Traumatic brain injury (TBI) is the leading cause of death and acquired disability in U.S. children. Interventions such as physical therapy may improve recovery, but few other treatments are available in the post-acute phase. 0ur long-term objective is to develop and validate new and more effective treatment strategies for traumatic brain injury in children based on an improved understanding of the neurobiology of recovery. Our group has demonstrated that amphetamine (AMPH) treatment coupled with relevant environmental experience in animals produces an immediate and enduring improvement after brain injury, possibly by enhancing neuronal synaptogenesis and ameliorating post-traumatic hypometabolism. Other investigators have shown that AMPH treatment in adult humans promotes functional recovery from brain injury. Although several groups have found that methvlphenidate improves behavioral and cognitive functioning after brain injury in children, it is unclear whether this treatment affects long-term functional outcome and neuronal recovery. Understanding the role of AMPH in children after TBI requires assessment tools that are optimally sensitive to treatment effects. Animal models and adult human studies of AMPH after brain injury have demonstrated improvement in gait and spatial memory, while in children with attention deficit/hyperactivity disorder AMPH improves behavior and cognitive function. We use an assessment battery sensitive to these functions in children that includes clinical measures of cognition, gait and balance. In addition, a powerful in vivo analysis of neurochemistry is obtained by performing magnetic resonance spectroscopic imaging (SI); this allows us to measure specific regional neuronal metabolites that we have shown in an adult brain-injured population to be predictive of long-term cognitive outcome. Incorporated into a longitudinal study, these methods will enable accurate and sensitive measures of the effect of AMPH on both functional and neuronal recovery in children recovering from TBI. Before proceeding to a full study, we propose this pilot study to answer the following critical questions: 1) is AMPH safe in children recovering from TBI, 2) is it feasible to perform various pediatric assessments throughout the recovery process, including SI, and 3) are our assessment tools sensitive to the effect AMPH has on recovery? We hypothesize that it is indeed safe to treat children recovering from TBI with therapeutic doses of AMPH, and that our clinical and neurochemical assessments are feasible and sensitive to treatment effects during this time as well.
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