We searched PubMed from Jan 1, 2010, to June 22, 2017, for papers published in English, with the search terms “traumatic brain injury” or “head injury”, “long-term”, “survivors”, “follow-up”, “mortality”, “longitudinal”, “dementia”, “Alzheimer”, “Parkinson”, and “degenerative”. We identified studies concerning adults with traumatic brain injury that included follow-up of 5 years or more after injury. Studies were selected that addressed the central theme of long-term deterioration after
SeriesThe chronic and evolving neurological consequences of traumatic brain injury
Introduction
Evidence accumulated in the past decades has led to recognition that, for many patients, traumatic brain injury (TBI) does not cease to evolve after the acute period and initial recovery. This injury is not a time-bound event, but a chronic health condition1 with lifelong effects on both morbidity and mortality. Estimates based on patients with TBI treated in hospital indicate that 1·1% of the US population have lifelong disabilities as a consequence of this injury,2 whereas if the substantial number of people who do not seek hospital treatment for injury are included, the percentage might be more than three times greater.3 Furthermore, outcomes in TBI are not fixed long term, and there can be improvement and deterioration many years after injury.4, 5
The long-term consequences of TBI are a matter of substantial concern for affected individuals and their families, and for society owing to the substantial economic burden; moreover, the costs are greater in the elderly and, therefore, set to increase in an ageing population.6 Multiple negative effects on lifelong health have been associated with TBI (panel), and there is growing evidence that many people in the chronic phase are living with under-recognised and poorly managed sequelae of injury.29, 30 Understanding of the long-term consequences of TBI is important because this knowledge will allow identification of risk factors for poor outcomes and appropriate targeting of health-care resources and interventions.
One area that has received recent attention is the long-term effects of repetitive concussion in sports.31, 32 The potential effects of concussion should be understood in the broader context of TBI as a risk factor for long-term neurological disease. Studies of cohorts with TBI of all severities and causes can help to elucidate the neurological consequences of brain injury, and neuroimaging and pathological investigations in the past decade have enabled better characterisation of late neurodegenerative features associated with TBI.
Other reviews have provided detailed accounts of long-term pathology,33, 34 imaging,35 disease,1, 10, 36 functioning,4 emotional adjustment,26 and cognition.12, 37 In this Series paper, we aim to bring together key evidence concerning the chronic consequences of TBI in adults, with an emphasis on neurological changes and how they evolve over time, focusing on studies that have included follow-up of 5 years or more after injury. We begin by examining studies of late changes in global functional outcome and long-term mortality. We then evaluate the specific contribution of TBI-related neurodegenerative and other neurological diseases to morbidity and mortality, and consider characterisation of underlying neurodegeneration. Finally, we emphasise the gaps in knowledge and highlight areas of research needed to improve understanding and awareness of the long-term consequences of TBI.
Section snippets
Dynamic long-term functional outcomes of TBI
A range of problems can persist after TBI, including postconcussion symptoms, emotional difficulties, cognitive impairment, and functional limitations.38 However, until recently, relatively little has been known about changes in outcome many years after injury. Understanding of global outcome changes has been enhanced by information from longitudinal studies involving two cohorts,28, 39, 40, 41, 42 both with follow-up of functional status of more than 10 years (table 1). In the USA, the TBI
Late mortality after TBI
Many studies have examined mortality within the first 6 months after brain injury,58 but far fewer studies have assessed mortality risks in the long term (table 1).28, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 There is consensus that moderate-to-severe injuries have an enhanced risk of mortality that might persist for many years, but a puzzling observation is that high mortality rates might be observed even after mild TBI.28
TBI as a risk factor for later neurological disease
The possibility that TBI is associated with neurological diseases, and neurodegenerative disease in particular, has had substantial attention over the years, and recent studies have provided new evidence concerning a link. TBI disproportionally affects young adults and, despite lengthy follow-up periods, most of the studies described earlier have involved substantial proportions of people with TBI who are still at a relatively young age. Any increased risk for neurodegenerative illness
Late neuropathology of TBI
Early observations on the brains of boxers formed the basis of Corsellis and colleagues'72 landmark publication in 1973 describing dementia pugilistica. However, only recently has due attention been paid to the significance of neurodegenerative pathology after TBI, which has now been documented in a growing number of serendipitously observed brains from individuals exposed to such injury in a range of contexts, including participants in boxing, American football, ice hockey, soccer, and rugby;19
Conclusions and future directions
Multiple lines of evidence suggest that, for many patients, TBI is a chronic, evolving, and perhaps lifelong disorder. This disorder manifests as altered risk not only for various neurological pathologies but also systemic pathologies, with associated increased morbidity and mortality, extending for many decades in survivors of TBI. These negative outcomes are a major concern. However, research to identify and quantify late outcomes from TBI has been remarkably scarce, with few studies
Search strategy and selection criteria
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