Levels of serum neurofilament light chain (sNfL) are a reliable marker for predicting a neurocognitive decline in patients with multiple sclerosis, showing progressing disease pathology, according to a study published in the Multiple Sclerosis Journal.

Multiple sclerosis (MS), a highly crippling disease, is characterized by cognitive debilitation which affects more than 70% of patients. Quantifying such cognitive decline is mainly based on a self-reported outcome part of the Expanded Disability Status Score (EDSS). However, cognition is not adequately captured by the EDSS.

More recently, blood markers such as serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) have emerged as potential tools to quantitatively estimate the underlying neurodegeneration and astrocytic reactivity occurring in patients with MS.

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To explore the association between sNfL and sGFAP, the research team included 94 patients with MS with a sustained EDSS greater than or equal to 3. The study also included patients with MS with the available serum samples and a cognitive assessment carried out by the Symbol Digit Modalities Test (SDMT) over a mean of 3.1 years.

Moreover, sGFAP/sNfL quantification was confirmed at EDSS of at least 3. The research team also assessed the association of log-transformed sGFAP/sNfL with the current and future SDMT using linear regression analysis.

The researchers also identified active and nonactive patients in this study based on their clinical and radiological activity status in the brain and spinal cord, such as relapse and/or new MRI lesions. Active patients showed acute inflammatory disease activity. 

Study results indicated that sNfL was associated with a change in the SDMT in active patients, but not in nonactive patients. Moreover, the analysis didn’t show any association of sGFAP with the change in SDMT. They inferred that neuronal damage (sNFL), but not astrocytic reactivity (sGFAP), may potentially be responsible for future cognitive decline.

“In summary, sNfL more than sGFAP can inform on pathological processes underpinning cognitive decline in progressive MS. Clinical care may target low sNfL levels to prevent cognitive decline,” the authors concluded


Barro C, Healy BC, Saxena S, et al. Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients. Mult Scler. Published online November 30, 2022. doi: 10.1177/13524585221137697.