The chronic and evolving neurological consequences of traumatic brain injury

Abstract

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population.

Figure 1.. Longitudinal trajectories, based on data modelling, for functional outcome after inpatient rehabilitation for traumatic brain injury in surviving versus deceased patients.

Trajectories are fitted curves showing expected change in functioning of patients with TBI as measured with the GOSE for survivors compared with those who were deceased (died >5 years after injury). These sample trajectories were generated with a modelling approach known as individual growth curve analysis with use of longitudinal data from the TBI Model Systems national database from patients aged ≥ 16 years who had completed at least three study visits (ie, having survived for a minimum of 2 years); the curves shown represent individuals, who were white, aged 26 years when their first GOSE score was recorded, had 30 days of rehabilitation, and had the same level of disability on admission to rehabilitation (cognitive FIM score of 11 and motor FIM score of 33). Although profiles vary substantially between individuals, it is evident from these examples that the trajectory for those who were deceased is markedly different from those who survived: those who were deceased started out with more disability initially–a GOSE score nearly a point below those who survived–and their trajectories suggest a near constant decline in function. By contrast, the trajectory for surviving patients shows slight improvement in outcomes, which could take many years to reach a peak, followed by a delayed decline from about 10 years after injury. Reproduced from Dams-O’Connor and colleagues, by permission of Wolters Kluwer Health. TBI= traumatic brain injury. GOSE = Glasgow Outcome Scale–extended. FIM=Functional Independence Measure.

Figure 2:. Neuropathology after traumatic brain injury.

Appearance of hyperphosphorylated tau aggregates within neurons and astrocytes (brown staining in panels A and B) clustered around small cortical vessels (arrows), characteristically in a patchy distribution towards the depths of cortical sulci, is emerging as the distinctive pathology of chronic traumatic encephalopathy. This pathology appears to be virtually exclusive to circumstances in which there has been exposure to brain injury in life, whether as repetitive mild TBI as shown in a 61-year-old male former boxer (A) or single moderate or severe TBI as shown in a 48-year-old man with 3 years of survival after single severe TBI (B). In addition to this distinctive tau pathology, neurodegeneration after TBI is increasingly recognised as a complex pathology, including abnormal amyloid plaque deposition (brown staining in panels C and D). As with tau, aspects of these pathologies can be recognised in case material from patients exposed to either repetitive mild TBI as shown in a 59-year-old male former soccer player (C) or single moderate or severe TBI (D; same patient as in panel B). Phosphorylated tau using antibody CP13 (A) or PHF-1 (B). Amyloid β was stained with antibody 6F3D (C and D). TBI= traumatic brain injury. Scale bar 100 microns for all images.