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Seizures after strokeCan we predict ?

พ.ญ.สุธิดา เย็นจันทร

PMK Epilepsy Annual Meeting 2016

Definition

Poststroke seizure

: single or multiple convulsive episode(s) after stroke and thought to be related to reversible or irreversible cerebral damage due to stroke regardless of time of onset following the stroke

Definition

Poststroke epilepsy

: recurrent seizures following stroke with confirmed diagnosis of epilepsy

Epidemiology• Stroke incidence increases with advancing age

• CVD is the number one cause of epilepsy in elderly

• Stroke registry data ,≈ 5%-20% will have poststroke seizure

• A small subset of this group develop epilepsy

Arch Neurol.2002;59:195-202.

Canada, Australia, Israel, Italy

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•Seizure occurred within 24 hours of stroke in 58% of children

• Youngest children (0-5 years) had early seizures > 6 years and older (p=0.28)

• No significance differences were found in the rate of seizure by stroke type

• The relative risk (95% CI) for seizure in the acute stroke setting in children vs. adults is 18

Epub: Sep 10, 2011

•21% had seizure as initial sign of stroke, 10% had seizures during the acute hospitalization

• 17% had SE, did not vary in stroke subtypes but common in infants and patients with cortical strokes

• NCSE was captured only with patients with VEM, and always within 24 hours of monitoring

• 24% had epilepsy in next 6 months after stroke, all of whom experienced early-onset seizures

Classification

Early –onset seizure: first 24 hours-2 weeks (1-4 weeks): peak within 24 hours after stroke

Late-onset seizure: after 2 weeks of stroke onset: peak within 6-12 months after stroke

Postgrad Med J 2006;82:568-572.

• Early seizures ( 24 hrs- 4 wks) ≈ 1.8%-15% , excitatory or inhibitory alterations in penumbral tissue

• Late seizures ( after 4 wks) ≈ 2.5%-15%, gliosis and development of meningocerebral scar, ≈ 3 times higher risk for subsequent strokes

• Status epilepticus occurs ≈ 1/4 - 1/6 of poststroke seizures

Acute ischemic stroke

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Hemorrhagic stroke

• 2-3 times higher risk of seizures than ischemic stroke, esp. lobar or cortical hemorrhage

• Immediate seizures (with 24 hr) ≈ 1.4-17%

• Cumulative risk of seizure is higher within 5 days

• 28% of comatose or stupor pts in status epilepticus

Neurology, 2011;77:1785-1793

• 31 Italian centers, 714 patients : 609 (85.3%) cerebral infarction, 32 with hemorrhagic change and 105 (14.7%) primary ICH

• Many strengths – large sample size– clear definition of time period for early seizure (first 7 days)– excellent stroke classification by etiology, stroke subtype (

neuroimaging in all patients), stroke severity (NIH Stroke Scale and modified Rankin scale)

– complete F/U

Neurology, 2011;77:1785-1793

• 6.3% (45/714 patients) had acute symptomatic seizures occurred within 1 week of stroke– most early seizures (73%) occurred within 24 hours

after stroke onset when acute physiologic derangements are most severe

– 68.1% were focal-onset seizure

• Early seizures– 16.2% ICH– 12.5% Cerebral infarction with hemorrhagic transformation– 4.2% Cerebral infarction without hemorrhage

Neurology, 2011;77:1785-1793

• In multivariate analysis : Independent predictors of early seizures were

– Stroke type ( ICH and hemorrhagic infarction)

– Cortical lesion

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Neurology, 2011;77:1794-1800

• 522 patients ( age 58 -79 years, median age of 72 years) with spontaneous ICH and no history of previous seizure

• Many strengths – large sample size– clear definition of time period for early seizure (first 7 days)– excellent assessment of risk factors– nearly complete F/U at 6 months

Neurology, 2011;77:1794-1800

• The incidence of early seizures was 22% with lobar ICH (compared to 8% in deep ICH, 9% in posterior fossa ICH)

• ≈ 51% focal seizure, 43% generalized seizure and 4% CSE

• Higher incidence of early seizures : cortical involvement, more severe stroke, previous ICH, and younger age

• Early seizures were not independent predictors for mortality at 7 days and 6 months and did not influence functional outcome at 6 months

Aneurysmal SAH

• Incidence of seizures following Sx 10-25%

• High risk : Hunt & Hess grade 3-4, MCA aneurysm, rebleeding, large hematoma, vasospasm with cerebral infarction, shunt-dependent hydrocephalus, persistent neurological deficits

Neurology, 2015;84:2229-2237

• 876 patients with SAH from saccular intracranial aneurysm ( sIA – SAH) and no history of previous epilepsy

• Cumulative incidence of epilepsy is 8% at 1 year and12% at 5 years

• Risk factors: ICH >15 cm3 , Hunt and Hess grade 3-4 and acute seizure

Cerebral venous and sinus thrombosis

• Seizure are common, 29%-50% of patients

• Early seizures (within 2 wks), predicted by motor or sensory deficits, ICH, and cortical vein thrombosis

• Late seizures, may be common in patients with early seizures and ICH

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Acute ischemic stroke• No prospective, randomized trials to examine the use of

prophylactic AEDs to reduce seizure incidence

• Isolated early seizure does not require Rx or can be easily controlled

• Some small clinical studies suggest that PHT, PB and BDZ should be avoided during the post-stroke : delay recovery

Neurocrit Care,2007;7: 175-184.

Seizure prophylaxis

Hemorrhagic stroke

• Alcoholic patients with ICH (≈ 3 times higher risk for SE) should be treated with BDZ. If late seizures occur (2 weeks from onset), consider long-term AEDs *

* Cervoni L, et al. Neurosurg Rev 1994;17:185-8.

Seizure prophylaxis

Hemorrhagic stroke

• EEG monitoring in unexplained change in mental status following ICH

• If EEG monitoring is unavailable, prophylactic treatment seems warranted 1, 2

1. Berger AR, et al. Neurology 1988; 38 : 1363-5.2. Diringer MN. Crit Care Med 1993; 21: 1591-603.

Seizure prophylaxis

Hemorrhagic stroke• American Heart Association guidelines suggest AEDs for

1 month in patients presented with seizures *

• Recommended prophylactics AEDs in selected cases : High risk : hemorrhage, large cortical involvement, acute confusional state, preexisting dementia

*Broderick JP, et al. Stroke 1999; 30: 905-15.

Seizure prophylaxis

aSAH• Highly significant reduction in seizures in endovascular

coiling group compared to aneurysm clipping group 1

• Meta-analysis of 4 prospective RCT ( n = 3,552) : old prophylactic AEDs ( PHT, PB, CBZ) revealed worse outcome at 3 months with AEDs use 2

1. ISAT collaborative group. Lancet 2005; 366 : 809-17.

2. Rosengart AJ, et al. Stroke 2004;35:250.

Seizure prophylaxis

aSAH• ↓ half-life oral nimodipine with hepatic enzyme-inducing

AEDs 1

• May consider in periprocedurally patients ( the day before clipping and up to a week after surgery) 2

• Three-day regimen of PHT prophylaxis is adequate to prevent seizures in aSAH 3

1. Tartara A, et al. Br J Clin Pharmacol1991;32:335-40.

2. Baker CJ, et al. Neurosurg 1995;37:863-70.

3. Chamnanvej S, et al. Neurosurgery 2007;60:99-102.

Seizure prophylaxis

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aSAH• Early treatment with AEDs in aSAH patients with high

risks of seizure - Hunt & Hess grade 3-4, MCA aneurysm, rebleeding, large hematoma, vasospasm with cerebral infarction, shunt-dependent hydrocephalus, persistent neurological deficits

• Long-term treatment with AEDs in aSAH patients remains controversial

Seizure prophylaxis

Cerebral venous and sinus thrombosis

• Absence data from randomized clinical trial

• May used prophylactic AEDs in this subset of patients with focal neurological deficits and focal abnormalities on CT/MRI

Neurocrit Care,2007;7: 175-184.

Seizure prophylaxis

Cochrane Database Syst Rev;2014 Jan 24

• Review randomised and qausi-randomisedcontrolled trials in which participants were assigned to treatment or control group up to August 2013

• Only one trial fulfilled the study criteria

• A prospective randomised, double-blind, placebo-controlled trial comparing valproic acid with placebo for primary prevention of seizures in 72 adults (over 18 years of age) with spontaneous non-aneurysmal, non-traumatic ICH

• No statistically significant difference in outcome (seizure occurrence at one year) was demonstrated between groups.

• Currently, there is insufficient evidence to support the routine use of antiepileptic drugs for the primary or secondary prevention of seizures after stroke

• Further well-conducted research is needed for this important clinical problem

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• 1,832 patients– 3.4% poststroke early-onset seizures– 5.0% poststroke epilepsy.

• Statin use was associated with a lower risk of poststroke early-onset seizures, mainly in patients who used a statin only in the acute phase

• No significant association between statin use and poststroke epilepsy

• In 63 patients with early-onset seizures, statin use was associated with reduced risk of poststroke epilepsy

Neurology 2015;85:701-707

• The effect of statins in reduction of poststrokeearly-onset seizures may be meidiated by

– Decrease in glutamateric synaptic transmission

– Reduction of infarction volume mediated by anti-inflammatory and antioxidative effects, inhibition of apoptosis of neural cells

– Reduction of permeability of the BBB and brain inflammation

Thank you