‘Brain Scars’ Seen in Many Blast Survivors

by Kay Jackson Contributing Writer, MedPage Today


More than half of active military personnel who have sustained mild traumatic brain injury (TBI) show evidence of brain structural abnormalities or “brain scars,” initial results out of the largest advanced brain imaging study of active duty military TBI now has shown.
A TBI-specific integrated MRI scan has demonstrated a high incidence of T2-weighted hyperintense areas in the white matter, as well as pituitary abnormalities and microhemorrhage in the chronic phase, according to Gerard Riedy, MD, PhD, of Walter Reed National Military Medical Center in Bethesda, Md., and colleagues.

“We were surprised to see so much damage in the brain as conventional wisdom says that in mild TBI the imaging should be normal, yet we saw small brain scars in over 50% of the TBI cases with our advance imaging scans,” Riedy and colleagues reported online in Radiology.

“We must caution that while these lesions are abnormal, we don’t have a clear understanding of what they mean and their true impact on patient’s symptoms and outcomes,” they noted. “We hope that additional research into the more advanced imaging portion of the brain scans will lead to those answers.”

Disruptions in brain wiring in individual TBI subjects, as well as overall changes in the neural network connectivity in the brains of military TBI patients, have been observed at the National Intrepid Center of Excellence (NICoE) at Walter Reed, where the advanced neuroimaging protocol was developed, said Riedy in a prepared statement.

But without a baseline MR image prior to injury, the source of T2-weighted hyperintense areas cannot be definitively determined, acknowledged the investigators.

This study is part of the National Capital Neuroimaging Consortium (NCNC) project, formed in 2009 to advance neuroimaging applications and improve evaluation of military TBI. Development of the TBI-specific integrated MRI scan has made it possible to collect 41,000 brain images per patient (versus about 350 images that would be provided by standard MRI), said Riedy. In addition to structural information, investigators have been able to collect unique patient information on brain function, brain connectivity, brain wiring, brain chemistry, and brain blood flow.

These findings could potentially have significant implications for clinical practice, should advanced medical imaging make it possible to objectively identify brain lesions that potentially serve as biomarkers for TBI and the so-called “invisible” wounds of war, including post traumatic stress disorder (PTSD), said the investigators.

“We hope to bring a better understanding of these injuries through medical imaging. For most of these guys, this is their chosen career,” Riedy told MedPage Today in an interview. “Some may opt for a desk job rather than risk another brain injury after seeing their NCNC brain scan.”

TBI and PTSD have a tremendous amount of overlap in terms of symptoms and yet the treatment paradigms are vastly different, Riedy noted. “An accurate diagnosis is key to any hope of meaningful recovery,” he said.

In the study, 834 participants with a history of TBI and 42 control participants without TBI were recruited and imaged between August 2009 and August 2014. Controls were not explicitly age- and sex- matched, noted the investigators; all participants were between 18 and 60 years of age.

Of the military personnel included, 92% had suffered chronic and mild TBI. Diagnosis was made a mean of 1,381 days after injury (median 888 days). Of these 817 participants, 84% reported one or more blast-related incidents and 63% reported loss of consciousness at the time of injury.

The study showed that:

White matter T2-weighted hyperintense areas was present in 51.8% of TBI participants (432 of 834; odds ratio 1.75 versus controls)

Cerebral microhemorrhages were present in 7.2% of participants with TBI (60 of 834, OR 6.64)

The incidence of cerebral microhemorrhages increased with TBI severity (P<0.001, moderate and severe versus mild)

T2-weighted hyperintense areas and microhemorrhages did not co-locate by visual inspection

Pituitary abnormalities were present in 29.0% of TBI participants (242 of 834, OR 16.8)

Development of a brain stress test, much like a cardiac stress test, could be a next step, Riedy told MedPage Today. “This would allow us to better determine the ability of the brain to respond to challenges and help us predict which service members are good to go and who should be held on the sidelines.”

Portions of the advanced imaging results are being used by the NICoE to treat military TBI patients on an individual basis, noted the investigators. “These injured service members and their families are looking for hard answers about their injuries and what to expect for their future. Providing an image of their injury often helps military personnel validate symptoms that have occurred since the time of injury. This can be an important part of their recovery process.”

As of Dec. 1, 2015, the military TBI neuroimaging database contained 1,395 patients and more than 57 million advanced images and 3.7 trillion unique data points of information about the effects of military TBI on the human brain, said Riedy. This data set is now being transferred to a federally funded TBI database, the Federal Interagency Traumatic Brain Injury Research Informatics System.

“This database will allow researchers from around the world to bring their expertise to a critical problem for the injured U.S. military population and their families, namely the accurate objective diagnosis of TBI and the related concern of possible progression to chronic traumatic encephalopathy,” said the investigators. “Further examination is required to fully evaluate structural image findings with clinical symptoms and neuropsychological measures to help develop objective biomarkers of TBI.”