Military veterans with a history of three or more
concussions were more likely to have high levels of exosomal and plasma
levels of neurofilament light (NfL) chain years after injury occurred, a
cross-sectional study suggested.
Moreover, elevations of NfL, a measure of axonal damage, were highest
in veterans with repetitive traumatic brain injury (TBI) who had
symptoms of chronic post-concussive syndrome, post-traumatic stress
disorder (PTSD), and depression, reported Kimbra Kenney, MD, of Walter
Reed National Military Medical Center in Bethesda, Maryland, and
colleagues, in
Neurology.
Blood
tests that include exosomal and plasma NfL markers may one day help
predict which people with mild TBIs will take longer to recover, Kenney
noted.
"Our study found there's great potential for this protein to predict
the problems people with concussions may experience years after their
injuries," she said in a statement.
"While most people with mild concussions recover completely, some
never get their lives back fully because of chronic disability," Kenney
added. "These people may benefit greatly from a test that could predict
those disabilities years ahead of time."
(Predicting crap like this does the patient no good at all. We need solutions for recovery.)
Most concussions are single and uncomplicated, but "a subset of
individuals experience persistent post-concussive symptoms and
substantial disability," noted Silvina Tonarelli, MD, of Texas Tech
University in El Paso, and Davin Quinn, MD, of the University of New
Mexico in Albuquerque, in an accompanying
commentary.
"There is a need for accurate and reliable biomarkers that are tied
to the pathophysiologic mechanisms of mild TBI, and that track and
predict neuropsychiatric outcomes," they wrote.
"A
promising avenue of biomarker development is exosomes, a type of
extracellular vesicle released by injured cells, whose contents can be
informative about neuronal pathophysiology," Tonarelli and Quinn added.
Exosomes of other proteins like are being studied as
potential biomarkers in Parkinson's and other neurodegenerative diseases. In other disorders, including
Alzheimer's disease and
multiple sclerosis, blood levels of NfL have been shown to correspond with hallmarks of disease progression.
In this study, Kenney's research team studied 195 military veterans in the
Chronic Effects of Neurotrauma Consortium (CENC) cohort. Participants had a history of combat exposure during deployment; their median age was 38, and 85% were men.
Excluded from the study were people with moderate or severe TBI, and
people who had coma that lasted more than 30 minutes, amnesia that
lasted more than 24 hours, traumatic intracranial lesion on head CT, or a
history of major neurologic or psychiatric disorder.
Besides
exosomal and plasma levels of NfL, the researchers looked at other
candidate biomarkers, including tumor necrosis factor (TNF)-α,
interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF).
The researchers divided participants into three groups:
- 45 people had no history of mild TBI
- 94 people had one or two mild TBIs
- 56 people had three or more TBIs
People
with one or two mild TBIs had their first concussion a median of 13.53
years ago and their last one 9.53 years ago. People with three or more
mild TBIs had their first concussion a median of 22.11 years ago and
their last one 6.83 years ago.
Exosomal and plasma levels of NfL were linked to repetitive mild TBIs
and correlated with severity of post-concussive, PTSD, and depressive
symptoms.
Plasma levels of TNF-α, an inflammatory marker, were tied to
post-concussive and PTSD symptoms. The lifetime number of concussions
correlated with exosomal and plasma NfL levels and with plasma IL-6,
another inflammatory marker.
Moreover,
an increased number of years since first concussion correlated with
higher levels of exosomal and plasma NfL. Years since first concussion
also was linked to plasma VEGF, which may modulate inflammatory
responses, and plasma TNF-α.
"These are encouraging findings, suggesting that an ongoing
neuroinflammatory process may be an important contributor to persistent
post-concussion syndrome in a military population subjected to
repetitive mild TBIs," Tonarelli and Quinn pointed out.
Strengths of the study include its "well-characterized cohort and
rigorous mild TBI confirmation process," they observed, but "further
confirmation of these relationships and clarification of confounding
effects of comorbidities is required before these biomarkers can be of
use."
The study had several limitations, Kenney and colleagues noted. The
sample size was relatively small and there was substantial variability
in the number of years in which injury occurred.
There also was variability in mechanisms of injury. "We included
participants with deployment-associated TBI, which includes but it is
not restricted to blast-related TBI, as well as TBIs sustained before
military service," the researchers said.
-
Judy George
covers neurology and neuroscience news for MedPage Today, writing about
brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy,
autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep,
pain, and more.
Follow
Disclosures
The study was supported by the Department of Defense, Department of Veterans Affairs, and NIH.
Kenney and co-authors, as well as Tonarelli and Quinn, disclosed no relevant relationships with industry.
Secondary Source
Neurology
