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Introduction Multiple sclerosis (MS) is a heterogeneous disease with an unpredictable course. Visual pathway is a target of the disease and may reflect mechanisms that lead to disability. Structural and functional changes in the visual pathway may be studied by noninvasive techniques such as optical coherence tomography (OCT), visual evoked potentials (VEP), or B‐mode transorbital sonography (TOS). Objectives The aim is to assess changes in the visual pathway in eyes of MS patients with and without a history of optic neuritis over a 3‐year period and to explore their relationship with disability. Materials and Methods In total, 112 eyes from 56 patients with relapsing MS were recruited: 29 with, and 83 without a history of ON (hON and nhON, respectively). Several parameters were measured by OCT, VEP, and TOS. Baseline measurements were also compared to 29 healthy controls. At 36 months, measurements were repeated in all eyes. Results At baseline, all tests showed significant differences in optic nerve structure and function in both patient cohorts in all the parameters studied, suggestive of more impairment of the visual pathway among the hON cohort. OCT showed significant differences between healthy controls and the nhON cohort. At 36 months, the nhON cohort showed significant changes by OCT, VEP, and TOS suggestive of further visual pathway impairment. OCT measurements also correlated with baseline EDSS among the nhON cohort. Conclusions OCT is the most suitable technique and outperforms VEP and TOS to detect subclinical damage in the visual pathway. It discriminated MS patients from healthy controls and showed a progressive decline in optic nerve thickness over time among these patients. We assesed the visual pathway in MS patients for 3 years using optical coherence tomography (OCT), visual evoked potentials and transorbital sonography. All techniques showed impairment of visual pathway over time and OCT resulted the best to detect subclinical damage.

Relapsing-remitting multiple sclerosis (RRMS) is characterized by neuroaxonal damage, astrogliosis and inflammation. These mechanisms may already be active from early disease stages, underscoring the need for sensitive biomarkers capable of capturing treatment-related biological effects beyond conventional clinical measures. In this multicenter, ambispective, observational real-world study, the longitudinal effects of ozanimod on serum biomarkers were evaluated, during the first year of treatment in patients with low-to-moderate activity RRMS. Serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP) and cytokines associated with immune activity (IFN-γ, IL-17, IL-6, IL-10, and IL-1β) were quantified at baseline, 6 months, and 12 months using an ultrasensitive single-molecule array (SIMOA). Ozanimod was associated with significant reductions in sNfLs and sGFAP at 12 months. Concomitantly, significant decreases in IFN-γ and IL-1β were observed. IL-17 levels remained unchanged in the overall cohort but decreased in patients with higher baseline IL-17 levels. These findings demonstrate coordinated modulation of biomarkers reflecting neuroaxonal damage, astroglial activation, and inflammatory activity under ozanimod treatment in early RRMS in real-world conditions. These results highlight the biological relevance of early intervention within a therapeutic window of opportunity and support the potential utility of serum biomarkers for monitoring biological treatment effects in clinical practice.

ObjectiveTo study the efficacy of interferon beta (IFNβ) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS).MethodThis is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFNβ or GA. Treatment decision was made blinded to the OCMB status. Time to first attack after starting therapy was compared by using Kaplan-Meier curves, and adjustment by Cox regression analysis was performed.ResultsTwo hundred and fifty-six patients entered in the study (141–55% received IFNβ; 115–45% received GA). After a mean follow-up of 41 and 65 months, 54.7% of patients remained free from further attacks (RF). The proportion of RF patients was higher in the GA group than in the IFNβ group (72.2 vs. 40.4%, p < 0.001). The IFNβ patients with OCMB+ presented the poorest response, 31.3% RF vs. 48.1% in IFNβ without OCMB, p = 0.03.ConclusionOCMB in CSF could be a biomarker of treatment response in multiple sclerosis.

IntroductionOcrelizumab, an antiCD-20 antibody, is the only drug approved to treat patients with primary progressive multiple sclerosis (pwPPMS). Not all candidates receive this treatment due to prescription limitations. Rituximab, another antiCD-20 antibody, has been used off-label in pwPPMS before and after ocrelizumab approval. However, studies comparing effectiveness of both drugs are lacking.ObjectiveTo evaluate effectiveness of rituximab and ocrelizumab in pwPPMS under real-life conditions.MethodsWe conducted a multicentric observational study of pwPPMS that started ocrelizumab or rituximab according to clinical practice, with a minimum follow-up of 1 year. Data was collected prospectively and retrospectively. Primary outcome was time to confirmed disability progression at 3 months (CDW). Secondary outcome was serum neurofilament light chain levels (sNFL) at the end of follow-up.Results95 out 111 pwPPMS fulfilled inclusion criteria and follow-up data availability: 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. Rituximab-treated patients had significantly higher baseline EDSS, disease duration and history of previous disease-modifying treatment (DMT) than ocrelizumab-treated patients. After a mean follow-up of 18.3 months (SD 5.9), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group. Survival analysis revealed no differences in time to CDW. sNFL were measured in 60 patients and no differences between groups were found.InterpretationWe provide real-world evidence of effectiveness of ocrelizumab and rituximab in pwPPMS. No differences in time to CDW were found between treatments. However, this study cannot establish equivalence of treatments and warrant clinical trial to confirm our findings.

The kappa-free light chain (κFLC) index has shown its value in detecting the intrathecal synthesis of immunoglobulins. We aimed to evaluate the diagnostic performance of the κFLC index for multiple sclerosis (MS) and compare different algorithms proposed in the literature to optimize its use for our population. Based on the results of the oligoclonal bands (OCBs) and κFLC index of 255 patients with suspected MS different optimization strategies were evaluated, for which the optimal κFLC index cut-off thresholds were calculated. The best diagnostic performance was achieved by using a reflexive algorithm, in which OCBs are only performed according to the κFLC index result. With a single cut-off (κFLC index = 7.9), an accuracy of 92.2% was obtained (sensitivity = 92.4%, specificity = 92%) with an OCB performance rate of 58.1%. When applying 2 cut-offs (κFLC index = 4.2 and 13), the accuracy was the same (92.2%, sensitivity = 89.6%, specificity = 94%), but the OCB performance rate dropped to 29.4%. The 2-step strategy proposed with κFLC determination followed by OCB analysis in the borderline cases appears to be the most suitable solution, further optimized by adjusting the decision thresholds to 4.2 < κFLC index < 13, resulting in high accuracy and the most saving of OCBs.

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Background : The assessment of serum neurofilament light chain (sNfL) is increasingly significant in the field of neurology. In multiple sclerosis (MS), it proves valuable as a marker for monitoring disease activity and treatment response. Objective : To compare the Simoa and Lumipulse platforms for measuring sNfL and to establish age‐specific reference ranges within a substantial cohort of individuals diagnosed with MS. Methods: Two hundred sixty‐one sNfL measurements from a cohort of 229 MS patients were analyzed with Simoa and Lumipulse. Reference ranges for sNfL were established for three age groups (18–39 years, 40–59 years, and > 60 years) selecting data from 166 patients with stable relapsing–remitting MS. Results: While sNfL levels correlated between assays, Lumipulse exhibited values higher than Simoa. Passing–Bablok’s analysis confirmed linearity between the two datasets, and the Bland–Altman comparison further supported the agreement between the methods. Analyzing reference ranges for sNfL across three age groups in stable RRMS patients revealed significant differences between the groups on each of the platforms. Although the values followed the same trend, each technology utilized distinct reference ranges. Conclusion: Simoa and Lumipulse platforms proved equally effective in monitoring patients with MS. The enhanced accessibility of the Lumipulse platform facilitates the expansion of research on sNfL as a biomarker for monitoring MS, thus offering promising opportunities for broader accessibility and advancement in this field.

Relapsing–remitting multiple sclerosis (RRMS) is characterized by neuroaxonal damage, astrogliosis and inflammation. These mechanisms may already be active from early disease stages, underscoring the need for sensitive biomarkers capable of capturing treatment-related biological effects beyond conventional clinical measures. In this multicenter, ambispective, observational real-world study, the longitudinal effects of ozanimod on serum biomarkers were evaluated, during the first year of treatment in patients with low-to-moderate activity RRMS. Serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP) and cytokines associated with immune activity (IFN-γ, IL-17, IL-6, IL-10, and IL-1β) were quantified at baseline, 6 months, and 12 months using an ultrasensitive single-molecule array (SIMOA). Ozanimod was associated with significant reductions in sNfLs and sGFAP at 12 months. Concomitantly, significant decreases in IFN-γ and IL-1β were observed. IL-17 levels remained unchanged in the overall cohort but decreased in patients with higher baseline IL-17 levels. These findings demonstrate coordinated modulation of biomarkers reflecting neuroaxonal damage, astroglial activation, and inflammatory activity under ozanimod treatment in early RRMS in real-world conditions. These results highlight the biological relevance of early intervention within a therapeutic window of opportunity and support the potential utility of serum biomarkers for monitoring biological treatment effects in clinical practice.