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Updated: Jul 29, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Factors contributing to CSF NfL reduction over time in those starting treatment for multiple sclerosis: An
Ide Smets1, David Holden2, Lucia Bianchi2
1Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, 4 Newark St, Whitechapel, London E1 2AT, UK; Clinical Board Medicine (Neuroscience), Department of Neurology, Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, UK.
Background:
In multiple sclerosis (MS) neurofilament light chain (NfL) is a marker of neuronal damage secondary to inflammation and neurodegeneration. NfL levels drop after commencement of disease-modifying treatment, especially the highly active ones. However, the factors that influence this drop are unknown.
Objective:
To examine the patient and treatment-related factors that influence CSF NfL before and after starting treatment.
Methods:
Eligible patients across two centres with two CSF NfL measurements, clinical and MRI data were included as part of an observational cohort study.
Results:
Data were available in 61 patients, of which 40 were untreated at the first CSF sampling (T1) and treated at the second (T2; mean T1-T2: 19 months). CSF NfL reduction correlated with age (beta = 1.24 95%CI(1.07,1.43); R2 = 0.17; p = 0.005), Expanded Disability Status Scale (EDSS) (beta = 1.12 95%CI(1.00,1.25); R2 = 0.21; p = 0.05) and the type of MS (beta = 0.63 95%CI(0.43, 0.92); R2 = 0.12; p = 0.018; reference=relapsing MS). The treatment effect on a baseline NfL of 702 pg/mL was 451 pg/ml 95%CI(374,509) in a 30-year-old versus 228 pg/ml 95%CI(63,350) in a 60-year-old. There was no association in CSF NfL reduction with BMI, disease duration or sex. In cladribine- and alemtuzumab-treated patients, the CSF NfL T2/T1 ratio did not correlate with lymphocyte depletion rate at 23 weeks.
Conclusions:
In this observational study, we found that factors reflecting early disease stage, including a younger age, lower disability and relapsing MS were associated with treatment response in CSF NfL. Other factors were not found to be related, including lymphopaenia in highly-active treatments.
