Poststroke Seizures Linked With Increased Mortality, Disability, Dementia

Shubham Misra, PhD

A recently published systematic review and meta-analysis showed that poststroke seizures (PSSs) are associated with increased mortality risk, poor function outcomes, disability, and dementia. Investigators concluded that collaborative scientific efforts are needed to address these challenges, as well as additional research understanding the role of stroke severity and lesion location or volume.

Using MEDLINE, Embase, PsychInfo, Cochrane, LILACS, LIPECS, and Web of Science, the search yielded 71 eligible articles, including 20,110 patients with PSS and 1,166,085 patients without PSS. In 57 studies, patients with PSS had approximately double the risk of death (OR, 2.1; 95% CI, 1.8-2.4; I2 = 86%) with substantial heterogeneity. The significant association persisted after removing 8 outlier studies with reduced heterogeneity (I2 = 59%).

Led by Shubham Misra, PhD, a clinical neuroscientist at Yale School of Medicine, the analysis included data from 1951 to January 2023. The inclusion criteria comprised of patients with a history of stroke (ischemic, hemorrhagic, or both) and those aged 18 years or older presenting with either early or late PSS. Coming into the analysis, patients with PSS had a significantly higher history of ischemic heart disease (OR, 1.3; 95% CI, 1.1-1.6), prior cerebrovascular disease (OR, 1.3; 95% CI, 1.0-1.6), atrial fibrillation (OR, 1.2; 95% CI, 1.1-1.4), and the presence of hemorrhagic transformation (OR, 2.2; 95% CI, 1.6-3.0) than patients without PSS.

In a subgroup analysis, early seizures were associated with an increased mortality risk but not late seizures (OR, 2.4; 95% CI [1.9-2.9] vs OR, 1.2 [95% CI, 0.8-2.0]). Based on stroke type, patients with ischemic (OR, 2.2; 95% CI, 1.8-2.7) or hemorrhagic (OR, 1.4; 95% CI, 1.0-1.8) who subsequently developed seizures had increased mortality risk. Notably, early seizures after ischemic stroke were associated with mortality but not late seizures (OR, 2.4 [95% CI, 1.8-3.2] vs OR, 0.7 [95% CI, 0.3-1.6]). A subgroup of patients with poststroke status epilepticus also presented with increased mortality (OR, 2.5; 95% CI, 1.7-3.8).

Poor functional outcome, defined as modified Rankin Scale (mRS) scores between 3 and 6, were more frequent for those with PSS than those without (OR, 2.2; 95% CI, 1.8-2.8; I2 = 57%). Investigators found that early and late-onset seizures after stroke (OR, 2.4 [95% CI, 1.6-3.4] vs OR, 2.7 [95% CI, 1.8-4.1]) and seizures after ischemic and hemorrhagic stroke (OR, 2.6 [95% CI, 1.9-3.7] vs OR, 1.9 [95% CI, 1.0-3.6]) were significantly associated with poor outcomes.

READ MORE: Significant Stroke Risk Disparities Reduced Following Intensive Medical Intervention

"Mechanisms of early and late seizures are very different and, not surprisingly, have very different clinical significance; therefore, early and late seizures must be treated separately in future studies, including meta-analyses,” Misra et al wrote. "Early seizures reflect acute reversible metabolic defects that might be life-threatening. In contrast, late seizures reflect structural changes that require time to develop and are not due to life-threatening underlying pathology."

In 10 studies, investigators observed a higher mean mRS disability among patients with PSS than those without (standardized mean difference [SMD], 0.6; 95% CI, 0.4-0.7; I2 = 71%), with age significantly accounting for 45.1% heterogeneity (estimate, –0.02; 95% CI, –0.04 to –0.003; P = .03). While seizures after ischemic stroke were associated with higher disability, seizures after hemorrhagic stroke were not.

In terms of recurrent stroke, 5 studies identified no association between PSS and recurrent stroke (OR, 1.3; 95% CI, 0.6-3.0). Two studies found an increased dementia risk in patients with PSS (OR, 3.1; 95% CI, 1.3-7.7). In the discussion section, the authors noted that patients with cerebrovascular disease are at an increased risk of vascular cognitive impairment and dementia, as well as that chronic seizure activity may contribute to the dementia risk.

REFERENCE
1. Misra S, Kasner SE, Dawson J, et al. Outcomes in patients with poststroke seizures: a systematic review and meta-analysis. JAMA Neurol. Published online September 18, 2023. doi:10.1001/jamaneurol.2023.3240