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Background: sNfL, a promising biomarker for neuroaxonal damage in Multiple Sclerosis (MS), requires cautious interpretation due to several comorbidity influences., Objectives: To investigate the impact of renal function on sNfL levels in MS patients., Methods: This retrospective study stratified patients by MS clinical phenotype, acute inflammatory activity (AIA) status-defined as relapse or gadolinium-enhancing lesions within 90 days of sample collection-renal function, assessed by estimated glomerular filtration rate (eGFR), and age (< 40 years, 40-60 years, > 60 years). Comparative analysis of sNfL levels across these groups was performed. The sNfL-eGFR relationship was examined using linear and non-linear regression models, with the best fit determined by R 2 and the F estimator., Results: Data from 2933 determinations across 800 patients were analyzed. Patients with renal insufficiency (RI) (eGFR < 60 mL/min/1.73 m 2 ) and mild renal impairment (MDRF) (eGFR 60-90 mL/min/1.73 m 2 ) showed significantly higher sNfL levels compared to those with normal renal function, a pattern also observed in age groups 40 years and older. No significant differences were found between MDRF patients and those with AIA. Among RI patients, no differences in sNfL levels were observed between relapsing-remitting and progressive MS phenotypes. A regression S-Curve model was identified as the best fit, illustrating a marked increase in sNfL levels beginning at an eGFR of approximately 75 mL/min/1.73 m 2 ., Discussion: Caution is advised when interpreting sNfL levels for monitoring MS in patients with impaired renal function., (© 2024. Fondazione Società Italiana di Neurologia.)

Objective: To determine baseline cerebrospinal fluid and magnetic resonance imaging (MRI) variables at the onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) that predict evolution to secondary progressive MS (SPMS)., Methods: 276 CIS patients with a minimum follow-up of 10 years were studied. Baseline presence of oligoclonal IgG and IgM bands (OCGB and OCMB respectively); number of brain T2 lesions (B-T2L), brain gadolinium enhancement lesions (brain-GEL), cervical spinal cord T2 lesions (cSC-T2L); and fulfillment of 2017 McDonald criteria among other variables were collected., Results: 14 patients ended up with a non-MS condition. 138/276 CIS patients fulfilled 2017 McDonald criteria. Mean age was 32.4 years, 185 female. 227 received treatment, 95 as CIS. After a mean follow-up of 12 years, 36 patients developed SPMS. Conversion to SPMS was associated with OCGB (p = 0.02), OCMB (p = 0.0001); ≥ 9 B-T2L (p = 0.03), brain-GEL (p = 0.03), and cSC-T2L (p = 0.03). However, after adjusting for sex, age, BT2L, brain-GEL, SC-T2, and OCMB status, only OCMB (HR 4.4, 1.9-10.6) and cSC-T2L (HR 2.2, 1.0-6.2) suggested an independent association with risk of conversion to SPMS. Patients with both risk factors had a HR of 6.12 (2.8-12.9)., Discussion: OCMB and SC-T2 lesions are potential independent predictors of conversion to SPMS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alcalá Vicente, Lacruz, Gascón, Carratalà, Quintanilla-Bordás, Sanz, Carcelén-Gadea, Mallada, Carreres, Gabaldón Torres, Dominguez, Cañizares, Gil-Perotin, Cubas, Gasqué Rubio, Castillo-Villalba, Pérez-Miralles and Casanova.)

Objective: Neurofilament light protein (NfL) and chitinase 3-like 1 (CHI3L1) are biomarkers for acute neuroaxonal damage and local inflammation, respectively. Thus, we set out to evaluate how these biomarkers were associated with clinical features of demyelinating diseases in parallel with the expression in brain autopsies from patients with similar disease stages, assuming their comparability., Methods: NfL and CHI3L1 in CSF and serum CHI3L1 were assessed retrospectively in a cross-sectional cohort of controls (n = 17) and patients diagnosed with MS (n = 224), relapsing (n = 163) or progressive (n = 61); neuromyelitis optica (NMO, n = 7); and acute disseminated encephalomyelitis (ADEM, n = 15). Inflammatory activity was evaluated at the time of sampling, and CSF biomarker levels were related to the degree of inflammation in 22 brain autopsy tissues., Results: During a clinical attack, the CSF NfL increased in MS, NMO, and ADEM, whereas CHI3L1 was only elevated in patients with NMO and ADEM and in outlier MS patients with extensive radiologic activity. Outside relapses, CHI3L1 levels only remained elevated in patients with progressive MS. CHI3L1 was detected in macrophages and astrocytes, predominantly in areas of active demyelination, and its expression by astrocytes in chronic lesions was independent of lymphocyte infiltrates and associated with active neurodegeneration., Conclusions: Both CSF NfL and CHI3L1 augment during acute inflammation in demyelinating diseases. In MS, CHI3L1 may be associated with low-grade nonlymphocytic inflammation and active neurodegeneration and therefore linked to progressive disease., Classification of Evidence: This study provides Class III evidence that CSF NfL and CHI3L1 levels increase in inflammatory brain diseases during acute inflammation., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital., Methods: Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions., Results: Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated., Conclusion: Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica., (Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)