Seizure Outcomes and Predictors of Recurrent Post-Stroke Seizure: A Retrospective Observational Cohort Study

Abstract

Background: Seizure is a common complication after stroke (termed "post-stroke seizure," PSS). Although many studies have assessed outcomes and risk factors of PSS, no reliable predictors are currently available to determine PSS recurrence. We compared baseline clinical characteristics and post-stroke treatment regimens between recurrent and non-recurrent PSS patients to identify factors predictive of recurrence.

Methods: Consecutive PSS patients admitted to our stroke center between January 2011 and July 2013 were monitored until February 2014 (median 357 days; IQR, 160-552) and retrospectively evaluated for baseline clinical characteristics and PSS recurrence. Cumulative recurrence rates at 90, 180, and 360 days post-stroke were estimated by Kaplan-Meier analysis. Independent predictors of recurrent PSS were identified by Cox proportional-hazards analysis.

Results: A total of 104 patients (71 men; mean age, 72.1 ± 11.2 years) were analyzed. PSS recurred in 31 patients (30%) during the follow-up. Factors significantly associated with PSS recurrence by log-rank analysis included previous PSS, valproic acid (VPA) monotherapy, polytherapy with antiepileptic drugs (AEDs), frontal cortical lesion, and higher modified Rankin Scale score at discharge (all p < 0.05). Independent predictors of recurrent PSS were age <74 years (HR 2.38, 95% CI 1.02-5.90), VPA monotherapy (HR 3.86, 95% CI 1.30-12.62), and convulsions on admission (HR 3.87, 95% CI 1.35-12.76).

Conclusions: Approximately one-third of PSS patients experienced seizure recurrence within one year. The predictors of recurrent PSS were younger age, presence of convulsions and VPA monotherapy. Our findings should be interpreted cautiously in countries where monotherapy with second-generation AEDs has been approved because this study was conducted while second-generation AEDs had not been officially approved for monotherapy in Japan.

Fig 1. Study design and protocol.

PSS, post-stroke seizures.

Fig 2. Kaplan—Meier curves for proportion without recurrent PSS.

A. After a median follow-up of 362 days, we identified recurrent PSS in 31 patients (29.8%). Dotted lines indicate the confidence interval. B. For patients who received (solid line) or did not receive (dotted line) valproic acid (VPA) monotherapy at the time of recurrence or end of follow-up. VPA monotherapy may be insufficient to prevent recurrent PSS (log-rank test, p = 0.013).

Fig 3. Association of designated factors with presence or absence of recurrent PSS.

Hazard ratios (HR) (dots), 95% confidence intervals (95% CI) (error bars), and P values are from Cox proportional hazards models adjusted for age (<74 years), previous post-stroke seizures (PSS), valproic acid (VPA) monotherapy, phenytoin (PHT) monotherapy, polytherapy, frontal cortical lesion, dyslipidemia, diabetes mellitus, atrial fibrillation, presence of convulsions on admission, and poor modified Rankin Scale (mRS) score (3–5).