Background and Objectives To study the clinical and laboratory features of antineurofascin-155 (NF155)–positive autoimmune nodopathy (AN). Methods Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. Results Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2–4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = −0.88, p < 0.001) and with maximum I-RODS achieved (r = −0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. Discussion Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. Classification of Evidence This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Multiple sclerosis (MS) is a chronic, inflammatory and degenerative disease affecting the central nervous system, the pathophysiology of which is unknown. Oxidative stress appears to play a significant role in the initiation and the perpetuation of the inflammatory and neurodegenerative processes associated with MS. We have analysed parameters relating to oxidative stress in people with multiple sclerosis (pwMS) and in healthy individuals.Superoxide dismutase (SOD) activity was higher in pwMS than the control group. Meanwhile, total antioxidant capacity (TAC), 4-hydroxynonenal (4-HNE) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were lower in pwMS. The TAC levels correlated with age and disease duration. Regarding the relationship with disease activity, SOD levels were related to T2-FLAIR lesion burden in MRI and 8-OHdG to annualised relapse rate. PwMS with slower processing speeds exhibited lower levels of TAC and higher 4-HNE levels. No relationship was found between oxidative stress and the presence of depression, fatigue or quality of life. These results link oxidative stress to the pathogenesis of MS. Our findings suggest that these parameters might vary in function of disease activity or be related to the presence of MS-associated symptoms such as CI.

To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability. This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system. Data comparisons and statistical analyses between cytokine levels and clinical outcomes were performed. Eighty-eight patients with MOGAD and 32 patients with MS were included. Patients with MOGAD showed higher IL6 (p = 0.036), IL8 (p = 0.012), and IL18 (p = 0.026) baseline levels compared with those with MS, in non-optic neuritis (ON) presentations. BAFF values increased over time, especially in patients with MOGAD treated with anti-CD20 (p = 0.002). Baseline BAFF, CXCL10, IL10, and IL8 levels correlated with disease severity at MOGAD onset (all p < 0.05). Finally, higher baseline BAFF levels predicted lower risk of relapses (hazard ratio 0.41 [0.19; 0.89], p = 0.024). This study suggests a proinflammatory Th17-dominant profile in non-ON MOGAD patients, with a novel finding of a potential protective role of BAFF on relapses. These results shed new light on the pathogenesis of MOGAD, potentially guiding therapeutic decisions.

Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective in improving clinical and radiological outcomes and reducing sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for their short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced ARR in 83% of PwMS and radiological activity in 80%. EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNfL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs.

Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups. A retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed. Of 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042). Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]). S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.