Time to be blunt about blast traumatic brain injury

In the past decade, there has been growing realisation that traumatic brain injury (TBI) can trigger a lifelong disease process.¹ In particular, there is increasing alarm around recognition of a form of neurodegenerative disease, chronic traumatic encephalopathy, in former athletes from an ever-expanding list of contact sports.² However, despite impressions from the popular media and certain sectors of the research community, TBI and its long-term consequences, including chronic traumatic encephalopathy, are far from exclusive to athletes.

Since 2001, more than 2 million US service members have been deployed to conflicts in Iraq and Afghanistan, with more than 313 000 soldiers sustaining at least one TBI most as concussion or mild TBI.³ Of particular concern among these injuries are those arising from exposure to blast shockwaves, such as from improvised explosive devices (IED; bombs constructed and deployed in ways other than those using conventional military procedure).⁴ Indeed, blast-associated TBI has often been referred to as a signature injury of modern military conflicts, with a combined US Veteran’s Administration and US Department of Defense research spending on military TBI in excess of US$2 billion in the past decade.⁵ While it is not known what proportion of this research money will be dedicated to blast TBI research specifically, to many military service members, military TBI and blast TBI are synonymous. Nevertheless, despite this substantial research investment, understanding of blast-associated TBI is paralysed by the absence of human neuropathology studies. As a consequence, no means to assess the relevance of preclinical models have been available, resulting in confusion over what constitutes blast-associated TBI. Furthermore, for service members with blast exposure and TBI, whether their symptoms are a result of blast alone or potential accompanying blunt forces from head impact remains unclear.

In The Lancet Neurology, Sharon Baughman Shively and colleagues⁶ report their observations on the neuropathology of eight former military personnel exposed to blast, compared with civilian controls with (n=5) or without (n=3) histories of TBI or with history of opiate misuse (n=5). The authors report a distinctive astroglial pathology in all chronic blast cases (more than 6 months after blast exposure), marked by dense astrogliosis at the boundary between cortical grey and underlying white matter, adjacent to the ventricles and subpially. Furthermore, they report reactive gliosis in a similar pattern of distribution in acute blast cases (4–60 day after blast exposure). By contrast, no similar astroglial pathology was observed in their small series of controls, including cases of blunt or impact TBI. In addition to this glial pathology, the authors report axonal pathology in all three acute and two of five chronic blast cases; however, the pattern and distribution of the axonal pathology was not formally characterised.

Remarkably, this short case series almost doubles the number of cases in the scientific literature describing the human neuropathology of blast TBI. Before this study, only ten contemporary cases of blast-associated TBI had been described, half reporting a pathology reminiscent of chronic traumatic encephalopathy,^7,8 and the remainder describing axonal pathology and no evidence of chronic traumatic encephalopathy.⁹ Thus, the picture of chronic pathology after blast-associated TBI remained unclear. However, although these previous reports failed to reach commonality in pathology described, they share many unavoidable weaknesses in design, most notably in the substantial heterogeneity in survival time following the blast and in exposure to non-blast TBI among their small number of cases.

Inevitably, this latest contribution also suffers from heterogeneity in survival from injury (4 days to 9 years) and in histories of exposure to non-blast TBI (unknown in six of eight cases).⁶ Whether the observations on specificity of this glial pathology to blast TBI stand up to scrutiny in future more comprehensive studies remains to be seen. Intriguingly, tau pathology reminiscent of chronic traumatic encephalopathy was only noted in two cases of this current series. However, as with previous neuropathological studies in blast TBI, whether this chronic traumatic encephalopathy pathology represents a consequence of blast exposure alone or is confounded by coincidental or previous non-blast injury cannot be determined. In this regard, one case of blast-associated TBI with chronic traumatic encephalopathy pathology had a history of non-blast head injury described as unknown, whereas the second had an extensive history of TBI exposure, including that from sports (wrestling, boxing) and non-sporting accidents (multiple motor vehicle accidents). A concern is the inability to rule out a previous TBI for almost any service member, in whom years of potential TBI exposure through military training, sports, and accidents are more likely the rule than the exception.¹⁰

Unquestionably, the study by Shively and colleagues⁶ is commendable in drawing attention to the need for careful study of human tissue to further understanding of traumatic brain injury. However, far from an answer to the question of what is blast traumatic brain injury, the work instead exposes the remarkable absence of robust human neuropathology studies in this field. Progress in TBI research, both blast and non-blast, can only benefit from efforts directed specifically to facilitate acquisition of human tissue samples linked to detailed clinical information to support robust and informative neuropathology studies.

Meanwhile, we must remain cautious in interpreting the significance of any single pathology as unique to blast-associated TBI based on a small and heterogeneous case series and little clinical information, and few control comparisons. The alternative is to risk repeating the errors of the past decade and to consider valid the premature assumption that chronic traumatic encephalopathy is a unique disease of athletes, or even exclusively tau-associated.