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Background: Delayed‐release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. Case presentation: We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36‐year‐old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta‐1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. Conclusions: Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a “wait and see.” A different immunotherapeutic strategy such as an anti‐B therapeutic approach could be considered. [ABSTRACT FROM AUTHOR]

Background: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials.Objectives: To track and evaluate post-market DMF profile in real-world setting.Materials and methods: Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data.Results: Among the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%).Conclusion: Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues. [ABSTRACT FROM AUTHOR]

Background: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events.Objective: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40.Methods: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied.Results: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059).Conclusions: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for  nocebo responses. Initial dose titration might reduce PIR frequency. [ABSTRACT FROM AUTHOR]

Background 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed. Objective to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools. Methods Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go - TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (T0) and after (T1) 14 days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI. Results We found a significant difference between T0 and T1 for T25FW, TUG, MSWS-12 (p ≤ 0.001) in the whole patients' sample (23 subjects, median EDSS 6.0) and decrease of Central Motor Conduction Time and increase of mean Amplitude (Amp) at T1 (p = 0.008 and p = 0.006). We also recorded a significant difference of T25FW, TUG, MSWS-12 and Amp in clinical responder (CR) patients (CR: amelioration > 20% at T25FW). TBSS showed a significant Mean and Radial Diffusivity reduction in the corticospinal tracts (p < 0.05) of the whole group of patients; this reduction was also found in the CR subgroup. Conclusion Neurophysiological and neuroradiological parameters were modified in MS patients treated with 4-AP, and most of them reported a subjective improvement of their motor performances after treatment. The use of clinical, subjective, neurophysiological and neuroradiological tools could help to better explore MS patients responsiveness to 4-AP. [ABSTRACT FROM AUTHOR]

Objective Multiple sclerosis ( MS) affects young adults of working age. Difficulties in work-related activities are usually ascribed to MS symptoms, while the impact of workplace features is underestimated. This article presents the Multiple Sclerosis Questionnaire for Job Difficulties ( MSQ-Job), designed to assess working difficulties due to MS symptoms and workplace features. Methods A sample of employed MS patients completed the MSQ-Job, the WHO-Disability Assessment Schedule ( WHODAS 2.0) and the 54-items MS Quality of Life Questionnaires ( MSQOL-54); the expanded disability status scale ( EDSS) was used to define MS severity. Factor structure was evaluated using principal component extraction and Oblimin rotation; internal consistency was assessed with Cronbach's alpha; construct and discriminant validity using t-test ( EDSS 0-2 vs >2; patients self-reporting need for support vs patients reporting no needs; full-time vs part-time employees); and Pearson's correlation with WHODAS 2.0 and MSQOL-54. Results The MSQ-Job is a 42-item questionnaire with six scales and an overall factor. Scores range on a 0-100 scale (higher scores indicate more and more severe difficulties); patients with EDSS>2 and self-reporting support needs had worse scores than those with EDSS 0-2 and without needs. Correlations with WHODAS 2.0 and MSQOL-54 were generally significant ( P < 0.0007) and below 0.70. Conclusions The MSQ-Job jointly measures the impact of respondents' symptoms and workplace features on work activities and enables to assess the effects of clinical and occupational interventions and better describe the impact of MS indirect costs. [ABSTRACT FROM AUTHOR]