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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

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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

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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