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Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis.
Ahmed Abdelhak1, Pascal Benkert2,3,4, Sabine Schaedelin2,3,4
1Weill Institute for Neurosciences, Department of Neurology, University of California at San Francisco, San Francisco.
JAMA Neurology
|November 6, 2023
Summary
Blood neurofilament light chain (NfL) levels rise before confirmed disability worsening in multiple sclerosis (MS). This finding may indicate a window for therapeutic intervention in MS patients.
Area of Science:
- Neuroscience
- Neurology
- Biomarkers
Background:
- Mechanisms of disability accumulation in multiple sclerosis (MS) remain unclear.
- Blood neurofilament light chain (NfL) is a marker of neuroaxonal injury, but its association with disability progression in MS is debated.
Purpose of the Study:
- To investigate if and when NfL levels elevate preceding confirmed disability worsening (CDW) in MS.
- To analyze NfL dynamics in relation to relapse-associated (CDW-R) and relapse-independent (CDW-NR) disability worsening.
Main Methods:
- Analysis of two observational cohorts: Expression, Proteomics, Imaging, Clinical (EPIC) and Swiss Multiple Sclerosis Cohort (SMSC).
- Inclusion of participants with available NfL results, with data extracted from 2004-2022.
- Mixed linear and Cox regression models used to assess NfL dynamics and association with future CDW.
Main Results:
- NfL z scores were significantly elevated preceding CDW-R and CDW-NR events in both cohorts.
- NfL elevation was detectable up to two visits prior to CDW-NR events.
- Time-to-event analysis confirmed NfL levels predict future CDW-R (within ~1 year) and CDW-NR (within ~1-2 years).
Conclusions:
- This study demonstrates NfL elevation precedes clinical disability worsening in MS.
- Elevated NfL levels may signal a window of active central nervous system pathology before diagnosis of CDW.
- Findings support NfL as a potential predictive biomarker for MS disability progression.
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