Abstracts

RATIONALE: Post-traumatic epilepsy (PTE) is a common complication of moderate and severe traumatic brain injury (TBI). However, only a fraction of patients with TBI develop PTE, and it is likely that host genetic factors may influence the epileptogenic process. Inheritance of the [italic]APOE[/italic] [epsilon]4 allele is associated with increased risk of Alzheimer[ssquote]s disease, increased disability in patients with multiple sclerosis, and poor outcome after TBI. This study was undertaken to determine whether inheritance of [italic]APOE[/italic] [epsilon]4 is associated with increased risk of developing late post-traumatic seizures.
METHODS: Patients admitted to the neurosurgical service with a diagnosis of moderate and severe TBI were enrolled in the study, and after informed consent obtained, a DNA sample was acquired. Patients with pre-existing epilepsy, brain tumors, or other brain lesions likely to result in epilepsy were excluded. Six months after injury patients were administered a structured questionnaire to determine functional outcome (according to the Glasgow Outcome Scale-Expanded (GOSE) and the presence of late post-traumatic seizures. Genotype at the [italic]APOE[/italic] locus was determined by restriction-fragment length polymorphism mapping of an amplified 244-mer oligonucleotide, using published techniques. Data was analyzed according to Fisher[ssquote]s Exact Test.
RESULTS: DNA and outcome information was obtained from 90 subjects. 22 (24%) inherited at least one copy of [italic]APOE[/italic] [epsilon]4. Six months after injury, 28 (31%) had a poor outcome (GOSE 1-4), 39 (43%) had an intermediate outcome (GOSE 5-6), and 23 (26%) had a favorable outcome (GOSE 7-8). 18 (20%) of cohort had experienced at least one late post-traumatic seizure. The relative risk (RR) of PTE for patients with the [epsilon]4 allele was 2.28 (95% CI 1.14 - 4.60, p = 0.036). In this cohort inheritance of [italic]APOE[/italic] [epsilon]4 was not associated with an unfavorable GOSE (RR 1.36, 95% CI 0.63 - 2.91, p = 0.574).
CONCLUSIONS: We conclude that inheritance of the [italic]APOE[/italic] [epsilon]4 allele is associated with increased risk of developing PTE. In this cohort, this risk appears to be independent of an effect of [epsilon]4 on functional outcome, as measured by the GOSE. [italic]APOE[/italic] may influence the reaction of neural tissue to injury, or may affect regeneration and repair of injured neurons. A better understanding of the molecular role of [italic]APOE][/italic] in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.
[Supported by: RD-A is supported by NIH RO1 AG17861, RO3 MH64889, and R24 MH59656.]