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Plasma neurofilament light levels are associated with risk of disability in multiple sclerosis
Ali Manouchehrinia1, Pernilla Stridh2, Mohsen Khademi2
1From the Department of Clinical Neuroscience (A.M., P.S., M.K., F.P., T.O., I.K.), The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Karolinska Institutet; Centre for Molecular Medicine (A.M., P.S., M.K., F.P., T.O., I.K.), Karolinska University Hospital, Stockholm, Sweden; Departments of Medicine, Biomedicine, and Clinical Research (D.L., C.B., Z.M., L.K., J.K.), Neurologic Clinic and Policlinic, University Hospital Basel, University of Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Switzerland; Institution of Neuroscience and Physiology (J.L.), Sahlgrenska Academy, University of Gothenburg, Gothenburg; Institute of Environmental Medicine (L.A.), Karolinska Institutet, Stockholm; and Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Sweden. ali.manouchehrinia@ki.se.
Objective:
To investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening.
Methods:
Concentrations of pNfL were determined in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. We assessed the impact of age-stratified pNfL levels above the 80th, 95th, and 99th percentiles among controls on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0, and 6.0 and conversion to secondary progressive multiple sclerosis (SPMS).
Results:
The median (interquartile range [IQR]) pNfL was 7.5 (4.1) pg/mL in controls and 11.4 (9.6) pg/mL in MS (p < 0.001). The median (IQR) duration of follow-up was 5 (5.1) years. High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals [CIs]: 1.1-1.8) and 1.7 (95% CI: 1.4-2.3). High pNfL was also associated with the risk of reaching a sustained EDSS score of 3.0, with adjusted rates ranging between 1.5 (95% CI: 1.2-1.8) and 1.55 (95% CI: 1.3-1.8) over all percentile cutoffs (all p < 0.001). Similar increases were observed for the risk of sustained EDSS score 4.0. In contrast, the risk of reaching sustained EDSS score 6.0 and conversion to SPMS was not consistently significant.
Conclusions:
Elevated pNfL levels at early stages of MS are associated with an increased risk of reaching sustained disability worsening. Hence, pNfL may serve as a prognostic tool to assess the risk of developing permanent disability in MS.
