This case report supports neurotrauma in the human brain following repetitive primary explosive blasts in a 55-year-old veteran, with evidence primarily for executive, perceptual-organization, psychomotor, visual-learning, and recognition-memory weaknesses on neuropsychological testing and white-matter structural abnormalities in corpus callosum and white-matter projections to frontal and parietal lobes visualized on DTI. His neuropsychological presentation is generally consistent with the neuroanatomic distribution of decreased FA.
Neuropsychological assessment revealed that although J.G.’s IQ is currently in the average range and may have been in the high-average range or better premorbidly from occupational history, he performed below expectation on tasks requiring processing speed, recognition memory, and, in particular, executive function, especially working memory. The deficit in executive function was evident on formal tests of sequencing, set switching, category fluency, and problem solving, in addition to behavioral observations of perseveration, concrete thinking, and word-finding difficulty during spontaneous speech and his reports of functional impairment in everyday life. The observed deficits in executive function are consistent with neuropsychological findings after repeated sports-related concussions including boxing (McLatchie et al., 1987
) and football injuries (Collins et al., 1999
), suggesting that repeated primary-blast injury may have similar consequences as other types of closed-head injuries.
DTI analysis revealed that patient J.G. had reduced FA in the corpus callosum and bilateral white-matter projections to frontal and parietal cortices relative to an age- and sex-matched reference sample without TBI, suggesting loss of structural integrity in these areas. This study adds to the growing literature supporting the sensitivity of DTI to detection of changes in white-matter integrity that may be associated with cognitive decline. Optimal cognitive performance is thought to rely on the structural integrity and coordinated function of distributed neural networks (Power, Fair, Schlaggar, & Petersen, 2010
), whereas disruption of these pathways may impede coactivation of key regions that give rise to integrated cognition. In particular, functional and structural alterations in frontoparietal regions have been implicated in impaired executive functions, memory, and processing speed (Andrews-Hanna et al., 2007
) and may explain J.G.’s neurocognitive profile and presentation. Furthermore, a reduction in anisotropy in the corpus callosum is one of the most commonly reported findings in patients with traumatic axonal injury (Hurley, McGowan, Arfanakis, & Taber, 2004
) and is likely associated with alterations in interhemispheric functional connectivity (Marquez de la Plata et al., 2011
). In general, these findings support the notion that cognitive dysfunction after multiple-blast injury is associated with structural changes distributed diffusely across key neural networks.
Only a handful of studies have examined blast injury using DTI, and other studies that have examined mild TBI in returning Afghanistan- and Iraq-warzone veterans have been unable to disentangle the effects of primary- versus secondary-and tertiary-blast effects (Polusny et al., 2011
). Furthermore, these studies have not systematically examined the number of head injuries post-deployed personnel have reported in relation to cognitive deficit (Hoge et al., 2008
). In contrast, the present study describes sustained neurotrauma after many cumulative primary blasts over a military career and compares results to a reference group of age- and sex-matched, well characterized controls without TBI history. Whereas most other studies report DTI findings across an averaged sample of individuals with TBI, limiting applicability to an individual case, our methodology is similar to that integral to normative neuropsychological and medical inference and may have utility in future clinical application to diagnostic discrimination of occult TBI (Lew et al., 2005
Ongoing debate centers on whether primary-blast injury can cause direct damage to the brain. Some researchers suggest that stress waves from a primary blast do not affect structures with homogenous water density such as the brain (Wightman & Gladish, 2001
). However, this notion has been actively challenged by the accumulating studies showing neural alterations and cognitive deficit after primary-blast injury. While the mechanism by which blast injury affects neural pathways may be different from the inertial forces typical of other closed TBIs, both types of events may result in progressive decline in axonal function and eventually lead to axonal disconnection (Büki & Povlishock, 2006
; Povlishock, 1993
). Supporting this idea, the animal literature is accumulating evidence for traumatic axonal injury after exposure to blast. Rats exposed to blast waves showed neural changes associated with altered axonal transport (Saljo, Bao, Haglid, & Hansson, 2000
) and oxidative stress (Cernak, Wang, Jiang, Bian, & Savic, 2001
). Lower FA in humans is thought to reflect axonal degradation and larger perivascular spaces, and therefore DTI is an advantageous tool in understanding neural pathology after blast.
The present study provides evidence for brain alterations after multiple primary-blast injuries. However, alternative possibilities that may produce a similar neurocognitive and neuroimaging profile are important to consider. It is unlikely that J.G.’s pattern of performance is reflective of premorbid executive dysfunction. Given the demands of the Explosive Ordnance Disposal Service, and that one mistake could have fatal consequences, the patient was likely highly organized, comfortable making rapid decisions, and had flexible thinking in order to identify different types of munitions and how to diffuse them (Madrid, William, & Holland, 1992
). Due to the demanding nature of the job, Explosive Ordnance Disposal Service training-attrition rates are high, and those who succeed in graduating have completed rigorous cognitive and physical challenges (Hogan & Hogan, 1985
). J.G.’s performance on hold tests in the current battery furthermore supported at least above-average premorbid intelligence (WAIS-III Information and Vocabulary scaled scores = 13). This likely premorbid profile is in striking contrast to J.G.’s current presentation of slowed processing speed, poor decision making, and reports of mild executive dysfunction and/or dyspraxia and loss of procedural knowledge. It is also unlikely that J.G.’s depressive and PTSD symptoms can explain his profile. J.G.’s deficits on neuropsychological measures do not cohere with the patterns typically seen in depressed or anxious patients. For example, comorbid depressed and anxious patients typically show greater impairment on free recall than recognition, a pattern that was reversed in the present case (Kizilbash, Vanderploeg, & Curtiss, 2002
). Additionally, depressed and anxious patients do not display high numbers of false positives on recognition tasks (Kizilbash et al., 2002
), whereas patients with TBI tend to show more intrusions and false positives (Crosson, Novack, Trenerry, & Craig, 1988
; Wiegner & Donders, 1999
) as observed in the present case. A meta-analysis of memory deficits in PTSD (Brewin, Kleiner, Vasterling, & Field, 2007
) reported average effect sizes indicative of impairment primarily in the verbal domain. However, J.G.’s performance was worse in the visuospatial memory domain. Additionally, evidence exists for reduced FA in mild-TBI patients even after adjusting for stress, anxiety, and depression (Lipton et al., 2009
Finally, a discussion of neurodegenerative and vascular disease is warranted to consider the possibility that J.G.’s deficits are due to onset of dementia not related to blast injuries, or that repetitive blast may have conferred vulnerability towards its development. Although somewhat controversial because of mixed results, some emerging evidence suggests that head injury is a risk factor for Alzheimer’s disease in men (Fleminger, Oliver, Lovestone, Rabe-Hesketh, & Giora, 2003
) as well as for frontotemporal dementia (Rosso et al., 2003
). However, several aspects of J.G.’s neurocognitive profile are inconsistent with early Alzheimer’s disease, the most prominent aspect of which is his intact delayed free recall on the CVLT-II, Wechsler Memory Scale-Third Edition Logical Memory, and Rey Osterrieth Complex Figure Test (see ). A rule out of frontotemporal dementia is more difficult because of his demonstrated poor performance on tasks of executive function, but nevertheless J.G.’s behavioral presentation is inconsistent with this diagnosis, which is characterized by early changes in social-interpersonal conduct (e.g., decline in manners, violation of interpersonal space, disinhibited sexual and physical behavior), dysregulation of personal conduct, emotional blunting, and loss of insight. However, it will be important to follow this veteran over time to examine whether this is a case of chronic traumatic encephalopathy, a neurodegenerative condition observed in individuals that have suffered repetitive head trauma (Clausen et al., 2005
; Drew et al., 1986
; Guskiewicz et al., 2005
). Some of the earliest signs of chronic traumatic encephalopathy include alterations in attention, memory dysfunction, and bouts of confusion (McKee et al., 2009
It is important to acknowledge that cerebrovascular risk factors are often associated with frontal-subcortical dysfunction and that cerebrovascular complications have frequently been noted in association with blast injuries from the Operation Enduring Freedom/Operation Iraqi Freedom warzones (Armonda et al., 2006
; Bauman et al., 2009
; Benzinger et al., 2009
; Bhattacharjee, 2008
; Cernak & Noble-Haeusslein, 2010
; DeWitt & Prough, 2009
), suggesting a strong relationship between blast per se and vascular-system impingement. J.G. was diagnosed with hypertension and hyperlipidemia, both risk factors for cerebrovascular disease. However, he had no history of frank stroke or cardiac problems, and his hypertension and hyperlipidemia were well controlled with medications. Importantly, J.G. showed a reduction in FA relative to a reference group that had a predominantly similar cerebrovascular risk-factor history. Further studies are required to discern neural injury attributable directly to blast-pressure forces on skull and brain tissue versus effects secondary to alterations in vasculature.