Traumatic brain injury is a longitudinal disease process
Traumatic brain injury (TBI) is a devastating public health problem that affects millions each year at a cost of over $46 billion/year. There remains no specific single curative treatment for TBI despite multiple failed clinical trials. The reasons for this dilemma center around three main concerns: TBI is a heterogeneous disease affecting different regions of the brain and hence a wide clinical phenotype; TBI is a complex disease process with multiple secondary injuries that in varying permutations; and TBI is a longitudinal disease process rather than an isolated injury, thus creating a moving target for any specific therapy. The longitudinal processes after TBI include cell death, network demise, network reorganization, immunological response, formation of aberrant neural networks (i.e. seizures), glial response, amyloid deposition and many other mechanisms. This longitudinal response appears to occur over many years, in somewhat unpredictable ways. The interaction of these varied processes and the effects of these processes on neurological outcome remains uncertain. The basic concept of injury first, and then rehabilitation later, is fundamentally incorrect. The realistic conceptual framework is injury followed by a series of overlapping processes of secondary injury and spontaneous adaptive and maladaptive restoration processes. Thus, creating an optimal treatment for injury recovery will be dependent on understanding these various processes.