Blast Injury–Specific Brain Damage Identified

June 16, 2016

Scientists have found for the first time a specific pattern of brain injury in individuals involved in explosions, which could explain some of the symptoms they experience as well as aid in diagnosis and treatment.

"Blast victims often experience a combination of neurologic and behavioural symptoms for many years following the event," senior author Daniel P. Perl, MD, Uniformed Services University of the Health Sciences, Bethesda, Maryland, explained to Medscape Medical News.

"These include difficulty sleeping and concentrating, headaches, problems with short-term memory and balance, as well as anxiety and depression. But until now there hasn't been any physical brain damage identified on imaging or a biomarker found to correlate with these symptoms, which is why it's often referred to as the invisible wound," he said.

"We have now identified a specific pattern of damage to the brain in individuals who have experienced blast exposure, which is different from damage seen in other types of traumatic brain injury. We are finally beginning to see the invisible wound."

Dr Perl describes the new findings as "a potential game changer."

"This is the beginning of a new era. It is the starting point for research that could help with better diagnosis and treatments for blast injury," he said.

The findings are reported in a paper published online June 9 in The Lancet Neurology.

For the study, Dr Perl and colleagues examined postmortem brain tissues of eight male former military personnel who survived explosive attacks in combat, five of whom lived for more than 6 months after blast exposure (chronic cases; all had received a diagnosis of post- traumatic stress disorder [PTSD]), and three who died shortly after the explosion (acute cases).

In all five chronic blast cases they found a distinctive, consistent, and unique pattern of prominent astroglial scarring at the boundaries between brain parenchyma and fluids (cerebrospinal and blood), namely the subpial zone, penetrating cerebral cortical blood vessels, and ventricles, and between grey and white matter in cortices.

The brain tissues from blast-exposed service members who died shortly after the explosion showed evidence of early-phase astroglial scar formation in the same locations, which the authors say provides temporal and topographic evidence that this astroglial pattern relates to the blast event.

Dr Perl elaborated on this: "Two of the blast patients died just 4 days after the explosion, and findings from their brains show the earliest formation of astroglial scarring. The astroglial cells show the same degree of damage as those in patients who have had a stroke 4 days previously. But in the blast patients the location of the damaged cells is different."

The researchers compared the soldiers' brains to those of male civilians, including five individuals with histories of exposure to impact traumatic brain injury through contact sports and motor vehicle accidents, five cases with exposure to opiates, and three individuals with no known neurologic disorders. None of these civilian brain tissues showed astroglial damage similar to that seen in the blast cases.

"The postmortem findings show a particular pattern of astroglial scarring," Dr Perl commented to Medscape Medical News. "Astroglial damage is seen in many conditions where the brain is injured, but in these patients with blast exposure the astroglial scarring is seen at specific locations — particularly at the interface between brain and fluid (CSF [cerebrospinal fluid] or blood) or the interface between white and gray matter. This distribution of astroglial scarring has not been seen before in other conditions."

He added: "We believe the blast produces a short high-pressure wave which produces damage, particularly at the interface of tissues with different densities. This has been seen before in other areas of the body, such as the lungs or the gut, but this is the first time we have seen it in the brain."

The authors suggest that knowing the nature of the damage in the brain gives leads on how to go forward in efforts to improve diagnosis and treatment. This was a postmortem study, but the next step could be to develop a technique to image this damage in patients while they are still alive and correlate it with symptoms.

Could Help With PTSD Research

The "invisible wound" symptoms experienced by blast victims has been considered a form of PSTD. Dr Perl said, "The question is whether damaged astroglial cells are producing these symptoms or whether they are the result of the response of the brain to this damage. It is likely that PTSD is not just one condition with one pathophysiology but develops as result of many different pathophysiologies. And we are just dealing with blast injury in this study. But our findings could help shed some light on PTSD research."

In an accompanying comment, William Stewart, MD, University of Glasgow, United Kingdom, and Douglas H. Smith, MD, Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, point out some limitations of the study: specifically the small sample size and large variation in survival from injury (4 days to 9 years) and unknown histories of exposure to nonblast traumatic brain injury in six of the eight cases.

"Whether the observations on specificity of this glial pathology to blast TBI [traumatic brain injury] stand up to scrutiny in future more comprehensive studies remains to be seen," they caution.

This study was funded by the US Department of Defense. The authors have disclosed no relevant financial relationships.

Lancet Neurol. Published online June 9, 2016. Abstract  Comment

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