Seizure onset timing as a predictor of mortality in pediatric bacterial meningitis: a post-hoc analysis

Abstract

Background: Acute symptomatic seizures (ASAs) are critical complications of pediatric bacterial meningitis (BM). This study is a post-hoc analysis of a 270-patient database originally described by Corrêa-Lima et al. (2015), exploring how seizure timing of clinical admission affects clinical outcomes. Objective: To determine if the timing of the first pre-hospital seizure serves as a predictor of intra-hospital recurrence and mortality. Methods: We analyzed a subset of 52 patients from the original 270-case cohort who presented with seizures prior to hospitalization. Patients were stratified into two groups based on diagnostic delay: Recent Seizure Group (onset ≤24h before admission) and Delayed Seizure Group (onset >24h before admission). Continuous variables were expressed as Median and Interquartile Range (IQR), and categorical variables were compared using Fisher’s exact test to identify risks of recurrence and death. Results: The study population consisted primarily of young infants (Median age: 0.40 years; IQR: 0.30–0.50), with S. pneumoniae as the most prevalent pathogen (55.8%). The Delayed Seizure Group (>24h delay) showed a significantly higher risk of intra-hospital seizure recurrence compared to the Recent Seizure Group (8/16 [50.0%] vs 8/36 [22.2%]; p < 0.05). The overall case fatality rate for this subset was 30.7% (16/52). Mortality was higher in patients who experienced subsequent intra-hospital recurrence compared to those with isolated pre-hospital events (9/24 [37.5%] vs 7/28 [25.0%]). Early deaths were linked to intracranial hypertension, while late deaths correlated with diagnostic delay and recurrent seizure activity. Conclusion: Intra-hospital seizure recurrence is a more potent marker of severe cerebral insult than isolated pre-hospital seizures. This study demonstrates that a seizure occurring more than 24 hours before admission acts as a critical "red flag." The study relies on caregiver reports, introducing potential observer bias. In infants, subtle seizures (e.g., ocular or autonomic signs) may be unrecognized or misidentified as benign febrile seizures. This ambiguity is a major hurdle in primary care. Furthermore, current literature remains inconclusive regarding whether starting anticonvulsants preemptively—based solely on home-seizure reports before a recurrence is witnessed in the hospital—effectively modifies mortality rates. However, data suggest that prolonged exposure to untreated CNS inflammation facilitates these recurrent discharges. A seizure occurring >24h before admission significantly increased the risk of intra-hospital recurrence. These findings urge primary care providers to strictly apply diagnostic criteria to differentiate benign febrile seizures from meningitis-related events. Rather than advocating for immediate prophylactic anticonvulsant use, a strategy still lacking consensus in the literature, these results highlight the importance of identifying diagnostic delays as markers of high-risk patients who require intensive monitoring.