SECTION VI • Clinical–Electrophysiologic Correlations

PART III • Motor Neuron Disease

28  Atypical Motor Neuron Disorders

There are a heterogeneous group of motor neuron disorders discussed in detail in Chapter 26. Patients present with
that are rare but nonetheless important to recognize, progressive, asymmetric weakness and wasting that often
because they often can mimic the presentation of amyo- affect the distal upper extremity muscles first. Weakness is
trophic lateral sclerosis (ALS). These often are referred to in the distribution of named motor nerves, often with
as atypical motor neuron disorders. Although many of the sparing of other nerves in the same myotome (clinical
atypical motor neuron disorders share some features with multifocal motor neuropathy). This pattern is not seen in
ALS, they often can be distinguished by their clinical and ALS or its progressive muscular atrophy variant, in which
electrophysiologic characteristics (Boxes 28–1 and 28–2). the entire myotome is characteristically affected at the
One of the most important atypical motor neuron disor- same time. Occasional patients have weakness without
ders that can be confused with motor neuron disease is the wasting, a finding usually associated with pure demyelina-
immune-mediated motor neuropathy multifocal motor neu- tion. The disease is slowly progressive, with a male predi-
ropathy with conduction block (MMNCB). Strictly speak- lection, generally presenting before the fifth decade.
ing, this is a disorder of the motor nerve and as such is Definite upper motor neuron signs are absent, although

Box 28–1.  Clinical Clues of An Atypical Motor Neuron Disorder

Acute onset Late-onset Tay–Sachs disease (adult-onset hexosaminidase A
Paralytic poliomyelitis deficiency)
West Nile encephalitis Spinal muscular atrophies
Non-myotomal pattern of weakness Hereditary spastic paraplegia
Multifocal motor neuropathy with conduction block Adult polyglucosan body disease
Absence of significant muscle wasting in chronically weak Onset of illness before age 40 years
limbs Late-onset Tay–Sachs disease (adult-onset hexosaminidase A
Multifocal motor neuropathy with conduction block deficiency)
Predominantly lower motor neuron signs Familial amyotrophic lateral sclerosis
Multifocal motor neuropathy with conduction block Spinal muscular atrophy
Kennedy’s disease Hereditary spastic paraplegia
Spinal muscular atrophy Monomelic amyotrophy
Radiation injury Positive family history
Paralytic poliomyelitis Kennedy’s disease
West Nile encephalitis Late-onset Tay–Sachs disease (adult-onset hexosaminidase A
Monomelic amyotrophy deficiency)
Presence of sensory symptoms and/or signs Familial amyotrophic lateral sclerosis
HTLV-1-associated myelopathy Spinal muscular atrophy
Adult polyglucosan body disease Hereditary spastic paraplegia
Late-onset Tay–Sachs disease (adult-onset hexosaminidase A Adult polyglucosan body disease
deficiency) History of radiation therapy
Bladder or bowel dysfunction Motor neuron disease associated with radiation injury
HTLV-1-associated myelopathy History of malignancy
Adult polyglucosan body disease Paraneoplastic motor neuron disease (especially lymphoma)
Cerebellar, extrapyramidal, cognitive, and/or psychiatric History of old poliomyelitis
dysfunction Postpoliomyelitis syndrome
Late-onset Tay–Sachs disease (adult-onset hexosaminidase A History of electrical injury
deficiency) Motor neuron disease associated with electrical injury
Hereditary spastic paraplegia (complicated) History of human immunodeficiency virus infection
Adult polyglucosan body disease Retrovirus-associated motor neuron disorder
Duration of illness longer than 5 years
Kennedy’s disease
Radiation injury
HTLV-1, human T cell lymphotropic virus-type 1.

©2013 Elsevier Inc

DOI: 10.1016/B978-1-4557-2672-1.00028-3
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 Chapter 28 • Atypical Motor Neuron Disorders 433

Box 28–2.  Electrodiagnostic Clues of An Atypical vaccine, the incidence of acute poliomyelitis has been dras-
Motor Neuron Disorder tically reduced. Most cases now are associated with the live
attenuated virus in the oral polio vaccine and occur either
Conduction block on motor nerve conduction studies (not
at entrapment sites) in vaccine recipients or in individuals who are in contact
Multifocal motor neuropathy with conduction block with vaccine recipients, especially immunocompromised
Markedly slowed conduction velocities or prolonged distal patients. Other cases occur in travelers to areas where
latencies (not at entrapment sites) poliomyelitis is endemic; in 2011, these countries were
Multifocal motor neuropathy with conduction block Afghanistan, India, Nigeria, and Pakistan. Sporadic out-
Sensory nerve conduction abnormalities
Kennedy’s disease
breaks have also occurred in other underdeveloped coun-
Adult polyglucosan body disease tries. In rare, sporadic cases, infection presumably is due
Late-onset Tay–Sachs disease (adult-onset hexosaminidase to incomplete immunization status. Most sporadic cases are
A deficiency) no longer associated with the poliovirus but are the result
Multifocal motor neuropathy with conduction block (rare) of coxsackievirus, echovirus, or enterovirus infection.
West Nile encephalitis (rare)
Patients with acute poliomyelitis present with fever,
Myokymic discharges
Radiation injury headache, myalgias, and gastrointestinal disturbance. Weak-
Prominent complex repetitive discharges ness, wasting, and depressed reflexes begin to appear during
Late-onset Tay–Sachs disease (adult-onset hexosaminidase the first or second week of the illness. The distribution of
A deficiency) weakness typically is asymmetric, and the lower extremi-
Facial fasciculations/grouped repetitive motor unit ties are most commonly involved. The upper extremities,
discharges with activation
trunk, diaphragm, and bulbar muscles are occasionally
Kennedy’s disease
Acute or subacute neuropathic pattern on needle involved. Sensation and autonomic function are spared.
electromyogram Cerebrospinal fluid (CSF) typically shows a lymphocytic
Paralytic poliomyelitis, including West Nile encephalitis pleocytosis, often in the range of 100 to 200 cells per cubic
millimeter (rarely, polymorphonuclear leukocytes may be
seen early), during the preparalytic phase of the illness.
Pleocytosis, while invariably present in the preparalytic
retained or inappropriately brisk reflexes for the degree of
phase of the illness, tends to clear with the onset of the
weakness and wasting may be seen. Bulbar function and
weakness. The CSF protein level is commonly elevated
sensation are characteristically spared. Mild or transient
within the first several weeks of the illness, whereas CSF
sensory symptoms may be present. The characteristic
glucose is normal. Cultures from CSF usually fail to isolate
finding on motor nerve conduction studies is that of con-
the virus, although the virus can commonly be isolated from
duction block, temporal dispersion, or both, along the
the stool if it is obtained within the first 10 days of the
motor nerves. Other signs of demyelination also may be
paralysis. In addition, antibody titers from the acute and
seen, including slowed conduction velocities, absent or
convalescent phases may allow virus identification.
impersistent F responses, and prolonged distal motor laten-
Weakness associated with poliomyelitis now is seen most
cies. Sensory conduction studies are typically normal.
often in the electromyography (EMG) laboratory not as an
Other than multifocal motor neuropathy with conduc-
acute process but in patients with postpolio syndrome
tion block, atypical motor neuron disorders are seen most
(PPS). PPS occurs in at least one fourth of previously
often in association with certain viral infections or as the
infected patients, usually 25 to 30 years after the attack of
result of specific genetic mutations. Rarely, atypical motor
acute poliomyelitis. Patients develop pain, fatigue, and
neuron disorders are seen as a remote effect of some neo-
weakness, often most prominent in the muscle groups pre-
plasms or as a result of electrical injuries or radiation.
viously affected by the poliomyelitis. However, muscles
Because the prognosis in ALS is uniformly poor compared
that were clinically normal may develop symptoms, reflect-
with these atypical motor neuron disorders, it is essential
ing the diffuse underlying nature of the previous poliomy-
that the correct diagnosis is reached. In addition, some
elitis. The etiology of PPS is not completely known, but it
are potentially treatable; in others, genetic counseling is
is most likely related to the normal aging process (i.e., most
important.
individuals lose some motor neurons after age 55 years)
superimposed on chronically denervated muscles. Patients
INFECTIOUS MOTOR   with PPS and worsening symptoms often are referred to
the EMG laboratory to exclude a new, superimposed
NEURON DISORDERS process, such as radiculopathy, entrapment neuropathy,
Paralytic Poliomyelitis   myopathy, or motor neuron disease as a source of increased
fatigue, pain, and weakness.
and Postpolio Syndrome
Paralytic poliomyelitis was once a common cause of
West Nile Encephalitis
acute lower motor neuron dysfunction. In the United States
from 1951 to 1955, an average of more than 15,000 cases Over the past several years, there have been an increasing
occurred per year. Through widespread use of the oral polio number of reports of a “polio-like” syndrome associated

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434 SECTION VI Clinical–Electrophysiologic Correlations

suggesting involvement of the dorsal root ganglia or periph-

eral sensory nerve as well. Needle EMG shows evidence of
axonal loss. The pattern of findings depends on when the
study is performed in relationship to the start of the illness.
Thus, in addition to coxsackievirus, echovirus, and enter-
ovirus, West Nile virus can be added to the list of infectious
agents that can result in an acute infection of the anterior
horn cells. Thus, paralytic poliomyelitis is best regarded as
a clinical syndrome that can be caused by a variety of
viruses, not simply the poliovirus.

Retrovirus-Associated Motor  
Neuron Disorders
Human immunodeficiency virus (HIV) is associated with a
FIGURE 28–1  West Nile virus. The vector for the West Nile virus
is the common mosquito. Although rare, an increasing number of variety of neuromuscular disorders, including peripheral
cases of poliomyelitis have been associated with this virus, either neuropathies, myopathies, and radiculopathies. Experimen-
alone or in association with encephalitis. tal studies in mice have shown that retroviruses can induce
(Courtesy of US Geological Survey.)
a lower motor neuron syndrome in mice and suggest a
relationship between retroviruses and the pathogenesis of
with West Nile encephalitis. The responsible virus, which is motor neuron disease. There are rare reports of patients
a member of the flavivirus family and is composed of a single with HIV infection and classic ALS, or a clinical syndrome
strand of RNA, was first isolated in 1937 in northern Uganda. resembling primary lateral sclerosis, without any other
In nature, the virus is transmitted between birds by mosqui- explanation for their symptoms. Other patients have had
toes (Figure 28–1). Jays, blackbirds, finches, warblers, spar- restricted lower motor neuron signs. Some reports have
rows, and crows appear to be most important in maintaining noted improvement or complete remission of the syndrome
the infection. Most infections in humans occur by way of a in these patients when they are treated with highly active
mosquito bite, although cases have been reported following antiretroviral therapy.
transplanted organs and infected blood products. Because Another retrovirus, the human T cell lymphotropic virus-
the disease is primarily spread to humans by mosquitoes, type 1 (HTLV-1), is well known to be associated with
patients typically are affected in the summer and early fall. spastic paraparesis in endemic areas (i.e., the Caribbean
Fortunately, most infections with the West Nile virus are basin, southwest Japan, southeast United States, southern
asymptomatic, with only one in 150 infections resulting in Italy, and sub-Saharan Africa) in a syndrome known as
neurologic involvement. The elderly and the immunocom- HTLV-1-associated myelopathy or Tropical Spastic Para-
promised appear to be at highest risk. After an incubation paresis (HAM/TSP). Along with spastic paraparesis,
period of several days, a nonspecific flulike illness develops, patients usually have bladder dysfunction and minor sensory
often with fever, headache, and joint and muscle pain. In symptoms. A motor neuron syndrome mimicking ALS is
some patients there may be additional features suggestive also observed in a series of patients with HTLV-1 infection.
of West Nile infection, including retro-orbital pain, facial The presence of spastic paraparesis or even typical ALS
congestion, and rash. Definitive diagnosis is made by the symptoms, with minor sensory findings or bladder dysfunc-
presence of immunoglobulin M antibodies in CSF or serum. tion, especially in an endemic area for HTLV-1, should
In patients with neurologic involvement, a combination prompt a search for HTLV-1 antibodies.
of encephalitis, meningitis, and myelitis can occur. Diffuse
weakness is common and often thought to be due to the INHERITED MOTOR  
encephalitis. Other patterns of weakness are also seen,
among them monoplegia, flaccid quadriplegia, bulbar weak-
NEURON DISORDERS
ness, and respiratory weakness. In some patients, an acute Familial Amyotrophic Lateral  
segmental flaccid paralysis has been described as an initial
presentation of West Nile virus, even in the absence of
Sclerosis (FALS)
meningitis or encephalitis. Such cases initially were attrib- Approximately 10% of cases of ALS are familial. Inherit-
uted to Guillain–Barré syndrome, although it now is clear ance is usually autosomal dominant. Over 10 different
that the weakness more likely was due to anterior horn cell genes have been identified, with the most common being a
disease. In patients in whom electrodiagnostic (EDX) mutation in the superoxide dismutase (SOD-1) gene on
studies have been performed, nerve conduction studies chromosome 21. The SOD-1 gene mutation accounts for
show reduced compound muscle action potential (CMAP) 15–20% of FALS. Other more commonly identified genes
amplitudes with relatively intact sensory conduction include the fused-in-sarcoma (FUS) and the TAR (transac-
studies. No evidence of demyelination is present. Rarely, tive response) DNA-binding protein (TDP-43) genes. These
patients have had abnormal sensory conduction studies, two genes account for approximately 3–5% and 1–3% of

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 Chapter 28 • Atypical Motor Neuron Disorders 435

FALS, respectively. Most recently, the gene encoding ubiq- develops. Proximal muscles are affected first, followed by
uilin 2 has been found to be a cause of X-linked FALS. In bulbar involvement, which may become marked. Dysarthria
addition, inclusions containing ubiquilin 2 have been found and dysphagia are associated with atrophy and weakness
in a large number of ALS patients suggesting a common of facial, jaw, and glossal muscles. Because of the prominent
pathology. Ubiquilin 2 is involved in the protein degradation bulbar involvement, Kennedy’s disease can be difficult to
pathway. Recently, a mutation in the chromosome 9 open differentiate from the bulbar variant of ALS. A classic and
reading frame 72 (C9ORF72) gene, resulting in an expanded striking clinical feature is the presence of facial fascicula-
hexanucleotide repeat in a noncoding region of the gene, tions, most prominent around the mouth and chin. Fas-
was found in a large percent of patients with familial ALS ciculations are present at rest, but they are more prominent
(23%) or frontotemporal dementia (12%). The clinical with contraction and are best elicited by having the patient
presentation and prognosis of patients with FALS are similar whistle or blow out the cheeks. Facial fasciculations are
to sporadic cases. One should consider the diagnosis of reported in more than 90% of case reports. Distal muscles
FALS in patients with ALS and a known family history or are affected later in the course. Reflexes typically are
in patients with an early clinical presentation. Commercial hypoactive or absent. There are no long-tract signs. Sensory
DNA testing is available for the more common genetic loss or sensory symptoms are rare. Although not universal,
mutations. Very rarely a patient with sporadic ALS (i.e., no most patients have gynecomastia, and some have other endo-
family history) is reported with one of these mutations. crine abnormalities, including diabetes and infertility.
Laboratory test results are normal except for a modestly
elevated creatine kinase (CK) level (often 500–1500 IU),
Spinal Muscular Atrophy
which is higher than the mild elevation typically seen in
A large number of inherited spinal muscular atrophies SMA or other motor neuron disorders. Nerve conduction
(SMA) result in selective degeneration of the lower motor studies often show normal motor studies. However, the
neurons. The characteristic clinical presentation is that of CMAP amplitudes may be low if they are recorded from
progressive, symmetric, proximal muscle weakness and weak and wasted muscles. Most patients have low-amplitude
atrophy, without upper motor neuron signs. Most are reces- or absent sensory nerve action potentials (SNAPs), which
sively inherited and linked to the survival motor neuron 1 reflect the association of Kennedy’s disease with degenera-
(SMN1) gene on chromosome 5q. Among the various tion of the dorsal root ganglia. This finding is very important
types, the most severe form occurs in infancy (Werdnig– because it is not seen in ALS and is an important clue in
Hoffmann disease), usually resulting in death before age 2 the recognition of Kennedy’s disease. Needle EMG shows
years. Others present in early childhood or during adoles- neurogenic changes, including increased insertional activity
cence or adulthood (Kugelberg–Welander disease) and have and reduced recruitment of large, prolonged duration, poly-
a much better prognosis. Although occasionally confused phasic motor unit action potentials (MUAPs) in affected
with ALS, adult-onset SMA is more commonly mistaken muscles. Needle EMG examination of the facial muscles
clinically for a myopathy. Direct DNA deletion analysis is may show grouped repetitive motor unit discharges, which
now commercially available but does not detect all cases. occur with mild activation of the facial muscles. Because
Although proximal muscles are most frequently involved, these discharges occur with mild voluntary contraction
other anatomic variants have been described, including rather than spontaneously, they are distinguished from
scapuloperoneal, facioscapulohumeral, and generalized myokymic or neuromyotonic discharges and are quite char-
forms. In addition, there is a rare distal SMA (also known acteristic of Kennedy’s disease.
as distal hereditary motor neuropathy or neuronopathy) Despite prominent bulbar weakness and the correspond-
that presents with a clinical phenotype similar to Charcot– ing risk of aspiration, longevity usually is not affected.
Marie–Tooth polyneuropathy, although with a notable lack Consequently, the correct diagnosis is important both for
of sensory symptoms or findings. This variant often is prognosis and for its value in genetic counseling. The diag-
referred to as the spinal form of Charcot–Marie–Tooth. nosis should be suspected in any male patient with motor
neuron disease who presents with proximal and bulbar
X-Linked Bulbospinal Muscular Atrophy weakness, a positive family history, facial fasciculations, or
gynecomastia and whose EDX studies show abnormal
(Kennedy’s Disease) sensory studies in addition to the typical widespread neuro­
The one inherited SMA that deserves special attention, nopathic pattern on needle EMG. An unusually elevated
because it can easily be confused with the progressive CK level is often an important clue as well. DNA testing
bulbar palsy variant of ALS, is X-linked bulbospinal mus- is commercially available. The gene is an androgen receptor
cular atrophy (Kennedy’s disease). It affects only men and gene with an expansion of a trinucleotide repeat (CAG).
has its onset between the third and fifth decades of life,
followed by a slow progression. Because there frequently is
no obvious family history in X-linked disorders, many of
Hereditary Spastic Paraplegia
these cases at first appear to be sporadic. Hereditary spastic paraplegia, also known as familial spastic
Some patients complain of exercise-induced muscle paraparesis, consists of a diverse group of genetic disorders
cramps and hand tremors several years before weakness characterized by progressive spasticity and sometimes

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436 SECTION VI Clinical–Electrophysiologic Correlations

weakness of the lower extremities. They are classified by which case the CMAP amplitudes are low, with normal or
their type of inheritance (autosomal dominant, autosomal slightly slowed conduction velocities. Sensory nerve con-
recessive, or X-linked) and whether the spasticity is the sole duction studies are also usually normal, but may be abnor-
manifestation of the disorder, termed uncomplicated or mal in approximately 25% of patients, consistent with
pure spastic paraplegia, or whether there are other accom- an axonal loss polyneuropathy. The needle EMG exam­
panying abnormalities (termed complicated spastic para­ ination shows abnormal spontaneous activity including
plegia). These other manifestations may include ataxia, fasciculation and fibrillation potentials. Complex repetitive
dementia, mental retardation, optic neuropathy, retinopa- discharges (CRDs) may be especially prominent. Large,
thy, peripheral neuropathy, amyotrophy, extrapyramidal polyphasic MUAPs with reduced recruitment are seen in
dysfunction, deafness, or ichthyosis. The clinical presenta- affected muscles.
tion, which includes age of onset, degree of deficit, and Adult-onset hexosaminidase A deficiency should be con-
associated symptoms, varies both within and between sidered in the differential diagnosis of any patient present-
families. ing with lower motor neuron disease, especially if there are
The diagnosis usually is straightforward if there is a coexistent cerebellar and/or psychiatric signs, or a family
known family history of pure progressive spastic parapare- history of similarly affected siblings. A definitive diagnosis
sis. If there is no known family history, other diagnoses are is made by measuring hexosaminidase A activity in serum,
considered, including HTLV-1-associated myelopathy (see leukocytes, or fibroblasts.
earlier), and most often the primary lateral sclerosis variant
of ALS.
Adult Polyglucosan Body Disease
Adult-Onset Hexosaminidase A Deficiency Adult polyglucosan body disease (APGBD) is an exceed-
ingly rare neurologic disorder; fewer than 30 cases have
(Late-Onset Tay–Sachs Disease)
been reported. The clinical presentation includes progres-
Hexosaminidase A is a lysosomal enzyme important in the sive upper and lower motor neuron dysfunction, sensori­
metabolism of gangliosides. Deficiency of this enzyme motor peripheral neuropathy, gait disturbance, urinary
results in an abnormal accumulation of GM2 ganglioside, incontinence, and dementia. All components of the disor-
leading to nerve cell degeneration. The adult-onset form of der may not be present initially, and motor symptoms may
hexosaminidase A deficiency (also known as late-onset Tay– predominate. The pathologic hallmark of the disease is the
Sachs disease) is a rare recessively inherited disorder, only presence of a large number of polyglucosan bodies, which
recognized in the late 1970s. In some affected individuals, structurally resemble Lafora bodies or corpora amylacea, in
the disorder can be mistaken for ALS or one of its variants, central and peripheral neuronal processes and astrocytes.
although most patients have coexistent cerebellar distur- Some cases appear to be sporadic and some familial (usually
bances, about half have psychiatric disturbance (especially autosomal recessive), with a high proportion occurring in
psychosis and depression), and approximately 25% have an families of Ashkenazi Jewish descent. The presumed cause
axon loss sensorimotor polyneuropathy. The adult-onset of adult polyglucosan body disease is genetic, especially in
form is quite different from the well-known rapidly pro- patients of Ashkenazi Jewish descent. A mutation in the
gressive infantile form of hexosaminidase A deficiency, glycogen branching enzyme gene, causing a deficiency of
known as infantile Tay–Sachs disease. An absolute defi- the glycogen branching enzyme, has been described in
ciency of hexosaminidase A causes infantile Tay–Sachs Ashkenazi Jewish patients with adult polyglucosan body
disease, whereas a partial deficiency results in the late- disease.
onset form. The diagnosis should be suspected in patients with pro-
Although the disorder affects multiple systems, nearly gressive upper and lower motor neuron dysfunction that
every affected patient has lower motor neuron involve- resembles typical ALS, but which is accompanied by
ment. Weakness and atrophy initially involve the lower urinary incontinence, sensorimotor polyneuropathy, and
extremities and are more prominent in the proximal dementia. If dementia and the motor neuron dysfunction
muscles. In the upper extremities, there is a predilection are prominent, one should also consider frontotemporal
for involvement of certain muscles, especially the triceps. dementia (see above) in addition to APGBD in the dif-
It is not uncommon for patients to initially be misdiagnosed ferential diagnosis. However, unlike frontotemporal
as adult-onset SMA. In one case series, nine of 14 patients dementia, in APGBD some distal sensory loss may be
also had upper motor neuron signs, but severe spasticity is found on clinical exam. EDX studies reveal mild to mod­
rare. Cerebellar signs are common, including dysarthria, erate slowing of motor nerve conduction velocity and
truncal ataxia, and dysmetria. If cerebellar signs are not low-amplitude or absent SNAPs. Extensive white matter
prominent, however, the neurologic picture can mimic abnormalities often are seen on brain magnetic resonance
SMA or the progressive muscular atrophy variant of ALS, imaging. A definitive diagnosis is based on pathologic find-
or classic ALS when upper and lower motor neuron signs ings of widespread deposition of polyglucosan bodies in the
predominate. central and peripheral nervous systems (Figure 28–2).
EDX studies usually show normal motor conduction Sural nerve biopsy shows multiple intra-axonal polyglu-
studies, unless they are recorded from weak muscles, in cosan bodies, which together with the appropriate clinical

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 Chapter 28 • Atypical Motor Neuron Disorders 437

FIGURE 28–2  Adult polyglucosan body

disease. Left: Longitudinal section of a
nerve biopsy from a patient with adult
polyglucosan body disease. Transverse
section is in the upper left. Note the
intra-axonal location of the polyglucosan
bodies. Right: Fluid attenuated inversion
recovery axial magnetic resonance
imaging of the brain in the same patient
shows bilateral white matter signal
abnormalities in periventricular and
subcortical white matter, which are
characteristic of adult polyglucosan body
disease.

manifestations can confirm the diagnosis of adult polyglu- The diagnosis is often made with the classic clinical pres-
cosan body disease. entation of distal hand weakness and atrophy, usually in a
young male. Laboratory investigations including blood
OTHER ATYPICAL MOTOR chemistries and CSF analysis are normal, with the excep-
tion of the serum CK, which may be slightly elevated. On
NEURON DISORDERS EDX testing, motor nerve conduction studies may be
normal or may reveal asymmetrically low median or ulnar
Monomelic Amyotrophy CMAP amplitudes in the affected hand. Slightly prolonged
Monomelic amyotrophy is a rare restricted form of motor distal motor latencies or slightly slowed conduction veloci-
neuron disease. Most cases are sporadic, although a familial ties may occur, depending on the degree of axonal loss. The
form has been reported. The male-to-female ratio is 5:1, SNAPs are always preserved.
with the majority of patients presenting between 18 and Recall that one of the patterns that may occur in typical
22 years old. Although first reported in Japan and India, sporadic ALS is the “split-hand syndrome,” wherein the
the disease has been described in young adults from all first dorsal interosseous (FDI) and abductor pollicis brevis
parts of the world. Many different names have been used (APB) are more affected than the abductor digiti minimi
for this condition, including monomelic atrophy, juvenile (ADM) (see Chapter 27). In monomelic amyotrophy, the
muscular atrophy of a unilateral upper extremity, benign reverse pattern is more often noted: the ADM is much
focal amyotrophy, Sobue disease, Hirayama’s disease and weaker and more wasted than the APB. The correlate of
juvenile segmental muscular atrophy. this clinical observation is a distinctive pattern on routine
Patients typically present with the insidious onset of uni- ulnar and median motor nerve conductions: an ADM/
lateral weakness and atrophy of the hand muscles that APB CMAP amplitude ratio of <0.6, which strongly sug-
often progresses to the forearm. In some cases, the syn- gests the diagnosis of monomelic atrophy rather than
drome is bilateral but often asymmetrical. Of note, the ALS. First described by Lyu et al., this ratio is calculated
brachioradialis muscle is usually spared. The syndrome simply by measuring the amplitudes of the CMAPs of the
affects C7–C8–T1 muscles with sparing of the C5–6 muscles. ADM and the APB, during routine ulnar and median
In most cases, no particular precipitating infection or trauma motor conduction studies. An ADM/APB CMAP ampli-
is identified. The weakness tends to progress slowly over 1 tude ratio of <0.6 is considered abnormal. Conversely,
to 3 years and then stabilizes. In some patients, there is an in cases wherein the ADM/APB CMAP amplitude ratio
aggravation of weakness when exposed to cold, a phenom- was >4.5 or when the median motor response was absent
enon known as cold paresis. Deep tendon reflexes are and the ulnar motor response recording the ADM was
usually normal, and upper motor neuron signs are absent. present, this pattern only occurred in ALS. Of course,
Sensation in the affected extremity is preserved, except these conclusions are predicated on the understanding
for a rare and mild sensory abnormality over the dorsum of that there is no additional lesion affecting the median
the hand. and/or ulnar nerves, especially median neuropathy at the
The etiology of monomelic amyotrophy is unknown. Pos- wrist or ulnar neuropathy at the elbow. In cases in which
tulated mechanisms include low-grade venous ischemia of the diagnoses of monomelic amyotrophy and ALS are
the spinal cord, especially the anterior horn cells, which lie being considered in a patient, paying attention to this
in the watershed area, possibly precipitated by trauma ratio may be helpful.
to the arm or neck, or by recurrent neck flexion and On needle EMG, fibrillation potentials are not promi-
extension. nent; they are found in slightly less than half of patients.

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438 SECTION VI Clinical–Electrophysiologic Correlations

MUAPs are large and prolonged in duration, and recruit- therapy, with typical total doses in the range from 5000 to
ment is invariably reduced. Low-amplitude, short-duration 6000 rads. The clinical syndrome is characterized by pro-
MUAPs, which represent early reinnervated motor unit gressive weakness, usually of the lower extremities, with
potentials, occur in approximately 20% of patients. Often, marked atrophy and fasciculations, which develops months
similar EDX abnormalities are detected, to a much lesser to years after radiation therapy. Deep tendon reflexes are
degree, in the clinically unaffected contralateral limb. Radi- depressed or absent in the affected limbs. Sphincter func-
ologic findings on computed tomographic myelogram or tion and sensation are spared, and upper motor neuron
magnetic resonance imaging may show segmental atrophy signs are absent. Interestingly, the lower extremities are
of the spinal cord at the level of the involved myotomes, preferentially involved, although radiation may involve
especially in the lower cervical and upper thoracic spinal the entire neuraxis. The weakness generally stabilizes
cord. The course in monomelic amyotrophy is generally after several months, although weakness continues to
benign. progress over years in some patients. A delayed lower
motor neuron bulbar palsy, consisting of dysarthria, dys-
phagia, and in some cases neck weakness, has been reported
Motor Neuron Disease Associated   follow­ing radiation to the head and neck for various cancers
with Electrical Injury (Figure 28–3).
There are rare case reports of adults and children who The diagnosis is based on a history of lower motor
develop a delayed upper and lower motor neuron syndrome neuron weakness primarily in the lower extremities,
after exposure to an electrical injury or lightning. Electrical months to years following radiation exposure. CSF usually
injuries usually occur from high-voltage lines, household is normal, although there may be a mild elevation of CSF
circuits, or lightning. Transient neurologic deficits immedi- protein. On EDX studies, nerve conduction studies show
ately after an electrical shock are well described and usually low CMAPs in the lower extremities, with intact SNAPs.
recover after hours to several days. In more severe electrical On EMG, prominent fibrillation potentials are often
injuries, spinal cord damage may occur, resulting in a non- present in the lower extremities. Of course, if the weak-
progressive syndrome that includes either lower or upper ness and wasting involves bulbofacial and neck muscles,
motor neuron damage, which often correlates with the these findings are seen in the bulbofacial and neck muscles.
level of the entrance and exit sites of the electrical current. Myokymic discharges may be seen in affected muscles and
Patients with non-progressive syndromes may recover par- are an important marker suggesting radiation-induced
tially or completely. injury (Figure 28–4). EDX testing of the upper extremi-
In contrast, a progressive motor neuron syndrome may ties is normal in most cases, depending on the site of
develop at variable time periods after the electrical injury. radiation. The clinical course is slowly progressive and
Weakness begins near the site of the trauma and progresses usually confined to the region of the spinal cord exposed
in an ALS-like fashion to the contralateral limb. Bulbar to the original radiation. Most patients stabilize after
weakness and upper motor neuron signs develop later on. several months and usually survive for 15 to 20 years after
Sensory symptoms can occur in the region of the electrical the initial presentation, although the weakness can be
injury. The clinical course in the progressive motor neuron severe and debilitating.
syndrome associated with electrical injury is similar to the
progression seen in typical ALS, with death typically occur-
ring within 3 years after the initial presentation. Whether
there is truly a causal relationship between the electrical
injury and the progressive motor neuron syndrome remains
unknown.
The underlying mechanism of the electrical injury and its
relationship to spinal cord damage, particularly to the ante-
rior horn cells, are unclear. Autopsy findings in one patient
with motor neuron disease after an electrical injury revealed
the classic changes found in ALS, including loss of anterior
horn cells and motor neurons in the hypoglossal nuclei, and
degeneration of the corticospinal tract. There was no evi-
dence of vascular cord injury or mechanical distortion of
the spinal cord. Thus, the relationship between electrical
injuries and ALS remains tenuous at best.
FIGURE 28–3  Delayed lower motor neuron bulbar palsy. A
Delayed Radiation-Induced Motor   41-year-old man developed progressive swallowing and speech
Neuron Syndrome disturbance 14 years after receiving radiation to the neck for
nasopharyngeal carcinoma. Speech was nasal and dysarthric; the
Progressive pure lower motor neuron syndromes have been palate did not elevate. Note the diffuse atrophy of the anterior
described in patients as a delayed response of radiation cervical musculature, more prominent on the left.

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 Chapter 28 • Atypical Motor Neuron Disorders 439

1 mV
Fasciculations
100 ms

Burst Burst Burst Burst Burst

FIGURE 28–4  Myokymic discharges and delayed radiation-induced motor neuron disorder. Tracing made from electromyogram of
the tongue from the same patient shown in Figure 28–3. Clinically, continuous undulating movements were present. Tracing shows grouped
repetitive bursts of motor unit action potentials (myokymic discharges) and fasciculations. Myokymic discharges, although seen in other
conditions, are characteristic of radiation-induced injury.

The pathogenesis of delayed radiation-induced injury is improvement or normalization of neurologic deficits, which
not well defined. Some evidence suggests that the disease appear to be independent of the course of the cancer. In
process in the lower extremities involves damage to the other patients, the disease is progressive, with accompany-
lumbosacral anterior nerve roots, whereas other evidence ing upper motor neuron signs and a clinical course similar
suggests that the pathology is in the anterior horn cells. to typical ALS.
Based on purported mechanisms involved in delayed
radiation-induced encephalopathy, it is likely that a combi-
nation of factors is involved in postradiation-induced motor ELECTROPHYSIOLOGIC
neuron syndrome. These include direct radiation-induced EVALUATION
damage to neurons and ischemic changes secondary to
radiation-induced damage to vascular endothelial cells. Nerve Conduction Studies
The nerve conduction study protocol for a suspected atypi-
Paraneoplastic Motor Neuron Disease cal motor neuron disorder is the same as that for ALS (see
Paraneoplastic disorders occur as a remote effect of cancer. Chapter 27). At a minimum, routine motor and sensory
Whether motor neuron disease occurs as a paraneoplastic conduction studies along with late responses should be
syndrome is controversial. Since several initial reports of a performed in a symptomatic upper and lower extremity
paraneoplastic motor neuron syndrome, many have ques- before proceeding to the needle EMG study. The most
tioned whether the association of cancer and motor neuron important reason to perform motor nerve conduction
disease is simply a coincidence of two relatively common studies is to look for the following:
diseases, or if there is a true etiologic relationship between • Unequivocal evidence of demyelination along motor
the two conditions. Several epidemiologic studies have nerves, especially conduction block, at non-
failed to find an increased incidence of cancer in patients entrapment sites. Demyelination is not present in
with ALS compared with the general population, although ALS, and its presence strongly supports an alternative,
several small studies have reported a co-occurrence of treatable diagnosis, usually multifocal motor neuro­
cancer and motor neuron disease that appears to be higher pathy with conduction block (Figure 28–5).
than the incidence expected in the general population. • Abnormalities on sensory nerve conduction studies.
One of the strongest cases for a paraneoplastic motor Sensory nerve conduction studies are always normal in
neuron disease occurs in association with lymphoma, ALS unless the patient has a superimposed disorder
wherein a clinical syndrome characterized by subacute pro- (e.g., polyneuropathy or entrapment neuropathies).
gressive, painless lower motor neuron weakness with The presence of abnormal sensory conduction studies
minimal or absent sensory symptoms has been reported. should always seriously question the diagnosis of ALS.
The progression of neurologic symptoms varies. In some Abnormal sensory conduction studies are often seen
patients the progression is slow; some even show clinical in Kennedy’s disease and adult polyglucosan body

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440 SECTION VI Clinical–Electrophysiologic Correlations

neuron disease, such as acute poliomyelitis or West Nile

1 mV encephalitis/myelitis, or demyelination with conduction
block and some secondary axonal loss.
2 ms

EXAMPLE CASES
Case 28–1
History and Physical Examination
A 49-year-old man was referred for progressive weakness
and fatigue. Over the past 6 months, he had complained
of more difficulty walking and noted increased weakness
in the left leg. He had a history of paralytic poliomyelitis
at age 5 years. He recalled being hospitalized for 2 weeks
at that time and developing weakness of both legs, left
more than right. The upper extremities and bulbofacial
and respiratory muscles were not affected. Within 1 year
FIGURE 28–5  Conduction block in a patient with multifocal following the poliomyelitis, he had regained full function
motor neuropathy. Motor nerve conduction of the median nerve of his legs. During high school and college, he had par-
recording abductor pollicis brevis muscle, stimulating wrist (top ticipated regularly in athletics without difficulty.
tracing) and antecubital fossa (bottom tracing). Note the drop in area
On examination, the left leg was slightly shorter and
and amplitude of the compound muscle action potential from the
wrist to the antecubital fossa. In a patient with a suspected motor smaller than the right. Neurologic examination revealed
neuron disorder, conduction block is not consistent with amyotrophic normal mental status and cranial nerves. In the upper
lateral sclerosis; it indicates a demyelinating motor neuropathy, usually extremities, muscle bulk, tone, and strength were normal.
multifocal motor neuropathy with conduction block. In the lower extremities, there was slight weakness of all
movements around the ankle, especially on the left. In
addition, there was mild weakness of hip extension and
disease. In addition, some cases of West Nile encepha- abduction bilaterally. Reflexes were absent in the lower
litis and demyelinating motor neuropathy with extremities and hypoactive in the upper extremities.
conduction block may rarely display sensory conduc- Sensory examination was normal to all modalities.
tion abnormalities.
Summary
The history is that of a 49-year-old man with mild pro-
Electromyographic Approach gressive weakness and fatigue in the lower extremities,
Akin to the nerve conduction studies, the EMG evaluation left greater than right. There is no pain or clear sensory
of patients with suspected atypical motor neuron disorders loss. From the history alone, the underlying etiology is
is similar to that of ALS. An extensive study is indicated, not clear. The symptoms could represent some type of
often of all four limbs, the paraspinal muscles, and the orthopedic problem of the hip or leg, or a subtle neuro-
bulbar muscles. Certain types of spontaneous discharges logic problem such as an entrapment neuropathy or, more
take on additional meaning in patients with suspected likely, a lumbosacral radiculopathy. The examination
atypical motor neuron disorders. CRDs are unusual in ALS shows only mild distal and proximal weakness in both
and imply a much more chronic condition. Prominent legs, somewhat in the distribution of the L5–S1 myo-
CRDs are reported most often in very chronic motor tomes. However, there is no corresponding sensory
neuron disorders, especially late-onset Tay–Sachs disease, abnormality in that distribution, making the diagnosis of
adult-onset spinal muscular atrophy, and some cases of radiculopathy less likely. The absent reflexes in both
old poliomyelitis. The presence of myokymic discharges lower extremities and the depressed reflexes in the upper
should always raise the possibility of prior radiation- extremities suggest a more widespread disorder.
induced injury. In addition, myokymic discharges are The left leg is shorter and smaller than the right, likely
sometimes seen in acquired demyelinating neuropathies. reflecting the patient’s prior poliomyelitis. When weak-
Lastly, prominent facial fasciculation potentials or grouped ness is present during childhood development, secondary
discharges with activation should raise the possibility of orthopedic problems often result. When the patient
Kennedy’s disease. recalled his prior history of poliomyelitis at age 5 years,
Almost all motor neuron disorders are slowly progressive. he remembered that the left leg was more affected than
Thus, MUAPs should be large, long, and polyphasic with the right. Despite weakness at the time, he made a fairly
decreased recruitment. The pattern of acute or subacute good recovery and was not subsequently disabled by the
neuropathic loss (active denervation, with decreased poliomyelitis in any meaningful way. He was able to
recruitment of normal configuration MUAPs) is not seen in participate regularly in athletics as a teenager and young
ALS. This pattern implies either an acute/subacute motor adult. Furthermore, we know that he was hospitalized for

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 Chapter 28 • Atypical Motor Neuron Disorders 441

CASE 28–1.  Nerve Conduction Studies

Amplitude
Motor = mV; Conduction F-Wave
Sensory = µV Latency (ms) Velocity (m/s) Latency (ms)
Nerve
Stimulated Stimulation Site Recording Site RT LT NL RT LT NL RT LT NL RT LT NL
Median (m) Wrist APB 6.2 ≥4 3.9 ≤4.4 25 ≤31
Antecubital fossa APB 6.0 6.7 54 ≥49
Ulnar (m) Wrist ADM 8.2 ≥6 3.1 ≤3.3 ≤32
Below elbow ADM 8.0 5.8 53 ≥49 26
Above elbow ADM 7.8 7.2 55 ≥49
Median (s) Wrist Index finger 29 ≥20 3.3 ≤3.5 57 ≥50
Ulnar (s) Wrist Little finger 22 ≥17 2.8 ≤3.1 58 ≥50
Tibial (m) Ankle AHB 5.3 4.2 ≥4 5.3 5.5 ≤5.8 44 45 ≤56
Popliteal fossa AHB 4.2 3.8 13.0 13.2 46 45 ≥41
Peroneal (m) Ankle EDB 2.8 2.3 ≥2 5.4 5.8 ≤6.5 43 44 ≤56
Below fibula EDB 2.6 2.2 9.9 10.3 46 45 ≥44
Lateral popliteal EDB 2.5 2.2 11.9 12.3 48 44 ≥44
fossa
Sural (s) Calf Posterior ankle 15 14 ≥6 4.2 4.2 ≤4.4 48 48 ≥40
m = motor study; s = sensory study; RT = right; LT = left; NL = normal; APB = abductor pollicis brevis; ADM = abductor digiti minimi; AHB = abductor
hallucis brevis; EDB = extensor digitorum brevis.
Note: All sensory latencies are peak latencies. All sensory conduction velocities are calculated using onset latencies. The reported F-wave latency represents
the minimum F-wave latency.

CASE 28–1.  Electromyography

Spontaneous Activity Voluntary Motor Unit Action Potentials
Configuration
Insertional Fibrillation
Muscle Activity Potentials Fasciculations Activation Recruitment Duration Amplitude Polyphasia
Left tibialis anterior ↑ 0 0 NL ↓↓↓ +3 +2 +2
Left medial NL 0 0 NL ↓↓↓ +2 +2 +2
gastrocnemius
Left peroneus longus CRD +1 0 NL ↓↓↓ +2 +3 +2
Left vastus lateralis NL 0 0 NL ↓↓ +2 +2 +2
Left iliacus NL 0 0 NL ↓↓ +2 +2 +2
Left gluteus medius NL 0 0 NL ↓↓ +3 +2 +2
Right tibialis anterior ↑ ± 0 NL ↓↓↓ +3 +2 +1
Right peroneus longus ↑ ± 0 NL ↓↓↓ +2 +1 +2
Right medial NL 0 0 NL ↓↓↓ +2 +2 +2
gastrocnemius
Right vastus lateralis NL 0 0 NL ↓↓ +2 +2 +3
Right iliacus NL 0 0 NL ↓↓ +2 +2 +2
Left first dorsal NL 0 0 NL ↓↓ +2 +2 +1
interosseous
Left abductor pollicis NL 0 0 NL ↓↓ +1 +2 +1
brevis
Left pronator teres NL 0 0 NL ↓↓ +2 +2 +1
Left biceps brachii NL 0 0 NL ↓↓ +2 +1 +2
Left medial deltoid NL 0 0 NL ↓↓ +2 +2 +2
↑ = increased; ↓↓ = moderately reduced; ↓↓↓ = markedly reduced; NL = normal; CRD = complex repetitive discharge.

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442 SECTION VI Clinical–Electrophysiologic Correlations

only 2 weeks at the time of the early illness, again sug- presents as fever, headache, myalgias, and gastrointestinal
gesting that the severity of his poliomyelitis was not great disturbance. The paralysis commonly is asymmetric and
(many more severely affected patients spent months in develops over the first 1 to 2 weeks. Acute denervation
the hospital or in rehabilitation facilities). Therefore, is then followed by reinnervation. If reinnervation is fairly
when the history and physical examination are com- successful, most of the denervated muscle fibers are rein-
pleted, the diagnosis remains unclear, except that the nervated. Accordingly, strength often returns to normal,
orthopedic changes in the left leg are likely due to the despite the fact that the number of underlying motor
prior poliomyelitis. neurons has been greatly reduced. Indeed, many patients
Nerve conduction studies are performed in both legs who have had poliomyelitis return to a normal level
and in one upper extremity. The CMAP amplitudes are of functioning. Deep tendon reflexes commonly are
within normal limits, and there is no evidence of focal depressed or lost early in the course and in some cases
slowing, conduction block, or prolonged distal latencies. never return.
All the minimum F-wave latencies are normal. Likewise, As individuals age, there is always some normal loss of
the SNAPs show normal amplitudes and latencies motor neurons, beginning at about age 50 to 60 years. At
throughout, including the sural potential. In general, that time, most individuals do not note any appreciable
these nerve conduction studies are not very informative, loss of strength from this normal aging process. However,
except to rule out certain conditions. The normal con- patients with old poliomyelitis, whose number of remain-
duction studies essentially exclude a polyneuropathy or ing motor neurons is dramatically reduced, may develop
plexopathy to account for the decreased reflexes and clinical symptoms with loss of further motor neurons.
weakness. Note that both lower extremities are tested When this occurs, the first symptom often is fatigue,
because the examination was asymmetric and showed followed by weakness and often pain. The extremities
only lower motor neuron signs, raising the possibility of most affected by the original polio usually are the ones
MMNCB or another demyelinating neuropathy. The most affected by PPS. The limbs apparently spared
absence of conduction blocks or other signs of demyelina- during the original infection also can be affected by PPS.
tion essentially excludes these diagnoses. During the original poliomyelitis infection, subclinical
Moving next to the EMG findings, muscles in both legs involvement of other body segments is the rule rather
are sampled. In both legs, nearly all muscles studied than the exception. In the case described here, the clini-
reveal very large, long-duration, polyphasic MUAPs with cally unaffected left upper extremity also shows rein-
moderately to markedly decreased recruitment. Similar nervated MUAPs, but the findings are not as marked as
changes are found on both sides, and there is no clear in the lower extremities, which bore the brunt of the
asymmetry between the two legs. A few muscles have original infection.
increased insertional activity, but only the left peroneus The SNAPs are always normal in PPS unless there is a
longus has any sustained fibrillation potentials. Clearly, superimposed process. Motor nerve conduction studies
the degree of reinnervation is much greater than the tend to be normal but may show evidence of axonal loss.
degree of ongoing denervation. CRDs are also seen in the In this case, the most important findings are on the
left peroneus longus. Muscles in the clinically unaffected needle EMG portion of the examination. Diffusely large,
left upper extremity are sampled next. Somewhat sur- prolonged, polyphasic MUAPs associated with decreased
prisingly, very large, long-duration polyphasic MUAPs are recruitment are found throughout, even in clinically unaf-
found, with moderately reduced recruitment. Although fected muscles. Although some active denervation can be
the changes are not as dramatic as in the lower extremi- seen in PPS, it is generally quite mild, especially in rela-
ties, they are still quite marked. tionship to the amount of reinnervation. CRDs, a marker
At this time, we are ready to formulate our electro- of chronic denervation, are seen occasionally, which is
physiologic impression. unusual in ALS.

IMPRESSION: The electrophysiologic findings are What is the Differential Diagnosis?

consistent with a chronic disorder of motor neurons, Patients with old poliomyelitis effectively have a
their axons, or both, affecting the lower more than the decreased reserve of motor neurons and motor nerves.
upper extremities. They are more susceptible to the effects of any superim-
posed neurologic or orthopedic condition, which may
Several important questions can be addressed. disproportionately increase their disability. EMG is often
used to evaluate patients with old poliomyelitis to help
Does the Clinical–Electromyographic Correlation exclude other superimposed processes such as radicu-
Make Sense? lopathy or myopathy. However, most patients with prior
The clinical diagnosis in this case is PPS. The clinical poliomyelitis will have diffuse, chronic, underlying abnor-
history and subsequent EMG study display many of malities on EMG. Thus, it may be difficult to find evi-
the important findings in PPS. Poliomyelitis is a viral dence of a new superimposed neurogenic process. This
infection of the anterior horn cells that subsequently situation often complicates the evaluation of a possible
leads to death of the infected anterior horn cells. It superimposed radiculopathy in a patient with PPS. In the

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 Chapter 28 • Atypical Motor Neuron Disorders 443

case discussed here, it would be difficult to exclude a Summary

superimposed mild L5–S1 radiculopathy as a cause of The history is that of a 60-year-old man who presents
exacerbated symptoms. with proximal weakness and an elevated CK level. He
has the typical symptoms of proximal muscle weakness
(i.e., difficulty getting out of low chairs and going up and
Case 28–2 down stairs). Initially, one would have thought that this
History and Physical Examination is a clear case of a myopathy. However, there is one
A 60-year-old man was referred for a 5-year history of important finding on physical examination that is not
gradually progressive lower extremity weakness. He consistent with a myopathy: the fasciculations around the
noted difficulty getting out of low chairs and going up or chin and face. Fasciculations are always a neuropathic
down stairs. He reported no pain except for occasional phenomenon and are never seen in myopathy. In addi-
cramps in his hands. He also reported mild difficulty with tion, on examination, there is some mild loss of sensation
the shoulder girdle muscles, for instance, when changing distally. This is also atypical for a myopathy or motor
the oil in his car. When asked directly, he reported some neuron disorder but could easily be seen in a peripheral
muscle twitches, especially around the chin and face. neuropathy. Thus, before starting the nerve conduction
There was no similar family history. Routine blood testing and EMG studies, we would still likely consider the pos-
was normal other than a CK level elevated at 1425 IU. sibility of a myopathy, but the fasciculations raise the
On examination, there were obvious fasciculations issue of an anterior horn cell or peripheral nerve disorder,
around the chin and the left face. The tongue looked and certainly the sensory loss raises the possibility of a
somewhat scalloped but not definitely atrophic. There peripheral neuropathy.
was no dysarthria. Motor examination showed mild Proceeding to the nerve conduction studies, the median
atrophy, both distally and proximally in the lower extrem- and ulnar motor conduction studies are completely
ities. Strength testing was essentially normal in the upper normal, along with their respective F responses. However,
extremities. In the lower extremities, confrontational all of the sensory responses in the upper extremities have
testing appeared normal. However, on functional testing, a low amplitude, consistent with an axonal loss pattern.
he could not arise from a low chair without using his In the lower extremities, the peroneal motor amplitude
arms. Deep tendon reflexes all were present but hypoac- is basically normal, with a borderline conduction velocity
tive. Toes were downgoing. Sensory examination showed and F response latency. The sural sensory response,
a mild distal loss to temperature. He walked with a however, is reduced. Thus, from the nerve conduction
combination of a steppage and waddling gait. Coordina- studies, we know that there is clearly a mild sensory
tion testing was normal. neuropathy.

CASE 28–2.  Nerve Conduction Studies

Amplitude
Motor = mV; Conduction F-wave Latency
Sensory = µV Latency (ms) Velocity (m/s) (ms)
Nerve
Stimulated Stimulation Site Recording Site RT LT NL RT LT NL RT LT NL RT LT NL
Median (m) Wrist APB 8.1 ≥4 3.2 ≤4.4 29.5 ≤31
Antecubital fossa APB 7.3 8.2 54 ≥49
Ulnar (m) Wrist ADM 8.4 ≥6 2.5 ≤3.3 32.8 ≤32
Below elbow ADM 7.2 7.1 57 ≥49
Above elbow ADM 7.0 9.5 63 ≥49
Median (s) Wrist Index finger 3 ≥20 3.5 ≤3.5 46 ≥50
Ulnar (s) Wrist Little finger 3 ≥17 3.0 ≤3.1 52 ≥50
Radial Forearm Snuffbox 12 ≥15 2.3 58 ≥50
Peroneal (m) Ankle EDB 4.3 ≥2 5.1 ≤6.5 58.5 ≤56
Below fibula EDB 3.7 12.2 40 ≥44
Lateral popliteal EDB 3.7 15.0 40 ≥44
fossa
Sural (s) Calf Posterior ankle 5 ≥6 4.3 ≤4.4 37 ≥40
m = motor study; s = sensory study; RT = right; LT = left; NL = normal; APB = abductor pollicis brevis; ADM = abductor digiti minimi; AHB = abductor
hallucis brevis; EDB = extensor digitorum brevis.
Note: All sensory latencies are peak latencies. All sensory conduction velocities are calculated using onset latencies. The reported F-wave latency represents
the minimum F-wave latency.

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444 SECTION VI Clinical–Electrophysiologic Correlations

CASE 28–2.  Electromyography

Spontaneous Activity Voluntary Motor Unit Action Potentials
Configuration
Insertional Fibrillation
Muscle Activity Potentials Fasciculations Activation Recruitment Duration Amplitude Polyphasia
Right tibialis ↑ +1 0 NL ↓ +1 +1 +1
anterior
Right extensor ↑ +2 0 NL ↓↓ +2 +1 +2
hallucis longus
Right medial ↑ +1 0 NL NL +1 NL/+1 NL
gastrocnemius
Right vastus ↑ +1 0 NL ↓↓ +2 +2 +2
lateralis
Right vastus ↑ +1 0 NL ↓↓ +2 +2 +2
medialis
Right iliacus NL 0 0 NL ↓ +1 +1 +1
Right first dorsal ↑ +1 0 NL ↓ +1 +1 +1
interosseous
Right extensor NL 0 0 NL ↓ +1 +1 +1
indicis proprius
Right pronator CRD 0 0 NL NL NL/+1 NL/+1 NL/+1
teres
Right biceps NL 0 0 NL ↓↓ +2 +2 +2
brachii
Right triceps NL 0 0 NL ↓↓ +2 +2 +2
Right medial NL 0 0 NL ↓↓ +2 +2 +2
deltoid
Right ↑ +1 0 NL ↓ +2 +1 +1
infraspinatus
Right rhomboid NL 0 0 NL NL NL NL NL
Right cervical NL 0 0 NL NL NL NL NL
paraspinals
Right T6 NL 0 0 NL NL NL NL NL
paraspinal
↑ = increased; ↓ = slightly reduced; ↓↓ = moderately reduced; NL = normal; CRD = complex repetitive discharge.

Moving on to the needle EMG, nearly every single Putting the Clinical, Laboratory, and EDX
muscle is abnormal, showing increased insertional activ- Information Together, What is the Most
ity, and most muscles, especially in the lower extremity, Likely Diagnosis?
showing fibrillation potentials. In addition, the motor This patient presented with proximal muscle weakness,
unit potentials are large, long, and polyphasic, with face and chin fasciculations, and an elevated CK level.
decreased recruitment in nearly all muscles. This wide- EDX studies found a diffuse motor neuron disease and
spread pattern is consistent with a diffuse disorder of the accompanying mild sensory neuropathy. Putting all the
motor neurons. Thus, at this point, we are ready to for- information together, this is consistent with the diagnosis
mulate our electrophysiologic impression. of X-linked bulbospinal atrophy, also known as Kennedy’s
disease. Many times, Kennedy’s disease is mistaken for a
IMPRESSION: The electrophysiologic findings are myopathy based on the proximal weakness and the ele-
consistent with an active and chronic generalized vated CK level. Because Kennedy’s disease presents with
disorder of the motor neurons and/or the axons, with a proximal muscle weakness, the elevated CK often is inap-
superimposed mild peripheral sensory neuropathy. propriately attributed to a myopathy. In this case, the
elevated CK is one more important piece of information
This case raises several important questions. that helps make the diagnosis of Kennedy’s disease.

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 Chapter 28 • Atypical Motor Neuron Disorders 445

After the EDX studies, blood was sent for DNA analy- One day after admission, she developed weakness of
sis, which demonstrated the expansion of the trinucle- the left arm. On examination, there was severe weakness
otide (CAG) repeat in the androgen receptor gene, which of the left biceps and triceps, and milder weakness in the
confirmed the diagnosis of Kennedy’s disease. distal hand muscles. All reflexes were absent in the left
upper extremity. Sensory examination was normal. Her
What Genetic Counseling Should be Advised? weakness remained unchanged several weeks later, when
In Kennedy’s disease, the genetics are X-linked. Only electrodiagnostic studies were done.
males are affected. Because the disorder is X-linked, all
sons of an affected father will be free of the disease and Summary
have no possibility of transferring the disease to their The patient is a previously healthy young woman who
children. However, all daughters of a patient with was admitted to the hospital with a clinical picture highly
Kennedy’s disease will be carriers. Although none will suggestive of meningitis. She had several days of fevers,
have the disease, they may transfer the abnormal X chro- chills, headache, and neck pain, along with a CSF pleo-
mosome to their children. Half of their daughters will be cytosis. The cells were predominantly lymphocytes,
carriers, while half of their sons will have the disease and which is most consistent with a nonbacterial infection. In
half will be free of the disease. Although Kennedy’s this setting, she developed acute flaccid weakness of her
disease is not generally associated with a change in lon- left arm, with loss of reflexes and completely normal
gevity, patients can become severely disabled; hence, sensation. This case is clearly unusual. The infection and
genetic counseling is very important. weakness are likely related, either directly or with the
weakness occurring as a postinfectious immunologic
event.
Case 28–3 Moving on to the nerve conduction studies, detailed
History and Physical Examination studies of the left upper extremity are performed with
A 25-year-old previously healthy woman was admitted limited comparison studies on the right side. Note that
to the hospital with a 3-day history of headache, neck the median, ulnar, and radial motor responses all show
pain, fever, and chills. With the exception of mild nuchal low amplitudes with relatively intact distal latencies,
rigidity, her neurologic examination was completely conduction velocities, and F responses. There is a clear
normal. CSF analysis showed an elevated protein asymmetry compared with the contralateral side. In con-
(152 mg/dL), normal glucose, and lymphocytic pleocy- trast, all of the sensory potentials, including the median,
tosis of 60 cells/mm3. Bacterial cultures were negative. ulnar, radial, lateral antebrachial cutaneous, and medial

CASE 28–3.  Nerve Conduction Studies

Amplitude
Motor = mV; Conduction F-Wave
Sensory = µV Latency (ms) Velocity (m/s) Latency (ms)
Nerve
Stimulated Stimulation Site Recording Site RT LT NL RT LT NL RT LT NL RT LT NL
Median (m) Wrist APB 6.5 1.7 ≥4 2.9 3.6 ≤4.4 26.3 ≤31
Antecubital fossa APB 1.4 7.9 48 ≥49
Ulnar (m) Wrist ADM 5.7 3.3 ≥6 2.9 3.1 ≤3.3 27.9 ≤32
Below elbow ADM 3.0 6.2 53 ≥49
Above elbow ADM 2.8 8.1 56 ≥49
Radial (m) Below spiral groove EIP 1.8 0.3 ≥2 4.2 4.3
Above spiral groove EIP 0.3 7.0 56 ≥49
Median (s) Wrist Index finger 41 ≥20 2.5 ≤3.5 57 ≥50
Ulnar (s) Wrist Little finger 38 41 ≥17 2.8 2.5 ≤3.1 54 58 ≥50
Radial (s) Forearm Snuffbox 54 ≥15 1.8 ≤2.9 62 ≥50
Lateral Elbow Lateral forearm 17 ≥10 2.5 ≤3.0 59 ≥55
antebrachial (s)
Medial Elbow Medial forearm 8 11 ≥5 2.4 2.4 ≤3.2 52 52 ≥50
antebrachial (s)
m = motor study; s = sensory study; RT = right; LT = left; NL = normal; NR = no response; APB = abductor pollicis brevis; ADM = abductor digiti minimi;
EIP = extensor indicis proprius.
Note: All sensory latencies are peak latencies. All sensory conduction velocities are calculated using onset latencies. The reported F-wave latency represents
the minimum F-wave latency.

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446 SECTION VI Clinical–Electrophysiologic Correlations

CASE 28–3.  Electromyography

Spontaneous Activity Voluntary Motor Unit Action Potentials
Configuration
Insertional Fibrillation
Muscle Activity Potentials Fasciculations Activation Recruitment Duration Amplitude Polyphasia
Left first dorsal ↑ 0 0 NL ↓↓ NL NL NL
interosseous
Left flexor pollicis ↑ +1 0 NL ↓↓ NL NL NL
longus
Left biceps brachii ↑ +2 0 NL ↓↓↓ NL NL NL
Left triceps brachii ↑ +3 0 NL ↓↓↓ NL NL NL
Left medial deltoid ↑ +2 0 NL None NL NL NL
Left rhomboid ↑ +2 0 NL ↓↓↓ NL NL NL
Left C5 paraspinal ↑ 0 0 NL None NL NL NL
Left C8 paraspinal ↑ +1 0 NL None NL NL NL
Let upper trapezius NL 0 0 NL NL NL NL NL
↓↓ = moderately reduced; ↓↓↓ = markedly reduced; NL = normal.

antebrachial cutaneous responses are completely normal. Are the EDX Studies Consistent with a Diagnosis of
Comparison with the contralateral ulnar and medial ante- Guillain–Barré Syndrome?
brachial cutaneous sensory responses shows no significant Given the acute weakness after an infection, one might
asymmetry. Thus, at the completion of the nerve conduc- have considered the possibility of a variant of Guillain–
tion studies, the findings point to a predominantly motor Barré syndrome. However, there is no evidence of
axonal loss lesion, based on the low motor amplitudes demyelination on the nerve conduction studies (i.e., no
with relatively intact conduction velocities and distal conduction block, conduction velocity slowing, prolonged
latencies and the absence of any sensory conduction latencies, or impersistent or absent late responses). In
abnormalities. Although a cervical polyradiculopathy addition, the study is very asymmetric, as is the clinical
might be considered, given the low motor amplitudes and examination, which would be distinctly uncommon for
preserved sensory potentials, remember that there is no Guillain–Barré syndrome.
sensory loss on examination. Thus, this pattern of nerve
conduction findings, in the current clinical setting, is Is the EDX Study Consistent
highly suggestive of a motor neuron disorder. Note that with a Cervical Polyradiculopathy?
the findings of low motor amplitudes in the left upper If one examines the nerve conduction studies and EMG
extremity might suggest a presynaptic neuromuscular data in isolation, the study is consistent with a cervical
junction disorder, but the significant asymmetry makes polyradiculopathy. All of the sensory potentials are
this unlikely. normal, as would be expected in a radiculopathy (i.e., in
Moving on to the needle EMG, nearly every muscle in a lesion proximal to the dorsal ganglion), with low distal
the left upper extremity shows increased insertional motor amplitudes and widespread denervation on the
activity and prominent fibrillation potentials. Of note, all needle EMG study. This case emphasizes that nerve
the MUAPs are normal in morphology, but there is mod- conduction studies and needle EMG are best inter-
erately to markedly reduced recruitment in nearly all preted in light of the clinical context. There is no differ-
muscles. Thus, at this time, we are ready to formulate ence on EDX studies between disorders of the nerve
our electrophysiologic impression. roots (e.g., radiculopathy/polyradiculopathy) versus dis-
orders of the anterior horn cells (focal motor neuron
disease/diffuse motor neuron disease). However, the
IMPRESSION: The electrophysiologic findings are
distinction is made quite easily clinically. Patients with
consistent with a severe subacute process affecting
radiculopathy have prominent pain and sensory symp-
the cervical motor neurons, their axons, or both on
toms or signs, neither of which is seen in patients with
the left. These findings are consistent with acute
motor neuron disease. In this case, the complete absence
poliomyelitis.
of sensory symptoms and signs strongly suggests that
this disorder is not at the root level but rather at the
This case raises several important questions. anterior horn cell level.

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 Chapter 28 • Atypical Motor Neuron Disorders 447

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