White Matter Damage Persists Over Time in Vets with TBI

Military veterans with moderate-to-severe traumatic brain injuries (TBI) had more changes to the brain’s white matter than uninjured peers, which did not show signs of recovery over time, a researcher reported.

In an ongoing study that used a novel neuroimaging technique, vets with moderate-to-severe TBIs had lower fractional anisotropy (FA) scores at baseline versus non-TBI controls, with lower scores observed in 52 regions (72%) of the former patients’ brains versus 17 regions (24%) in the latter group, according to Ping-Hong Yeh, PhD, of the Walter Reed National Military Medical Center in Bethesda, Maryland.

Also, for the FA trajectory over the 15 years of follow-up, non-TBI controls had significant FA increases (higher slope) between baseline and timepoint 2 (TP2) than those in the moderate-to-severe TBI group over 13 regions (18%), Yeh reported at the Radiological Society of North America virtual meeting.

“Traumatic brain injury patients have varying trajectories of white matter microstructural changes, which could be used as potential markers of recovery or deterioration,” Yeh said, also noting in a statement that “Questions remain regarding the long-term impact of blast exposures. This study, with up to 15 years’ follow-up, assesses the long-term effects of combat blast exposures.”

However, Yeh cautioned that “We don’t have the results regarding the correlates between neuroimaging findings and neuropsychological functions/symptoms yet. “Those will be our next study.”

He added that “Currently there are no reliable biomarkers to predict the long-term outcome of combat-related brain injury. The findings of this research provide support for the potential prognostic utility of quantitative neuroimaging approach, and highlight the role that these imaging changes could play in potential stratification for clinical trial intervention.”

Yeh and colleagues enrolled 285 military vets with TBIs (majority male; age 36.55) and 14 non-injured controls. For the MR neuroimaging, “An automated white matter tract segmentation method using a novel convolutional neural network based approach was applied to directly segment tracts,” the authors explained.

They reported that most of the tracts were in the regions where the TBI group had lower FA than non-TBI controls at baseline. Also, the moderate-to-severe TBI group did not show significant changes of FA trajectory before TP2, and none of the participants had significant changes in FA trajectory after TP2.

Vincent Mathews, MD, of the Medical College of Wisconsin in Milwaukee, told MedPage Today, that “This study did not look at the effect of treatment on the observed magnetic resonance findings.”

“However, one could potentially use this technique to evaluate if clinical improvement following therapy is related to improvement in these microstructural changes,” said Mathews, who was not involved in the study.

“This is a continuing study and we will incorporate other modalities, such as functional MRI and neuropsychological testing, to better understand and validate whether this approach would be sensitive to identifying a therapeutic response, as well as the implication of these findings as they pertain to aging and the potential link to downstream dementia,” Yeh said.

Yeh and colleagues conducted a related study in 2015 that demonstrated white matter T2 hyperintensities on MRI in a significant percentage of active duty military personnel with mild TBIs. At the time of publication in Radiology, co-author Gerard Riedy, MD, PhD, also at Walter Reed, stated, “This paper is just the tip of the iceberg. We have several more papers coming up that build on these findings and look at brain function, brain wiring, connectivity and perfusion, or brain blood flow.”