficiency in
the prenatal and neonatal period. 79. Natural History of Canavan Disease: Twenty-three
Methods: Retrospective case report of two children seen at a New Cases and Comparison with the Literature
tertiary pediatric hospital diagnosed in infancy with PDHc Eichler F (Boston, MA), Schön G, Corre C, Denecke J,
deficiency. Misko A, Hempel M, Hischke S, Bley A
Results: Fetal consults were initiated for migrational and cor- Objective: To identify clinical features that could serve as
pus callosal abnormalities detected in two singleton female endpoints for treatment trials we compared clinical data from
fetuses. Postnatal testing was negative for congenital cytomeg- a recent cohort of Canavan disease (CD, OMIM # 271900)
alovirus infection. Metabolic screening showed elevated lac- patients with that of older reports from the literature.
tate. Whole Exome Sequencing (WES) confirmed PDHc Methods: The clinical course of CD was studied retrospec-
deficiency. Thiamine and Ketogenic diet (KD) were initiated. tively in 23 CD patients. Results were compared with data of
Patient 1 was encephalopathic after birth. Brain MRI showed CD patients reported in three prior large series. Kaplan Meier
ventriculomegaly, corpus callosal agenesis, small cerebellum Survival analysis including Log Rank Test was performed for
and fused diencephalon. WES showed missense mutation in pooled data of 82 CD patients (study cohort and literature
PDHA1. KD was initiated by 3 months of age. Infantile patients).
spasms developed at 4 months. At 23 months of age, she Results: Onset of symptoms was between 0 and 6 months.
receives levetiracetam and vigabatrin. Patient 2 was dysmor- Psychomotor development of CD patients was limited to
phic at birth. Brain MRI showed bilateral ventriculomegaly, abilities that are usually gained within the first year of life.
microcephaly, hypoplastic corpus callosum and poly- Seizure frequency was highest towards the end of the first
microgyria. WES showed frameshift mutation in PDHA1. decade (Figure 1). Macrocephaly became apparent between

FIGURE 1: Abstract 78 [Color figure can be viewed at www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S79

FIGURE 1: Seizure frequency of Canavan patients over the course of disease. Seizure frequency of CD patients over the decade
of life is shown. Seizure Frequency is classified in 4 groups: no seizures/year, 1-2 seizures/year, <12 seizures/year, >12
seizures/year. Percentage means: Number of patients with a certain seizure frequency / number of all study participant of
this age. Abstract 79

4 and 18 months of age (Figure 2). Ethnic background was increase in frequency over time in most patients. CD occurs
more diverse than in studies previously reported. Seventy- more frequently outside Ashkenazi communities than previ-
three % of the CD patients reached the age of 10 years. ously thought. Concordance of phenotypes between siblings
Conclusions: Early hallmarks of CD are severe psychomotor but not patients with identical ASPA mutations suggest the
disability and macrocephaly that develop within the first influence of yet unknown modifiers.
18 months of life. While rare in the first year of life, seizures Keywords: Genetics, Demyelinating Disorders, Rare Diseases

FIGURE 2: Head circumference of 9 female and 10 male patients with Canavan disease within the first 6.5 years of life Legend:
Bold lines stand for patient’s data series. Dotted lines indicate males, continuous lines females. Local regression (loess) and 95%
confidence interval of loess was estimated. Thin lines and grey area indicates reference percentiles for head circumference of
girls and boys (Robert-Koch-Institute, KIGGS). Abstract 79

S80 Annals of Neurology Vol 86 (suppl 23) 2019

80. Felbamate Induced Thrombocytopenia in a Previously number variant (CNV) detection from NGS data was
Nondiagnosed Case of Cornelia de Lange Sequence included. Variant interpretation was performed according to
Fain D (Grand Rapids, MI), Andersen N, Mark P, Sweet K ACMG guidelines. Program results (Oct/2017-Nov/2018)
Objective: Cornelia de Lange Syndrome (CdL) is a develop- are reported from 210 patients (Europe, Middle East) with
mental disorder affecting several body systems including an inclusion criteria: Age 24-60 months, first seizure at/after
elevated risk of thrombocytopenia. Definitive diagnosis is 24 months, and at least one additional finding. The program
determined by genetic tests. Mutations in the three known was sponsored by BioMarin Pharmaceutical Inc.
genes associate with CdL; SCM1A gene mutations associate Results: Median age-at-testing: 42 months; median age-of-
with a mild form. Drug interactions are reported in children first-seizure-onset: 30 months; average delay from first seizure
with CdL during sedation. To our knowledge, felbamate to comprehensive genetic testing: 10.3 months. Genetic diag-
induced thrombocytopenia is unreported in patients nosis was established in 42 patients; 20.0% MDx
with CdL. yield. CNVs were reported in 26.2% of diagnosed patients;
Methods: We describe a patient with an epileptic encepha- 27.3% of CNVs identified were intragenic. MDx included
lopathy who failed other anticonvulsant medication and 5 CLN2 (TPP1 gene) diagnoses, 4 MECP2, 3 SCN1A,
developed thrombocytopenia following initiating felbamate. 3 Angelman syndrome, 2 each of CHD2, KCNA2, MFSD8,
The patient’s metabolic work up did not reveal any contrain- SCN2A and STXBP1.
dication to starting treatment. We performed a Whole Conclusions: This program demonstrates the clinical utility
Exosome Sequencing (WES) to evaluate the cause of of a comprehensive epilepsy gene panel for patients with first
epilepsy. seizures at/after 2 years for MDx of pediatric epilepsy and
Results: We report a female patient with epileptic encepha- CLN2 disease to guide management and treatment.
lopathy (with seizure onset at age 13 months) that failed Keywords: Genetics
other anticonvulsant medication. Initial genetic work up was
unremarkable. Patient began felbamate treatment at 4 years 82. Developmental Outcomes of Aicardi Goutières
of age and subsequently developed persistent thrombocytope- Syndrome
nia. No prior metabolic testing indicated a risk for thrombo- Gavazzi F (Philadelphia, PA), Adang L, De Simone M,
cytopenia; platelet levels were normal prior to starting Fazzi E, Galli J, Koh J, Kramer-Golinkoff J, De Giorgis V,
felbamate. We then performed WES and identified a likely Orcesi S, Peer K, Woidill S, Ulrick N, Shults J
pathogenic de novo SMC1A variant, c.3652_3663del (p. Objective: Aicardi Goutières Syndrome (AGS) is a mono-
Phe1218_Thr1221del). Based on her presentation with genic interferonopathy caused by abnormalities in the intra-
infantile epileptic encephalopathy, a diagnosis of CdLS cellular nucleic acid sensing machinery (TREX1,
was made. RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1,
Conclusions: This patient had a mild CdLS phenotype that or IFIH1). Most individuals affected by AGS exhibit some
went undiagnosed despite infantile epileptic encephalopathy degree of neurologic impairment, from spastic paraparesis
until WES following acquired persistent thrombocytopenia. with relatively preserved cognition to tetraparesis and severe
We suggest that WES may provide vital information in cases intellectual disability. Because of this heterogeneity, it is
of undiagnosed epileptic encephalopathy and advocate WES important to fully characterize the developmental trajectory
prior to starting treatments with potential life threatening in AGS.
side effects, such as felbamate. Methods: To characterize the clinical presentation in AGS,
Keywords: Genetics, Epilepsy early features were collected from an international cohort of
children (n=88) with genetically confirmed AGS.
81. Utility of Gene Panel Testing in Children with Results: There was a heterogeneous age of onset, with over-
Seizure Onset After 2 Years of Age: Results from a lapping clusters of presenting symptoms: altered mental sta-
European and Middle Eastern Epilepsy Genetic Testing tus, systemic inflammatory symptoms, and acute neurologic
Program disability. Next, we created genotype-specific developmental
Izzo E (Novato, CA), Gall K, Miller N, Alakurtti K, milestone acquisition curves. Individuals with microcephaly
Seppala E, Koskinen L, Koskenvuo j, Alastalo T-P or TREX1-related AGS secondary were the most severely
Objective: Epilepsy is one of the most common childhood- affected, and less likely to reach milestones, including head
onset neurological conditions with a genetic basis. Genetic diag- control, sitting, and nonspecific mama/dada (p-value <
nosis provides potential for etiologically-based management and 0.005). Individuals affected by SAMHD1, IFIH1, and ADAR
treatment. Existing research has focused on early-onset (<2 years) attained the most advanced milestones, with 44% achieved
epilepsies while data regarding later-onset epilepsies is limited. verbal communication and 31% independently ambulated.
Program goals: Determine, in a selected pediatric epilepsy Retrospective function scales (Gross Motor Function Classifi-
cohort, the overall and actionable molecular diagnostic (MDx) cation System, Manual Ability Classification Scale, and Com-
yield and the CLN2 disease MDx yield. CLN2 is a severe, rap- munication Function Classification System) demonstrated
idly progressive neurodegenerative disease with onset of seizures that two-thirds of the AGS population are severely affected.
at/after 2 years and average age-of-diagnosis of 5 years. Conclusions: Our results suggest multifactorial influences on
Methods: Blueprint Genetics’ next-generation sequencing developmental trajectory, including a strong contribution
(NGS)-based 283-gene epilepsy panel was used. Copy from genotype. Further studies are needed to identify the

Program and Abstracts, Child Neurology Society S81

additional factors that influence overall outcomes to better exome sequencing was performed to elucidate a genetic
counsel families and to design clinical trials with appropriate diagnosis.
clinical endpoints. Results: Continuous EEG revealed that episodes of apnea
Keywords: Genetics, Rare Diseases and tonic stiffening had no EEG correlate and a diagnosis of
hyperekplexia was made. The patient progressed to axial
83. Heterogeneity of Neuroimaging and Genotype- hypertonia and frequent desaturations requiring oxygen sup-
phenotype Correlations in Leigh Syndrome plementation. Trio exome sequencing showed a novel, de
Gordon-Lipkin E (Bethesda, MD), Kruk S, McGuire P novo, heterozygous variant in SCN8A(c.4409A>G; p.
Q1470R). This variant was not reported in the healthy popu-
Objective: To understand the spectrum and genotype-
lation and prediction scores were damaging.
phenotype correlations of neuroimaging findings in Leigh
Conclusions: Hyperekplexia is described as a benign disorder
Syndrome (LS).
of infancy with most children outgrowing the phenotype over
Methods: Individuals were recruited for the Metabolism,
time. This study highlights that individuals with SCN8A may
Infection and Immunity (MINI) study at the National Insti-
initially present with hyperekplexia. Therefore, obtaining
tutes of Health and included if they had a mutation in a gene
comprehensive genetic testing in a timely manner for hyper-
known to be involved in mitochondrial metabolism and asso-
ekplexia has the potential to change management, prognosis
ciated with LS or Leigh-like Syndrome. Imaging was
and counseling. However, further studies are required to link
obtained by retrospective record review. If images were
the role of SCN8A and isolated hyperekplexia as the initial
unavailable, MRI reports were used for analysis.
presentation of early epileptic encephalopathy.
Results: 19 children were recruited for the study. Affected genes
Keywords: Genetics, Epilepsy, Neonatal Neurology
included both mDNA (n=10) and nuclear DNA (n=10) muta-
tions. One patient had mutations in both. 18 had available
imaging. 9(50%) had classic lesions for LS, including 6(33%) 85. The c.1353C>G (p.D451E) Variant of SLC6A1 Gene
with basal ganglia lesions and 6(33%) with brainstem lesions. is Associated with Intractable Myoclonic-atonic Epilepsy
3/4 with available MR spectroscopy had lactate peaks. 11(61%) and Absence Seizures in a Family with Autosomal
had neuroimaging consistent with other cases of the same gene Dominant Mode of Inheritance
in literature. 2 cases were new phenotypes for an affected gene Johnson D (Johnson City, TN), Culp J, Yoon S,
which included SDHA mut with isolated cerebellar atrophy and Hajianpour MJ
MICU1/MTCYB mutation with “MS-like” lesions. Objective: SLC6A1 encodes a GABA transporter that
Conclusions: As modern genetic testing identifies more indi- removes GABA from the synaptic cleft. Pathogenic mutations
viduals with mitochondrial disease, the spectrum of central present with myoclonic-atonic epilepsy, absence seizures,
nervous system (CNS) disease is broadening and patients developmental delay, and intellectual disabilities—typically in
more frequently fit a clinical/radiological picture consistent autosomal recessive patterns. We are investigating autosomal
with their genotype rather than a classic LS picture. Recon- dominant pattern of inheritance in an affected family. To our
sideration of LS as a family of mitochondrial diseases with knowledge, this variant [c1353C>G (p.D451E)] has not been
CNS involvement rather than one syndrome may be more characterized as pathogenic or benign.
appropriate. Better defining genotype-phenotype correlations Methods: Proband is an 11-year-old female with intractable
has the potential to lead to less heterogeneity amongst seizures, developmental delay, intellectual disability (IQ 45),
patients which is helpful for clinical trials and patient care. ADHD, disruptive mood dysregulation, bicuspid aortic valve,
Keywords: Genetics, Neuroimaging, Rare Diseases SVT, joint hypermobility, and dysmorphic features (dolicho-
cephaly, low-set ears, high nasal bridge, high-arched palate,
84. Hyperekplexia and Apnea of Infancy as the Initial retrognathia, pes planus). Born 5lbs at 32wks to a 19 yo,
Presentation of a Novel Variant in SCN8A G3P2 mother. She has a 12 yo full brother with seizures and
Herman I (Houston, TX), Diaz-Medina G, Potocki L, ID (IQ 40), a 14 yo maternal half-brother with “drop-type /
Pehlivan D absence seizures,” ID (IQ 48), autism, ADHD, and bipolar
Objective: Hyperekplexia is a rare neurological disorder that disorder; and a 9 yo full sister with joint hypermobility, IQ
affects infants and is characterized by excessive startle 80, and no seizures. Father has ID; mother has joint hyper-
response to stimulation, including touch and noise. Most mobility, mild ID, and possible seizures. The children
cases of hyperekplexia are benign and children outgrow received molecular studies for intellectual disability.
symptoms. Several genes have been identified to be the Results: Molecular studies for ID panel showed alteration of
hereditary cause of hyperekplexia, including GLRA1, SLC6A1 gene: c1353C>G (p.D451E), reported as a variant of
SLC6A5, GLRB, GPHN, and ARHGEF9.A recent report rev- uncertain significance (VUS), present in two affected full-siblings,
ealed that an individual with SCN8A variant presented with their affected maternal half-brother and their mother (obligate
hyperekplexia and eventually converted to epileptic encepha- carrier—not tested), but not present in their unaffected 8 yo sister.
lopathy. Here, we present an infant with a novel SCN8A var- Conclusions: The affected family members show similar but
iant who initially presented with hyperekplexia. variable clinical features, and all carry the SLC6A1 variant p.
Methods: A 2-month-old twin infant was admitted for apnea D451E, which seems to be the cause of this family’s pheno-
and tonic stiffening episodes. Continuous EEG monitoring type with an autosomal dominant mode of inheritance.
was initiated to capture the episodes. Clinical trio whole Keywords: Genetics

S82 Annals of Neurology Vol 86 (suppl 23) 2019

86. Human Genetic Risk and Protective Factors in Schaaf optic atrophy syndrome (BBSOAS), due to a muta-
Congenital Zika Syndrome tion in NR2F1, causing developmental delay, intellectual dis-
Kousa Y (Washington, MD), Mansour T, Mulkey S, Leslie E, ability, optic atrophy, dysmorphic features, and occasionally
Dick A, Vezina G, Bulas D, Cavalcanti D, Murray J, epilepsy.
DeBiasi R, Cure C, Cordero J, Vilain E, Maximilian M, du Methods: A comprehensive chart review was performed.
Plessis A Results: The patient is an adolescent female diagnosed with
Objective: Congenital Zika Syndrome is a condition caused MPS VI at age 5, history significant for coarse facial features,
by a pregnancy infection. It is not clear why some fetuses recurrent acute otitis media requiring myringotomy tubes,
exposed to Zika virus in-utero are affected, while others are mitral valve stenosis and regurgitation, hydrocephalus requir-
not. Zika virus has a strong predilection for the fetal nervous ing ventriculo-peritoneal shunt, cervical spine compression
system, leading to severe brain injury/malformations. Emerg- requiring surgical intervention, dysostosis multiplex, corneal
ing evidence suggests that maternal and fetal genetic factors clouding, and optic atrophy. Severe intellectual disability was
may contribute to brain injury/malformations with Zika virus recognized early with absence language development, but
infection. additional genetic evaluation was initially declined. At age
Methods: Our multicentered nested case-control association 15, trio whole exome sequencing revealed a de novo likely
study seeks to identify maternal and fetal genetic risk and pathogenic variant in NR2F1, confirming a second diagnosis
protective factors in Congenital Zika Syndrome. We per- of BBSOAS.
formed in-silicoanalyses of putative neurodevelopmental and Conclusions: This case reminds physicians that in atypical
viral-responsive genes that might be interacting with Zika presentations of a rare disease, additional diagnoses must be
virus. We then performed whole exome sequencing on considered. The presence of intellectual disability in a patient
124 women and infants enrolled in our centers in Colombia with MPS VI should prompt further evaluation, as in this
and Brazil, where fetal-infant participants were apparently case, which led to a second diagnosis.
unaffected or had 1) Congenital Zika Syndrome (clinical Keywords: Genetics, Rare Diseases, Cognitive/Behavioral
diagnosis), 2) severe brain malformations, or 3) mild imaging Disorders
changes.
Results: Using bioinformatic solutions, we identified over 88. Exome Sequencing in Patients with Cerebral Palsy
2,400 predicated genes of interest. Of these, 127 genes were Identifies an Etiology in One-third of Cases,
found to be shared between neurodevelopmental and immu- Underscoring the Need for Broad Genetic Testing and a
nity pathways, including CSF2, IGF1 and PTCH1. Analyses Significant Recurrence Risk for Families
of human sequencing data are ongoing. Millan F (Gaithersburg, MD), Elloumi H, Teigen C, Scuffins J,
Conclusions: We are currently working toward enrolling Torene R, McKnight D
over 5,000 mother-infant dyads, at 14 international centers Objective: To establish the positive diagnostic rate (PDR) of
in collaboration with the National Institutes of Health and exome sequencing (ES) for patients with cerebral palsy (CP).
Centers for Disease Control. Our design is innovative, Methods: ES results from 1346 patients with CP were retro-
enabling comparison within and between populations, and spectively reviewed. A positive result was defined as the iden-
combines deep clinical, neurodevelopmental and neuroimag- tification of one or two pathogenic or likely pathogenic
ing data sets. This work may contribute to a ‘natural model’ variants in a single gene, depending on the mode of inheri-
of brain infection and inform the mechanism of brain tance of the disorder.
injury/malformation and protection in human brain Results: ES yielded a positive result in 32.7% of cases
development. (440/1346). Testing of a proband concurrently with parents
Keywords: Genetics, Neonatal Neurology, Rare Diseases (trio) significantly improved the PDR compared to proband-
only testing (35.3% vs. 23.3%, p<0.005). Positive findings
87. Neurologic Manifestations of Mucopolysaccaridosis were identified in 225 different genes, demonstrating the vast
Type VI Do Not Include Intellectual Disability: genetic heterogeneity of CP. Causative variants were identi-
Reminder to Consider a Second Diagnosis When Faced fied in genes associated with autosomal dominant (AD,
with Atypical Presentations 65.7%), autosomal recessive (AR, 20.9%), and X-linked dis-
Lau H (New York, NY), Famiglietti H, Anstett K orders (XL, 13.4%). Additionally, 12% (53/440) of cases had
Objective: Mucopolysaccaridos is Type VI is a lysosomal positive results in recently published disease-associated genes.
storage disorder due to deficiency of arylsulfatase B enzyme, Trio testing revealed a high de novo rate (71.9%). A signifi-
leading to accumulation of the glycosaminoglycan (GAG) cant recurrence risk was revealed in 30% (130/440) of cases:
dermatan sulfate, and subsequent multisystemic dysfunction. 21% (92/440) had biallelic AR variants, 3% (13/440) were
Neurologic manifestations of MPS VI include cervical spine inherited XL, 4% (18/440) were inherited AD, and 1.6%
compression, median nerve compression neuropathy, hearing (7/440) were inherited from a mosaic parent.
loss and hydrocephalus. MPS VI does not impact cognition, Conclusions: ES revealed a genetic etiology in almost a third
attributed to the lack of neurotoxic heparan sulfate accumula- of patients with CP, supporting the use of genetic testing in
tion. Here we describe a 15 year old MPS VI patient with this group. The high rate of de novo positive findings sup-
intellectual disability and optic atrophy, which led to a ports utilizing a trio approach. Genetic testing of patients
2ndrare diagnosis of the genetic condition Bosch-Boonstra- with CP can inform an accurate recurrence risk, and also

Program and Abstracts, Child Neurology Society S83

provide information for prognosis, adjusted therapies, and adeno-associated virus serotype 2 (AAV2)-hAADC to the
management options. substantia nigra (SNc) and ventral tegmental area (VTA).
Keywords: Genetics, Movement Disorders Methods: Six subjects (3 female, 3 male; ages 4-9 years) were
treated with either a low (Cohort 1) or high (Cohort 2) dose of vec-
89. Novel Variants in Phosphatidylinositol Glycan tor (1.3 x 1011and 4.2 x 1011vector genomes). At the time of this
Anchor Biosynthesis Class G Protein (PIGG) and submission, follow-up duration after treatment is 3-24 months.
Mitochondrial Spectrophotometric Analysis Expand the Results: Real-time MR imaging confirmed 70-100% cover-
Clinical Spectrum of PIGG-related Disease age of the SNc/VTA. The surgical intervention was well-
Nagy A (Boston, MA), Osman M, Walker M tolerated by all subjects. All subjects developed mild to mod-
erate dyskinesia post-gene transfer, peaking in severity
Objective: Phosphatidylinositol glycan (PIG) genes are
between 1-3 months. OGCs completely resolved in 5/6 sub-
required for synthesis of Glycosylphosphatidylinositol (GPI)-
jects. Sleep and mood improved dramatically in all subjects.
anchored proteins, and when mutated can lead to inherited
Motor function improved by 9-30 points at 6-12 months
GPI deficiency, a disorder of intellectual impairment, hypoto-
(GMFM-88 scale; baseline scores <15 in all), and 2 subjects
nia, and seizures1. All previously reported cases presented
attained the ability to sit independently and take steps with
with hypotonia, early seizures, and developmental delay2.
support. CSF homovanillic acid (HVA) increased in all sub-
Here we report novel PIGG mutations and an associated,
jects from <10% of the lower limit of normal at baseline, to
attenuated phenotype with secondary mitochondrial dysfunc-
24-47% at 6-12 months post-gene transfer, consistent with
tion not previously reported.
increased brain dopamine synthesis. 18FDOPA PET demon-
Methods: We present case history, clinical findings, spectro-
strated increased uptake in the midbrain and striatum.
photometric analysis of skeletal muscle biopsy, genetic find-
Conclusions: AADC gene transfer to SNc/VTA is well-toler-
ings from clinical whole exome sequencing (WES) of the
ated, safe, and leads to improvement in disease symptoms
proband, mother, and sister.
and motor function.
Results: Our patient had myoclonic epilepsy as a young child
Keywords: Genetics, Movement Disorders, Translational/
that resolved on Banzel. She subsequently developed general-
Experimental Therapeutics
ized epilepsy, with excellent response to ketogenic diet and
subsequent resolution of seizures without treatment by age
10 years. Spectrophotometric analysis of skeletal muscle 91. A Case of 5,1 0-methenyltetrahydrofolate Synthetase
biopsy revealed complex I and II deficiencies. WES revealed Deficiency Due to Biallelic Null Mutations with Novel
previously unreported compound heterozygous c.1210delC Findings of Elevated Neopterin and Macrocytic Anemia
and c.901+1delG pathogenic PIGG variants in trans. Her sis- Romero J (Philadelphia, PA), Abdelmoumen I, Khurana D,
ter, who was diagnosed with nystagmus, dyslexia, and hemi- Schneider M
plegic migraine, but no developmental delay or epilepsy, also Objective: To describe a patient with microcephaly, global
inherited these variants. Her unaffected mother carried only developmental delay, spasticity, epilepsy, and cerebral hyp-
the c.1210delC. omyelination found to be homozygous for nonsense muta-
Conclusions: PIGG gene mutations have been previously tions in the MTHFS gene.
reported in patients with intellectual disability and seizures. Methods: A retrospective chart review of this patient was
Here we report novel mutations in the PIGG gene associated obtained for medical history, brain MRI imaging and labora-
with an attenuated phenotype and likely secondary mito- tory studies including CSF neurotransmitters and whole
chondrial dysfunction. Intriguingly, our patient’s mutations exome sequencing (WES).
are deletions while most prior, more severely affected cases Results: Our proband presented at the age of 9 months with
involved missense mutations, though the mechanism for this hypertonia and microcephaly. Brain MRI showed unmyelin-
difference is unknown. Importantly, the marked response to ated internal capsules and thin corpus callosum. She developed
ketogenic diet points to a possible therapeutic pathway in generalized seizures, and also macrocytic anemia requiring
similarly affected individuals. blood transfusions. CSF studies showed decreased 5-MTHF
Keywords: Genetics, Rare Diseases, Epilepsy and elevated neopterin. At 4 years of age, WES showed homo-
zygosity for the R74X mutation in the MTHFS gene. The par-
90. Gene Therapy for AADC deficiency: MRI-Guided ents are both from Haiti and heterozygous for this mutation.
Delivery of AAV2-hAADC to the Midbrain Conclusions: This is the third case reported in the world of
Pearson T (St. Louis, MO), Gupta N, Grijalvo-Perez A, MTHFS deficiency. The findings of elevated neopterin and
Viehoever A, San Sebastian W, Imamura-Ching J, Seo Y, macrocytic anemia have not been reported in previously
Larson P, Bankiewicz K described patients and may provide clues to the diagnosis of
Objective: Aromatic L-amino acid decarboxylase (AADC) this neurometabolic disorder. The anemia suggests that
deficiency is a rare autosomal recessive disorder that causes MTHFS deficiency is not just a neuronal problem, but also
congenital impairment of dopamine and serotonin synthesis. has hematopoietic effects. We will follow the patient’s CSF
The disease presents with hypotonia, oculogyric crises neopterin and 5-MTHF levels, and hemoglobin after the com-
(OGC), dystonia, autonomic dysfunction, sleep disruption, mencement of treatment with oral L-5-methyltetrahydrofolate
and global developmental delay. This study aims to evaluate and intramuscular methylcobalamin.
the safety and efficacy of real-time MR-guided delivery of Keywords: Genetics

S84 Annals of Neurology Vol 86 (suppl 23) 2019

92. Expanding the Clinical Phenotype of Results: Positive FMR1 full expansions were identified in
MSTO1-associated Mitochondrial Myopathy only 0.8% (7/896) of cases. Chromosomal microarray
Schultz-Rogers L (Rochester, MN), Ferrer A, Zimmermann M, (CMA) testing identified causative copy number variants
Dsouza N, Smith B, Klee E, Dhamija R (CNVs) in 5.7% (51/896) of cases. 77.7% of individuals
Objective: Mitochondrial disorders caused by nuclear and (n=696) proceeded to second-tier testing with the Autism/ID
mitochondrial pathogenic variants lead to defects in mito- Xpanded panel. The PDR of the panel was 8.2% (57/696).
chondrial dynamics and cellular respiration. Recently the Five positive CMA cases continued with the panel; all five
nuclear-encoded mitochondrial fusion gene MSTO1(Misato CNVs were identified by next-generation sequencing (NGS).
1) has been implicated in mitochondrial myopathy and Conclusions: The data demonstrates a low diagnostic yield
ataxia. The majority of reported patients have combined loss of FMR1 repeat testing in the general ASD/GDD/ID popula-
of function and missense variants suggesting autosomal reces- tion. This data support the growing literature that FMR1
sive inheritance. However, there has been a report of autoso- testing is not an effective first-tier test despite the relatively
mal dominant inheritance. Here we report on a 30 year old low cost. CMA yielded a higher PDR and the Autism/ID
man with muscle weakness, hypotonia, motor delay, pectus Xpanded panel had the highest diagnostic yield (~8%). CMA
excavatum, and scoliosis. as a first-tier test is more cost effective currently, however, as
Methods: The patient underwent biochemical screening and technology continues to improve, the detection of CNVs
whole exome and mitochondrial sequencing. along with sequence variants from NGS data will likely
Results: Tests revealed elevated plasma CK and EMG results become the more cost-effective, higher yield first-tier genetic
were consistent with longstanding, generalized myopathy. test for patients with ASD/GDD/ID.
These phenotypes overlap well with previously reported Keywords: Genetics, Cognitive/Behavioral Disorders
patients with bi-allelic MSTO1variants. Additionally, our
patient presents with an expanded phenotype including dys- 94. Ischemic Stroke in Cockayne Syndrome
phagia and restrictive lung disease. WES revealed a mater- Tochen L (Washington, DC), Rhee J, Ahmad A, Whitehead M,
nally inherited c.651C>G, p.F217L missense variant as well Pergami P, Fraser J
as a paternally inherited deletion encompassing exons 7-14 of
Objective: Cockayne syndrome (CS) is an autosomal reces-
MSTO1. in silicoprotein modeling of the F217L variant
sive disorder of nucleotide excision repair due to mutations
shows that is it present in the tubulin domain and may affect
in either ERCC8 or ERCC6 genes. Clinical manifestations
the structural conformation as it is the only hydrophobic resi-
include advanced aging, spasticity, ataxia, retinal degenera-
due within a region of charged and hydrophilic residues.
tion, photosensitivity, short stature, and dysmorphic facies.
Conclusions: The pattern of inheritance in this case is con-
Typical MRIs show leukoencephalopathy, basal
sistent with the majority of previous reports and suggests a
ganglia/cortical calcifications, and cerebellar atrophy. Stroke
mechanism of haploinsufficiency. With reports of both auto-
is a rare phenomenon in CS. This case report describes the
somal recessive and dominant inheritance associated with var-
youngest patient to date with CS who developed an ischemic
iants in MSTO1, more work is needed to clarify the exact
stroke.
mechanism through which pathogenic variants result in
Methods: Clinical data was extracted from medical records
abnormal mitochondrial fusion dynamics.
and MRI imaging.
Keywords: Genetics, Neuromuscular Disorders, Rare
Results: A 7 year old female with CS presented to the emer-
Diseases
gency department with acute decreased movement of her
right arm. Initial neuroimaging was significant for a small
93. Genetic Test Results for 896 Patients with ASD/ID: cortical/juxtacortical area of restricted diffusion within the
The Diagnostic Yield of Multigene Analysis (Autism/ID distal left MCA territory. There were stable but persistent
Xpanded Test) is Higher than Conventional First-tier extensive cerebral and basal ganglia calcifications and white
Tests, Such as FMR1 Repeat Analysis and Chromosomal matter changes consistent with CS, with noted higher burden
Microarray of calcifications on the left in the area of the infarct. She was
Shanmugham A (Elmwood Park, NJ), Brandt T, Scuffins J, admitted to the PICU for initial management. A
McKnight D thrombophilia evaluation was unremarkable, and an echocar-
Objective: To evaluate the clinical utility of including FMR1 diogram with agitated saline injection showed an intact atrial
repeat analysis as a first-tier genetic test for children with septum. Antiplatelet treatment was initiated. Right arm
autism spectrum disorder (ASD), global developmental delay strength improved during her hospitalization; at the time of
(GDD) and/or intellectual disability (ID). discharge she had slight residual right facial weakness.
Methods: A retrospective study to evaluate the positive diag- Conclusions: CS is a disorder of ineffective DNA repair
nostic rate (PDR) of first-tier genetic tests (FMR1repeat anal- characterized by advanced aging; early atherosclerosis and
ysis and chromosomal microarray) compared to a second-tier mineralizing vasculopathy are features of CS in neuropathol-
test, the Autism/ID Xpanded panel (next generation sequenc- ogy reports and may be responsible for increased risk for
ing of >2300 genes associated with ASD/ID). Study includes ischemic stroke in CS. Early screening for increased stroke
896 patients (227 females; 669 males) with ASD/GDD/ID risk may be warranted.
referred to GeneDx for genetic testing. Keywords: Genetics, Stroke, Rare Diseases

Program and Abstracts, Child Neurology Society S85

HEADACHE/MIGRAINE There was no statistically significant correlation between the
type of screen exposure (including TV, computer, cell phone,
video games, and/or tablets) or the duration of screen use per
day with regards to monthly headache frequency, school
95. New Persistent Post-Concussion Headache in
attendance, or school functioning. While most adolescents
Children and Adolescents
reported prolonged screen use (58.6%) and lighting from
Barissi M (Grand Rapids, MI), Rothner A
screens (64.6%) worsened their headaches, no statistical dif-
Objective: There is little data exploring new persistent post- ference was seen in the average number of headache days
concussion headache in children and adolescents (NPPCH). experienced per month in this population.
This entity is defined in the ICHD-3 as a headache lasting Conclusions: Average monthly headache frequency in an
longer than 3 months post-injury without any previous his- adolescent population was not significantly correlated with
tory of headache. The objective was to determine the progno- type or duration of screen exposure. Future studies are
sis of patients with NPPCH to describe the entity and to needed to further elucidate how daily screen utilization
identify any beneficial treatment methods. impacts pediatric headache and associated disability.
Methods: 259 patients diagnosed with a concussion were Keywords: Headache/Migraine
seen in the Cleveland Clinic Pediatric Neurology Department
between June 2017 and August 2018. 69 (27%) met 97. Using Mobile Technologies to Investigate Proximal
NPPCH criteria and were included in the study. Information Environmental Triggers of Migraine
from a medical chart review provided insight into their initial Lateef T (Washington, DC), Xiao Y, Cui L, Zipunnikov V,
assessment. To obtain more up-to-date information, a ques- Merikangas K
tionnaire was sent out within 12 months of previous visits.
Objective: Substantial literature exists on headache triggers,
IRB approval was attained.
however most of the information relies on retrospective
Results: 48 (70%) patients indicated they had two types of
reporting or diaries based on recall of exposures. We used
headache, with migraines and chronic daily headache (CDH)
mobile technology to prospectively assess potential changes in
being the most common. 48 (70%) had a family history of
sleep, energy, and mood states and investigate their direc-
headache. 65 (94%) had MRI/CT scans with 0% of the results
tional associations with headache onset.
contributing to a better understanding of etiology or treatment.
Methods: Sample- 289 participants, aged 10-82 years, enrolled
64 (93%) had used a headache medication, with the most pop-
in the National Institute of Mental Health’s Family Study of
ular ones being amitriptyline, topiramate, and cyproheptadine.
Affective Spectrum Disorders, in the greater Washington DC
At their follow-up visits, few patients remained on these medi-
metropolitan area. Electronic diary information was collected
cations. 33 (48%) filled out the questionnaire. 25 (78%) indi-
four times per day over a two-week period (56 assessments in
cated they still had headache at their follow-up.
total) and included ratings of sleep, mood, energy, stress and
Conclusions: It is important to emphasize that patients with-
headache symptoms. Generalized linear mixed effect models
out previous headaches can develop chronic headaches for a
were used to estimate the directional associations between
long duration from concussions. These results could be uti-
sleep, mood and stressful events on headache onset and
lized in the future to construct better treatment plans to pre-
timing. Lifetime headache disorders were characterized the
vent unnecessary suffering.
Diagnostic Interview for Headache Syndromes (DIHS).
Keywords: Headache/Migraine
Results: Headache was more common among females
(OR 2.17, P <.01). Subjects who had migraine with aura
96. Pediatric Screen Exposure and Headache Disability were more likely to have morning headache (OR 2.25,
Langdon R (Washington, DC), Cameron M, Strelzik J, P<0.01) compared to those without aura. Sleep quality
McClintock W, DiSabella M (OR 1.33, P <.01), low energy (OR 1.67.60, P <.01), stress
(OR 1.46, P <.01) and low mood (OR 1.52, P <.01) were
Objective: Prolonged and excessive screen exposures are
associated with headache across the day, in the full sample.
often cited as potential triggering or exacerbating factors for
People with a lifetime history of migraine, particularly
pediatric headaches. There are limited studies to date
females, were more likely to have morning onset headache
assessing the effects of screen use on headache pain. We pre-
(OR 1.5, P<.01), that was associated with poor sleep.
sent initial findings evaluating the association between head-
Conclusions: The specific association between sleep quality
ache disability and adolescent screen use.
and morning onset headache warrants further evaluation of
Methods: All new patients age 12-17 years presenting to the
the sleep characteristics that provoke migraine.
Headache Clinic at Children’s National were screened and
Keywords: Headache/Migraine
asked to complete a survey regarding headache characteristics,
behavioral habits, school attendance, and screen utilization.
Results: 99 adolescents completed the survey (29 M, 70 F) 98. Predictability of Disease Recurrence in Pediatric
with an average age of 14.8 years and average headache fre- Primary Intracranial Hypertension Based on Opening
quency of 16.66 days per month (median = 15). Patients Pressure Measurement Prior to Medication Wean
reported missing an average of 5.44 full days (median = 2) Pabst L (Columbus, OH), Aylward B, Rogers D, Aylward S
and 2.86 partial days (median = 1) of school due to head- Objective: Primary intracranial hypertension (PIH) is diag-
aches over the preceding 90 days prior to survey completion. nosed based on elevated lumbar puncture opening pressure

S86 Annals of Neurology Vol 86 (suppl 23) 2019

(LPOP) in conjunction with clinical signs and symptoms that with preoperative headaches had an increase in headaches
may include headaches, optic disc edema, or other ophthal- afterwards! The most common type of headache was tension-
mologic deficits without a secondary cause. Once symptoms type. Hemispherectomy patients should be questioned
improve and vision is preserved, weaning medication is con- regarding headache symptoms. Patients should be treated
sidered. The objective of this study is to determine if LPOP quickly to decrease suffering/increase function. Prospective
measurements change significantly between time of diagnosis, studies are needed to establish the true frequency of this
prior to and after medication weaning. condition.
Methods: An institutional database of pediatric patients Keywords: Headache/Migraine, Epilepsy
undergoing lumbar punctures was queried to identify PIH
patients. Chart were reviewed to collect data regarding medi- 100. New Daily Persistent Headaches in a Pediatric
cations and clinical course. A one-way repeated measures Population
ANOVA was conducted to examine mean changes in open- Pierce E (New London, CT), Cameron M, Furda M,
ing pressure at time of diagnosis, prior to and after medica- McClintock W, Strelzik J, Langdon R, DiSabella M
tion weaning.
Objective: New Daily Persistent Headache (NDPH) is char-
Results: 29 patients with PIH were identified, 13 had com-
acterized by a daily and unremitting headache lasting for at
plete initial, pre- and post-wean lumbar puncture opening
least three months. The objective of the current study is to
pressure data. There was no statistically significant difference
describe the characteristics of NDPH in pediatric patients
in the mean LPOP between times of diagnosis (M = 33.4,
presenting to a headache program at a tertiary referral center.
SD = 9.6), prior to weaning (M = 30.6, SD = 6.1) and after
Methods: The participants in this study were pediatric
weaning medication (M = 34.0, SD = 9.1) (p =0.497). 3 of
patients who attended the Headache Clinic at Children’s
the 13 patients had recurrence of PIH with visual field deficit
National Medical Center between 2016 and 2018. All
or papilledema after weaning.
patients seen in the Headache Clinic were enrolled in an
Conclusions: This study suggests that LPOP measurements
IRB-approved patient registry. The registry was queried for
in patients with PIH remain elevated before and after medi-
NDPH (ICD-10 G44.52) and these records were reviewed
cation wean, despite symptom resolution, and are not predic-
to examine their clinical presentation.
tive of disease recurrence.
Results: Between 2016 and 2018 there were a total of 3260
Keywords: Headache/Migraine
patient encounters. 454 of the encounters were identified as
having NDPH, representing 13.9% of the total. NDPH
99. Headache Frequency in Children After patients were predominantly female (78%) and white (72%).
Hemispherectomy The median age was 14.8 years (SD=1.58). Headache pain
Pandit I (Cleveland, OH), Rothner A, Bingaman W most often localized to the frontal head region, with throb-
Objective: Hemispherectomy is used to treat intractable bing quality, associated photophobia, phonophobia, nausea,
epilepsy. Postoperative results include changes in behavior, and decreased activity. The median pain intensity was 6 of
cognition, motor/speech function, and seizures. Little data 10 (SD= 1.52). 56% of patients failed at least one abortive
exists on postoperative headaches. Our objective was to medication (SD= 1.35). 36% of patients were additionally
determine whether headaches are significant post- diagnosed with Medication Overuse Headache (MOH), most
hemispherectomy. This data can lead to earlier treatment often with Ibuprofen.
for future patients. Conclusions: The findings of this study suggest that NDPH
Methods: We looked at 74 pediatric hemispherectomy is a relatively frequent disorder among pediatric patients pre-
patients from the last 5 years. 14 were excluded because they senting to a pediatric headache program. The majority of
were too young or did not respond. Medical records of patients fulfill criteria for the migraine subtype of NDPH
60 patients were reviewed and followed up with letters and and one-third have co-existing MOH. Further studies are
10-minute phone interviews. IRB approval was obtained. needed in order to better understand NDPH in the pediatric
Results: 60 of 74 patients were contacted and 22 (36.7%) population.
responded. 38 did not participate. Of 22, 11 were male Keywords: Headache/Migraine
(50%) and 11 were female (50%). The median age at surgery
was 6.5 years. Most common hemispherectomies were left 101. Joint Hypermobility and Associated Headache
functional (50.0%) and right functional (31.8%). 9 of Disability
22 (39.1%) had preoperative headaches, and 7 (31.8%) Sahjwani D (Washington, DC), Cameron M, Strelzik J,
reported family history of headaches. 19 of 22 (86.4%) had Langdon R, DiSabella M
postoperative headaches, while 10 of 22 (45.5%) had head- Objective: The purpose of this study was to identify the
aches beginning only after surgery! Of 9 with preoperative association between joint hypermobility and headache disabil-
headaches, 6 (66.6%) reported an increase in ity in children.
frequency/intensity of headache postoperatively. 3 reported Methods: Participants in this study were pediatric patients
no change or a decrease. seen in the Headache Clinic at Children’s National Medical
Conclusions: The study showed that a majority of hemi- Center between October 2018 and January 2019. All Head-
spherectomy patients reported headache after surgery! Most ache Clinic patients were enrolled in an IRB-approved

Program and Abstracts, Child Neurology Society S87

patient registry. Patients were scored on their headache dis- Conclusions: Our study supports theories that NDPH in
ability using Headache Impact Test-6 questionnaire (HIT- children and adolescents is an unremitting condition. How-
6). Joint hypermobility was assessed using the Beighton ever, our patient sample indicates that the headaches may
scoring system with scores > 4 diagnostic of joint change in character over time and may have a more favorable
hypermobility. prognosis. Further efforts are needed to establish etiology,
Results: 76 patients were scored using Beighton and disabil- treatment, and prognosis.
ity questionnaires. The median age was 13.7 years Keywords: Headache/Migraine
(SD=3.3). Beighton scores were diagnostic of joint hyper-
mobility in 26% of patients. 65% of the patients with joint
hypermobility had a diagnosis of migraine without aura.
80% of patients with joint hypermobility had severe head-
ache disability based on the HIT-6 disability criteria (Score
INFECTIONS/
≥60). The average pain intensity in patients with hyper- NEUROIMMUNOLOGY
mobile joints was 6.1 out of 10. (SD=1.8). Of the patients
without significant joint hypermobility, 90% had mild dis-
ability on HIT-6. 103. A Neurodevelopmental Mouse Model of Congenital
Conclusions: The findings of this study suggest that Zika Virus Infection
approximately one-quarter of children presenting to a Agner S (St. Louis, MO), Smith A, Diamond M, Miner J,
headache clinic have significant joint hypermobility. Joint Klein R
hypermobile patients have a high rate of headache disabil- Objective: To develop a mouse model of congenital Zika
ity, and most often have headaches consistent with virus infection to evaluate effects on cognitive and behavioral
migraine without aura. Conversely, patients without joint development.
hypermobility have less headache disability. Further studies Methods: C57BL6/J mice (Jackson Laboratories) were
are needed to better understand the relationship between mated, and timed pregnancies were established. MAR1 anti-
headache and joint hypermobility in the pediatric body was administered on E5.5. On E6.5, either 105focus
population. forming units of mouse adapted Zika- Dakar or mock infec-
Keywords: Headache/Migraine tion with phosphate-buffered saline was administered intra-
peritoneally. At 8 weeks old, social behavior of mice born to
102. Prognosis of New Daily Persistent Headache in Zika virus (ZIKV)- or mock- infected dams was evaluated by
Children and Adolescents social approach test.
Simmons A (Cleveland, OH), Rothner A Results: Mice exposed to in uteroZika virus infection demon-
Objective: To our knowledge, this is the first study that strated increased time spent investigating the inanimate stim-
aimed to establish the prognosis of New daily persistent ulus compared to social stimulus. In contrast, mock-infection
headache (NDPH) in children and adolescents. exposed animals spent more time investigating the social
Methods: We conducted a retrospective chart review of pedi- stimulus.
atric patients (6-18 years) who were diagnosed with NDPH Conclusions: In a mouse model of congenital Zika virus, we
between June 2017 and August 2018. Patients were con- demonstrate decreased social behavior in a test that is often
tacted via phone to follow up on their headaches. IRB used in mouse models of autism. Recent data suggests that
approval was obtained. even children exposed to in uteroZIKV without structural
Results: Of 84 patients reviewed, 70% were female, as brain abnormalities may have cognitive and behavioral defi-
previously noted in literature. The median age of onset cits. Evaluation of toddlers exposed to in uteroZika infection
was 15 years. Etiology was attributed to: trauma (23%), has demonstrated not only neurodevelopmental delays, but
immunization or infection (20%), and unknown causes also behavioral abnormalities, including autistic features.
(42%). Patients with both migraine and tension-type head- Future studies will probe brain tissue of the model for
aches comprised 67% of our sample, while 31% of infection-related inflammatory response in conjunction with
patients had tension-type headaches alone, and 2% had an expanded cognitive and behavioral testing panel.
migraines alone. Immediate family history of headache was Keywords: Infections/Neuroimmunology, Cognitive/Behav-
noted in 5% of patients. Thirty-three patients (39%) com- ioral Disorders
pleted the phone interview. Their current median age was
16, median age of diagnosis was 15, and 70% were female. 104. Acute Flaccid Myelitis at a Tertiary Care Institution
Etiology was attributed to: trauma (18%), infections in Western Pennsylvania
(18%), and unknown causes (39%). 49% had migraine Albashiti B (Pittsburgh, PA), Abdel-Hamid H, Thakkar K
and tension-type headaches, 3% had tension-type head- Objective: To characterize the spectrum of Acute Flaccid
aches alone, and 2% had migraines alone. 12% reported Myelitis (AFM) at our tertiary center, due to the nationally
having no headaches. Of the 88% of patients still experienc- increased incidence of AFM
ing headaches, 46% were better, 33% were the same, and Methods: Review of demographic, clinical and outcome data
9% were worse. of patients who met the CDC case definition of AFM (acute

S88 Annals of Neurology Vol 86 (suppl 23) 2019

flaccid weakness with MRI findings of T2 hyperintensities in encephalitis first reported in 2007. A reversible diffuse cere-
the spinal cord grey matter), from January 2012 to March bral atrophy (DCA) following the acute phase of the disease
2019 has been described, suggesting the underlying mechanism of
Results: 14 patients were identified (10 male,71 %). Median brain volume loss is related to downregulated neuronal func-
age was 3.7yrs (range 0.9-13.8). 12/14(86%) patients pres- tion rather than true cell death. To date, observations of
ented between August-October. Majority had antecedent DCA in NMDARE have been qualitative and there is limited
upper respiratory tract infection (9/14, 64%). Peak clinical data exploring this in the pediatric population. We propose a
presentation included quadriplegia (5/14,36%), monoplegia quantitative approach using MRI image volume analysis to
(5/14,36%), diplegia (3/14,21%), combination of paraplegia clarify both the severity of brain atrophy and expected time
and monoplegia (1/14,7%). Bulbar symptoms were noted in to recovery of normal volume in the pediatric NMDARE
4/14 (29%) patients. Grey-matter T2 hyperintensity in the population.
spinal cord ranged from localized (1-3 segments) in 3/14 Methods: This is a retrospective observational study. Patients
(21%) and diffuse in 11/14(79%) patients. Electromyogra- diagnosed with NMDARE will be identified in a EHR data-
phy revealed motor axon loss in those with localized lesions. base search. High quality T1 weighted 3D SPGR image
CSF was available in 11/14 patients. Pleocytosis (WBC >5 found in PACS will be evaluated with Neuroquant volume
cells/mm3) was seen in 8/11(73%) and elevated protein analysis software, which is licensed by Barrow Neurologic
(>45mg/dl) was seen in 4/11 (36%) patients. Polymerase Institute. We will determine if there is brain atrophy and vol-
chain reaction for Enterovirus was negative in all available ume recovery in patients who have diagnosed NDMARE,
CSF and positive in 3/11(27%) nasopharyngeal swabs. All and determine if degree of brain atrophy corresponds to
patients received steroids, intravenous immunoglobulin or severity of condition or long-term outcome. Alongside gen-
plasma exchange alone or in combination. Mean hospital stay eral imaging features and brain volume results, relevant clini-
was 13.4 days (range 4-38). Within 3months, 2/13(15%) cal data will be collected from the medical record including
recovered completely, 6/13(46%) had partial recovery and estimated date of symptom onset, symptom severity, recovery
5/13(39%) demonstrated no change from their peak clinical status/length to recovery, demographics, concurrent illnesses,
presentation autoantibody titers, medications, and treatment history.
Conclusions: AFM has a clinical and radiological spectrum Results: Preliminary database search has yielded
ranging from mild to severe. Our study adds to the ongoing 15 NMDARE pediatric patients. MRI images for each
national research efforts for evaluation and identification of patient will be processed through Neuroquant brain volume
the etiology of this condition analysis software, which is still pending.
Keywords: Infections/Neuroimmunology Conclusions: Pending Neuroquant brain volume analysis.
Keywords: Infections/Neuroimmunology, Neuroimaging,
105. NMDA Receptor Encephalitis and Brain Volume Rare Diseases
Loss in Children, A Quantitative Study
Bassal F (Phoenix, AZ), Oh A, Cornejo P, Hughes J, 106. Genetic Mimics of Autoimmune Encephalitis
Harwood M, Narayan R Calame D (Houston, TX), Herman I, Emrick L, Lotze T
Objective: Anti-N-methyl-D-aspertate receptor encephalitis Objective: There is increased awareness for autoimmune
(NMDARE) is a rare and potentially fatal autoimmune encephalitis (AIE) as a potential etiology for new onset

TABLE 1: Findings that help fulfill diagnostic criteria for possible AIE are highlight in bold. Abstract 106 [Color figure can be
viewed at www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S89

encephalopathy, movement disorders, seizures and psychiatric 31 days. Four patients required intensive care (median
symptoms. In the absence of pathogenic antibodies, seronega- 31 days). Five patients required inpatient rehabilitation
tive cases are often treated acutely with immunomodulatory (median 27 days). Patients had variable improvement in
agents for a presumptive diagnosis of AIE. However, certain deficits. Two patients required tracheostomy with
genetic disorders, some with specific treatments, may present decannulation before discharge. Of six patients seen in neu-
in a similar fashion and should be considered in the differen- rology follow-up, all have residual deficits (one patient
tial diagnosis before initiation of long-term AIE treatment remains nonambulatory, and five display weakness of vary-
with immunosuppressive agents. ing degree in involved extremities).
Methods: We describe three cases of genetic disorders that Conclusions: Like other published cohorts, AFM typically
mimicked AIE. presented with prodromal illness, pain, and arm greater than
Results: The clinical, imaging and laboratory features of each leg weakness. Recovery was limited, although improvements
case are summarized in Table 1. All were suspected to have occurred including those with respiratory failure.
autoimmune encephalitis at some point throughout their Keywords: Infections/Neuroimmunology, Rare Diseases
clinical course, and indeed all met published diagnostic
criteria for possible autoimmune encephalitis. Symptoms 108. Pediatric anti-NMDA Receptor Encephalitis: A Case
included seizures, encephalopathy, behavioral changes, regres- Series
sion, dystonia, dysautonomia, catatonia and bladder and Marcus L (Birmingham, AL), Ness J
bowel incontinence. Two patients had abnormal CSF studies Objective: The purpose of our study is to determine which
suggestive of an inflammatory disorder. EEG was abnormal factors influence outcomes in pediatric patients with anti-
in all cases. MRI was normal in one case and abnormal in N-methyl-D-aspartate receptor (NMDAR) encephalitis. Since
the others. Two patients received steroids and/or IVIG, but NMDAR encephalitis was first described in 2007, it is the
none advanced to second-line immunotherapy. Genetic test- second most common cause of autoimmune encephalitis in
ing yielded diagnoses of POLG-related mitochondrial disor- pediatric patients. NMDAR encephalitis is a severe neuro-
der, Aicardi-Goutières syndrome (ADAR) and cobalamin C logic inflammatory disease with the potential to cause perma-
disease (MMACHC). nent disability and even death, so although most patients
Conclusions: Here we describe cases of genetic diseases that have good recovery, it is essential to provide timely and
demonstrated clinical and laboratory features of possible sero- appropriate treatment.
negative AIE, based upon current case definition. While Methods: All patients treated at Children’s of Alabama with
empiric treatment with corticosteroids and IVIG may be ini- NMDAR encephalitis between 2012 and 2019 were prospec-
tiated, further investigation with expedited whole exome tively followed and characterized with respect to demo-
sequencing should be considered prior to initiation of long- graphics, symptomatology, clinical course, ancillary testing,
term immunosuppressive AIE treatment. treatment, and outcomes. Functional outcomes were mea-
Keywords: Infections/Neuroimmunology, Genetics sured using the Pediatric Cerebral Performance Category
(PCPC) scale. Residual deficits and disease recurrence were
107. Pediatric Acute Flaccid Myelitis (AFM): Single also used to evaluate outcomes.
Institution Experience During 2018 Season Results: Seventeen patients with NMDAR encephalitis were
Fisher K (Houston, TX), Shukla N, Lotze T included. Mean age was 9.4 years (range 0.6-19.1 years),
with female to male ratio of 3:2. Patients were 47% Cauca-
Objective: Describe the clinical presentation, course, and sian, 40% African-American, and 13% Hispanic. 53% of
short-term outcome of nine AFM patients at Texas Chil- patients were postpubertal. Concomitant herpes simplex
dren’s Hospital in 2018. encephalitis was seen in 33% of patients. A majority of
Methods: Retrospective review of demographic, clinical, and patients had residual symptoms at last follow-up.
statistical data for patients meeting AFM diagnostic criteria Conclusions: As patients with more severe disease generally
Results: All patients presented between July - November require more aggressive treatment, it can be difficult to clarify
2018 at mean age of 5.9 years old (range 4-10 years). Pro- whether more aggressive treatment provides better outcomes.
dromal infection occurred in seven patients. Isolated arm However, many of our patients were treated with a somewhat
weakness occurred in 55%, 33% had arm and leg weakness, standardized regimen of both first and second line treatments
and 11% only leg weakness. 44% of patients had unilateral regardless of disease severity. We demonstrated that more ini-
weakness; the remainder had bilateral weakness (60% were tial aggressive treatment can provide better outcomes and has
asymmetric). One patient had cranial nerve VII involve- few detrimental side effects.
ment. 67% had neck and/or back pain, 33% had arm pain. Keywords: Infections/Neuroimmunology, Rare Diseases
All spinal MRIs demonstrated gray matter predominant
T2-hyperintensities. CSF median cell count was 27 (range
109. Patient Characteristics of Diagnosed Opsoclonus
3-154), 78% having lymphocytic predominance, and pro-
Myoclonus Syndrome at a Single Center
tein was 47 (range 28-58). Infectious studies identified
Melendez-Zaidi A (Houston, TX), Balasa A, Evankovich K,
enterovirus in three patients and eastern equine virus in
Lotze T
one. Treatment included intravenous corticosteroid, IVIG,
and plasmapheresis in three patients, IVIG alone in four, Objective: Opsoclonus myoclonus syndrome (OMS) is an
and two were untreated. Median hospitalization was inflammatory disease that causes significant motor and

S90 Annals of Neurology Vol 86 (suppl 23) 2019

neurodevelopmental morbidity. Reports have described the with perivascular and leptomeningeal lymphocytic inflamma-
features of OMS however, a majority of these are limited by tion. Four of these cases demonstrated the presence of
small cohorts and the potential for inconsistency given het- multinucleated giant cells. In our study we were unable to
erogeneous parties involved in establishing diagnostic criteria. identify genetic polymorphisms in any of the genes in the
To circumvent these shortcomings, we analyzed the cases of TLR3 pathway studied.
OMS at our hospital over 21 years. Conclusions: Evidence of chronic granulomatous inflam-
Methods: We chart reviewed all diagnoses of OMS utilizing mation is not typically a common feature of chronic
personal databases in conjunction with the EMR reporting HSE however our study identified these elements in 4 of
tool “SlicerDicer.” All charts were reviewed for validity in 7 patients. These findings suggest that a severe destruc-
diagnosis by two independent personnel. tive inflammatory process may be a long term sequela of
Results: Of 65 total cases, 13 were excluded for alterna- HSE. Nevertheless, the limited nature of our study was
tive diagnoses after workup, the most common being unable to fully assess the genetic pre-disposing factors
Spasms nutans. Of the remaining 52, median age at diag- associated in our subset of patients who developed
nosis was 19.2 months (Q1=15.6, Q3=28.8). Symptoms refractory HSE.
at presentation were robust: 91.3% opsoclonus, 56.5% Keywords: Infections/Neuroimmunology
myoclonus, 100% ataxia. OMS was associated with neuro-
blastoma in 52.2% of cases. IVIG was exclusive or
included in first line therapy 65.2% of the time, steroids
111. Neurodevelopment in Apparently Normal Newborns
alone in 26.1%. 69.6% and 56.5% of patients went on
from Zika Virus Positive Pregnancies
to receive second- and third-line treatments, respectively;
Mulkey S (Washington, DC), Arroyave-Wessel M, Bulas D,
78% of patients continued maintenance therapy. At follow
Vezina G, Fourzali Y, Morales A, Russo S, Kousa Y, Peyton C,
up, 13% and 26.1% had remaining symptoms of
Msall M, Jiang J, McCarter R, DeBiasi R, du Plessis D, Cure C
opsoclonus and ataxia. As previously reported for this
cohort, 15 patients underwent neuropsychological testing Objective: Determine if infants without Congenital Zika
that was notable for significant deficits in attention and Syndrome (CZS) exposed to ZIKV in utero, have normal
inattention. neurodevelopment.
Conclusions: Patients characteristics in our cohort were com- Methods: We performed a longitudinal study of neuro-
parable to that reported in other studies. A significant num- development in Colombia for infants exposed to ZIKV in
ber of patients initially considered (20%) had an alternative utero who had normal fetal brain MRI (Mulkey et al, JAMA
diagnosis after workup underscoring the potential for mis- Peds 2019) and normal birth head circumference. Infant
diagnosis and inclusion. development was assessed by the Warner Initial Developmen-
Keywords: Infections/Neuroimmunology, Movement Disor- tal Evaluation of Adaptive and Functional Skills (WIDEA)
ders, Rare Diseases and the Alberta Infant Motor Scale (AIMS). In-person train-
ing was done by a neurologist. The AIMS were video-
recorded and scored centrally. Results were converted to
110. A Histopathologic Review of Post-herpes Simplex Z-scores compared to normative samples. Infants had cranial
Virus Encephalitis with Neurologic Relapse US and we compared development between infants with nor-
Mwangi M (St. Louis, MO), Movassaghi M, Krogstad P, mal and non-specific findings.
Mathern G, Vinters H Results: 72 non-CZS infants had neurodevelopmental tests.
Objective: Herpes simplex encephalitis (HSE) is the most Forty were at a mean of 5.7(0.9) months and 66 were at
common cause of fatal sporadic encephalitis in the United 13.5(3.2) months of age. Thirty-four had two assessments.
States. While most cases of HSE occur in individuals without The total WIDEA, social cognition, and mobility domain
clearly predisposing conditions, recent evidence suggests HSE scores grew more abnormal with postnatal age (Figure). The
in many cases may be secondary to a primary immunodefi- AIMS scores were similar to the normative sample. Three
ciency state. In this study we sought to characterize the infants had an AIMS score <2 SD’s below the norm. On cra-
chronic nature of HSV encephalitis by histopathological and nial US, 19 infants (26%) had a non-specific finding (len-
genomic DNA analysis. ticulostriate vasculopathy, choroid plexus cysts,
Methods: In this study seven children who had a neurologi- subependymal cysts, and/or calcification). Infants with an
cal relapse at least one year subsequent to their initial HSE imaging finding had a lower WIDEA mobility score than
were selected from UCLA pathology archives and the histo- infants with normal US (P=.054). There was a trend towards
pathologic changes in their brains were reviewed. Addition- lower AIMS scores in infants with US findings compared to
ally, DNA extracted from tissue available for two individuals infants with normal US (P=.26).
was submitted for whole exome sequence analysis of the Conclusions: ZIKV-exposed infants without CZS are at risk
genes encoding Toll-like receptor 3 (TLR3) associated with for neurodevelopmental decline. Non-specific cranial US
increased HSV susceptibility. findings may represent mild ZIKV-related injury.
Results: All seven cases showed multifocal cystic Keywords: Infections/Neuroimmunology, Cognitive/
encephalomalecia with pronounced reactive gliosis, along Behavioral Disorders

Program and Abstracts, Child Neurology Society S91

FIGURE 1: WIDEA Total and Domain Z-Scores in ZIKV-Exposed Cohort. Abstract 111 [Color figure can be viewed at www.
wileyonlinelibrary.com]

112. Central Nervous System Virus Infection in African retinopathy-positive CM were hypothesized to have a non-
Children with Cerebral Malaria malarial etiology of illness coupled with asymptomatic
Postels D (Washington, DC), Osei-Tutu L, Seydel K, Xu Q, malaria parasitemia, the latter reflecting residence in an area
Li C, Taylor T, John C, Mallewa M, Solomon T, Opoka R, of high transmission intensity. As children with viral enceph-
Ansong D, Khan L, Leon K, Langelier C, Wilson M alitis have a similar phenotype to those with CM, our goal
Objective: Cerebral malaria (CM) affects African children was to identify the contribution of central nervous system
and presents with coma, fever, and seizures. Two-thirds of (CNS) viral infection to illness in children with retinopathy-
African children with CM have a malaria-specific retinopathy. negative CM.
In autopsy studies, children with retinopathy-positive CM Methods: We collected cerebrospinal fluid (CSF) from
have malaria infection exclusively responsible for their illness. 272 Ghanian, Ugandan, and Malawian children with CM,
Children dying of retinopathy-negative CM have non- and selected CSF from 111 of these children (38 retinopa-
malarial causes of death. Previously, children with thy-positive, 71 retinopathy-negative, 2 retinopathy-

S92 Annals of Neurology Vol 86 (suppl 23) 2019

unknown) for analysis by metagenomic next-generation 114. A Rare Case of an Intramedullary Spinal Cord
sequencing (mNGS) Abscess due to Escherichia Coli in a Pediatric Patient
Results: We found CSF viral co-infections in 7/38 (18.4%) Sehgal R (Maywood, IL), Budnik E, Mallik A, Leischner M
retinopathy-positive children and in 18/71 (25.4%) Objective: There have been few case reports of intramedullary
retinopathy-negatives. Excluding HIV-1, human herpesvi- spinal cord abscess (ISCA) since the first description in 1830.
ruses (HHV) represented 75% of viruses identified. CNS A high degree of clinical suspicion and radiographic imaging is
viral co-infection was equally likely in retinopathy-positive essential for early diagnosis and initiation of treatment to avoid
and retinopathy-negative children (p= 0.1431). Neither mor- irreversible spinal cord damage. Our work describes an uncom-
tality nor neurological morbidity was associated with viral co- mon case presentation of an ISCA in the setting of a dermal
infection (OR=0.276, 95% CI: 0.056-1.363). Level of con- sinus tract as a possible reservoir for infection.
sciousness at admission was not associated with CNS viral Methods: Clinical file review and extensive literature search
co-infection. on ISCA in a pediatric patient
Conclusions: CNS co-infection is unlikely to contribute to Results: A two year old male with a history of neonatal men-
coma in children with CM. The herpesviruses other than ingitis due to Escherichia Coli who presented with refusal to
HSV may represent incidental bystanders in CM, reactivating walk. Physical exam was remarkable for a pit over his midline
during acute malaria infection. sacral spine. Magnetic resonance imaging revealed multiple
Keywords: Infections/Neuroimmunology cord abscesses - intramedullary at the conus and
extramedullary at the L4-L5 spinal level (Fig. 1). Imaging
113. Autoimmune Encephalitis in Children: A Case Series also revealed a tract that communicated between the skin and
at a Tertiary Care Center posterior spinal canal consistent with a dorsal dermal sinus
Rutatangwa A (San Francisco, CA), Mittal N, Francisco C, tract (Fig. 2). The patient underwent a laminectomy with tis-
Nash K, Waubant E sue culture positive for Escherichia Coli. Following an
Objective: To highlight the common presenting symptoms, extended course of intravenous antibiotics, further surgical
diagnostic workup and effectiveness of treatments used in the drainage and physical therapy, the patient regained full
various types of autoimmune encephalitis (AE) in children. strength and is currently meeting developmental milestones.
Methods: Pediatric patients evaluated at UCSF for AE Conclusions: It is important to consider ISCA in the differ-
between February 2015-July 2018 were identified from the ential diagnosis when a patient presents with neurologic
clinic database and inpatient consults. Data were collected symptoms localizing to a spinal cord level. The presence of a
from chart review.
Results: Twelve patients were identified with AE (median
age at presentation 9 years (range 1.67 – 18 years), 77%
females). The most common type of encephalitis was steroid-
responsive encephalopathy associated with thyroiditis
(SREAT) (n=5), followed by anti-N-methyl-D-aspartate
receptor (NMDAr) encephalitis (n=3) and glial fibrillary
acidic protein (GFAP)-associated encephalitis (n=1). Three
patients had antibody-negative AE. Only one of the patients
with SREAT had a medical and family history of autoim-
mune disease. The most common presenting symptoms
included changes in behavior (58%) and seizures (67%).
Brain MRI abnormalities were seen in 3 patients (NMDAr
and GFAP). All but one patient were surveilled for malig-
nancy and none was identified. Over 90% of patients showed
improvement following initial immunotherapy, i.e. pulse ste-
roids or IVIG. 68% of patients also received a 2ndline treat-
ment (rituximab and/or cyclophosphamide). One patient
with NMDAr encephalitis died within 65 days of initial pre-
sentation despite treatment with pulse steroids, IVIG, plasma
exchange, cyclophosphamide and rituximab. None of the
other patients have shown complete recovery or return to
baseline function after a median follow-up of 7 months
(range 0.5 – 66 months).
FIGURE 1: A, B: Sagittal T1 postcontrast and Sagittal T2
Conclusions: AE has a diverse presentation in children.
images two rim enhancing intradural abcesses. The more
Although there is generally good response to therapy, signifi- superior abscess is an intramedullary abscess in the conus
cant residual deficits may remain. medullaris. C, D: Axial T1 postcontrast and Axial T2 images
Keywords: Infections/Neuroimmunology, Cognitive/Behav- (at the level of the dotted line in A) demonstrate the
ioral Disorders, Rare Diseases intramedullary abscess within the conus. Abstract 114

Program and Abstracts, Child Neurology Society S93

 (E350, WE2.2 and Clone 13). Cellular targets of infection,
histopathology, lymphocytic responses, cytokine profiles, and
behavioral deficits were determined.
Results: Different viral strains induced markedly different pat-
terns of infection, neuropathology, immune responses, and
behavioral deficits. The cellular target of the E350 strain was
glial cells, while the other strains targeted neurons. In the cere-
bellum, E350 induced destructive lesions (arrow), while the
other strains induced hypoplasia (see figure below). The E350
strain attracted large numbers of CD8+ lymphocytes early in
the disease course, while Clone 13 attracted CD4+ lympho-
cytes, and the infiltration occurred late. The E350 and WE2.2
strains induced large increases in expression of
proinflammatory cytokines, while Clone 13 did not. The
E350 and WE2.2 strains caused ataxia and olfactory deficits,
while Clone 13 caused generalized body growth failure.
Conclusions: In the developing brain, different LCMV
strains have different cellular targets of infection and forms of
neuropathology involving different brain regions, induce dif-
ferent immune responses, and cause different disease states.
FIGURE 2: A, B: Sequential axial T2 images at the level of These results suggest that the different outcomes in human
L4-L5 near the more inferior abscess demonstrate a sinus tract
congenital LCMV infection may be due to infection with dif-
communicating between the skin and the posterior spinal
ferent strains of the virus.
canal (!). C-F: Sequential sagittal STIR and T1 postcontrast
images demonstrate the dermal sinus tract. Abstract 114 Keywords: Infections/Neuroimmunology, Neonatal Neurology
[Color figure can be viewed at www.wileyonlinelibrary.com]
116. Extended Immunotherapy for Pediatric Anti-
NMDAR Encephalitis
midline sacral pit should alert the clinician to the possibility Wells E (Washington, DC), Kahn I, Sady M, Doslea A,
of a dermal sinus tract, as demonstrated in our case. Fleming M, Ball L, Parker M, Suslovic W
Keywords: Infections/Neuroimmunology, Neonatal Neurology
Objective: Six-month duration of immunotherapy for anti-
NMDAR encephalitis is common in adults; however pediat-
115. Viral Strain Determines Disease Symptoms, ric recoveries may take up to 2 years or longer with more
Pathology, and Immune Response in a Rat Model of adverse neurologic sequelae. We report our experience with
Congenital LCM Virus Infection extended immunotherapy.
Todd D (Iowa City, IA), Plume J, Bonthius D Methods: A retrospective review of non-paraneoplastic anti-
Objective: Congenital lymphocytic choriomeningitis virus NMDAR patients in an IRB-approved clinical-biorepository
(LCMV) infection injures the fetal brain. However, the effects identified 5 children diagnosed and treated in a multi-
differ substantially among cases. The cause of this diversity is disciplinary program with B-cell depleting therapy and monthly
unclear. Possibly, fetuses are infected with different strains of IVIG beyond 6 months. Initial therapy, reasons for extended
virus. We utilized a rat model to investigate how differences in therapy, adverse effects, and longitudinal modified Rankin sub-
viral strain affect outcome in congenital LCMV infection. scale (MRS) scores (1-6 with 6 being dead) were assessed.
Methods: Neonatal rats were injected intracranially with Results: All received PLEX, IVIG and rituximab during
saline (control) or one of three different strains of LCMV induction; 4/5 received IV methylprednisolone which was

FIGURE 1: Abstract 115 [Color figure can be viewed at www.wileyonlinelibrary.com]

S94 Annals of Neurology Vol 86 (suppl 23) 2019

discontinued during maintenance. Duration of rituximab and chorea/dystonia associated with life threatening complications.
monthly IVIG ranged from 9 months to ongoing at These movements have been exceedingly resistant to medica-
52 months post diagnosis. Wheezing and headaches but no tions, however, GPi-DBS has been the most effective thus far.
serious adverse effects occurred. At 6 months, 3/5 had MRS Keywords: Movement Disorders, Critical Care, Rare
4, 2/5 had MRS 3 and all had expressive language impair- Diseases
ment. When immunotherapy was discontinued in 3/5, MRS
was 2 with improved expressive language. At last follow-up 118. Cerebral Palsy Spectrum Disorder in Canadian
all patients had adverse sequelae but continued to make neu- Indigenous Children
ropsychiatric, developmental and educational gains. Chen A (Montreal, Quebec), Dyck Holzinger S, Andersen J,
Conclusions: Differentiating direct and indirect effects of Buckley D, Fehlings D, Kirton A, Koclas L, Pigeon N, Van
anti-body mediated disease is difficult in developing children Rensburg E, Wood E, Oskoui M, Shevell M
recovering from anti-NMDAR encephalitis. This retrospec-
Objective: Inequity in health outcomes for Indigenous Peo-
tive case series demonstrates clinician and family preference
ples of Canada has been demonstrated across determinants.
for prolonged, step-down therapy in patients with moderate
This study aims to describe differences in cerebral palsy
to poor 6-month outcomes, without serious adverse effects.
(CP) profile in Indigenous children compared to non-
Optimal treatment length should be evaluated in pediatric-
Indigenous children with CP in Canada.
focused clinical effectiveness research or clinical trials; stake-
Methods: Using the Canadian Cerebral Palsy Registry, we
holder preference for aggressive, step-down immunotherapy
conducted a retrospective cohort study. Differences in perinatal
should be considered, particularly in tumor-negative cases.
factors, CP phenotype, presence of comorbidities, imaging
Keywords: Infections/Neuroimmunology, Critical Care
findings, and risk factors for CP were explored between Indig-
enous and non-Indigenous children, using univariate analysis.
Results: 94 Indigenous[MO1] children with CP had higher
MOVEMENT DISORDERS odds of having comorbidities (OR=4.458, 95%
CI=1.619-12.280), especially cognitive (OR[MO2] =4.532,
95% CI=2.269-9.051), communication (OR=2.661, 95%
117. Management of Life Threatening Movement CI=1.536-4.612), and feeding (OR=2.211, 95%
Disorder in GNAO1 Mutations: Two New Cases and CI=1.302-3.755) impairment than non-Indigenous children
Review of the Literature with CP in our cohort. No differences were found for CP
Hull M (Houston, TX), Parnes M subtype, GMFCS scores, and prematurity. Also, no signifi-
Objective: To present two cases of GNAO1 related move- cant differences were detected for the etiologic cause
ment disorder associated with life threatening persistent cho- (pre/perinatal vs postnatal) of CP. However, Indigenous chil-
rea successfully managed with bilateral GPi deep brain dren had 5.111 times the odds (95% CI=1.089-23.978) of
stimulation (GPi-DBS) and review previously reported cases having non-accidental head injury as the cause of their post-
in the literature with emphasis on treatment. natal CP[MO3], instead of infection and cerebral vascular
Methods: More than 40 patients have been reported in the lit- accident as seen in non-Indigenous children. As for
erature of GNAO1 mutations; phenotypes include neu- pre/perinatal risk factors for CP, Indigenous children have
rodevelopmental disability, infantile epileptic encephalopathy, higher odds of having had antenatal toxic exposure
hypotonia, and involuntary movements. The involuntary (OR=8.849, 95% CI=5.195-15.074), hyperbilirubinemia
movements include chorea and/or dystonia resulting in life (OR=1.809, 95% CI=1.379-5.012), umbilical cord problems
threatening “storms” requiring several intensive care unit stays [MO4] [AC5] (OR=9.710, 95% CI=1.344-70.168), and
due to fractures, lactic acidosis, and rhabdomyolysis. Several IUGR (OR=2.629, 95% CI=1.379-5.012).
treatments have been utilized with varying success. We Conclusions: Comorbidities are more common in Indige-
describe two new cases, a 14 year old male and 3 year old nous children with CP, reinforcing the need for a multi-
female, admitted to the ICU in the setting of febrile illness disciplinary approach to management. Furthermore, targeted
associated with life threatening chorea. Both courses were com- prevention programs against potentially preventable causes of
plicated by rhabdomyolysis and respiratory failure. Neither had CP, such as non-accidental head injury, antenatal toxin, and
improvement in chorea with administration of benzodiaze- hyperbilirubinemia, may be beneficial.
pines, tetrabenazine, and other medications. Both had bilateral Keywords: Movement Disorders
GPi-DBS emergently implanted with significant improvement.
Results: We present two additional cases of pharmacoresistant
119. Losing a Diagnosis of Cerebral Palsy: Comparison of
chorea in patients with GNAO1 mutations that resulted in
Characteristics at Age 2 Between Eventual Confirmed and
significant improvement of symptoms following DBS. While
Non-Confirmed Cerebral Palsy at Age 5
one patient was only recently implanted, the other has not had
Chen A (Montreal, Quebec), Dyck Holzinger S, Andersen J,
recurrent ICU admission since implantation three years ago.
Buckley D, Fehlings D, Kirton A, Koclas L, Pigeon N, Van
Conclusions: GNAO1 mutations have been associated with
Rensburg E, Wood E, Oskoui M, Shevell M
multiple phenotypes including epileptic encephalopathy and
involuntary movements. These movements can have several Objective: Cerebral palsy (CP) diagnosis features a ‘probable’
triggers including fever, pain, etc. and result in storms of diagnosis at 2 years, often ‘confirmed’ at 5 years. However,

Program and Abstracts, Child Neurology Society S95

some children are misdiagnosed as CP at age 2, and receive a Methods: Initial analysis includes 10 adult subjects with
diagnosis other than CP at age 5. This study aims to identify cerebral palsy (Gross Motor Functional Classification Status
characteristics at age 2 that differ between eventually con- I-V) able to self-report and 5 typical control graduate-level
firmed and non-confirmed CP at age 5 student subjects (TC). Pain intensity, interference, and qual-
Methods: Using retrospective cohort analysis, 1683 children ity were reported using PROMIS short forms and the
diagnosed as CP at age 2 were identified from the Canadian PainDETECT neuropathic screening questionnaire. A struc-
Cerebral Palsy Registry, of which 48 received a non-CP diag- tured physical examination included 1) quantitative measures
nosis at age 5 (“non-confirmed CP”). Perinatal adversity, pre- of mechanical sensory detection (Von Frey monofilaments)
maturity, disease severity, presence of comorbidities, MRI and cortical somatosensory discrimination (JVP dome thresh-
findings, and initial CP type were compared between the two old), 2) qualitative sensation of thermal stimuli, and 3) motor
groups by univariate and logistic regression analyses. evaluation.
Results: Chi-square analysis and multivariate analysis (MVA) Results: Individuals with CP reported significantly greater
both confirmed that children without CP at age 5 were more pain intensity, pain interference, neuropathic qualities, and
likely to have normal MRI (Chi-Square OR=7.8, 95% nociceptive qualities (by nonparametric ranksum test) than
CI=3.8-16.1; MVA OR=5.4, 95% CI=2.4-12.5), initial diag- typical controls (Figure 1)). Median between-group difference
nosis of ataxic-hypotonic (Chi-Square OR=10.1, 95% in pain interference (ΔT=8.6) was approximately two times
CI=4.9-21.2; MVA OR=6.1, 95% CI=2.2-16.2) or dyski- the previously-published minimally important difference.
netic CP (Chi-Square OR=2.7, 95% CI=1.2-5.9; MVA Group differences in sensory thresholds were not statistically
OR=2.9, 95% CI=1.0-7.6), lack prematurity (Chi-Square significant, but cortical sensory deficits were more prominent
OR=3.7, 95% CI=1.7-8.0; MVA OR=3.6, 95% (Figure 2). Anecdotally, individuals with positive
CI=1.0-12.1), and lack perinatal adversity (Chi-Square PainDETECT neuropathic screens (N=2) had qualitative
OR=4.1, 95% CI=1.6-10.7; MVA OR=3.4, 95% alterations in cool sensation (allodynia and decreased sensa-
CI=1.0-11.7). tion, respectively).
Conclusions: Normal MRI, ataxic-hypotonic or dyskinetic Conclusions: Neuropathic and nociceptive pain as well as
CP, lack of perinatal adversity, and term birth are associated cortical sensory deficits appear to be common in individuals
with a higher odds of eventual non-CP diagnosis. The pres- with CP. A subset of individuals with CP have phenotypes
ence of these features in a 2-year-old child may guide clini- suggestive of central pain. Identification of pain-relevant sen-
cians to the possibility of a diagnosis other than CP, thus sory features may be detectable with a quick bedside screen-
enhancing diagnostic work-up and suggesting closer follow- ing exam
up for a possible alternative diagnosis. Keywords: Movement Disorders, Palliative Care
Keywords: Movement Disorders
121. Methyldopa Causing Parkinsonism in a Young Adult
120. Pain and Sensory Features in Individuals with Fraser S (Houston, TX), Aertker B, Butler I
Cerebral Palsy Objective: Methyldopa is an antihypertensive that is also
Chin E (Baltimore, MD), Lenz C, Johnson J, Ye X, used for behavioral disturbance. There is evidence from phar-
Campbell C, Hoon A, Robinson S macologic data that methyldopa can affect dopaminergic
Objective: To define phenotypes of pain and sensory abnor- activity in the basal ganglia. Our objective is to describe a
malities in individuals with cerebral palsy (CP). While case of drug induced parkinsonism in a young adult caused
chronic pain and sensory dysfunction are each known to be by methyldopa and to discuss mechanisms of action of drug
prevalent in adults with CP, cortical and primary sensory sen- induced parkinsonism from methyldopa.
sitivity have not been compared, and pain mechanisms in this Methods: Description of a case of parkinsonism induced by
population are not clear. methyldopa.

FIGURE 1: Group pain characteristics in CP and TC. Abstract 120 [Color figure can be viewed at www.wileyonlinelibrary.com]

S96 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 2: Group sensory testing characteristics. Abstract 120 [Color figure can be viewed at www.wileyonlinelibrary.com]

Results: The patient is a 25 year old female with interval (CI) of sham-exposed values. Dystonic (N=6), non-
velocardiofacial syndrome followed in the child neurology dystonic (N=5), and sham-exposed animals (N=5) were ran-
clinic for behavioral disturbances. She was on methyldopa domly selected for initial histologic analysis. Parvalbumin
for years for behavioral disturbance. The family noted gait (PVA) positive and choline acetyltransferase (ChAT) positive
slowing and bilateral tremor in 2018. On exam, she had interneuron numbers in the dorsal striatum were estimated
bilateral upper extremity resting tremor. She also had shuf- using unbiased stereology. Statistical comparisons were with
fling gait with decreased arm swing bilaterally. She had made with Kruskal-Wallis tests.
cogwheeling at the neck as well as bilateral upper extremi- Results: Hypoxia-exposed rats had a greater number of
ties. She had no changes in behavior or mood, and no ChAT-positive interneurons (95%CI 14777-26537 neurons)
orthostatic intolerance. Her symptoms resolved with cessa- compared to sham-exposed rats (95%CI 5046-23565 neu-
tion of methyldopa. rons, p=0.01), but without a significant difference between
Conclusions: There are reports of methyldopa induced par- dystonic and non-dystonic rats. Dystonic rats had a preserved
kinsonism in the 1960s, 70s, and 80s in older adults. Phar- number of PVA-positive interneurons (95%CI
macologic data on methyldopa was first published in the 17636-31170), comparable to sham-exposed rats (95% CI
1960s and 70s. Methyldopa is a competitive inhibitor of 18305-32626), but greater than in non-dystonic rats which
dopa decarboxylase, which converts dopa to dopamine. demonstrated a significant loss of PVA-positive interneurons
Methyldopa is metabolized to alpha-methylnorepinephrine, (95%CI 14390-24030, p=0.03).
which competes with dopamine for post-synaptic receptors in Conclusions: Dystonia following neonatal brain injury in
the striatum. As such, it is potentially able to effectively rats is associated with an increased number of cholinergic
decrease dopaminergic activity in the striatum, mimicking interneurons and a preserved number of PVA-positive
the pathophysiology of classic parkinson’s disease. To our GABAergic interneurons in the dorsal striatum. These striatal
knowledge, this is the first case report of methyldopa induced interneurons may play critical roles in the emergence of dys-
parkinsonism in a young adult. tonia following neonatal brain injury. Since both these inter-
Keywords: Movement Disorders, Cognitive/Behavioral Dis- neuron populations are decreased in genetic animal models of
orders, Rare Diseases dystonia, these results also highlight the distinct pathophysi-
ology of dystonic CP.
122. Striatal Interneurons are Increased or Selectively Keywords: Movement Disorders, Neonatal Neurology
Preserved in Dystonic Rats Following Neonatal Brain
Injury 123. The Natural History of AADC Deficiency: A
Gandham S (St. Louis, MO), Tak Y, Aravamuthan B Retrospective Study
Objective: To determine the striatal interneuron histopathol- Gilbert L (St. Louis, MO), Black K, Opladen T, Jeltsch K,
ogy associated with dystonic cerebral palsy (CP) Garcia-Cazorla A, Leuzzi V, Tay S, Sykut-Cegielska J,
Methods: We developed a model of dystonic CP in rats fol- Andrews S, Kato M, Luecke T, Oppeboen M, Kurian M,
lowing global hypoxia at human term-equivalent gestation. Flint L, Pearson T
Hypoxia-exposed rats were classified as dystonic if antagonist Objective: To assess the disease characteristics of a large
muscle cross-correlogram amplitudes during voluntary iso- international cohort of patients with aromatic l-amino acid
metric hindlimb contraction were above the 95% confidence decarboxylase deficiency (AADCD). AADCD is a rare,

Program and Abstracts, Child Neurology Society S97

autosomal recessive, neurometabolic disorder that presents threshold of p<0.05, data sets within the clusters were similar
with motor impairment, behavioral symptoms, and intellec- and significantly different from other clusters.
tual disability due to impaired synthesis of the monoamine Conclusions: Fidgety infants have greater variability in COP
neurotransmitters dopamine and serotonin. patterns than their mature counterparts. We anticipate addi-
Methods: In this retrospective study, we created a written tional COP measurements will correspond with qualitative
questionnaire to be completed by patients’ caregivers and/or GMA analyses. Quantification of GMA may be useful in ear-
physicians to obtain data about disease onset, symptom lier detection or prediction NDD outcomes.
course, developmental outcome, and mortality. Patients were Keywords: Movement Disorders
recruited via: 1) The International Working Group of
Neurotransmitter-Related Disorders (iNTD) Registry or 2) 125. A Novel DYT1A Mutation Associated with
the AADC Research Trust, a parent-run foundation. Secondary Tic Disorder
Results: 64 patients (39 female, 25 male) from 23 individual Kaul S (Houston, TX), Thakur N, Butler I
countries participated. Ages ranged from 6 months to Objective: Tics are sudden, repetitive, involuntary, non-
36.8 years (median 7 years). Symptom onset occurred at a rhythmic, rapid movements or vocalization. Secondary tics
median age of 3 months (range: 0-12 months). The most disorders or “Tourettism “suggests tics associated with medi-
common initial symptoms were hypotonia, developmental cal conditions, surgery, genetic etiologies and neurodegenera-
delay, and oculogyric crises, each reported in >50% of sub- tive diseases.
jects. Oculogyric crises were present in 90-100% of patients Methods: We present a 26-year-old male who began
aged 2-12 years, and also occurred in the majority of experiencing abdominal tics, described as “spasms”, as well as
patients <2 and >12 years. Other symptoms classified as vocalization (hiccups) when he was 14 years old. Nine years
“major” by over half of the respondents were feeding diffi- later, he experienced ocular tics, described as “bilateral eye
culties, sleep disturbance, and irritable mood. 70% of sub- twitching”. He then developed daily dystonic curling of right
jects had severe physical disability and were fully dependent foot, occurring at rest, and increasing in severity with time. At
for routine daily activities. However, 19% attained indepen- presentation, abdominal tics involving the trunk were observed
dent walking. throughout evaluation. Progressive nature of tics and dystonic
Conclusions: The majority of patients with AADCD have curling of foot was concerning for an underlying genetic etiol-
severe motor impairment. Oculogyric crises typically persist ogy, and whole exome sequencing was obtained. He was
throughout childhood and adolescence. Gastrointestinal, found to have a heterozygous, paternally inherited pathogenic
mood and sleep disturbances are additional prominent disease variant in TOR1A !p.F205I, c.613T>A.
features. Results: TOR1A is a DYT1 gene, member of the AAA fam-
Keywords: Movement Disorders, Rare Diseases ily of ATPases, and located on chromosome 9q34.11.
TOR1A encodes an AAA-ATPase, this region ΔGAG muta-
124. Quantification of the General Movement Assessment tion is characteristic of early onset, generalized dystonia. Our
Using Center of Pressure Patterns in Healthy Infants patient displayed a different genetic variant, involving a mis-
Kapil N (Little Rock, AR), Escapita A, Simpson H, Siddicky S, sense mutation on position 205 of exon 3 of TOR1A that
Wang J, Mannen E, Johnson T changed a phenylalanine to an isoleucine (c.613!A, p.
Objective: One in six children in the U.S. has a Neu- F205I). Only one other case of this genetic variant compar-
rodevelopmental Disability (NDD). Prechtl’s General Move- ing phenotypic expression of TOR1A gene with novel muta-
ment Assessment (GMA) is a predictor of early motor tion to ΔGAG mutation in cultured cells is reported in
dysfunction and a qualitative assessment of infant movement. literature.
However, no quantitative biomechanical assessment exists to Conclusions: It is possible that the DYT1 mutation found
accurately identify patients with NDD, and the qualitative in our patient is responsible for his early onset tics, even in
GMA may not be sensitive enough to detect motor dysfunc- absence of dystonia, and may represent a broader clinical
tion in some patients. phenotype than previously described
Methods: With UAMS IRB approval, as part of a larger Keywords: Movement Disorders, Genetics, Rare Diseases
study, healthy infants were filmed while lying supine on a
force plate for 2 minutes. Video footage was used to qualita- 126. Lower Limb Injections of OnabotulinumtoxinA:
tively confirm fidgety movements based on the GMA. Center Improvement in Gait and Treatment Goal Achievement
of pressure (COP) path-lengths were gathered from the force in Pediatric Patients with Cerebral Palsy
plate at 1000 Hz. We grouped our data with K-means clus- Kim H (St. Louis, MO), Racette B, Dunn C, Mukherjee S,
tering and performed statistical analysis with ANOVA. McCusker E, Liu C, Dimitrova R
Results: We studied 8 infants born at >37 weeks gestation, Objective: In a phase 3, double-blind, placebo-controlled
(38.9
1.5): 3 transitioning to fidgety period, (≤3 months), study onabotulinumtoxinA was demonstrated to be well-
3 in fidgety period, (3-5 months), and 2 matured beyond tolerated and effective for the treatment of lower-limb spas-
fidgety period (>5 months). The 3 fidgety infants and the ticity in children with cerebral palsy (CP). Here we report
2 mature infants clustered into 2 groups; 2 of 3 infants in specific functional outcomes from that study.
the transitional period clustered into a third group. A GMA Methods: Children (aged 2–<17 years) were included who
reader (TJ) qualitatively confirmed these findings. Using a had CP and ankle plantar flexor Modified Ashworth Scale-

S98 Annals of Neurology Vol 86 (suppl 23) 2019

Bohannon (MAS) score ≥2. OnabotulinumtoxinA 8 U/kg, 128. Long-term Safety and Efficacy of
4 U/kg, or placebo was injected into ankle plantar flexors; OnabotulinumtoxinA for the Treatment of Upper Limb
patients also received standardized physiotherapy (PT). Out- Spasticity in Children with Cerebral Palsy: Open-label
comes include Physician assessed Goal Attainment Scale Extension Study
(GAS) and the Edinburgh Visual Gait (EVG) which included McCusker E (Irvine, CA), Fehlings D, Dimitrova R, Chen K,
a subset of patients (n=65). Banach M, Bonikowski M,
Results: Overall, 384 patients were randomized Objective: In a phase 3, double-blind, placebo-controlled
(onabotulinumtoxinA: 8 U/kg, n=128; 4 U/kg, n=126; pla- study onabotulinumtoxinA was demonstrated to be well-
cebo, n=130). At baseline, 265 patients (~70%) set active goals tolerated and effective for treatment of upper-limb spasticity
related to walking and moving; 289 patients (~ 76%) set pas- in children with cerebral palsy (CP).The aim of this open-
sive goals related to symptoms of pain, spasm or orthosis/brace
label extension of the double-blind study was to evaluate
wear. Improvements in GAS were significant for
long-term safety and efficacy of repeated doses of
onabotulinumtoxinA + PT vs placebo + PT for both active
onabotulinumtoxinA in this population.
and passive goals at Weeks 8 and 12 for 8 U/kg (p ≤ 0.010)
Methods: Each patient could receive up to 5 doses of
and at week 8 for 4 U/kg (p ≤ 0.047). Patients evaluated with
onabotulinumtoxinA (maximum 8 U/kg [300 U] in Cycle
the EVG, 4 and 8 U/kg demonstrated dose dependent
1 and 10 U/kg [340 U] in Cycles 2-5) over 60 weeks.
improvement (statistical significance at 8 U/kg vs placebo at
Week 8; p = 0.018) in the total score and select individual Retreatment criteria: MAS-B score ≥1+ and ≥12 weeks since
items (associated with foot stance and swing) over placebo. last treatment. Key efficacy endpoints included change from
Conclusions: OnabotulinumtoxinA and PT led to greater baseline in MAS-B and mean Clinical Global Impression of
improvement in gait and significant achievement in active and Overall Change (CGI).
passive treatment goals compared with placebo and PT alone. Results: 211 patients from the double-blind study and 2 de
Keywords: Movement Disorders novo patients were included. Patients were on average
8.3 years old, 60.1% male, and 61.0% white. Most patients
(149/213 [70.0%]) received ≥3 upper-limb treatments. Over-
127. Ataxic-Hypotonic Cerebral Palsy in a Cerebral Palsy
all, 125/213 (58.7%) patients experienced ≥1 AE; 68/213
Registry: Insights into a Distinct Subtype
(31.9%) during Cycle 1 decreasing to 8/75 (10.7%) during
Levy J (Montreal, Quebec), Oskoui M, Ng P, Andersen J,
Cycle 5. Most common treatment-emergent AEs were upper
Buckley D, Fehlings D, Kirton A, Koclas L, Pigeon N, Van
Rensburg E, Wood E, Shevell M respiratory infection and nasopharyngitis. Serious AEs were
infrequent (6.1%) and none treatment-related. Improvements
Objective: To specifically report on ataxic-hypotonic cerebral in MAS-B from baseline (3.1) to week 6 were consistent
palsy (CP) using registry data, and to directly compare its fea- across repeat treatments (range: −1.5 to −1.7). Improve-
tures with other CP subtypes.
ments in mean CGI were also consistent following repeat
Methods: Data on prenatal, perinatal, and neonatal charac-
treatments to week 6 (range: 2.0 to 2.2).
teristics, as well as gross motor function (GMFCS) and com-
Conclusions: These results demonstrate that in children with
orbidities in 35 children with ataxic-hypotonic CP was
CP and upper-limb spasticity, improvements in muscle tone
extracted from the Canadian Cerebral Palsy Registry and
and global treatment response with onabotulinumtoxinA
compared with 1804 patients with other subtypes of CP.
were consistent with repeat treatment. No new safety con-
Results: Perinatal adversity was detected significantly more
cerns were identified.
frequently in other subtypes of CP (OR 4.3, 95% CI
Keywords: Movement Disorders
1.5-11.7). The gestational age at birth was higher in ataxic-
hypotonic CP (median 39.0 weeks vs. 37.0 weeks, p=0.027).
Children with ataxic-hypotonic CP displayed more intrauter- 129. Long-term Safety and Efficacy of
ine growth restriction (OR 2.6, 95% CI 1.0-6.8) and con- OnabotulinumtoxinA for the Treatment of Lower Limb
genital malformation (OR 2.4, 95% CI 1.2-4.8). MRI was Spasticity in Children With Cerebral Palsy: Open-label
more likely to be either normal (OR 3.8, 95% CI 1.4-10.5) Extension Study
or to show a cerebral malformation (OR 4.2, 95% CI Meilahn J (Marshfield, WI), Kim H, Racette B, Gul F,
1.5-11.9) in ataxic-hypotonic CP. There was no significant Chambers H, McCusker E, Chen K, Dimitrova R
difference in terms of GMFCS or the presence of com- Objective: In a phase 3, double-blind, placebo-controlled
orbidities, except for more frequent communication impair- study onabotulinumtoxinA was demonstrated to be well-
ment in ataxic-hypotonic CP (OR 4.2, 95% CI 1.5-11.6). tolerated and effective for treatment of lower-limb spasticity
Conclusions: Our results suggest a predominantly genetic or pre- in children with cerebral palsy (CP).The aim of this open-
natal etiology for ataxic-hypotonic CP and imply that a diagnosis label extension of this double-blind study was to evaluate
of ataxic-hypotonic CP does not impart a worse prognosis with long-term safety and efficacy of repeated doses of
respect to comorbidities or functional impairment. This study onabotulinumtoxinA in this population.
contributes towards a better understanding of ataxic-hypotonic Methods: Each patient could receive up to 5 doses of
CP as a distinct nosologic entity within the spectrum of CP with onabotulinumtoxinA (maximum 8 U/kg [300 U] in Cycle
its own pathogenesis, risk factors, clinical profile, and prognosis. 1 and 10 U/kg [340 U] in Cycles 2 to 5) over 60 weeks.
Keywords: Movement Disorders, Neonatal Neurology Retreatment criteria: MAS-B score ≥1+ and ≥12 weeks since

Program and Abstracts, Child Neurology Society S99

last treatment. Key efficacy endpoints included change from 131. Deep Brain Stimulation for Pediatric Dystonia
baseline in MAS-B and mean Clinical Global Impression of Tsering D (Washington, DC), Oluigbo C, Berl M, Cameron M,
Overall Change (CGI). Tochen L
Results: 367 patients were included in this analysis, 4 of Objective: When conservative measures fail to relieve painful
which were de novo. Patients were on average 6.9 years old, muscle contractions caused by dystonia, surgery is consid-
54.4% male, and 61.2% white. Most patients (308/367 ered. Deep brain stimulation (DBS) of the globus pallidus
[83.9%]) received ≥3 lower-limb treatments. Overall, internus (GPi) is an intervention that may be performed for
240/367 (65.4%) patients experienced ≥1 AE; 150/367 medication-resistant dystonia. Our objective is to describe
(40.9%) during Cycle 1 decreasing to 18/100 (18.0%) dur- DBS outcomes for pediatric dystonia patients.
ing Cycle 5. Most common AEs were upper respiratory infec- Methods: Our Interdisciplinary Movement Disorders group
tion and nasopharyngitis. Serious AEs were infrequent prospectively reviewed DBS performed by COO (IRB 3799).
(6.5%) and none treatment-related. Improvements in MAS- Demographics and clinical outcomes were analyzed.
B from baseline (3.49) to week 6 were consistent across Results: DBS of the GPi was performed on eight subjects
repeat treatments (range: −1.14 to −1.30). Improvements in (3F,5M) at CNMC. Mean age at first DBS stimulation and
mean CGI were also consistent following repeat treatments length of follow-up were 15.6(9.2-24.8) years and 28.7
to week 6 (range: 1.8 to 1.9). (3.1-59.3) months. 6/8 had bilateral leads. 1/8 used Cle-
Conclusions: These results demonstrate that in children with arpoint navigation. Etiologies were anoxic brain injury (2/8),
CP and lower-limb spasticity, improvements in muscle tone traumatic brain injury (2/8), DYT1primary dystonia (1/8),
and global function with onabotulinumtoxinA were consis- glutaric acidemia type I (1/8), pantothenate kinase-associated
tent with repeat treatment. No new safety concerns were neurodegeneration (1/8), and undetermined (1/8). Mean
identified. changes in Barry-Albright Dystonia (BAD) and Burke-Fahn-
Keywords: Movement Disorders Marsden Disability Rating (BFMDR) scores relative to pre-
op scores were 22.9(-12.5-100)% and 28.4(2.1-100)%.
130. “Your Child Has Cerebral Palsy:” Parental There were no post-operative infections.
Understanding and Misconceptions Conclusions: Patients with longer follow-up generally experi-
Mohanty M (Boston, MA), Beaulieu F, Sampath S, enced greater score improvements than those with shorter
Tambunan D, Kataria S, Rosman N follow-up, consistent with literature suggesting DBS benefits
Objective: To assess parental/caregiver understanding of compound over time. In 7/8, both BAD and BFMDR
Cerebral Palsy (CP) remained stable or improved. For 1/8, BAD increased
Methods: This was a cross-sectional study to assess under- 12.5%, while BFMDR decreased 23.3%. This subject had
standing of the term Cerebral Palsy (CP) by primary care- the longest stimulation history (59.3 months), but was also
givers of 52 children and adolescents with CP, obtained by the oldest at surgery (24.8 years) and a 24-year history of
querying hospital EMRs. Telephone surveys were conducted progressive dystonia. Thus, we conclude DBS is safe and
by the investigators. Health literacy was evaluated. Caregiver effective for pediatric dystonia, especially that which is refrac-
understanding of CP was assessed by their open- ended tory to less invasive alternatives. Further studies are necessary
responses (50%) and their success in answering true/false for elucidating which cohorts may improve most.
questions about CP (50%). Keywords: Movement Disorders
Results: 58% of caregivers suspected something was wrong
with their child during pregnancy, at birth, or during the first 132. GNAO1 Associated Neurologic Disease: Results from
year. 17/52 (33%) of caregivers denied ever being told that the 1st Annual Research Clinic
their child has CP. Most caregivers identified CP as a brain Viehoever A (St. Louis, MO), Wash E, Novak O, Balk K,
problem (79%), lifelong (73%), sometimes caused by an Patterson J, Smith E, Fox A, Bell E, Goodkin H
insult at birth (60%) or before birth (40%). 52% knew that Objective: To define the natural history of GNAO1 associ-
CP was non-progressive. 62% of caregivers believed they had ated neurologic disease in a prospective manner
good or better understanding of the term CP, while the Methods: 22 subjects were evaluated by a multi-disciplinary
investigators found 69% of caregivers to have comparable team including a pediatric epileptologist, pediatric movement
understanding of CP, based on their narratives and their disorders neurologist, 2 pediatric physical therapists, and a
answers to true/false questions (P=0.0064). In 66% of chil- pediatric occupational therapist during a 2 day research clinic
dren with CP, a child neurologist was first medical person to at Washington University in St. Louis, MO. A range of qual-
discuss this diagnosis with the caregiver, while in 31% it was itative and quantitative measures were obtained including
a non-neurological physician. Two-thirds of the caregivers dystonia and chorea rating scales, Gross Motor Function
were very satisfied with the setting where the diagnosis was Measure, Modified Ashworth Scale and Peabody Fine Motor
discussed, the amount of time spent, and the explanations Assessment were assessed for each subject. CPChild quality
provided. of life measure was given to each family.
Conclusions: Following discussion with their child’s physi- Results: 6/22 had epilepsy. All had hypotonia as infants, and
cian, most primary caregivers of children with cerebral palsy all had some degree of motor developmental delay although
have a good (or better) understanding of that term. the range of motor developmental delay was vast. 5/22 have
Keywords: Movement Disorders undergone Deep Brain Stimulation to treat the movement

S100 Annals of Neurology Vol 86 (suppl 23) 2019

disorder. New symptoms of dysautonomia and light sensitiv- Methods: Rats underwent 12 minutes of graded global hyp-
ity were obtained on expanded review of systems that were oxia culminating in anoxia at post-natal day 7-8 (equivalent
previously unknown. to human term gestation). Spasticity was quantified as soleus
Conclusions: GNAO1 associated neurologic disease is an Hoffman (H) reflex suppression with 2Hz tibial nerve stimu-
emerging cause of previously undiagnosed hypotonia, move- lation (suggestive of upper motor neuron injury yielding
ment disorder (sometimes fatal), and epilepsy. Further under- hyperreflexia). Dystonia was quantified during voluntary iso-
standing of the natural history of this disorder is needed metric hindlimb contraction by calculating tibialis anterior
before quality clinical trials can be carried out. This research and triceps surae complex electromyography cross correlation
clinic is the first step in that direction and can be an example (increased amplitude suggestive of dystonic overflow
for other rare disease research clinics. activation).
Keywords: Movement Disorders, Epilepsy, Translational/ Results: Hypoxia affected spasticity and dystonia measures
Experimental Therapeutics and motor performance in a sex-dependent manner
(MANOVA Pillai’s trace p=0.02). At post-natal day
133. Striatal Cholinergic Interneurons May Play Different 28 (equivalent to human early adolescence), rat survivors of
Roles in Dystonia Pathogenesis Across Development neonatal hypoxia exposure (N=43) demonstrated diminished
Aravamuthan B (St. Louis, MO), McCall J H-reflex suppression (post-hoc Tukey HSD p=0.002) and
increased cross correlation (p=0.002) compared to sham
Objective: To determine whether striatal cholinergic inter-
exposure (N=24). Male rat survivors of neonatal hypoxia
neuron (ChI) hyperactivity is sufficient to yield dystonia
demonstrated diminished H-reflex suppression (p=0.002) but
Methods: Dystonia has been associated with striatal ChI
no change in cross correlation (p=0.6). Female rat survivors
hyperexcitability, but it is unclear whether striatal ChIs play a
of neonatal hypoxia demonstrated increased cross-correlation
causal role in dystonia pathogenesis. We examined this by
(p=0.02), but no change in H-reflex suppression (p=0.2).
chemogenetically exciting striatal ChIs across development.
Conclusions: Rats following neonatal brain injury demon-
Two weeks following AAV8-hSyn-DIO-hM3d(Gq)-mCherry
strate electrophysiologic signatures of spasticity and dystonia.
striatal injections, mice received 1 mg/kg clozapine-N-oxide
There is segregation of electrophysiologic phenotypes based
(CNO) intraperitoneally either: 1) daily from postnatal day
on sex with males preferentially demonstrating spasticity and
(P) 15 to P30, or 2) once at P42. At P42, bilateral tibialis
females preferentially demonstrating dystonia. This sex differ-
anterior electromyography (EMG) was recorded during contin-
ence requires clinical confirmation but is suggestive that sex
uous treadmill gait at 3.0 meters/min. Cross-correlogram lag
could play a critical role in the development of dystonia fol-
was calculated as a measure of overflow muscle activation.
lowing neonatal brain injury.
Decreased lags suggest increased overflow, as seen in dystonia.
Keywords: Neonatal Neurology, Movement Disorders
Results: Virally-mediated mCherry expression confined to
the dorsal striatum was confirmed histologically. Preliminary
results suggest that acute striatal ChI excitation in adult mice 135. Hospitalizations in School Aged Children with
produced lower lags (n=3, 92+/-41 msec) compared to con- Cerebral Palsy: A Nested Case Control Study
trols (n=2, 193+/-15 msec). In contrast, chronic ChI excita- Fortin O (Montreal, Quebec), Ng P, Dorais M, Koclas L,
tion in childhood produced higher lags in adult mice (n=3, Pigeon N, Shevell M, Oskoui M
337+/-38 msec) compared to controls (n=5, 260+/-7 msec, Objective: To characterize the hospitalization pattern and
Mann Whitney U p=0.03). risk factors for admission of children with cerebral
Conclusions: Acute striatal ChI excitation in adulthood palsy (CP).
increases overflow muscle activation, as would be expected Methods: The Registre de paralysie cérébral du Québec pro-
based on striatal pathology in dystonia animal models. Para- spectively identified cases of CP born between 1999 and
doxically, chronic striatal ChI excitation exclusively in child- 2002 in 6 administrative regions of Quebec; these cases were
hood decreases overflow muscle activation in adulthood. linked to provincial administrative health databases. Peers
While preliminary, these results suggest that striatal ChI without CP (controls) were sampled from the same database
hyperexcitability early in life may be protective against and were matched in a 20:1 ratio. Risk Ratios (RR) and 95%
dystonia. confidence intervals were calculated to identify factors associ-
Keywords: Movement Disorders ated with an increased risk of hospitalization. Chi-square and
Student’s T-tests were used to compare groups.
Results: The study population included 301 children with
CP and 6040 peer controls. The mean age at diagnosis of CP
NEONATAL NEUROLOGY was 3.6 years. Mean hospitalizations per child were higher in
children with CP than peers (raw mean difference (RMD)
5.0) with significantly longer length of stay (RMD 2.8) and
134. Sexual Dichotomy in Outcomes Following Neonatal number of diagnoses (RMD 1.6). Increased risk of hospitali-
Brain Injury in Rats zation was observed in children who were non-ambulant
Aravamuthan B (St. Louis, MO), Rutkove S (RR 1.12), had spastic tri/quadriplegic CP (RR 1.15), and
Objective: To examine risk factors for the development of those with feeding (RR 1.12), cortical visual (RR 1.22), cog-
spasticity and dystonia in a rat model of cerebral palsy (CP) nitive (RR 1.16) and communication (RR 1.26) imapirment.

Program and Abstracts, Child Neurology Society S101

Conclusions: We demonstrate the feasibility of linking a reasons for ED visits in children with CP were respiratory ill-
population-based registry to administrative databases for nesses (26%), injuries (11%) and diseases of the nervous sys-
health services research.We demonstrate the feasibility of tem (10%).
linking a population-based registry to administrative data- Conclusions: Children with CP have a higher need for
bases for health services research. Children with a more severe urgent or semi-urgent health assessments than their peers,
profile of CP have greater health care complexity, and face resulting in increased use of ED services. Health system fac-
more frequent and longer hospital stays than their peers. tors and barriers should be explored to ensure optimal and
Coordinated care is needed in school-aged children with CP. appropriate use of these services.
Keywords: Neonatal Neurology Keywords: Neonatal Neurology

136. Emergency Department Use in Children with 137. Neurodevelopmental Outcomes in Infants with
Cerebral Palsy: A nested Case Control Study Congenital Zika Virus Exposure: Data from a Prospective
Fortin O (Montreal, Quebec), Ng, P, Koclas L, Dorais M, Cohort in Vitoria, Brazil
Pigeon N, Shevell M, Oskoui M Chamberlain L (Durham, NC), Giuberti C, Dietze R,
Objective: To estimate the risk of Emergency Department Abraham T, Webster H, Singh T, Corey G, Permar S,
(ED) consultation in children with cerebral palsy Tchapyjnikov D
(CP) compared to peers, compare reasons for ED visits and Objective: To describe the prevalence of cerebral anomalies,
describe risk factors for high ED use. microcephaly, and neurodevelopmental outcomes among
Methods: The Registre de paralysie cérébral du Québec pro- infants with congenital zika virus (ZIKV) exposure.
spectively identified cases of CP born between 1999 and Methods: Inclusion criteria was having an exanthematic
2002 in 6 administrative regions of Quebec; these cases were and/or febrile illness during pregnancy in Vitoria, Brazil from
linked to provincial administrative health databases. Peers 2016-2017. ZIKV status was confirmed via serum PCR.
without CP (controls) were sampled from the same adminis- Mothers and infants (regardless of ZIKV positivity) were
trative database. Data pertaining to the ED presentations followed until three years of age. Additional infants were rec-
between 1999 and 2012 were obtained, with ≥4 visits rep- ruited after birth if their mothers tested positive for ZIKV at
resenting high ED use. Risk Ratios (RR) and 95% confi- the state laboratory during pregnancy and were subsequently
dence intervals were calculated. Chi-square tests were used to prospectively followed. Language and visual-motor skills were
compare group characteristics. assessed via the Capute Scales. Motor development was
Results: The study population included 301 children with assessed using the Alberta Infant Motor Scale (AIMS).
CP and 6040 peer controls. Children with CP had a higher Median developmental scores were derived based on age
risk of having at least one ED visit compared to peers range in months (0-6, 7-12, 13-18, 19-24). Delay was
(RR 1.23, 95% CI 1.18-1.27). They also had an increased defined as a Capute Score <70 and/or <1stpercentile for age
risk of high ED use (RR 2.32, 95% CI 1.79-2.99). Co- on AIMS. Fisher’s exact test was used to assess for differences
existing epilepsy (RR 1.23 95% CI 1.04-1.46) and presence in neurodevelopmental outcome between ZIKV-exposed and
of multiple comorbidities (RR 1.34 95% CI 1.10-1.62) were unexposed infants in terms of frequency of cerebral anoma-
the best predictors of high ED use in children with CP. Top lies, microcephaly, and developmental delay.

TABLE 1. Median Capute and AIMS Scores among ZIKV Exposed and Unexposed Infants Abstract 137
Infant Age Maternal ZIKV AIMS Percentile*
(months) Status (n) CAT (IQR) CLAMS (IQR) (IQR)

0-6 Positive (n=2) 109 (106-112) 117 (114-120) 3 (3)

Negative (n=19) 100 (82-116) 130 (108-145) 2 (2-3)
7-12 Positive (n=7) 112 (104-118) 110 (83-119) 5 (3-5)
Negative (n=8) 106 (101-108) 102 (96-118) 4 (3-5)
13-18 Positive (n=4) 105 (80-111) 103 (80-111) 5 (3-5)
Negative (n=7) 115 (107-115) 112 (106-116) 5 (4.5-5)
19-24 Positive (n=3) 100 (74-103) 92 (79-115) 5 (3-5)
Negative (n=3) 115 (90-112) 112 (86-107) 5 (5)
CAT, Clinical Adaptive Test; CLAMS, Clinical Linguistic & Auditory Milestone Scale; AIMS, Alberta Infant Motor Scale; *AIMS Percentile Catego-
ries: 0, <1st percentile; 1, 1st to <5th percentile; 2, 5thto <10th percentile; 3, 10th to <25th percentile; 4, 25th to <50th percentile; 5, 50th to <75th per-
centile; 6, 75th to <90th percentile; 7, 90th to <95th percentile; 8, 95th to <99th percentile; 9, >99th percentile.

S102 Annals of Neurology Vol 86 (suppl 23) 2019

Results: 51 infants were enrolled, 14 with prenatal ZIKV
exposure. 29% (n=4) of ZIKV-exposed infants had cerebral
anomalies on head imaging at birth compared to 3% (n=1)
in the control group (p=0.02). One infant in the ZIKV-
exposed group had microcephaly and developmental delay
compared to none in ZIKV-unexposed patients (p=0.27). All
ZIKV-exposed infants without microcephaly had develop-
mental scores in the normal range.
Conclusions: Our study suggests a higher prevalence of cere-
bral anomalies but overall positive developmental outcomes
in the first two years of life among infants with congenital TABLE 1: Epilepsy incidence and seizures in the newborn
ZIKV exposure without microcephaly. period. Abstract 138 [Color figure can be viewed at www.
Keywords: Neonatal Neurology, Infections/ wileyonlinelibrary.com]
Neuroimmunology, Cognitive/Behavioral Disorders
Though not significant, severe HIE newborns showed a
138. Epilepsy Outcomes in Mild, Moderate, and Severe higher association with epilepsy (p=0.065 & 0.063 in mild &
Hypoxic-ischemic Encephalopathy (HIE) moderate HIE, respectively). No difference was noted
DeLaGarza-Pineda O (Monterrey, Mexico), Anwar T, between mild and moderate HIE (p=0.611).
McGowan M, O’Kane A, Scafidi J, Tsuchida T, Chang T Conclusions: Seizures in the newborn period are associated
with higher rates of epilepsy in newborns with moderate HIE.
Objective: Therapeutic hypothermia is standard of care for
A larger study is needed to confirm the lack of difference in
newborns with moderate or severe HIE. The effects of
epilepsy outcomes between mild and moderate HIE newborns.
cooling in mild HIE newborns have not been examined,
Keywords: Neonatal Neurology, Epilepsy, Critical Care
though some center have lower their criteria due to concerns
about their outcomes. We examined the incidence of epilepsy
in newborns with mild HIE (currently not-cooled) and those 139. Characteristics of Neonatal Seizures Related to
with moderate or severe HIE (both cooled). Intracranial Hemorrhage in Term Neonates: A Study of
Methods: This is a retrospective study of newborns ≥ the Neonatal Seizure Registry
35weeks admitted with HIE at birth to a Level-IV NICU. Herzberg E (Boston, MA), Machie M, Landers J, Chu C,
HIE severity was assessed by modified-Sarnat exam before Massey S, Wusthoff C, Chang T, Cilio M, Bonifacio S,
6 hours of life. Those with mild HIE were not cooled while Abend N, Shellhaas R, Glass H, Soul J
newborns with moderate or severe HIE were cooled follow- Objective: To examine seizure burden, treatment response,
ing institutional protocol. Neonates lost to follow-up before and outcome in term neonates with seizures primarily attrib-
2 years of age were excluded. uted to intracranial hemorrhage (ICH) versus ICH as a sec-
Results: Of 482 newborns from 2006-2016, 25 mild, ondary seizure etiology.
74 moderate, and 20 severe HIE neonates were evaluated Methods: We analyzed prospective data from neonates with
(Figure 1). Epilepsy by 2 years of age occurred in 12%, 16% seizures enrolled in the multicenter Neonatal Seizure Registry.
and 35%, respectively (Table 1). Seizures in the newborn Results: ICH was the primary seizure etiology for 48/512
period were associated with epilepsy in moderate HIE term neonates (9%), of which 29 (60%) had no other seizure
(p=0.001) and showed a trend in severe HIE (p=0.051). etiology identified. The remaining 19 (40%) had additional

FIGURE 1: Study population categorized according to HIE severity. Abstract 138 [Color figure can be viewed at www.
wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S103

TABLE 1: Abstract 139

diagnoses of: ICH in an additional intracranial compartment outcomes in neonates with cerebral sinus venous thrombo-
(N=14), stroke (N=7), or HIE (N=4). Fewer neonates had sis (CSVT).
ICH as a secondary etiology (29/512, 6%), with primary sei- Methods: This was a retrospective study analyzing the data
zure etiologies of HIE (45%) and stroke (35%). Neonates from neonates with CSVT at a single tertiary referral center
with ICH as primary seizure etiology had higher 1 and between 2000 and 2018.
5 minute Apgar scores (p≤0.001, Table) and were less likely to Results: 79 neonates were included. Average follow-up dura-
die in the NICU compared to those with ICH as secondary tion was 40 months (range 3 days to 16 years). 54 (68%)
etiology, although this was not significant. Seizure burden, neonates were male. Common underlying risk factor included
number of anti-seizure medications (ASM), and incomplete cardiac diseases (23%), meningitis (19%), systemic febrile ill-
response to an initial ASM were not different between groups. ness (16%), hypoxia (13%), and dehydration (10%). Pre-
However, more neonates with seizures attributed to multi- senting clinical features included seizure (49%),
compartment vs. single-compartment ICH had incomplete cardiorespiratory symptoms (31%), fever (15%), lethargy
response to the initial ASM (100% vs. 69%, p=0.04) and a (11%) and dehydration (9%). Neuroimaging findings
trend towards higher seizure burden (p=0.07). included only ischemic infarction (16%), both infarction and
Conclusions: Seizure burden and treatment response were hemorrhage (38%), other intracranial hemorrhage (19%),
similar in neonates with ICH as a primary versus secondary and no parenchymal lesions (27%). Common sites of throm-
seizure etiology, despite less perinatal depression and a lower bosis included left transverse sinus in 59%, followed by right
rate of death. Neonates with seizures from multi- transverse sinus in 48% and superior sagittal sinus (44%).
compartment ICH are less likely to respond to an initial Treatment included low molecular weight heparin (29%),
ASM and therefore may benefit from early EEG monitoring, unfractionated heparin (14%) and aspirin (4%). 49/59
novel ASMs, and aggressive treatment. neonate were treated with supportive care only
Keywords: Neonatal Neurology
(no anticoagulation or antiplatelet). Follow up neurological
status was normal in 48%, abnormal in 32%, and death was
140. Clinical Presentation, Neuroimaging Features and reported in 20%.
Long-term Outcome in Neonatal Cerebral Sinus Venous Conclusions: Seizure was the most common presenting clini-
Thrombosis: A Retrospective Analysis cal feature in neonates with CSVT. Neonatal CSVT could be
Karakas C (Houston, TX), Takacs D, Edmondson E, Fisher K, associated with significant morbidity and neurological disabil-
Shukla N, Clark G, Pehlivan D ity on long term follow up. Thus, early intervention and
Objective: To examine the clinical findings, neuroimaging aggressive treatment are necessary.
features, risk factors, treatment and long-term neurological Keywords: Neonatal Neurology, Stroke

S104 Annals of Neurology Vol 86 (suppl 23) 2019

141. Association of Circulating Pro- and Anti-
inflammatory Protein Biomarkers in the First Two TABLE 2. Association of inflammatory proteins
Postnatal Weeks with Brain MRI Volumes and Cognitive with IQ, controlling for sex (n=164) after adjusting
Function at Age 10 Years in Extremely Preterm Born for other brain compartments. Abstract 141
Children
Adjusting for sex
Kuban K (Boston, MA), Jara H, O’Shea T, Heeren T,
Adjusting only and other brain
Joseph R, Fichorova R, Alshamrani K, Aakil A, Beaulieu F,
for sex1 volumes2
Horn M, Douglass L, Frazier J, Hirtz D, Rollins J, Paneth N
Objective: To examine elevated neonatal inflammatory and Slope3 Slope
neurotrophic proteins in relation to age-ten brain MRI vol- (SE) p-value (SE) p-value
umes and cognition in children born extremely preterm.
Methods: We measured circulating inflammation-related Grey -2.67 0.029 -1.05 0.492
proteins (IP) and neurotrophic proteins (NTP) on postnatal Matter (1.21) (1.52)
days 1, 7, and 14 in 166 10 year-old children (73 males;
White -3.36 0.004 -2.50 0.051
93 females). Top quartile levels on ≥2 days for ≥3 IPs and for
Matter (1.15) (1.27)
≥4 NTPs defined exposure. We examined associations among
protein levels, brain volumes, and cognition with multiple CBBS -5.11 <0.001 -3.80 0.016
linear and logistic regressions. (1.15) (1.56)
Results: Analyses were adjusted for gestation age at birth and
1 – Separate regression analyses for each brain volume, controlling
sex. Children with 3+ elevated IPs had smaller grey matter
for sex
(GM), brain stem/cerebellar (CBBS), and total brain
2 – A single multiple regression model with grey matter, white mat-
(TB) volumes than those without elevated IPs, controlling
ter, CBBS, and sex as independent variables
for NTPs (Table 1). Compared to children with no NTPs,
3 – Slopes are scaled to reflect the difference in IQ associated with a
those with 4+ NTPs had larger GM and TB volumes. Higher
1 standard deviation decrease in brain compartment volume
GM, WM and CBBS volumes were significantly correlated
with higher IQ. Grey and white matter (WM) volumes were
correlated with each other (r=-0.18, p=0.021), and CBBS CBBS was associated with IQ (p=0.016), but the association
was highly correlated with GM (r=0.55, p<0.001) and with with WM was marginally significant (p=0.051). GM was not
WM (r=0.29, p<0.001). Adjusting for other compartments, associated with IQ (Table 2). Controlling for brain volumes,

TABLE 1. Association between elevated inflammatory (IP) and neurotrophic proteins (NTP), using number of
inflammatory and neurotrophic proteins as risk categories, and MRI volumetrics (cm3), controlling for sex for
total brain matter (TBM), cerebral matter (CM), total, deep, and cortical grey matter (GM), white matter (WM),
and cerebellum and brain stem (CBBS). Slopes (SE) from multiple linear regression models that include sex,
inflammatory and neurotrophic proteins. Abstract 141
Variable TBM CM GM Cortical GM Deep GM WM CBBS

Sex -11 (5)*

Ref
Female -121 (27)*** -136 (28)*** -75 (26)** -62 (23)** -2 (1) -48 (15)**
Male Ref Ref Ref Ref Ref Ref
IP number
Ref
0 Ref Ref Ref Ref Ref Ref
-4 (6)
1-2 -82 (33)* -107 (35)** -61 (32)+ -25 (29) 0 -23 (18) -32 (6)***
3+ -157 (34)*** -175 (35)*** -126 (33)*** -88 (30)** -5 (1)** -31 (18)
NTP number
Ref
0-1 Ref Ref Ref Ref Ref Ref
0 (6)
2-3 20 (32) 52 (34) 11 (32) 6 (29) 0 (1) 8 (18) 10 (6)+
4+ 60 (34)+ 91 (36)* 34 (33) 62 (30)* 3 (1)* 24 (19)
Slopes are the mean difference in brain volume vs. the reference category
+ p<0.10, * p<0.05, ** p<0.01, *** p<0.001

Program and Abstracts, Child Neurology Society S105

elevated IPs remained significantly associated with lower IQ, spells in calendar year 2017 and had neuroimaging performed
while elevated NTPs remained associated with higher IQ. within 180 days of EEG. Patients with a history of ICH in
Conclusions: Newborn inflammatory and neurotrophin pro- the neonatal period were excluded. Subjects were classified as
tein levels are associated with later brain volumes and cogni- cases or controls based on the presence of ICH on neuroim-
tion, but their effects on cognition are not entirely explained aging. The Pittsburgh Infant Brain Injury Score (PIBIS),
by altered brain volumes. which consists of head circumference, serum hemoglobin,
Keywords: Neonatal Neurology, Cognitive/Behavioral Disor- age, and abnormalities on dermatologic examination, was ret-
ders, Neuroimaging rospectively calculated. PIBIS >=2 was used as a cutoff. The
presence of EEG abnormalities was also analyzed.
142. When EEG is Not Enough: Catching Intracranial Results: There were 45 subjects; 8 cases and 37 controls.
Hemorrhage in Infants with Spells Using the Pittsburgh PIBIS score was >=2 in 88% of cases versus 49% of controls
Infant Brain Injury Score (p<0.05). EEG was abnormal in 3/8 (38%) cases versus
Ortman C (Pittsburgh, PA), Asato M, Sogawa Y, Berger R 10/37 (27%) of controls but rates of epileptiform abnormali-
ties were similar (3/8, 38% versus 8/37, 22%). There were
Objective: Spells and seizure-like activity in infants is com-
five case patients (5/8, 13%) with a normal EEG identified
mon. ICH is an uncommon cause, but needs to be identified
by PIBIS as candidates for emergency neuroimaging.
emergently. This study assesses the clinical usefulness of the
Conclusions: A normal EEG is not sufficient to rule out
Pittsburgh Infant Brain Injury Score (PIBIS) to supplement
ICH. The presence of PIBIS >=2 was more frequent in cases,
EEG to identify which infants with spells or seizures should
indicating that PIBIS may be helpful to determine the need
undergo emergency neuroimaging.
for emergent neuroimaging in this population.
Methods: This was a retrospective analysis of infants age
Keywords: Neonatal Neurology, Epilepsy, Stroke
1-11.9 months old who underwent EEG for evaluation of

143. Utility of aEEG for Seizure Screening in Three

TABLE 1. Pittsburgh Infant Brain Injury (PIBIS) score Clinical Scenarios
with non-epileptiform versus epileptiform EEG Sandoval Karamian A (Palo Alto, CA), Wusthoff C
findings in case and control patients. Abstract 142 Objective: Amplitude integrated EEG (aEEG) is a common
PIBIS score with normal screening tool for neonatal seizures. Yield of aEEG is dependent
vs. epileptiform EEG Cases Controls on seizure prevalence and sensitivity (Sn) and specificity (Sp) of
findings (%), n=8 (%), n=37 aEEG when used by providers of varying skill levels. Statistical
approaches can model aEEG use in varying clinical settings.
Methods: Using the example of hypoxic-ischemic encepha-
PIBIS score <2 with 0 (0%) 14 (38%)
lopathy (HIE), the prevalence, Sn, and Sp of aEEG for sei-
non-epileptiform EEG
zure detection were derived from the literature and used to
PIBIS score <2 with 1 (13%) 5 (14%) calculate aEEG utility in three models: ideal interpretation,
epileptiform EEG intermediate interpretation, and lowest reported Sn/Sp.
Results: Seizure prevalence in HIE is 40%. In the ideal inter-
PIBIS score >=2 with 5 (63%) 15 (41%) pretation model (best reported Sn=85%, Sp=90%), the posi-
non-epileptiform EEG tive likelihood ratio (LR+) was 8.5 and negative likelihood
PIBIS score >=2 with 2 (25%) 3 (8%) ratio (LR-) 0.17, giving posttest probabilities of 0.85 of sei-
epileptiform EEG zures with positive aEEG and 0.1 of seizures with negative
aEEG. In the intermediate model (Sn=65%, Sp=70%), LR+

FIGURE 1: Percentage of case and control patients versus Pittsburgh Infant Brain Injury Score (PIBIS) parameters. Abstract 142
[Color figure can be viewed at www.wileyonlinelibrary.com]

S106 Annals of Neurology Vol 86 (suppl 23) 2019

was 2.17 and LR- 0.5, giving posttest probabilities of 0.59 of others based on expression of clinical or molecular profiles
seizures after positive aEEG and 0.25 of seizures after nega- congruent with the therapeutic SC mechanism-of-action for
tive aEEG. Using the lowest/most commonly reported values that condition. We addressed this issue in a model of neona-
(Sn=40%, Sp=50%), LR+ was 0.80 and LR- 1.2, giving post- tal hypoxia-ischemic injury.
test probabilities of 0.35 of seizures after positive aEEG, and Methods: We transplanted human neural SCs into the con-
0.44 of seizures after negative aEEG, reflecting no meaning- tralateral ventricle of rat pups 3d post-unilateral HII and used
ful information added from the test. serial high field MRI subjecting the image to “hierarchical
Conclusions: Information provided by aEEG is useful (with region splitting” (HRS) to visualize and quantify total lesion,
good LRs) in settings of ideal use. However, under less ideal core, and penumbral volumes which were correlated with
circumstances it can be less helpful and even negligible. Pro- 90d histology/behavior.
viders using aEEG must develop skill levels to ensure high Sn Results: hNSCs improved histologic/motor/cognitive out-
and Sp in interpretation and recognize limitations when used comes only when there was a MRI-detectable penumbra
in more typical settings. that could be forestalled from evolving into necrotic core;
Keywords: Neonatal Neurology, Critical Care the core was never improved. The penumbra on MRI was
characterized by a molecular profile associated with salvage-
144. Fetal Neurology Consultations: A Single Institution ability and induction of neuroprotective mechanisms, the
Experience surrogate marker for which is heat shock protein 27 (HSP27).
Sharp A (Baltimore, MD), Barañano K The penumbra was reduced only when hNSCs migrated
there; hNSCs were plentiful only in regions where HSP27
Objective: Referral for fetal neurology consultation has
was upregulated, and HSP27 was induced only in the pen-
increased over the past decade in response to improvements in
umbra. ‘Moderate HII’ (PEN>CORE) was responsive to
prenatal diagnosis via genetic testing and fetal imaging. We
hNSCs whereas ‘severe’ (CORE>PEN) and ‘mild HII’
aim to describe our 5-year experience with fetal consultations.
(no CORE, little PEN) were unaltered. Host cells
Methods: A retrospective chart review of outpatient fetal
upregulated HSP27 as did engrafted cells which migrated to
consultations for neurological anomalies was conducted for PEN where volume was reduced and functional outcomes
2014-2018. Visits were identified by EMR encounter data. better than controls.
Individual charts were reviewed for information regarding Conclusions: MRI can stratify HII severity, identifying
maternal and fetal data, testing performed, and follow-up. the same molecularly responsive regions, facilitating selec-
Results: Over 5 years, 47 consultations were completed. tion of moderate HII neonates who would be most
Ventriculomegaly was the most common reason for referral, responsive to SC therapy while sparing others an invasive
presenting in 49% of fetuses. Midline defects, such as agenesis intervention.
of the corpus callosum, were seen in 26%. Neural tube defects Keywords: Neonatal Neurology, Neuroimaging
and posterior fossa malformations were each reported in 19%
of referrals. Multiple anomalies were seen in 43%. Chorionic
146. Intracranial Hemorrhage in Term Neonates: An
villus sampling or amniocentesis was performed in 52%
Institutional Perspective
(24/46) with 21% (5/24) of those receiving a genetic or infec-
Yang Brown J (Palo Alto, CA), Sandoval Karamian A, Yeom K
tious diagnosis. Elective termination occurred in 8% (4/46).
Of 38 infants born in-house, 58% were seen inpatient prior to Objective: Intracranial hemorrhages (ICH) in term neonates
discharge. Postnatal MRI was performed in 84%. Imaging range from asymptomatic to potentially devastating. With
findings were similar in almost all cases. Postnatal genetic diag- differing pathophysiology of the intracranial compartments,
noses were made in an additional 8% of patients. 58% of these ICH data is typically specific to the compartment involved.
newborns were seen by neurology prior to hospital discharge We investigate the distribution of ICH types across term
with 47% seen as an outpatient. 32% currently have ongoing neonates at one institution.
neurological follow-up at our institution. Methods: Term neonates (gestational age (GA) >36 weeks)
Conclusions: Fetal neurology consultation combined with with ICH on MRI brain consecutively from January 2011 to
prenatal genetic testing and MRI can provide early diagnoses August 2018 were included. Neonates with meningitis, ische-
with good accuracy in a majority of cases, which is beneficial mic infarct, venous thrombosis, or hypoxic ischemic encepha-
for long-term care and follow-up planning. lopathy (HIE) alone were excluded. Patient data included GA,
Keywords: Neonatal Neurology, Genetics, Neuroimaging delivery method, Apgar scores, seizures, and clinical diagnosis
of HIE. MRI data included indication, type of ICH (intraven-
tricular, subarachnoid, subdural, intraparenchymal, and sub-
145. A “Biomarker” that Predicts Responsiveness to Stem pial/leptomeningeal), MRA and MRV.
Cell Therapy Based on Mechanism-of-action: Evidence Results: From 602 term neonates with MRI during the study
from Imaging Neonatal Rat Brain Hypoxic-ischemic Injury period, 33 met inclusion criteria with a mean GA of
Ashwal S (Loma Linda, CA), Hartman R, Nathan N, 39.0 weeks (
1.2).10(30%) were delivered via cesarean sec-
Ghosh N, Law J, Nuryyev R, Plaia A, Yusof A, Tone B, tion, one of which was vacuum assisted, and 4(12%) were
Dulcich M, Pernia C, Sidman R, Obenaus A, Snyder E delivered via instrumented vaginal delivery. Indication for
Objective: No stem cell therapy for any condition has been MRI was HIE in 6(23%) and clinical seizures in 10(30%).
directed to specific recipients and, conversely, withheld from Intraventricular hemorrhage and subdural hemorrhage were

Program and Abstracts, Child Neurology Society S107

the most common types of intracranial hemorrhage, occur-
ring in 21(64%) and 20(61%) respectively. Intraparenchymal
hemorrhage occurred in 12(36%), subarachnoid in 7(21%),
and subpial in 5(15%). 18(55%) had more than one type of
hemorrhage. 15(45%) underwent MRA and 12(36%) under-
went MRV, with only 1 abnormal of each study type.
Conclusions: Amongst a sample of 33 term neonates with
intracranial hemorrhage, intraventricular hemorrhage and
subdural hemorrhage were the most common types. This is
the largest reported sample categorizing intracranial hemor-
rhage in term neonates to date.
Keywords: Neonatal Neurology, Neuroimaging FIGURE 2: Abstract 147

147. Two Cases of Neonatal Arterial Ischemic Stroke in

the setting of Neonatal Alloimmune Methods: Two neonates with thrombocytopenia at birth
Thrombocytopenia (NAIT) presented with neonatal seizures (Case 1), and perinatal
Osman M (Boston, MA), Laheji F, Walker M, Buonanno F, encephalopathy undergoing therapeutic hypothermia (Case
Grabowski E, Musolino P 2). Laboratory work-up for NAIT was positive for both.
Objective: NAIT leading to severe isolated thrombocytope- Results: Case 1: Female born at 40 weeks gestation. A diag-
nia occurs in 1 in 12001 live births with associated intracra- nosis of NAIT was suspected when patient presented with
nial hemorrhage in 15-20%, often antenatally2. Significant petechiae and bruising at 5 hours of life with a platelet count
potential morbidity and mortality result. However, no cases of 25,000. She had a seizure at day 4 of life. Brain MRI rev-
of NAIT with concurrent ischemic stroke have been ealed bilateral basal ganglial ischemic infarcts and multiple
reported. Here we report two cases, one with both intracra- hemorrhagic lesions in the right and left temporal, parietal
nial hemorrhage and ischemic stroke. and frontal areas. NAIT screen was positive for a maternal
anti-HPA-1a antibody. Case 2: Female born at 39 weeks ges-
tation via vaginal delivery complicated by nuchal cord x
1 and 3 vacuum attempts, with terminal meconium, who
met criteria for therapeutic hypothermia. Platelet count at
birth was 80,000. Post cooling MRI brain revealed a small
infarct at the right posterior insula. NAIT screen was positive
for a maternal anti-HPA-5b antibody.
Conclusions: NAIT and its treatment should be considered
in the differential diagnosis of FT infants presenting with
thrombocytopenia and cerebral ischemic or hemorrhagic
lesions. Maternal-paternal screening for NAIT can confirm
the diagnosis and assist with risk management for subsequent
pregnancies.
Keywords: Neonatal Neurology, Stroke, Rare Diseases

148. Pilot Study of Prenatal Hypoxia-exposed Mice

Reveal Potential Sex-dependent Differences in Anxiety-
related Behaviors
Cristancho A (Philadelphia, PA), Gadra E, Samba I,
Yardeni T, Wallace D, Anderson S, Marsh E
Objective: To develop and characterize the behavior of a
model of prenatal hypoxic injury.
Methods: Pregnant C57BL/6N mice were exposed to 5%
FiO2during late gestation (E17.5) for 2, 4, 6, or 8 hours
(prenatal hypoxia, “PH”). Quantitative PCR was used to
determine if PH induced VEGFA mRNA, a known hypoxic
marker. Survival and growth was monitored in offspring from
normoxia or 4, 6, or 8 hours of PH. Elevated zero maze and
open field testing were performed in adult offspring to deter-
mine if PH promotes anxiety-related behaviors.
Results: VEGFA mRNA was induced in the fetal brain after
4 hours of PH exposure and remained elevated with pro-
FIGURE 1: Abstract 147 longed exposure. Normoxic cohorts were born at E20.5,

S108 Annals of Neurology Vol 86 (suppl 23) 2019

whereas all PH cohorts were born at E19.5. There is no sig- or aortic abnormalities strengthens the likelihood of this diag-
nificant survival difference between normoxic and hypoxic nosis. In addition, early postnatal evaluation by Dermatology,
cohorts. PH-exposed males for 6 hours tended to have Cardiology, Neurology, and Ophthalmology are critical for
decreased time in the open arm of elevated zero maze or cen- effectively managing patients with PHACE syndrome.
ter zone of open field testing, consistent with increased Keywords: Neuroimaging, Rare Diseases
anxiety-related behaviors. Surprisingly, males exposed to
8 hours PH had increased time in open arm or center zone. 150. Altered Cortical Development in Living Fetuses with
By contrast, female PH-exposed mice had a propensity for Dandy-Walker Malformation
increased time in open arm or center square. Akiyama S (Sendai, Japan), Madan N, Graham G, Samura O,
Conclusions: These data suggest PH may promote anxiety- Kitano R, Craig A, Grant E, Bianchi D, Im K, Tarui T
related behaviors in a sex-dependent manner. Results will be Objective: Dandy-Walker malformation (DWM) is a com-
validated in future cohorts and tested for PH-related hyperac- mon prenatally diagnosed cerebellar malformation by fetal
tivity phenotypes that could obscure an anxiety phenotype. sonogram and/or magnetic resonance imaging (MRI) with
Social skills, learning, and seizure threshold studies will also vermian hypoplasia, dilatation of fourth ventricle and elevated
be performed to characterize the long term effects of PH torcular. However, its associated neurodevelopmental abnor-
exposure on the developing brain. malities are variable and difficult to predict in prenatal
Keywords: Neonatal Neurology, Cognitive/Behavioral counseling. We hypothesized that DWM may have com-
Disorders monly shared anomalies beyond cerebellar and posterior fossa
anomalies potentially impacting neurodevelopmental
variations.
Methods: We retrospectively reviewed medical record and
NEUROIMAGING fetal MRIs of 15 fetuses with DWM. We performed post-
acquisition regional volumetric fetal MRI analysis in
12 fetuses with DWM (23.6
4.2 weeks) and 12 control
149. Characterization of Features of PHACE Syndrome fetuses (25.2
5.0weeks) to measure volumes of cortical plate,
on Fetal MRI and Natural History of Postnatal subcortical parenchyma, cerebellar hemispheres and vermis.
Management Growth trajectories of each structure were modeled for each
Cristancho A (Philadelphia, PA), Streicher D, Vossough A, group by fitted linear regression model of logarithmic trans-
Treat J, Licht D, Streicher J formed volume data. Intergroup measures were compared
Objective: Characterize fetal MRI findings of PHACE syn- using ANCOVA.
drome and implications for postnatal management Results: Fetal MRI identified associated brain anomalies in
Methods: The etiology of PHACE syndrome (posterior fossa 9 fetuses with DWM (3 hydrocephalus, 3 cerebral
defects, hemangioma, arterial anomalies, coarctation of the ventriculomegaly, 3 complete and 2 partial agenesis of corpus
aorta and cardiac defects, eye abnormalities) is unknown. We callosum, and 1 cranial meningocele). Seven fetuses had
report nine patients with ultimate diagnosis of PHACE syn- extracerebral abnormalities determined by sonography. Four
drome who were found to have abnormal brain findings on of 13 fetuses had chromosomal microarray abnormalities.
prenatal anatomy ultrasounds, which were further character- Fetuses with DWM had smaller vermis growth trajectory
ized by fetal MRI. Patients were seen in our Center for Fetal than controls (p value=0.0005). In addition, fetuses with
Diagnosis and Treatment from 2007 to 2016. Electronic DWM had larger growth trajectory of bilateral cortical plate
health records were reviewed to determine the additional than controls (right p=0.0025 and left 0.0065).
work-up for PHACE syndrome, including postnatal imaging, Conclusions: Fetuses with DWM had larger cortical plate
management, and postnatal outcomes. and smaller cerebellar vermis growth between 18 and
Results: Fetal MRI studies demonstrated unilateral cerebellar 33 weeks’ gestation detected by regional volumetric analysis
hypoplasia or cystic lesions in all patients with confirmed of fetal brain MRI. Associations with postnatal neuro-
postnatal diagnosis of PHACE syndrome. Other intracranial development should be studied.
findings included ventricular abnormalities. Initial postnatal Keywords: Neuroimaging, Genetics, Neonatal Neurology
brain imaging was performed within the first several weeks of
life, demonstrating evidence of unilateral hemangiomas ipsi- 151. Validation of Breath-Hold Cerebrovascular
lateral to the cerebellar lesions. Children were treated with Reactivity Imaging in Healthy Children
prednisone or propranolol within the first two months of life. Alhadid K (Toronto, Ontario), Kassner A, Robertson A,
When available, repeat postnatal brain MRIs were reviewed, Shroff M, deVeber G, Logan W, Dlamini N
demonstrating involution of previously seen hemangiomas. Objective: Cerebrovascular reactivity (CVR) reflects the cere-
Multiple patients had other characteristics of PHACE syn- bral blood vessels’ response to a vasoactive stimulus. CVR
drome, including cardiovascular and ocular abnormalities. imaging has been used in patients with intracranial
Conclusions: Unilateral cerebellar cystic or dysplastic lesions arteriopathies, and cerebrovascular disease as a predictor of
found on fetal MRI should raise suspicion for diagnosis of ischemic risk and cognitive decline. The gold standard of
PHACE syndrome. This should prompt further evaluation in CVR imaging is utilizing controlled exogenous carbon diox-
utero, including fetal echocardiogram, as presence of cardiac ide (CO2) as a stimulus. This quantitative technique has been

Program and Abstracts, Child Neurology Society S109

validated in adults and children. Here we demonstrate that in Conclusions: Detection of parenchymal hemorrhagic lesions,
healthy children, breath-holding to induce endogenous rises which is enhanced with SWI, after pediatric TBI is impor-
in CO2 can produce quantitative measures of CVR that are tant, as the extent of lesion load predicts neurologic and neu-
comparable to the gold standard technique. ropsychologic outcomes. A significant amount of hemorrhage
Methods: Prospective study. Healthy volunteers aged 7-18 persists after 1 year, which may affect clinical recovery,
underwent two MRI sessions in same day with the following although the overall degree of hemorrhage resolution does
acquisitions: quantitative RespirActTM BOLD-CVR scan, not appear to be associated with severity of initial injury or
breath-hold CVR scans (a total of 3 acquisitions: with and extent of recovery.
without end-tidal CO2 measurements). Data analysis Keywords: Neuroimaging, Critical Care
included qualitative scoring and within-subject repeatability
analyses. 153. Static and Dynamic Organization of EEG
Results: Seven healthy right-handed children (4 female, Oscillations During a Visual-Motor Task: A
median age 13, range 9 -14 years). All participants tolerated Developmental Perspective
CVR studies well and no side effects were reported. Breath- Chin E (Baltimore, MD), Ewen J
hold CVR paradigm was modified after third dataset acquired
Objective: Identify static (task-independent) and dynamic
due to challenges with performing breath-hold studies after
(task-related) patterns of whole-brain functional connectivity
exhalation. Interim analyses showed good reproducibility
across development using a motor task. Dysfunctional intrin-
within subjects for breath-hold CVR. Blinded visual scoring
sic and dynamic connectivity have been suggested in many
showed comparable results between breath-hold CVR and
neuropsychiatric disorders, but typical patterns and func-
RespirActTM studies.
tional significance of task-related oscillation changes are not
Conclusions: Our data shows that breath-hold CVR, a non-
established.
invasive, inexpensive technique can be utilized to generate
Methods: Scalp EEG was recorded as groups of typically-
quantitative and reproducible CVR data in healthy children.
developing adults (N=16, age 26.2
4.2) and children
Our research aims to develop an optimal imaging technique
(N=28, age 10.5
1.3) performed a visually-cued right hand
that can provide reliable and reproducible data and serve as a
praxis task. After conventional pre-processing, long-distance
biomarker of ischemic risk in pediatric patients.
connectivity (measured as oscillation phase consistency
Keywords: Neuroimaging, Stroke
(PLV)) was prominent in alpha and beta bands. Graph theo-
retic analyses estimated modularity and identified consistently
152. Acute and 1-Year Susceptibility Weighted MRI After highly-connected clusters of brain regions. Dynamics were
Pediatric TBI: Relationship of Lesion Load, Regional described as task-related PLV changes within/between identi-
Distribution and Resolution of Traumatic Cerebral fied clusters.
Microbleeds; to Neurological and Neuropsychological Results: All subjects in all task phases demonstrated
Outcomes modularly-organized (high Q) alpha and beta oscillations
Ashwal S (Loma Linda, CA), Pivonka-James J, Nichols J, (p<0.001). Task-invariant oscillation patterns were more
Oyoyo U, Holshouser B, Tong K
Objective: Susceptibility-weighted imaging (SWI) improves
the detection of micro- and macro-hemorrhagic lesions after
pediatric and adult TBI. However, the fate of these lesions
and their relation to neurologic and neuropsychologic out-
comes are not clearly understood. We followed the evolution
of hemorrhages to determine their relation to outcomes up to
1 year post-TBI.
Methods: Total and regional number and volume of SWI
lesions were measured in 74 TBI patients (ages 4-17 years) at
initial imaging (6-17 days post-injury) and at 1 year. Initial
clinical evaluation included GCS scores and various clinical
parameters. Neurologic assessment was performed at 3, 6,
12 months and included PCPCS, KOSCHI and Barthel
scores. One-year neuropsychologic testing included measures
of memory, attention, and IQ (Verbal/Full-scale/Performance).
Results: Initial total and regional SWI lesion number/volume
discriminated between GCS injury severity groups (compli-
cated mild versus moderate/severe) as well as 12-month
PCPCS and neuropsychologic outcomes. Approximately
50% of SWI lesions resolved by 1 year irrespective of lesion
size and location. The degree of hemorrhage resolution was
not related to initial injury severity or the extent of neurologi- FIGURE 1: Abstract 153 [Color figure can be viewed at www.
cal and neuropsychologic recovery. wileyonlinelibrary.com]

S110 Annals of Neurology Vol 86 (suppl 23) 2019

 normative functional connectivity data. We also tested the
specificity and generalizability of identified connections.
Results: 74 of 123 children with TSC had a history of IS. IS
was associated with higher tuber burden (2.59% vs 0.85%,
p<.001) with no effect of lobar distribution. No specific
tuber location was associated with IS; however, negative con-
nectivity between tubers and the globus pallidi (GP) and cer-
ebellar vermis were both highly sensitive and specific for
IS. A binary logistic regression model found that GP connec-
tivity was a stronger predictor of IS than tuber burden
(OR 1.96, 95%CI [1.097, 3.502] vs. OR 1.65, 95%CI
[0.895-3.039]), with a mean ROC AUC of 0.73 (+/-0.1).
Increased tuber burden and negative GP connectivity were
also both associated with IS in the independent validation
data set.
Conclusions: While no single tuber location strongly
predicted IS, tuber distributions negatively correlated with
the GP was a consistent feature. Given the involvement of
the GP in GABAergic inhibitory regulation, these findings
provide novel insight into the pathophysiology underlying IS.
Keywords: Neuroimaging, Epilepsy, Genetics
FIGURE 2: Abstract 153 [Color figure can be viewed at www.
wileyonlinelibrary.com] 155. Deep Learning Model of Ventricle Volume Predicts
Developmental Outcomes in Prematurity
Han M (Palo Alto, CA), Griswold D, Kim L, Quon J,
consistent within adult and child groups (interindividual Edwards M, Yeom K
IQR r=0.86-0.96, 0.91-0.97, respectively) than between
Objective: The two objectives of this study were: 1) Develop
groups (IQR r=0.71-0.79). Group averages demonstrated
a deep learning model that segments and outputs volumetric
bilateral and midline clusters (filled circles) in both adults
data of ventricles from pediatric brain MRIs; and 2) Evaluate
and children (Figure 1) with networks of consistent connec-
the relationship between model-calculated ventricle volume
tions (black lines). PLV in adults significantly decreases
from term-equivalent MRI and developmental outcomes at
within/between modules (Figure 2; blue ovals/lines, respec-
two years of age in infants born prematurely (<32 weeks).
tively), particularly in classical praxis networks in alpha. Chil-
Methods: We trained a deep learning model with a encoder-
dren show significant increases (red ovals/lines) and decreases
decoder convolutional neural network architecture using
in task-related PLV.
600 manually segmented pediatric brain MRIs (400 normal,
Conclusions: -Alpha and beta oscillations contain well-
200 with ventriculomegaly). The model performance was
defined, consistent connectivity architectures in typical chil-
evaluated with a Dice score, which measured the agreement
dren and adults-Motor task-related decreases in alpha and
between manual segmentations and model output. This
beta oscillation phase-locking in adults may correspond to
model was then applied to 241 term-equivalent MRIs from
network dissociation seen in fMRI studies
infants born at <32 weeks who had Bayley III scores at two
Keywords: Neuroimaging, Cognitive/Behavioral Disorders
years of age. The relationship between model-calculated ven-
tricular volume and developmental outcomes were evaluated
154. Tubers Associated with Infantile Spasms Impact a using a Pearson correlation test.
Common Brain Network in Tuberous Sclerosis Complex Results: The model segmented cerebral ventricles with a
Cohen A (Boston, MA), Mulder B, Prohl A, Soussand L, Dice score of 0.936, reflective of high concordance between
Davis P, Gholipour A, Scherrer B, Sahin M, Krueger D, model and manual segmentations (figure 1). Model output
Bebin E, Wu J, Northrup H, Fox M, Warfield S, Peters J correlated significantly with adjusted cognitive (r=-0.19,
Objective: Up to 55% of patients with Tuberous Sclerosis p=0.0018), motor composite (r=-0.22, p=0.0012), and lan-
Complex (TSC) develop infantile spasms (IS), a sudden- guage composite scores (r=-0.15, p=0.010) (figure 2).
onset epileptic syndrome strongly associated with poor Conclusions: We were able to create a deep learning model
neurological outcome; however the lesional nature of TSC that automatically and accurately segments ventricles and
provides a unique opportunity to study the pathophysiol- outputs volumetric data. Moreover, we demonstrated that
ogy of IS. model-generated data from at-term equivalency relates to
Methods: We identified children with and without IS from multi-domain developmental outcomes at two years of age.
the TACERN dataset and identified all cortical tubers in each This study not only establishes a proof of concept in integrat-
patient. We assessed whether specific tuber locations were ing modern machine learning methods with neuroimaging,
associated with IS and whether specific brain regions were but also explores its applications in the clinical space.
connected to all/most IS+ patients’ tuber distributions using Keywords: Neuroimaging, Neonatal Neurology

Program and Abstracts, Child Neurology Society S111

FIGURE 1: A. Model output (blue) and manual segmentation (green) in a representative patient without hydrocephalus. B. Model
output (blue) and manual segmentation (green) in a representative patient with hydrocephalus. Abstract 155 [Color figure can be
viewed at www.wileyonlinelibrary.com]

FIGURE 2: Scatterplots with linear regression for model-generated ventricle volumes vs Bayley III Scores in the developmental
domains of: motor, language, and cognition. Abstract 155 [Color figure can be viewed at www.wileyonlinelibrary.com]

S112 Annals of Neurology Vol 86 (suppl 23) 2019

156. Lenti-D Gene Therapy Attenuates Microvascular progressive cerebral inflammatory demyelination in up to
Perfusion Abnormalities and Halts Cerebral 45% of affected males. Lenti-D gene therapy (GT) is being
Adrenoleukodystrophy Lesion Progression studied in ALD-102 as an alternative to allogeneic hemato-
Musolino P (Boston, MA), Lauer A, Choi M, Da X, Speroni S, poietic stem-cell transplantation (HSCT) in boys with
Hansen M, Kalpathy-Cramer J, Mouridsen K, Eichler F CALD. HSCT has been previously shown to improve cere-
Objective: Cerebral X-linked adrenoleukodystrophy bral microvascular perfusion in CALD. Here we studied the
(CALD) is a devastating neurodegenerative disorder caused effects of GT on microvascular physiology and lesion
by mutations in the ABCD1 gene, which lead to a rapidly progression.

FIGURE 1: Abstract 156 [Color figure can be viewed at www.wileyonlinelibrary.com]

FIGURE 2: Abstract 156 [Color figure can be viewed at www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S113

Methods: CALD patients treated with either GT (n=12) or 158. Fetal Diagnosis of Posterior Fossa Abnormalities is
HSCT (n=9) and with available Dynamic Susceptibility Enhanced by Fetal MRI
(DSC)-MR perfusion data before and at least 2 years post- Schlatterer S (Washington, DC), Labban F, Sanapo L, Russo S,
therapy were evaluated. Cerebral T2 hyperintense lesions du Plessis A, Whitehead M, Mulkey S
were quantified semi-automatically. Corresponding and peri- Objective: Our aims were to determine whether fetal MRI and
lesional microvascular flow heterogeneity patterns (CTH) neurology consultation lead to alternate diagnoses for maternal-
and contrast leakage maps (Kapp) were estimated from raw fetal dyads referred to a fetal neurology program due to concern
DSC-MRI perfusion data. for a fetal posterior fossa anomaly and to determine how often
Results: T2-weighted lesion progression rapidly decreased the postnatal evaluation differed from fetal diagnosis.
post-treatment in both groups (Fig.1a) while perilesional Methods: We performed a retrospective study of cases referred
microvascular perfusion improved as demonstrated by a to the Fetal Medicine Institute at Children’s National,
decrease in CTH (Fig.1b). Significant reduction in contrast Washington, DC, from January 2012 to June 2018. The fol-
extravasation within the lesion determined on Kapp maps lowing referral diagnoses were included: Dandy-Walker contin-
correlated with arrest of inflammatory demyelination uum (DWC), cerebellar hypoplasia (CH), vermis hypoplasia
(p=0.048; pre vs. 2Y post-GT, Fig.2a). Higher contrast (VH), Blake’s pouch cyst (BPC), mega cisterna magna
lesional leakage and perilesional CTH values one-year post- (MCM), or “other” posterior fossa anomaly (PF).
treatment are associated with delayed attenuation of lesion Results: We identified 188 cases that underwent fetal MRI and
growth in both groups (Fig.2b). In the GT group, the vector neurology consultation. Fetal MRI and neurology consultation
copy number in the administered drug product inversely cor- resulted in a change from the referral diagnosis or additional
relates with overall T2 growth (Fig.2c). information about the fetus in 124 (66%) cases. Postnatal diag-
Conclusions: Lenti-D gene therapy attenuates white matter nosis was obtained for 60/138 (43%) live-born infants. Postna-
microvascular perfusion abnormalities and effectively arrests tally, 6/6 (100%) cases of fetally diagnosed DWC had DWC;
CALD lesion growth. DSC-MRI perfusion may provide a 7/13 (54%) cases of fetally diagnosed VH had stable findings,
powerful biomarker to monitor treatment effects in CALD. 3/13 (23%) normalized, and diagnosis changed in 3/13 (23%);
Keywords: Neuroimaging, Demyelinating Disorders, Rare 8/17 (47%) fetally diagnosed BPC remained stable, 5/17 (29%)
Diseases normalized, and diagnosis changed in 4/17 (24%); 4/9 (44%)
cases of fetally diagnosed MCM remained stable, 2/9 (22%)nor-
157. Chronic Subdural Hygroma in Suspected Abusive malized, and diagnosis changed in 3/9 (33%).
Head Trauma Conclusions: Fetal MRI and neurology consultation provide
Scheller J (Baltimore, MD) significant added value for the fetal diagnosis of posterior
Objective: An unexplained acute subdural hematoma in an fossa anomalies over that provided by prenatal US and
infant commonly triggers an investigation into the possibility Ob/MFM evaluation only, with important repercussions on
of abusive head trauma. We questioned whether a chronic pregnancy management and infant neurologic care.
subdural hygroma might be an important contributing factor Keywords: Neuroimaging, Neonatal Neurology
to acute subdural hematoma.
Methods: The author has an active pediatric neurology and 159. Quantitative MRI Analyses of Regional Brain
forensic neurology practice. We reviewed all infants referred Growth and Cerebral Sulcal Development in Living
to our clinic for a second opinion regarding the cause of an Fetuses with Down Syndrome and Isolated
acute subdural hematoma. We included infants who had Ventriculomegaly
both head CT and MRI, a neck MRI, an eye exam, and a Tarui T (Boston, MA), Im K, Madan N, Graham G,
skeletal survey. We eliminated infants who had evidence of Madankumar R, Skotko B, Schwartz A, Sharr C, Ralston S,
external injury, acute or chronic limb or rib fractures, scalp Samura O, Kitano R, Craig A, Grant E, Bianchi D
swelling, neck injury, MRI diffusion abnormalities, and skull Objective: Fetuses with isolated cerebral ventriculomegaly
fracture. (IVM) and Down syndrome (DS) are indistinguishable by
Results: 21 infants had acute subdural hematoma and sub- conventional neuroimaging despite distinct neurodevelopment
dural hygromas. Average age was 4 months. 14 of 21 had a differences after birth. We hypothesized that fetuses with IVM
head circumference greater than the 90th percentile. 12/21 and DS have distinct brain development features detected with
presented to the ER with seizures. 9 of 21 had bilateral non-invasive, quantitative fetal (qf) MRI.
multilayer retinal hemorrhage, and 4 of 21 had no retinal Methods: Pregnant women carrying fetuses diagnosed with
hemorrhage, All recovered fully at 3 months post IVM (n=15, 26.2
4.8 week of gestation, mean
SD) or DS
hospitalization. (n=10, 29.1
4.2) were recruited prospectively. Healthy preg-
Conclusions: Seizures, acute subdural hematoma, and retinal nant women carrying fetuses without anomalies on sonogram
hemorrhage sometimes occur in the presence of chronic sub- were recruited as controls (n=13, 25.2
5.0). We processed
dural hygroma without other evidence of trauma. Neurolo- conventional fetal MR images for post-acquisition qfMRI
gists need to consider the acute findings as a possible analyses, including regional volumetric analyses and Similar-
complication of chronic subdural hygroma. ity Index based sulcal pattern matching/similarity analyses.
Keywords: Neuroimaging, Critical Care We compared fitted regional growth curves between groups

S114 Annals of Neurology Vol 86 (suppl 23) 2019

 Similarity Index based sulcal pattern matching/similarity ana-
lyses. Between fetuses with abnormal and normal outcomes,
we compared regional growth trajectories using non-linear
regression models and sulcal developmental patterns using
two-sample t-test, with significance set at 0.05.
Results: Ten of 31 fetuses have completed developmental testing
to date at age range of 18.4 ~ 22.7 months. Five had abnormal
outcomes; four with speech delay and three with behavioral
problems (1 female, MRI gestational age ranges 18.7 ~
31.3 weeks). Five had normal outcomes (1 female, 23.0 ~
32.1 weeks). Regional growth trajectories were indifferent
between the groups. The abnormal group had poorer combined
sulcal (position, depth and basin area) development in the left
hemisphere (p value= 0.002) and sulcal position development in
the right hemisphere (p=0.048) compared to the normal group.
Conclusions: In fetuses with IVM, abnormal sulcal develop-
mental patterns correlate with abnormal neurodevelopmental
outcomes at 18 month. Such anatomical differences may be
useful in predicting postnatal neurodevelopmental outcomes.
FIGURE 1: Abstract 159 [Color figure can be viewed at www. Outcomes for the remaining subjects is ongoing.
wileyonlinelibrary.com] Keywords: Neuroimaging, Genetics, Neonatal Neurology

161. Giant Tumefactive Perivascular Spaces in a Pediatric

using non-linear regression models and sulcal developmental Patient with Neurofibromatosis Type-2
patterns using two-sample t-test, with significance set at 0.05. Tittle B (Wauwatosa, WI), Mondok L
Results: None of the cases or controls had brain anomalies
Objective: Perivascular spaces (PVS) are cystic structures in
detected by visual review. Fitted growth curves of cerebellar
the brain that course alongside arterioles. PVS are now
hemispheres and subcortical parenchyma (white matter and
thought to be part of the glymphatic system where cerebro-
basal ganglia) showed smaller growth curves in DS compared
spinal fluid and interstitial fluid exchanges occur. In rare
to controls. Fetuses with IVM had significantly larger growth
cases, PVS can enlarge to >1.5cm and are then labeled as
curves in the cortical plate and subcortical parenchyma com-
giant tumefactive PVS, which can be commonly mis-
pared to the controls. In the sulcal pattern analysis, both fetuses
interpreted as cystic neoplasm. Many of these lesions are
with DS and IVM had altered sulcal positions compared to
asymptomatic and do not require treatment.
controls but fetuses with IVM also had altered sulcal depths.
Methods: Case report.
Conclusions: qfMRI detected distinct regional growth curves in
Results: A 14-year-old boy was evaluated for chronic right upper
living fetuses with DS and IVM during the second and third tri-
extremity weakness beginning in early childhood. His weakness
mester, despite similar imaging findings using conventional MRI.
Fetuses with DS and IVM have distinct sulcal development com-
pared to controls that are unique to each of the conditions.
Keywords: Neuroimaging, Genetics, Neonatal Neurology

160. Quantitative Fetal MRI Measures of Isolated

Cerebral Ventriculomegaly Associated with Postnatal
Neurodevelopmental Outcomes
Tarui T (Boston, MA), Im K, Lee P, Madan N, Graham G,
Samura O, Kitano R, Akiyama S, Craig A, Grant E, Bianchi D
Objective: Isolated cerebral ventriculomegaly (IVM) is the
most common prenatally diagnosed fetal brain finding but its
developmental outcomes are heterogeneous and difficult to
predict. We determined which quantitative fetal magnetic
resonance imaging (qfMRI) measures are correlated with
18-month developmental outcomes.
Methods: We prospectively recruited 31 fetuses with MRI
diagnosis of mild to moderate IVM (atrial diameter ~15 mm)
and followed up their 18-month neurodevelopmental out-
comes. Cases of hydrocephalus were excluded. We processed FIGURE 1: MRI brain axial T2 sequence showing giant
conventional fetal MR images for post-acquisition qfMRI tumefactive PVS in right frontal lobe. Abstract 161
analyses, including regional volumetric analyses and

Program and Abstracts, Child Neurology Society S115

 located on the X chromosome, responsible for the production
of dystrophin. The diagnosis is confirmed by finding a patho-
logic mutation in the Dystrophin (DMD) gene with genetic
testing, or less often by muscle biopsy.
Methods: We report a 5 year old with developmental delay,
work up revealed Xp21.1 duplication of 483 kb. The dupli-
cated interval contained exon 2-17 of the DMD gene, likely
pathogenic. However, our patient’s clinical phenotype was
atypical for DMD with a reportedly normal CK on 2 separate
occasions, 5 months apart. A similar duplication of the DMD
genes has been reported in a Chinese family with DMD and in
two individuals with dystrophinopathy (Wang et al., 2017;
Mah et al., 2011).
Results: On exam, our patient had mild proximal limb weak-
ness, axial weakness, lumbar lordosis, and a positive Gower’s
sign. Mother was found to have the same duplication of
Xp21.1, which confirmed the maternal inheritance of this
variant.
Conclusions: While most of the duplications are in tandem
and disrupt the normal DMD gene function, sometimes, the
duplication may be inserted elsewhere in the genome that
FIGURE 2: MRI brain axial T1 with gadolinium showing giant would not impact the normal function of DMD gene. There
tumefactive PVS isointense to CSF and non-enhancing. is no clinical test to distinguish whether the duplication is in
Abstract 161 tandem and the orientation of that duplication at this time,
hence the clinical significance of this change remains to be
was non-progressive; however, it became more pronounced somewhat uncertain and will continue to follow our patient
during athletic training sessions. Physical examination clinically.
showed no neurocutaneous stigmata and a smaller right arm Keywords: Neuromuscular Disorders, Genetics, Rare Diseases
with decreased muscle bulk and strength. Magnetic resonance
imaging (MRI) of the cervical spine showed a large intra-
163. Nusinersen Improves Motor Function which
dural, extra-axial C4-6 tumor in the right spinal canal causing
Correspond to Improved Swallowing, Body Mass Index,
the weakness. He also had small bilateral acoustic neuromas
Pulmonary Function Tests, Sleep and Decreased
consistent with neurofibromatosis type 2 (NF-2). Deafness
Requirement of Mechanical Ventilation
and presumed nerve sheath tumor in his deceased father
Arya K (Little Rock, AR), Veerapandiyan A, Stefans V,
supported NF-2 diagnosis. His brain MRI showed numerous
Agarwal A
enlarged perivascular spaces throughout cerebral white mat-
ter, the largest seen in the right frontal lobe, consistent with Objective: Practitioners and patients have only sparse data
giant tumefactive PVS. He had no associated symptoms with from independent studies detailing institutional/ multicenter
these brain parenchymal lesions. experience showing motor function improvement in SMA
Conclusions: Our patient exhibited characteristic MRI find- patients receiving nusinersen. We largely lack data showing
ings of NF-2. Giant tumefactive PVS have not been previously that use of nusinersen in SMA patients leads to improve-
described in this patient population. Expanding the list of clin- ment in swallowing, metabolism, body mass index, pulmo-
ical diagnoses associated with giant tumefactive PVS improves nary function parameters or sleep. We report our
recognition and reduces unnecessary procedural work-up. institutional experience with SMA patients receiving
Keywords: Neuroimaging nusinersen to study improvement in the parameters listed
above.
Methods: Retrospective review
Results: Total patients: 13 (1 with 2 copies of SMN2,
NEUROMUSCULAR 11 with 3 copies, 1 with >4 copies). Median duration of
nusinersen administration: 16, 7, and 5 months respectively
DISORDERS for SMA patients with 2, 3, and >4 copies of SMN2.
Median CHOP-Intend prior to nusinersen were 4, 35,
64, and post-nusinersen were 19, 53, 64 respectively for
162. Incidentally Identified Duplication on Xp21.1 patients with 2, 3, and >4 copies of SMN2. Improvements
Encoding the Dystrophin Gene in a 5 Year Old Boy with in BMI was noticed in the three groups: median BMI 12.6,
Normal Creatine Kinase (CK) 15.17, 18.8 to 14, 15.19, and 21.38. Improvements in
Osman M (Boston, MA), Chen J, Dredge D FVC, MEP, and MIP were noted in our patients. Mean
Objective: Duchenne Muscle Dystrophy (DMD) and Becker duration of ventilator use decreased from 24 hours to
Muscle Dystrophy (BMD) are caused by a defective gene 16 hours/day. Subjectively, a majority of patients reported

S116 Annals of Neurology Vol 86 (suppl 23) 2019

increased stamina and endurance, greater ability to from the ongoing NURTURE study (NCT02386553)
cooperate in physical therapy, decreased tiredness at the end examining efficacy/safety of intrathecal nusinersen, initiated
of the day or after exercise, decreased drooling, appetite, prior to symptom onset, in infants with 2 or 3 SMN2
faster sleep onset, longer duration of sleep and more restful copies.
sleep. Methods: Enrolled infants were age ≤6 weeks at first dose,
Conclusions: Our data demonstrate improvements in clinically presymptomatic, and genetically diagnosed with
motor function, BMI, sleep, and pulmonary function in SMA. Primary endpoint is time to death or respiratory inter-
patients with SMA after nusinersen administration. Fur- vention (≥6 hours/day continuously for ≥7 days or
ther studies are needed to provide more robust objec- tracheostomy).
tive data Results: As of 15 May 2018, 25 infants (2 copies SMN2,
Keywords: Neuromuscular Disorders, Rare Diseases n=15; 3 copies, n=10) were enrolled. Median age at last visit
was 26.0 (range 14.0–34.3) months. All infants were alive
and none required permanent ventilation. Median time to
164. HUI, WPAI, and Neuromuscular PedsQL Scores in death or respiratory intervention could not be estimated
Patients with Spinal Muscular Atrophy: Findings from because of too few events. Four infants (all with 2 SMN2
the 2019 Cure SMA Community Update Survey copies) required respiratory intervention for ≥6 hours/day
Belter L (Elk Grove Village, IL), Cruz R, Jarecki J continuously for ≥7 days, with all cases initiated during
Objective: Spinal muscular atrophy (SMA) is a rare autoso- acute, reversible illness. All infants achieved the WHO motor
mal disease that affects the motor nerve cells in the spinal milestone sitting without support and 22/25 (88%) achieved
cord, which leads to wasting of muscles. As new SMA thera- walking with assistance; 17/22 (77%) were walking alone.
pies have become available, the need to understand the care- Phosphorylated neurofilament heavy chain levels rapidly
giver and patient’s health related quality of life (HRQoL), declined during the nusinersen loading phase and then stabi-
has become more important. The purpose of this analysis is lized. AEs occurred in all infants; 20/25 had AEs
to present a baseline analysis of caregiver and patient’s quality mild/moderate in severity; 9 had SAEs. No new safety con-
of life among the Cure SMA community. cerns were identified. Results from a new, Spring 2019
Methods: In March 2019, Cure SMA launched their third interim analysis, including additional assessments, will be
annual community update survey. The purpose of the com- presented.
munity update survey is to collect the most current informa- Conclusions: There was continued benefit to infants who
tion from those affected with SMA, such as caregiver burden initiated nusinersen before symptom onset, emphasizing the
and patient’s HRQoL. These outcomes were measured value of early treatment and newborn screening. Updated
through the following validated instruments: Health Utilities analyses will provide further information.Study Support:
Index (HUI), the Neuromuscular PedsQL, and the Biogen
Work Productivity and Activity Impairment (WPAI) Keywords: Neuromuscular Disorders, Rare Diseases
questionnaires.
Results: HUI, PedsQL, and WPAI scores will be described
by subtype of SMA and by patient or caregiver perspective. 166. Interim Report on the Safety and Efficacy of Longer-
Furthermore, all three scores will be described by maximum term Treatment with Nusinersen in Later-onset Spinal
motor function ever achieved as well as current motor func- Muscular Atrophy (SMA): Results from the SHINE
tion. For those with permanent ventilation, their three scores Study
will be compared to those not on permanent ventilation. Chiriboga C (New York, NY), Darras B, Farrar M, Mercuri E,
Lastly, all three scores will be described and compared among Kirschner J, Kuntz N, Shieh P, Tulinius M, Montes J, Reyna S,
those who have had scoliosis surgery to those who have not. Gambino G, Foster R, Bhan I, Wong J, Farwell W
Conclusions: The finding from this study will provide a base-
line understanding of the current quality of life experienced by Objective: To present baseline and interim results from
those affected with SMA which will be able to be compared to the SHINE study (NCT02594124) for participants
future quality of life measures as new therapies emerge. with later-onset SMA (most likely to develop Type
Keywords: Neuromuscular Disorders, Rare Diseases II/III) who transitioned from the nusinersen CHERISH
study.
Methods: SHINE is an open-label extension for previous
165. Nusinersen in Infants who Initiate Treatment in a nusinersen study participants. Safety/tolerability is the pri-
Presymptomatic Stage of Spinal Muscular Atrophy: mary endpoint; secondary endpoints include WHO motor
Interim Results from the Phase 2 NURTURE Study milestones achievement, Hammersmith Functional Motor
Butterfield R (Salt Lake City, UT), De Vivo D, Bertini E, Scale - Expanded (HFMSE), and Revised Upper Limb Mod-
Hwu W-L, Crawford T, Swoboda K, Finkel R, Kirschner J, ule. These integrated analyses focus on children treated with
Kuntz N, Parsons J, Ryan M, Topaloglu H, Ben Omran T, nusinersen or sham control in CHERISH who transitioned
Sansone V, Jong Y-J, Shu F, Johnson K, Foster R, Bhan I, to SHINE.
Fradette S, Farwell W, on behalf of the NUTURE Study Group Results: In CHERISH, 84 participants received nusinersen
Objective: Nusinersen is the first approved treatment for and 83 transitioned to SHINE; all 42 participants in the
spinal muscular atrophy (SMA). We present interim results sham control group transitioned. Baseline data are

Program and Abstracts, Child Neurology Society S117

presented for 3 groups: previous sham control (CHERISH 168. Assessment of Awareness of the Early Clinical
data; n=42); previous sham control/SHINE data (n=42); Features of Spinal Muscular Atrophy (SMA) Amongst
previous nusinersen in CHERISH/SHINE data (n=84). Pediatricians
Median (range) age at first dose/sham procedure was 43.3 Curry M (Chicago, IL), Cruz R, Belter L, Jarecki J
(25-90), 58.2 (40-107) and 49.7 (25-111) months, and Objective: Spinal muscular atrophy (SMA) is an autoso-
median age at symptom onset was 11.0 (6-20), 11.0 mal recessive neuromuscular disease characterized by pro-
(6-20), and 10.0 (6-20) months; 50%, 50% and 55% were gressive muscle weakness and atrophy. SMA is the
female, respectively. Mean baseline (SD) WHO motor number one genetic cause of death for infants. Until
milestones were 1.5 (1.02), 1.4 (1.11) and 1.4 (0.96); recently, there was no disease modifying treatment. Clini-
mean (SD) HFMSE scores were 19.9 (7.23), 19.8 (8.39), cal trials’ data suggests that early treatment is critical to
and 22.4 (8.33), in the 3 groups respectively. Results from modifying disease progression and improving health out-
an interim analysis (15 October 2018 data cutoff ) will be comes. Though early diagnosis and treatment is critical
presented. diagnostic delays persist.
Conclusions: Continued analysis of data from children Methods: Cure SMA conducted a survey gaging the diagnos-
treated with nusinersen via the SHINE study will increase tic patterns in SMA. It was distributed via email by
the information available on the long-term safety/tolerability Medscape Education from September 19, 2018 through
and efficacy of repeated nusinersen doses. September 28, 2018 and 300 pediatricians completed the
Keywords: Neuromuscular Disorders, Rare Diseases survey.
Results: With the option to select multiple responses, upon
observation of hypotonia, 55.33% of pediatricians indicated
167. Genotypic and Sociodemographic Associations they would immediately refer to early intervention, while
with Increased Age of Diagnosis in Patients with 52.00% would immediately refer to a pediatric neurologist
Duchenne Muscular Dystrophy without a Known Family for further evaluation. Although 52.67% correctly
History indicated that genetic testing is required to make a defini-
Counterman K (Boston, MA), Wang R, Martin A tive diagnosis of SMA, 31.00% chose muscle biopsy.
Objective: To investigate the effect genotypic and Additionally,70.33% of respondents indicated comfort
sociodemographic factors have on the age of diagnosis in identifying the early signs of neuromuscular disease
Duchenne muscular dystrophy (DMD) patients without a (Extremely comfortable 3.33%; Very comfortable 18.67%;
known family history in the United States. Moderately comfortable 48.33%). Likewise, 67.3% of
Methods: Using data from The Duchenne Registry, we respondents noted a familiarity with SMA (Extremely
assessed the impact genotype, race/ethnicity, neighborhood familiar 4.33%; Very Familiar 13.67%; Moderately familiar
poverty levels and other sociodemographics factors have on 49.33%), yet of this group, just 59.41% identified the
the age of diagnosis in DMD using univariate and multivari- genetic testing requirement.
able linear regression. Data was collected from the years 2007 Conclusions: This research yielded important insights into
to 2019. Census tract poverty data was obtained from the current clinical knowledge gaps regarding diagnosis of SMA.
U.S. Census Bureau’s Public Health Disparities Geocoding Amongst pediatricians, the clinical response upon observation
project. of hypotonia varied. Practice guidelines encouraging universal
Results: The overall mean age of diagnosis was 4.43 years. assessment of hypotonia and continuing education emphasiz-
Non-white patients and patients from high poverty ing treatment urgency may alleviate variation while reducing
neighborhoods were diagnosed at significantly later than diagnostic delay.
average ages (P = <0.01). Increased year of birth was Funding for this research was provided by the SMA Industry
associated with decreasing age of diagnosis (P = <0.001). Collaboration, Astellas, AveXis, Biogen, Genentech/Roche, Cyto-
Specific genetic mutation subtypes were associated kinetics, Novartis, and Scholar Rock.
with later ages of symptom onset and diagnosis Keywords: Neuromuscular Disorders, Rare Diseases
(P = 0.005).
Conclusions: After adjusting for genotype and year of
birth, significant disparities in diagnosis were identified for 169. Onasemnogene Abeparvovec Gene-Replacement
non-white patients and patients from high poverty neigh- Therapy (GRT) for Spinal Muscular Atrophy Type
borhoods. The implementation of a national public health 1 (SMA1): Pivotal Phase 3 Study (STR1VE) Update
system such as newborn screening would eliminate the Day J (Stanford, CA), Chiriboga C, Crawford T, Darras B,
observed disparities. Increasing education of the signs and Finkel R, Connolly A, Iannaccone S, Kuntz N, Pena L,
symptoms of DMD to primary care providers, with an Schultz M, Shieh P, Smith E, Feltner D, Ogrinc F, Shah A,
emphasis on those practicing in underserved areas or Ouyang H, Macek T, Kernbauer E, L’Italien J, Sproule D,
among at risk populations, may also help diminish these Kaspar B, Mendell J
disparities. Objective: The survival motor neuron (SMN)GRT
Keywords: Neuromuscular Disorders, Rare Diseases onasemnogene abeparvovec (AVXS-101) treats the genetic

S118 Annals of Neurology Vol 86 (suppl 23) 2019

TABLE 1. Basic Demographic and Genotypic Analysis of the age of diagnosis in patients with Duchenne
muscular dystrophy using ANOVA and Tukey Kramer HSD for post hoc analysis. The results of the post hoc
analysis are demonstrated using compact letter display. Groups with the same letter are not statistically
different at α = 0.05. Genetic mutation subtypes were defined by the patient’s eligibility for exon skipping
therapies. All ANOVA P-values were < 0.01. Abstract 167
Variable No. (%) Mean (SD) Median

Overall 1282 (100) 4.43 (2.1) 4

Year of Birth
≥2010 172 (14) 3.14A (1.7) 3
B
2005-2009 352 (27) 4.23 (2.1) 4
C
2000-2004 351 (27) 4.85 (2.1) 5
<2000 408 (32) 4.81C (2.2) 5
Race
White 969 (75) 4.27A (2.0) 4
B
African-American 52 (4) 5.44 (2.6) 5
B
Hispanic 147 (12) 4.97 (2.2) 5
A,B
Asian/Pacific Islander 107 (8) 4.74 (2.0) 5
A,B
Native American 7 (1) 4.00 (1.6) 3
Insurance Type
Private/Commercial 911 (71) 4.31A (2.1) 4
B
Medicaid/Uninsured 254 (20) 4.80 (2.2) 5
A,B
Military/TRICARE 42 (3) 4.57 (2.0) 5
A,B
Missing 73 (6) 4.69 (2.1) 5
Median Household Income
Quartile 4 545 (42) 4.14A (2.0) 4
A,B
Quartile 3 300 (23) 4.46 (2.2) 5
Quartile 2 212 (17) 4.76B (2.0) 5
B
Quartile 1 225 (18) 4.84 (2.1) 5
Poverty Rate
<5% 387 (30) 4.23A (2.0) 4
A
5-10% 378 (30) 4.31 (2.1) 4
A,B
11-20% 352 (27) 4.59 (2.1) 5
B
>20% 165 (13) 4.91 (2.3) 5
Genetic Mutation Subtype
Nonsense 142 (11) 4.13A (2.1) 4
A,B
Duplication 142 (11) 4.62 (2.2) 5
B
Exon 8 amenable 33 (3) 5.70 (2.2) 6
A,B
Exon 44 amenable 80 (6) 4.79 (2.4) 5
A
Exon 45 amenable 116 (9) 4.38 (1.8) 4
A,B
Exon 50 amenable 50 (4) 4.64 (2.2) 5
A,B
Exon 51 amenable 128 (10) 4.46 (1.9) 4
A
Exon 53 amenable 96 (7) 4.04 (1.9) 4
A
Other 495 (39) 4.38 (2.1) 4

Program and Abstracts, Child Neurology Society S119

 TABLE 2. Linear regression model predicting the age of diagnosis in months. All P values were <0.001. Genetic
mutations were divided dichotomously based off of univariate results. Mutations with median age of diagnosis
of 5 or higher, including duplications and exons amenable to exon 8, 44, and 50 AON skipping were separated
from the remaining mutation subtypes. Abstract 167
Variable B Coefficients SE B β Coefficients t value

Constant 1765.28 192.74

Year of Birth -0.86 0.10 -0.24 -8.99
Race/Ethnicity 8.96 1.57 0.16 5.68
Poverty 0.35 0.08 0.13 4.61
Genetic Mutation 6.34 1.56 0.11 4.04
2
R 0.11

FIGURE 1: Providers Typical Course of Action Upon

Observation of Hypotonia in an Infant or Toddler Organized FIGURE 2: Provider Awareness of Diagnostic Requirements
by Self-Reported Comfort Identifying the Early Signs and for SMA Organized by Self-Reported Familiarity with the
Symptoms of Neuromuscular Disease. Each pediatrician was Disease. Genetic testing is the only requirement for
given the option to ‘select all that apply’ for the provided confirmation of a diagnosis of SMA. Other testing may
responses. The breakdown of self-reported comfort contribute to further delays in diagnosis in SMA patients.
identifying the early signs of SMA is as follows: Extremely The breakdown of self-reported familiarity with SMA is as
Comfortable: 10 participants, Very Comfortable: follows: Extremely Familiar: 13 participants, Very Familiar:
56 participants, Moderately Comfortable: 145, Slightly 41 participants, Moderately Familiar: 148, Slightly Familiar:
Comfortable: 80, Not at All Comfortable: 9. Abstract 168 91, Not at All Familiar: 4. Abstract 168 [Color figure can be
[Color figure can be viewed at www.wileyonlinelibrary.com] viewed at www.wileyonlinelibrary.com]

S120 Annals of Neurology Vol 86 (suppl 23) 2019

root cause of SMA. In a phase 1/2a study (NCT02122952), CL-101 [NCT02122952], STR1VE [NCT03306277],
AVXS-101 demonstrated significantly improved outcomes in STR1VE-EU [NCT03461289]) or intrathecal (STRONG
SMA1 patients vs natural history. We report data from the [NCT03381729]) AVXS-101 dose; patients were not eligible
multicenter, open-label, pivotal phase 3 STR1VE study if AAV9 antibody titers were >1:50.
(NCT03306277) investigating intravenous AVXS-101 in Results: In SPR1NT, 1/26 asymptomatic newborn patients
SMA1 patients (bi-allelic SMN1 mutations/deletions, 2xSMN2) aged ≤6 weeks had exclusionary antibody titers. In STR1VE,
aged <6 months. 0/25 symptomatic patients aged 0–6 months had exclusion-
Methods: Primary outcomes of STR1VE are independent ary titers. In STR1VE-EU and CL-101, 4/29 and 1/16
sitting (≥30 seconds; aged 18 months), and survival symptomatic patients had exclusionary titers, respectively.
(avoidance of death/permanent ventilation; 14 months). Among older patients in STRONG (ages: 6–60 months),
Secondary outcomes include ability to thrive and 3/34 patients had exclusionary titers. As of 3/29/2019, 0/47
ventilatory support (18 months). Exploratory outcomes patients in the MAP aged 0.5–26 months had exclusionary
include motor function improvements (Bayley-III, CHOP titers.
INTEND). Conclusions: Initial screening from the AVXS-101 clinical
Results: As of 6/08/2018, enrollment is complete (N=22 trials and MAP show 9/177 SMA patients had exclusionary
dosed patients). Mean (range) age at symptom onset, genetic AAV9 antibody titers >1:50; elevated titers should not impact
diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), AAV9-based GRT eligibility in most SMA patients. AAV9
and 3.7 (0.5–5.9) months, respectively. At baseline, no titers continue to be screened in SMA patients for AVXS-101
patient required ventilatory/nutritional support; all exclusively eligibility; updated data will be presented.
fed by mouth. As of 9/27/2018, 22/22 patients had Keywords: Neuromuscular Disorders, Trans-
≥3 months of CHOP INTEND data. The mean (standard lational/Experimental Therapeutics, Rare Diseases
deviation [SD]) baseline score was 32.0 (9.9) points. Mean
(SD) score and change from baseline were 38.9 (8.3) and 7.0 171. A Child with Congenital Lambert-Eaton-like
(5.6) points, respectively (month 1), and 43.7 (8.4) and 11.8 Myasthenia Syndrome
(6.7) points (month 3). As of 12/31/2018, 8/22 patients DiMario, Jr. F (Hartford, CT), Zara M, Cruz-Zeno E
achieved independent sitting and 20/21 surviving patients are
Objective: Lambert-Eaton syndrome is extremely rare in
free of permanent ventilation (aged 8–16.3 months, 6.5–-
children. Congenital forms of Lambert-Eaton-like myasthenia
14.1 months post-dose). 18/21 patients used no non-invasive
syndrome due to mutations in the synaptotagmin 2 gene
ventilation support.
(SYT2) have been reported in two prior families. We report a
Conclusions: Data from STR1VE show rapid motor func-
third individual presenting in infancy with a novel mutation
tion improvements in SMA1 patients that parallel phase 1/2a
of SYT2.
study findings. Updated data will be presented.
Methods: The clinical course at baseline and after treatment
Keywords: Neuromuscular Disorders, Translational/Experi-
with pyridostigmine and 3,4 DAP is reported along with
mental Therapeutics, Rare Diseases
the Patient Global Impression of Change scale (PGIC) and
the modified Quantitative Myasthenia Gravis test
170. Adeno-Associated Virus Serotype 9 (AAV9) (mQMGT).
Antibodies in Patients With Spinal Muscular Results: A non-dysmorphic infant presented at 12 days of
Atrophy (SMA) Screened for Treatment With age with profound weakness, hypotonia and arreflexia. Ini-
Gene-Replacement Therapy (GRT) Onasemnogene tial studies were normal or negative and excluded SMA.
Abeparvovec Electromyography demonstrated reduced compound mus-
Day J (Stanford, CA), Finkel R, Mercuri E, Swoboda K, cle action potential (CMAP) amplitude (left tibial motor
Kernbauer E, Ogrinc F, Menier M, Sproule D, Feltner D, <0.1mV, left ulnar 0.04mV), preserved sensory nerve
Mendell J action potential (SNAP) (normal left peroneal at 2 mV,
Objective: SMA is a rapidly progressing neurologic disease and normal left sural sensory nerve at 8 mV) and a decre-
caused by biallelic deletion/mutation of the survival motor ment of 23.4% in CMAP response to low-frequency repet-
neuron 1 gene(SMN1). Onasemnogene abeparvovec (AVXS- itive nerve stimulation (RNS) at 2 Hz. There was a
101) is an AAV9-based GRT that treats the genetic root marked increment in CMAP response to high-frequency
cause of SMA. AVXS-101 is designed for immediate and RNS at 30 Hz of >100% with normal needle study.
sustained expression of SMN protein, allowing for rapid Genetic testing revealed a compound heterozygote de novo
onset and durable therapeutic effect. In a phase 1/2a trial, mutation in the SYT2(c.802-3C>G) IVS6-3 variant and a
AVXS-101 improved SMA patient outcomes. This study (c.977 C>A) TK32K variant carried by his asymptomatic
reports AAV9 antibody titers in SMA patients screened for mother.
eligibility in the AVXS-101 clinical trials and managed access Conclusions: A novel de novo SYT2 gene mutation associ-
program (MAP). ated with a congenital form of Lambert-Eaton-like myasthe-
Methods: Patients with SMA (biallelic SMN1 loss, nia syndrome will be presented.
1–3xSMN2) aged 0–60 months were screened for eligibility Keywords: Neuromuscular Disorders, Neonatal Neurology,
for a one-time intravenous (SPR1NT [NCT03505099], Genetics

Program and Abstracts, Child Neurology Society S121

172. Burden of Illness of Spinal Muscular Atrophy Type Plasma pNF-H levels were evaluated at various time points
1 (SMA1) using the ProteinSimple®SimplePlex ELLA immunoassay.
Droege M (Bannockburn, IL), Dabbous O, Arjunji R, Seda J, Regression analyses were performed using change from base-
Gauthier-Loiselle M, Cloutier M, Sproule D line in motor milestones total score at Day 302 as the
Objective: SMA1 is a rapidly progressing, debilitating, response variable and Day 64 log plasma pNF-H as the pre-
genetic neuromuscular disease. Cost burden data are limited dictor; age at first dose and baseline CHOP INTEND total
and must be updated as the treatment landscape evolves. score were additional covariates.
The first SMA treatment, nusinersen, was recently approved Results: Mean baseline pNF-H level (
SE) was
in the US (12/23/2016) and EU (5/30/2017). We under- 19,241.5
4093.14 pg/ml (n=22). pNF-H rapidly declined
took two retrospective claims analyses of real-world during the nusinersen loading period then stabilized by Day
healthcare resource utilization (HRU) and costs among 64 and remained at lower levels (1133.1
358.85 pg/ml at
SMA1 patients. Day 778; n=9). Univariate regression analysis demonstrated
Methods: SMA1 patients ≤1-year old were identified and an association between pNF-H level and future motor func-
matched (1:1) with a random sample of infants in the tion. This association was maintained after controlling for
QuintilesIMS PharMetrics Plus Health Plan Claims Data- baseline motor function and age (multivariate regression ana-
base (US; Feb 2011–Nov 2016). SMA1 patients were lyses): in NURTURE participants with Day 64 pNF-H
identified in Symphony Health’s Integrated Dataverse® assessment and Day 302 evaluation, Day 64 log plasma
(US; Sep 2016–Aug 2018). HRU and costs were pNF-H appears to be associated with greater improvement in
described. motor function at Day 302 as measured by change from
Results: Significantly more SMA1 patients in PharMetrics baseline in motor milestones total score (slope -2.32;
(n=119) had ≥1 all-cause HRU claims vs. matched p=0.0002; n=23).
patients (98.3% vs. 54.6%, P<0.0001). Mean all-cause Conclusions: These findings suggest plasma pNF-H levels
HRU and costs were higher for SMA1 infants; extrapo- are high in most infants with presymptomatic SMA and
lated all-cause total annual costs, based on month 1 post- decrease with nusinersen treatment, and pNF-H may be a
diagnosis, were $324,751 (SMA1) vs. $3,294 (matched). useful biomarker for predicting motor function in SMA that
SMA1 patients in Symphony (n=349, median follow-up warrants further analyses.
of 7.9 months) had an average 59.4 days with medical Keywords: Neuromuscular Disorders, Neonatal Neurology,
visits/year (inpatient, 14.1; related to respiratory failure, Genetics
13.4). In nusinersen-treated patients (n=45), those values
were 56.6, 4.6, and 11.4 days following treatment initia- 174. Interim Report on the Safety and Efficacy of Longer-
tion. Excluding nusinersen-related costs, mean healthcare term Treatment with Nusinersen in Infantile-onset Spinal
costs per-patient-per-year were $137,627 (median: Muscular Atrophy (SMA): Updated Results from the
$43,167) for all patients and $92,618 (median: $29,425) SHINE Study
for nusinersen-treated patients. Mean nusinersen-related Finkel R (Orlando, FL), Castro D, Farrar M, Tulinius M,
costs were $191,909/month (median: $144,487) for the Krosschell K, Saito K, Reyna S, Zhang Y, Bhan I, Wong J,
first 3 months (loading phase) and $36,882/month Farwell W
(median: $16,132) thereafter.
Objective: To report interim results from the SHINE study
Conclusions: The economic burden of SMA1 is substantial,
(NCT02594124) for individuals with infantile-onset SMA
even among patients treated with nusinersen.
(most likely to develop Type I) who transitioned from the
Keywords: Neuromuscular Disorders, Rare Diseases,
nusinersen ENDEAR study.
Genetics
Methods: Nusinersen doses were initially administered
according to participant’s previous trial cohort/regimen. The
173. Association Between Plasma Phosphorylated primary endpoint is safety/tolerability; secondary endpoints
Neurofilament Heavy Chain and Efficacy Endpoints in include achievement of HINE-2 motor milestones and
the Nusinersen NURTURE Study event-free survival (EFS; time to death or permanent
Finkel R (Orlando, FL), Sumner C, Darras B, Muntoni F, ventilation).
Crawford T, Mercuri E, De Vivo D, Oskoui M, Tizzano E, Results: The cutoff date for the previous interim analyses was
Ryan M, Liu Y, Petrillo M, Stebbins C, Koenig E, Fradette S, June 30, 2017; 89 infants transitioned from ENDEAR, 65/81
Farwell W were previously randomized to nusinersen and 24/41 to sham-
Objective: To assess whether phosphorylated neurofilament control. Within SHINE only, 83 infants had an adverse event
heavy chain (pNF-H) is a predictive biomarker of treat- (AE). Infants who received sham-control in ENDEAR and
ment response in SMA, we measured plasma levels in par- nusinersen in SHINE (n=20/24) and those who received
ticipants in the open-label nusinersen NURTURE trial, nusinersen in ENDEAR and SHINE (n=74/81; pooled
and investigated the association with motor function ENDEAR/SHINE data) demonstrated continued improve-
achievement. ments in HINE-2 total score from nusinersen initiation to last
Methods: NURTURE participants (n=25) had a genetic observed visit (mean [95%CI] change: 1.1 [0.20–1.90] and 5.8
diagnosis of SMA and were presymptomatic at enrollment. [4.58–7.04], respectively). Median (95%CI) EFS time among

S122 Annals of Neurology Vol 86 (suppl 23) 2019

sham-control infants in ENDEAR was 22.6 (13.6–31.3) weeks clinical features, investigation, management and outcome of
vs 73.0 (36.3–NA) weeks for those who received nusinersen in erythromelalgia at a single center.
ENDEAR and SHINE. Results from an interim analysis with Methods: Retrospective chart review of 31 children, <18 years
an October 15, 2018 cutoff date will be presented. of age with erythromelalgia seen at the Cleveland Clinic from
Conclusions: At the time of the previous data cutoff, 2005-2018. Data on demographics, presenting symptoms,
motor function and EFS continued to improve in infants clinical features, investigation, management and outcome
who initiated nusinersen in ENDEAR and motor func- were analyzed.
tion stabilized or started to show improvement in those Results: 31 children (16 F; age 2-18 years) diagnosed with
who initiated nusinersen in SHINE. Data from more erythromelalgia. The time-to-diagnosis was 2.5
3.3 years,
recent analyses will provide additional information on the 68% diagnosed at initial visit. FH included 20% with
long-term efficacy and safety of nusinersen in infantile- erythromelalgia, 80% with pain syndromes, including auto-
onset SMA. immune/autonomic disorders. Symptoms included pain
Keywords: Neuromuscular Disorders, Rare Diseases (90%), redness (81%), warmth (68%), tingling and numbness.
Feet and hands were equally (65%) affected (bilateral in 96%).
175. Rituximab as Immunomodulatory Agent in Pre- Major triggers-physical activity (87%) and heat-exposure
adolescent Pediatric Onset Isaacs’ Syndrome: Case Report (78%), cooling (78%) was the leading relieving factor. School
of Favorable Longitudinal Response absenteeism -46%; 17% quit sports/physical activity. SCN9A
Fisher K (Houston, TX), Lotze T gene-mutation test -positive in 1/5 patients. 12/13 (92%) had
abnormal QSART; 48% had anxiety/depression, 45% had pri-
Objective: Isaacs’ Syndrome is an autoimmune condition mary headache/other chronic pain syndromes. Effective medi-
that results from axonal hyperexcitability and activation of cations included carbamazepine, gabapentin, lidocaine,
muscle fibers. Up to 50% of patients test positive for voltage pregabalin, duloxetine and mexilitine. 21 patients were
gated potassium channel antibodies. While there is no cur- followed long term; 29% complete resolution, 38% partial
rent approved treatment, reports of use of immune modula- recovery, 24% unchanged, and 9% deteriorated.
tors (such as rituximab), mostly in adult patients, have Conclusions: This is the second largest pediatric series with
emerged. We present a pediatric patient with Isaac’s Syn- EM. Most patients had associated small fiber neuropathy and
drome who responded to rituximab treatment. a small percentage were SCN9a gene positive. Increasing
Methods: Single-patient case report, review of clinical presen- awareness of this condition will help early diagnosis and
tation, management, course of hospitalization and outpatient appropriate management. QSART is valuable in diagnosis.
follow up. PT/OT combined with carbamazepine, gabapentin, lyrica,
Results: A 6 year-old healthy female presented for abrupt topical lidocaine and mexilitine may be effective treatments.
onset of painful muscle spasms isolated to lower extremities. Keywords: Neuromuscular Disorders, Rare Diseases
Examination was notable for myokymia. Initial trials of car-
bamazepine, and high dose steroids provided only transient
improvement with symptom recurrence upon cessation of 177. Mini-COMET Study: Safety Data and
treatment. She was unresponsive to plasmapheresis. Severity Immunogenicity for Repeat Avalglucosidase Alfa Dosing
of symptoms led to neuromytonia with increased tone in in Patients with Infantile-onset Pompe Disease who were
lower extremities and early achillean contractures, requiring Previously Treated with Alglucosidase Alfa and
botulinum toxin management. She ultimately received Demonstrated Clinical Decline
rituximab 9 weeks after presentation, leading to complete Hug C (Cambridge, MA), Chien Y-H, Kumada S, Labarthe F,
resolution of symptoms 2 weeks after infusion. At last Ohki H, Pichard S, An Haack K, Fraser P, Liu K, Kronn D,
follow up, 9 months after initial visit, she remains Mini-COMET Investigators
asymptomatic.
Conclusions: We describe a patient with Isaacs’ Syndrome Objective: To report interim safety/immunogenicity data for
refractory to symptomatic and standard immunomodulatory Cohorts1&2 in the Mini-COMET (NCT03019406) clinical trial.
treatment, with otherwise exceptional response to rituximab Methods: Mini-COMET, a phase 2, open-label, ascending-
infusion in long-term follow up. To the best of our knowl- dose, 3-cohort study, is evaluating safety, pharmacokinetics,
edge, this is the first pre-adolescent patient with reported and preliminary efficacy of avalglucosidase alfa in patients
favorable longitudinal response to rituximab infusion for aged <18 years with infantile-onset Pompe disease (IOPD)
Issacs’ syndrome. previously treated with alglucosidase alfa demonstrating clini-
Keywords: Neuromuscular Disorders cal decline (Cohorts1&2) or sub-optimal response (Cohort3).
Cohorts1&2 receive avalglucosidase alfa 20 or 40 mg/kg IV
qow, respectively, for 6 months. Cohort3 patients are ran-
176. Erythromelalgia in Children: A Single Center domized (1:1) to avalglucosidase alfa (maximum tolerated
Experience dose [MTD] determined in Cohorts1&2) or alglucosidase
Ghosh D (Cleveland, OH), Moodley M alfa (current stable dose) for 6 months. Thereafter, patients
Objective: Erythromelalgia is a poorly characterized painful can enter an extension phase (≤3 years on-study) receiving
disorder in children whose pathophysiology is not well- avalglucosidase alfa (20 or 40 mg/kg qow or previously deter-
understood and lacks definitive therapy. We describe the mined MTD).

Program and Abstracts, Child Neurology Society S123

 patients experiencing treatment-emergent adverse events
TABLE 1. Avalglucosidase alfa exposure by (TEAEs). TEAEs were generally mild; the most fre-
September 2018. Abstract 177 quently reported treatment-related TEAE was fall
Cohort 1 Cohort 2 (Cohort1, 2 patients). Four patients presented with seri-
ous TEAEs. One patient (Cohort2) had an infusion-
(n = 6) (n = 5)
associated reaction. No patient developed anti-
avalglucosidase alfa antibodies or tested positive for inhi-
Duration of 35.2
11.3 16.5
2.0 bition of enzyme activity. At screening and Day 8, anti-
exposure, (39.3 (17.2 alglucosidase alfa antibodies were present in 4 Cohort1
weeks, [19.9, 46.3]) [14.1, 18.1]) patients (titers: <100-800) and 1 Cohort2 patient (<100)
mean
SD and were negative thereafter; no patient tested positive
(median [min, for enzyme activity inhibition. No patient developed IgE
max]) antibodies.
Conclusions: These interim results demonstrate that
Duration of
avalglucosidase alfa was well-tolerated in enzyme replacement
exposure,
therapy-experienced IOPD patients. Funding: Sanofi Genzyme.
n (%)
Keywords: Neuromuscular Disorders, Rare Diseases, Trans-
13–25 weeks 2 (33.3) 5 (100) lational/Experimental Therapeutics
26–49 weeks 4 (66.7) 0 (0)
178. Anti-MuSK Antibody-positive Ocular Myasthenia
Total number 18.5
5.6 8.8
0.8 Gravis
of infusions, (20.5 [11, 24]) (9.0 [8, 10]) Yu J (Cheonan, Korea), Hwang J
mean
SD
Objective: Myasthenia gravis (MG) is characterized by fluctuat-
(median [min,
ing muscle weakness. Usually, MG is caused by autoimmune
max])
mechanism and most of them have acetylcholine receptor
SD, standard deviation (AChR) antibody. Recently other autoantibodies, such as
muscle-specific receptor tyrosine kinase (MuSK) antibody and
lipoprotein receptor-related protein 4 (LRP4) antibody, have
Results: Mean ages at avalglucosidase alfa initiation were: been found in MG. The case with anti-MuSK antibody usu-
Cohort1 (n=6): 7.6(SD:3.4, range:2-11) years and Cohort2 ally was reported to have prominent oculo-bulbar symptoms
(n=5): 8.1(SD:4.1, range:1-12) years. Table 1 shows and it usually occurs in young female adults or female infants
avalglucosidase alfa exposure duration. Table 2 shows or toddlers.
Methods: Anti MuSK autoantibody was checked based on
radioimmunoassay.
TABLE 2. Infantile-onset Pompe disease patients Results: A 13-year-old girl was referred to the depart-
experiencing treatment-emergent adverse events. ment of pediatric neurology due to recently developed
bilateral ptosis. The symptom gradually worsened over
Abstract 177
time and accompanied with diplopia and dysarthria. Ini-
Cohort 1 Cohort 2 tially, muscle power, muscle tone, and deep tendon
(n = 6) (n = 5) reflexes were all intact, but extraocular movement was
limited, especially in lateral gaze. Magnetic resonance
Any TEAE, n (%) 6 (100) 5 (100) imaging of the brain did not show any abnormality.
Neostigmine test revealed positive response, and repeti-
TEAE leading to 0 0 tive nerve stimulation test showed a decrement of com-
discontinuation, n (%) pound muscle action potential. Serum creatine kinase
TEAE leading to death, n (%) 0 0 was normal, and anti-AChR antibody was negative.
However, anti-MuSK antibody in blood was positive
Patients with ≥1 SAE, n (%) 1 (17)* 3 (60)† (65.1nmol/L, reference value ≤0.02). Initially,
Infusion-associated reaction, 0 1 (20)‡ pyridostigmine was prescribed without dramatic effect.
n (%) Steroid was added at day 8, and then azathioprine was
added at day 20. She showed complete recovery at day
SAE, serious adverse event; TEAE, treatment-emergent adverse event 28 on medication. During follow-up of 1 year, she did
*Respiratory distress not show any discomfort.
†
Respiratory distress and pyrexia (1 patient), eyelid ptosis Conclusions: We report a case of anti-Musk antibody-
(acute-onset, recovered within 3 days; 1 patient), and eyelid ptosis positive ocular MG developed in a 13-year-old-girl who
(since birth with planned surgery) and pyrexia (1 patient) showed complete improvement with immunosuppressants.
‡
Urticaria at patient’s 8th avalglucosidase alfa infusion
Keywords: Neuromuscular Disorders, Rare Diseases

S124 Annals of Neurology Vol 86 (suppl 23) 2019

179. The AveXis, Inc. Managed Access Program (MAP): Results: Undiscounted quality-adjusted life-years (QALYs)/
Single-Patient Investigational New Drug (IND) Requests patient were 30.3 for AVXS-101 and 7.2 for nusinersen
for Gene-Replacement Therapy (GRT) Onasemnogene (discounted 3%: 15.9 and 5.3, respectively). Estimated
Abeparvovec for Spinal Muscular Atrophy (SMA) discounted lifetime costs/patient were $6.33M for nusinersen
Kichula E (Philadelphia, PA), Modrcin A, Roach E, Scharf R, and $3.7-4.7M for AVXS-101 ($2-3M price points),
Lakhotia A, Leigh F, Tawil R, Konersman C, Schultz M, resulting in cost savings and QALY gains (undiscounted, up
Okposo K, Dvorak C, Barry S, Manganaro S, Sproule D, to 57.5; discounted 3%, 21.9); i.e., AVXS-101 was domi-
Swoboda K nant. For U.S. payers covering 1,000,000 individuals/year,
Objective: SMA is a rapidly progressive neurologic disease. 0.68 SMA1 patients would be treated annually. At place-
Onasemnogene abeparvovec (AVXS-101), AAV9–based sur- holder cost of $2M, the 5-year per-member-per-month
vival motor neuron (SMN) GRT treats the genetic root cause (PMPM) budget impact of adding AVXS-101 to the formu-
of SMA. In a phase 1/2a trial, AVXS-101 improved symp- lary was $0.05 ($3M: $0.11), which decreases each year, and
tomatic SMA type 1 patient outcomes. Clinical trials in pre- resulted in a -$15K offset of SMA care costs in year 5. Install-
symptomatic patients and other SMA types are plan- ment plans will reduce the budget impact further.
ned/ongoing. This report describes the AVXS-101 MAP. Conclusions: AVXS-101 is cost-effective compared to
Methods: The AVXS-101 MAP allows physicians to submit nusinersen with potential to offset payers’ SMA care costs by
single-patient IND requests for pre-approval AVXS-101, using year 5. Discounting QALYs (3%) substantially underesti-
Form FDA 3926, for patients with a serious/life-threatening dis- mates health benefits; therefore, we recommend that U.S.-
ease/condition and no comparable/satisfactory alternative therapy. based decision makers also consider undiscounted QALY
The patient must be unable to access ongoing SMA clinical trials gains when assessing innovative therapy value.
Results: As of 4/5/2019, 37 SMA patients have received Keywords: Neuromuscular Disorders, Translational/Experi-
AVXS-101 in the MAP. Based on confirmed data from Form mental Therapeutics, Rare Diseases
FDA 3926 requests (N=20) at the time of IND request, median
(range) patient age and weight were 5 (1–9) months and 6.4 181. Comparing Hospital Respiratory Outcomes Pre- and
(3.5–8.0) kg; 9/20 were male; 17/20 were being treated with Post- Nusinersen Treatment in Children with Spinal
nusinersen. 2, 13, and 1 of 16 patients with available data had Muscular Atrophy (SMA)
1x-, 2x-, and 3xSMN2, respectively. Among all requests (pend- Matesanz S (Philadelphia, PA), Brandsema J, Mayer O,
ing and treated) with completed AAV9 antibody testing, 0/47 Kichula E
had exclusionary antibody titers (>1:50). Reasons for AVXS-101 Objective: Nusinersen treatment improved motor outcomes
requests included: limitations of current therapy (e.g., repeat life- in phase 3 clinical trials of SMA1 and SMA2 patients, but
time intrathecal injections; suboptimal response); possibility of also showed a trend toward increased full time ventilation in
enhanced outcomes with AVXS-101; desire for an alternative to SMA1 and respiratory tract infections in SMA1. The effect
current therapy; burden of existing treatments; desire for a of nusinersen on respiratory status in a broader population of
longer-term treatment option. patients with SMA than those included in the trials remains
Conclusions: The AVXS-101 MAP provides pre-approval unknown. This study aimed to evaluate for change in rates
AVXS-101 for SMA patients who are ineligible for current and length of respiratory hospitalizations in children with
trials. AAV9 antibody levels did not impact AAV9-based SMA receiving nusinersen.
GRT eligibility in most SMA patients. Methods: A retrospective chart review was conducted on all
Keywords: Neuromuscular Disorders, Rare Diseases, Trans- children under age 18 with SMA who completed four load-
lational/Experimental Therapeutics ing doses of nusinersen at a single center prior to September
2017. Data included demographics, baseline disease charac-
180. Cost-Utility and Budget Impact Analyses of One-Time teristics, and information regarding hospital course for respi-
Gene-Replacement Therapy for Spinal Muscular Atrophy ratory related hospitalizations for 1 year prior to and 1 year
Type 1 Compared to Chronic Nusinersen Treatment following initial nusinersen dose.
Malone D (Tucson, AZ), Miller B, Dean R, Arjunji R, Results: Of the 39 qualifying patients, 17.9% had SMA1,
Feltner D, Sproule D, Jensen I, Maru B, Dabbous O 33.3% had SMA2, and 48.7% had type SMA3. Average age
Objective: To assess the cost utility and 5-year budget at first dose of nusinersen was 8.2 years. Total hospitaliza-
impact of one-time AVXS-101 (onasemnogene abeparvovec) tions in the cohort decreased from 24 to 12, and total hospi-
versus chronic nusinersen in U.S. spinal muscular atrophy talization days decreased from 413 to 147 (65% reduction).
type 1 (SMA1) patients. Average hospital days per patient decreased from 10.6 to
Methods: We developed a multi-state survival Markov model 3.8 days (p = 0.02, paired t-test).
with health-state transitions based on milestone attainment Conclusions: Total respiratory hospitalization days decreased
from published clinical trials. Survival benefit was estimated by more than half in the year after initiation of nusinersen,
using long-term survival and natural history data. Eligible with significant improvement in overall hospitalization days
population size and expected market share were estimated per patient. This suggests that there may be improvement in
using published sources. Costs were sourced from published respiratory status related to treatment in individuals with a
claims analysis data, literature, and expert opinion. Utilities broad spectrum of SMA severity, which may lead to
were from the CHERISH trial. decreased hospitalization utilization.

Program and Abstracts, Child Neurology Society S125

 183. Gene-Replacement Therapy (GRT) in Spinal
TABLE 1. Abstract 181 Muscular Atrophy Type 1 (SMA1): Long-Term Follow-
Year Pre Year Post Up From the Onasemnogene Abeparvovec Phase 1/2a
Nusinersen Nusinersen Clinical Trial
Mendell J (Columbus, OH), Shell R, Lehman K, McColly M,
Dosing Dosing
Lowes L, Alfano L, Miller N, Iammarino M, Church K,
Ogrinc F, Ouyang H, Kernbauer E, Shah S, L’Italien J,
Patients with a 12 (30.7%) 7 (17.9%) Sproule D, Feltner D, Al-Zaidy S
hospitalization (n=39)
Objective: SMA1 is a rapidly progressing neurologic disease
Total hospitalizations in 24 12 caused by biallelic survival motor neuron 1 gene (SMN1)
cohort deletion/mutation. The SMN GRT onasemnogene abe-
parvovec (AVXS-101) treats the genetic root cause of SMA
Average length of hospital 17.2 (range 11.8 (range
and is designed for immediate, sustained SMN protein
stay 2-66) 2-27)
expression. In a phase 1/2a trial (CL-101; NCT02122952),
Total hospitalization days 413 147 SMA1 patients received a one-time AVXS-101 infusion at
for Entire cohort low dose (Cohort 1, n=3) or proposed therapeutic dose
(Cohort 2, n=12), and demonstrated improved outcomes ver-
Total ICU days for entire 355 144
sus natural history.
cohort
Methods: SMA1 patients in CL-101 could rollover into a
long-term follow-up (LTFU) study (Study LT-001;
Keywords: Neuromuscular Disorders NCT03421977). The primary objective is long-term safety.
Patients have annual visits (5 years), then phone contact
(additional 10 years). Patient record transfers are requested.
182. Preservation of Function over time as Measured by
Safety assessments include medical history and record review,
North Star Ambulatory Assessment in Ambulatory Boys
physical examination, clinical laboratory evaluation, and pul-
with Nonsense Mutation Muscular Dystrophy Treated
monary assessments. Efficacy assessments include develop-
with Ataluren
mental milestone evaluation to determine maintenance of the
McDonald C (Sacramento, CA), Wei L-J, Elfring G, Trifillis P,
Bibbiani F, Souza M, McIntosh J, Peltz S, Muntoni F highest achieved milestone in the parent study.
Results: As of 12/31/2018, 13 patients (Cohort 1, n=3;
Objective: Ataluren is promotes readthrough of a nonsense Cohort 2, n=10) had enrolled in Study LT-001 and had a
mutation to produce full-length functional dystrophin protein. baseline visit. Seven patients completed a 1-year post-
ACT DMD was a 48-week, multicenter, randomized, double- baseline visit. 13/13 patients were alive. No developmental
blind, placebo controlled study that compared the efficacy and milestones achieved in the CL-101 study were lost, and
safety of ataluren vs placebo in ambulatory boys with nmDMD
new milestones have been achieved. Patient ages ranged
and enrolled boys aged 7−16 years and a baseline 6-minute
from 39.1–62.4 months (Cohort 2, 39.1–55.3 months),
walk distance (6MWD) of 150 m or more and having ≤80% of
and time since dosing ranged from 37–56.5 months
the predicted normal value at baseline (n=228). The North Star
(Cohort 2, 37–49.7 months). Continuing LTFU data will
Ambulatory Assessment (NSAA) is a validated tool that assesses
be presented.
disease progression in ambulatory boys with DMD.
Conclusions: One-time AVXS-101 administration at the
Methods: In the present analysis, loss of function (failures)
proposed therapeutic dose continues to provide prolonged
from 17 tasks was evaluated for each patient at various time
and durable efficacy with milestone development in LT-001.
points over the entire study duration. The average cumulative
Keywords: Neuromuscular Disorders, Tran-
number of failures over time was then obtained over all study
slational/Experiemental Therapeutics, Rare Diseases
patients for each treatment group, which can be plotted to
show the temporal profile of treatment.
Results: Graphically, the curve for the placebo is uniformly 184. Timed-function Test Data in Patients with
higher than that of ataluren. The ratio of the above two cur- Duchenne Muscular Dystrophy from the Strategic
ves can then be used as an overall measure of treatment effect Targeting of Registries and International Database of
(i.e., treatment divided by placebo) This a resulted in a ratio Excellence (STRIDE) Registry and the CINRG Natural
of 0.73 (95% CI, 0.55-0.97; p=0.027), indicating that, History Study: A Matched Cohort Analysis
ataluren treatment significantly reduces the cumulative num- Mercuri E (Rome, Italy), Buccella F, Desguerre I, Kirschner J,
ber of failures by 27% over 48 weeks vs placebo. Separation Muntoni F, Nascimento Osorio A, Delage A, Zhu J,
between these two curves is seen as early as 32 weeks and Kristensen A, Trifillis P, Santos C, McDonald C
continues to diverge over the 48 weeks. Objective: STRIDE is a multicenter, observational registry
Conclusions: The results suggest preservation of physical providing real-world evidence of ataluren use in patients with
function with ataluren therapy in ambulatory boys with nonsense mutation Duchenne muscular dystrophy
nmDMD. (nmDMD) (NCT02369731). This analysis compared
Keywords: Neuromuscular Disorders, Rare Diseases patients with nmDMD receiving ataluren+standard of care

S126 Annals of Neurology Vol 86 (suppl 23) 2019

(SoC) (STRIDE) with patients with DMD receiving SoC mutation-specific investigational drug for DMD were
alone (Cooperative International Neuromuscular Research excluded. Kaplan–Meier analyses estimated age at LOA.
Group [CINRG] Natural History Study [NCT00468832]). Results: Mean (SD) age at first symptom onset in the
Methods: Propensity score matching identified patients from STRIDE and CINRG cohorts (each n=187) was 2.7(1.8)
STRIDE and CINRG with comparable predictors of disease and 2.9(1.6) years, respectively. The majority of patients
progression: age at first symptom; duration of deflazacort use; (STRIDE vs CINRG) received corticosteroids for ≥12 months
and duration of other corticosteroid use. .CINRG patients (56.7% vs 55.1%), with a similar proportion receiving
who received any other mutation-specific investigational drug deflazacort (24.6% vs 23.5%) or other corticosteroids
for DMD were excluded. Kaplan–Meier analyses estimated (34.8% vs 34.8%). In the STRIDE cohort, 19.3% of
age at transition to ≥5 seconds(s) and ≥10s to stand from patients (36/187) lost ambulation versus 59.2% of patients
supine and climb four stairs. (109/184) in the CINRG cohort. Median (95% CI) age at
Results: Matched patients (n=187/cohort) had a mean age LOA in the STRIDE and CINRG cohorts was 14.5(13.9,-
at first symptom of 2.7 and 2.9 years in STRIDE and incalculable) years and 11.0(10.5,11.9) years, respectively.
CINRG, respectively. Most patients (STRIDE vs CINRG) Kaplan–Meier analyses demonstrated that ataluren+SoC del-
received corticosteroids for ≥12 months (56.7% vs 55.1%), ayed age at LOA compared with SoC alone (p<0.0001).
with a similar proportion receiving deflazacort (24.6% vs Conclusions: These data suggest that ataluren+SoC treat-
23.5%) or other corticosteroids (34.8% vs 34.8%). Median ment slows disease progression in nmDMD patients.
(95% confidence interval, CI) age at transition, to ≥5s and Keywords: Neuromuscular Disorders, Rare Diseases
≥10s to stand from supine, was higher in STRIDE vs
CINRG (≥5s, 11.9 [8.5,14.6] vs 8.6 [8.3,9.7] years, 186. Two Phase 2 Trials to Assess Production of
p=0.0028; ≥10s, 14.0 [11.8,18.6] vs 10.3 [9.5,11.2] years; Dystrophin in Patients with Nonsense Mutation
p=0.0164). For ≥5s and ≥10s to climb four stairs, median Duchenne Muscular Dystrophy Receiving Ataluren
(CI) age at transition was higher in STRIDE vs CINRG Nelson S (Los Angeles, CA), Penematsa V, Chou C, Trifillis P,
(≥5s, 12.3 [10.9,14.0] vs 9.7 [8.5,11.3] years, p=0.0359; Bibbiani F, McIntosh J
≥10s, not calculable, NC [15.4,NC] vs 13.2 [11.1,NC]
years; p=0.0118). Objective: Ataluren (Translarna™, PTC Therapeutics Inter-
Conclusions: These data suggest that,treatment with national Limited, Ireland) is an orally bioavailable treatment
ataluren+SoC slows disease progression in patients with for patients with nonsense mutation Duchenne Muscular
nmDMD. Dystrophy (nmDMD) and is the first drug approved in the
Keywords: Neuromuscular Disorders, Rare Diseases, Tran- EU to treat the underlying cause of the disease in ambulatory
slational/Experiemental Therapeutics patients with nmDMD aged ≥2 years, based on clinical bene-
fit in prior placebo-controlled trials. Ataluren promotes ribo-
somal readthrough of a nonsense mutation in DMD,
185. Age at Loss of Ambulation in Patients with enabling synthesis of full-length dystrophin protein. Two cur-
Duchenne Muscular Dystrophy from the STRIDE rent phase 2 clinical trials (studies 045 [NCT03648827] and
Registry and the CINRG Natural History Study: A 046[NCT03796637]) aim to quantify dystrophin production
Matched Cohort Analysis in ambulatory patients with nmDMD before and after treat-
Muntoni F (London, United Kingdom), Buccella F, ment with ataluren.
Desguerre I, Kirschner J, Mercuri E, Nascimento Osorio A, Methods: Study 045 will enroll ataluren-naïve patients aged
Tulinius M, Delage A, Zhu J, Kristensen A, Triffilis P, ≥2 and <8 years with documented nmDMD. The primary
Santos C, McDonald C and secondary endpoints for study 045 are the percent change
Objective: Strategic Targeting of Registries and Interna- at week 40 from baseline in dystrophin level from biopsied
tional Database of Excellence (STRIDE) [NCT02369731] muscle tissue measured using electrochemiluminescence or a
is an ongoing, multicentre, observational registry providing validated immunohistochemistry assay, respectively. Patients in
data on ataluren use in nonsense mutation Duchenne mus- study 046 must be currently receiving ataluren daily for
cular dystrophy (nmDMD) patients in routine clinical prac- ≥9 months. Study 046 will also measure dystrophin levels as
tice. We examined whether nmDMD patients receiving primary and secondary endpoints in a manner similar to study
ataluren+standard of care (SoC) experienced a delay in age 045, but from biopsies taken in a single visit and compared to
at loss of ambulation (LOA) compared with those receiving untreated controls. Both studies rely on multiple core biopsies
SoC alone (Cooperative International Neuromuscular from two different muscles using two highly sensitive and vali-
Research Group [CINRG] Natural History Study dated assays to increase the likelihood that each muscle biopsy
[NCT00468832]). sample will yield robust results.
Methods: Propensity score matching was performed to iden- Results: n/a
tify STRIDE and CINRG patients who were comparable in Conclusions: These studies will generate additional data on
established predictors of disease progression: age at first the amount of full-length dystrophin protein produced in
symptom onset, and duration of deflazacort use and of other response to ataluren administration in patients with nmDMD.
corticosteroid use. The majority of patients from CINRG Keywords: Neuromuscular Disorders, Rare Diseases
were included; however, those who received any other

Program and Abstracts, Child Neurology Society S127

187. Dystrophin Restoration by Exon 53 Skipping in ≥20% SGCB-positive fibers (60-day muscle biopsy) and
Patients with Duchenne Muscular Dystrophy after safety. Secondary endpoints: CK decrease and functional
Viltolarsen Treatment: Phase 2 Study Update endpoints.
Rao V (Chicago, IL), Connolly A, Zaidman C, Harper A, Results: For the first 3 patients (age 13, n=2; age 4; n=1),
Mah J, Smith E, McDonald C, Morgenroth L, Yamashita T, robust SGCB expression was observed (immunohistochemis-
Hoffman E, Clemens P try), demonstrated by mean of 51% SGCB expression posi-
Objective: Duchenne muscular dystrophy (DMD) is caused tive fibers (range 42-63%) with a 47% mean intensity (range
by the absence of dystrophin leading to progressive motor 38-57%). Co-localization of α-sarcoglycan was also observed.
and cardiac dysfunction and premature death. Exon skipping Western blot showed mean 36.1% SCGB expression vs nor-
allows for restitution of an out-of-frame deletion in the dys- mal (range 34-39%). Mean CK levels reduced by 90% (range
trophin mRNA to yield a truncated, in-frame transcript. 83-97%), suggesting slowed muscle destruction. Two
Viltolarsen is a novel antisense oligonucleotide that promotes patients had elevated liver enzymes (1 serious) following ste-
exon 53 skipping for individuals with DMD whose dystro- roid taper, which returned to baseline. Two patients had
phin deletions are amenable to skipping exon 53 such as transient mild nausea with increased steroid dosing.
43-52, 45-52, 47-52, 48-52, 49-52, 50-52, or 52. The aim Conclusions: Gene transfer in patients with LGMD2E fol-
was to assess additional exploratory safety, timed function lowing infusion of rAAVrh74.MHCK7.SGCB was successful.
and strength outcomes following 73 weeks on viltolarsen. This is the second gene therapy inducing protein production
Methods: 16 DMD boys aged 4-10 years old with DMD post transgene delivery with rAAVrh74 vector and MHCK7,
deletions amenable to exon 53 skipping received weekly demonstrating potential benefits of a rationally designed
viltolarsen infusions. RNA and protein expression in muscle delivery system.
biopsy samples were used to assess target engagement. Func- Keywords: Neuromuscular Disorders
tional outcome measures including timed function tests and
strength measurements were collected as well as regular safety 189. Deflazacort or Prednisone Treatment for Duchenne
assessments. Muscular Dystrophy: A Meta-analysis of Disease
Results: A recently concluded Phase 2 study, established the Progression Rates in Two Multicenter Clinical Trials
safety and tolerability of viltolarsen. Target engagement by Signorovitch J (Boston, MA), Sajeev G, Yao Z, McDonnell E,
viltolarsen was noted in RNA and protein in muscle biopsies Elfring G, Trifillis P, Souza M, Speltz S, Darras B, Shieh P,
collected after 24 weeks of treatment, demonstrating skipping McDonald C
of exon 53 with accompanying expression of a truncated dys- Objective: Compare rates of decline in ambulatory function
trophin protein in muscle. between deflazacort or prednisone/prednisolone cohorts, in
Conclusions: All participants from the completed study were conjunction with current standards of care.
subsequently enrolled into a Phase 2 extension study. This Methods: Ambulatory patients with DMD were included
presentation will focus on additional exploratory investiga- from placebo arms of recently-concluded Phase III trials of
tions into safety, timed function and strength measures ataluren (n=115, all with nonsense mutations) and tadalafil
observed after 73 weeks of total treatment with viltolarsen. (n=116, unselected by genotype). Both trials required ≥6
Keywords: Neuromuscular Disorders mo. of prior corticosteroid (CS) use and stable baseline dos-
ing. Steroid assignment was not randomized. Associations
188. Systemic Gene Transfer with rAAVrh74.MHCK7. between CS type and 48-wk changes in ambulatory function
SGCB Increased β-sarcoglycan Expression in Patients were estimated using mixed models with repeated measures
with Limb Girdle Muscular Dystrophy Type 2E (MMRM) analyses adjusting for baseline age, CS duration,
Rodino-Klapac L (Cambridge, MA), Pozsgai E, Lewis S, and functional assessments including six minute walk dis-
Griffin D, Meadows A, Lehman K, Church K, Miller N, tance (6MWD), visit week, and interactions between visit
Iammarino M, Lowes L, Mendell J week and other characteristics. Placebo arm analytic results
Objective: Limb girdle muscular dystrophies (LGMD) usu- (MMRM analysis) from the ataluren trial were extracted from
ally manifest with progressive hip/shoulder muscle weakness. a publication; placebo data from the tadalafil trial were ana-
LGMD2E (due to β-sarcoglycan [SGCB] deficiency) often lyzed directly. Adjusted differences between CS cohorts were
includes cardiac involvement and elevated creatine kinase pooled across trials in a meta-analysis.
(CK). These are initial phase 1 findings of rAAVrh74. Results: Compared with patients receiving
MHCK7.SGCB gene transfer in LGMD2E. prednisone/prednisolone, those receiving deflazacort pre-
Methods: Multiple ascending-dose study of ≤9 patients with served 28.3 meters of 6MWD [95% confidence interval:
LGMD2E (NCT03652259). Eligibility: aged 4-15 y, con- (5.7, 50.9); p=0.01)], 2.9 seconds on rise from supine, [(0.9,
firmed SGCB mutation (both alleles), negative for antibodies 4.9); p<0.01], 2.3 seconds on 4 stair climb [(0.5, 4.1); p
against rAAVrh74, and >40%n on 100-meter timed test. =0.01], 1.2 points on NSAA total score [(-0.01, 2.3);
Treatment: single IV infusion of 5x1013vg/kg rAAVrh74. p=0.05] and 2.9 points on NSAA linearized score [(0.1, 5.8);
MHCK7.SGCB, an rAAVrh74-mediated therapy containing p=0.04] in the meta-analysis results. Changes in 4-stair
a human SGCB gene driven by muscle-specific promoter descend and 10-meter walk/run did not differ between
(MHCK7). Prednisone 1 mg/kg/day was initiated 1 day groups. Associations were generally consistent in magnitude
before treatment, tapering after 30 days. Primary endpoints: and direction across trials.

S128 Annals of Neurology Vol 86 (suppl 23) 2019

Conclusions: In this adjusted analysis, patients receiving vs. patients with DMD receiving standard of care alone
deflazacort experienced significantly slower rates of functional (Cooperative International Neuromuscular Research Group
decline over 48 wks than those receiving prednisone/ [CINRG] Natural History Study.
prednisolone. Methods: Propensity score matching identified patient cohorts
Keywords: Neuromuscular Disorders, Rare Diseases from STRIDE and CINRG who had comparable predictors of
disease progression: age at onset of first symptom; duration of
190. The Therapeutic Effect of Myostatin Oral Vaccine in deflazacort use; and duration of other corticosteroid use. The
Duchenne Muscular Dystrophy Mouse Model majority of patients from CINRG were included in this analy-
Sung DK (Seoul, Korea), Lee J, Hahm K-S, Park H-K, Lee J sis; patients from CINRG who received other mutation-
specific investigational drug for DMD were excluded. The pro-
Objective: The aim of this study is to prove the efficacy of
portion of patients in each cohort with a predicted forced vital
the myostatin oral vaccine in the mouse model of Duchenne
capacity (FVC) < 50% or FVC < 1 L was determined.
muscular dystrophy.
Results: The mean (SD) age at onset of first symptom in the
Methods: Six-week-old male mdx mice (C57BL/10ScSn-
STRIDE and CINRG cohorts (n=187 in each) was 2.7 (1.8)
Dmdmdx/J) were randomized into control or treated groups
and 2.9 (1.6) years, respectively. The majority of patients
being fed with the feed containing 3% of Lactobacillus casei
(STRIDE vs CINRG) received corticosteroids for ≥12 months
with pgsA (control) or Lactobacillus casei with pgsA-
(56.7% vs 55.1%), with similar proportions receiving
myostatin (treated) for 10 weeks. Serial measurement of body
deflazacort (24.6% vs 23.5%) or other corticosteroids
weight and serum creatine kinase was done at two weeks’
(34.8% vs 34.8%). In the STRIDE cohort, 2.1% (3/140) of
intervals. At end point, the Rota-rod test was executed. After
patients had a predicted FVC < 50% vs 32.5% (37/114) of
scarification, measurements of individual muscle weight,
patients in the CINRG cohort. No patients in the STRIDE
serum creatine kinase, serum anti-myostatin IgG antibodies
cohort had an FVC < 1 L compared with 24.3% (33/136) in
were done. Histologic analysis was done with the gastrocne-
the CINRG cohort.
mius and soleus muscles.
Conclusions: These data suggest that treatment with ataluren
Results: A significant difference was observed in the change
and standard of care slows disease progression in patients
of body weight (P=0.001). Serum creatine kinase of the
with nmDMD.
treated mdx mice decreased to about 14% of the control
Keywords: Neuromuscular Disorders, Rare Diseases
group (P=0.001). Serum anti-myostatin antibody titer
increased about 5.5 fold more than that of the control group
(P=0.001). In the Rota-rod test, the treated mdx group 192. Plectinopathies Causing Congenital Myasthenic
showed 5.8 fold longer duration than the control group at Syndrome (CMS): A Case Study and Review of Literature
20 rpm (P=0.003). Histology revealed decreased size varia- Tutmaher M (Atlanta, GA), Gonzalez Garcia A,
tion and fibrosis with remarkable hypertrophy of myocytes. Upadhyayula S, Sanchez Russo R, Verma S
There were no remarkable adverse effects associated with Objective: Plectin (PLEC) is a large multifunctional protein
myostatin oral vaccine. that helps maintain cytoskeleton stability, and the integrity of
Conclusions: Myostatin oral vaccine which was made via the the neuromuscular junction. Pathogenic variants in the
presentation of myostatin antigenic moiety conjoined to the PLECgene are known to cause autosomal recessive
pgsA vector to the surface of Lactobacillus casei successfully epidermolysis bullosa simplex with muscular dystrophy (EBS-
blocked myostatin via producing circulatory antibodies in MD), and rarely myasthenia. We describe a family with
mdx mice. The myostatin blockade resulted in the functional PLECmutation with congenital myasthenia syndrome
and histologic improvements of dystrophic features in (CMS), and review the available published case studies in the
mdx mice. English literature.
Keywords: Neuromuscular Disorders, Rare Diseases, Trans- Methods: We identified 3 cases of PLEC mutation in one
lational/Experimental Therapeutics non-consanguineous family at a tertiary care center. Retro-
spective review of the clinical history, three generation pedi-
gree, neurological exam, creatine kinase (CK),
191. Pulmonary Function in Patients with Duchenne electromyography (EMG), molecular testing and follow-up
Muscular Dystrophy from the Strategic Targeting of exam data were obtained.
Registries and International Database of Excellence Results: Three children presented with symptoms of EBS
(STRIDE) Registry and the CINRG Natural History shortly after birth with varying degrees of gross motor delay,
Study: A Matched Cohort Analysis proximal muscle weakness, ptosis, feeding difficulty, and
Tulinius M (Gothenborg, Sweden), Buccella F, Desguerre I, Gowers’ sign (Figure1A). CK ranged from 180-904
Kirschner J, Mercuri E, Muntoni F, Nascimento Osorio A, (nl 60-305 U/L). EBS genetic panel showed them to be com-
Delage A, Zhu J, Kristensen A, Trifillis P, Santos C, pound heterozygous for novel PLECgene likely pathogenic
McDonald C variant c.3086G>A (p.R1029H) and pathogenic variant
Objective: To investigate whether patients with nonsense c.9679 _9766del88 (p.D3229VfsX21) confirmed to be in
mutation DMD (nmDMD) receiving ataluren plus standard trans. Stimulated single fiber EMG and repetitive motor
of care in STRIDE, a multicenter, observational registry, nerve stimulation showed neuromuscular junction transmis-
experienced a lesser decline in pulmonary function sion defect in 2 of the children (Figure 1B,C,D,E).

Program and Abstracts, Child Neurology Society S129

FIGURE 1: (A) Family with children affected by PLEC mutation (patient1: girl 11 years, patients 2 and 3: boys 1 and 2 years). (B, C)
Patient 1 and 3. (D, E) Stimulated single fiber EMG of the right orbicularis oculi muscle with mean jitter 86μs (nl <26μs) and 22%
decrement (nl <10%) on 3 hz RNS of right median-APB pair for patient 3. Written consent was obtained from the family to be published.
Abstract 192 [Color figure can be viewed at www.wileyonlinelibrary.com]

Pyridostigmine trial was given with improvement in motor nusinersen. Mean Revised Upper Limb Module (RULM)
strength noted on follow-up. score at baseline, after loading and first maintenance doses of
Conclusions: Wide phenotypic variability is noted in PLEC nusinersen were 14.4
9.3, 17.3
10.5, and 19.8
9.9
mutation subjects. Review of literature and our experience respectively. Two type 3 patients were ambulatory at baseline
suggests to have high degree of suspicion for CMS in PLE- and the ambulation was preserved after loading and first
Ccases with ptosis, muscle weakness, abnormal EMG regard- maintenance doses. Improvements in endurance, hand move-
less of CK values (table 1). Trial of pyridostigmine should be ments, hand writing, and louder/clearer speech were
considered to improve motor function. reported. All patients had scoliosis and 10 had spinal fusion
Keywords: Neuromuscular Disorders, Rare Diseases, Genetics and instrumentation. 37 lumbar and 18 cervical punctures
were performed with successful administration of intrathecal
193. Intrathecal Nusinersen in Older Children and Adults nusinersen. Post lumbar puncture site pain and headache
with Spinal Muscular Atrophy were reported in 5 occurrences.
Veerapandiyan A (Little Rock, AR), Eichinger K, Guntrum D, Conclusions: Improvements and stability in motor func-
Kwon J, Collins E, Ciafaloni E tions and ambulation was noted in our cohort of older
Objective: Spinal muscular atrophy (SMA) is characterized children and adults with SMA. Our data demonstrate fea-
by progressive muscle weakness, atrophy, respiratory compro- sibility and safety of intrathecal nusinersen in such
mise, and paralysis. Nusinersen, the first FDA approved treat- patients.
ment, was effective in phase III randomized controlled trials Keywords: Neuromuscular Disorders, Rare Diseases
in infants with SMA1 and children with later onset SMA in
improving motor function. Data on efficacy and safety of 194. Dilated Cerebral Arteriopathy in Pompe’s Disease
intrathecal nusinersen in older children and adults with SMA Viamonte M (Gainesville, FL), Tuna I, Rees J
is lacking. We report our experience of treating SMA patients Objective: To review the history and clinical features of
with intrathecal nusinersen who are of 12 years of age and Pompe’s Disease with particular attention to imaging findings
older at the time of first injection. of dilative arteriopathy and to propose possible molecular
Methods: Retrospective review mechanisms. Thus far there is no case in the literature of an
Results: 12 patients (6 males; 1 type 1, 4 type 2 and 7 type infantile onset patient with dilative arteriopathy. But in late
3 SMA) between 12 and 52 years of age were treated with onset disease there appears to be an unknown incidence of

S130 Annals of Neurology Vol 86 (suppl 23) 2019

TABLE 1. Review of published English literature on PLEC and myasthenia. Abstract 192
Age Genetics
Author Ethnicity EB* MD† CMS‡ Type Exon Response to
§ k ¶
Year n Gender Onset Onset Onset CK EMG RNS affected therapy

Banwell 20 years + + + 5 fold Myopathic motor unit c.6169C>T c.12043dupG No response to

(1999) old Infant Age 9 Age 9 upper potentials, increased p.Gln2057X p.Glu4015GlyfsX6 Pyridostigmine but
n=1 African limit of electrical irritability with Truncating Truncating responsive to
american normal myotonic discharges and Exon 31 Exon 32 3,4- DAP#
Female fibrillation potentials
11-25% decrement
response in 2 Hz RNS
consistent with a defect
of neuromuscular
transmission
Forrest 8 years + + + 3493 RNS of the median nerve c.10187delTGTC IVS11+2 T > G Responsive to
(2010) old Insidious Birth Age 7 U/L showed a 16% Truncating Donor splice site Pyridostigmine at age 7
n=2 Caucasian Birth decrement of compound Exon 32 abolition 3,4- DAP# added,
Male 410 U/L motor action potential at Intron 11 response not
age 2 1 Hz stimulation, 25% documented
at 3 Hz, and >20% of
radial nerve at 3 Hz.
Selcen 42 years + + + 827 U/L 2 Hz RNS showed a c.6955C>T c.12043dupG No response to
(2011) old 6 weeks Age 3 Age 15 Age 11 decremental response of p.Arg2319X p.Glu4015GlyfsX6 pyridostigmine at age
n=3 African old 67% in hypothenar Truncating Truncating 15. No response to 3,4-
american muscles partially Exon 31 Exon 32 DAP# at age 42
Male corrected by IV
edrophonium chloride.
In vitro electrophysiology
study of the intercostal
muscles revealed
reduction of the mean
miniature endplate
potential amplitude to
50% of normal; the
quantal content of the
end-plate potential was in
the low-normal range
Current 11 years + + + 904 U/L 3 Hz RNS ADMa-Ulnar c.3086G>A c.9679_9766del88 Responsive to
Study old Neonate Age 7 Age 11 182 U/L nerve pair showed 14% p.Arg1029His p. Pyridostigmine at age 11
(2019) Hispanic + + + 602 U/L decrement of area and Missense Asp3229ValfsX21 Responsive to
n=3 Female Neonate Age 2 Age 2 amplitude. Exon 25 Truncating Pyridostigmine age 2
2 years + + - The stimulated jitter c.3086G>A p. Exon 33 N/A
old Neonate Age 1 analysis of the right Arg1029His c.9679_9766del88
Hispanic orbicularis oculi mean Missense p.
Male MCDb of 74 μs (nl <26 Exon 25 Asp3229ValfsX21
1 year old μs) and 63% blocking of c.3086G>A Truncating
Hispanic apparent single fiber p.Arg1029His Exon 33
Male action potentials. Missense c.9679_9766del88
3 Hz RNS median-APBc Exon 25 p.
showed 22% with Asp3229ValfsX21
post-exercise facilitation. Truncating
Stimulated jitter analysis Exon 33
of the right orbicularis
oculi muscle mean
MCDb of 86 μs (nl
<26μs) and 77%
blocking of apparent
single fiber action
potentials.
The 3 Hz RNS was
normal.
The stimulated jitter
analysis of the right
orbicularis oculi
unremarkable.

*
EB: Epidermolysis bullosa, †MD: Muscular dystrophy, ‡CMS: congenital myasthenic syndrome, §CK: Creatine kinase, kEMG: Electromyography,
¶
RNS: Repetitive nerve stimulation, # 3,4 DAP: 3,4-diaminopyridine, aADM: abductor digiti minimi, b MCD: mean of the absolute consecutive dif-
ferences, cAPB: abductor pollicis brevis
Abbreviations:
EB: Epidermolysis bullosa
MD: Muscular dystrophy
CMS: Congenital Myasthenic Syndrome
CK: Creatine kinase
EMG: Electromyography
RNS: Repetitive Nerve Stimulation
3,4 DAP: 3,4-Diaminopyridine
ADM: Abductor Digiti Minimi
MCD: Mean Consecutive Differences

Program and Abstracts, Child Neurology Society S131

dolichoectasia of the vertebral basilar system. Both groups are Keywords: Neuromuscular Disorders, Rare Diseases, Neona-
at risk for aneurysm formation. tal Neurology
Methods: We examine clinical and imaging data on a 14 year
old boy with infantile onset Pompe’s Disease on enzyme 196. Drisapersen Associated with Elevated Factor VIII
replacement therapy (ERT), and a 23 year old woman with and von Willebrand Factor in Duchenne Muscular
late onset Pompe’s also on ERT. Dystrophy
Results: Both our patients exhibit cerebral dolichoectasia, McMillan H (Ottawa, Ontario), Amid A, Gonorazky H,
primarily basilar in the 14 y/o and more diffuse in the 23 year Campbell C
old woman. Our 14 year old patient is notable in that doli- Objective: Drisapersen is an antisense oligonucleotide (ASO)
choectasia in an infantile onset Pompe’s patient has never designed as a disease-modifying therapy for boys with
been previously reported. Duchenne muscular dystrophy. ASO’s have been associated
Conclusions: Pathologic samples of patients with cerebral with increased risk of bleeding. Less is known about any
arteriopathy showed marked vacuolization and glycogen-filled potential pro-thrombotic effects of these drugs.
vacuoles in smooth muscle cells of cerebral arteries. With Methods: We report 3 young men with genetically-
deposition of glycogen the subsequent dilation is thought to confirmed DMD who participated in the regulated clinical
occur via multiple pathologic processes. The primary model trial (BioMarin Pharma; NCT01803412) and who later
being that with glycogen deposition there is an augmentation obtained access to receive weekly intravenous driaspersen
of blood flow. This alteration in stimuli results in tyrosine through Health Canada’s Special Access Program. Each
kinase and integrin signaling within the endothelial cells. The received weekly surveillance blood testing.
discovery of cerebral dilated arteriopathy in a patient with Results: One 17-year old non-ambulatory male was found
classical variant at 14 years of age is novel and not previously to have an elevated Factor VIII (FVIII) level 1.55 U/mL
reported and brings to attention need to be aware of this (normal 0.5-1.54 U/mL) after 2 months of initiation of his
complication in patient with Infantile disease. treatment which gradually increased to 3.5 U/mL over a
Keywords: Neuromuscular Disorders, Rare Diseases, Stroke ten-month period. An interruption of the weekly infusions
was associated with a decline in the FVIII levels, only to
195. Compound Heterozygous CACNA1H Mutations increase again when the infusion was restarted. Furthermore,
Associated with Severe Congenital Amyotrophy his von Willebrand factor (vWF) levels were also elevated
McMillan H (Ottawa, Ontario), Carter M, Tomin A, Weiss N (peak 2.57 U/mL; normal 0.45-1.80 U/mL) but all
Objective: The CaV3.2 T-type calcium channel (CACNA1H) other coagulation tests were normal. Discontinuation of
is expressed in neurons. Autosomal recessive mutations have drisapersen resulted in gradual normalization of his FVIII
been previously linked to amyotrophic lateral sclerosis in a and vWF. Two other boys (14y, 18y) showed similar eleva-
young man. tion in FVIII. None of the patients had any thrombotic
Methods: A 13 month old girl was born at term. Her mother events.
had severe polyhydramnios requiring amnioreduction at Conclusions: We report 3 patients with DMD who had a
31 weeks. Birth weight was 2.9 kg (20%ile). Apgars were 2 at significance elevation of FVIII and VWF as pro-thrombotic
1-min and 5-min. She was intubated for poor respiratory effort, risk factors that were associated with driaspersen. Further
absent gag and suck. She had arthrogryposis, areflexia and no studies are required to investigate the etiology and signifi-
antigravity movements. Nerve conduction studies showed cance of our observation. We suggest monitoring of FVIII
intact sensory but absent motor responses. MRI brain was and vWF be considered in future clinical trial design with
unremarkable. MRI muscle noted severe, diffuse amyoplasia ASO’s and post-marketing surveillance studies.
with largest muscles being right biceps femoris (widest diame- Keywords: Neuromuscular Disorders, Rare Diseases
ter, 8 x 5 mm) and medial gastrocnemius (8 x 3 mm). Biopsy
of vastus lateralis revealed no viable muscle with repeat biopsy 197. Spinal Muscular Atrophy Patients Treated with
of gastrocnemius noting strong type 1 fiber predominance and Onasemnogene Abeparvovec through a Managed Access
marked variability of fiber type size but otherwise no diagnostic Program: A Case Series
findings. She remains fully ventilated via tracheostomy with no Schultz M (Bannockburn, IL), Richardson R, Patterson K
antigravity movement at 13 months old. Objective: To present a single-center case series of spinal
Results: Whole exome sequencing noted compound hetero- muscular atrophy (SMA) patients previously treated with
zygous VUS in CACNA1H: p.V681L and p.D1233H from nusinersen, which was suspended following AVXS-101 dos-
her father and mother respectively. Electrophysiological anal- ing through a managed access program (MAP).
ysis using transiently expressed human Cav3.2 channels in Methods: Three SMA patients were treated with pre-
tsA-201 cells showed that the two mutations cause alterations approval AVXS-101.
of the voltage-dependences of activation and inactivation of Results: Patient 1 (asymptomatic male; 3 SMN2copies) was
the channel, along with a decrease of the window current. identified through newborn screening. At 2 weeks of age,
Conclusions: The clinical, biopsy and electrophysiological nusinersen was initiated with the loading phase completed.
findings in our patient suggest that severe congential He was dosed with AVXS-101 at 2.6 months of age. CHOP
amyoplasia may be related to CACNA1Hwhich would repre- INTEND score increased from a baseline of 35 to 56 at
sent a new phenotype associated with mutations in this gene. 1 month postdosing. Patient 2 (symptomatic male;

S132 Annals of Neurology Vol 86 (suppl 23) 2019

3 SMN2copies) with a SMA1 family history was diagnosed at Conclusions: Preliminary data from SPR1NT show rapid
~1.5 months of age. Nusinersen was initiated with 1 dose motor function improvements in pre-symptomatic SMA
completed followed by AVXS-101 dosing at 2.7 months of patients.
age. He continues to feed exclusively by mouth. Patient Keywords: Neuromuscular Disorders, Translational/
3 (symptomatic female; 2 SMN2copies) was diagnosed with Experimental Therapeutics, Rare Diseases
SMA1 at 4 months. At ~5 months of age, nusinersen was ini-
tiated; loading doses were completed with maintenance doses 199. The Value of AVXS-101 Gene-Replacement Therapy
followed by AVXS-101 dosing at 11 months of age. CHOP (GRT) for Spinal Muscular Atrophy Type 1 (SMA1):
INTEND scores increased from 44 (~3.5 months post- Improved Survival, Pulmonary and Nutritional Support,
nusinersen) to 58 at ~2 months postdosing. Nusinersen was and Motor Function with Decreased Hospitalization
suspended following AVXS-101 dosing; no adverse events Dabbous O (Bannockburn, IL), Sproule D, Feltner D,
were observed. Droege M, Khan F, Arjunji R
Conclusions: This study confirms the ability to safely dose
Objective: SMA1 is a progressive neurologic disease that cau-
patients previously treated with nusinersen. Following AVXS-
ses loss of motor muscle function and death/permanent venti-
101, functional improvements were observed. All three MAP
lation by 2 years of age. The GRT onasemnogene abeparvovec
requests aimed to minimize cost and avoid lifelong intrathecal
(AVXS-101) treats the genetic root cause of SMA, biallelic
injections, demonstrating the significance of one-time treat-
mutation/deletion of survival motor neuron 1 (SMN1) gene.
ment. Patient 1 remains asymptomatic, highlighting the
Methods: In a phase 1/2a study, 12 SMA1 patients (enrolled:
importance of newborn screening. Further follow-up data will
12/2014–12/2015) were treated with a one-time intravenous
be presented.
infusion of AVXS-101 (CL-101; NCT02122952; proposed
Keywords: Neuromuscular Disorders, Rare Diseases
therapeutic dose). Event-free survival (absence of
death/permanent ventilation), pulmonary/nutritional interven-
198. Onasemnogene Abeparvovec Gene-Replacement tions, swallowing, hospitalization, CHOP INTEND scores,
Therapy (GRT) in Pre-symptomatic Spinal Muscular and safety were assessed for 2 years.
Atrophy (SMA) Results: By study end, all patients (therapeutic dose) survived
Schultz M (Bannockburn, IL), Swoboda K, Farrar M, event-free; 7 did not need daily noninvasive ventilation;
McMillan H, Parsons J, Kernbauer E, Farrow M, Ogrinc F, 11 had stable/improved swallowing (i.e., fed orally, 6 exclu-
Kavanagh S, Feltner D, McGill B, Spector S, L’Italien J, sively by mouth); 11 spoke. Participants experienced a mean
Sproule D, Strauss K (range) 1.4 (0–4.8) respiratory hospitalizations/year. Mean
Objective: SMA is a rapidly progressing neurologic disease (range) proportion of time hospitalized, hospitalization
caused by biallelic survival motor neuron 1 gene (SMN1) rate/year, and length of stay were 4.4% (0–18.3%) 2.1
deletion/mutation. Genomic copies of a similar gene (SMN2) (0–7.6), and 6.7 (3.0–12.1) days, respectively. CHOP
modify disease severity. In a phase 1/2a study, the SMN INTEND increased 9.8 (standard deviation [SD]=3.9) and
GRT onasemnogene abeparvovec (AVXS-101) improved out- 15.4 (SD=6.4) points at 1- and 3-months post-dose from
comes in symptomatic SMA type 1 patients (2xSMN2) dosed baseline. Patients who received AVXS-101 (therapeutic dose)
≤6 months. This study evaluated AVXS-101 in pre- have maintained motor milestones at long-term follow-up
symptomatic SMA patients. (NCT03421977), supporting long-term treatment durability.
Methods: SPR1NT is a multicenter, open-label, phase Adverse events included elevated serum aminotransferase
3 study. Asymptomatic SMA patients (≥27; 2–3xSMN2) levels, attenuated by prednisolone.
≤6 weeks will receive a one-time AVXS-101 infusion Conclusions: AVXS-101 resulted in rapid, sustained
(1.1x10e14 vg/kg). Safety and efficacy are assessed through improvements in CHOP INTEND scores, dramatic survival,
study end (2xSMN2: 18 months; 3xSMN2: 24 months). Pri- and motor function improvements at long-term follow-up,
mary outcomes: independent sitting ≥30 seconds (2xSMN2), viewed as a clinical demonstration of continuous SMN
assisted standing (3xSMN2); exploratory outcomes: motor expression. The reduced healthcare utilization in treated
function improvement (CHOP INTEND, Bayley-III). infants could decrease cost; alleviate patient, caregiver, and
Results: As of 9/27/2018, 7 infants received AVXS-101 societal burden; and improve quality of life.
(aged 8–37 days [median: 12; mean: 21]; 4 female; 6 with Keywords: Neuromuscular Disorders, Rare Diseases, Trans-
2xSMN2). At screening, mean (range) scaled Bayley gross lational/Experimental Therapeutics
and fine motor scores were 9.7 (7–14) and 9.6 (7–12) points.
In 6/7 patients, ≥1 pair of Bayley subtest scores was available; 200. Event-Free Survival and Motor Milestone
all patients with ≥2 sets of scores had increased Bayley scores Achievement Following Onasemnogene Abeparvovec and
versus baseline. Mean baseline CHOP INTEND score was Nusinersen Interventions Contrasted to Natural History
41.7 points (maximum 64), which increased by a mean of for Spinal Muscular Atrophy Type 1 (SMA1) Patients
6.8 (n=4), 11.0 (n=3), 18.0 (n=3), and 22.5 (n=2) points at Dabbous O (Bannockburn, IL), Sproule D, Feltner D,
14 days, 1, 2, and 3 months; 2 patients scored ≥60 points. Ogrinc F, Menier M, Droege M, Maru B, Khan F, Arjunji R
As of 3/22/2019, 20 patients (2xSMN2: n=8; 3xSMN2: Objective: SMA1 is a rapidly progressing neurologic disease
n=12) were dosed. Additional follow-up will be presented. resulting from biallelic survival motor neuron 1 (SMN1) gene

Program and Abstracts, Child Neurology Society S133

deletion/mutation. This study describes the clinical outcomes hospital admissions, while length-of-stay was lower in youn-
of onasemnogene abeparvovec (AVXS-101), a one-time SMN ger patients. Mean recovery-stay after scoliosis-correcting sur-
gene-replacement therapy, in SMA1 patients contrasted with gery was 18.2 and 12.3 days in each of two studies. Care
nusinersen and untreated patients. integration improved outcomes and reduced costs. 18/19
Methods: SMA1 patients (2xSMN2) were treated with clinical studies (14 randomized controlled trials, 5 single-arm;
AVXS-101 (CL-101; NCT02122952; Cohort 2; n=12) or N=8–73; follow-up 1–26 months) focused on pharmacologi-
nusinersen (ENDEAR; NCT02193074; N=80). Event-free cal symptom treatment; none targeted the underlying cause.
survival (EFS, composite endpoint of time to death or perma- Most common primary endpoints: Rett syndrome Gross
nent ventilation), motor milestone achievement, and Motor Scale; Clinical Severity Score; Motor and Behavioral
nutritional/ventilatory support (CL-101, ≥20 months; Assessment; Anxiety Depression and Mood Scale. Clinical
ENDEAR, ≥14 months of age) were contrasted with two benefits were demonstrated for naltrexone, trofinetide, and
comparable natural history studies (up to 14 months of age): mecasermin versus placebo, but most treatments showed no
Pediatric Neuromuscular Clinical Research network (PNCR; significant improvement. Recent clinical practice guidelines
N=23) and NeuroNEXT (NN101, NCT01736553; N=16). and treatment patterns data were limited.
Results: The proportions of patients achieving EFS at Conclusions: Data on costs of managing Rett syndrome
≥14 months were 30% (PNCR), 50% (NN101), 61% patients are limited. Effective therapies are also lacking; those
(nusinersen-treated), and 100% (AVXS-101-treated). No available only manage symptoms. There is a need for safe and
patient in PNCR or NN101 achieved motor milestones. In effective treatments that target the underlying cause of Rett
ENDEAR, 8% of patients sat independently; 1% stood. In syndrome, which could improve patient quality of life and
CL-101, 92% of patients sat unassisted; 17% stood with assis- prognosis.
tance; 17% walked independently. The maintenance of Keywords: Rare Diseases, Movement Disorders, Genetics
highest acquired developmental motor milestones in long-term
follow-up supports AVXS-101 durability. Seventy percent of 202. Intrathecal VTS-270 For The Treatment of
PNCR patients received nutritional support. In contrast, 86% Niemann-Pick Disease, Type C1
of AVXS-101-treated patients who were independent of nutri- Berry-Kravis E (Chicago, IL), VanMeter S, Porter F
tional support at baseline continued to eat exclusively by
mouth; 92% of all AVXS-101-treated patients achieved the Objective: To evaluate the effects of intrathecal VTS-270, a
ability to speak or had stable/improved swallowing function. specific, well-characterized 2-hydroxypropyl-β-cyclodextrin,
Conclusions: AVXS-101 in the CL-101 study improved clini- on neurological progression Niemann-Pick disease type
cal outcomes, including survival, motor milestone achieve- C1 (NPC1).
ment, and reduced ventilatory/nutritional support relative to Methods: Participants with NPC1 have received open-label
nusinersen (ENDEAR study) and natural history cohorts. IT VTS-270 by LP for 1-5 years in a Phase 1/2a study
Keywords: Neuromuscular Disorders, Translational/Experi- (NCT01747135; N=14) or an Expanded Access Protocol
mental Therapeutics, Rare Diseases (RUMC-EAP, IND 119856 (EBK); N=20). A Phase 2b/3
trial (NCT02534844) studied IT VTS-270 versus sham LP
over 52 weeks (N=56), followed by open-label treatment.
The Natural History (NHx) (NCT00344331) conducted
RARE DISEASES by the NIH is an ongoing evaluation of all referred
patients with NPC (N=30). In all studies patients were
followed with the NPC-Neurological Severity Scale (NPC-
201. Economic Burden of Care and Treatment Options NSS, 0-61 point scale, increases with worsening) adminis-
for Patients with Rett Syndrome: Two Systematic tered 6-monthly.
Literature Reviews Results: The mean change from baseline in NPC-NSS at years
Dabbous O (Bannockburn, IL), Taieb V, Abdennadher E, 1, 2, 3 and 4 in the Phase 1/2a study was 0.71, -0.20, 0.55,
Bouchemi M, Chorą_z y J, Borkowska K, Georgieva V, McGill B, 0.88, respectively; and over 1-5 years in the RUMC-EAP was
Macek T, Maru B, Arjunji R 0.45, -0.44, -2.00, -1.33, -1.00. In untreated patients in the
Objective: Rett syndrome is caused by mutations in the X- NHx study, mean change from baseline over 1-5 years was
linked MECP2gene. It occurs almost exclusively in girls and 2.23, 3.35, 0.75, 6.60, 7.50. In the Phase 2b/3 study, there
leads to severe developmental impairment. was no separation in NPC-NSS between VTS-270- and sham-
Methods: Two systematic, Rett syndrome-related literature treated participants, with no disease progression in either group.
reviews were performed (25June2018) using Medline, Conclusions: Long-term treatment with IT VTS-270 in
Embase, Cochrane Library, and Database of Abstracts of 2 unrelated cohorts for up to 5 years results in minimal overall
Reviews of Effects (DARE) or ClinicalTrials.gov. An eco- disease progression, a very different result from that predicted
nomic burden search yielded 133 articles; intervention by natural history. This data illustrates the challenges of dem-
types/cost were extracted from 9 articles (4 studies). A clinical onstrating effectiveness of disease-targeted agents for gradually
trial search yielded 652 articles; outcomes were extracted progressive variable rare childhood-onset neurodegenerative
from 28 articles (19 studies). diseases in short-term controlled trials; new models are needed.
Results: In the economic burden studies, enteral feeding and Keywords: Rare Diseases, Translational/Experimental Thera-
assisted walking increased the risk of respiratory-related peutics, Genetics

S134 Annals of Neurology Vol 86 (suppl 23) 2019

203. Impact of Intrathecal 2-Hydroxypropyl-Beta- Keywords: Rare Diseases, Translational/Experimental Thera-
Cyclodextrin (HP-B-CD, VTS-270) on Cognitive Decline peutics, Genetics
in Niemann-Pick Type C1 (NPC1)
Berry-Kravis E (Chicago, IL), Chin J, Jaeger R, Friedmann K, 204. Interim Results from the First Clinical Gene
Hoffmann A, Wainer A, Leonczyk C, Soorya L, Thurm A, Therapy Trial for CLN6 Batten Disease
Farmer C, Farhat N, Porter F de los Reyes E (Columbus, OH), Lehwald L, Meyer K,
Objective: To evaluate long-term effects of intrathecal VTS- Castelli J, Jiang H, Reha A, Barth J
270 on cognition in NPC1 relative to published natural Objective: Mutations in the CLN6 gene cause variant late
history data. infantile neuronal ceroid lipofuscinosis, or Batten disease, which
Methods: Cognitive function was evaluated yearly for all par- is a fatal neurodegenerative disorder leading to motor impair-
ticipants enrolled and treated with 2-weekly IT VTS-270 at ment, seizures, and loss of language/cognitive ability and vision,
RUMC through a phase 2/3 trial (Vtesse/Sucampo/ with death often occurring in childhood. There is currently no
Mallinckrodt, NCT02534844) or expanded access protocol treatment for the underlying cause of disease. The goal of this
(IND119856 (EBK)). Data was analyzed from all (N=18) study is to evaluate the safety and effectiveness of AAV9 CLN6
patients age 4 or older, able to complete a Weschler IQ test, gene transfer in children with CLN6 Batten disease.
used English as the primary language, and had at least one Methods: This is an open-label, single-site phase I/II trial of
year of follow up data. CLN6 gene transfer in children (≥1 year) with confirmed
Results: Demographic data for this cohort and a natural history
CLN6 gene mutation and a score of ≥3 on the Hamburg
(NHx) cohort (N=18) is shown in the Table. The NHx cohort
motor-language scale. The CLN6 gene is delivered using self-
was somewhat younger and more mildly affected at baseline
complementary adeno-associated virus (scAAV) serotype
than the treated group, factors which might balance expected
9 under the control of chicken-β-actin hybrid promoter.
rates of decline. The annualized rate of change was 0.23
4.7
Twelve patients received a single dose of scAAV9.CB.CLN6
(VIQ) and -0.04
3.16 (NVIQ) in the treated group and
delivered via intrathecal injection into the subarachnoid
-2.38
9.32 (VIQ) and -3.62
8 (NVIQ) in the NHx group
space. After gene transfer, patients are monitored on days
(p=0.29 VIQ, p=0.08 NVIQ; treated vs NHx). 15/18 (Chi-
square p=0.005) of treated patients were progressing more 7, 14, 21, 30, and every 3 months thereafter up to 2 years.
slowly than natural history for VIQ and 13/18 (p=0.02) for Results: Enrollment of 12 pediatric patients is now complete.
NVIQ. In the NHx cohort 11/18 (58%, VIQ) and 8/18 Patient demographics were as follows: 42% male; 75% Cau-
(42%, NVIQ) decreased >5 points, compared to only 3/18 casian; 8% African American; and 8% other. The mean
(17%, same for VIQ and NVIQ) in the treated group, but the (standard deviation [SD]) age was 55.0 (18.3) months (range,
treated cohort has on average a year less of follow up. 19-79 months). Mean (SD) Hamburg motor and language
Conclusions: This data suggests that VTS-270 may protect score at baseline was 4.2 (0.9).
from VIQ and NVIQ decline in NPC1 but further analyses Conclusions: Enrollment of the first gene therapy clinical
are needed with larger numbers, longer follow up and better trial for CLN6 Batten disease has completed. Interim safety
age balance between cohorts. and efficacy data will be reported.

TABLE 1. Demographic Data. Abstract 203

RUMC Treatment Cohort (N=18) NIH Natural History Cohort (N=18)*
Characteristic Mean/Number (SD) Range Mean/Number (SD) Range

Sex 6F, 12M - 8F, 10M -

Age 18.1 (8.2) 5-31 10.8 (4.1) 4.5-18
Percent on Miglustat 61% - 65% -
NPC-NSS at entry** 16 (8.1) 2-32 11.7 (7.3) 1-22
Baseline FSIQ 66.1 (16.3) 45-102 - -
Baseline VIQ 78.2 (18.1) 45-111 78.4 (15.5) 47-104
Baseline NVIQ 74.2 (18.8) 52-117 68.1 (18.2) 46-115
Follow up period 2.2 (1.3) y 1-5y 3.3 (2.8) y 0.4-8y
*Thurm et al. DMCN 2016, follow up data N=19, 18 with WPPSI/WISC/WAIS
**NPC-Neurological Severity Scale total score including hearing (max score = 61)

Program and Abstracts, Child Neurology Society S135

Keywords: Rare Diseases, Translational/Experimental neurological manifestations in pediatric patients applying
Therapeutics to this program.
Methods: We reviewed the UDP database (UDPICS) for
205. Intracerebroventricular Cerliponase Alfa for CLN2 neurological manifestations in pediatric patients evaluated in
Disease: Clinical Practice Considerations from US Clinics the UDP from 2008 to 2018.
de los Reyes E (Columbus, OH), Lehwald L, Wang R, Results: Since 2008, 4800 applications have been received.
Augustine E, Berry-Kravis E, Butler K, Cormier N, Demarest S, 350 (19.4%) of applicants accepted and evaluated at the NIH-
Lu S, Madden J, Olaya J, See S, Vierhile A, Yang A, Leal- CC: 37.6% were pediatric cases, 6% were international cases and
Pardinas F for 52% the chief complaint was neurological. Molecular diagno-
ses were made in 43% of pediatric cases. We highlight the clini-
Objective: CLN2 disease, a rare, autosomal recessive, neuro-
cal presentation of cases accepted into the UDP, prior workup at
degenerative lysosomal storage disorder caused by TPP1 defi-
the time of application and why they remain unsolved.
ciency, is characterized by language delay, epilepsy,
Conclusions: Neurological manifestations were present in
progressive motor and cognitive decline, blindness, and early
52% pediatric cases accepted into the UDP. Complex clinical
death. Intracerebroventricular (ICV)-administered cerliponase
and genetic evaluations provided a diagnosis in half of the
alfa, a recombinant human TPP1 enzyme, is an approved
cases. Initially located NIH campus and with funding from
treatment for CLN2 disease in the United States and
the NIH Common Fund, the UDP has been expanded to
European Union. ICV infusion represents a novel delivery
multiple sites around the country to create the and
method for enzyme replacement therapy. Here, key practice
Undiagnosed Diseases Network (UDN; https://undiagnosed.
considerations are presented to facilitate safe administration
hms.harvard.edu/ ) with 12 clinical sites, a Coordinating
of cerliponase alfa.
Center, and core laboratories, for metabolomics, sequencing,
Methods: 15 healthcare professionals (neurosurgeons, neurol-
and the generation of model organisms. The UDP has also
ogists, hospitalists, registered and advanced practice nurses)
expanded internationally to 15 countries into the
from 9 institutions in the US met to share current practices
Undiagnosed Diseases International (UDNI; http://www.
in administering ICV-delivered cerliponase alfa, and
udninternational.org/). Child neurologists across the country
preventing and managing associated complications.
and worldwide could benefit from the UDN and UDNI in
Results: Common practices among the participants that
evaluating difficult neurologic cases.
were deemed essential to achieving successful infusions
Keywords: Rare Diseases, Genetics
include developing an institutional protocol for infusions,
high sterility standards, and a multidisciplinary infusion
team with a designated staff member to coordinate care. 207. AGIL-AADC Gene Therapy Results in Sustained
The use of multiple different cleansing agents as part of Improvements in Motor and Developmental Milestones
aseptic technique is common. Considerable variations in through 5 Years in Children with AADC Deficiency
practice exist, based on experience, regarding CSF sampling Chien Y-H (Taipei, Taiwan), Lee N-C, Tseng S-H, Tai C-H,
frequency for infection monitoring and actions taken with a Conway A, Pykett M, Hwu W-L
positive culture, infusion setting, and post-infusion proce- Objective: To evaluate clinical outcomes through 5 years in
dures, such as length of stay and monitoring. Clear commu- children with aromatic l-amino acid decarboxylase (AADC)
nication across departments and with families throughout deficiency, a rare genetic disorder of neurotransmitter synthe-
the process is critical. sis, [SL1] treated with AGIL-AADC, a recombinant adeno-
Conclusions: The sharing of practices among institutions associated virus vector containing the human cDNA
familiar with cerliponase alfa has identified similar as well as encoding the AADC enzyme.
differing practices which new institutions may adapt in Methods: In 2 open-label clinical studies, children with AADC
developing their policies. Continued sharing of experiences deficiency received AGIL-AADC (total dose, 1.8x1011vg) as
is essential for developing standards and guidelines for bilateral, intraputaminal, stereotactic infusions during a single
patient care. operative session. The primary endpoint was improvement on
Keywords: Rare Diseases the Peabody Developmental Motor Scale, Second Edition
(PDMS-2). The Alberta Infant Motor Scale (AIMS) and Bayley
206. Child Neurology Cases at the NIH-Undiagnosed Scales of Infant and Toddler Development, 3rdEdition (Bayley-
Diseases Program: 2008-2019 III) also assessed developmental milestones. De novo dopamine
Acosta M (Bethesda, MD), Adams D, Toro C, Macnamara E, production was evaluated with 6-[18F]fluorodopa positron
Wolfe L, D’Souza P, Estwick T, Yang J, Gahl W, Tifft C emission tomography imaging. Adverse events were recorded.
Objective: The Undiagnosed Diseases Program (UDP) Findings were compared with those from a natural history
was established by the National Institutes of Health cohort of severe AADC patients (N=82).
(NIH) to provide diagnosis and treatment for patients Results: Patients aged 21 months to 8.5 years (N=18)
with unknown disorders. Many medical specialties received AGIL-AADC. None had full head control or could
from other NIH resources also contribute the expertise sit unassisted or stand at baseline. In this update, all patients
needed to conduct the program. We present details of had 2 years of posttreatment data; 8 patients had 5 years of

S136 Annals of Neurology Vol 86 (suppl 23) 2019

posttreatment data. PDMS-2 total score and single-item Objective: We investigated whether a case-based educational
motor developmental milestones demonstrated clinically activity was able to improve the knowledge and competence
meaningful improvements versus natural history controls. among neurologists and pediatricians regarding the diagnosis
AIMS and Bayley-III total and cognitive and language sub- and management of SMA.
scale scores also improved. All patients demonstrated Methods: An online, text-based educational intervention
sustained de novo dopamine production. No new safety sig- comprised of 2 patient case scenarios was developed. Clini-
nals were observed. cians were presented with multiple-choice questions to evalu-
Conclusions: In children with AADC deficiency, AGIL- ate their application of evidence-based recommendations.
AADC gene therapy achieved clinically meaningful, sustained Each response was followed by detailed, referenced, feedback
improvements in motor, cognitive, and language milestones to teach. A chi-square test was utilized to identify whether
for up to 5 years, with no new safety signals. proportions of correct answers at pre and post were signifi-
Keywords: Rare Diseases, Movement Disorders, Trans- cantly different. Cramer’s Vwas used to calculate the effect
lational/Experimental Therapeutics size of the intervention. Data were collected between
December 5, 2018 and January 14, 2019.
208. Delays in Diagnosis are Associated with Poor Results: The education resulted in a considerable educa-
Clinical Outcomes in Patients with Arginase 1 Deficiency tional effect for neurologists (n=100; V=.196) and an exten-
Diaz G (New York, NY), Longo N, Bubb G, Eckert S, sive educational effect for pediatricians (n=437; V=.271).
Bechter M, Wooldridge J, Merritt L Significant improvements were observed in several areas for
both groups (P <.05 for all comparisons) including: inter-
Objective: Arginase 1 Deficiency (ARG1-D) is an inherited,
pretation of genetic testing for SMA; personalizing the selec-
metabolic disease with elevated plasma arginine and promi-
tion of supportive therapy; and identification of the
nent neurological manifestations (spasticity, seizures, and
appropriate SMA subtype where nusinersen is most effec-
intellectual disability). Although diagnostic testing by
tive. Participation in the education resulted in 35% of neu-
plasma arginine is widely available, the variable presentation
rologists and 49% of pediatricians reporting an increase in
and rarity of the condition may lead to delayed or mis-diag-
confidence regarding managing patients with hereditary
nosis. Given the impact of plasma arginine reduction with
motor disorders.
diet, prompt diagnosis is important to optimize patient
Conclusions: This study demonstrated the success of an
outcomes.
online, interactive, case-based educational intervention on
Methods: An extensive review of published literature identi-
improving the knowledge and competence among both neu-
fied 140 unique ARG1-D cases from 1965 to 2018.
rologists and pediatricians regarding the care of patients with
Results: Lower limb spasticity was present in 84% of
SMA. The results indicated that both clinician groups would
117 patients. Intellectual disability was noted in 82% of the
benefit from continued education on the clinical recognition
97 patients with available data and was moderate or severe in
and management of SMA.
39%. Seizures and upper limb spasticity were present in 70%
Keywords: Rare Diseases, Genetics, Neuromuscular Disorders
and 50% of patients, respectively. Maximal plasma arginine
exceeded 4.5xULN (n=112 ULN=115μM) in >50% of
patients. Despite disease management, arginine values 210. Development and Reliability of a Scale for
remained elevated beyond 200μM for most patients (n=33 Neurologic Function in Children with Aicardi Goutieres
with data). Median age at presentation was 2 years (n=81). Syndrome
Delays in diagnosis of ≥2 years were reported in 39% of Gavazzi F (Philadelphia, PA), Adang L, De Simone M,
patients and of ≥5 years in 24% of patients; the median age Fazzi E, Galli J, Orcesi S, De Giorgis V, Vanderver A
at death was 17 (n=20). Objective: Neurologic dysfunction is key feature of Aicardi-
Conclusions: These results confirm ARG1-D has signifi- Goutieres Syndrome (AGS), a rare, inflammatory disorder.
cant delays in time to diagnosis and presents with promi- Due to disease severity, assessment of the course is difficult
nent neurological manifestations. Patients are at risk of with traditional tools, which often fail to discriminate
progression to severe complications and early mortality. among children with severe impairing. There is a need for a
Plasma amino acid analysis to assess arginine levels in scale that is capable of quantitating the longitudinal change
patients presenting with spasticity, seizures and cognitive in neurologic function in this population. To address this
impairment could lead to early diagnosis and interventions need, we aimed to develop a scale applicable with retrospec-
that reduce morbidity and mortality risk in this patient tive and prospective collection to measure skills of AGS
population. population.
Keywords: Rare Diseases, Movement Disorders, Cognitive/ Methods: To develop functional classification scales for
Behavioral Disorders AGS, detailed developmental data were collected from chil-
dren (n=88) with AGS. Individuals were classified as severe
209. Diagnosis and Treatment of Spinal Muscular (GMFCS level V), designated at Type-I, or moderate
Atrophy: Online, Case-based Education Successfully (GMFCS level >V), was designated at Type-II. We evaluated
Improved Knowledge and Competence of Neurologists the performance of traditional outcome measures, including
and Pediatricians the GMFM-88 and Peabody, to assess neurologic abilities in
Finnegan T (Glenside, PA), Aboulsaoud P Type-I versus Type-II individuals. We found that only 1/3 of

Program and Abstracts, Child Neurology Society S137

individuals with AGS scored above the 15thpercentile on the Objective: Peroxisomal biosynthesis disorders are rare and present
GMFM-88, suggestive of floor effect. To develop a novel with hypotonia, epileptic encephalopathy, neuronal migration
disease-specific scale suited to assessing neurologic function defects, and hepatic dysfunction. Several causative genes have
in AGS, we selected items for the scale based on prevalence been associated, most commonly in the family of PEX genes.
within Type-I category. We then applied the scale to retro- However, other, less well studied genes have been reported. Here,
spective cohort of patients with AGS. Results were compared we rpresent two infants with peroxisomal disorder due to novel
to GMFM-88 performance. the scale was then apllied per- variants in HSD17B, causing D-bifunctional protein deficiency.
pectively to an AGS population. Methods: Two neonates with hypotonia, epileptic encepha-
Results: We found that the AGS scale was more sensitive to lopathy, polymicrogyria, and hepatic dysfunction underwent
change, compared to traditional measures. very long chain fatty acid testing and simultaneous critical
Conclusions: This scale will need to be validated in future trio whole exome sequencing.
cohorts, but shows promise as a potential clinical outcome Results: In both cases, very long chain fatty acids showed
measure for clinical trials. abnormalities of peroxisomal function. Exome analysis for
Keywords: Rare Diseases, Genetics patient 1 revealed a compound heterozygous variant in
HSD17B4 (c936_937delTA, p.T1313 maternally,
211. Neurological Manifestations of TANGO2-Related c1768-1G>A paternally). Patient 2 was the product of con-
Metabolic Encephalopathy and Arrhythmias in Children sanguinity and had a homozygous novel variant in HSD17B4
Hannibal M (Ann Arbor, MI), Neil E, Ames E, Mackenzi S, (c.292A>G, p.N98D).
Powell A Conclusions: Peroxisomal biosynthesis disorders constitute a
spectrum of disease with phenotype related to genetic etiology.
Objective: To describe the variable presentations, symptoms, Classically, PEX genes have been implicated. Here, we present
and characteristics of patients diagnosed with the autosomal two infants with refractory epileptic encephalopathy, hypotonia,
recessive inherited TANGO2 (Transport and Golgi Organiza- neuronal migrational defects, and liver dysfunction caused by
tion 2 homolog) related metabolic encephalopathy and novel variants in HSD17B4, producing D-bifunctional protein
arrhythmias (TRMEA) condition at a tertiary care center. deficiency. Currently, no treatment exists and most cases are
Methods: Retrospective chart review of 4 patients with discovered in the early neonatal period due to severity of presen-
molecularly-confirmed TRMEA and comparison with previ- tations. Our study found a faster turnaround time for critical
ously published findings from the literature. trio exome sequencing than very long chain fatty acid analysis,
Results: At time of diagnosis, patients ranged from 1 year of supporting the importance of timely genetic testing to elucidate
age to 7 years, 9 months of age. The most common neurologi- a diagnosis. Overall, more studies on the molecular mechanism
cal signs and symptoms were episodic ataxia (4 patients), and pathogenicity of D-bifunctional protein deficiency are
developmental delay/intellectual disability (3 patients), seizures needed to develop potential targets for medical intervention.
(2 patients), and microcephaly (2 patients). These features fre- Keywords: Rare Diseases, Genetics, Neonatal Neurology
quently preceded life-threatening symptoms such as metabolic
decompensation with lactic acidosis (4 patients), dilated cardio-
myopathy (4 patients), and cardiac arrhythmia (4 patients with 213. Epidemiology, Molecular Genetics, and New
intermittent prolonged QT interval and 1 patient with Tor- Treatment Options for Aromatic Amino Acid
sades de points leading to cardiac arrest). Novel biallelic patho- Decarboxylase Deficiency
genic variants observed in this patient cohort will be reviewed, Himmelreich N (Heidelberg, Germany), Montioli R,
as will the phenotypic overlap between TRMEA and chromo- Bertoldi M, Carducci C, Leuzzi V, Gemperle C, Berner T,
some 22q11.2 deletion syndrome (1 patient). Hyland K, Thony B, Hoffmann G, Voltattorni C, Blau N
Conclusions: TRMEA is a newly recognized and likely under- Objective: To summarize the state of knowledge on aromatic
diagnosed condition that may present initially with phenotypi- amino acid decarboxylase (AADC) deficiency, an ultra-rare
cally variable and non-specific neurologic signs and symptoms. inherited autosomal recessive disorder characterized by defi-
Patients with TRMEA may go on to experience life- ciency of the neurotransmitters serotonin, dopamine, epi-
threatening complications such as metabolic decompensation, nephrine, and norepinephrine. Symptoms, including
cardiomyopathy, tachyarrhythmias, and/or rhabdomyolysis, hypotonia, movement disorders, autonomic dysfunction, and
underscoring the need for pediatric neurologists to be familiar behavioral disorders, vary and emerge in infancy. Diagnosis
with this diagnosis. Patients with chromosome 22q11.2 dele- requires analysis of cerebrospinal fluid (CSF), assessment of
tion syndrome are at a relatively higher risk for TRMEA com- plasma AADC activity, and/or DNA sequence analysis.
pared to the population at large given the relatively high Methods: A literature review was conducted; genotypes were
carrier rate of pathogenic alleles of the TANGO2 gene. accessed from the database at www.biopku.org/home/pnddb.asp.
Keywords: Rare Diseases, Genetics Results: 82 dopa decarboxylase (DDC)variants causing AADC
deficiency were identified for all 123 known patients. Biochemi-
cal and bioinformatics studies provided insight into the impact
212. Early Epileptic Encephalopathy, Hypotonia, and of many mutations. c.714+4A>T, p.S250F, p.R347Q, and p.
Liver Dysfunction caused by D-bifunctional Protein G102S are the most frequent variants (cumulative allele fre-
Deficiency quency=57%), and c.[714+4A>T];[714+4A>T], p.[S250F];
Herman I (Houston, TX), Lim J, Kayyal S, Erklauer J [S250F], and p.[G102S];[G102S] are the most frequent

S138 Annals of Neurology Vol 86 (suppl 23) 2019

genotypes (cumulative genotype frequency=40%). Known or Objective: Design and execute a patient-advocacy group driven
predicted molecular effect was defined for 79/82 variants. Based initiative to partner with families and clinicians experienced in
on genomic DNA sequence databases and abnormal CSF pro- CLN1, a type of Batten disease, to identify management strate-
files in US patients, estimated prevalence of AADC deficiency is gies. To date, this ultra-rare disease has lacked a published clini-
1/42,000 newborns. Most patients experience an unrelenting cal consensus, likely due to low prevalence, disease course
disease course with poor or no response to dopamine agonists, variances, lack of existing care networks and other factors.
monoamine oxidase inhibitors, and pyridoxine derivatives. Gene Methods: Taylor’s Tale, a CLN1 disease patient advocacy
therapy is a promising new treatment. Clinical studies of group, in collaboration with several international advocacy
intraputaminal infusion of engineered adeno-associated virus group partners, funded and managed an initiative to develop
type 2 vectors have demonstrated acceptable safety and tolerabil- consensus CLN1 disease clinical care strategies. The group
ity and improved motor milestones and cognitive symptoms. conducted a survey of families and clinicians with CLN1
Conclusions: Success of gene therapy in AADC deficiency will experience, then hosted an international multidisciplinary
depend on timely diagnosis to facilitate treatment before onset advisory board to identify and discuss family experiences, care
of irreversible neurologic damage. Screening for the 3-O-methyl- priorities and approaches to advance consensus on key com-
dopa biomarker in dried blood spots may enable early diagnosis. ponents of effective CLN1 disease clinical care.
Keywords: Rare Diseases, Genetics, Movement Disorders Results: In May 2019, Taylor’s Tale collects more than
35 family surveys and convened 15 clinicians and subject
214. An Observational Study of Outcomes of Allogeneic matter experts from seven countries for a meeting to discuss
Hematopoietic Stem Cell Transplant in Patients with management strategies for CLN1 disease. Represented areas
Cerebral Adrenoleukodystrophy (CALD) included neurology, neuropsychology, ophthalmology, physi-
Kenney-Jung D (Minneapolis, MN), Boelens JJ, Chiesa R, cal therapy, palliative care and patient advocacy, and the fam-
Duncan C, Jones S, Kapoor N, Kühl J-S, Lindemans C, ily survey results informed areas of focus for the meeting.
Prasad V, Shamir E, Chin W, McNeil E, Orchard P Meeting participants developed consensus around approaches
Objective: Cerebral adrenoleukodystrophy (CALD) is char- to symptom management and family-prioritized aspects of
acterized by inflammatory demyelination leading to progres- disease.
sive loss of neurologic function and death. Allogeneic Conclusions: This advocacy-driven effort was highly success-
hematopoietic stem cell transplantation (allo-HSCT) can halt ful in providing novel, unique insights to advance clinical
disease progression, if performed early. Here, we aim to bet- care in CLN1 disease. It can serve as a model for advocacy
ter understand outcomes of allo-HSCT in CALD. and family groups worldwide to partner with clinicians and
Methods: ALD-103 is an ongoing observational study designed clinical researchers to help advance care for rare diseases.
to evaluate outcomes in patients with CALD ≤17 years old Keywords: Rare Diseases
who received allo-HSCT. Retrospective data (patients receiving
transplants January 2013 or later) are collected, or patients are 216. A Multi-Center, Multi-National Retrospective and
followed prospectively, for 4 years after their last allo-HSCT. Prospective Natural History Study of Canavan Disease
Assessments include survival free of major functional disabilities Lau H (New York, NY), Shaywitz A, Kirby K, Balser J,
(MFD-free), and neurologic and safety evaluations. Eichler F, Bley A
Results: Of the 41 patients enrolled as of April 2018, 25 had
Objective: Canavan Disease (CD) is a rare, autosomal reces-
early cerebral disease (baseline Neurologic Function Score≤1,
Loes score≤9, and Loes score≥0.5 or gadolinium enhancement sive, leukodystrophy caused by aspartoacylase deficiency, lead-
on MRI); median follow-up time was 18.2 months (min-max, ing to brain accumulation of its substrate N-acetylaspartic acid
0.9-49.2). Generally, neurologic disease progression stabilized (NAA) and severe impairment of psychomotor development.
post-transplantation. Month 24 MFD-free survival was 80% CD progression can be most pronounced in the earliest months
(12/15 evaluable patients). Graft rejection requiring a second of life. There is a paucity of longitudinally collected data from
transplant occurred in 5 patients (20%), all without a matched CD patients and no approved therapies for CD exist. Advanc-
sibling donor (MSD). Five patients (20%), 2 of which had an ing the understanding of CD and facilitating the development
MSD, experienced acute Grade≥2 or chronic graft-versus-host of therapeutic options requires a comprehensive, precise delin-
disease. One-year treatment-related mortality rate was 8%; all eation of CD natural history. Therefore, the objective of this
deaths occurred in patients without an MSD. As of January study is to rigorously collect data from CD patients, define
2019, a total of 47 patients have received allo-HSCT, and endpoints for interventional trials, and identify gaps in disease
updated data on the entire cohort will be presented. management across ranges of ages and disease severity.
Conclusions: Preliminary data suggest that while allo-HSCT is Methods: This multi-center natural history study will enroll
efficacious in halting disease progression in patients with early pediatric CD patients for prospective, longitudinal collection
cerebral disease, there are significant transplant-associated risks. of clinical data using standardized instruments and intervals on
Keywords: Rare Diseases, Demyelinating Disorders an observational basis and for retrospective collection of medi-
cal record data. As most classic CD patients do not obtain the
215. Patient Advocacy Leadership in Advancing Clinical ability to sit up, infant early development scales were chosen.
Recommendations in Ultra-Rare Disease: The CLN1 Gross and fine motor development, cognitive development,
Batten Disease Experience quality of life, and general and disease-specific symptoms will
King S (Charlotte, NC), Frazier M be assessed. Beyond milestones, symptom occurrence will be

Program and Abstracts, Child Neurology Society S139

extracted from medical records and assessed prospectively to Lundborg diseases. One child with DRPLA was reported to
populate a CD-specific disease scale. Quantitative brain imag- respond to PER with decreased myoclonus and seizures and
ing modalities will measure structure, morphology, and NAA. improved neurological function. We are reporting PER’s
Results: Demography and enrollment status will be presented. effect in two patients with severe DRPLA.
Conclusions: The CD natural history study is enrolling and Methods: Two patients diagnosed with DRPLA were
expected to continue for 3 years. The natural history database treated with PER as adjunctive therapy. Medical charts were
will be available for meaningful research towards treatment of reviewed and caretakers interviewed to confirm clinical
CD patients. characteristics and symptoms. Family reports and examina-
Keywords: Rare Diseases, Demyelinating Disorders tion were used to assess response to treatment and side
effects.
217. Improved Myoclonus and Seizure Control and Results: Before starting PER both patients had severe myoc-
Dramatic Improvement of Neurological Function in lonus, GTC seizures, and were non-ambulating and non-
Patients with Dentatorubral Pallidoluysian Atrophy verbal with limited environmental interaction. (Table 1.)
(DRPLA) Treated with Perampanel Both patients had improved myoclonus, ambulation, and
Zook-Lewis C (Chapel Hill, NC), Greenwood R, Shiloh- dramatic improvement in language, communication and
Malawsky Y interaction. (Table 2.) All benefits were maintained for over a
year of follow-up.
Objective: Dentatorubral pallidoluysian atrophy (DRPLA) is
Conclusions: We report two patients with DRPLA who had
an autosomal dominant form of progressive myoclonic epi-
improved myoclonus and motor ability and striking improve-
lepsy (PME) caused by excessive CAG trinucleotide repeats
ment in language and communication following PER treat-
in ATN1 gene. Neurological manifestations are progressive
ment. We suggest that PER should be considered in patients
ataxia, myoclonus, epilepsy, and dementia. Treatment is
with DRPLA. Larger clinical trials and study of underlying
symptomatic with no disease modifying interventions. Case
mechanisms will be important to confirm and further under-
reports and open-label studies suggest perampanel (PER), a
stand PER’s effect on symptoms and disease progression.
noncompetitive antagonist of AMPA receptor, may be effec-
tive in reducing seizures and myoclonus in patients with Keywords: Rare Diseases, Translational/Experimental Thera-
other forms of PME, such as Lafora and Unverricht- peutics, Epilepsy

TABLE 1. Patient characteristics. Abstract 217

Patient #1 Patient #2

Current age 13y 7m 21y 11m

Gender Male Female
CAG repeats 74 69
Function and development prior to Normal development until age 4 then Mild cognitive impairment, at age of 9
DRPLA symptoms onset had regression. years was functioning at a second-grade
Diagnosed in preschool with autism level, could write, play soccer, and
spectrum disorder and ADHD. participated in gymnastics/cheerleading
Special education classroom, never able
to read, write, or identify numbers
Age DRPLA diagnosis (yrs) 9 11
Age of first seizure (yrs) 7 7
Age of DRPLA symptoms onset (yrs) 7 10
Age of myoclonus onset (yrs) 7 10
Age of becoming wheelchair bound (yrs) 11 15
Age return to diaper use (yrs) 10 16
Age of starting gastric-tube nutrition (yrs) 12 16
Age of loss of expressive language (yrs) 11 15

S140 Annals of Neurology Vol 86 (suppl 23) 2019

 TABLE 2. Perampanel treatment. Abstract 217
Pt #1 Pt #2

Current Age 13y 7m 21y 11m

Gender Male Female
Duration of 15 months 16 months
PER treatment
Concomitant clobazam, divalproex,
AEDs levetiracetam, lamotrigine,
zonisamide levetiracetam
PER maximal 8 10
dose (mg)
Side effects Irritability initially, Drowsiness, resolved
later resolved with lower dose
Prior to PER: After PER: Prior to PER: After PER:
Myoclonus frequent improved frequent resolved
Tonic-clonic several per month Improvement, with acute rare none
seizures illness only
Language Non-verbal for 2.5 Speaking in two word Non-verbal for 7 Speaking in short phrases
years phrases years
Communication minimal Communicating his wishes minimal Communicating her wishes
(e.g. requesting specific (e.g. refusing tube feeds,
cartoons, “Happy Feet”) requesting specific food to eat)
Oral feeds none none none Drinking and Eating solids
Ambulation none Ambulating with assistance none Ambulating with assistance

218. Deflazacort or Prednisone Treatment for Duchenne was lower by 6.9kg and height was lower by 6.2cm; %
Muscular Dystrophy (DMD): Real-world Outcomes at lean body mass was higher by 4.4%. No significant differ-
Cincinnati Children’s Hospital Medical Center ence was observed in whole-body bone mineral density or
(CCHMC) in left ventricular ejection fraction. In Kaplan-Meier ana-
Marden J (Boston, MA), Santos C, Schilling T, Freimark J, lyses, by age 15 (age 20), 56.4% (85.1%) of prednisone-
Yao Z, Signorovitch J, Tian C, Wong B initiated patients used a wheelchair as their primary means
Objective: This study assessed real-world data for deflazacort of mobility, compared to 43.7% (78.7%) of deflazacort-
or prednisone steroid treatment, and ambulatory, pulmonary, initiated patients (P<0.01). By age 15 (20), 13.7%
cardiac, growth and bone-health outcomes. (64.8%) of prednisone-initiated patients had scoliosis com-
Methods: Over 200 boys at CCHMC were included in the pared to 8.9% (33.7%) of deflazacort-initiated patients
analysis. About 75% received deflazacort (~95% daily) and (P=0.05). These differences persisted after adjusting for age
13% prednisone (~75% daily). The remaining 12% switched at steroid initiation. In sensitivity analyses, risk of scoliosis
from prednisone to deflazacort (average duration 3.1 years on and wheelchair use among switchers was numerically lower
prednisone and 2.5 years on deflazacort). vs consistent prednisone but higher versus consistent
Results: On average, after accounting for age and steroid deflazacort.
duration in a regression model, patients on deflazacort Conclusions: This study adds evidence associating
compared with prednisone had: 0.59 stairs/second greater deflazacort use with greater functional preservation relative to
4-stair climb velocity, 4.6 points higher North Star Ambu- prednisone, and further indicates concurrent preservation of
latory Assessment total score and 9.9% higher forced vital lean body mass and delay of scoliosis.
capacity %-predicted (P<0.05 for each). Total body mass Keywords: Rare Diseases, Neuromuscular Disorders

Program and Abstracts, Child Neurology Society S141

219. Progression of Cervical Stenosis in Children Treated
with Stem Cell Transplant for Mucopolysaccharidosis
Type 1
Mathias S (Minneapolis, MN), Gupta A, Orchard P, Kenney-
Jung D
Objective: Mucopolysaccharidosis type 1 (MPS1) is a multi-
system disorder associated with mutations in alpha-L-
iduronasase, resulting in the inability to break down glycos-
aminoglycan molecules with deposition at multiple sites.
Among the comorbidities of MPS1 is progressive cervical ste-
nosis (CS), associated with capping of the odontoid process
(OC). Hematopoeitic stem cell transplant (HSCT) can
improve the trajectory of MPS1; however, the effects of
HSCT on progression of CS are not yet clear. FIGURE 1: Abstract 220 [Color figure can be viewed at www.
Methods: We retrospectively investigated a cohort of wileyonlinelibrary.com]
43 patients with MPS1 who had undergone HSCT between
January 2008 and July 2017 and who underwent at least one
cervical spine MRI pre and post HSCT. Radiological reports 9.86 years). In total, 31 patients completed the trial.
were reviewed to determine the presence and severity of CS Over the 6 – 14 months’ observation period, NPCCSS
and OC (both as rated by the clinical radiologist as mild, showed progression (increased values) in 22 patients,
moderate or severe). Transplant outcomes were identified 3 patients had an indication of a better function (lower
as well. values), and 7 patients were stable. The total NPCCSS
Results: Median age was 1.2 years at the time of transplant. score showed a mean increase of 2.7 (SD=4.0) with a
Of 28 patients who had undergone cervical spine MRI prior mean rate of change of 1.47/6 months (SD=2.25). The
to HSCT, 10 did not have CS and only 4 (14%) had CS in 5-domain NPCCSS score showed a mean increase of
the moderate or severe categories. All patients had some 1.4 (SD=2.9) with a mean rate of change of
degree of OC, with 2 (7%) in the moderate or severe catego- 0.75/6 months (SD=1.58). The biomarker levels of
ries. Among those who had prior MRI (median age 1.1 years), HSP70 was dramatically decreased in white blood cells
11 had at least a 6-year follow up with yearly MRIs. CS was compared to healthy controls.
eventually noted in all patients, with majority (64%) in the Conclusions: Progression rates from this observational study
moderate or severe categories. were comparable to previously reported studies (Yanjanin
Conclusions: These data suggest that while the phenotype 2010; Ory 2017). Interestingly, HSP70 levels were very low
for MPS1 is substantially ameliorated by SCT, continued in NPC patients.
periodic monitoring for CS is warranted. Keywords: Rare Diseases
Keywords: Rare Diseases, Genetics

220. Clinical and Biomarker Results from an 221. From Bench to Bedside: Gene Therapy for Batten
Observational Trial in Niemann Pick Type C Patients (CLN6) Disease
Mengel E (Mainz, Germany), Bembi B, Del Toro M, Meyer K (Columbus, OH), Timm D, White K, Cain J, Denny-
Deodarto F, Gautschi M, Giraldo P, Grunewald S, Grønborg S, Rivers C, Rinaldi F, Motti D, Corcoran S, Weimer J, Kaspar B,
Heron B, Maier E, Roubertie A, Santra S, Tylki-Szymanska A, Likhite S, de los Reyes E
Ingemann L, i Dali C Objective: Currently, there is no cure or therapeutic treat-
Objective: Niemann Pick Type C (NPC) is a rare, lysosomal ment for CLN6-Batten disease, a rare neurodegenerative lyso-
storage disorder caused by mutations of the NPC1 or 2 pro- somal storage disorder. Mutations in the neuronal ceroid-
tein. Systemic and neurological symptoms are progressive and lipofuscinosis 6 (CLN6) gene mainly affect children with loss
lead to death. To understand disease progression and investi- of visual and motor functions, leading to death within the
gate possible new biomarkers, a prospective multi-center first 15 years of life. Mutations cause absence or reduced
observational trial in NPC patients was conducted. abundance of CLN6 protein, making gene therapy a promis-
Methods: Diagnosed NPC patients, age: 2-18 years, who ing therapeutic strategy. Our objective was to develop a gene
had at least one neurological symptom and the ability to walk therapy vector (AAV9.CLN6) that was administered by a sin-
with assistance were eligible. Patients were maintained on gle, postnatal intracerebroventricular injection in
routine clinical care. NPC-severity score (NPCCSS), an CLN6 mice.
abbreviated 5-domain NPCCSS (ambulation, fine motor Methods: CLN6 Mice were assessed for histopathological,
skills, speech, swallowing, cognition) and biomarkers were behavioral and survival changes. To further translate this
assessed at baseline and end of trial to observe the natural dis- approach towards clinic, we dosed three 4-year old
ease course. Cynomolgus Macaques with AAV9.CLN6 by intrathecal
Results: 36 patients (30 on miglustat) were enrolled across lumbar injection and monitored them for up to 6 months
7 European countries; 21 females and 15 males (mean age post injection.

S142 Annals of Neurology Vol 86 (suppl 23) 2019

Results: The treatment resulted in drastic reduction of auto- 223. A Study to Assess the Inter- and Intra-rater
fluorescent storage material accumulation and other hall- Reliability of the 5-Domain NPCCSS
marks of the disease. The treatment significantly improved Patterson M (Rochester, MN), i Dali C, Symonds T,
motor performance, learning and memory. Importantly, Guldberg C, Hudgens S, Mengel E
while all untreated CLN6 mice died between 12-14 months Objective: Niemann Pick Type C (NPC) is a rare, genetic,
of age, AAV9.CLN6 administration significantly extended fatal, lysosomal storage disorder. Most patients present
the median survival beyond 22 months of age. To our between early childhood and adolescences with signs of neu-
knowledge, this is the longest survival extension reported in rological impairment. The NPC Clinical Severity Scale
this mouse model to date. In the macaques, no adverse effects (NPCCSS) is a clinician reported measure of 17 domains,
or pathology were observed, while high levels of transgene designed to measure disease severity and progression
expression were found throughout the brain and spinal cord (Yanjanin 2010). The 5-domain NPCCSS represents an
in animals. abbreviated version assessing the clinically most relevant
Conclusions: Collectively, this study provided a strong foun- symptoms: Ambulation, Fine Motor Skills, Swallowing, Cog-
dation for the currently ongoing first in-human phase I clini- nition, and Speech (Fig 1). The abbreviated scale is highly
cal trial for intrathecal administration of scAAV9.CB.CLN6 correlated with the full-length NPCCSS. This study was con-
in CLN6-Batten disease patients. ducted to evaluate the reliability of the 5-domain NPCCSS.
Keywords: Rare Diseases, Translational/Experimental Thera- Methods: Using the 5-domain NPCCSS, 14 clinicians were
peutics, Genetics asked to score four videos of children with NPC representing
different disease severities and ages. A repeat assessment
occurred after a 3-week interval with videos presented in ran-
222. The Clinical Features, Investigation, Genetic Profiles dom order. Inter- and intra-rater reliability was assessed using
and Management of Pediatric Hereditary Spastic Intra-Class Correlation (ICC) coefficients (score level) and
Paraplegia kappa statistics (item level) at a 0.70 acceptability criteria
Palanisamy D (Cleveland, OH), Moodley M threshold. The interaction between clinician, video, and item
Objective: Hereditary Spastic Paraplegia (HSP) is a rare was evaluated by a many-FACETs analysis.
genetically and clinically heterogeneous disease of the central Results: The ICC for the total score of the 5-domain
nervous system that often mimics cerebral palsy. We describe NPCCSS was very high for the intra-rater (within clinician;
one of the largest series of pediatric patients with (HSP) and ICC=0.937) and inter-rater (between clinician; ICC=0.995)
highlight significant clinical and genetic aspects of analysis. Item-level agreement was acceptable for all items
pediatric HSP. (kappa range 0.68-0.95). The FACETS analysis indicated
Methods: Retrospective chart review of all children < 18 years strong agreement among the clinicians (57.3% exact agree-
seen at the Cleveland Clinic between 2002-2018 who met ment; 0.87 correlation across ratings).
clinical criteria of HSP. Information gathered included
patients demography, presenting symptoms, family history,
clinical features, investigation, management and outcome.
Results: 14 patients fulfilled the clinical criteria of HSP.
Birth history was noncontributory to symptom onset and
development. All symptomatic patients exhibited convinc-
ing upper motor neuron (UMN) signs. The most consis-
tent UMN signs included bilateral lower limb spasticity,
brisk lower limb DTR’s; bilateral ankle clonus and bilat-
eral extensor plantar responses. Investigations revealed pos-
itive genetic tests in 10 of the 14 patients with 50% of
the cohort presenting with a SPG4 mutation and age of
onset varying from 6 months to 14 months with two
remaining asymptomatic. Concurrent gene mutations were
detected in 3 patients, while one patient had a mitochon-
drial gene variant.
Conclusions: Spastic Paraplegia is a relatively common prob-
lem in pediatric neurology, most due to acquired brain disor-
ders and presenting as cerebral palsy. In a minority of
patients the cause is HSP highlighting the need for pediatri-
cians to recognize this entity so that appropriate treatment
can be provided to this group of patients. It is also important
to recognize that mitochondrial disease may also present as a
HSP like illness.
Keywords: Rare Diseases, Genetics, Neuromuscular FIGURE 1: 5-domain NPC Severity Scale. Abstract 223 [Color
Disorders figure can be viewed at www.wileyonlinelibrary.com]

Program and Abstracts, Child Neurology Society S143

Conclusions: This study confirms that clinicians are able to Methods: Cerliponase alfa was dosed based on age (subjects
rate patients similarly and consistently over time and that the ≤2 years receive under 300 mg). Safety was assessed by
5-domain NPCCSS is useful for assessing NPC disease pro- adverse events (AEs); efficacy was assessed by change in
gression in a clinical trial setting. motor-language (ML) score (ranging from 0 to 6, with 0 rep-
Keywords: Rare Diseases resenting no function and 3 representing normal function in
each domain). One subject with uninterpretable language
224. Clinical and Neuroimaging Features of Labrune function was excluded from ML score evaluation.
Syndrome (Leukoencephalopathy with Calcifications and Results: 11 subjects (7 female, 4 male; mean (SD) age 3.5
Cysts)
(1.3) years), including 5 aged ≤3 years at baseline, enrolled.
Rhee J (Washington, DC), Whitehead M, Fraser J, Tochen L
Mean baseline ML score was 4.6 (SD=1.4). Subjects received a
Objective: Leukoencephalopathy with calcifications and cysts mean (SD) of 67 (32.5) weeks of cerliponase alfa (range
(LCC), also known as Labrune Syndrome, is a recently 42-114). Common AEs included seizure, pyrexia, upper respi-
described leukodystrophy that is associated with biallelic muta- ratory tract infection, and vomiting. Nine (82%) subjects
tions in the SNORD118 gene. In this case series, we describe experienced ≥1 serious AE with pyrexia the most frequently
the neurological symptoms and neuroimaging findings of three reported. ML score from baseline to last visit was unchanged
patients to illustrate the variability in presentation for LCC. in 7 (70%) subjects; 2 (20%) subjects had a 1-point gain and
Methods: Subjects gave informed consent for participation 1 (10%) had a 1-point loss. One subject with uninterpretable
in natural history and biorepository data collection through language function had no change in motor score.
the ongoing Myelin Disorders Biorepository Project. Retro- Conclusions: ICV-administered cerliponase alfa, including in
spective data for individuals with LCC were collected children ≤3 years old, has acceptable safety and a similar effi-
through family survey and chart review. cacy profile to prior studies.
Results: Three subjects met clinical or radiologic criteria for Keywords: Rare Diseases
LCC. All three had seizures: one had an isolated febrile seizure,
one had infantile-onset seizures that resolved, and one had
childhood-onset epilepsy requiring ongoing treatment. All sub- 226. Suicide Screening in Sturge-Weber syndrome Versus
jects had motor dysfunction: 2/3 subjects had spasticity or pyra- General Neurology Clinic
midal signs, 1/3 patients had prominent dystonia, and 2/3 Sebold A (Baltimore, MD), Ahmed A, Ryan T, Comi A,
subjects had cerebellar ataxia. One subject had elevated intracra- Rybczynski S
nial pressure that required shunting. All subjects had some
degree of neurocognitive involvement. On MRI, all subjects Objective: We aimed to determine clinical factors associated
had diffuse and confluent white matter changes, cortical and with suicide risk in Sturge-Weber syndrome (SWS). Suicidal
subcortical cystic changes but of varying location and size, and thoughts or attempts occur in about 16% of high
calcifications within the bilateral basal ganglia and thalami. Two schoolers,15-10% of adults,2and in females > males. SWS is
subjects also had unilateral cerebellar hemisphere/peduncle calci- associated with epilepsy, glaucoma, cognitive impairments,
fication. All subjects displayed peripheral enhancement of some, and a port wine birthmark.3 Little is known about suicidal
but not all, cystic lesions. One subject had midline shift. ideation and attempts in SWS patients.
Conclusions: LCC presents with diverse neurological symp- Methods: 34 consented subjects with SWS brain involve-
toms including spasticity, ataxia, dystonia, seizures, hydro- ment (19 females, 21 children, median age 16 years, range
cephalus, and neurocognitive changes. Cortical cysts, 8-47 years) seen by neurology (08/2017- 11/2018), com-
calcifications, and white matter changes can be present to pleted either the Ask Suicide-Screening Questions4(8-17
varying degrees. Precise genotype-phenotype and MRI- years) or the Ask Suicide-Screening Questions to Everyone in
clinical phenotype correlations will be further delineated. Medical Settings5(≥18 years) during triage. This data was
Keywords: Rare Diseases, Neuroimaging, Genetics compared to screening data from the remaining neurology
clinics (n=369, 125 female, 258 children; median age
14 years, range 8-78 years). SWS data studied included SWS
225. Cerliponase Alfa for the Treatment of CLN2 Disease
involvement, comorbidities, and medications.
in an Expanded Patient Cohort Including Children
Results: 6 of 34 SWS patients (17.6%, 2 female, 3 children<
Younger than Three Years: Interim Results from an
18 years, 3 adults) screened positive for suicide risk compared
Ongoing Clinical Study
to 7% of neurology patients (27/369, p<0.05). Positive
Schulz A (Hamburg, Germany), de los Reyes, E, Specchio N,
screens were particularly higher in SWS males (4/15; 27%)
Gissen P, Cahan H, Slasor P, Ajayi T
versus neurology clinic males (15/244; 6%, p<0.05). SWS
Objective: Open-label studies have demonstrated that intra- positive screening was associated with SSRI use (p<0.05); one
cerebroventricular (ICV) infusion of 300 mg cerliponase alfa case pre-dated hospitalization for an attempt. A trend
(rhTPP1) every two weeks for 96 weeks slowed deterioration suggested that SWS patients with cognitive impairment may
in motor and language function in patients with CLN2 dis- be lesslikely to have a history of suicide related behav-
ease, a rare, inherited, neurodegenerative lysosomal storage iors (p=0.07).
disorder. This study (NCT02678689) assesses safety and effi- Conclusions: Suicidal thoughts and attempts are impor-
cacy of cerliponase alfa in an expanded cohort including chil- tant issues in SWS. Males and those who are relatively
dren ≤3 years old. cognitively intact may be particularly vulnerable. Use of

S144 Annals of Neurology Vol 86 (suppl 23) 2019

SSRIs was associated with suicide risk. More research is challenging diagnosis because of its non-specific early presen-
needed. tation. A high index of clinical suspicion, targeted investiga-
Keywords: Rare Diseases, Epilepsy, Cognitive/Behavioral tive approach, attention to biomarkers like isolated AST
Disorders elevation, and combination genetic tests offers an efficient
access to an otherwise elusive diagnosis. Long term natural
227. Diagnosing and Managing A Rare Case of history, potential biochemical markers, clinical trials and effi-
Late-infantile GM1-Gangliosidosis: A Case Report cacy data is underway. Such clinical trials are essential in rare
Shekar S (New Brunswick, NJ), Brooks S, Jarnes J, Venkat A disorders for early diagnosis, treatment interventions and dis-
ease stabilization.
Objective: We present a rare diagnosis of late-infantile Keywords: Rare Diseases, Genetics, Translational/Experi-
GM1-Gangliosidosis, a lysosomal storage disease with less mental Therapeutics
than 50 reported cases
Methods: 34 month old presented with developmental
228. Wearable Sensors Detect Impaired Balance and
regression, poor ambulation and autistic regression. Exam
Coordination in LBSL During Remote, Home-Based
was consistent with progressive encephalopathy. Stepwise
Assessments
diagnostic approach to the workup of developmental delay
Smith Fine A (Baltimore, MD), Kaufman M, Keller J,
was performed.
Joseph C, Goodman J, Bastian A, Fatemi A
Results: Karyotype revealed an apparently balanced transloca-
tion between chromosome 1 and 11. In addition, there was Objective: The objective is to identify neuromotor bio-
uniparental isodisomy of chromosome 3. WES identified markers that can detect disease severity in the disease leu-
homozygosity for p.R590H, c.1769G> A in GLB1 located koencephalopathy with brainstem and spinal cord
on chromosome 3. Leukocyte GM1 beta galactosidase activ- involvement and lactate elevation (LBSL). LBSL is a rare,
ity was 0. These findings confirmed the diagnosis of late neurologic disorder with motor impairment due to biallelic
infantile GM1 gangliosidosis. MRI brain at 35 months of age mutations in DARS2, which encodes mitochondrial aspartyl
was normal except for delayed terminal zones of myelination; tRNA synthetase. There are white matter changes in the cor-
follow up at 50 months reveals mild white matter signal tex, cerebellum, pyramidal tracts and dorsal columns,
abnormality posteriorly (Graphic 1). Elevated AST levels resulting in ataxia and spasticity. There are no targeted thera-
noted. EEG confirmed hypomotor seizures at 48 months. pies for LBSL.
She has odontoid hypoplasia with no other skeletal changes. Methods: The study design uses wearable sensors and web-
There was no retinal change, organomegaly or cardiac based clinical scales to quantitatively assess gait and postural
involvement. Patient enrolled in an observational clinical sway in LBSL and control participants’ homes through video
trial. conferencing (e.g. 2-Minute Walk Test, Sway Tests on a firm
Conclusions: Majority of lysosomal disorders have a neuro- surface). We previously demonstrated that wearable sensor
degenerative course with variable clinical presentations data obtained using the OPAL™ system is well-validated
(Graphic 2). Late infantile GM1 gangliosidosis is a against gold standard measures.
Results: There is good reliability of remotely collected gait
(intra-class correlation coefficient 0.86-0.99) and sway mea-
sures (intra-class correlation coefficient 0.53-0.96). LBSL par-
ticipants have a slower stride velocity (1.01 vs. 1.13 m/s) and
shorter stride length (1.0 vs. 1.13 m) than their counterparts.
Lateral step variability, which indicates a wider walking base,
is increased for LBSL patients (4.1 vs. 5.8cm). During stance
with the eyes closed or feet together, LBSL participants show
rapid accelerations and decelerations of body movement cov-
ering a large sway area. These variables correlate strongly with
the standardized assessment and rating of ataxia scale
(r=0.6-0.9).
Conclusions: Overall, the sensors are reliable and sensitive
for detecting balance impairment in LBSL patients, which
appears to relate to cerebellar and sensory ataxia.
Keywords: Rare Diseases, Genetics

229. Progression of Cerebral Lesion Patterns in Patients

with ACTA2 Arginine 179 Gene Mutation
FIGURE 1: MRI brain T2 axial flair image showing mild white Speroni S (Boston, MA), Lauer A, Laheji F, Regalado E,
matter signal abnormality affecting the periatrial white Smith E, Milewicz D, Caruso P, Musolino P
matter bilaterally and posterior frontal/parietal subcortical
white matter. Abstract 227 [Color figure can be viewed at Objective: ACTA2 Arg179 gene mutations causes smooth
www.wileyonlinelibrary.com] muscle multisystemic dysfunction syndrome including

Program and Abstracts, Child Neurology Society S145

 TABLE 1. Abstract 227
Lysosomal disorder Gene and Chromosomal Localization Enzyme deficiency

Mucopolysaccridosis
Hurler IDUA gene (4p16.3) α-l-iduronidase
Hunter IDS (Xq28) Iduronate-2-sulfatase
Sandfilippo A-SGSH (17q25.3) Heparan-N-sulfatase;
B-NAGLU (17q21.2) α NAG; Acetyl-CoA α- glucosaminide
C-HGSNAT(8p11.21) Acetyltransferase;
D- GNS (12q14.3) N-Acetylglucosamine 6-sulfatase
Morquio A / B A- GALNS (16q24.3) Galactose-6-sulfatase;
B-GLB1 (3p22.3) β-Galactosidase
Maroteaux-Lamy ARSB (5q14.1) Arylsulfatase-β
Sly GUSB (7q11.21) β-glucuronidase
Glycogen Storage Disorders
Pompe’s GAA (17q25.2-q25.3) Alpha-glucosidase
Glycoprotein Storage Disorders
Mucolipidosis type 1-3 MCOLN1 (19p13.2-13.3) α-N-acetylneuraminidase
Alpha-mannosidosis MAN2B1 (19cen-q12) N-acetylglucosamine-1-phosphotransferase
Oligosaccharidoses
Schindler’s disease NAGA (22q13.2) α NAGA
Alpha-fucosidosis FUCA1 (1q34) α-fucosidase
Sialidosis NEU1 (6p21.3) Sialidase
Aspartyl AGA (4q32-q33) AGA (aspartylglucosaminidase)
glucosaminuria
Sphingolipidoses
Niemann-Pick A&B NPC1/C1 (18q11-q12, 14q24.3) Acid Sphingomyelinase
Gaucher GBA (1q21) Glucocerebrosidase
Krabbe GALC (14q31) Galactosyl ceramidase
Fabry GLA (Xq22) α-galactosidase A
GM1 Gangliosidosis GLB1 (3q21.33) Β galactosidase,galactosamine-6
GM2: Tay Sachs, Sandhoff A/B Tay Sach’s (5q31.3-q33.1) Hexosaminidase A or B
Farber HEXA AB ( 15q23-q24 / 5q13) Ceramidase
Metachromatic LD ASAH (8p22-p21.3) Arylsulfatase A
ARSA (22q13.31-qter)
Lysosomal Transport Disorder Sialic SLC17A5 (6q14-q15)
Cystinosis
Sialic Acid Storage
-All Lysosomal disorders are AR except 3 that are X linked – Hunters, Fabry’s and Danon’s
-Protean clinical manifestations- coarse facial features, tone abnormalities, skeletal changes, cherry red spots, psychomotor regression, seizures, extra
pyramidal symptoms, organomegaly, cardiomyopathy and ataxia
MRI brain T2 axial flair image showing mild white matter signal abnormality affecting the periatrial white matter bilaterally and posterior front-
al/parietal subcortical white matter

cerebrovascular disease characterized by white matter hyper- Methods: N=83 cerebral MRI scans of 21 patients were eval-
intensities (WMH), arterial ischemic stroke (IS) and large ves- uated (p.Arg179Cys:p.Arg179His mutation= 5:6), follow up
sel steno-occlusive disease. Here we performed the first (FU) MRI in 81%, mean observation interval in years
SD:
systematic quantitative analysis of parenchymal and vascular 4.51
3.68). Scans were screened for IS and cystic white
lesions. matter lesions (CL). WMH were quantified on T2-/

S146 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 1: Left panel: Longitudinal data on white matter hyperintensities, numbers of cystic lesions (CL) and critical stenosis (CS).
Right panel: A) Representative FLAIR images to illustrate the range of white matter hyperintensities found in ACTA2 R179
patients, both patients are between 11-12y of age. B) Representative T2 weighted images of a 4.79 year old male and follow up
visit 10 years later indicating stable extension of white matter hyperintensities. C) Baseline and D) 2 year follow up FLAIR
sequences of the same ACTA2 R179 patient illustrating appearance of additional CL in the white matter (white arrows). E) and F)
representative magnifications of maximum intensity projections of time of flight angiographies of the same ACTA2 R179 patient
illustrating the appearance of new CS defined as intermittent signal loss following the vessels course (white arrows). Abstract
229 [Color figure can be viewed at www.wileyonlinelibrary.com]

FIGURE 2: Left panel: Maximum intensity projections of time of flight angiographies of three patients illustrating typical vessel
abnormalities associated with ACTA2 (R179) gene mutations with intermitted stenotic changes in vessel caliber and abnormal straight
course of the basal cerebral arteries. Right panel: A) White matter abnormalities typically found in patients with ACTA2 (R179) gene
mutations. B) Acute and chronic ischemic stroke lesions related to large artery occlusion. C) Cystic white matter lesion frequently found
in ACTA2 (R179) gene mutation patients. Arrow indicates angulation of the lesser forceps of the corpus callosum is increased. D) The
midbrain shows narrowing of the cerebral peduncles produced by straightening of the posterior cerebral arteries (PCA). Abstract 229

Program and Abstracts, Child Neurology Society S147

T2-FLAIR weighted imaging using planimetric methods. revealed low muscle tone, no spontaneous movement of the
Cerebral MR-angiographies were screened for presence of shoulder but some antigravity movements of elbow and
critical stenosis (CS). hands, no response to noxious stimuli, absent elbow reflexes,
Results: Vessel and acute and subacute white matter abnor- no joint/muscle tenderness. Otherwise normal physical exam
malities were detected in 5/6 patient’s imaging during noted. Normal/negative studies included: CRP, ESR, Lyme
infancy. Quantifiable WMH were present in all patients studies, serum CK, ganglioside antibodies, ANA, ANCA, sol-
>1.4 years and while their volumes did not significantly uble interleukin-2; and CSF routine analysis, Tourtellote,
change (baseline vs. FU median cc. [IQR]: 53.17 [38.23] and oligoclonal bands. X-rays of the arm were normal. MRI
vs. 43.78 [35.56]; p=0.96, n=11), the numbers of cystic of brain and full spine was normal. He was diagnosed with
lesions (baseline vs. FU, median no. [IQR]: 14 [8.75] INA and treated with high dose steroids with a taper. His
vs. 14 [23.25]; p=0.03, n=11) and CS (28.6%) increased weakness improved 80% in 1 month and almost 100% in
over time (Figure 1). Large artery IS were present in 42.9% 5 month follow up.
while dilatation of the distal carotid artery, straightening of Conclusions: INA in children has different presentation than
adults: less common shoulder pain and bilateral involvement,
vessels, narrowing of the cerebral peduncles the angle of the
milder presentation, faster recovery, and better prognosis.
corpus callosum forceps in 100% of non-infant patients
About 30 % of pediatric cases had a preceding viral URI.
(Figure 2).
Although less frequently performed in children, nerve con-
Conclusions: We found characteristic, quantifiable and pro-
duction studies/electromyography is the gold standard for
gressive cerebral lesion patterns in patients with ACTA2 Arg179
diagnosis. Even though INA is a rare disease, it should be
mutations. These metrics could potentially be used to evaluate
kept in the differential diagnosis for upper girdle weakness
and monitor outcomes for current and future treatments.
when laboratory studies and imaging are negative.
Keywords: Rare Diseases, Neuroimaging, Genetics
Keywords: Rare Diseases, Infections/Neuroimmunology,
Neuromuscular Disorders
230. Sudden Painless Right Arm Weakness in a 2 Year
Old Male-A Case Presentation and Literature Review 231. Safety and Improved Efficacy Outcomes in Children
Tunc E (Cleveland, OH), Hsich G, Adams J with AADC Deficiency Treated with AGIL-AADC Gene
Objective: Idiopathic Neuralgic Amyotrophy (INA) is a rare Therapy: Results from Three Clinical Trials
disorder that presents with upper extremity paresis with Hwu P W-L (Taipei, Taiwan), Chien Y-H, Lee N-C, Tseng S-
severe shoulder girdle pain. INA has been well described in H, Tai C-H, Conway A, Berner T, Pykett M
adults, but there are only limited case reports in children. Objective: To evaluate clinical outcomes in children with
Methods: Case Report aromatic l-amino acid decarboxylase (AADC) deficiency
Results: 2 year old previously healthy male, presented with treated with AGIL-AADC, a recombinant adeno-associated
sudden onset painless right arm weakness for 1 day following virus vector containing the human cDNA encoding the
an upper respiratory illness (URI). Parents denied any AADC enzyme. AADC deficiency, a rare genetic disorder of
trauma, fevers, weight loss. Physical exam of right arm neurotransmitter synthesis, is characterized by motor

FIGURE 1: Abstract 231 [Color figure can be viewed at www.wileyonlinelibrary.com]

S148 Annals of Neurology Vol 86 (suppl 23) 2019

developmental deficits and clinical features associated with
the autonomic nervous system, including dyskinesia,
oculogyric crisis, and feeding/swallowing problems.
Methods: In 3 open-label clinical studies, children with
AADC deficiency who had no full head control and no ability
to sit, stand, or walk received AGIL-AADC as bilateral,
intraputaminal, stereotactic infusions during a single operative
session (total dose, 1.8x1011vg). Body weight, oculogyric crisis
episodes, and adverse events (AEs) were recorded.
Results: In the 3 studies, patients aged 21 months to 8.5 years
(N=26) received AGIL-AADC, constituting the safety popula-
tion. In the intent-to-treat population (N=21), mean body
weight at baseline was 12.0 kg (median 10.5 kg) and increased
to 15.2 kg (median 13.2 kg) at 12 months posttreatment. Fre-
quency of oculogyric crises was improved at 12 months post-
treatment. Dyskinesia was recorded as an AE in 23 patients in
the safety population; most events were mild or moderate,
occurred within 3 months after AGIL-AADC treatment, and
resolved in all patients by 10 months (Figure).
Conclusions: In children with AADC deficiency who
received AGIL-AADC gene therapy, body weight increased
and oculogyric crises and dyskinesia improved. FIGURE 1: Patient 1 at 10 months old. MRI Brain without
Keywords: Rare Diseases, Movement Disorders, Trans- contrast, sagittal T1-weighted image. Abstract 232
lational/Experimental Therapeutics

232. Two Novel RARS2 Mutations in Two Siblings with the differential diagnosis in infants with early epileptic
Pontocerebellar Hypoplasia Type 6 Presenting as Early encephalopathy or infantile spasms. RARS2may not be
included on genetic epilepsy panels; therefore, PCH6 as a
Epileptic Encephalopathy
cause of epileptic encephalopathy may be missed.
Xiao W (New York, NY), Anstett K, Pappas J,
Keywords: Rare Diseases, Genetics, Epilepsy
Bluvstein J, Lau H
Objective: Pontocerebellar hypoplasia type 6 (PCH6) is a 233. Evolution of Radiographic Abnormalities
rare autosomal recessive genetic disorder characterized by Distinguishes Isolated Sulfite Oxidase Deficiency and
developmental regression, encephalopathy, and intractable Molybdenum Cofactor Deficiency from Neonatal
epilepsy. PCH6 is caused by mutations in RARS2, and has Hypoxic Ischemic Encephalopathy
been reported in 29 patients. Here, we describe two siblings Misko A (Boston, MA), Buch K, Musolino P, Confer N,
with early epileptic encephalopathy found to have two novel Eichler F, Caruso P
mutations in RARS2.
Methods: A retrospective chart review of both patients and Objective: To delineate the evolution of brain MRI abnor-
literature review were conducted. Trio whole exome sequenc- malities in isolated sulfite oxidase deficiency (ISOD) and
ing was performed on patient 1 at a commercial, CLIA- molybdenum cofactor deficiency (MoCD) and discern fea-
approved laboratory. Variants identified on next generation tures that distinguish them from neonatal hypoxic ischemic
sequencing were confirmed by Sanger sequencing. Targeted encephalopathy (HIE). Differentiation is critical now thatas
variant analysis of the RARS2gene was conducted in patient substrate replacement therapy with cyclic pyraryanopterin
2 at the same laboratory. A 21 channel video- monophosphate substitution therapyis under development
electroencephalogram recording using the 10-20 system was for MoCD TypeA, an effective treatment for MoCD typeA,
performed utilizing the NicOne System. is widely available.
Results: Both patients presented in early infancy with a burst Methods: MRI studies from 15 consented patients with
suppression pattern on electroencephalogram, which evolved early onset ISOD and MoCD were obtained through Ori-
into infantile spasms with hypsarrhythmia, eventually leading to gin Biosciences and analyzed. To overcome limited avail-
refractory epilepsy. Both patients were homozygous for a com- ability of longitudinal imaging, studies were compiled and
plex RARS2 allele with two novel variants, c.296A>C (p.K99T) ordered by amount of time between symptom onset and
and c.251G>C (p.G84A). The proband initially had generalized imaging.
cerebral atrophy, and later demonstrated disproportionate cere- Results: Radiographic abnormalities in typical cases of ISOD
bellar atrophy. In patient 2, brain MRI at age 3 already demon- and MoCD mimicked features of neonatal HIE with a simi-
strated cerebellar atrophy. Both children were severely globally lar time course of evolution, which allowed categorization of
delayed and required gastrostomy tube feedings. studies into acute (0-7 days), subacute (8-29 days) and
Conclusions: These cases contribute to the genotypic and chronic (>30 days) phases. Abnormalities consistent with crit-
phenotypic spectrum of PCH6. PCH6 should be included in ical energy failure and excitotoxicity were frequent in the

Program and Abstracts, Child Neurology Society S149

forebrain and midbrain with relative sparring of the hind- Conclusions: Spatial and temporal characteristics of brain
brain and cerebellum. Diffusion restriction was prominent MRI abnormalities in ISOD and MoCD are largely congru-
throughout the forebrain and persisted through the chronic ent with neonatal HIE; however, persistent diffusion restric-
period suggesting an ongoing disease process. In the chronic tion and evidence of prenatal brain injury are useful
phase, catastrophic atrophy of the forebrain juxtaposed discriminators. Radiographic discriminators that can guide
milder volume loss in the brainstem and cerebellum. One treatment before irreversible damage occurs are still needed.
patient had evidence of prenatal brain injury at birth. Keywords: Rare Diseases, Neuroimaging

FIGURE 1: Evolution of brain MRI abnormalities in typical cases suggests widespread, persistent energy failure and excitotoxicity
in the forebrain. Abstract 233 [Color figure can be viewed at www.wileyonlinelibrary.com]

S150 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 2: The midbrain, hindbrain and cerebellum are relatively preserved in the acute phase of disease with subsequent
development of cerebellar volume loss and brainstem atrophy secondary to Wallerian degeneration. Abstract 233 [Color figure
can be viewed at www.wileyonlinelibrary.com]

234. Cross Sectional Observations on the Natural History brief assessment of motor function (BAMF), gross motor
of Mucolipidosis Type IV Reveal Extrapyramidal Signs function classification system (GMFCS), modified Ashworth
and Progressive Pyschomotor Decline scale, and Burke-Fahn-Marsden (BFM) dystonia rating scales
Misko A (Boston, MA), Oberman R, Haxton L, Schiffmann R, were applied. Parents were also interviewed with the Oregon
Raas-Rothschild A, Eichler F Project developmental checklist.
Objective: To gain insights on the natural history of Results: Of the 26 patients, 7 presented with atypical milder
mucolipidosis type IV (MLIV) that would inform future clin- symptoms and were analyzed separately. Among the 19 typical
ical trial design. patients, GMFCS and BAMF illustrated functional decline with
Methods: We travelled across the US and Israel to enroll age in gross and fine motor function (Fig. 1). Using the Oregon
26 patients with a confirmed diagnosis of MLIV into our Project checklist, we established age thresholds beyond which
IRB approved natural history study. Each underwent a full regression occurred in several domains (Fig. 2). While hyperto-
neurological examination by a pediatric neurologist and the nicity and spasticity increased with age, we also found prominent

Program and Abstracts, Child Neurology Society S151

FIGURE 1: BAMF and GMFCS scores illustrate motor decline in a cross-sectional analysis of patients with MLIV. Abstract 234
[Color figure can be viewed at www.wileyonlinelibrary.com]
extrapyramidal signs (rigidity, dystonic posturing, bradykinesia) 31, 2018 with concern for acute stroke who have the Stroke
in a subset of patients that have not been reported in MLIV. Alert Process and Powerplan activated.
Among atypical patients, identical symptoms with milder severity Results: There were a total of 61 stroke activations between
were appreciated and a genotype-phenotype relationship with September of 2016 through August of 2018. 14/61 patients
partial preservation of TRPML1 channel function was suggested. (23%) met final diagnosis of ischemic stroke or TIA. Of the
Conclusions: Though previously considered a static condi- patients that met the final diagnosis of ischemic stroke, the
tion, functional decline with age is a clinically assessable fea- most common presenting symptom was unilateral weakness.
ture of MLIV. Extrapyramidal signs are variably present but Two were candidates for intervention with mechanical
can be prominent. Genotype explains a portion of variance in thrombectomy and none received tPA. Average age of all acti-
symptom severity. Our findings expand the clinical descrip- vations was 14years, while average age of patients who had
tion of MLIV and can guide future gene therapy trials which final diagnosis of ischemic stroke or TIA was 4years. 61% of
are currently in the preclinical phase. (37/61) activations were female and the most common racial
Keywords: Rare Diseases, Genetics, Movement Disorders demographic was Caucasian. Ischemic stroke/TIA was the
most common diagnosis of all activations. Seizure/Todd’s
paralysis (12/61, 20 %) and migraine (12/61, 20 %) were
STROKE the second leading diagnoses. Other common diagnoses
included psychogenic/conversion disorder (15%), complica-
tions of meningitis/encephalitis (6.6%), and oncologic pro-
235. Retrospective Chart Review: Pediatric Demographics cess (5.0%). No intra-cranial hemorrhages were identified in
in Children Presenting with Acute Neurological Deficit this patient population.
Concerning for Acute Ischemic Stroke: An Evaluation of Conclusions: Ischemic stroke or TIA comprised nearly one-
the Stroke Alert Process fourth of all pediatric stroke activations and is the leading
Barkley T (Kansas City, MO), Flint J, Khalid R, Sharma M diagnosis in all activations obtained in this study. These find-
Objective: To describe the demographics and characteristics ings are consistent with current reported literature. This data
of patients who present with stroke-like symptoms to Chil- in conjunction with previous studies highlights the impor-
dren’s Mercy Hospital tance of developing protocols for early recognition and evalu-
Methods: Descriptive retrospective chart review of patients ation of children who present with stroke like symptoms.
who presented to CMH from September 1, 2016-August Keywords: Stroke

S152 Annals of Neurology Vol 86 (suppl 23) 2019

FIGURE 2: Age at regression thresholds in patients with MLIV. Abstract 234 [Color figure can be viewed at www.
wileyonlinelibrary.com]

236. Radiographic Patterns of Injury and Risk Factors in Discovery Network (CP Hemi-NET) from nine clinical cen-
Children with Hemiplegic Cerebral Palsy tres across Ontario, Canada. Lesion characteristics were deter-
Domi T (Toronto, Ontario), Slim M, Dlamini N, Krishnan P, mined by 2 blinded pediatric neuroradiologists.
Fehlings D, deVeber G, CP-NET Group Results: A total of 211 children with hemiplegic cerebral palsy
Objective: To describe radiographic characteristics of perina- were included (median age at diagnosis 12 months; 62% males).
tal arterial ischemic stroke (PAIS) and periventricular injury Cerebrovascular lesions were classified as PAIS in 101 and PVI
(PVI) and the associated clinical risk factors in each group. in 110 patients (36% with periventricular venous infarction).
Methods: Patients were identified through the Childhood Males and females were equally represented (males: 60% in
Hemiplegic Cerebral Palsy Integrated Neuroscience PAIS, 64% in PVI, p=0.5). Children with PAIS were diagnosed

Program and Abstracts, Child Neurology Society S153

younger (median 9 months vs. 13 months, p<0.01), weighed 238. Mechanical Thrombectomy in Pediatric Stroke:
more at birth (3237
801 vs 2688
1114 grams, p<0.01), and Report of Three New Cases and a Review of the
more likely to have seizures within 24 hours after birth (58% vs Literature
25.7%, p<0.001). Children with PVI were more likely to be pre- Gervelis W (Indianapolis, IN), Golomb M
mature (40% vs 18%, p<0.001) and require resuscitation at Objective: To report 3 new cases of pediatric stroke treated
birth (39% vs 25%, p=0.04). Univariate analysis revealed higher using mechanical thrombectomy and review previously
odds for PAIS diagnosis with a maternal history of blood clots reported cases of mechanical thrombectomy with modern
(OR=4.9; 95% confidence interval [CI]:1.01-23.5) or smoking devices for pediatric stroke.
(OR=2.4; 95%CI:1-5.9). Premature placental rupture and use of Methods: Three new cases of pediatric stroke treated with
fertility treatments increased the odds of PVI diagnosis (OR=9; thrombectomy were identified from 2018 pediatric stroke
95%CI:1.1-71 and OR=4.1; 95%CI:1.3-12.7, respectively). clinic records. A literature review was performed in the
Conclusions: PAIS and PVI imaging characteristics were deter- PubMed and EMBASE databases from January 2010-January
mined by neuroradiologists blinded to diagnosis of CP. In 2019 using the MESH keywords “stroke”, “thrombectomy”,
PAIS, the increased odds of maternal history of blood clots and “clot retrieval”, and “cerebral sinus thrombosis” in children
smoking, and in PVI prematurity, birth following premature age 0-17 years. Cases treated with modern devices and
placental rupture, and fertility treatments are novel findings. reporting outcomes were included. Favorable outcome was
Keywords: Stroke, Neuroimaging, Neonatal Neurology defined as modified Rankin score 0-2 or NIH stroke
scale 0-4.
237. Neuroplasticity Following Early Childhood Brain Results: Two new cases of arterial ischemic stroke (AIS) and
Injury Supports Language Development one case of cerebral venous thrombosis (CVT) treated with
Emami Z (Toronto, Ontario), Dunkley B, Westmacott R, thrombectomy were identified. When combined with previ-
Robertson A, Hess M, Krishnan P, Bhathal I, Moharir M, ously reported cases, there were 47 children with AIS and
MacGregor D, Pang E, Dlamini N 10 children with CVT treated with thrombectomy. For pedi-
Objective: This study investigates the functional atric AIS treated with thrombectomy, 87% (41/47) had
networks underlying language processing in children with a favorable outcomes. For pediatric CVT treated with
neonatal arterial ischemic stroke (NAIS) as a model of thrombectomy, 90% (9/10) had favorable outcomes. Com-
plications included vasospasm, difficulty maneuvering
neuroplasticity following early brain injury. We examine how
devices, device failure, clot fragmentation, and concern for
atypical patterns of functional connectivity correlate with lan-
long-term sequelae from vessel manipulation. These results
guage outcomes to serve as a biomarker in prognostication.
are comparable to prior literature reviews of mechanical
Methods: Eight children with unilateral MCA-NAIS (5F;
thrombectomy for pediatric AIS and CVT.
mean 12.3
3.3 years) and seven neurotypical children (2F;
Conclusions: Mechanical thrombectomy is being increas-
mean 13.4
2.7 years) listened to syntactically correct and
ingly used for pediatric stroke treatment. Questions remain
incorrect sentences while magnetoencephalography was
about the safety and efficacy of thrombectomy in children
recorded. Task-related functional connectivity was calculated
with stroke since large randomized controlled studies are
using an index of phase synchronicity between brain regions.
not feasible. This study suggests thrombectomy holds
Language networks were derived from the mean connectivity
promise as a treatment for carefully selected pediatric
in time windows and frequency bands of interest. Language
stroke patient
outcomes were assessed using neuropsychological tests.
Keywords: Stroke
Results: Patients exhibit a disconnected functional sub-
network involving language areas, including bilateral inferior
frontal areas, bilateral middle temporal poles, and the right 239. Creation of a Suspected Stroke Protocol:
superior temporal pole (theta band, 1.2-1.4s, pcorr=0.025). Streamlining Evaluation and Diagnosis of Children with
While a left-lateralized language network is typically posi- a Focal Neurological Deficit
tively correlated with language skill, the involvement of left Goeden M (Kansas City, KS), Khalid R, Sharma M, Flint J,
temporal brain areas is correlated with poorer language skill Tarantino C, Zinkus T, McDougall Kestner V
in patients (p=0.02). Conversely, good outcome in patients, Objective: 13/100,000 children suffer from an acute ische-
particularly in visuomotor learning, is correlated with atypi- mic stroke per year, resulting in one of the top 10 causes of
cal right frontal connectivity in the language network death in children. Literature shows that two-thirds of chil-
(p=0.003). dren with an acute stroke present to a hospital within 3-6
Conclusions: These findings suggest that the reorganization hours of symptom onset yet there remains a delay in diagno-
of the language network outside of typical language areas is a sis due to lack of awareness and lack of protocols for neuro-
possible compensatory mechanism, and may underlie the lan- imaging and treatment. Our goal was to improve the care of
guage outcomes seen in NAIS. Functional connectivity as a pediatric patients with symptoms of an acute ischemic stroke
marker of neuroplasticity following MCA-early childhood by streamlining early recognition of symptoms and diagnosis.
stroke may be used as a prognostic tool for language develop- Methods: We created a stroke protocol for our hospital that
ment, ultimately guiding precision medicine and improving allows for rapid neuroimaging of patients with an acute neu-
long-term outcomes. rological deficit who are eligible for thrombolysis or clot
Keywords: Stroke, Neuroimaging, Neonatal Neurology retrieval.

S154 Annals of Neurology Vol 86 (suppl 23) 2019

TABLE 1. Summary of Mechanical Thrombectomy using modern devices in CVT and arterial thrombosis in
pediatric patients age 0-17. Abstract 238
Length of Favorable
Type References Age Sex Etiology Vessel Device type Outcome measures follow up Outcome†

CVT Kulcsár 16 yrs F Anemia SSS, Left TS, VG Penumbra, LT mRS 1 2 years 1
et al., 2010

CVT Jankowitz "Age F Dehydration/ SSS, bilateral TS Penumbra, ReFlex mRS of 3 3 months 0
et al., 2013 1-5" hypercoagulable catheter, LT

CVT Li et al., 10 yrs M Trauma ND Terumo microcatheter, mRS of 1 6 months 1

2013 LT

CVT Mortimer 22 mon 4F unknown; hypoplastic left SSS, SS, bilateral Penumbra system, mRS 0-1, unknown 3 weeks-2 3/3(1
et al., 2013 -14 yrs heart TS, VG local tPA years patient
(4) ICV unknown)

CVT Rammos 3 yrs M unknown deep venous AngioJet, LT, mRS 0 1 year 1
et al., 2013 system, left TS, microcatheter
SS, IJV

CVT Yakovlev 14 yrs F Anemia SSS, right LS Solitaire AB unknown unknown unknown
et al., 2014

CVT Shaikh "Pre- ND Infection VG, SS Penumbra, Solitaire mRS 1 2 months 1

et al., 2014 teen" FR

CVT Drofa 9 days M Dehydration SSS, SS, TS MindFrame Capture unknown 3 months unknown
et al., 2016 LP

CVT Omoto 17 yrs M Leukemia SSS, TS Excelsior mRS 0 1 month 1

et al., 2018 microcatheter,
Thrombuster
aspiration

CVT This 8 yrs M Infection, dehydration ICV, VG, StS Solitaire FR mRS 1 8 months 1
Report

AIS Gerstl 3 yrs M CHD, cardiac thrombus BA, MCA Preset stent retriever mRS 1 4 months 1
et al., 2016

AIS Lena et al., "Child" M unknown BA, PCA Penumbra mRS 1 9 days 1
2016

AIS Madaelil 7- 17 yrs 3M GSW; unknown BA, MCA Penumbra, CAPTURE mRS 0,0,0 1 month- 3/3
et al., (3) 3 months
2016*

AIS See et al., 6 yrs M CHD, mitral valve balloon L MCA MindFrame Capture mRS 1 1 week 1
2016 dilation LP

AIS Kulhari 9 years M primary restrictive R MCA Trevo stent retriever mRS 1 1 year 1
et al., 2017 cardiomyopathy

AIS Satti et al., 2-17 yrs 13 M, 7 Dissection; hematologic BA, MCA, ICA Solitaire, Trevo, mRS 0 in 9, mRS 1 in discharge- 19/22
2017 (22) F, 2 risk factors; Crohn’s; Revive, Merci, 9, mRS 2 in 1, mRS 3 90 days
ND unknown Penumbra in 3

AIS Bigi et al., 2-15 yrs ND cardioembolic;unknown 2 patients MCA/ stent retriever mRS 0-1, 1 death discharge- 5/6
2018 (6) 3 ICA/ 1 BA 2 years

AIS Cappellari 4-15 yrs 2 F, 3 HF, cardiac embolus; MCA Penumbra, Trevo, NIHSS 0-4 8 hours-2 5/5
et al*., (5) M ECMO; cardiac myxoma Solitaire months
2018

AIS Kim et al., 14 yrs M possible intracranial ICA, MCA Trevo stent retriever mRS 1 6 months 1
2018 arteriopathy

AIS Stowe 9 yrs M cardiomyopathy with MCA Trevo stent retriever mRS 1 20 days 1
et al., 2018 VAD

AIS Sun et al., 9 mon M respiratory failure BA Solitaire stent retriever mRS 6, Death Death 0
2018 requiring ECMO

AIS Wilkinson 17 mon F infection, anemia Vertebral, BA Solitaire stent retriever mRS 0 3 months 1
et al., 2018

AIS Gandhe 3 yrs F infectious endocarditis R MCA Suction aspiration mRS 1 discharge 1
et al., 2018 device

AIS This 7 - 14 2F dissection; hypercoaguable ICA/ MCA Solitaire, SOPHIA mRS 1,3 6 months 1/2
Report yrs (2)

CVT, Cerebral venous thrombosis; AIS, arterial ischemic stroke; yrs, years; mon, months; ND, not disclosed; mRS, modified Rankin scale; SSS, supe-
rior sagittal sinus; TS, transverse sinus; SS, sigmoid sinus; IJV, internal jugular vein; StS, straight sinus; ICV, internal cerebral vein; VG, Vein of Galen;
CHD, congenital heart disease; GSW, gunshot wound; BA, Basilar Artery; MCA, middle cerebral artery; PCA, posterior cerebral artery; ICA, internal
carotid artery; ECMO, Extracorporeal membrane oxygenation; VAD, ventricular assist device; HF, heart failure; NIHSS, NIH stroke scale.
†Defined as favorable clinical outcome at last follow up (asymptomatic, NIHSS 0–4, modified Rankin Scale (mRS) 0–2)
* Cases included are those not included in Satti et al

Program and Abstracts, Child Neurology Society S155

Results: Before development of the stroke protocol at our from 2002 – 2018. All cases underwent extensive investigations
hospital, a 2 year old patient presented to the Emergency including transthoracic echocardiogram, thrombophilia work-up
Department 1.5 hours after acute onset of left sided weak- and evaluation for cerebral arteriopathy.
ness. He was admitted to the Neurology service and MRI Results: Twelve children were included [male 8 (67%);
performed 22 hours after the onset of symptoms demon- mean age 31.3 months (6 – 83)]. Eight (67%) presented
strated an acute infarct. After development of the stroke pro- with hemiparesis, 3 (25%) with additional seizures. The
tocol, a 7 year old female developed acute onset of left sided mean time interval between minor head trauma and symp-
weakness while inpatient. The stroke protocol was initiated tom onset was 8.3 hours (0 – 36). Eight (67%) presented
and an acute ischemic stroke was identified on MRI within with right basal ganglia stroke. Ten (83%) were treated
4 hours. She was able to receive intravenous tPA as well as with anticoagulation for an average duration of 2.6

undergo thrombectomy. 1.3 years. There was no clinical stroke recurrence (mean
Conclusions: The development of an acute stroke protocol duration of follow-up 2.8
1.5 years). At last follow-up
at our hospital has improved the evaluation and diagnosis of 7 (58%) were without neurological deficits while 5 (42%)
children with focal neurological deficits and allows for rapid had hemiparesis and/or dystonia. Our expanded phenotype
diagnoses and treatment of patients with acute ischemic includes 7 (58%) children older than 24 months and
strokes. 2 (17%) with silent basal ganglia infarcts detected at the
Keywords: Stroke, Neuroimaging time of acute presentation. Other previously unreported
findings include 2 (17%) children with thrombophilia,
240. Expanding the Clinical and Radiological 1 (8%) with basal ganglia hemorrhage, 1 (8%) with tha-
Phenotype of Mineralizing Angiopathy and lamic involvement and 1 (8%) with additional calcifications
Pediatric Stroke – A 15 Year Single-center in the parietal lobe.
Experience Conclusions: This comprehensive case-series expands the cur-
Gorodetsky C (Toronto, Ontario), Pulcine L, Krishan P, rently recognized phenotype of mineralizing angiopathy. Further
Singh J, Moharir M, MacGregor D, Dlamini N studies are required to improve understanding of the pathophys-
iologic basis of this syndrome and inform management.
Objective: Mineralizing angiopathy is a unique stroke syn-
Keywords: Stroke
drome presenting with basal ganglia infarction after minor
head injury in infants and children. There is limited literature
on the clinical phenotype, pathophysiology, management, 241. Variability in Thrombolytic and Endovascular
recurrence risk and outcome. Therapy use in Pediatric Stroke: A Cross-Sectional Survey
Methods: Single-center, retrospective, consecutive case-series of Grewal P (Lexington KY), Lightner D
children presenting with basal ganglia stroke, normal vascular Objective: Challenges in childhood stroke include lack of
imaging and radiologically-confirmed mineralizing angiopathy awareness and consensus. RCT’s in adult population have

TABLE 1. Salient demographic, clinical, radiological and follow-up details of individual patients. Abstract 240
Age
(months) Presenting Head Interval Stroke Follow-Up Unique Features and
Case and Sex Symptoms Trauma (hours) Location Treatment Outcome (years) Findings

1 37 F LH, seizures --- --- C,P ASA Moderate hemiparesis ---

2 66 M Seizures Yes 0 GP,P --- Moderate hemiparesis 3.5 BG bleeding
3 36 M LH Yes 5-6 C,P,T Heparin, ASA Asymptomatic 5 Thalamic calcifications
4 7F LH Yes 24 C, GP, Heparin, Mild hemiparesis, 5
IC LMWH, ASA dystonia
5 25 F LH Yes 3 C,P,IC Heparin, Asymptomatic 4.5 WM abnormalities
LMWH, ASA
6 7M RH Yes 36 C,P,IC Heparin, Asymptomatic 3
LMWH, ASA
7 6M LH --- --- C,P Heparin, ASA Mild hemiparesis 3
8 13 M RH, Seizures Yes 6-8 C,P,IC Heparin, ASA Dystonia 1.5 Parietal lobe calcifications
9 55 M RH Yes 0 C,P Heparin, Asymptomatic 2 Remote BG infarct
LMWH, ASA
10 27 M RH Yes 8 C,P,IC Heparin, ASA Asymptomatic 1.5
11 83 F Irritability Yes 0 C --- Asymptomatic 1 Remote caudate infarct
12 14 M LH, seizures Yes 1 C, GP Heparin, ASA Asymptomatic 1

Abbreviations: RH=right hemiparesis; LH= left hemiparesis; C=caudate; P=putamen; GP=globus pallidum; IC=internal capsule; ASA=Aspirin;
LMWH=low molecular weight heparin; BG=basal ganglia; WM=white matter.

S156 Annals of Neurology Vol 86 (suppl 23) 2019

 to be just as important as the implementation of treatment
therapies in improvement of patient outcome measure.
Keywords: Stroke

242. Concordance of Blood-brain Barrier Permeability

Measures in a Juvenile Rat Model of Photothrombotic
Stroke
Honarvar F (Toronto, Ontario), Domi T, Stirrat E,
Dlamini N, Kassner A
Objective: To assess the evolution of blood-brain barrier
(BBB) permeability after photothrombotic ischemia using
both in-vivo MRI and ex-vivo histology.
Methods: Stroke was photothrombotically induced on
13, 5-week-old male Sprague-Dawley rats, weighing
m=155
20 g. The Garcia test was used to test behavioral out-
come. Five rats had triphenyl tetrazolium chloride (TTC)
staining and MRI (DWI, T2, T2W) assessed longitudinally on
Days 0, 2, and 7 post-ischemia. Eight rats had Evans Blue
(EB) staining and dynamic contrast-enhanced (DCE) imaging
on the same three Days to test for BBB permeability. The
FIGURE 1: (A) Axial and (B) coronal unenhanced CT Wilcoxon two-sample test was conducted to test for differences
demonstrating (red arrows) bilateral punctate basal ganglia in behavioral outcome, and to compare EB and DCE results.
calcifications surrounding the anatomical location of the Results: The stroke group had significant behavioral impair-
bilateral lenticulostriate arteries in a 27-month-old child who ment (mean=7.85) compared to controls (mean=13.4,
presented with right-sided hemiparesis 8 hours after minor p<0.01). MRI and TTC corresponded in terms of size and
head injury. (C) Axial diffusion-weighted imaging MRI of the
location of lesion on Days 0, 2, and 7 (Figure 1). The penum-
same patient showing diffusion restriction in the left basal
ganglia consistent with an acute ischemic infarct. Vascular
bra was detected on MRI on Day 0 and remained visible on
imaging was normal. No other stroke risk factors were Days 2 and 7. However, TTC showed the penumbra only on
identified. (D) Axial FLAIR MRI of a 55-month-old child who Day 0. DCE results showed a high rate of BBB leakage on
presented with right sided hemiparesis and was found to have coronal maps corresponding to the same areas where EB
an acute left basal ganglia infarct. Clinically silent chronic right extravasation occurred (Figure 2). Leakage was greatest at the
basal ganglia infarct (red arrow head) also seen. Abstract 240 hyper-acute stage. The Wilcoxon two-sample test conducted at
[Color figure can be viewed at www.wileyonlinelibrary.com]
every time point indicated no significant differences between
the two techniques (Day 0: z=-1.4201, p=0.19, Day 2: z=-
shown efficacy of thrombolytics and EVT, leading to 2.1149, p=0.06, Day 7: z=-0.6496, p=0.52).
AHA/ASA guidelines for adult stroke patients. TIPS was for- Conclusions: Our findings indicate that the BBB in juvenile
mulation to determine pharmacokinetics of thrombolytics rats is particularly compromised at the hyper-acute stage, and
but was closed due to poor recruitment. The study neverthe- is decreasingly, yet persistently, permeable up to Day 7.
less raised awareness and spurred development of protocols. Keywords: Stroke, Neuroimaging
We aim to review the variability in treatment of pediatric
stroke between different institutions. 243. Clinical Phenotypes of Pediatric Moyamoya: Clinical
Methods: Using survey monkey, an anonymous survey was and Radiographic Characteristics at Presentation
created with primary aim of identifying age criteria used for Kaseka M (Toronto, Ontario), Slim M, Dlamini N
thrombolytic or EVT administration at various institutes in Objective: To compare clinical and radiographic characteris-
US and Canada. The link was posted on Child Neurology tics of children with moyamoya disease (MMD) and
Society (CNS) webpage for members to participate. moyamoya syndrome (MMS) at presentation.
Results: Data was collected from 13 hospitals nationwide. Methods: We reviewed the charts of children with
10 hospitals had functional pediatric stoke protocols. Three hos- moyamoya followed at our institution between 2003 and
pitals did not have a protocol; however, 2 were in progress of 2018. Between group (MMD vs MMS) and within group
formulating one. Wide variability was observed for use of (MMS: neurofibromatosis type 1 [NF1] vs sickle cell disease
thrombolytic therapy in stroke patients with some places having [SCD]) comparisons of clinical and radiographic characteris-
no age limit to others having contraindication to TPA below tics at diagnosis were conducted. Comparisons were con-
12 years of age. Similar variability was true for EVT therapy. ducted using independent t, analysis of variance, or chi-
Conclusions: This study highlights the lack of clarity for square tests.
pediatric stroke population. Inconsistencies are due to pro- Results: Ninety-two patients (45.65% male; 56 (60.87%)
vider discomfort, lack of RCTs, and evolving evidence for MMD; 20 (21.74%) NF1; 19 (20.65%) SCD) were identi-
adult stroke treatment, providing a conundrum when devel- fied. The median age at presentation for MMD and MMS
oping childhood stroke guidelines. Standardized care is likely were 7.72 years and 8.94 years respectively (p=0.3067).

Program and Abstracts, Child Neurology Society S157

FIGURE 1: Visual comparison of structural MRI data with their corresponding histological TTC-stained slice. Penumbral area was
distinguishable from lesion area in DWI, T2, and T2W images (all three days). Penumbral area not distinguishable from lesion
area on TTC slices (Days 2 and 7). * indicates # of hours after the end of light illumination. All images have been configured to
represent actual right and left. Abstract 242 [Color figure can be viewed at www.wileyonlinelibrary.com]

FIGURE 2: Visual comparison between representative coronal permeability maps and EB slices on the three assigned time points.
Qualitatively, the degree of Gadolinium extravasation in DCE images matches EB extravasation in all three days. Yellow arrows
on Day 0 indicate the location of penumbra on the permeability map as well as the EB-stained slice. Yellow and red outlines
(in permeability map images and EB-stained images, accordingly) demonstrated the tissue areas where the contrast agent leaked
through BBB from vessels to tissue. Images have been configured to represent actual right and left hemispheres. Abstract 242
[Color figure can be viewed at www.wileyonlinelibrary.com]

MMD patients presented more frequently with transient presentation and by Suzuki stage. Compared to MMD and
ischemic attacks (TIA) (41.67% vs 10.71%, p=0.0006) and SCD patients, NF1 patients experienced less acute stroke at
bilateral disease (75% vs 47.27%, p=0.0135). More MMS presentation (5% vs 25% and 36.84% respectively,
patients were asymptomatic at presentation being diagnosed p=0.0032), had less infarcts on imaging (5% vs 63.89% and
following syndrome-specific screening (44.64% vs 8.33%, 78.95%, p<0.001) and had less frequently bilateral disease at
p<0.001). There was no difference between MMD and presentation ( 15% vs 75% and 77.78%, p<0.001).
MMS patients by frequency of acute stroke, headaches, Conclusions: MMD patients present more frequently with
seizures and infarcts (acute and remote) on imaging at TIA compared to MMS patients. MMD and SCD-MMS

S158 Annals of Neurology Vol 86 (suppl 23) 2019

patients present more with stroke and bilateral disease than
MMS-NF1 patients suggesting different phenotypes among TABLE 1. Patient Characteristics and Presentation.
moyamoya subpopulations. Abstract 245
Keywords: Stroke, Rare Diseases Patient Characteristics and Presentation

244. A Multisite Blinded Comparative Efficacy Trial of Age at Presentation

CIMT Dose Levels and Constraint Variations for
2 – 8 Year Olds with Hemiparetic Cerebral Palsy Median 9 years
Ramey S (Roanoke, VA), DeLuca S, Stevenson R, Darragh A, Average 9.35 years
Lo W, Conaway M
Range 7 months-17 years
Objective: Constraint-Induced Movement Therapy (CIMT)
shows benefits for treating hemiparetic CP. Widely varied Sex
doses and constraint types preclude comparison of different Male 28 (54.9%)
protocols. An NIH-funded, Phase 2 multisite comparative
efficacy RCT, Children with Hemiparesis Arm Movement Female 23 (45.1%)
Project, was powered to compare 2 doses and 2 types of con- Race
straint with Usual, Customary Care (UCC) on uni- and
White 33 (64.7%)
bilateral upper extremity gains.
Methods: 124 hemiparetic CP, 2-8 y/o, GMFCS I–IV, Black 4 (7.8%)
MACS II–V. Treatment in community/homelike settings by
Asian 3 (5.9%)
protocol-trained occupational/physical therapists. A blinded
2X2 factorial RCT tested two doses and two constraint types: Middle Eastern 6 (11.8%)
High Dose (3 hrs/day X5 days X4wks) vs Moderate Dose
South American 1 (1.9%)
(2.5 hrs/day X3days X4wks); Full-time Cast worn continu-
ously vs Part-time Splint worn only during treatment. Con- Unknown 4 (7.8%)
straints removed the last 20% of treatment days to allow Laterally
bimanual shaping. Blinded assessments included Peabody
Developmental Motor, QUEST, AHA. Parent ratings Unilaterally 17 (33.3%)
included the PEDI and PMAL. Primary analysis controlled Bilaterally 26 (50.9%)
for multiple comparisons; focused on pre-, post-treatment
scores. Individual rank orders for gain magnitude comprised Unknown 8 (15.6%)
group means. p set at 0.01; confidence intervals at 95%. Location
Results: CIMT vs UCC, and CIMT Dose exerted main
ICA alone 19 (37.3%)
effects (p=.01) for unilateral, and integrated uni- and biman-
ual outcomes. High Dose, either constraint, produced signifi- MCA alone 7 (13.7%)
cantly greater gains (M=49.85, SD=11.88) than UCC
ACA alone 1 (1.9%)
(M=38.6, SD=12.12) and Moderate Dose (M=42.55,
SD=10.81). Moderate Dose didn’t differ from UCC. Full- Posterior circulation involvement 1 (1.9%)
time Cast produced larger gains than Part-time Splint, not
Multiple 15 (29.4%)
significant. Outcomes were significantly influenced by indi-
vidual variables and prior treatment. Unknown 8 (15.7%)
Conclusions: High Dose CIMT –either constraint method – Presentation
produced significant, clinically impactful gains. Moderate
Dose was no better than UCC. Stroke 22 (43.1%)
Keywords: Stroke, Translational/Experimental Therapeutics TIA 12 (23.5%)

Tremor 1 (1.9%)
245. Retrospective Study of Moyamoya Disease in a
Chorea 2 (3.8)
Pediatric Cohort
Rodriguez D (Phoenix, AZ), Pines A, Dhamija R Behavioral change 1 (1.9%)

Objective: Moyamoya angiopathy (MMA) is a rare cerebral Seizure 6 (11.8%)

vasculopathy characterized by a progressive stenosis of the ter-
Headache 7 (13.7%)
minal portion of the internal carotid arteries and the develop-
ment of abnormal collateral vessels. Children with MMA Memory decline 1 (1.9%)
become symptomatic due to cerebral ischemic complications Syncopy 1 (1.9%)
and many patients eventually need revascularization. In most
pediatric patients with this disease the cause is not known Incidental 3 (5.9%)
though genetic etiology is more likely to be an underlying

Program and Abstracts, Child Neurology Society S159

 cause. We aim to report clinical characteristics of a cohort of
TABLE 2. Comorbidities. Abstract 245 pediatric patients with moyamoya from a single center identi-
Number of fied retrospectively.
Comorbidities Patients (%) Methods: Retrospective chart review of patients < 18 years
with angiographically confirmed moyamoya disease evaluated
Family history of Moyamoya 3 (5.8%)
at our institution was performed. An in-house text search
tool, Advanced Cohort Explorer, was utilized to filter elec-
Born of a consanguineous couple 2 (3.9%) tronic medical records for patients with diagnosis of MMA
Syndromic 12 (22.8%) from January 1999 to December 2018. Inclusion criteria was
age < 18 years at the time of onset of disease and a diagnosis
Down syndrome 8 (15.7%) confirmed at Mayo clinic.
Neurofibromatosis type 1 2 (3.9%) Results: Fifty-one patients meet the inclusion criteria. Boys
were 55% and median age was 9 years. Three patients had a
Skeletal 4 (7.6%)
family history of moyamoya disease. Table 1 lists demographic.
Spondylodysplasia 1 (1.9%) Approximately half had bilateral disease. 16 patients had a
genetic diagnosis (Downs syndrome and NF1 being most com-
Scoliosis 3 (5.7%)
mon). Congenital anomalies like heart defects and renal dyspla-
Immunological 4 (7.6%) sia were also noted. Table 2 lists associated features.
Juvenile rheumatoid arthritis 1 (1.9%) Conclusions: This study is unique in being a large study on
pediatric patients with MMA. It also highlights the impor-
Recurrent pneumonia 2 (3.9%) tance of considering genetic syndromes as an underlying
Schimke immuno osseous dysplasia with T cell 1 (1.9%) cause when MMA starts early in life.
immunodeficiency Keywords: Stroke, Genetics
Hemotological 6 (11.8%)
246. Perinatal Strokes and Hemiplegic Cerebral Palsy:
Factor V Leiden mutation 2 (3.9%)
Associated Factors from a Controlled National Registry
Beta-thalassemia 1 (1.9%) Cohort
Vitagliano M (Montreal, Quebec), Oskoui M, Shevell M,
Hypertension 2 (3.9%)
Kirton A, Dyck Holzinger S
Sickle cell disease 1 (1.9%)
Objective: Perinatal stroke causes most cases of hemiplegic
Neurological 7 (13.7%) cerebral palsy (HCP). However, many studies continue to
lump all HCP subjects together instead of studying disease-
Seizure disorder 1 (1.9%)
specific etiologies such as perinatal stroke and its definitive
Chiari malformation 2(3.9%) forms (arterial, venous). We hypothesized that perinatal stro-
Aneurysm 2 (3.9%)
kes carry unique risk factor profiles and outcomes as com-
pared to their non-stroke HCP counterparts.
Polycystic astrocytoma 1 (1.9%) Methods: Data current to January 2019 (2093 cases) was
Congenital anisocoria 1 (1.9%) extracted and analyzed from the Canadian Cerebral Palsy
Registry database. Participants included term neonates with
Cardiac 6 (11.4%) MRI confirmed HCP stratified by expert review into
Congenital heart disease 1 (1.9%) (1) definitive stroke (arterial, venous), (2)probable stroke, or
(3)non-stroke. Using univariate analyses, risk factor and out-
Wolff-parkinson-white syndrome 1 (1.9%)
come variables were compared between stroke (definitive and
Tricuspid regurgitation 1 (1.9%) probable) and non-stroke HCP, as well as stroke subtypes
(arterial vs. venous). Student t-tests and chi-squares for con-
Supravalvular pulmonary stenosis 1 (1.9%)
tinuous and categorical variables were used to compare vari-
Mitral valve prolapse 1 (1.9%) ables between groups.
Mitral valve insufficiency 1 (1.9%) Results: Of the 2093 CCRP cases, 662(26%) had HCP, mak-
ing it the most common subtype. Of these, 490(74%) had suf-
Renal 3 (5.9%) ficient data for these analyses. Perinatal stroke occurred in 342
Left upper pole multicystic dysplastic kidney 1 (1.9%) (70%):139 venous (41%),181(53%) arterial. Risk factors associ-
ated with stroke versus other HCP included young maternal age
Chronic kidney disease 1 (1.9%)
(p<0.01) and chorioamnionitis (p<0.05). Risk factors did not
Bilateral renal dysplasia 1 (1.9%) differ between stroke subtypes. Outcomes associated with stroke
included multiple comorbidities (p<0.01) and remote
Endocrine
epilepsy(p<0.01). Outcomes associated with arterial stroke sub-
Diabetes mellitus type 1 2 (3.9%) type included multiple comorbidities (p<0.05), higher GMFCS
score (p<0.05), and remote epilepsy (p<0.01).

S160 Annals of Neurology Vol 86 (suppl 23) 2019

Conclusions: Syndrome-controlled analyses offer a unique per-
spective on pathogenic factors of perinatal stroke and larger CP TABLE 1. Comparison of Demographics, Patient
registries facilitate such investigations. While evidence suggests Location and Time-to-Imaging. Abstract 247
unique distinctions between stroke and non-stroke HCP, future Period 1,
efforts are required to further define these relationships.
n=150 Period 2, n=235
Keywords: Stroke

247. Trends in Pediatric Acute Stroke Protocol Age, median, 12 years 10 years (IQR
Utilization over 7 Years interquartile range (IQR 7-15) 3-10)
Wharton J (Nashville, TN), Barry M, Lee C, Jordan L Male, n (%) 75 (50%) 122 (52%)
Objective: We examined trends in pediatric acute stroke pro-
Sedation needed for 17 (0.11%) 33 (0.14%)
tocol utilization, imaging studies obtained, final diagnoses,
imaging, n (%)
and interventions at our children’s hospital over a 7-year
period. Stroke alert from ED, 124 (83%) 163 (69%)
Methods: Clinical and demographic information was n (%)
obtained from a quality improvement database and medical
Stroke alert from 7 (0.05%) 35 (0.15%)
records for children for whom the acute stroke protocol was
activated. We compared the initial 43 months of the proto- ICU, n (%)
col, April 2011-October 2014 to the subsequent 43 months, Door-to-imaging time 79 min (IQR 98 minutes
November 2014-May 2018. (ED only) 45-422) (IQR 65-148)
Results: During the study period, 385 pediatric stroke alerts
were activated. Of these 150 (39%) were in the initial period; Confirmed stroke as 38 (25%) 42 (18%)
235 (61%) were in the later period. During the later period, final diagnosis
42 (18%) had confirmed stroke on imaging, 3 (1%) had Non-stroke 20 (13%) 40 (17%)
TIA. Non-stroke neurological emergencies were found in neurological
40 additional children (17%), Figure. Urgent neuroimaging emergency
was completed in 205/235; 79% had MRI as initial neuroim-
aging. Time-to-imaging was slightly longer in the second
time period due to younger age and increased sedation needs, 248. A Retrospective Analysis of Clinical Features,
Table. Stroke protocol activation increased by 56% from the Neuroimaging Findings and Long-term Outcome in
initial to the later period. Rate of confirmed stroke in combi- Pediatric Cerebral Venous Sinus Thrombosis
nation with other neurologic emergencies remained overall Karakas C (Houston, TX), Takacs D, Edmondson E, Fisher K,
stable at >35%. Rate of stroke intervention remained rela- Shukla N, Clark G, Pehlivan D
tively stable; 2 patients received thrombectomy during the Objective: To examine the clinical features, risk factors,
initial period versus 3 patients in the later period. One teen treatment and long-term neurological outcomes in children
received intravenous tissue plasminogen activator prior to with cerebral sinus venous thrombosis (CSVT).
thrombectomy. Methods: This was a retrospective study in children diag-
Conclusions: Greater awareness of the acute pediatric stroke pro- nosed with CSVT between 1991 and 2018.
tocol led to increased activation by medical personnel throughout Results: 215 patients with CSVT were included in this
the hospital. Frequency of confirmed stroke and MRI as the first study. Average follow-up duration was 38.4 months (range
imaging study remained relatively stable over time. 1 week to 22 years). Average age was 5.8 years (range
Keywords: Stroke 1 month to 19 year of age). 137 (63%) were males. Head
and neck infections (37%), prothrombotic disorders (13%),
hematologic malignancies (8%) and trauma (13%) were com-
mon risk factors. Common presenting clinical features
included headache (35%), fever (28%), and seizure (20%).
On initial neurological exam; 38% were normal, 20% had
motor deficit, 20% had altered mental status, 17% had cra-
nial nerve deficit, and 13% had papilledema. Neuroimaging
features included both infarction and hemorrhage (14%),
only ischemic infarction (11%), other intracranial hemor-
rhages (8%), and no parenchymal lesions (67%). Common
sites of thrombosis consisted of left transverse (37%), right
transverse (37%) and superior sagittal sinus (36%). Treat-
ment choice were low molecular weight heparin (65%),
unfractionated heparin (16%) and warfarin (6%). Follow up
neurological status was normal in 65%, abnormal in 25%,
FIGURE 1: Abstract 247 and death was reported in 6% of all children.

Program and Abstracts, Child Neurology Society S161

Conclusions: CSVT may be associated with detrimental Methods: A standardized survey, Pediatric Quality of Life
long-term outcome in pediatric patients. Thus, appropriate Inventory (PedsQL), was administered to guardians of chil-
management and early intervention are necessary. dren with Phelan-McDermid Syndrome (n= 213), Rett Syn-
Keywords: Stroke drome (n= 148), and SYNGAP1 related intellectual
disability (n= 30).
Results: The survey revealed that across all categories for
quality of life, the greatest impairment for syndromic ASDs
TEACHING OF CHILD was in physical functioning. When parsing the data based on
genetic diagnosis, the greatest impairment for Phelan-
NEUROLOGY McDermid Syndrome was in social functioning. In contrast,
the greatest impairment for Rett syndrome was physical func-
tioning. When directly comparing each domain between
249. Quality of Life in Individuals with Syndromic Phelan-McDermid syndrome and Rett syndrome, there was
Autism Spectrum Disorders greater reported dysfunction in physical functioning of girls
Andujar F (Houston, TX), Suter B, Bolbocean C, Holder J with Rett syndrome (t-test p<0.01). For all other domains,
Objective: To evaluate the quality of life of children with there was no significant difference.
three syndromic Autism Spectrum Disorders (ASDs): Phelan- Conclusions: Quality of life instruments can provide insight
McDermid syndrome, Rett syndrome, and SYNGAP1 related into caregiver preferences in neurodevelopmental disorders.
intellectual disability. While such studies have been conducted for idiopathic

TABLE 1. Abstract 250

Baseline QI Implementation
n=76 (39.8%) n=115 (60.2%) p- value

Age in years, Mean (
SD) 8(
5.5) 7 (
5.4) 0.47

Gender Female 29 (38.2%) 49 (42.6%) 0.32
Race/ethnicity African American 14 (18.7%) 25 (21.7%) 0.94
Asian 9 (12%) 12 (10.4%)
Caucasian 27 (36%) 37 (32.6%)
Hispanic 11 (14.7%) 16 (13.9%)
Others 14 (18.7%) 25 (21.7%)
Insurance Plan CMS/Medicaid 29 (38.2%) 58 (50.4%) 0.10
Private 47 (61.8%) 57 (49.6%)
Elective admissions 25 (32.9%) 30 (26.1%) 0.33
Admitted for seizure management 58 (76.3%) 96 (83.5%) 0.26
Length of stay (days) (Baseline vs. QI intervention) 2.77
1.4 3.02
2.8 0.3
30-day readmits (%) (Baseline vs. QI intervention) 10 (5.2%) 3 (1.6%) 0.007
Discharge Before Noon 31 (40.7%) 70 (60.8%) 0.008
Delayed Discharges 45 (59.2%) 45 (39.1%)
Reason for Delayed Discharge Awaiting MRI 14 (18.4%) 11 (9.5%) 0.31
Pending Discharge Paper Work 9 (11.8%) 9 (7.8%) 0.60
Awaiting Transport 5 (6.5%) 8 (6.9%) 0.27
Delayed Treatment 4 (5.2%) 4 (3.4%) 0.64
Busy Neurology Service 4 (5.2%) 3 (2.6%) 0.5
Other Reasons 9 (11.8%) 10 (8.6%) 0.5

S162 Annals of Neurology Vol 86 (suppl 23) 2019

autism, few have focused on syndromic ASDs. Here we percentage increased in the intervention period; from a base-
show that overall, physical functioning is of greatest concern line of 40.7% to 60.8% (table 1). Survival analysis showed
for caregivers of individuals with syndromic ASDs. However, discharge time after QI implementation improved signifi-
when parsing based on genetic diagnosis, we found physical cantly (p=0.043) (fig.1)
functioning to be a significantly greater concern for Rett Conclusions: Our study successfully identified the
syndrome than Phelan-McDermid syndrome. This is con- factors associated with late discharge and successful
gruent with the physical regression typically associated with strategies to improve DBN in an inpatient pediatric neurol-
Rett syndrome. Overall, this study demonstrates the utility ogy setting.
of caregiver surveys in prioritizing phenotypes important for Keywords: Teaching of Child Neurology
targeting as clinical endpoints in genetically-defined autism
spectrum disorders.
Keywords: Teaching of Child Neurology, Cognitive/Behav-
ioral Disorders, Genetics
TRANSLATIONAL/
EXPERIMENTAL
250. Quality Improvement Strategies Improve Pediatric THERAPEUTICS
Neurology Inpatient Discharges Before Noon
Eksambe P (Glen Oaks, NY), Shah Y, Singh K, Karkare S,
Kothare S 251. Lentiviral (LV) Hematopoietic Stem Cell Gene
Objective: Early hospital discharge is an important quality Therapy (HSC-GT) for Metachromatic Leukodystrophy
improvement measure that has not been well studied in pedi- (MLD) Provides Sustained Clinical Benefit
atric neurology. The objective of our study was to implement Fumagalli F (Milan, Italy), Calbi V, Sessa M, Zambon A,
strategies to improve hospital discharge times for patients Baldoli C, Cugnata F, Rancoita P, Acquati S, Redaelli D,
admitted to the pediatric neurology service Miglietta S, Magni S, Recupero S, Ferrua F, Barzaghi F,
Methods: This was a quality improvement (QI) study of Cicalese M, Migliavacca M, Tucci F, Gallo V, Ciotti F,
hospital discharge before noon (DBN) in pediatric neurol- Fraschini M, Sarzana M, Silvani P, Spiga I, Ferrari M,
ogy patients admitted to a tertiary care children’s hospital. Facchini M, Locatelli S, Antonioli G, Zancan S, Calabria A,
Study duration was 6 months – first three months pre- and Montini E, Farinelli G, Morena F, Segovia J, Schwab L,
next 3 months post-intervention. Strategies focusing on Downey G, Gabaldo M, Martino S, Di Serio C, Ciceri F,
pre-identifying MRI candidates and those needing home Comi G, Natali Sora M, Bernardo M, Naldini L, Biffi A,
care services, identifying pharmacy preference, reviewing Aiuti A
overnight vEEGs first thing in the morning, and Objective: MLD is a fatal demyelinating lysosomal disease
implementing morning huddles etc. were implemented. caused by arylsulfatase A (ARSA) deficiency with no
Demographic and clinical data were collected, including approved treatment. We report data of HSC-GT in 29 MLD
age, gender, race and reasons for delay in discharge. Chi patients with 1-8 years follow-up.
square, t test, and survival analysis (log-rank test) were per- Methods: HSC-GT consists of autologous transplant of
formed to determine differences between baseline and post HSCs transduced ex vivo with LV vector encoding for the
QI implementation human ARSA gene, infused following busulfan conditioning.
Results: One hundred ninety-one patients were included in 29 early-onset MLD patients (16 late infantile [LI], 13 early
the study. There were 76 subjects before the implementation juvenile [EJ]) were treated: 20 in a clinical trial, 9 in
of the study and 115 subjects during the study. DBN expanded access programs (EAP). Efficacy endpoints included
pharmacodynamic effects, improvement of motor and cogni-
tive function, and demyelination process compared to a natu-
ral history cohort.
Results: 18/20 clinical trial patients are alive with follow-up
of 3-8 years; 2 EJ patients treated after symptom onset died
from disease progression. We observed stable engraftment of
gene-corrected cells, no treatment-related mortality, and no
abnormal clonal expansion. ARSA activity was restored in
peripheral blood and cerebrospinal fluid. Patients treated
before overt symptom onset at time of GT displayed normal
motor function or stabilization/slower progression of motor
impairment compared to the natural history cohort. Most
patients, including patients symptomatic at GT, maintained
cognitive performance within normal range. Improvement or
stabilization of the demyelination process (per MRI) was
documented in most of the patients. Outcome results includ-
FIGURE 1: Abstract 250 ing 9 EAP patients are in progress.

Program and Abstracts, Child Neurology Society S163

Conclusions: Long term (≤8 years) follow-up demonstrates We compared HRQOL, self-management, and self-efficacy in
that HSC-GT is safe and well-tolerated. HSC-GT may pre- children with neurological conditions (CNC) and children with
vent or stabilize motor and cognitive decline and progressive other chronic illness and medical complexity (CIMC) during
demyelination and atrophy, particularly when patients are acute hospitalization.
treated before symptom onset. Methods: Children (8-17) and parent/guardian participated
Keywords: Translational/Experimental Therapeutics, Genet- in a 45-60 minute interview using three questionnaires
ics, Rare Diseases PedsQL, Patient Activation Measure (PAM), and Self-
Efficacy Scale (SES). Only those with complete data for both
252. Differences in Health-Related Quality of Life, Self- children and parents (n=32/35) were included.
Management, & Self-Efficacy Between Children with Results: There were no significant differences in Total
Neurological Conditions and Other Chronic Illness & PedsQL (71.4
19.3 vs. 68.9
11.0), PAM (3.5
0.8 vs
Medical Complexity 3.4
0.9), and SES (2.0
1.4 vs. 2.5
1.1) scores
Reyes B (Los Angeles, CA), Soliven RJ, Huang C-C, Lerner J, between the CNC (n=8; 13.13
2.7 years; 6F) and CIMC
Jacob E (n=24; 13.6
2.9 years; 10F), respectively in both children
Objective: Children with neurological conditions suffer from and parent ratings. While there were no significant differ-
disabilities that impact health-related quality of life (HRQOL). ences between the two groups, there were differences by

TABLE 1. Abstract 252

Descriptives
95% Confidence Interval
for Mean
Std. Std. Lower Upper
N Mean Deviation Error Bound Bound Minimum Maximum

PAMScoresChildTeen 1.2 10 1.02 .063 .020 .97 1.07 1 1

3.0 12 2.17 .389 .112 1.92 2.41 2 3
4.0 10 3.90 .316 .100 3.67 4.13 3 4
Total 32 2.35 1.201 .212 1.92 2.78 1 4
TotalSESScoreChildTeen 1.2 10 28.60 3.718 1.176 25.94 31.26 23 35
3.0 12 33.83 5.254 1.517 30.50 37.17 28 44
4.0 10 36.70 6.783 2.145 31.85 41.55 23 45
Total 32 33.09 6.172 1.091 30.87 35.32 23 45
TotalPedsQL 1.2 10 62.42 11.831 3.741 53.96 70.89 45 79
3.0 12 68.33 12.931 3.733 60.12 76.55 45 93
4.0 10 78.08 10.914 3.451 70.27 85.89 63 95
Total 32 69.53 13.228 2.338 64.76 74.30 45 95

ANOVA
Sum of Squares df Mean Square F Sig.

PAMScoresChildTeen Between Groups 42.117 2 21.059 234.644 .000

Within Groups 2.603 29 .090
Total 44.720 31
TotalSESScoreChildTeen Between Groups 338.552 2 169.276 5.829 .007
Within Groups 842.167 29 29.040
Total 1180.719 31
TotalPedsQL Between Groups 1252.921 2 626.460 4.355 .022
Within Groups 4171.132 29 143.832
Total 5424.053 31

S164 Annals of Neurology Vol 86 (suppl 23) 2019

self-management abilities in both the CNC and CIMC decreased and the patient can be rendered seizure free if the
groups. Collectively, they had low (n=10; 1.02
.06), focus is correctly identified.
medium (n=12; 2.17
.39), and high (n=10; 3.90
.32) Keywords: ACNN
self-management abilities with corresponding lower Total
PAM (F=234.64, p =.000), Total SES (F=5.83, p =.007), 254. Managing Students with Seizures ECHO: The
Total PedsQL (F=4.36, p=.022) scores. Importance of School Nurses
Conclusions: Our findings indicated no significant differ- Schultz R (Houston, TX), Shafer P, Radecki L, Shah A,
ences between the two groups in HRQOL, self-management, Hueneke S, Newborn-Palmer L
and self-efficacy. However, self-management abilities, regard-
Objective: Epilepsy is the most common childhood neuro-
less of groups varied, were lower with corresponding lower
logic condition in the United States with approximately
HRQOL and self-efficacy. We recommend early assessment
470,000 children aged birth to 17 years affected, or
and intervention of self-management skills in children with
approximately 6 out of every 1,000 students. Often, school
neurological conditions to promote increased self-efficacy and
nurses are responsible for managing seizures in school set-
HRQOL.
tings, addressing seizure-related concerns including com-
Keywords: Translational/Experimental Therapeutics
orbidities and academic accommodations, and training
other school personnel. School nurses face multifaceted
challenges in addressing the unique and complex needs of
ACNN this population. The American Academy of Pediatrics’
(AAP) National Coordinating Center for Epilepsy par-
tnered with the Epilepsy Foundation (EF) to close the gap
253. Insular Epilepsy in awareness and management of seizures and comorbidities
Michon A (Royal Oak, MI), Soresi S, Arndt D by educating school nurses through a telementoring pro-
Objective: Defining insular epilepsy and the associated sei- gram, Project ECHO (Extension for Community
zure semiology Healthcare Outcomes).
Methods: The seizure semiology is important to help local- Methods: This ECHO creates a virtual learning network,
ize the symptomatogenic zone, which is near or overlaps the bringing together school nurses and a team of regional center
epileptogenic zone. The provider needs to identify subtle experts to improve knowledge and confidence around seizure
symptoms which may be an integral part of the patient’s sei- management fostering an “all teach all learn” approach.
zures. Subtle symptoms may include: gagging, tingling or School nurses participate in the 8-session ECHO; curriculum
warmth sensation, fear, tachycardia, throat/stomach/chest topics include seizure recognition, delegation, rescue thera-
constriction, wiping of nose, facial reddening, or tongue pies, and social-emotional impact on students.
protrusion. The described symptoms could be derived from Results: 48 school nurses from 9 states with high prevalence
the insula and warrant further investigation. Video EEG of epilepsy enrolled in the ECHO. The ECHO model has
may capture subtle mouth pouting, ipsilateral eye blinking, historically demonstrated improved capacity among
hyper salivation, or asymmetric tonic seizures. The insula is healthcare professionals around management of patients with
a small vascular structure deep within the lateral sulcus of chronic health conditions. Preliminary findings indicate high
the brain and is not visible due to the coverage by opercula participant satisfaction with individual sessions and value in
of the parietal, frontal, and temporal lobes. Insular functions the didactic dialogue between multidisciplinary experts, case
range from sensorimotor, pain, and social-emotional pro- presentations and access to supportive resources.
cesses to high-level attention and decision making. If the Conclusions: We hypothesize additional improvements in
patient’s history strongly supports the hypothesis of insular knowledge and confidence in managing students with sei-
epilepsy, a sEEG procedure is warranted for confirmation. zures in a school setting based on post-session surveys and
sEEG is a diagnostic test indicated in a patient with: a nega- focus group data.
tive MRI, suspect for deep seeded focus or network seizures. Keywords: ACNN
The process of sEEG is the implantation of depth electrodes
to identify the epileptogenic zone. If the seizures are local- 255. Implementation of Building the M-CHAT-R into
ized to the insula, the patient can undergo epilepsy surgery the Electronic Medical Record
and experience a significant reduction or elimination of sei- Fisher B (Chicago, IL), Berg A, Crawford P, Divinagracia E,
zure burden. O’Connor J
Results: Our center has been able to identify several patients Objective: To build the M-CHAT-R into the electronic
who have completed a presurgical evaluation, including medical record (EMR) in order to routinely assess for autism
sEEG, which has led to the diagnosis and surgical interven- in epilepsy clinic. Prior work was done to show value of sys-
tion for Insular Epilepsy. tematic screening for such co-morbidities in the epilepsy
Conclusions: Insular Epilepsy should be considered in a clinic; however due to time constraints and burden of scor-
patient with medically refractory epilepsy. Presurgical evalua- ing, the practice of routine screening was not always possible.
tion is warranted including completion of a sEEG procedure Methods: A working group consisting of members from
if Insular Epilepsy is suspected. Seizure burden can be Patient Reported Outcomes and Assessments (PROA), Data

Program and Abstracts, Child Neurology Society S165

Analytics and Reporting (DAR), Information Management Results: The M-CHAT-R has been built into our EMR.
(IM), Epic training, a research professor, a clinical research New patients between the age of 16 and 30 months are
coordinator and a clinician representative held regularly assigned the M-CHAT-R through MyChart. If the family
scheduled meetings to discuss the process, build, and imple- does not complete the M-CHAT via MyChart it can be
mentation of the project. It was decided to start assigning the assigned by the provider at the time of the initial visit.
M-CHAT-R to those patients seen by an Advanced Practice This is also the case for patients who are established but
Provider (APP) in new onset epilepsy clinic as well as infan- meet the criteria and have not yet completed the
tile spasms clinic. M-CHAT.

FIGURE 1: The following diagram summarizes the overall process for the workflow for administering the M-CHAT-R, a revised
autism screener. The red boxes correspond to EPIC electronic procedures, blue boxes correspond to steps taken by the clinician,
white boxes correspond to steps taken by the parent, and green boxes direct different workflow pathways. Abstract 255 [Color
figure can be viewed at www.wileyonlinelibrary.com]

S166 Annals of Neurology Vol 86 (suppl 23) 2019

Conclusions: The M-CHAT-R has been built into the elec- 257. De Novo EIF2AK1 and EIF2AK2 Variants are
tronic medical record so that routine screening can be per- Associated with Developmental Delay, Movement
formed in new onset epilepsy and infantile spasms clinics. Disorders, Cerebellar Ataxia, Leukoencephalopathy, and
The DAR team will track responses over time and validate Neurologic Decompensation
the data. Once the M-CHAT-R has been used regularly in Chao H-T (Houston, TX), Mao D, Reuter C, Ruzhnikov M,
this limited setting its use will expand to all providers in all Beck A, Farrow E, Emrick L, Mackenzie K, Robak L,
clinic settings within the epilepsy center. There will also be Wheeler M, Calame D, Thiffault I, Agarwal P, Bernstein J,
the build of additional screeners to assess for co-morbidities Bellen H
other than autism such as developmental delay and behav- Objective: EIF2AK1 and EIF2AK2 encode members of the
ioral concerns. Eukaryotic Translation Initiation Factor 2 Alpha Kinase
Keywords: ACNN (EIF2AK) family that inhibits protein synthesis in response to
different stress conditions. EIF2AKs also mediate the phos-
phorylation of EIF2S1 (eukaryotic translation initiation factor
2 subunit alpha, eIF2α), which then inhibits EIF2Bs. Intrigu-
ingly, deleterious gene variants in EIF2Bs are associated with
LATE BREAKING Vanishing White Matter (VWM) disease. However, despite
key physiologic roles of the EIF2AK family, neither EIF2AK1
nor EIF2AK2 has been linked to Mendelian diseases.
256. Lenti-D Hematopoietic Stem Cell Gene Therapy
Methods: We describe seven unrelated individuals identified
Stabilizes Neurologic Function in Boys with Cerebral
Adrenoleukodystrophy through the Undiagnosed Diseases Network and
McNeil E (Cambridge, MA), Eichler F, Duncan C, Orchard P, GeneMatcher with heterozygous de novo missense variants in
De Oliveira S, Thrasher A, Lund T, Kühl J-S, Sevin C, EIF2AK1 or EIF2AK2 that map to key functional domains.
Gissen P, Amartino H, Smith N, Shamir E, Chin W, To characterize the functional effects of the
Aubourg P, Williams D EIF2AK1/2variants, we cloned full-length human cDNA
encoding the wildtype EIF2AK1 and EIF2AK2 protein into
Objective: There is currently no treatment approved for cere-
the mammalian expression vector, pcDNA-DEST40, and
bral adrenoleukodystrophy (CALD), a rare metabolic disorder
performed transfection studies in two human cell lines,
in which rapid and progressive inflammatory cerebral demye-
HEK293T and HeLa. The effects of the variants on protein
lination leads to irreversible loss of neurologic function and
expression and the phosphorylation of EIF2S1 was assessed
death. We have previously shown promising results for the
in both transfected human cell lines and three independent
ALD-102 clinical study of Lenti-D Drug Product (DP), an
patient-derived fibroblast cell lines.
investigational autologous hematopoietic stem cell gene ther-
Results: Recurrent features seen in these individuals include
apy for the treatment of CALD in boys ≤17 years old; based
developmental delays (7/7), hypotonia (6/7), hypertonia (5/7),
on data from 29 patients, Lenti-D DP was generally safe and
involuntary movements and tremors (3/7), cerebellar ataxia
led to stabilization of disease progression.
(4/7), and cognitive impairments (5/7). All patients with
Methods: Study ALD-102 has completed enrollment, with
EIF2AK2 variants had white matter abnormalities on imaging
32 boys having received Lenti-D DP as of April 2019.
(6/6). Notably, individuals with EIF2AK2 variants exhibit sen-
Results: The median follow-up time for the cohort is
sitivity to febrile infections with neurological deterioration.
21.2 months (min-max, 0.0–60.2). Fifteen patients have
Conclusions: Our findings indicate that loss-of-function var-
completed 24 months of follow-up in ALD-102 and con-
iants in EIF2AK1 and EIF2AK2 cause a neurodevelopmental
tinue to be free of major functional disabilities (MFD)
syndrome that may share common pathogenic mechanisms
through their last follow-up in a long-term extension study.
with Vanishing White Matter disease.
Fourteen patients remain in ALD-102; the longest follow-up
Keywords: Genetics, Rare Diseases, Demyelinating
among these patients is 20.4 months. Two patients were
Disorders
withdrawn and referred for allo-HSCT before their Month
24 visit; another experienced early and rapid disease progres-
sion while on-study resulting in MFDs and death. All other 258. Chimeric Antigen Receptor (CAR) T Cell
Lenti-D DP-treated patients generally showed evidence of Neurotoxicity Correlates with Pretreatment and Acute
neurologic function stabilization at their last follow-up. There CSF Neurofilament Light Chain (NFL) Levels
have been no reports of graft failure, GVHD, or transplant- Gust J (Seattle, WA), Wilson A, Finney O, Hartsuyker K,
related mortality; recorded adverse events are consistent with Annesley C, Gardner R, Garden G
myeloablative conditioning. There is no evidence of replica- Objective: Immunotherapy for hematologic malignancies
tion competent lentivirus or insertional oncogenesis. with CD19-directed CAR T cells is complicated by neuro-
Conclusions: Lenti-D DP appears to stabilize neurologic dis- toxicity in approximately 40% of patients. We have previ-
ease progression and continues to show favorable safety with ously reported evidence of glial injury in pediatric patients
the longest follow-up at 60.2 months. with CAR T neurotoxicity by elevated CSF levels of GFAP
Keywords: Demyelinating Disorders, Rare Diseases and S100b. We now hypothesize that NFL is also a useful

Program and Abstracts, Child Neurology Society S167

biomarker of neuronal injury related to abnormal blood- 10.7
3.4), 54% are male (adults=52%; pediatric=57%), and
brain-barrier and glial function. 51% are white (adults=56%; pediatric=43%). PKAN-ADL total
Methods: We used the Mesoscale Discovery platform to score (mean
SD) at baseline was 27.8
11.4; range=7-48
measure CSF and serum NFL levels in a consecutive cohort (adults=25.4
10.5; pediatric = 32.2
11.7). Four DMC
of 43 pediatric patients with B cell ALL who received reviews were completed, each endorsed continued enrollment of
CD19-directed CAR T cells. adult and pediatric patients after safety data review. Topline
Results: CSF NFL levels prior to CAR T cell infusion pos- results will be presented and their impact on the treatment para-
itively correlated with the risk of subsequently developing digm for PKAN will be discussed.
severe neurotoxicity (no neurotoxicity, median 275pg/mL, Conclusions: The FORT trial has completed enrollment and
mild 378pg/mL, severe 951pg/mL, P=0.0182 for severe vs randomized 84 patients with PKAN, making it one of the larg-
none, P=0.0458 for severe vs mild). During neurotoxicity, est trials to date for this rare, neurodegenerative genetic disorder.
mean CSF NFL levels increased to 1179pg/mL (mild neu- Keywords: Movement Disorders, Rare Diseases
rotoxicity, P=0.0338) and 1345 pg/mL (severe neurotoxic-
ity, P=0.0148), respectively. In serum, pretreatment NFL
levels were highly abnormal in many patients (median 260. First-In-Human Intrathecal Gene Transfer Study for
368pg/mL, range 10-56,321pg/mL; healthy control median Giant Axonal Neuropathy: Three-Year Study Review of
4pg/mL, range 1-7.5pg/mL). However, there was no corre- Safety, Immunologic Responses and Interim Analysis of
lation with neurotoxicity, history of CNS radiation, periph- Efficacy
eral neuropathy, stem cell transplant, or number of prior Bharucha-Goebel D (Washington, DC), Saade D, Jain M,
chemotherapies. Day 7 serum NFL levels did not change Waite M, Norato G, Cheung K, Foley AR, Soldatos A,
significantly (median 439pg/mL, range 5-17,439pg/mL, Rybin D, Lehky T, Calcedo Del Hoyo R, Jacobson S,
P=0.3254). Samulski RJ, Gray S, Bonnemann C
Conclusions: We conclude that CSF NFL is promising bio- Objective: GAN is a rare pediatric neurodegenerative disor-
marker of CAR T neurotoxicity risk and severity. The abnor- der affecting the central and peripheral nervous system.
mal baseline serum NFL concentrations remain unexplained Recessive GAN mutations cause dysfunction of gigaxonin, a
and require further study. cytoskeletal regulatory protein, leading to progressive weak-
Keywords: Brain Tumors/Oncology, Infections/ ness and respiratory failure with death by the 2nd to 3rd
Neuroimmunology, Translational/Experiemental Therapeutics decade of life. We are conducting a first-in-human intrathecal
(IT) AAV9 mediated gene transfer trial for GAN
259. The FOsmetpantotenate Replacement Therapy (NCT02362438). We present here a review of safety and
(FORT) Pivotal Trial in Patients with Pantothenate interim study analysis data evaluating efficacy in this study.
Kinase-Associated Neurodegeneration (PKAN) Methods: This is a single site, phase I, non-randomized,
Escolar M (Pittsburgh, PA), Pérez Dueñas B, Jinnah H, open label dose escalation study. Eleven GAN patients have
Klopstock T, Videnovic A, Simonetta Zorzi G, Burns C, been dosed at three dose levels (ranging from 3.5x1013vg to
Greblikas F 1.8x1014vg) with scAAV9-JeT-GAN, with follow up data
Objective: To evaluate the efficacy and safety of 24 weeks of out to 36 months post gene transfer.
treatment with fosmetpantotenate in patients with PKAN Results: We utilize natural history study data for GAN for
enrolled in the FORT trial. comparison of outcome measures in this analysis. Outcome
Methods: FORT is a phase 3, randomized, double-blind, measures of interest include functional scales (eg: MFM32,
placebo-controlled pivotal trial of the efficacy and safety of fos- FARS), strength and electrophysiologic (nerve conduction)
metpantotenate in patients with PKAN. The FORT trial is a data. We review the overall safety and feasibility of an intra-
24-week double-blind study. Eligible patients have confirmed thecal route of AAV9 based gene transfer. We further review
mutations in the PANK2gene, are ages 6-65 years, with a here novel and systematically studied immunologic analyses
PKAN-Activities of Daily Living (PKAN-ADL) total score of including: 1) B and T cell profiles following IT gene transfer;
≥6 (the PKAN-ADL total score ranges from 0-48). The FORT 2) Effect of baseline AAV9 seropositive status, 3) Feasibility
primary efficacy endpoint is change in PKAN-ADL total score of inclusion of biallelic null mutation patients with targeted
from baseline to end of double-blind. The secondary efficacy T cell immune modulation.
endpoint is change in UPDRS Part III score from baseline to Conclusions: This study represents a proof of concept for
end of double-blind. The Data Monitoring Committee (DMC) the employment of IT gene transfer as a strategy for gene
conducts pre-planned and periodic safety reviews. replacement in disorders affecting the central nervous system,
Results: Across 20 study sites in North America and Europe, and we report here on safety as well as efficacy findings base
84 patients with PKAN (54=adult; 30=pediatric) were random- upon interim study analysis.
ized to fosmetpantotenate vs placebo. Mean
SD age is Keywords: Neuromuscular Disorders, Translational/
22.9
12.1 (range=6-58) years (adults=29.6
9.7; pediatric = Experimental Therapeutics, Genetics

S168 Annals of Neurology Vol 86 (suppl 23) 2019

 INDEX OF AUTHORS

Aakil A 141 Amid A 196 Bassal F 105

Abdala J 23 Amin H 78 Bastian A 228
Abdel-Hamid H 104 An Haack K 177 Basu E 2
Abdelmoumen I 33, 91 Ananth A 37 Battaglia D 41
Abdennadher E 201 Andersen J 118, 119, 127 Baumer F 13
Abend N PL2-2, 139 Andersen N 80 Bayrak-Toydemir P 31
Aboulsaoud P 209 Anderson A PL2-2 Beaulieu F 130, 141
Abraham T 137 Anderson S 148 Bebin E 154
Abreu Molnar D 34 Andrews S 123 Bechter M 208
Acosta M 206 Andujar F 249 Beck A 257
Acquati S 251 Annesley C 258 Behne R PL3-5
Adams D 206 Ansong D 112 Beimer N 50
Adams J 230 Anstett K 87, 232 Bell E 132
Adang L PL1-6, 29, Antonioli G 251 Bellen H 257
82, 210 Anwar T 138 Belter L 164, 168
Adesina A 3 Aravamuthan B 122, 133, 134 Bembi B 220
Aertker B 121 Archuleta P PL2-4 Ben Omran T 165
Agarwal A 62 Arenkiel B 9 Benedetti G PL3-4
Agarwal A 163 Arjunji R 172, 180, 199, Berg A 47, 255
Agarwal P 257 200, 201 Berger R 142
Agarwal S 21 Armangue T PL1-6 Berl M 131
Agner S 103 Arndt D 253 Berner T 213, 231
Ahmad A 94 Arroyave-Wessel M 111 Bernstein J 257
Ahmed A 226 Arya K 163 Berry M 35
Aiuti A 251 Arya R PL2-2 Berry-Kravis E 202, 203, 205
Ajayi T PL1-4, 225 Asato M 142 Bertini E 165
Akiyama S 150, 160 Ashwal S 17, 23, 145, 152 Bertoldi M 213
Al-Zaidy S 183 Aubourg P 256 Berton F 12
Alakurtti K 81 Augustine E 205 Besnier C PL1-6
Alam J 50 Aylward B 98 Bhan I 165, 166, 174
Alasmari A 76 Aylward S 98 Bharucha-Goebel D 260
Alastalo T-P 81 Aziz A PL3-2 Bhathal I 237
Albashiti B 104 Badalamenti V 54 Bianchi D 150, 159, 160
Albassam F PL3-7 Bailey B PL2-3 Bibbiani F 182, 186
Aldave G 3 Baird J 5 Biffi A 251
Aldhalaan H 76 Balasa A 109 Bingaman W 99
Alfadhel M 76 Baldoli C 251 Bird L PL1-2
Alfaifi A 76 Balk K 132 Bishop K 36
Alfano L 183 Ball L 26, 116 Black K 123
Alfarano A 69 Balser J 216 Blau N 213
Alhadid K 151 Banach M 128 Bley A 79, 216
Alhashem A 76 Bankiewicz K 90 Bluvstein J 232
Alkuraya F 76 Barañano K 144 Boelens JJ 214
Almuhaizae M 77 Barissi M 95 Bolbocean C 249
Almutairi F 76 Barkley T 235 Bolton J 69
Alsahli S 75, 76 Barks M PL2-3 Bonifacio S 139
Alshahwan S 76, 77 Barnik-Olson B 17 Bonikowski M 128
Alshamrani K 141 Barry M 247 Bonkowsky J 30, 31, 32
Alsubhi S 76, 77 Barry S 179 Bonnemann C 260
Altuwaijri W 76 Barth J 204 Bonthius D 115
Alzaidan H 77 Bartnik-Olson B 23 Borasino P 37
Amartino H 256 Barzaghi F 251 Borghs S 54
Ames E 211 Basma N PL2-1 Borkowska K 201

Program and Abstracts, Child Neurology Society S169

Bornhorst M PL3-6 Chapin A 31 Crawford P 255
Bouchemi M 201 Chapman K PL2-2, 69 Crawford T PL1-5, 165,
Boyd B 38 Checketts D 56, 61,70 169, 173
Bramley H 18 Chen A 118, 119 Cristancho A 148, 149
Brandao L PL3-1 Chen D 28, 53 Critchley D 45
Brandsema J 181 Chen D 52 Cross JH 41
Brandt T 93 Chen I PL3-5 Cross Z PL1-6, 29
Braverman L 49 Chen J 162 Cruz R 164, 168
Brenton N PL2-2 Chen K 128, 129 Cruz-Zeno E 171
Brooks S 227 Cheung K 260 Cugnata F 251
Brown L PL2-4 Chien Y-H 177, 207, 231 Cui L 97
Brown W 5 Chiesa R 214 Culp J 85
Bubb G 208 Chin E 120, 153 Cure C 86, 111
Buccella F 184, 185, 191 Chin J 203 Curry M 168
Buch K 233 Chin R 71 D’Amore A PL3-5
Buchhalter J 47 Chin W 214, 256 D’Souza P 206
Buckley D 118, 119, 127 Chintagumpala M 3, 4 Da X 156
Budnik E 114 Chiriboga C 166, 169 Dabbous O 172, 180, 199,
Bulas D 86, 111 Choi M 156 200, 201
Bumbut A 59 Choi S 42 Darragh A 244
Buonanno F 147 Chong J 24 Darras B PL1-5, 166, 169
Burdine R PL1-2 Chorąży J 201 173, 189
Burns C 259 Chou C 186 Davis P 154
Butler I 121, 125 Chu C PL2-3, 139 Day J PL1-5, 169, 170
Butler K 205 Church K 183, 188 De Giorgis V 82, 210
Butterfield R PL1-5, 165 Ciafaloni E 193 de los Reyes E PL1-4, 204,
Buttermore E PL3-5 Cicalese M 251 205, 221, 225
Caffo B 14 Ciceri F 251 De Oliveira S 256
Cahan H PL1-4, 225 Ciftci-Kavaklioglu B PL3-7, 25 De Simone M 82, 210
Cain J 221 Cilio M 139 De Vivo D 165, 173
Calabrese T PL2-4 Ciotti F 251 Dean R 180
Calabria A 251 Clark G 140, 248 DeBiasi R 86, 111
Calame D 106, 257 Clark S 50 DeBraganca K 2
Calbi V 251 Clarke D 69 Del Toro M 220
Calcedo Del Hoyo R 260 Clemens P 187 DeLaGarza-Pineda O 138
Calley C 39 Cleveland J 54 Delage A 184, 185, 191
Cameron M 96, 100, Cloutier M 172 DeLuca S 244
101, 131 Cohen A 154 Demarest S 205
Campbell C 120 Cokley J 72 Denecke J 79
Campbell C 196 Collins E 193 Denny-Rivers C 221
Carbone L 50 Comi A 226 Deodarto F 220
Carducci C 213 Comi G 251 Desguerre I 184, 185, 191
Carmody E PL3-5 Conaway M 244 deVeber G PL3-1, PL3-2,
Carpenter J PL2-2 Confer N 233 151, 236
Carrazana E 60, 64 Connolly A PL1-5, 169, 187 Devinsky O 41
Carter M 195 Conway AM 207, 231 Dhamija R 92, 245
Caruso P 229, 233 Corcoran S 221 Diamond M 103
Castelli J 204 Cordero J 86 DIAZ 001.04
Castro D 174 Corey G 137 Study Group 60, 64
Cauley E 11 Cormier N 205 Diaz G 208
Cavalcanti D 86 Cornejo P 105 Diaz-Medina G 84
Chamberlain L 137 Corre C 79 Dick A 86
Chambers H 129 Counterman K 167 Dies K PL3-5
Chang T PL2-3, 40, Cracco J 52 Dietz R 137
138, 139 Craig A PL3-3, 150 DiMario Jr. F 171
Chao H-T 257 159, 160 Dimitrova R 126, 128, 129

S170 Annals of Neurology Vol 86 (suppl 23) 2019

DiSabella M 96, 100, 101 Faqeih E 76 Frazier M 215
DiSerio C 251 Farfel G 36, 38, 41, 44, 62 Freimark J 218
Divinagracia E 255 Farhat N 203 Friedmann K 203
Dlamini N PL3-1, PL3-2, 151, Farias-Moeller R 22 Fumagalli F 251
236, 237, 240, 242, 243 Farinelli G 251 Fung L 13
Dlugos D 44, 47, 60 Farmer C 203 Furda M 100
Domi T 236, 242 Farrar M 166, 174, 198 Gabaldo M 251
Donovan J PL1-3 Farrow E 257 Gadra E 148
Dorais M 135, 136 Farrow M 198 Gahl W 206
Doslea A 26, 116 Farwell W 165, 166, 173, 174 Gaillard W PL2-2, 40, 47, 59
Douglass L 141 Fatemi A 228 Gainza-Lein M PL2-2
Downey G 251 Fazzi E 82, 210 Galer B 36, 41, 44, 62
Dredge D 162 Fedak Romanowski E 42, 69 Gali K PL2-4
Droege M 172, 199, 200 Fehlings D 118, 119, 127, Gall K 81
Dsouza N 92 128, 236 Galli J 82, 210
du Plessis A 86, 111, 158 Feinstein L PL2-2 Gallo V 251
Duke E 1 Feldman A 18 Gambino G 166
Dulcich M 145 Feltner D PL1-5, 169, 170, 180, Gammaitoni A 36, 41, 44, 62
Dunayevich E 70 183, 198, 199, 200 Gandham S 122
Duncan C 214, 256 Ferrari M 251 Garcia-Cazorla A 123
Dunkley B 237 Ferrer A 92 Garden G 258
Dunn C 126 Ferrua F 251 Gardner R 258
Dure L 37 Fichorova R 141 Gasalla T 54
During M PL1-2 Figueroa J 23 Gauthier-Loiselle M 172
Dutt M 53 Finanger E PL1-3 Gautschi M 220
Dvorak C 179 Finkel R PL1-3, PL1-5, 165, Gavazzi F PL1-6, 82, 210
Dyck Holzinger S 118, 119, 246 169, 170, 173, 174 Gavi N 48
Ebrahimi-Fakhari D PL3-5 Finnegan T 209 Gebremarium A 50
Eckert S 208 Finney O 258 Gemperle C 213
Edmondson E 140, 248 Fischer C 2 Georgieva V 201
Edwards M 155 Fisher B 255 Gervelis W 238
Eichinger K 193 Fisher K 43, 107, 140, Gerwin J PL1-7
Eichler F 79, 156, 216, 233, 175, 248 Gholipour A 154
234, 256 Fleming M 26, 116 Ghosh D 176
Ejaz L 27 Fletcher L 50 Ghosh N 145
Eksambe P 250 Flint J 235, 239 Gidal B 45
Elfring G 182, 189 Flint L 123 Gil-Nagel A 41, 70, 71
Elguen S 29 Foley A 260 Gilbert D 16
Elloumi H 88 Forbes S PL1-3 Gilbert L 123
Elshoff J-P 54 Fortin O 135,136 Gioia G 36
Emami Z 237 Foster R 165, 166 Giraldo P 220
Emerson N 48 Fourzali Y 111 Girkar U 19
Emrick L 78, 106, 257 Fox A 132 Gissen P PL1-4, 225, 256
Engbrecht B 18 Fox L PL3-3 Giuberti C 137
Epstein L PL2-6 Fox M 154 Glaittli K 32
Erklauer J 212 Frade-Garcia A 34 Glass H PL2-3, 139
Escapita A 124 Fradette S 165, 173 Glauser T PL2-2
Escolar M 8, 259 Francesconi W 12 Glinton K 3
Ester Bernardo M 251 Francisco C 113 Goeden M 239
Estwick T 206 Franck L PL2-3 Gofshteyn J 46
Evankovich K 109 Franz D 66 Goldback-Mansky R PL1-6
Ewen J 14, 15, 16, 153 Fraschini M 251 Goldenholz D 55
Facchini M 251 Fraser J 94, 224 Goldstein J PL2-2
Fain D 80 Fraser P 177 Golomb M 238
Fajardo M 65 Fraser S 121 Gombolay G 28
Famiglietti H 87 Frazier J 141 Gonorazky H 196

Program and Abstracts, Child Neurology Society S171

Gonzalez Garcia A 192 Heimer G PL1-2 Jara H 141
Goodkin H PL2-2, 47, 132 Heller D PL1-7 Jarecki J 164, 168
Goodman J 228 Helman G PL1-6 Jarjour I 72
Gordon-Lipkin E PL2-7, 83 Hempel M 79 Jarnes J 227
Gorodetsky C 240 Herman I 84, 106, 212 Jayakar A 34
Gourley D 46 Heron B 220 Jecrois E PL3-6
Grabowski E 147 Herzberg E 139 Jehi L 51
Graham G 150, 159, 160 Hess J 18 Jeltsch K 123
Grant E 150, 159, 160 Hess M 237 Jensen I 180
Grant K PL2-3 Himmelreich N 213 Jiang H 204
Gray S 260 Hirtz D 141 Jiang J 111
Greblikas F 259 Hischke S 79 Jimenez S 33
Greenblatt M PL1-7 Hitchins L PL2-6 Jimenez-Gomez A 43
Greenwood R 217 Hixson J 49 Jinnah H 259
Greiner H 66 Hoffman E 187 John C 112
Grewal P 241 Hoffmann A 203 Johnson D 85
Griffin D 188 Hoffmann G 213 Johnson J 120
Grijalvo-Perez A 90 Holder J 249 Johnson K 165
Grinspan Z PL2-1, 46, 47, Holland K PL2-5 Johnson T 124
55, 69 Holshouser B 17, 23, 152 Jones S 214
Griswold D 155 Holt P 28 Jong Y-J 165
Groeschel S 29 Honarvar F 242 Jordan L 247
Grønborg S 220 Hoon A 120 Joseph C 228
Grossbauer L PL2-3 Horn M 141 Joseph R 141
CP-NET Group 236 Horn P PL2-5, 6, 16 Joshi S PL2-4, 42, 50
Grover S PL3-7, 25 Hsich G 230 Kahn I 26, 116
Grunewald S 220 Huang C-C 252 Kaimal R 20
Guenther E 35 Hudgens S 223 Kalpathy-Cramer J 156
Gul F 129 Hueneke S PL2-4, 254 Kantamneni T 51
Guldberg C 223 Hug C 177 Kapil N 124
Gunning B 41, 70 Hughes J 105 Kapoor N 214
Guntrum D 193 Hull M 72, 117 Karakas C 52, 140, 248
Gupta A 19 Humphrey K 6 Karkare S 250
Gupta A 219 Hundallah K 76 Kaseka ML 243
Gupta N 90 Hwang J 178 Kaspar B PL1-5, 169, 221
Gurcharran K 46 Hwu P W-L 231 Kassner A 151, 242
Gust J 258 Hwu W-L 165, 207 Kataria S 130
Guyot J 50 Hyland K 213 Kato M 123
Hahm K-S 190 i Dali C 220, 223 Kaufman M 228
Hajianpour MJ 85 Iammarino M 183, 188 Kaul S 125
Halford J 61 Iannaccone S PL1-5, 169 Kavanagh S PL1-5, 198
Hallman-Cooper J 28 Im K 150, 159, 160 Kayyal S 212
Han M 155 Imamura-Ching J 90 Keefe M 32
Haney D 44 Ingemann L 220 Kehrer C 29
Hannibal M 211 Mini-COMET Keller J 228
Hansen M 156 Investigators 177 Kenney-Jung D 214, 219
Hanson E 9 Iqbal M 20 Kerashvili N 73, 74
Hardy D 21 Iruthayanathan R PL3-7 Kerecman J PL3-3
Harper A 187 Isquith P 36 Kern-Smith E 53
Harris M 48 Izzo E 81 Kernbauer E PL1-5, 169, 170,
Hartman R 145 Jack R 10 183, 198
Hartsuyker K 258 Jacob E 252 Khakoo Y PL2-1, 2
Harwood M 105 Jacobson S 260 Khalid R 235, 239
Hashmi N PL3-3 Jacoby D PL1-4 Khan F 199, 200
Haxton L 234 Jaeger R 203 Khan L 112
Heeren T 141 Jain M 260 Khurana D 91

S172 Annals of Neurology Vol 86 (suppl 23) 2019

Kichula E 179, 181 LaGrant B 55 Lo W 244
Kiguchi H PL1-7 Laheji F 147, 229 Locatelli S 251
Kim A 8 Lai Y-C PL2-2 Lock M 36
Kim H 126, 129 Lakhotia A 179 Loddenkemper T PL2-2, 47
Kim L 155 LaMothe J 46 Logan W 151
Kim SH 7 Landers J 139 Longo N 208
Kim SK 7 Langdon R 96, 100, 101 Longoni G PL3-7, 25
Kimball E PL2-4 Langelier C 112 Lotze T 106, 107, 109, 175
King S 215 Lapin B 51 Lowes L 183, 188
Kirby K 216 Larson P 90 Lu S 205
Kirschner J 165, 166, 184, Lateef T 97 Lucas F PL3-3
185, 191 Lau H 87, 216, 232 Luecke T 123
Kirton A 118, 119, 127, 246 Lauer A 156, 229 Lui A 24
Kitano R 150, 159, 160 Laux L 62 Lund T 256
Klee E 92 Law J 145 Lyons-Warren A 9
Klein R 103 Leal-Pardinas F 205 MacDougall J PL1-3
Klopstock T 259 Ledet D 10 Macek T 169, 201
Knappertz V 56, 70 Lee C 247 MacGregor D PL3-2, 237, 240
Knupp K 62 Lee J 190 Machie M 139
Koclas L 118, 119, 127, 135, 136 Lee J 190 Mackenzie K 257
Koenig E 173 Lee N-C 207, 231 Mackenzie S 211
Koh J PL1-6, 82 Lee P 160 Macnamara E 206
Koh S 47 Legido A 33 Madan N 150, 159, 160
Kolevzon A PL1-2 Lehky T 260 Madankumar R 159
Konersman C 179 Lehman K 183, 188 Madden J 205
Koskenvuo J 81 Lehmann L 1 Magni S 251
Koskinen L 81 Lehwald L 204, 205 Mah J 187
Koster K 12 Leigh F 179 Mahmoud A 76
Kothare S 250 Leischner M 114 Maier E 220
Kousa Y 86, 111 Lemmon M PL2-3 Malbari F 3, 4
Kraegeloh-Mann I 29 Lenz C 120 Mallewa M 112
Kramer-Golinkoff J 29, 82 Leon K 112 Mallik A 114
Kratimenos P 40 Leonczyk C 203 Malone D 180
Krishan P 240 Lerner J 48, 252 Mancini M PL1-3
Krishnan P 236, 237 Leslie E 86 Manganaro S 179
Kristensen A 184, 185, 191 Lester-Pelham S 42 Mannen E 124
Kriz P 5 Leuzzi V 123, 213 Mansour T 86
Krogstad P 110 Levy A 4 Manzari M PL1-7
Kroner B 59 Levy J 127 Manzini M 11
Kronn D 177 Levy R 20 Mao D 257
Krosschell K 174 Lewis M 18 Mar S 24
Krueger D 154 Lewis S 188 Marashly A 69
Kruk S PL2-7, 83 Li C 112 Marcus L 108
Krysko K 24 Li N PL1-7 Marden J 218
Kuban K 141 Li W PL3-6 Mark P 80
Kühl J-S 214, 256 Licht D 149 Marquis B 46
Kukreja M 3 Lightner D 241 Marsh E 56, 148
Kumada S 177 Likhite S 221 Martin A 167
Kuntz N PL1-5, 165, 166, 169 Lim J 212 Martin M 54
Kurian M 123 Lin F 3 Martino S 251
Kushner B 2 Lin Y-C 2 Maru B 180, 200, 201
Kwon J 193 Lindemans C 214 Massey S PL2-3, 139
L’Italien J PL1-5, 169, 183, 198 Lipkin P 15 Matesanz S 181
Labarthe F 177 Liu C 126 Mathern G 110
Labban F 158 Liu K 177 Mathias S 219
Lagae L 54 Liu Y 173 Maximilian M 86

Program and Abstracts, Child Neurology Society S173

May A 69 Misko A 79, 233, 234 Nichols J 17, 152
Mayer O 181 Mistry A 36, 41, 62 Norato G 260
Mayne E 20 Mitchell W 71 Northrup H 154
Mazurkiewicz-Bełdzi
nska M 56 Mithal D PL2-6 Novak O 132
McAllister L PL3-3 Mittal N 113 Novara S 37
McCaffery H PL3-4 Modrcin A 179 Nuryyev R 145
McCall J 133 Mohamed I 69 O’Connor J 255
McCarter R 111 Mohanty M 130 O’Kane A 138
McClintock W 96, 100 Moharir M PL3-1, PL3-2, O’Shea T 141
McColly M 183 237, 240 Obenaus A 145
McCoy E 10 Mondok L 22, 161 Oberman R 234
McCusker E 126, 128, 129 Montes J 166 Ochoa-Lubinoff C PL1-2
McDonald C 182, 184, 185, Montini E 251 Ogrinc F PL1-5, 169, 170,
187, 189, 191 Montioli R 213 183, 198, 200
McDonald K PL1-6 Moodley M 176, 222 Oh A 105
McDonnell E 189 Mora M 11 Ohki H 177
McDonough T PL2-2 Morales A 111 Okposo K 179
McDougall Kestner V 239 Morena F 251 Olaya J 205
McGill B 198, 201 Morgan L PL2-2, 47 Olshavsky L 6
McGoldrick P 47, 69 Morgenroth L 187 Oluigbo C 40, 131
McGowan M 138 Moroni I 11 Opladen T 123
McGuire P PL2-7, 83 Morrison G 36, 38, 41, 44, 62 Opoka R 112
McIntosh J 182, 186 Morrison G 45 Oppeboen M 123
McKnight D 88, 93 Moss R 55 Orcesi S 82, 210
McManus M PL2-4 Mostofsky S 14, 16 Orchard P 214, 219, 256
McMillan H 195, 196, 198 Motti D 221 Ortman C 142
McNamara N 42 Mouridsen K 156 Osei-Tutu L 112
McNeil E 214, 256 Movassaghi M 110 Oskoui M 118, 119, 127,
Meadows A 188 Msall M 111 135, 136, 173, 246
Meilahn J 129 Mukherjee S 126 Osman M 27, 89, 147, 162
Melendez-Zaidi A 109 Mulder B 154 Ouyang H 169, 183
Melendi M PL3-3 Mulkey S 86, 111, 158 Oyoyo U 17, 152
Melmed R PL1-2 Muntoni F 173, 182, 184, Pabst L 98
Melvin J 33 185, 191 Pace R PL3-4
Mendell J PL1-5, 169, 170, Murray J 86 Palacios R 19
183, 188 Musolino P 147, 156, 229, 233 Palanisamy D 222
Mengel E 220, 223 Mwangi M 110 Palasamudram S PL3-1
Menier M 170, 200 Nabbout R 44, 61, 62 Pandit I 99
Mercuri E 166, 170, 173, Nadal-Nicolas F PL3-6 Paneth N 141
184, 185, 191 Nagy A 89 Pang E 237
Merikangas K 97 Naldini L 251 Pappas J 232
Merritt L 208 Nangia S 46 Paprad T 58
Messer R 67 Narayan R 105 Park H-K 190
Meyer K 204, 221 Nascimento Park K 67
Michon A 253 Osorio A 184, 185, 191 Parker M 26, 116
Migliavacca M 251 Nash K 113 Parnes M 117
Miglietta S 251 Natali-Sora M 251 Parsons J 165, 198
Mikati M PL2-2 Nataraj S 68 Patel A 2
Milewicz D 229 Nathan N 145 Patel K 29
Millan F 88 Nayak A 57 Patel A 47, 50, 71
Miller B 180 Neil E 211 Patsalos P 45
Miller I 60, 70 Nelson E-L PL2-4 Patterson Gentile C 21
Miller N 81 Nelson S 186 Patterson J 132
Miller N 183, 188 Ness J 108 Patterson K 197
Minard C 4 Newborn-Palmer L 254 Patterson M 223
Miner J 103 Ng P 127, 135, 136 Pawlowski K PL2-3

S174 Annals of Neurology Vol 86 (suppl 23) 2019

Peariso K PL2-2 Reebals L 6 Sandoval Karamian A 20, 143,
Pearl M 40 Rees J 194 146
Pearson T 90, 123 Regalado E 229 Sands T PL2-2
Peer K PL1-6, 82 Reha A 204 Saneto R 70
Pehlivan D 84, 140, 248 Reilly S PL2-6 Sansone V 165
Peltz S 182 Resnick T 65 Santoro J 27
Pena L 169 Reuter C 257 Santos C 184, 185, 191, 218
Penematsa V 186 Reyes B 48, 252 Santra S 220
Pérez Dueñas B 259 Reyna S 166, 174 Saredi S 11
Pergami P 94 Rhee J PL1-6, 94, 224 Sarzana M 251
Permar S 137 Richardson R 197 Sattar S 68
Pernia C 145 Rinaldi F 221 Scafidi J 138
Perry M 69, 70, 71 Riney K 41 Scharf R 179
Pestana Knight E 51 Ritter D PL2-5 Scheffer I 61, 70
Peters J 154 Riviello J PL2-2, 57 Scheller J 157
Peters W 73 Roach E 179 Scherrer B 154
Petrillo M 173 Robak L 3, 257 Schiffmann R 234
Peyton C 111 Robertson A 151, 237 Schilling T 218
Philbrook B 28 Robinson S 120 Schlatterer S 158
Pichard S 177 Rodino-Klapac L 188 Schmiedel M 30
Pierce E 100 Rodriguez A 65 Schneider M 33, 91
Pigeon N 118, 119, 127, Rodriguez D 245 Scholl E 32
135, 136 Rogers D 98 Schön G 79
Pina-Garza J 54 Rollins J 141 Schoonjans A-S 62
Pines A 245 Romero J 91 Schultz M 169, 179, 197, 198
Pivonka-James J 17, 152 Rooney W PL1-3 Schultz R 254
Plaia A 145 Rosman N 130 Schultz-Rogers L 92
Plume J 115 Rothner A 95, 99, 102 Schulz A PL1-4, 225
Poe M 8 Roubertie A 220 Schwab L 251
Porter F 202, 203 Russo S 111, 158 Schwartz A 159
Postels D 112 Rutatangwa A 24, 113 Scuffins J 88, 93
Potocki L 84 Rutkove S 134 Sebold A 226
Powell A 211 Ruzhnikov M 257 Seda J 172
Pozsgai E 188 Ryan K 20 See S 205
Prasad V 214 Ryan M 165, 173 Seed M PL3-1
Privitera M 56 Ryan T 226 Segal E 60, 64
Prohl A 154 Rybczynski S 226 Segovia J 251
Pulcine E PL3-1, 240 Rybin D 260 Sehgal R 114
Purington N 20 Saade D 260 Seo Y 90
Pykett M 207, 231 Sachdeva R PL2-4 Seppala E 81
Quon J 155 Sady M 26, 116 Sessa M 251
Raas-Rothschild A 234 Sahin M PL3-5, 154 Sevin C 256
Rabinowicz A 64 Sahjwani D 101 Seydel K 112
Racette B 126, 129 Saito K 174 Shafer P 254
Radecki L PL2-4, 254 Sajeev G 189 Shah A 169
Raju P PL1-7 Sale M PL3-3 Shah A PL2-4, 254
Ralston S 159 Samba I 148 Shah S 183
Ramey S 244 Sampth S 130 Shah V 43
Rancoita P 251 Samulski R 260 Shah Y 250
Rao M 10 Samura O 150, 159, Shamir E 214, 256
Rao V 187 160 Shanmugham A 93
Rau S 42 San Sebastian W 90 Sharma M 235, 239
Record E 59 Sanapo L 158 Sharp A 144
Recupero S 251 Sanchez Russo R 192 Sharr C 159
Redaelli D 251 Sánchez-Carpintero R 61, 70 Shaywitz A 216
Rednam S 3 Sanchez-Fernandez I PL2-2 Shekar S 227

Program and Abstracts, Child Neurology Society S175

Shell R 183 Spivey T 11 Thiele E 62
Shellhaas R PL2-3, PL3-4, Sproule D PL1-5, 169, 170, Thiffault I 257
42, 47, 139 172, 179, 180, 183, Thomas C PL2-3
Sherbini O 29 198, 199, 200 Thomas S 18
Shevell M 118, 119, 127, Srinivasan R 12 Thony B 213
135, 136, 246 Staggers K 4 Thorwall R 42
Shieh P PL1-3, PL1-5, Standridge S 6 Thrasher A 256
166, 169, 189 Stasheff S PL3-6 Thurm A 203
Shiloh-Malawsky Y 61, 217 Stebbins C 173 Tian C 218
Shirk B 18 Stefans V 163 Tifft C 206
Shrey D 69 Stephenson D 32 Timm D 221
Shroff M PL3-1, 151 Stevenson R 244 Tittle B 161
Shu F 165 Stevenson T 32 Tizzano E 173
Shukla N 107, 140, 248 Stirrat E 242 Tochen L 94, 131, 224
Shults J PL1-6, 29, 82 Stowe R 72 Todd D 115
Siddicky S 124 Strauss K 198 Tomin A 195
Siddiqui S 22 Streicher D 149 Tone B 23, 145
Sidman R 145 Streicher J 149 Tong K 17, 152
Siebold L 23 Strelzik J 96, 100, 101 Topaloglu H 165
Signorovitch J 189, 218 Stutterd C 29 Topjian A PL2-2
Silvani P 251 Sullivan J 44, 62 Torene R 88
Simmons A 102 Sumner C 173 Toro C 206
Simonetta Zorzi G 259 Sung D-K 190 Trandafir C 63
Simpson H 124 Suslovic W 26, 116 Treat J 149
Singh J 240 Suter B 249 Trifillis P 182, 184, 185, 186,
Singh K 250 Swartwood S 63 189, 191
Singh T 137 Sweeney H PL1-3 Triplett W PL1-3
Singhal N 47 Sweet K 80 Tseng S-H 207, 231
Singhal R 69 Swoboda K 165, 170, 179, 198 Tsering D 131
Skotko B 159 Sykut-Cegielska J 123 Tsuboyama M 65
Slasor P PL1-4, 225 Symonds T 223 Tsuchida T 40, 138
Slavin A 48 Szaflarski J 45 Tucci F 251
Slim M PL3-1, PL3-2, 236, 243 Tabarki B 76, 77 Tulinius M 166, 174, 185, 191
Smith A 103 Tai C-H 207, 231 Tuna I 194
Smith B 92 Taieb V 201 Tunc E 230
Smith E 132 Tak Y 122 Tutmaher M 28, 192
Smith E 169, 187, 229 Takacs D 140, 248 Tylki-Szymanska A 220
Smith Fine A 228 Takanohashi A PL1-6 Ullrich N 1
Smith N 256 Tambunan D 130 Ulrick N PL1-6, 82
Smith S 38 Tan W-H PL1-2 Upadhyayula S 192
Snyder E 145 Tang R 50 Urbik V 30
Soderholm H 30, 31, 32 Tarantino C 239 Valencia I 33
Sogawa Y 142 Tarquinio D 60, 64 Van Rensburg E 118, 119, 127
Soldatos A 260 Tarui T 150, 159, 160 Vandenborne K PL1-3
Soliven RJ 252 Tasker R PL2-2 Vanderver A PL1-6, 29, 210
Solomon T 112 Tawil R 179 VanLandingham K 61, 71
Soorya L 203 Tay S 123 VanMeter S 202
Soresi S 253 Taylor T 112 Vannest J 39
Soul J PL2-3, 139 Tchapyjnikov D PL2-2, 137 Vartanian R PL3-4
Soussand L 154 Teigen C 88 Vawter-Lee M 66
Souza M 182, 189 Teinert J PL3-5 Vaynshteyn J PL1-7
Specchio N PL1-4, 225 Tennekoon G PL1-3, PL1-5 Veerapandiyan A 163, 193
Spector S PL1-5, 198 Tenney J 39 Veeravigrom M 58
Speltz S 189 Thakkar K 104 Vega-Torres J 23
Speroni S 156, 229 Thakur N 125 Venkat A 227
Spiga I 251 Thibert R PL1-2 Venkatesh Y 74

S176 Annals of Neurology Vol 86 (suppl 23) 2019

Verma S 192 Wheeler M 35 Yang A 205
Vezina G 40, 86, 111 Wheeler M 257 Yang Brown JJ 13, 146
Viamonte M 194 Wheless J 10, 60, 64 Yang J 68
Videnovic A 259 White K 221 Yang J 206
Viehoever A 90, 132 White P PL2-4 Yao Z 189, 218
Vierhile A 205 Whitehead W 3, 94, 158, 224 Yardeni T 148
Vilain E 86 Whittle J PL1-5 Yash S 250
Villanueva V 56 Wilfong A PL2-2 Yau I PL3-2
Vinters H 110 Willcocks R PL1-3 Ye X 120
Visootsak J PL1-2 Williams D 256 Yea C PL3-7, 25
Vitagliano M 246 Williams K PL2-2 Yeh EA PL3-7, 25
Voltattorni C 213 Wilson A 258 Yeom K 146, 155
Vossough A 149 Wilson C 23 Yoon S 85
Wainer A 203 Wilson M 112 Yoshii A 12
Wainwright M PL2-2 Wiltrout K 24 Yozawitz E 47
Waite M 260 Wimmer M PL3-5 Yu J 178
Waite S 27 Wirrell E 62 Yum S PL1-3
Walker M 89, 147 Woidill S 82 Yun M PL2-1
Wallace D 148 Wolf S 47, 69 Yusof A 145
Walter G PL1-3 Wolfe L 206 Zaidman C 187
Wang J 124 Wong B 218 Zambon A 251
Wang R 167 Wong J 166, 174 Zancan S 251
Wang R 205 Wong M 61 Zara M 171
Warfield S 154 Wong-Kisiel L 69 Zhang M PL2-1
Wash E 132 Wood D PL2-4 Zhang Y 174
Waubant E 24, 113 Wood E 67 Zhao Y 14
Webster H 137 Wood E 118, 119, 127 Zheng W PL3-6
Wei L-J 182 Wooldridge J 208 Zhu J 184, 185, 191
Weimer J 221 Wu J 8 Zhu Y PL3-6
Weiner H 4 Wu J 154 Zimmermann M 92
Weinstock A 71 Wusthoff C PL2-3, 20, 139, 143 Zinkus T 239
Weiss N 195 Xiao W 232 Zipunnikov V 97
Wells E 26, 116 Xiao Y 97 Zook-Lewis C 217
Westmacott R PL3-2, 237 Xu Q 112 Zuccoli G 8
Wharton J 247 Yamashita T 187

Program and Abstracts, Child Neurology Society S177