Botulinum toxin (BT) is an effective treatment for spasticity symptoms in multiple sclerosis (MS). Despite its wide use in clinical practices, only few studies have explored long-term persistence. We aim to evaluate the rate of discontinuation of BT treatment and the correlation with MS, spasticity, and injection variables. This retrospective study on 3-year prospectively collected data included 122 MS patients receiving BT injections for spasticity. We collected MS clinical variables (disease durations, Expanded Disability Status Scales [EDSSs], disease-modifying treatments [DMT], and Symbol Digit Modalities Tests [SDMTs]), modified Ashworth scales [MASs], concomitant treatments, and injection variables (formulation, dose, number of injections, and intervals between injections). A total of 14 out of the 122 patients discontinued BT after a mean time of 3.0 ± 1.5 years. In the Cox regression model including the MS clinical variables, the probability of BT discontinuations increased in patients with DMT changes during follow-ups (HR = 6.34; 95%Cl = 2.47, 18.08; p < 0.01) and with impaired SDMTs (HR = 1.20; 95%Cl = 1.04, 1.96; p < 0.01). In the model including the spasticity variables, there were no associations between BT discontinuation and MAS or other spasticity treatments. In the model including the injection variables, the probability of discontinuation decreased by 80% for each cumulative injection (HR = 0.16; 95%Cl = 0.05, 0.45; p < 0.01), but increased by 1% for each additional day over the 3-month interval between injections (HR = 1.27; 95%Cl = 1.07, 1.83; p < 0.01). BT discontinuation was associated with concomitant MS-related issues (e.g., treatment failure and DMT change) and the presence of cognitive impairment, which should be accounted for when planning injections. The interval between injections should be kept as short as possible from regulatory and clinical perspectives to maximize the response across all of the spasticity symptoms and to reduce discontinuation in the long term.

Multiple sclerosis (MS) is an autoimmune chronic disease characterized by inflammation and demyelination of the central nervous system (CNS). Despite numerous studies conducted, valid biomarkers enabling a definitive diagnosis of MS are not yet available. The aim of our study was to identify a marker from a blood sample to ease the diagnosis of MS. In this study, since there is evidence connecting the serotonin pathway to MS, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to detect serum MS-specific auto-antibodies (auto-Ab) against the extracellular loop 1 (ECL-1) of the 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A). We utilized an ELISA format employing poly-D-lysine as a pre-coating agent. The binding of 208 serum samples from controls, both healthy and pathological, and of 104 serum samples from relapsing–remitting MS (RRMS) patients was tested. We observed that the serum-binding activity in control cohort sera, including those with autoimmune and neurological diseases, was ten times lower compared to the RRMS patient cohort (p = 1.2 × 10⁻⁴⁷), with a sensitivity and a specificity of 98% and 100%, respectively. These results show that in the serum of patients with MS there are auto-Ab against the serotonin receptor type 2A which can be successfully used in the diagnosis of MS due to their high sensitivity and specificity.

Background/Objectives: Autoimmune nodopathies are a distinct subgroup of immune-mediated peripheral neuropathies caused by antibodies targeting nodal and paranodal proteins, including contactin-1 (CNTN1). These disorders are frequently misclassified as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), despite fundamental differences in pathophysiology, clinical course, and treatment response. Growing evidence indicates that systemic manifestations, such as proteinuria, may represent relevant diagnostic red flags. We report a case of anti-CNTN1 autoimmune nodopathy with renal involvement and long-term follow-up after rituximab therapy. Methods: We describe the longitudinal clinical, electrophysiological, laboratory, and therapeutic features of a patient presenting with an acute/subacute sensory ataxic neuropathy evolving into a chronic immune-mediated disorder. Serial nerve conduction studies were performed during multiple hospital admissions and follow-up visits. Autoantibody testing for nodal/paranodal antigens was undertaken, and systemic biomarkers were monitored over time. Results: The patient initially exhibited a robust response to intravenous immunoglobulin (IVIg), consistent with an acute inflammatory neuropathy. Subsequent relapse was characterized by cranial nerve involvement, worsening sensory ataxia, peripheral edema, albuminocytologic dissociation on cerebrospinal fluid analysis, proteinuria, and an inverted albumin/gamma globulin ratio, redirecting the diagnostic hypothesis toward CIDP. The detection of anti-CNTN1 antibodies ultimately established the diagnosis of autoimmune nodopathy. Owing to poor durability of IVIg, rituximab was initiated, resulting in sustained clinical improvement and near-complete recovery of motor and sensory nerve conduction parameters at one-year follow-up (November 2025). Conclusions: This case emphasizes the diagnostic relevance of extraneurological biomarkers, including proteinuria and peripheral edema, in autoimmune nodopathies and supports early nodal/paranodal antibody testing in atypical demyelinating neuropathies. Prompt B-cell-directed therapy may enable functional recovery of nodal integrity and improve long-term outcomes. Further studies are needed to clarify potential immunological triggers, including anti-IL-23 therapies, in the pathogenesis of anti-CNTN1 autoimmune nodopathy.

Background: The definition of motor conduction block (CB) and proximal temporal dispersion (TD) for the diagnosis of CIDP and MMN remains debated, particularly regarding whether CB should be based on amplitude or area reduction, and whether proximal TD is best assessed using negative peak or total CMAP duration. Methods: Nerve conduction waveforms from 106 CIDP, 87 MMN, and 234 controls were analyzed. Motor CB was defined by ≥ 30%, ≥ 40%, or ≥ 50% amplitude or area reduction. Proximal TD was defined as a ≥ 30% increase in negative peak duration, total CMAP duration, or either criterion. Sensitivity, specificity, and inter‐rater reliability were analyzed. Results: Across both CIDP and MMN, a ≥ 30% reduction in CMAP amplitude showed diagnostic performance comparable to area‐based CB definitions and outperformed higher cutoff values. Requiring CB in multiple nerves increased specificity but reduced sensitivity. For proximal TD, negative peak duration was the most robust single parameter. Total CMAP duration identified additional abnormalities and, when combined with negative peak duration, improved diagnostic sensitivity in both disorders while maintaining high specificity. Total CMAP duration demonstrated good inter‐rater agreement at the patient level. CMAP morphology showed substantial overlap between CIDP and MMN and limited discriminatory value. Conclusions: A ≥ 30% reduction in CMAP amplitude can be used as a universal definition of motor CB in both CIDP and MMN, providing diagnostic performance comparable to area‐based criteria with greater simplicity. In addition, proximal TD assessed using total CMAP duration may represent a complementary electrophysiological criterion in both disorders.