Understanding the Evolution of Traumatic Brain Injury

One of the big questions in the world of traumatic brain injury (TBI) is how concussions (and sub-concussive events) evolve over time. Current thinking is that a new baseline is reached somewhere around one year post-injury.

However, new longitudinal research in military personnel who suffered blast and non-blast injuries gives us more information on changes about short- and long-term changes associated with TBI. The study, called EVOLVE (EValuation Of mild TBI and Long-term outcome in active-duty military and VEterans) followed the same subjects over five years from the point of injury. Researchers have been able to start to understand the progression of injury over time by obtaining imaging studies and tracking neurobehavioral symptoms. The result is better answers to many unanswered questions about TBI.

The results of the study to date were presented to the American Academy of Neurology at the 2018 annual meeting by Christine Mac Donald, PhD, from the University of Washington Department of Neurological Surgery. EVOLVE is a prospective, observational, longitudinal study that includes 591 combat veterans in four different cohorts. Individuals with a previous history of psychiatric diagnoses or severe traumatic brain injury were excluded from the study.

Participants in each cohort were divided into four groups:

1. Individuals who experienced a blast concussion while on active duty
2. Individuals who experienced a non-blast concussion while on active duty
3. A blast control group who had blast exposure while on active duty, but no traumatic brain injury (TBI), i.e., a subconcussive control group
4. A non-blast, non-TBI control group who had been on active duty

Those included in the two concussion groups met the Department of Defense definition for mild, uncomplicated TBI. In other words, the subjects in the study groups did not appear to have severe brain injuries.

Researchers evaluated the subjects at time of injury, at one month, at one year, and at five years post-injury. They obtained imaging studies and performed neurological, psychological, and cognitive function testing.

Neuroimaging Findings After TBI

Confirming what we have come to expect from concussion, researchers found no changes indicative of an injury on conventional MRI—not acutely, subacutely, at one year, or at five-year follow-up.

However, there was an interesting finding on quantitative neuroimaging. As Dr. Mac Donald explains, “New imaging methods, quantitative methods, demonstrated abnormalities consistent with brain injury that were not apparent on a conventional MRI collected at the same time.” Diffusion tensor imaging (DTI) revealed subacute reductions in anisotropy. Further, this abnormality continued to evolve at one month post-injury, indicating it was a new, not pre-existing, finding.

Of particular interest is that this finding was sensitive at both the group level and at the individual level, making it a potentially valuable marker for the clinician evaluating an individual patient.

How Did These Patients Look Over Time?

At one year, a large percentage of those with a mild concussive TBI had progressed to moderate to severe disability on Glasgow Outcome Scale Extended, whether they were exposed to a blast or not. Further, the blast control group (those exposed to a blast but with no evident injury), had worse outcomes than the non-blast control group, suggesting that attention to sub-concussive injury is needed. In addition, symptoms of depression and PTSD were more pronounced in all TBI groups. Cognitive performance remained normal.

Extending the timeline, 11 percent of combat-deployed controls had a decline in Glasgow outcomes at five years, compared to a whopping 72 percent of the concussive blast (mild TBI) group. This substantial decline in function included symptoms of PTSD, depression, anxiety, and poor sleep.

Tying It All Together

Relating these findings back to imaging, researchers were able to predict who would have poor imaging features at five years. They included those with a TBI diagnosis, older age, depression, and impaired word generation.

There was no difference in outcomes between those who had TBI due to a blast and those who had TBI due to other injuries, suggesting the mechanism of injury may not change the progression of outcomes. However, the blast-exposed controls had a worse outcome than the non-blast exposed controls, meaning sub-concussive trauma is significant.

But perhaps the biggest takeaway from the research to date is the idea that TBI continues to evolve over time, with specific changes evident on neuroimaging and worsening symptoms. According to Dr. Mac Donald, “Combat concussion appears to worsen in outcome, both at one year and at five years.”

So this particular question has been answered—one year is not the endpoint for TBI. But it leaves many more unanswered—what are the medical, social, and economic impacts of evolving TBI and how do we address it? Neurologists will certainly play an important role answering these questions.