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• W2560178287 abstract "During 15 years of war in Iraq and Afghanistan, blast-related traumatic brain injury (TBI) was heralded as the so-called signature injury, and subsequent research yielded putative associations with wide-ranging outcomes (eg, subtle white matter changes, chronic traumatic encephalopathy, and post-traumatic stress disorder [PTSD]).1Hoge CW Castro CA Blast-related traumatic brain injury in US military personnel.N Engl J Med. 2011; 365: 860PubMed Google Scholar, 2Hoge CW Castro CA Treatment of generalized war-related health concerns: placing TBI and PTSD in context.JAMA. 2014; 312: 1685-1686Crossref PubMed Scopus (28) Google Scholar Adding to this list is the study from Sharon Shively and colleagues,3Shively SB Horkayne-Szakaly I Jones RV Kelly JP Armstrong RC Perl DP Characterisation of interface astroglial scarring in human brain after blast exposure: a post-mortem case series.Lancet Neurol. 2016; 15: 944-953Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar a post-mortem convenience sample of five veterans with variable histories of blast exposure (between 2 months and 9 years before death) and additional impact concussions, who died of disparate causes (methadone or multidrug overdoses, gunshot to head, or cause unknown). It is necessary to critically assess the causal inferences suggested by the authors. First, we question their hypothesis that non-penetrating blast causes a unique pattern of astroglial scarring. While tantalising and biologically-plausible, the researchers provide little evidence for causation. Strength of association was unmeasured; no information was provided on how many deaths were reviewed or how blast histories were ascertained to find these five cases. Specificity and consistency were poorly assessed; the researchers presented no systematic approach to selecting controls (impact TBI, opioid abuse, or non-TBI), nor information about whether they were aware of other cases that did not fit their hypothesis (scarring in absence of blast or blast-history without scarring). Dose response was not considered; details were not provided as to whether cases met mild, moderate, or severe TBI criteria. Experimental evidence from blast animal models is scarce. While three acute blast comparison cases3Shively SB Horkayne-Szakaly I Jones RV Kelly JP Armstrong RC Perl DP Characterisation of interface astroglial scarring in human brain after blast exposure: a post-mortem case series.Lancet Neurol. 2016; 15: 944-953Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar lend support to biological plausibility, these cases included injuries with severe secondary, tertiary, or burn effects inconsistent with clinical histories of most veterans treated for blast-related concussions. The second causal inference that astroglial scaring might have something to do with PTSD3Shively SB Horkayne-Szakaly I Jones RV Kelly JP Armstrong RC Perl DP Characterisation of interface astroglial scarring in human brain after blast exposure: a post-mortem case series.Lancet Neurol. 2016; 15: 944-953Summary Full Text Full Text PDF PubMed Scopus (122) Google Scholar had even less scientific support, and produced sensationalised news reports.4Alexander C ‘Shell shock’—the 100-year mystery may now be solved.National Geographic. June 9, 2016; (accessed Nov 18, 2016).http://news.nationalgeographic.com/2016/06/blast-shock-tbi-ptsd-ied-shell-shock-world-war-one/Google Scholar, 5Worth RF What if PTSD is more physical than psychological: a new study supports what a small group of military researchers has suspected for decades: that modern warfare destroys the brain.New York Times. June 10, 2016; (accessed Nov 18, 2016).http://www.nytimes.com/2016/06/12/magazine/what-if-ptsd-is-more-physical-than-psychological.html?_r=0Google Scholar Although the five cases of chronic TBI also carried a PTSD diagnosis among other co-morbidities, no evidence was presented that the neuropathology had anything to do with PTSD. Most cases of PTSD, both in veterans and civilians, stem from traumas not involving blast, and efficacious treatments exist based on well-established neurobiological models. While epidemiological studies have shown strong associations of blast concussions with PTSD,2Hoge CW Castro CA Treatment of generalized war-related health concerns: placing TBI and PTSD in context.JAMA. 2014; 312: 1685-1686Crossref PubMed Scopus (28) Google Scholar being knocked unconscious or dazed from a blast is a highly life-threatening event frequently associated with other devastating casualties. Thus, the context of blast puts blast concussions at the extreme end of the trauma spectrum, readily explaining any association with PTSD independent of neurological damage. In summary, Shively and colleagues' paper paves the way for further research, but caution is necessary in reaching causal or clinical conclusions at this time. This letter expresses the views of the authors and is not an official position of the US Army or Department of Defense. We declare no competing interests. Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case seriesThe blast exposure cases showed a distinct and previously undescribed pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and at junctions between grey and white matter. This distinctive pattern of scarring may indicate specific areas of damage from blast exposure consistent with the general principles of blast biophysics, and further, could account for aspects of the neuropsychiatric clinical sequelae reported. The generalisability of these findings needs to be explored in future studies, as the number of cases, clinical data, and tissue availability were limited. Full-Text PDF Astroglial scarring after blast exposure: unproven causality – Authors' replyWe thank Charles Hoge and colleagues for their comments on our Article.1 The authors used several components of the Bradford Hill criteria to evaluate the association between blast exposure and interface astroglial scarring in the human brain: strength, plausibility, specificity, consistency, biological gradient, temporality, and coherence.1,2 We accepted every case with documentation of blast exposure, a challenging task because US service members dismissed mild traumatic brain injury (TBI) secondary to blast exposure until 2010. Full-Text PDF" @default.
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• W2560178287 title "Astroglial scarring after blast exposure: unproven causality" @default.
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