Plasma glial fibrillary acidic protein and neurofilament light chain in relation to disability worsening in multiple sclerosis.

BACKGROUND: Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce. OBJECTIVE: To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening. METHODS: We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure. RESULTS: In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 ± 0.82 years, while p-NfL (HR = 1.046, p = 0.001), EDSS (HR = 1.24, p = 0.039), and disease duration (HR = 1.048, p = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP (p = 0.031) and 0.63 for p-NfL (p = 0.015). Kaplan-Meier curves showed similar patterns for both proteins. CONCLUSION: p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.

Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis.

Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.

Serum Neurofilaments and OCT Metrics Predict EDSS-Plus Score Progression in Early Relapse-Remitting Multiple Sclerosis.

(1) Background: Early disability accrual in RRMS patients is frequent and is associated with worse long-term prognosis. Correctly identifying the patients that present a high risk of early disability progression is of utmost importance, and may be aided by the use of predictive biomarkers. (2) Methods: We performed a prospective cohort study that included newly diagnosed RRMS patients, with a minimum follow-up period of one year. Biomarker samples were collected at baseline, 3-, 6- and 12-month follow-ups. Disability progression was measured using the EDSS-plus score. (3) Results: A logistic regression model based on baseline and 6-month follow-up sNfL z-scores, RNFL and GCL-IPL thickness and BREMSO score was statistically significant, with χ2(4) = 19.542, p < 0.0001, R2 = 0.791. The model correctly classified 89.1% of cases, with a sensitivity of 80%, a specificity of 93.5%, a positive predictive value of 85.7% and a negative predictive value of 90.62%. (4) Conclusions: Serum biomarkers (adjusted sNfL z-scores at baseline and 6 months) combined with OCT metrics (RNFL and GCL-IPL layer thickness) and the clinical score BREMSO can accurately predict early disability progression using the EDSS-plus score for newly diagnosed RRMS patients.