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Traumatic brain injury is a longitudinal disease process

Vespa, Paul

doi: 10.1097/WCO.0000000000000506
TRAUMA AND REHABILITATION: Edited by Paul Vespa

Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Correspondence to Paul Vespa, MD, FCCM, FAAN, FANA, FNCS, Assistant Dean of Critical Care Medicine (Research), Gary L. Brinderson Family Chair in Neurocritical Care, Professor of Neurology, Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. E-mail: PVespa@mednet.ucla.edu

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.

In this special supplement of Current Opinion in Neurology, we begin with Dr Au's (pp. 565–572) discussion pediatric TBI to review many of the prognostic indicators after TBI. Important new discoveries in blood and imaging biomarkers in the early stages after injury have improved our abilities for prognostication and also have led to innovative treatment strategies. Pediatric TBI represents a unique condition in which injury recovery occurs in the setting of evolving development. Adaptive network connections may be more amenable to recovery. Biomarkers of injury and the recovery process have just begun to be discovered. One can envision a pathway for monitoring the recovery process and using biomarkers to test response to specific recovery therapies and hence create the setting for proof of mechanism studies. Precision medicine proteomics arrays are just beginning to be tested in this setting.

We move next to Dr Monti's (pp. 573–579) discussion of prolonged disorders of consciousness after TBI. The features of the spectrum of minimally conscious state and persistent vegetative state are beginning to become formalized. The imaging and clinical indicators of these disorders of consciousness are being defined. Although no treatment has clearly emerged as curative, promising studies of stimulant medications, deep brain stimulation and focused beam ultrasound are just beginning to accrue data. The potential future of these treatments is unclear, but our understanding of how to document consciousness and track the response to treatment is a clear advancement in our quest for rehabilitative treatments for TBI.

Finally, we consider Dr Zimmermann's (pp. 580–586) discussion of post-traumatic epilepsy (PTE). PTE plays an important role along the entire longitudinal spectrum after TBI. In the acute settings, post-traumatic seizures can worsen the extent of the brain injury. In the more subacute to chronic time points, seizures and their antiseizure treatments can impair the recovery of function. The network changes that occur in the subacute setting may evoke PTE rather than lead to enhanced rehabilitation. The use of antiseizure medications can further impair cognitive function. The clinical decisions to continue antiseizure medications or adjust those medications to enhance recovery are complex and lack fundamental data for selective treatment.

In summary, TBI is a longitudinal disease process that involves ongoing cellular damage that is intermixed with restorative processes in the chronic phase. Our challenge will be to identify how best to stop the ongoing damage while enhancing those restorative processes that lead to full recovery.

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