The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Pathophysiology
Status epilepticus
Surat Tanprawate, MD, FRCPT, MSc(Lond.)
The Northern Neuroscience Center,
Division of Neurology, Chaing Mai University
status epilepticus
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Definition
Conventional textbook definition of status
epileptics:
Single seizure > 30 minutes
Series of seizures > 30 minutes without full
recovery
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Why 30 minutes?
Animal experiments in the 1970s and 1980s had
shown that
neuronal injury could be demonstrated after 30
mins of seizure activity, even while maintaining
respiration and circulation
Nevander G. Ann Neurol 1985:18(3):281-290
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Typical seizure in adults
Age > 5 years:
Typical, generalised tonic-clonic seizure lasts < 5
minutes
Young children and infants
Paucity of data. Suggested time frame for typical
tonic-clonic seizure: <10-15 minutes
Lowenstein DH. Epilepsia 1999;40(1):120-2
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Term and use
Status epilepticus (SE) is the term used to describe an
abnormally prolonged state of self-perpetuating and
evolving seizure activity, specifically defined by time,
as a 5 minute seizure or an episode of briefer seizures
with reduced recovery of awareness in between seizure
Type of SE
convulsive and non-convulsive
Simple partial status, complex partial status,
myoclonic status (often associated with coma)
Lowenstein DH, et al. Epilepsia. 1999;40(1):120-2.
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Classification of status epilepticus
Trinka E, et al. Epilepsia 2015; 56:15151523
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Status epilepticus
Mortality 7.6-39%
Cause : 50% no cause
Kinney M et al. Ulster Med J 2015;84(2):88-93
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Uncommon cause you might concern
Tan RY, et al. Epilepsy Res. 2010; 91(2-3):111-22.
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Predictive factors
Epilepsy with provoked seizure or low AEDs level lowest mortality (4-6%)
Age (38% in elderly vs 14% in young adults)
Duration of SE (< 30 mins 2.6%; > 30 mins 19%)
Kinney M et al. Ulster Med J 2015;84(2):88-93
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
A comparison of
survival by duration
in status epileptics
shows a marked
increase in mortality
for patients in
prolonged status
epileptics (Towne et
al. 1994)
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Hirsch LJ, et al Continuum (Minneap Minn) 2013;19:767-794
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Stage of status epilepticus
Receptor tracking
GABAA receptor internalized in Clathrin coated
vesicle and destroyed in Lysosome
NMDA synapses subunits are mobilised to the
Chen JW. Lancet Neurol 2006; 5: 24656
synaptic membrane
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Receptor trafficking
Initiation of self-sustaining status epileptics is easily
blocked by many drugs that increase inhibition or
reduce excitation
Once self-sustaining occurred
GABAergic drug become ineffective, and need
high dose that toxic side effect
drug which directly or indirectly inhibit
glutaminergic neurotransmission are more effective
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Substance P is expressed in hippocampal principal neurons during
status epilepticus and plays a critical role in the maintenance of
status epilepticus
Liu H,et al. Natl Acad Sci USA 1999; 96: 528691.
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Grael JD et al. J Neurosci 2009;29(14):4430-4441
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
J.A. Gorter et al. Epilepsy & Behavior (2015)
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
Transforming
growth factor
receptor 2
(TGFR2)
Within hours following BBB breakdown albumin diffuses into the brains extracellular
space, binds to astrocytic TGF receptors and induces transcriptional change
Friedman A. et al. Epilepsy Res 2009 Aug; 85(0): 142149.
Pathophysiologi
cal cascade of
inflammatory
events in
epilepsy
Nat Rev Neurol
2011;7(1):31-40
Shorvon S. Brain 2011:
134; 28022818
The Northern Neuroscience Centre
Chiang Mai University
NNC CMU
