BACKGROUND: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application. OBJECTIVE: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs). METHODS: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios. sNfL levels were defined as "high" (>90th percentile) vs "normal" (<80th percentile), based on normative values of control persons. In three rounds, 10 international and 18 Swiss MS experts, and 3 patient consultants rated their agreement on treatment algorithms. Consensus thresholds were defined as moderate (50%-79%), broad (80%-94%), strong (≥95%), and full (100%). RESULTS: The Delphi provided 9 escalation algorithms (e.g. initiating treatment based on high sNfL), 11 horizontal switch (e.g. switching natalizumab to another high-efficacy DMT based on high sNfL), and 3 de-escalation (e.g. stopping DMT or extending intervals in B-cell depleting therapies). CONCLUSION: The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice.

• Keywords
• Delphi study, de-escalation, escalation, personalized treatment strategies, serum neurofilament light chain,
• MeSH
• Algorithms * MeSH
• Delphi Technique MeSH
• Adult MeSH
• Immunologic Factors * therapeutic use   MeSH
• Precision Medicine * methods   MeSH
• Clinical Decision-Making * methods   MeSH
• Consensus MeSH
• Middle Aged MeSH
• Humans MeSH
• Neurofilament Proteins * blood   MeSH
• Multiple Sclerosis * blood   drug therapy   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Immunologic Factors * MeSH
• neurofilament protein L MeSH Browser
• Neurofilament Proteins * MeSH

In this prospective longitudinal study, we quantified regional brain volume and susceptibility changes during the first two years after the diagnosis of multiple sclerosis (MS) and identified their association with cerebrospinal fluid (CSF) markers at baseline. Seventy patients underwent MRI (T1 and susceptibility weighted images processed to quantitative susceptibility maps, QSM) with neurological examination at the diagnosis and after two years. In CSF obtained at baseline, the levels of oxidative stress, products of lipid peroxidation, and neurofilaments light chain (NfL) were determined. Brain volumetry and QSM were compared with a group of 58 healthy controls. In MS patients, regional atrophy was identified in the striatum, thalamus, and substantia nigra. Magnetic susceptibility increased in the striatum, globus pallidus, and dentate and decreased in the thalamus. Compared to controls, MS patients developed greater atrophy of the thalamus, and a greater increase in susceptibility in the caudate, putamen, globus pallidus and a decrease in the thalamus. Of the multiple calculated correlations, only the decrease in brain parenchymal fraction, total white matter, and thalamic volume in MS patients negatively correlated with increased NfL in CSF. Additionally, negative correlation was found between QSM value in the substantia nigra and peroxiredoxin-2, and QSM value in the dentate and lipid peroxidation levels.

• Keywords
• cerebrospinal fluid, iron, magnetic resonance imaging, multiple sclerosis, oxidative stress, susceptibility,
• MeSH
• Atrophy pathology   MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Magnetic Resonance Imaging methods   MeSH
• Brain diagnostic imaging   pathology   MeSH
• Central Nervous System Diseases * pathology   MeSH
• Oxidative Stress MeSH
• Prospective Studies MeSH
• Multiple Sclerosis * diagnostic imaging   pathology   MeSH
• Gray Matter pathology   MeSH
• Iron MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Iron MeSH