Seizures after stroke Can we predict? พ.ญ.ส ธ ดา เย นจ นทร 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 1
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 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 Epub: Sep 10, 2011 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. Acute ischemic stroke 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 2
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 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 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 Neurology, 2011;77:1785-1793 In multivariate analysis : Independent predictors of early seizures were Stroke type ( ICH and hemorrhagic infarction) Cortical lesion Neurology, 2011;77:1785-1793 3
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 Neurology, 2011;77:1794-1800 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 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 cm 3, 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 Neurology, 2015;84:2229-2237 4
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 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 * Some small clinical studies suggest that PHT, PB and BDZ should be avoided during the post-stroke : delay recovery * Cervoni L, et al. Neurosurg Rev 1994;17:185-8. Neurocrit Care,2007;7: 175-184. EEG monitoring in unexplained change in mental status following ICH If EEG monitoring is unavailable, prophylactic treatment seems warranted 1, 2 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 1. Berger AR, et al. Neurology 1988; 38 : 1363-5. 2. Diringer MN. Crit Care Med 1993; 21: 1591-603. *Broderick JP, et al. Stroke 1999; 30: 905-15. 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. 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. 5
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 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. Review randomised and qausi-randomised controlled trials in which participants were assigned to treatment or control group up to August 2013 Only one trial fulfilled the study criteria Cochrane Database Syst Rev;2014 Jan 24 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 6
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 poststroke early-onset seizures may be meidiated by Decrease in glutamateric synaptic transmission Thank you Reduction of infarction volume mediated by antiinflammatory and antioxidative effects, inhibition of apoptosis of neural cells Reduction of permeability of the BBB and brain inflammation 7