traumatic brain injury

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Dr FrederickKorley

|August 13, 2015

Measuring tau protein or brainderived neurotrophic factor (BDNF) in blood may provide prognostic information in peoplewith traumatic brain injury (TBI), two research groups report.

In one study published online July 10 in the Journal of Neurotrauma, researchers led by Frederick Korley, MD, PhD, ofJohns Hopkins University School of Medicine, Baltimore, Maryland, found that dayofinjury BDNF blood levels areassociated with TBI severity and outcome.

In a separate study, investigators report that elevated levels of tau are related to chronic neurologic symptoms in militarypersonnel with TBI.

"Our findings may provide a framework for identifying patients who are most at risk for experiencing chronic symptomsrelated to TBI," Jessica Gill, PhD, RN, chief of the Brain Injury Unit at the National Institute of Nursing Research (NINR),said in a news release.

Their study was published online August 3 in JAMA Neurology.

BDNF Levels

"BDNF has been implicated in reducing secondary brain injury, with elevations providing neuroprotection and restoringconnectivity after TBI," Dr Korley and colleagues note.

For this analysis, the researchers assessed serum BDNF levels in two independent cohorts of TBI patients presenting tothe emergency department (ED) at Johns Hopkins Hospital (JHH, 76 patients) and San Francisco General Hospital(SFGH, 80 patients) and a control group of 150 JHH ED patients without TBI.

They found that median BDNF concentrations on the day of injury were significantly lower (P = .0001) in TBI patients atboth JHH and SFGH (17.5 and 13.8 ng/mL, respectively) than in nonTBI control patients (60.3 ng/mL).

In addition, among 159 TBI patients from the Transforming Research and Clinical Knowledge in TBI (TRACKTBI) pilotstudy, they observed that median BDNF concentrations in the first 24 hours post injury were significantly lower in casesof moderate or severe TBI (4.3 and 4.0 ng/mL, respectively) compared with cases of mild TBI (8.3 ng/mL; P = .004).

In this cohort, the 75 patients (71.4%) with very low BDNF levels (less than the first percentilefor nonTBI control patients, < 14.2 ng/ml) had a higher likelihood of incomplete recovery thanthose without very low levels (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.5 11.0).They defined incomplete recovery as either postconcussive syndrome (PCS) or a GlasgowOutcome Scale Extended score of less than 8 at 6 months.

"This study has a number of potential clinical implications," Dr Korley told Medscape MedicalNews. "First, it provides insights into why some patients with TBI recover fully and others donot. Secondly, it may result in a new blood test that may help clinicians diagnose TBI moreaccurately. Thirdly, it may lead to the development of new treatment strategies that may helpimprove the healing and quality of life of persons suffering from TBI."

"Some of the next steps to further this research include conducting a similar study at differentmedical centers to validate our findings, and conducting studies to determine whether strategies that increase BDNF

Proteins in Blood Prognostic in TBIMegan Brooks



expression (such as early exercise and diet therapy) can help improve patient outcomes in TBI," Dr Korley said.

Tau Telling in TBI

Tau protein, which has previously been linked to acute TBI symptoms, may also be involved in longterm complications

that can result from TBI, according to researchers from the NINR.

Elevated levels of tau are a known sign of axonal injury and can be measured in cerebrospinal fluid (CSF) and in blood

immediately after a severe TBI. Blood levels of tau may be elevated in the hours and days following TBI, but were

thought to return to normal levels within the months following the injury.

In their analysis, Dr Gill and colleagues studied 70 military personnel with a history of selfreported mild TBI and 28

without a history of TBI who served in Iraq or Afghanistan. Plasma total tau concentrations were measured 3 to 18

months after injury using a novel ultrasensitive singlemolecule enzymelinked immunosorbent assay (Simoa, QuanterixCorp).

They found that tau levels were significantly elevated in the TBI group compared with the nonTBI group (mean, 1.13 vs

0.63 pg/mL; P = .03).

Plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self

reported TBI only (mean, 1.57 vs 0.85 pg/mL; P = .02).

Additionally, individuals with three or more deploymentrelated TBIs had significantly higher tau levels relative to

individuals with fewer TBIs (mean, 1.52 vs 0.82 pg/mL; P = .008). The severity of postconcussive symptoms correlatedwith total tau concentrations in the selfreported TBI group (P = .003).

This research shows that "tau plays a continuing role in TBI and highlights its significant effects on longterm health and

quality of life," NINR Director Patricia A. Grady, PhD, RN, said in the news release.

"It's possible that further research could examine methods to reduce the accumulation of tau and discover ways to

mitigate or eliminate associated chronic neurological symptoms," Dr Grady added.

"Whether plasma tau is a useful marker of brain tau pathology in mTBI [mild TBI] remains to be seen," write Elaine R.

Peskind, MD, from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington, and colleagues in an

editorial in JAMA Neurology.

"The ultimate meaning of plasma tau will depend on correlating plasma and CSF tau; longitudinal studies of clinical

outcomes in service members, veterans, and athletes with repetitive mTBI; and autopsy studies of persons in whom

plasma tau was obtained during their lives. In addition, the measurement of central nervous system–derived exosomes

is an active area of investigation that may provide a more direct measure of brain tau pathology in mTBI," they note.

The study by Dr Korley's group was supported by the National Institute of Neurological Disorders and Stroke and theNational Heart, Lung, and Blood Institute. The authors have disclosed no relevant financial relationships. The study byDr Gill's team was supported by the NINR and the Center for Neuroscience and Regenerative Medicine. One author isan advisor to Quanterix, Inc, and receives compensation and stock options. The other authors have disclosed norelevant financial relationships.

J Neurotrauma. Published online July 10, 2015. Abstract

JAMA Neurol. Published online August 3, 2015. Abstract, Editorial



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Cite this article: Proteins in Blood Prognostic in TBI. Medscape. Aug 13, 2015.

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