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Serum Neurofilament Levels May Help Determine MS Prognosis

By monitoring serum levels of neurofilament light chain (NfL), doctors may be able to monitor disease activity and refine the prognosis for patients with multiple sclerosis (MS), researchers suggested at the 2021 virtual AAN Annual Meeting.

“Overall, the highest levels of NfL were observed in people who were younger and were in the earlier stages of MS," reported Elias Sotirchos, MD, assistant professor of neurology at Johns Hopkins University.

Other factors associated with higher levels of neurofilament light chain in the blood were smoking status and diabetes, he told Neurology Today At the Meetings.

“The goal of this study and others is to monitor these people longitudinally and to see whether these elevated levels are predictive of future risks of clinical disability or worsening brain atrophy, and to determine the accuracy of using serum NfL chain to predict that."

For the study, Dr. Sotirchos and colleagues in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network identified a subset of 6,968 MS PATHS participants who provided biospecimens for research. They also collected biospecimens from 201 healthy controls across MS PATHS sites. Age-specific cut-offs for serum NfL levels were derived from the controls. They considered serum NfL levels greater than the 97.5 percentile for age as elevated.

Measures of NfL in the blood of the MS patients showed 17 percent were above the 97.5 percentile, 31 percent were in the 75 to 97.5 percentile, 22 percent were in the 50th to 75th percentile, and 30 percent were less than the 50th percentile.

Approximately 16.7 percent of women had high NfL levels compared with 18.7 percent of men (p=0.077).

“This was a cross-sectional study," Dr. Sotirchos explained. “One of the main objectives of this study was to see how the NfL levels were associated with demographic factors, comorbidities, and lifestyle factors. Our results suggest that these factors need to be taken into account when interpreting NfL results."

 The researchers found that 16.5 percent of never-smokers had elevated levels compared to 17.9 percent of former smokers (p=0.004), and 18.8 percent of current smokers (p<0.001).

About 16.8 percent of patients who were not diagnosed with diabetes had high NfL levels in the blood, compared with 25.4 percent of the patients who had received a diabetes diagnosis (p<0.001).

If someone had elevated NfL levels and also was an active smoker and had diabetes, the result would need to be interpreted with caution, as the elevation could be related to these comorbid factors rather than MS activity, Dr. Sotirchos said.

 “Ultimately, we do envision that the goal would be to monitor disease activity in the clinic down the road, and that could be used for prognosticating for patients as well as monitoring disease activity. This could potentially inform therapeutic decision-making in patients who do not seem well controlled on a therapy," he said.

To do that, Dr. Sotirchos said, scientists still have work to do in defining what levels are abnormal and what the thresholds are to interpret NfL levels. “At the moment, this is a research tool," he said. “We need more studies to help us define these factors before we use them in decision-making. I do anticipate we will be able to use serum neurofilament light chain levels in clinical practice in the future."

Commenting on the study, Jeffrey A. Cohen, MD, FAAN, professor of neurology at the Cleveland Clinic Lerner College of Medicine and director of experimental therapeutics at the Mellen MS Center said: “Emerging evidence from this study and many others support the utility of NfL level in cerebrospinal fluid and, importantly, also in blood, to assess multiple sclerosis severity and prognosis, and to monitor treatment response."

“These data indicate that blood NfL level is affected by a sizable number of factors, which complicates interpretation of a single value at one point in time in an individual patient," Dr. Cohen said.

He noted that while the Cleveland Clinic patients and doctors participated in the study, he was not personally involved in the report.

The study was supported by the National Institutes of Health (NIH), National Multiple Sclerosis Society (NMSS), and Biogen.

Dr. Sotirchos has received personal compensation for serving on a scientific advisory and data safety monitoring board for Viela Bio. He also disclosed relationships with Genentech, Alexion, and Biogen. Dr. Cohen . reports personal compensation for consulting for Convelo, Mylan, and Population Council, and serving as an editor of Multiple Sclerosis Journal.

Link Up for More Information:

AAN Abstract S25.001: Sotirchos E, Fitzgerald K, Smith M, et al. Associations of serum neurofilament light chain with clinico-radiological characteristics in the MSPATHS network: A cross-sectional evaluation.​