Increased Risk of Late Posttraumatic Seizures Associated with Inheritance of APOE Epsilon4 Allele

Background: Late posttraumatic seizures are a common complication of moderate and severe traumatic brain injury. Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with increased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury.

Objective: To determine whether inheritance of APOE epsilon4 is associated with increased risk of developing late posttraumatic seizures.

Design: Prospective study.

Setting: Neurosurgical service at an urban level I trauma center.Patients Patients admitted with a diagnosis of moderate and severe traumatic brain injury were enrolled.

Methods: Six months after injury, patients were contacted to determine functional outcome (according to the Glasgow Outcome Scale-Expanded [GOS-E]) and the presence of late posttraumatic seizures. Genotype at the APOE locus was determined by restriction fragment length polymorphism analysis.

Results: DNA and outcome information was obtained from 106 subjects. Six months after injury, 31 (29%) had a poor outcome (GOS-E score, 1-4), 47 (44%) had an intermediate outcome (GOS-E score, 5-6), and 28 (26%) had a favorable outcome (GOS-E score, 7-8). Twenty-one patients (20%) had at least 1 late posttraumatic seizure. The relative risk of late posttraumatic seizures for patients with the epsilon4 allele was 2.41 (95% confidence interval, 1.15-5.07; P =.03). In this cohort, inheritance of APOE epsilon4 was not associated with an unfavorable GOS-E score 6 (P =.47).

Conclusions: Inheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizures. In this cohort, this risk appears to be independent of an effect of epsilon4 on functional outcome. A better understanding of the molecular role of APOE in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.