Stroke is a debilitating neurological injury associated with significant morbidity and mortality. The prevalence of stroke is more pronounced among the adult population due to the cumulative impact of comorbidities. Pediatric stroke is an acute neurological deficit in children aged 18 years or younger, with radiological evidence of cerebral infarction corresponding to the clinical manifestations (1). The death rate among children with stroke ranges from 10 to 25%, ranking among the top 10 causes of death in children (2–4). Pediatric stroke is classified into two types, hemorrhagic and ischemic, with an incidence of approximately 1.2 to 13 cases per 100,000 children. Pediatric stroke often results in death or considerable disabilities imposing serious consequences (5, 6). Despite advances in stroke management, the diagnosis of stroke among the pediatric population is usually delayed. Furthermore, there is a lack of knowledge regarding the most effective interventions for pediatric stroke. Therefore, the majority of pediatric stroke survivors experience long-term consequences with a greater loss of disability-free life years compared to adults. Notably, 50–85% of pediatric stroke survivors usually experience considerable behavioral problems, language impairment, sensorimotor deficits, and epilepsy (7, 8). The burden of pediatric strokes on the patients and healthcare systems warrants greater attention and further evaluation.

Epilepsy is a common complication among stroke survivors. Post-stroke epilepsy (PSE) is defined as the occurrence of at least two unprovoked seizures beyond 2 weeks of an acute stroke that are not due to any other identifiable cause. The incidence of PSE ranges from 4 to 13% among patients with hemorrhagic stroke and from 3 to 7% among patients with ischemic stroke (9–11). The 10-year cumulative incidence of PSE is nearly 30% among childhood stroke survivors (12). Importantly, PSE is attributable to the structural changes associated with stroke. This included neuronal loss, subsequent gliosis, and the significant remodeling of the neuronal networks (13, 14). In contrast, early or acute symptomatic seizures that occur within a week after stroke are attributed to metabolic dysfunction, abrupt disruption of cerebral integrity, and transient neuro-depolarization (15). PSE represents a significant threat in children with stroke and negatively impacts short- and long-term management. Pediatric patients have worse parent-reported health outcomes with substantial cognitive and performance disabilities (16). This included retardation in achieving independence, social responsibility, and learning disabilities (17).

Pediatric stroke is a rare entity that is often diagnosed with significant delays or misdiagnosed. PSE is associated with a high risk of all-cause mortality and morbidity. With improved survival after stroke, the impact of PSE on the quality of life is a growing area in the literature. Identifying risk factors of PSE is of great importance to improve the management of pediatric patients with stroke (9, 18). Several risk factors for PSE have been investigated among stroke survivors. These include stroke severity, lesion size, age at onset, cortical involvement, stroke subtype, and the presence of early seizures. Paradoxically, the findings of previous reports are often contradictory, with most articles focusing on adult populations. In this respect, substantial heterogeneity exists among these studies in terms of recruitment criteria, sampling methods, follow-up protocols, and the characteristics of the population (19–21). Consequently, the present systematic review aimed to identify patient-related, stroke-related, and seizure-related risk factors for epilepsy in the pediatric population following stroke. Understanding these risk factors is essential for improving prognostication and optimizing treatment strategies, thereby enhancing the quality of life for affected children and their families.

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (22), and the methodological recommendations of the Cochrane Collaboration (23). The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023431824¹.

A comprehensive search across 12 databases identified 568 articles. Following the removal of 131 duplicates, 437 studies remained for title and abstract screening. Of these, 398 reports were excluded, leaving 39 studies eligible for full-text screening. Subsequently, 23 articles were excluded, resulting in 16 studies eligible for data extraction, of which two were further excluded. An additional article was identified through citation tracking, culminating in 15 articles included in the initial meta-analysis. An updated database search later identified one more article, resulting in 16 articles finally being included for meta-analysis (Figure 1).

The development of PSE is a debilitating consequence of stroke. The incidence of PSE among the pediatric population remains inadequately identified, with various estimations. Subsequently, predictors of PSE among the pediatric population have not been comprehensively investigated, and there are contradictory findings from previously published studies (43). The management and prognostication of PSE remain a challenge in the literature (21). The present systematic review highlighted the significant risk of PSE among pediatric stroke survivors. This risk was determined in approximately one of every three patients after a stroke. Patients younger at stroke onset, those with cortical involvement, or those with middle cerebral artery involvement at the time of stroke were at higher risk of PSE. Subsequently, patients with acute or prolonged seizures were at higher risk of PSE. Neither the type of stroke nor the presence of neurological deficits was associated with a significantly higher risk of PSE. These findings highlighted the urgent need to establish guidelines for diagnosing and treating pediatric patients at higher risk of PSE early and effectively. This systematic review revealed the significant risk of PSE among pediatric patients with stroke. The higher risk of PSE reflects the severity of stroke, conferring a considerable risk of long-term morbidities and mortality (44). Rattani et al. (45) reported a risk of PSE of 27.2% among perinatal arterial ischemic stroke survivors with an average duration of approximately 10 years since stroke onset. In parallel with these findings, Ren et al. (18) reported a significant association between PSE and all-cause mortality, suggesting the independent impact of PSE on death after stroke. Phan et al. (21) reported an increased risk of PSE among the younger population, male gender, and stroke affecting the cortex.

The present systematic review confirmed the association between younger age at stroke onset and PSE. Patients with neonatal arterial or perinatal ischemic strokes were at approximately six- and eight-times higher risk of PSE. These findings are consistent with Gao et al. (1) study. They revealed the significant neurological impairment associated with neonatal ischemic stroke. The average time to diagnose neonates with ischemic stroke is 22 h from the beginning of symptoms. Such a delay in the diagnosis is associated with a delay in management beyond the time window for intravenous thrombolysis or thrombectomy. This is associated with life-threatening consequences, highlighting the utmost importance of early diagnosis and effective therapy for stroke patients (46).

Patients with acute or prolonged seizures at the onset of stroke were associated with a higher risk of PSE. Anti-epileptic medications in such patients can be clinically significant in decreasing the risk of PSE (47). Similarly, Rattani et al. (45) confirmed the association between seizures at the stroke onset and PSE among perinatal arterial ischemic stroke survivors. Pediatric patients with acute symptomatic seizures are more likely to have epileptiform discharges and electrographic seizures on EEG. Furthermore, Patients with cortical involvement or middle cerebral artery involvement were at higher risk of PSE. This finding was consistent with Zhang et al. (19) who reported a significant risk of late seizures among patients with cortical involvement. Such patients may benefit from close monitoring and prophylactic anti-convulsive medications. However, the present systematic review showed a non-significant association between abnormal EEG changes and the risk of PSE. This finding supports the phenomenon of electroclinical dissociation in which a considerable number of neonatal seizures are subclinical. This highlighted the need for closer electroencephalographic monitoring of the pediatric population after stroke (48). Abnormal acute EEG findings may not reliably predict post-stroke epilepsy in neonates due to electroclinical dissociation, where epileptiform activity may occur without overt clinical seizures. Immature cortical networks and evolving seizure semiology further limit EEG sensitivity, underscoring the need for cautious interpretation and long-term clinical follow-up. Further studies are needed to evaluate the impact of prophylactic anti-epileptic medications on the long-term risk of PSE among the pediatric population.

This systematic review synthesized existing evidence concerning the risk factors associated with PSE. While the study possesses several strengths, certain limitations warrant consideration. All included studies employed observational designs, with a substantial proportion being retrospective, thereby introducing a potential risk of information bias. Additionally, variability existed among the studies in terms of PSE definitions, follow-up durations, age ranges, and statistical methodologies. This heterogeneity was reflected in the meta-analysis through significant statistical variability across multiple outcomes. To address this, a random-effects model was applied. Further research is necessary to elucidate the long-term effects of stroke on the risk of PSE and its subsequent clinical outcomes.

The present systematic review highlights the significant risk of PSE among pediatric stroke survivors. Younger pediatric patients, as well as those with cortical or middle cerebral artery involvement, demonstrate an increased susceptibility to developing PSE. Furthermore, the occurrence of acute symptomatic seizures at stroke onset, especially when prolonged, substantially elevates the risk of subsequent epilepsy. Early identification of pediatric patients at heightened risk for PSE may enable clinicians to target vulnerable populations and implement timely preventive interventions aimed at reducing the incidence of PSE.