Abstract: The aim of this review was to explain the role played by pituitary hormonal deficiencies in the traumatic brain injury (TBI) disease process. Chronic dysfunction of the pituitary axis is observed in approximately 35% of individuals who sustain a moderate-to-severe TBI. The most common deficiency is that of growth hormone, followed by gonadotropin, cortisol, and thyroid. The medical, psychological, and psychiatric consequences of untreated hypopituitarism are extensive and can be devastating. Many of the consequences of a chronic symptomatic TBI have, in the past, been solely attributed to the brain injury per se. Analysis of the signs and symptoms of pituitary axis dysfunction suggests that many of these consequences can be attributed to post-traumatic hypopituitarism (PTH). PTH may well play a significant role in the progressive signs and symptoms that follow a chronic TBI.

Abstract: Asearch for articles related to traumatic brain injury (TBI) using search terms such as ‘‘traumatic brain injury,’’ ‘‘brain injuries,’’ or ‘‘craniocerebral trauma’’ yields approximately 50,000 to 120,000 references, depending on the search terms. Combining these terms with ‘‘chronic’’ or ‘‘long-term’’ reduces the number by more than 90%. Although hardly a rigorous ‘‘study,’’ the results suggest that less than 10% of TBI research is related to chronic effects or long-term outcomes. Although research on the chronic consequences of neurotrauma is expensive and time-consuming, it is very important. Implicit in the nomenclature of TBI is the concept that trauma to the brain is the result of an injury and that the injury will heal. Injuries frequently have a proscribed protocol for treatment that may result in significant improvement and possibly a cure. This, however, is not always the case with TBI. After 15 years, as many as one in three persons with a moderate-severe TBI has declined from a previously achieved outcome. The Institute of Medicine’s report also endorsed the chronicity of TBIs and clearly recognized that far more work remains to be done to deal with these issues. There are more than 5.3 million and 7.7 million persons living with disabilities from TBI in the European Union and United States, respectively. Thus, while there are approximately 250,000 new hospitalizations for TBI in the United States annually, there are millions of TBI survivors in the United States and worldwide. Unfortunately, some of these survivors are affected by the consequences of TBI their entire lives. By its very nature, every TBI has its own unique multifaceted signature, which will manifest as one of a constellation of neurological effects. TBI is an important cause of disability and death for children and is an exponentially increasing source of mortality and morbidity in older adults. While many, if not most, of the 1.5 million TBIs sustained annually in the United States are indeed injuries from which each patient recovers, or is cured, more than 125,000 of these injuries are permanent and incurable. The articles presented in this special edition support the concept that many TBIs are chronic and that a TBI is the beginning of an evolving process of medical issues that negatively impact the lives of those affected. With its high prevalence, especially in the young, and its vast medical, psychological, and social consequences, a TBI carries incredibly high personal, economic, and social costs. Unless one is actively engaged in the field, experimental TBI in animals can be confusing and difficult to understand. Osier and associates summarize the various models of TBI, histopathologic outcomes, and behavioral outcomes in a manner that will be used as a reference in the future by many scientists. For the longest time, the elephant in the room has been the mechanisms of chronic and/or delayed neurodegeneration that may occur long after a TBI. Bramlett and colleagues review the various pathomechanisms that may contribute to this problem and discuss potential therapies for these processes. The article by Harrison-Felix and coworkers showing reduced life expectancy, consistent risk factors, and uniquely common causes of death furthers the case for increased research on the chronic effects of a TBI. The article by Greenwald and colleagues digs deeper into this issue and identifies that persons with a TBI who are unable to follow command on admission to rehabilitation are at an even greater risk for earlier death. Babikian and associates address the woefully understudied issue of chronic TBI in the pediatric population. They make it quite clear that pediatric brains are not just ‘‘little adult brains’’ and that a TBI to a brain that is in rapid change and development has an enormous impact— medically, emotionally socially, and cognitively. The reader will clearly have an understanding of pediatric TBI including monitoring and treatment strategies. Clinicians treating persons with TBIs are readily aware of the enormous impact that psychological and psychiatric disorders as well as substance abuse play in recovery and return to the community. Zgaljardic and coworkers address these issues in detail including etiology and treatment. Masel and associates shed further light on the neuroendocrine issues after a TBI and how they may impact recovery and long-term outcome. As scientists and clinicians, our challenge is to look at TBI in an entirely different light. Researchers must focus beyond the first few precious hours during which the acute injury is negatively impacted by a toxic cascade of cellular events. The focus also needs to be on the mechanisms causing some persons to have a lifetime of ‘‘toxic’’ medical events from their TBI. With a better understanding of the issues that occur with a chronic TBI, perhaps some day there will be a special edition of the Journal of Neurotrauma devoted entirely to effective cures for TBIs.