Biomarker Can Detect, Predict Severity of Traumatic Brain Injury

Neurofilament light chain as a blood biomarker can detect brain injury and predict recovery in different groups, including professional hockey players with acute or chronic concussions, according to a study published in Neurology.

Traumatic brain injury is a leading cause of death and disability in the US, with more than 2.87 million emergency department visits, hospitalizations, and deaths annually. While the majority of all traumatic brain injuries are classified as mild, it remains difficult to diagnose this condition.

There are a wide range of variable behavioral and observational tests to help determine a patient’s injuries, but most of these tests rely on the patient to self-report signs and symptoms. Imaging also has limitations with detecting micro-structural injuries in the brain.

After a traumatic brain injury, neurofilament light chain breaks away from neurons in the brain and collects in the cerebrospinal fluid (CSF). The researchers confirmed that neurofilament light chain also collects in the blood in levels that correlate closely with the levels in the CSF.

The group showed that neurofilament light chain in the blood can detect brain injury and predict recovery across all stages of traumatic brain injury.

“Currently, there are no validated blood-based biomarkers to provide an objective diagnosis of mild traumatic brain injury or to predict recovery,” said Leighton Chan, MD, MPH, chief of the Rehabilitation Medicine Department at the NIH Clinical Center.

“Our study reinforces the need and a way forward for a non-invasive test of neurofilament light chain to aid in the diagnosis of patients and athletes whose brain injuries are often unrecognized, undiagnosed or underreported.”

Researchers studied multiple groups including professional hockey players in Sweden with sports-related concussions, hockey players without concussions, hockey players with persistent post-concussion symptoms, non-athlete controls, and clinic-based patients at the NIH Clinical Center who were healthy or with acute, subacute, and chronic mild traumatic brain injuries.

The study showed that neurofilament light chain in the blood correlated closely with CSF neurofilament light chain in hockey players with concussions and non-athlete healthy controls, indicating that blood neurofilament light chain could be used instead of CSF neurofilament light chain.

Neurofilament light chain in the blood also demonstrated strong diagnostic ability for sports-related concussions, where it could identify hockey players with concussions from hockey players without concussions. Neurofilament light chain could identify clinic-based patients with mild, moderate, and severe traumatic brain injuries from each other and controls.

Additionally, neurofilament light chain in the blood could distinguish with high accuracy hockey players who could return to play after ten days from those who developed persistent post-concussion symptoms and eventually retired from the game.

In the clinic-based patients, the levels of blood neurofilament light chain at five years after a single mild, moderate, or severe traumatic brain injury were significantly increased compared to healthy controls. This suggests that even a single mild traumatic brain injury may cause long-term brain injury, and serum neurofilament light could be a sensitive biomarker to detect even that far out from initial injury.

“This study is the first to do a detailed assessment of serum neurofilament light chain and advanced brain imaging in multiple cohorts, brain injury severities, and time points after injury,” said the study’s lead author, Pashtun Shahim, MD, PhD, NIH Clinical Center.

“Our results suggest that serum neurofilament light chain may provide a valuable compliment to imaging by detecting underlying neuronal damage which may be responsible for the long-term symptoms experienced by a significant number of athletes with acute concussions, and patients with more severe brain injuries.”