Brain Injury from Stroke Assessed by Blood-Based Biomarker

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Stroke, illustration
[Source: KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty Images]

The current scale for measuring the severity of a stroke does not correlate well with brain tissue damage. Therefore, markers of tissue damage would allow for better prediction of outcomes and treatment development. Now, a research group has discovered that a biomarker in the blood—a protein known as neurofilament light (NFL)—may help determine the extent of brain injury from different types of strokes and predict prognosis in patients.

This research is published in Science Translational Medicine in a paper titled, “Plasma neurofilament light predicts mortality in patients with stroke.

NFL protein is abundant in neurons found in the brain. When neurons are injured following a stroke or from other neurological diseases, NFL is released into cerebrospinal fluid and then the blood. The amount of NFL released is indicative of neuron injury in the brain, according to the research team. Stroke is a leading cause of death, but symptoms vary widely from temporary and non-disabling, to severe, long-term impairment.

“Estimating the severity of a stroke and how well a person is expected to recover is important to patients and their loved ones,” said Tania Gendron, PhD, assistant professor at the Mayo Clinic in Florida and first author of the paper. “Reliably predicting a patient’s prognosis is also important to their care, as it informs treatment and rehabilitation decisions. We sought to determine whether the amount of NFL in patients’ blood could be used to predict their prognosis after a stroke—be it an ischemic stroke, which occurs when blood flow to the brain is blocked by a clot, or a hemorrhagic stroke, which occurs when a weak blood vessel bursts and bleeds into the brain.”

Researchers used an investigative blood test to measure NFL concentrations in blood collected from 314 patients following a stroke and in blood from 79 healthy individuals. The patients had either acute cerebral infarction (N = 227), aneurysmal subarachnoid hemorrhage (N = 58), or nontraumatic intracerebral hemorrhage (N = 29). The team  additionally validated the nontraumatic intracerebral hemorrhage findings in two independent cohorts of patients with (N = 96 and N = 54) because of the “scarcity of blood biomarker studies for this deadliest stroke type.” This analysis allowed the scientists to determine whether NFL is elevated after a stroke. They also examined whether NFL levels are indicative of stroke severity and eventual recovery.

The researchers found that NFL levels were higher for all stroke types.

The researchers examined correlations between NFL levels and the degree of brain injury, in addition to neurological, functional, or cognitive status of patients at the time their blood was collected. The study also examined whether NFL levels could anticipate future recovery by reliably predicting post-stroke outcomes and survival. To verify their findings, they used a similar approach to evaluate NFL as a prognostic biomarker in two additional groups of stroke patients (150 total) and 48 healthy controls; they also showed that patients with lower NFL levels recovered day-to-day function better six months after stroke.

“We discovered that blood levels of NFL do predict stroke severity,” said Leonard Petrucelli, PhD, professor of neuroscience at the Mayo Clinic in Florida. “We found that higher NFL levels forecast worse functional outcomes and shorter survival time after a stroke. We found this to be the case for ischemic stroke and hemorrhagic strokes. Our study establishes NFL as a promising prognostic biomarker for stroke.”

Currently, brain imaging is used to determine damage from a stroke. While a blood test for NFL is not yet available in the clinical setting, researchers hope that in the future, physicians may be able to decrease use of imaging—using instead an NFL blood test to better determine the best course of treatment—as well as boost clinical trials with better matched groups of patients based on degree of brain injury and severity of symptoms.

The authors noted that one key step to clinical translation will be to determine exactly when blood NFL levels begin to correlate with long-term outcomes in the aftermath of stroke.

“We are hopeful that our findings will ultimately change how patients are treated by using NFL biomarkers in clinical trials to allow for more rapid and reliable detection of therapeutic effects,” said James Meschia, MD, neurologist at the Mayo Clinic in Florida. “Our findings may also help us better plan rehabilitation needs for patients who need it most and for longer term.”

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