Future Directions
The numerous trials of neuroprotective agents in recent decades have had largely negative results; hence, there is still an unmet need for effective therapies against TBI. A major challenge is to improve trial design and validate new outcome scales to detect smaller but clinically meaningful treatment effects. Decompressive craniectomy, therapeutic hypothermia, hyperoxia (hyperbaric and normobaric) and progesterone are the subject of ongoing phase III randomised trials. Also underway are systematic studies of genetic risk factors in TBI that should improve prognostic models and suggest new treatment targets. As multimodality neuromonitoring (ICP waveform analysis, brain tissue oxygenation, microdialysis, advanced neuroimaging) becomes more established in the clinical arena, our ability to detect secondary insults and deliver individualised targeted interventions will improve. Therapeutic approaches that promote repair of the primary injury to the central nervous system, including stem cell treatments, remain experimental and have not yet been tested clinically.