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| Item Type: | Article |
|---|---|
| Title: | Clinical utility of serum neurofilament light chain and glial fibrillary acidic protein for tracking disease activity in multiple sclerosis |
| Creators: |
Martinez-Serrat, Maria  ORCID: https://orcid.org/0009-0003-4086-9819, Tafrali, Cansu ORCID: https://orcid.org/0009-0003-2910-3791, Demjaha, Rina ORCID: https://orcid.org/0000-0001-9725-9809, Kaiser, Timothy ORCID: https://orcid.org/0009-0002-6288-4588, Haindl, Michaela Tanja, Helmlinger, Birgit ORCID: https://orcid.org/0000-0001-5022-2910, Hofer, Edith ORCID: https://orcid.org/0000-0003-2964-0987, Ropele, Stefan ORCID: https://orcid.org/0000-0002-5559-768X, Heschl, Bettina ORCID: https://orcid.org/0009-0006-7935-9228, Damulina, Anna ORCID: https://orcid.org/0000-0001-8241-2727, Platos, Emilia, Pinter, Daniela ORCID: https://orcid.org/0000-0003-3138-5225, Wohlrab, Felix ORCID: https://orcid.org/0000-0002-1396-4138, Usnich, Tatiana ORCID: https://orcid.org/0000-0001-7335-8888, Paul, Friedemann ORCID: https://orcid.org/0000-0002-6378-0070, Leppert, David ORCID: https://orcid.org/0000-0001-6172-801X, Benkert, Pascal ORCID: https://orcid.org/0000-0001-6525-8174, Kuhle, Jens ORCID: https://orcid.org/0000-0002-6963-8892, Enzinger, Christian ORCID: https://orcid.org/0000-0001-9764-7617 and Khalil, Michael ORCID: https://orcid.org/0000-0002-5350-3328
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| Abstract: | BACKGROUND AND OBJECTIVES: Monitoring disease activity in patients with multiple sclerosis (MS) remains challenging, and studying blood-based biomarkers that improve prognostic accuracy in routine clinical practice is needed. The objective of this study was to investigate the dynamic behavior of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) throughout the timeline of clinical relapses. In addition, we assessed which sampling time points provide the most relevant prognostic information to identify patients at risk of future disease activity. This study also assessed the influence of high-efficacy therapies. METHODS: We conducted a longitudinal cohort study using serum samples from patients followed at the MS outpatient clinic of the Medical University of Graz, Austria. Inclusion criteria were age older than 18 years, diagnosis of MS according to the 2024 McDonald criteria, and availability of at least 5 serum samples over a minimum of 5 years. sNfL and sGFAP were measured from the repeated sampling using Simoa HD-X and correcting for age, sex, and BMI with Z-scores calculated from a large healthy aging reference cohort. RESULTS: The study included 160 patients with MS (1,228 samples, 64.4% female; mean age 32.5 years; median follow-up of 10.4 years). sNfL Z-scores showed a nonlinear increase before (p < 0.05), during, and up to 1 year after a relapse (all p < 0.001). sGFAP Z-scores were increased during a relapse and up to 2 years afterward (all p < 0.01), although with less consistent temporal patterns. When measuring sNfL 9 months after a relapse, higher values (Z-score >1.5) were associated with the highest odds ratio ([OR] 2.94 [95% CI 1.73–5.0]; p < 0.001) of developing future disease activity within the next 1.5 years. In this context, sGFAP did not show any predictive value. DISCUSSION: These findings provide a better insight into the dynamics of these proteins, highlighting that sNfL provides clinically meaningful short-term prognostic information when measured during remission, whereas sGFAP shows limited prognostic utility in this context, despite detectable changes around relapses. Our results support the integration of optimized sampling strategies into routine MS monitoring to improve individualized care. |
| Source: | Neurology Open Access |
| ISSN: | 2998-7601 |
| Publisher: | American Academy of Neurology |
| Volume: | 2 |
| Number: | 3 |
| Page Range: | e000161 |
| Date: | September 2026 |
| Official Publication: | https://doi.org/10.1212/wn9.0000000000000161 |
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