Risk factors for post-stroke seizures: A systematic review and meta-analysis
Introduction
Cerebrovascular disease is the most common cause of acute symptomatic seizures and secondary epilepsy in adults, accounting for approximately 11% of epilepsy diagnoses (Hauser et al., 1993). Post-stroke seizures have been categorized as either early-onset seizures (ES) or late-onset seizures (LS). There are different time-based definitions of stroke-associated ES. ES are defined as those occurring within 7–30 days after stroke onset. Seizures occurring after this time window are defined as LS, which may account for the variable incidences of ES and LS across studies. Investigators have reported higher rates of disability and mortality in patients with ES (Bladin et al., 2000, Lamy et al., 2003, Arboix et al., 1997). Over the long term (de Boer et al., 2008, Lamy et al., 2003, Neau et al., 1998), LS and epilepsy not only dramatically diminish the quality of life and cause serious morbidity but also negatively affect patients’ families and the broader community. Identifying risk factors for post-stroke seizures is thus crucial for the appropriate management of patients with acute stroke.
A number of seizure predictors have been studied, including stroke subtype, size, location and severity. However, the findings of previous studies are inconsistent and occasionally contradictory. These differences are largely due to the varying recruitment criteria, such as stroke type, follow-up duration, uncontrolled use of antiepileptic drugs and different time windows for distinguishing between ES and LS.
We therefore performed a systematic review and meta-analysis of studies investigating risk factors for post-stroke seizures, which are pertinent for physicians managing patients with acute stroke.
Section snippets
Search strategy and selection criteria
We performed a comprehensive literature search of MEDLINE and EMBASE. Our search strategy involved the use of medical subject headings and text words to identify studies on seizure and stroke. The search strategy used for MEDLINE (PubMed) is described in Appendix A. We also searched the bibliographies of reviews, original articles and book chapters and consulted experts on post-stroke seizures to find other studies.
Studies were collected according to the following inclusion criteria: (1)
Results
Of the 1054 unique articles initially identified, 100 appeared to be relevant to the meta-analysis upon initial review. A total of 25 studies met our inclusion criteria for the systematic review and meta-analysis, including 9 studies with 6632 participants for the analysis of ES and 19 studies with 21,392 patients for the analysis of LS.
Study characteristics
All studies involving ES collected data prospectively and included patients suffering from both hemorrhagic and infarction strokes, with the exception of one study that only included patients with hemorrhagic stroke (De Herdt et al., 2011). The incidence of ES within 1 week after stroke ranged from approximately 3.2–6.3%, but 2 studies reported rates of 12.6% (De Herdt et al., 2011) and 17.9% (Goswami et al., 2012). The ES study characteristics are listed in Table 1.
For LS, the included studies
Discussion
According to the ILAE, seizures after stroke are classified as ES when they occur within 7 days of a stroke and as LS when they take place over 7 days after a stroke (Guidelines for Epidemiologic Studies on Epilepsy, 1993). In the current study, post-stroke epilepsy was defined according to the most recent report by the ILAE (Fisher et al., 2014), which indicated that patients with a single seizure episode associated with an enduring condition that could cause epilepsy (such as stroke) met the
Limitation
Our study design has several potential limitations. We may not have included all relevant studies despite our comprehensive search strategy. Other limitations pertain to the quality of the evidence provided by the included studies. All included studies were observational. In several studies, the onset of epileptic seizures during follow-up was reported by the family or caregivers. Moderate heterogeneity existed among the studies included in the outcome analysis.
Conclusion
The conclusions from this systematic review and meta-analysis can be summarized as follows. First, intracerebral hemorrhagic stroke, cerebral infarction with hemorrhagic transformation and alcohol intake were significantly associated with ES occurring within 7 days after stroke. Second, there was no significant difference in the probability of a single LS episode between patients with intracerebral hemorrhage and infarction stroke, but intracerebral hemorrhage may predict recurrent LS after
Acknowledgements
This work was supported by the Beijing Municipal Cultivation Program of High-Level Health Technical Personnel from the Beijing Health Bureau (No. 2011-3-029) and the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (Nos. XM201304 and ZY201305).
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Chao Zhang and Xiu Wang contributed to this work equally.