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Background and Objectives: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy., Methods: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation., Results: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80)., Discussion: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod)., Classification of Evidence: This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy., (© 2022 American Academy of Neurology.)

Objective: To investigate the hypothesis that vaccination is a risk factor for multiple sclerosis (MS) by use of German ambulatory claims data in a case-control study., Methods: Using the ambulatory claims data of the Bavarian Association of Statutory Health Insurance Physicians covering 2005-2017, logistic regression models were used to assess the relation between MS (n = 12,262) and vaccinations in the 5 years before first diagnosis. Participants newly diagnosed with Crohn disease (n = 19,296) or psoriasis (n = 112,292) and participants with no history of these autoimmune diseases (n = 79,185) served as controls., Results: The odds of MS were lower in participants with a recorded vaccination (odds ratio [OR] 0.870, p < 0.001 vs participants without autoimmune disease; OR 0.919, p < 0.001 vs participants with Crohn disease; OR 0.973, p = 0.177 vs participants with psoriasis). Lower odds were most pronounced for vaccinations against influenza and tick-borne encephalitis. These effects were consistently observed for different time frames, control cohorts, and definitions of the MS cohort. Effect sizes increased toward the time of first diagnosis., Conclusions: Results of the present study do not reveal vaccination to be a risk factor for MS. On the contrary, they consistently suggest that vaccination is associated with a lower likelihood of being diagnosed with MS within the next 5 years. Whether this is a protective effect needs to be addressed by future studies., (© 2019 American Academy of Neurology.)

Objective: We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes., Methods: Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction., Results: Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2-1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB1*15, and absence of HLA-A*02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure., Conclusion: The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: The aim of this study was to estimate the influence of tobacco smoking and Swedish snuff use on the risk of developing multiple sclerosis (MS)., Methods: A population-based case-control study was performed in Sweden, using incident cases of MS (902 cases and 1,855 controls). A case was defined as a subject from the study base who had received a diagnosis of MS, and controls were randomly selected from the study base. The incidence of MS among smokers was compared with that of never-smokers. We also investigated whether the use of Swedish snuff had an impact on the risk of developing MS., Results: Smokers of both sexes had an increased risk of developing MS (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.7 for women, and OR 1.8, 95% CI 1.3-2.5 for men). The increased risk was apparent even among subjects who had previously smoked moderately (< or =5 pack-years) prior to index, and the risk increased with increasing cumulative dose (p < 0.0001). The increased risk for MS associated with smoking remained up to 5 years after stopping smoking. In contrast, taking Swedish snuff for more than 15 years decreased the risk of developing MS (OR 0.3, 95% CI 0.1-0.8)., Conclusions: Smokers of both sexes run an increased risk of developing multiple sclerosis (MS), and the risk increases with cumulative dose of smoking. However, the use of Swedish snuff is not associated with elevated risk for MS, which may indicate that nicotine is not the substance responsible for the increased risk of developing MS among smokers.

We report imaging and clinical findings of leukoencephalopathy occurring after levamisole. The lesions were hypoattenuating on CT and appeared as multifocal oval or elliptical foci in the white matter or along the subependymal veins on MRI. Most lesions resolve after prompt withdrawal of levamisole. Detailed history taking is important for diagnosing levamisole-induced leukoencephalopathy because multiple sclerosis and acute disseminated encephalomyelitis cannot be differentiated by neuroimaging findings alone.

Background: There is little information regarding the potential of interferon beta (IFNbeta) to induce or exacerbate autoimmune disease. Existing data from uncontrolled studies are contradictory and do not differentiate between autoimmune dysfunction, which is frequent in patients with multiple sclerosis (MS), and untoward drug effects., Objective: To evaluate the impact of IFNbeta on hepatic, thyroid, and other markers of autoimmunity using data from the European placebo-controlled double-blind, multicenter study of IFNbeta-1b in patients with secondary progressive MS (SPMS)., Methods: Serum samples obtained at baseline and at 6-month intervals for 24 months were analyzed for the following autoantibodies (AAbs): antinuclear (ANA), antimitochondrial (AMA), smooth muscle (SMA), liver kidney microsome (LKM), thyroid microsome (TPO), and human thyroglobulin (TG). AAb status at baseline and during treatment was related to respective laboratory and clinical deviations., Results: The analysis of AAb data included 355 patients receiving IFNbeta-1b and 353 receiving placebo. There was no difference between treatment groups in de novo AAb positivity. A greater proportion of women were AAb positive at baseline and during treatment. No association was found between liver enzyme elevations and ANA, AMA, or SMA antibody formation in either treatment group. Laboratory-based thyroid alterations during the study were significantly related to TG/TPO status at baseline but were not associated with IFNbeta-1b treatment. Adverse events possibly indicative of other diseases with autoimmune links were not associated with respective AAb status., Conclusion: Interferon beta-1b treatment did not induce autoantibody formation in this population of patients with secondary progressive multiple sclerosis.

Therapies aimed at inhibiting tumor necrosis factor (TNF), a proinflammatory cytokine implicated in autoimmune disease are effective, especially for rheumatoid arthritis. We report a patient with new onset MS closely associated with the initiation of anti-TNF therapy for juvenile rheumatoid arthritis. It is possible that the inhibition of TNF triggered MS in this individual.

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.