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One hundred years (and counting) of blast-associated traumatic brain injury
  1. Kevin Kinch1,
  2. J L Fullerton2 and
  3. W Stewart1,2
  1. 1 Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow, UK
  2. 2 Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Kevin Kinch, Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; kevin.kinch{at}nhs.net

Abstract

Blast-associated traumatic brain injury (TBI) has become one of the signature issues of modern warfare and is increasingly a concern in the civilian population due to a rise in terrorist attacks. Despite being a recognised feature of combat since the introduction of high explosives in conventional warfare over a century ago, only recently has there been interest in understanding the biology and pathology of blast TBI and the potential long-term consequences. Progress made has been slow and there remain remarkably few robust human neuropathology studies in this field. This article provides a broad overview of the history of blast TBI and reviews the pathology described in the limitedscientific studies found in the literature.

  • neurological injury
  • neuropathology
  • histopathology
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Introduction

The improvised explosive device (IED) has become synonymous with recent military conflicts and modern terrorism, with the preferential use of such devices responsible for the increasing incidence of traumatic brain injury (TBI) among military personnel. Since 2001, more than 2 million US service personnel have been deployed in operational theatres, of which approximately 400 000 have reported TBI.1 The vast majority of in theatre TBI reported are due to mild TBI, with blast exposure the most common mechanism of injury in this population.2 3 Indeed, such is the prevalence of blast-associated TBI in modern warfare it has been referred to as a signature injury of the conflicts in Iraq and Afghanistan. However, despite recent attention to the injury and recognition of the potential for long-term morbidity from blast-associated TBI, it is not a new phenomenon. Blast TBI has been a recognised feature of combat since the introduction of high explosive weaponry over 100 years ago. Nevertheless, only recently has there been interest in understanding the biology and pathology of blast TBI and the potential long-term consequences of such exposure.

Mechanics of blast

An explosive blast results in the formation of a high-pressure wave caused by the almost instantaneous transformation of the explosive material from a solid or liquid to a gas.4 This blast overpressure wave expands radially from the epicentre and then dissipates rapidly. This is followed by a more prolonged blast underpressure wave. Blast injuries occur through multiple mechanisms (Table 1). Theoretically, blast may result in four types of independent mechanisms of injury: primary, secondary, tertiary and quaternary. One or all of these mechanisms can occur simultaneously, resulting in casualties with significant polytrauma. Whereas secondary and tertiary blast injuries are responsible for severe head trauma, it is the primary blast wave that is implicated in blast TBI.5 Exactly how the primary blast wave affects the brain is, at present, incompletely understood.

Table 1

Classification of blast injury

Brief history of blast TBI

Primary blast TBI was believed to be widespread in World War I (WWI), with servicemen fighting on the frontlines of Europe exposed to shell fire from heavy artillery barrages and mortar attacks. No sooner had conflict begun, the soldiers started to report symptoms such as tremor, poor concentration, dizziness, hypersensitivity to noise, amnesia, headache and tinnitus following exposure to blast and in the absence of signs of external head injury.6 The term ‘shell shock’ was used to describe such patients, which has since become the signature injury of WWI. However, the usage of such a term was short lived and in World War II (WWII) the British authorities banned its use, perhaps thinking that disavowing the existence of the disorder would prevent another epidemic.7 Unsurprisingly, this did nothing to protect soldiers from blast exposure or prevent them from reporting associated symptoms. By 1941, the term post-concussion neurosis had become ersatz shell shock, with victims describing familiar symptoms of headache, dizziness, fatigue, tinnitus, memory impairment, poor concentration and nervousness.8 Several decades later, this same group of symptoms is recognised as the syndrome of blast TBI in modern conflicts. Nevertheless, despite in excess of US$2 billion research spending on military TBI over the past decade by the US Veteran’s Administration and US Department of Defense,9 our understanding of the biology and pathology of blast-associated TBI has not progressed significantly since WWI.

Limited insight into acute blast neuropathology

Despite a century of recognition of blast TBI, remarkably few cases have been examined at autopsy. In the first reported series dating to WWI of three soldiers who had been exposed to blast, but showed no external evidence of injury to the head, Major Frederick Mott described punctate, petechial haemorrhages in the white matter of the centrum semiovale, corpus callosum and internal capsule, with extravasation of blood into the subarachnoid space.10–12 Following WWII, a further nine cases were added to the literature, again describing prominent haemorrhagic features, with diffuse leptomeningeal bleeding, intracerebral clots and multifocal white matter haemorrhages.13 More recently, Shively and colleagues14 report pathology in three further cases regarded by the authors as acute blast TBI (survival 4 days or 2 months). In these examples, the authors describe reactive gliosis at the boundary between cortical grey and underlying white matter, in periventricular areas and subpially. Furthermore, they describe focal axonal pathology in cortical white matter and corpus callosum, without further comment on the pattern and distribution of this pathology, although they do report an absence of amyloid β plaques or tau pathology in all cases. These 15 cases remain the only published neuropathological findings of acute blast TBI to date (Table 2).

Table 2

Summary of all studies in the literature examining the neuropathology of acute and chronic blast traumatic brain injury (TBI) (McKee et al 19 is excluded due to significant confounding factors and absence of survival time data)

No clear understanding of late blast neuropathology

Studies examining the chronic pathology of blast TBI are equally few in number and observations only started to appear in the literature in 2011, with the case report of a former marine subject to blast. The authors described neurofibrillary tangles and tau pathology15 similar to that seen in chronic traumatic encephalopathy (CTE).16 This pathology was also implicated in a subsequent study from a second group of authors reporting on the neuropathology of four military veterans exposed to blast.17 However, despite these early accounts of CTE pathology in blast-exposed military personnel, there have been inconsistent findings in later studies. In their case series of six former military veterans, Ryu and colleagues18 reported no evidence of CTE pathology. Instead, the authors described axonal pathology in five cases, four of which had a survival time greater than 2 months following blast exposure. Adding further to the wide variation of pathological diagnoses described in late survivors of blast TBI, Shively and colleagues14 report pathology in five cases of chronic blast TBI (survival greater than 6 months). In all five cases, the authors described a distinctive astroglial pathology, marked by a prominent interface astrogliosis mirroring the reactive gliosis seen in each of their three acute blast TBI cases reported in the same study. Interestingly, the authors also described tau pathology, similar to CTE, in two out of five of these late survival cases (Table 2).

There is little commonality in pathology between studies, and a reliable consensus on what precisely characterises blast TBI pathology is lacking. Just under half of all studies into chronic blast TBI show pathology resembling CTE and survival time corresponds to time between most recent blast exposure and death. McKee et al 19 described CTE-like pathology in 21 military veterans (most of whom were also athletes) with a history of mild repetitive TBI, this being the principal inclusion criteria of the study. Incidentally, in three cases, there is a concomitant history of exposure to blast, although the survival time in each case is not commented on.

It is worth acknowledging that despite limited human studies into both the acute and chronic neuropathological sequelae on the brain, there exist an abundance of animal models, of varying clinical relevance. The most valuable animal models, certainly in translational research, recognise the need to accurately replicate the pathophysiological mechanisms and neuropathological features of blast TBI observed in humans and clinically relevant endpoints. In this regard, the careful study of human tissue perhaps offers the greatest promise in furthering our understanding of blast TBI.

Moving forward

As we approach the centenary of the end of WWI, and despite almost a century of recognition of the neurological complications of exposure to explosive blast injury, remarkably little progress has been made in our understanding of the biology and pathology of blast TBI and its long-term consequences. Moreover, what was formerly an injury confined to military personnel, the recent increase in terrorist activities worldwide has the potential to increase the incidence of TBI in the civilian population.

Among the recurring problems in studies thus far reporting on the neuropathology of individuals exposed to blast are inconsistencies in definitions of blast exposure and survival time. In addition, confounding factors are not always acknowledged, such as exposure to non-blast TBI, particularly due to sports. Given this, it is perhaps not surprising that in the few cases thus far described, there is lack of consensus in descriptions of both acute and late blast TBI pathology. There is, therefore, a pressing need to gain a better understanding of the injury to inform research into strategies for its identification and monitoring in life and, ultimately, the development of effective therapeutic options for blast TBI. A first step to achieving this might be coordinated efforts to obtain human tissue samples to support robust neuropathology studies, together with detailed longitudinal cognitive and imaging studies in cases of chronic blast TBI.

References

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Footnotes

  • Contributors KK and WS contributed to the formulation of the topic. All authors contributed to revising and finalising the manuscript.

  • Funding This study was funded by the National Institutes of Health.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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