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Updated: May 5, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With
Robert J Fox1, Bruce A C Cree1, Jérôme de Sèze1
1From the Mellen Center for Multiple Sclerosis (R.J.F.), Neurological Institute, Cleveland Clinic, OH; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (J.S.), Hôpital Civil, Strasbourg, France; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Brain and Mind Center, University of Sydney, Australia; Department of Neurology, Palacky University Olomouc, Czech Republic; Piedmont HealthCare (D.J.), Mooresville, NC; Research Center for Clinical Neuroimmunology and Neuroscience and MS Center (L.K.); Departments of Head, Spine and Neuromedicine, Clinical Research and Biomedical Engineering, University Hospital and University of Basel, Switzerland; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Jacobs Multiple Sclerosis Center and Pediatric Multiple Sclerosis Center of Excellence (B.W.-G.), Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; and Biogen (C.M.S., A.A., N.B., R.L.A., P.-R.H., R.S., R.E., D.S., C.M., E.F., B.C.K., R.A.R.), Cambridge, MA.
Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity. However, most MS patients with new gadolinium-enhancing lesions did not show elevated sNfL levels during natalizumab treatment interruption.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Clinical Trials
Background:
- Serum neurofilament light chain (sNfL) is a biomarker for multiple sclerosis (MS) disease activity.
- The dynamic relationship between sNfL and radiologic MS disease activity requires further investigation.
Purpose of the Study:
- To evaluate the correlation between sNfL levels and radiologic MS disease activity.
- To assess sNfL dynamics during a natalizumab treatment interruption period in the RESTORE trial.
Main Methods:
- Monthly MRI and sNfL measurements were conducted over 28 weeks in relapsing MS patients during natalizumab interruption.
- Generalized estimating equations modeled longitudinal sNfL trends and correlated them with gadolinium-enhancing (Gd+) lesions.
Main Results:
- sNfL levels increased in patients with Gd+ lesions compared to those without (12.1 vs 3.2 pg/mL).
- A dose-dependent increase in peak sNfL was observed with increasing numbers of Gd+ lesions.
- However, 71% of patients with Gd+ lesions did not exceed the 95th percentile of sNfL levels seen in patients without Gd+ lesions.
Conclusions:
- sNfL levels correlate with the presence of Gd+ lesions in MS.
- Most patients with Gd+ lesions did not exhibit elevated sNfL, suggesting limitations for sNfL as a sole biomarker for monitoring MS activity.
