Neurofilament Protein Is Promising Neurosarcoidosis Biomarker

A protein called neurofilament light chain (NFL), which supports nerve fibers, is elevated in adults with neurosarcoidosis — and appears to increase with more extensive brain inflammation — a study demonstrated.

These findings support the neurofilament protein as a biomarker for disease activity in neurosarcoidosis, a form of sarcoidosis that affects the nervous system.

NFL levels also may distinguish between those with neurosarcoidosis and sarcoidosis occurring outside the nervous system, according to researchers.

The study, “Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis,” was published in the journal Brain Sciences.

Sarcoidosis is characterized by the formation of granulomas, which are immune cell clumps that occur in different parts of the body and interfere with the normal function of organs and tissues.

About 5-15% of people with sarcoidosis develop granulomas in the nervous system, which is then known as neurosarcoidosis. This form of the disease can be challenging to diagnose, as most symptoms — headaches, disorientation, cognitive impairment, hearing or vision loss, muscle weakness, numbness, or tingling — also occur also in other distinct conditions.

Diagnostic methods for neurosarcoidosis, such as MRI or CT scans, detect inflammation of the brain and spinal cord, and lab tests can measure elevated immune cells and proteins in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord.

However, results from these tests can be non-specific, and only a few specific biomarkers have been assessed for far.

Neurofilaments are proteins that provide structural support for nerve fibers, called axons. One component of neurofilaments is the NFL protein, exclusively found in nerve cells. Studies show that damage to axons releases NFL into the CSF and bloodstream.

Researchers based at the University of Southern Denmark now wondered if neurofilament light chain could be used as a biomarker in neurosarcoidosis. Their theory is that NFL might reflect nerve cell damage due to granuloma formation.

To find out, the team compared MRI findings and NFL levels among neurosarcoidosis patients and healthy controls, as well as with those with granuloma formation occurring outside the nervous system — a condition called extra-neurologic sarcoidosis. Whether neurofilament light chain levels correlated with more extensive inflammation on MRI scans of neurosarcoidosis patients also was investigated.

“The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis,” the team wrote.

The study enrolled 20 people with neurosarcoidosis, including 11 men and nine women, with a median age of 51.6. The most common neurological symptoms reported by these patients were headaches, followed by vertigo or a sensation of spinning dizziness, and tinnitus, which is ringing in the ears.

The extra-neurologic sarcoidosis group had a median age of 44.5, with six men and 14 women, and controls included one man and 10 women, with a median age of 37. Both patient groups had similar numbers receiving immunosuppression therapies, and none had severe co-existing medical conditions.

CSF was examined in all neurosarcoidosis participants and controls, and in the seven extra-neurologic patients with neurological symptoms. Abnormal CSF was found in 19 (95%) of those with neurosarcoidosis, including 16 with elevated immune cells and 17 with high protein levels. Among neurosarcoidosis patients, 12 (60%) also had abnormal MRI findings.

An analysis of the CSF revealed the median NFL level from neurosarcoidosis patients was 2,304 picograms per milliliter (pg/mL), which was significantly higher than the 426 pg/mL in extra-neurologic patients, and the 336 pg/mL in healthy controls.

In blood samples, the median NFL also was higher in those with neurosarcoidosis, with a median of 28.2 pg/mL, compared with both patients with extra-neurologic manifestations, at 6.2 pg/mL, and controls, for whom the median was 7.1 pg/mL.

Of note, the use of immunosuppressive therapies did not influence NFL levels in either sarcoidosis group.

Based on MRI scans, the patients were then classified as having moderate to severe brain lesions due to inflammation, or mild lesions, or no lesions.

Those results demonstrated that neurosarcoidosis patients with moderate to severe lesions had significantly greater levels of NFL than patients with mild lesions in both the blood and CSF. There were no differences in NFL levels between patients without or mild lesions.

“The NFL level in both CSF and plasma reflected the inflammatory activity on MRI,” the team wrote.

A statistical calculation was done to determine if NFL in CSF and blood could distinguish between neurosarcoidosis, extra-neurologic sarcoidosis, and healthy controls. From CSF data, a measure of 630 pg/mL of NFL was found to have an accuracy of 88.9%, nearly reaching statistical significance.

From blood sample data, the accuracy was 85.5% and was statistically significant with a cut-off concentration of 11.4 pg/mL.

“This study has demonstrated that NFL is a potential biomarker in neurosarcoidosis that can help distinguish these patients from extra-neurologic sarcoidosis patients and healthy controls,” the researchers concluded. “Further extensive studies are required to evaluate NFL as a screening biomarker for neurosarcoidosis and its potential as a biomarker for disease activity and prognosis [future outcomes].”