Traumatic brain injury: physiology, mechanisms, and outcome

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Abstract
This review on traumatic brain injury consolidates the substantial current literature available on the pathophysiology, mechanisms, developments, and their subsequent effects on outcome. In particular, it tries to conceptualize why our greatly improved understanding of pathophysiology and neurobiology in traumatic brain injury has not translated into clear outcome improvements. Early cerebral ischaemia has been characterized further, with ischaemic brain volume correlating with 6-month outcome. The Brain Trauma Foundation has revised perfusion pressure targets, and there are additional data on the outcome impact of brain tissue oxygen response and asymmetric patterns of cerebral autoregulation. Mechanistic studies have highlighted the role of inflammation and introduced concepts such as therapeutic vaccination and immune modulation. Experimental neurogenesis and repair strategies show promise. Despite continuing gains in knowledge, the experimental successes have not yet translated to the clinic. Indeed, several major articles have attempted to understand the clinical failure of highly promising strategies such as hypothermia, and set out the framework for further studies (e.g. addressing decompressive craniectomy). High-dose mannitol has shown promise in poor grade patients, while hypertonic saline has shown better intracranial pressure control. Negative results may be the consequence of ineffective therapies. However, there is a gathering body of work that highlights the outcome impact of subtle neurocognitive changes, which may not be quantified adequately by outcome measures used in previous trials. Such knowledge has also informed improved definition of mild traumatic brain injury, and allowed validation of management guidelines. The evidence base for current therapies in this heterogeneous patient group is being refined, with greater emphasis on long-term functional outcomes. Improved monitoring techniques emphasize the need for individualization of therapeutic interventions.