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Neurofilament Light Concentration Indicates Repetitive Concussive TBI

The biomarker can distinguish between patients with short and long durations of postconcussion syndrome.


LOS ANGELES—Plasma levels of neurofilament light indicate repetitive concussive traumatic brain injury (TBI) and axonal injury, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. Differences in this biomarker are detectable for more than a year after the insult. Furthermore, plasma levels of neurofilament light reflect CSF levels of neurofilament light and may identify patients at increased risk of persistent postconcussion syndrome (PCS), according to the researchers.

In a previous study of boxers, Pashtun Shahim, MD, PhD, researcher at the University of Gothenburg in Sweden, and colleagues found that CSF levels of neurofilament light increased more after a bout than did other potential biomarkers such as total tau, phosphorylated tau, and amyloid beta. They also observed that concentrations of serum neurofilament light were higher in boxers with severe head impact, compared with those with mild head impact. In a study of hockey players, Dr. Shahim and colleagues found that neurofilament light measured in the acute setting could distinguish those who would have a prolonged return to play from those who would have a quick return to play.

Pashtun Shahim, MD, PhD

A Study of Professional Athletes

In their latest study, Dr. Shahim and colleagues sought to determine whether professional athletes with PCS resulting from repetitive concussive TBI have elevated CSF and plasma neurofilament light and tau, compared with controls. They also investigated whether elevated concentrations of these biomarkers are associated with persistent PCS.

Between September 2013 and September 2017, the investigators enrolled 31 athletes (ie, professional players of hockey and soccer) with PCS resulting from repetitive concussive TBI, 48 athletes with concussion but without PCS, and 30 control athletes into their study. Participants underwent CSF and plasma biomarker assessments, responded to the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and underwent structural brain MRI. The population’s median time since the last concussion was 1.5 years. The three groups were matched on sport.

Biomarker Indicated Duration of PCS

Dr. Shahim and colleagues found “a tight correlation between plasma concentrations of neurofilament [light] and CSF neurofilament [light], while there was no correlation between plasma tau and CSF tau.”

Plasma neurofilament light concentrations were significantly increased in participants with concussion and those with PCS, compared with controls. The concentration of plasma neurofilament light was higher in patients with concussion but without PCS, compared with the PCS group. This finding was “expected, as we are comparing acute cases of concussion versus chronic cases,” said Dr. Shahim.

When they examined only participants with PCS, athletes who had had PCS for more than one year had higher concentrations of neurofilament light, compared with athletes who had had PCS for less than one year. The latter returned to play, while the former resigned, said Dr. Shahim. In addition, plasma neurofilament light concentration correlated with RPQ scores and lifetime number of concussions.

Levels of tau were lower among participants with PCS than among control athletes, and the researchers found no correlation between tau level and duration of PCS. Levels of tau also had no association with RPQ scores.

Dr. Shahim and colleagues next examined whether these biomarkers had prognostic value. They found that CSF neurofilament concentrations could distinguish between participants who had had PCS for less than a year and those who had had PCS for more than a year (area under the curve [AUC], 0.86). Plasma neurofilament light distinguished between these groups with an AUC of 0.85. Neither CSF tau nor plasma tau reliably indicated duration of PCS, however. In addition, the investigators found no correlation between CSF and plasma tau concentrations from the same individual. This finding casts doubt on the hypothesis that tau concentrations reflect axonal injury, said Dr. Shahim.

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