Clinical risk factors for post-traumatic seizures: a systematic review and meta-analysis

Post-traumatic seizure (PTS) is a significant complication of traumatic brain injury (TBI), associated with unfavourable outcomes. However, reported risk factors for PTS are inconsistent, and considerable variation exists in clinical practice regarding seizure prophylaxis. This systematic review and meta-analysis aimed to identify and evaluate the risk factors for early and late PTS in adults.

A systematic search was conducted on PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies published from 1975 to November 2024, investigating risk factors for PTS in adults with TBI. The protocol was registered with PROSPERO (CRD42021287959). Two independent reviewers screened studies, extracted data, and assessed the risk of bias using the Critical Appraisal Skills Programme (CASP) tool. A narrative synthesis and random-effects meta-analysis were performed to pool data on PTS incidence and key risk factors.

From 13,999 records identified, 11 studies involving 242,803 patients were included. The pooled incidence of PTS was 7.2% (95% CI 5.4-9.3, I² = 98%). Most studies were prospective (58.3%) and from the USA (41.7%). On multivariable analysis within individual studies, the most consistently reported significant risk factors were severe TBI (or lower Glasgow Coma Scale score), subdural hematoma, age, and cortical contusions. Our meta-analysis found that severe TBI was associated with an increased risk of PTS, although this did not reach statistical significance (RR 2.98, 95% CI 0.81-11.01, p = 0.08). Similarly, specific radiological features including subdural hematoma (p 0.468, RR 1.42, 95% CI 0.26-7.80), subarachnoid haemorrhage (p 0.838, RR 1.07, 95% CI 0.32-3.58), extradural hematoma (p 0.237, RR 0.91, 95% CI 0.37-2.20), and contusion (p 0.2345, RR 1.24, 95% CI 0.71-2.17) were not significantly associated with PTS in the pooled analysis, which was limited by high heterogeneity. A major limitation across the studies is the lack of a rigorous approach to accurately diagnose and detect seizures, thereby compromising all subsequent association.

This systematic review highlights that while individual high-quality studies identify severe TBI, ASDH, contusions and age as key risk factors for PTS, significant heterogeneity and inadequate definitions of seizure occurrence across studies complicates definitive conclusions from meta-analysis. The high overall incidence of PTS underscores the need for better risk stratification models to guide targeted prophylactic strategies, to be achieved through large, prospective, multicentre studies randomised clinical trials [36].