ONE-CARBON METABOLISM MARKERS IN POST-TRAUMATIC EPILEPSY

We recently found that individuals who have a particular common genetic mutation (MTHFR C677T) are at increased risk of epilepsy including in particular epilepsy resulting from head trauma (e.g. post-traumatic epilepsy). It is known that people with this genetic mutation are likely to have elevated levels of homocysteine in their blood, which is a byproduct of faulty folate (folic acid) metabolism. Homocysteine has been shown to lower seizure thresholds so we reasoned that people with this particular genetic mutation would be at higher than average risk of developing seizures following head trauma. Homocysteine levels can be lowered with dietary intake of folic acid and other B vitamins.In this proposed follow-on study, we aim to confirm our prior results by measuring pre-diagnosis levels of homocysteine, folate, and related blood markers in a new cohort of active duty military personnel. We hypothesize that the study subjects who develop post-traumatic epilepsy will have abnormal levels of these biomarkers compared to the control subjects.The results from this study, if positive, have near-term implications for risk assessment and neuroprotection that can be tested in a clinical trial:a) These metabolic markers may be used to identify individuals who are at higher than average risk of adverse neurological outcome following head injuryb) A clinical trial can be conducted to determine whether supplementation with folic acid or related compounds will lower the risk of seizures or epilepsy in high risk populations such as deployed military personnel