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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. [ABSTRACT FROM AUTHOR]

Background and purpose: Pediatric‐onset multiple sclerosis (PoMS) is associated with high health care use. To plan resource allocation for this patient group, knowledge of the incidence rate and prevalence is important. However, such studies are scarce, few are population‐based, and the methodology varies widely. We aimed to address this knowledge gap by performing a nationwide study of the incidence rate and prevalence of PoMS in Sweden, an area of high multiple sclerosis (MS) incidence and prevalence. Methods: MS cases were identified by linking two nationwide registers, the National Patient Register and the Swedish MS Registry. MS cases having their first central nervous system demyelinating event or MS clinical onset before age 18 years were classified as pediatric onset. Incidence rate and prevalence were estimated annually over the study period (2006–2016) for the total population and stratified by sex and age group (<12, 12–15, and 16–17 years). Temporal trends and ratios between sexes and age groups were estimated. Results: We identified 238 incident cases from 2006 to 2016, corresponding to an overall crude incidence rate of 1.12 per 100,000 person‐years and an overall crude prevalence of 2.82 per 100,000 population. There was a higher incidence rate among females and the highest age category. The overall incidence rate and prevalence estimates remained stable during the study period. Conclusions: Sweden exhibits a consistently high incidence rate and prevalence of PoMS that has remained stable over time. This knowledge serves as a tool to aid in planning resource allocation and health services for this patient population. [ABSTRACT FROM AUTHOR]

Objective: There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population. Methods: Population‐based health data were accessed for 2 cohorts of HIV‐positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV‐positive cohort was compared to the expected age‐, sex‐, calendar year‐, income‐specific, and region of birth‐specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART‐exposed") was also calculated. Results: The combined Sweden‐Canada cohort included 29,163 (75% men) HIV‐positive persons. During 242,248 person‐years of follow‐up, 14 incident MS cases were observed in the HIV‐positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV‐positive population was 0.53 (95% confidence interval [CI] = 0.32–0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31–0.96). Interpretation: This international population‐based study demonstrated a lower risk of MS among HIV‐positive individuals, and HIV‐positive ART‐exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2024;95:487–494 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to explore the longitudinal relationship between multiple sclerosis (MS) relapses and information processing efficiency among persons with relapsing–remitting MS. Methods: We conducted a Swedish nationwide cohort study of persons with incident relapsing–remitting MS (2001–2019). Relapse information and symbol digit modalities test (SDMT) scores were obtained from the Swedish MS Registry. Follow‐up was categorized into 2 periods based on relapse status: "relapse" (90 days pre‐relapse to 730 days post‐relapse, subdivided into 10 periods) and "remission." Linear mixed models compared SDMT scores during the relapse periods to SDMT scores recorded during remission (reference) with results reported as β‐coefficients and 95% confidence intervals (CIs), adjusted for age, sex, SDMT type (written vs oral), time‐varying, disease‐modifying therapy exposure and sequence of SDMT. Results: Over a mean (SD) follow‐up of 10.7 (4.3) years, 31,529 distinct SDMTs were recorded among 3,877 persons with MS. There was a significant decline in information processing efficiency that lasted from 30 days pre‐relapse up to 550 days post‐relapse, with the largest decline occurring 0 to 30 days post‐relapse (β‐coefficient: −4.00 (95% CI = −4.61 to −3.39), relative to the period of remission. Interpretation: We found evidence of cognitive change up to 1 month prior to relapse onset. The reduction in SDMT lasted 1.5 years and was clinically significant up to 3 months post‐relapse. These results suggest that the effects of a relapse on cognition are longer than previously thought and highlight the importance of reducing relapse rates as a potential means of preserving cognitive function. ANN NEUROL 2022;91:417–423 [ABSTRACT FROM AUTHOR]

Abstract: Background: Several environmental and lifestyle factors have been associated with multiple sclerosis (MS) risk, including some pharmacological treatments. We systematically reviewed the literature on prescription drug exposure and MS risk. Methods: Six databases were searched for original observational studies reporting drug exposure and MS risk published before 2017. Results: Thirteen articles fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was associated with MS (adjusted hazard ratio (adj.HR = 1.34;95% CI:0.81–2.20; adj.HR = 1.30;95%CI:0.44–3.80, respectively). Four studies explored oral contraceptive exposure and reported no association with MS; while a single study found an increased risk (odds ratio [adj.OR] = 1.52;95%CI:1.21–1.91). While penicillin exposure was associated with reduced risk of developing MS (adj.OR = 0.5;95%CI:0.3–0.9), a later study observed an elevated risk for penicillin (adj.OR = 1.21;95%CI:1.10–1.27) and all antibiotics (adj.OR = 1.41;95%CI:1.29–1.53), which was potentially attributed to underlying infection. Anti‐tumor necrosis factor‐alpha (TNFα) was not associated with MS risk in persons with inflammatory bowel disease (standard morbidity ratio = 4.2;95%CI:0.1–23.0) and arthritis (standardized incidence ratio = 1.38;95%CI:0.69–2.77); however, men exposed to anti‐TNFα who also had arthritis and individuals with ankylosing spondylitis were at an increased risk (standardized incidence ratios = 3.91;95%CI:1.47–10.42 and 3.48;95%CI:1.45–8.37, respectively). A reduced risk of MS was observed with exposure to the beta2‐adrenergic agonist fenoterol (adj.OR = 0.58;95%CI:0.45–0.76), and the sedating histamine 1‐receptor antagonists (adj.OR = 0.2;95%CI:0.1–0.8), but not the non‐sedating equivalent (adj.OR = 0.8;95%CI:0.4–1.6). Conclusions: The suggestion that some drugs may prevent MS is intriguing and warrants further study. In addition, further pharmacovigilance is needed to assess the safety of anti‐TNFα drugs in specific populations in the context of MS risk. [ABSTRACT FROM AUTHOR]

Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. Identifying MS at the population level is important for disease surveillance and allocation of resources. The Swedish National Patient Registry (NPR) has been used to study the epidemiology of MS, but the accuracy of this resource is not known. We aimed to validate a definition of MS using the Swedish NPR in Värmland County using a longitudinal cohort design., Materials and Methods: Data were extracted from the NPR, the Total Population Register, the Swedish MS Register, and medical records for the years 2001-2013. Fifteen algorithms of hospitalizations and clinic visits for MS were developed and compared with findings in medical records, which acted as the "gold standard" definition. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were estimated., Results: Of 805 eligible persons identified in the NPR, 763 had MS (94.8%) according to medical records. Of these, 544 (71.3%) were also registered in the SMSreg. The case definition that had a well-balanced sensitivity and specificity required three or more clinic or hospital visits for MS (sensitivity of 85.3% (95% CI: 82.6-87.8) and specificity of 81.0% (95%CI: 65.9-91.4)., Conclusions: Multiple case definitions with high sensitivity and moderate specificity were found, suggesting that the NPR can be used to accurately identify persons with MS., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: The cause of amyotrophic lateral sclerosis (ALS) is unknown, but occupations have been explored as a potential proxy measure of risk. There is a substantial body of literature connecting military service to ALS. We aimed to summarize and assess the quality of this evidence., Methods: Systematic review of the literature, including observational studies which explored one of the following exposures: general military service (army, air force, marines, or navy); or specific exposures associated with military service measured among military personnel. The outcome of interest was ALS incidence, which could include onset, diagnosis, or death from ALS., Results: A total of 2642 articles were screened. Following exclusion, 19 articles remained for inclusion in the systematic review, including 1 meta-analysis and 18 original observational studies. Most studies were of moderate quality. In general, the relationship between military service was suggestive of an increased risk, particularly among Gulf War and WWII veterans. Exposure to pesticides (including Agent Orange) certain chemicals (exhaust, burning agents), heavy metals, and head trauma appeared to increase the risk of ALS among military personnel., Conclusions: There is a possible association between military service and the subsequent development of ALS; however, the evidence was limited. Studies were generally hindered by small sample sizes and inadequate follow-up time. Future studies should endeavor to objectively measure specific exposures, or combinations thereof, associated with military service, as this will be of vital importance in implementing preventative strategies into military organizations., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)