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Abstract Objective Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2‐item scale polygenic score with anxiety in MS. Methods Using a case–control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview‐diagnosed, and lifetime self‐report physician‐diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome‐wide association study and was tested using regression. Results A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta‐analyses identified that in MS, each 1‐SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09–1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. Interpretation Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

BackgroundPeople with multiple sclerosis (PwMS) face health and social challenges of living with a chronic and potentially disabling condition. To disclose or conceal MS at work may critically affect individuals’ work situation, career opportunities, and health. PwMS may experience a dilemma when assessing if the possible benefits of disclosing the diagnosis outweigh the possible risks. However, concealing in the long-term may have health implications and prevent opportunities for support and work adjustments. Few studies have examined what drives PwMS to disclose or conceal MS at work and the consequences of these ways of managing MS.ObjectivesTo explore the reasons PwMS report for disclosing and/or concealing their MS diagnosis in the workplace, as well as the consequences they have experienced.MethodsA web-based survey of PwMS was conducted in 2021. All individuals aged 20–50 listed in the Swedish MS registry were invited to participate. The response rate was 52% and among these participants, 3,810 (86%) completed questions regarding workplace disclosure and/or concealment of MS. Free-text responses on these topics were analyzed using inductive content analysis.ResultsIt was common to disclose MS in the workplace (85%). Identified drivers for disclosure and concealment related to four categories: Work-related, Social, Personal and Circumstantial. Work-related drivers focused on employment or protecting one’s career, and changing one’s work situation versus maintaining it. Social drivers included the need for support, addressing or preventing stigma, and being considerate of others. Personal drivers were linked to moral values/personal beliefs and processing of the diagnosis. Circumstantial drivers related to involuntary or unforeseen events, timing factors, one’s medical condition and external opinion/advice. Identified consequences for disclosure and concealment related to three categories: Work-life, Social, and Personal. Work-life consequences included work arrangements, and career opportunities. Social consequences were linked to MS awareness, stigma, interactions and social support, as well as dynamics of work relationships. Personal consequences involved levels of disease acceptance, and attitudes toward managing MS.ConclusionPwMS often described the question of disclosure as challenging and navigated it with caution, as both disclosure and concealment can yield favorable and unfavorable outcomes.

Abstract Background Studying whether medications act as potential risk factors for amyotrophic lateral sclerosis (ALS) can contribute to the understanding of disease etiology as well as the identification of novel therapeutic targets. Therefore, we conducted a systematic review to summarize the existing evidence on the association between medication use and the subsequent ALS risk. Methods A systematic review was conducted in Medline, Embase, and Web of Science from the date of database establishment to December 10, 2021. References of identified articles were further searched for additional relevant articles. Studies were included if (1) published in English, (2) explored medication use as exposure and development of ALS as outcome, and (3) the design was a human observational study. Clinical trials, reviews, comments, editorials, and case reports were excluded. Quality assessment was performed using a pre-validated tool for non-randomized studies, the Newcastle–Ottawa Assessment Scale (NOS). Results Of the 4760 studies identified, 25 articles, including 13 case–control studies, five nested case–control studies, six cohort studies, and one retrospective chart review, were included in the review. Among these studies, there were 22 distinct study populations that included 171,407 patients with ALS, seven classes of medication examined, and 23 studies with a NOS ≥ 5. There was a general lack of agreement between studies on the associations of cholesterol-lowering drugs, anti-inflammatory drugs, immunosuppressants, antibiotics, oral contraceptives (OCs) or hormone replacement therapy (HRT), antihypertensive drugs, antidiabetics, and drugs for psychiatric and neurological disorders with the subsequent risk of ALS. However, it appeared that statins, aspirin, OCs/HRT, antihypertensives, and antidiabetics were unlikely related to a higher risk of ALS. The positive associations noted for antibiotics, antidepressants, and skeletal muscle relaxants might be attributable to prodromal symptoms of ALS. Conclusions There is currently no strong evidence to link any medication use with ALS risk.

Abstract To investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset

Abstract Objective To estimate risks for all‐cause mortality and for severe COVID‐19 in multiple sclerosis patients and across relapsing–remitting multiple sclerosis patients exposed to disease‐modifying therapies. Methods We conducted a Swedish nationwide population‐based multi‐register linkage cohort study and followed all multiple sclerosis patients (n = 17,692 in March 2020), individually age‐, sex‐, and region‐matched to five population‐based controls (n = 86,176 in March 2020) during March 2020–June 2021. We compared annual all‐cause mortality within and across cohorts, and assessed incidence rates and relative risks for hospitalization, intensive care admission, and death due to COVID‐19 in relation to disease‐modifying therapy use, using Cox regression. Results Absolute all‐cause mortality among multiple sclerosis patients was higher from March to December 2020 than in previous years, but relative risks versus the population‐based controls were similar to preceding years. Incidence rates of hospitalization, intensive care admission, and death due to COVID‐19 remained in line with those for all‐cause hospitalization, intensive care admission, and mortality. Among relapsing–remitting patients on rituximab, trends for differences in risk of hospitalization due to COVID‐19 remained in the demographics‐, socioeconomic status‐, comorbidity‐, and multiple sclerosis severity‐adjusted model. Interpretation Risks of severe COVID‐19‐related outcomes were increased among multiple sclerosis patients as a whole compared to population controls, but risk increases were also seen for non‐COVID‐19 hospitalization, intensive care admission, and mortality, and did not significantly differ during the pandemic compared to pre‐pandemic years. The risk conveyed by disease‐modifying therapies was smaller than previously assumed, likely as a consequence of the possibility to better control for confounders.

Objective Maternal exposure to cardiovascular disease (CVD) is associated with adverse maternal and neonatal health outcomes. However, its association with offspring’s long-term neurodevelopmental disorders (NDDs) is not yet known. We aimed to investigate the association between maternal pre-existing CVDs and children’s NDDs. Approach This nationwide cohort study included 2.7 million live singleton births recorded in the Swedish Medical Birth Register between 1990 and 2019. Information on maternal pre-pregnancy CVDs was extracted from the National Patient Register, including diagnosis of cerebrovascular disease, heart failure, arrhythmia, valvular and congenital heart diseases. Registered diagnoses of offspring NDDs included Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and intellectual disability. Cox proportional hazards models were fitted to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the associations. All estimates were adjusted for offspring’s age at diagnosis, sex, calendar period, and maternal characteristics including age at birth, parity, education, country of birth, cohabitation status, smoking, psychiatric illness, pre-gestational diabetes, and hypertension. Results The overall prevalence of maternal CVDs was 0.8% between 1990 and 2019. A total of 141 651 individuals (5.2%) received a diagnosis of ADHD, 64 691 (2.4%) of ASD, and 22 913 (0.9%) received a diagnosis of intellectual disability. The adjusted analyses showed that offspring of mothers with CVD had 16% higher rate of ADHD (HR 1.16; 95% CI: 1.09-1.24) and 12% higher rate of ASD (HR 1.12; 95% CI: 1.02-1.23), compared with offspring of mothers without CVD. Specifically, maternal heart failure was associated with 1.93-fold increased HR of ASD (95% CI: 1.21-3.08), maternal arrhythmia with 14% increased rate of ADHD (95% CI: 1.04-1.24), and maternal cerebrovascular disease was associated with 30% elevated rate of ASD (95% CI: 1.07-1.59) and 17% elevated rate of ADHD (95% CI: 1.02-1.36). No association was found between maternal CVDs and intellectual disability. Conclusion Maternal CVD before pregnancy may be a risk factor for offspring’s ADHD and ASD, with varied risks by CVD subtypes. The mechanisms behind the associations warrant further investigations.