Moderate and severe traumatic brain injury (TBI) remains a major public health challenge. It affects the young and elderly disproportionately, having a magnified societal impact early in life and during retirement. The consequent cognitive and behavioral changes after TBI can at times be subtle and unrecognized. Mild TBI, while resulting in less severe – albeit very real – deficits, has an important societal impact because of the number of individuals affected, and still unknown factors predispose some with mild TBI to have a higher risk than others of developing a late-life neurodegenerative disorder. While preventive measures such as the use of helmets and vehicular restraints may reduce the incidence of severe TBI, such injury will not be eliminated. Early in our careers, both of us became involved in the study of Vietnam veterans with penetrating traumatic brain injury, and we appreciated the advances in acute care medicine that enabled many of those veterans to survive. Major advances in our understanding of the brain’s response to, and recovery from, injury have continued in the past few decades but generally have failed to be translated into clinical practice. Thus, one major motivation for us to edit these two volumes on TBI in the Handbook of Clinical Neurology series has been the opportunity to help strengthen the link between basic science and clinical management in a way that can inform both bench scientists and practitioners. We believe we have accomplished this goal by providing the reader with an updated review of emerging approaches to TBI research, clinical management, and rehabilitation of affected patients that offers new and unique perspectives on TBI. Chapters in this volume have been written by leaders in the field, and include epidemiology and pathologic mechanisms of injury, neuroprotection, functional sequelae, prediction of long-term outcomes, and neuroplasticity, with a strong emphasis on current neurobiologic approaches to describing the consequences and mechanisms of recovery from TBI. Contemporary investigations on blast injury are presented, highlighting the contributions that war medicine has made to TBI management over the past century and demonstrating that combat-related TBI draws public and scientific attention to TBI research and management, often leading to increased support for research and advances in medical knowledge and practice. The recognition of the risk for chronic traumatic encephalopathy, even after mild sports TBI, is another recent development that is lending clarity to our understanding of the long-term consequences and recovery from TBI, including its link to more common neurodegenerative conditions such as Alzheimer disease. Finally, the volumes conclude with chapters that discuss the challenges in design of clinical trials for neuroprotection and rehabilitation, echoing a theme that is also introduced by other authors throughout the volume. It remains challenging to take time away from writing data-driven papers, grant writing, and other day-to-day responsibilities to write a review chapter – even if the chapter is on a topic dear to the heart. Nevertheless, such chapters offer a unique opportunity to summarize an area of research and study and to advance hypotheses based on this appraisal. We believe our contributors exemplify this approach and we gratefully acknowledge their contributions. Many of us who study and work with TBI patients know the sacrifice that patients make to contribute to research that may lead to future improvements in clinical care. We are forever indebted to them for their help, trust, and devotion. Finally, we thank our families for their support and patience in allowing us to prepare and complete these volumes. Andres M. Salazar, M.D. Jordan Grafman, Ph.D.


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