Traumatic brain injuries represent an important health problem: they occur with high frequency, the population affected contains many previously healthy young people, and they are associated with high mortality and morbidity. This study continues on our 20 years of experience in conducting clinical trials evaluating treatments for preventing seizures following head injury (Dilantin Prophylaxis of Post-traumatic Seizures. Valproate for Prophylaxis of Post-traumatic Seizures) and in examining neurobehavioral outcome after head injury. The trials and outcome studies found that epileptic seizures, serious cognitive difficulties, high unemployment, and inability to live independently are common among survivors of moderate or severe head injury the ongoing trial tests whether these consequence can be ameliorated by magnesium sulfate. Using a randomized, double-blind design, the present study evaluates magnesium sulfate as a neuroprotectant and anti-epileptogenic agent following head injury. Magnesium sulfate is a widely used, well tolerated compound that has been shown in the laboratory to be effective in reducing seizures and also in limiting neuronal damage and in improving functional outcome following experimental head injury. Specifically, the study will test the hypothesis that magnesium sulfate, when given 8 hours of a moderate or severe head injury, a) increases survival b) decreases seizures, and c) improves neurobehavioral functioning. Additionally, the study will: assess the effects of timing of dosage (e.g. <4 hours vs. 4-8 hours), gender, and race; determine the rate of adverse events; and evaluate the time course and correlates of total and ionized magnesium concentrations. Patients with moderate or severe head injury (post-resuscitation Glasgow Coma Scale 3-12 or having an early craniotomy) are randomized to receive moderate doses of magnesium sulfate or placebo. Treatment is started as soon as possible, and definitely within 8 hours of injury. The initial bolus of magnesium sulfate is followed by a 5 day infusion to keep the magnesium levels elevated during the period when secondary damage from the head injury is most likely. Patients are closely monitored for survival and seizures over the first six months after injury and have a brief neurobehavioral assessment at I and 3 months and a comprehensive neurobehavioral assessment at six months after injury. In summary, this placebo-controlled, randomized double-masked clinical trial will determine the effects of magnesium sulfate on survival, post-traumatic seizures, and the patients' functional status and neurobehavioral functioning following traumatic brain injury.
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