Abstracts

Multiple authors have looked at the relationship of APOE genotype and outcome after TBI. About half have found that those with the e4 allele have worse outcome and half have found no relationship. Haptoglobin has not received much attention with respect to outcome after TBI, but oxidative stress is one aspect of the secondary injury cascade following traumatic brain injury. Hb and iron can enhance oxidative stress. The brain is susceptible to oxidative damage due to is high oxygen consumption, high lipid content and low antioxidant activity. Haptoglobin (Hp) is a plasma glycoprotein that removes free Hb and prevents Hb-induced damage. Hp has three different phenotypes, HP-1-, Hp 2-1 and Hp 2-2. Hp 1-1 is biologically the most and Hp 2-2 is the least active in Hb binding, antioxidant activity. Thus we hypothesize that those with APOE e4 genotype or Hp 2-2 or Hp 2-1 phenotype will have worse neuropsychological outcome after TBI., Patients were recruited from our valproate prophylaxis study ([italic]Temkin et al. J Neurosurg 1999;91:593-600)[/italic] to evaluate the relationship of these genetic markers and seizure occurrence. We followed at about 10 years after injury 25 of the 51 who had post-traumatic seizures, and 26 controls, group matched for age, sex, PTS risk factor and treatment group (valproate vs. placebo). Neuropsychological testing was done at 1, 6, and 12 months after injury as part of the original protocol and at the 10 year follow-up. Statistical analysis was performed using distribution-free methods (Mann-Whitney tests, Kruskal-Wallis tests and regression of the ranked neuropsychological test scores on genetic markers, seizure group, and education.), Those with APOE e4 genotype or HP 2-1 or 2-2 phenotype had higher education prior to injury (p=.004 and .02). APOE genotype was not related to outcome at any of the times with or without adjustment for seizures or education (p-values between .06 and .97 with no adjustment for multiple comparisons). Those with Hp 1-1 scored worse on VIQ at 6 and 12 month and PIQ at 12 months after injury (each p[lt].01 unadjusted) with occasional other tests showing similar trends., We could not confirm the association of APOE e4 genotype and poor outcome. The Haptoglobin results suggest a possible effect in the direction opposite that hypothesized. Association of both markers with pre-injury education raises intriguing questions about whether associations predate injury., (Supported by Research Initiative Award from the American Epilepsy Society. NIH/NINDS R01 19463.)