Incident Cases Of Multiple Sclerosis Research Articles

The Role of Diet in Multiple Sclerosis Onset: A Prospective Study Using UK Biobank.

Multiple sclerosis (MS) is a debilitating autoimmune condition primarily affecting young adults, and its rise is evident globally. Despite this, its precise etiology remains elusive. Both genetic and environmental factors contribute to MS susceptibility; however, the link between diet and MS lacks substantial evidence due to limited large-scale studies. We exploited the UK Biobank resources to explore the nexus between diet, lifestyle, and MS risk. The dietary and lifestyle habits of MS incident cases, derived from a general food frequency questionnaire (FFQ) completed by all participants at study enrollment, were compared to those of subjects who did not develop MS during the follow-up. Our findings suggest the protective role of moderate oily fish consumption and weekly alcohol intake. Furthermore, by analyzing food intake data obtained through 24 h recall, completed by a subset of participants, we found a protective, though non-significant, trend of an increased adherence to the Mediterranean diet (MD). These findings, derived from the analysis of the UK Biobank and representing an unprecedented approach for this inquiry, warrant further exploration and integration in future research.

Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis.

A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow-up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31-52) were considered PwUD. They completed a modified questionnaire, previously used in a population-based case-control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS-like symptoms. Compared to controls (n=548) and PwMS (n=277), fewer PwUD were currently smoking (p=.4 and p=.03), consumed less alcohol (p=.04 and p=.01), and had children (p=.02 and p=.002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p<.001 and p<.001). UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.

Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.

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. 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. 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). 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.

A Global, Regional, and National Survey on Burden and Quality of Care Index of Multiple Sclerosis: Global Burden of Disease Systematic Analysis 1990–2019

Background: Multiple sclerosis (MS) is a common neurologic autoimmune disorder. We have used a newly introduced measure, Quality of Care Index (QCI), which is associated with the efficacy of care given to patients suffering from MS. Objectives: The aims of the study were to report and compare the quality of care given to MS patients in different regions and country. Methods: Primary measures were retrieved from Global Burden of Disease (GBD) from 1990 to 2019. Secondary measures (mortality-to-incidence ratio, DALY-to-prevalence ratio, prevalence-to-incidence ratio, and YLL-to-YLD ratio) were combined using principal component analysis, to form an essential component (QCI) (0–100 index with higher values representing better condition). Results: In 2019, there were 59,345 (95% UI: 51,818–66,943) new MS incident cases globally. Global QCI of 88.4 was calculated for 2019. At national level, Qatar had the highest quality of care (100) followed by Kuwait (98.5) and Greenland (98.1). The lowest QCI was observed in Kiribati (13.5), Nauru (31.5), and Seychelles (36.3), respectively. Most countries have reached gender equity during the 30 years. Also, QCI was lowest in ages from 55 to 80 in global scale. Conclusion: MS QCI is better among those countries of higher socioeconomic status, possibly due to better healthcare access and early detection in these regions. Countries could benefit from adopting the introduced QCI to evaluate the quality of care given to MS patients at national and global level.

Inverse association between Mediterranean diet and risk of multiple sclerosis

Objective: There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). Methods: We used a population-based case–control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits. Results: Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34–0.86, p = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75–1.24, p = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60–1.42, p = 0.518). Conclusions: Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet.

Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis: A data lake cohort study.

There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.

Epidemiology of multiple sclerosis in the Campania Region (Italy): Derivation and validation of an algorithm to calculate the 2015-2020 incidence.

We aim to validate an algorithm based on routinely-collected healthcare data to detect incidence of multiple sclerosis (MS) in the Campania Region (South Italy) and to explore its spatial and temporal variations. We included individuals resident in the Campania Region who had at least one MS record in administrative datasets (drug prescriptions, hospital discharge, outpatients), from 2015 to 2020. We merged administrative to the clinical datasets to ascertain the actual date of diagnosis, and validated the minimum interval from our study baseline (Jan 1, 2015) to first MS records in administrative datasets to detect incident cases. We used Bayesian approach to explore geographical distribution, also including deprivation index as a covariate in the estimation model. We used the capture-recapture method to estimate the proportion of undetected cases. The best performance was achieved by the 12-month interval algorithm, detecting 2,150 incident MS cases, with 74.4% sensitivity (95%CI=64.1%, 85.9%) and 95.3% specificity (95%CI=90.7%, 99.8%). The cumulative incidence was 36.68 (95%CI=35.15, 38.26) per 100,000 from 2016 to 2020. The mean annual incidence was 7.34 (95%CI=7.03, 7.65) per 100,000 people-year. The geographical distribution of MS relative risk shows a decreasing east-west incidence gradient. The number of expected MS cases was 11% higher than the detected cases. We validated a case-finding algorithm based on administrative data to estimate MS incidence, and its spatial/temporal variations. This algorithm provides up-to-date estimates of MS incidence, and will be used in future studies to evaluate changes in MS incidence in relation to different risk factors.

Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019.

The global rising prevalence and incidence of multiple sclerosis (MS) has been reported during the past decades. However, details regarding the evolution of MS burden have not been fully studied. This study aimed to investigate the global, regional, and national burden and temporal trends in MS incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2019 using the age-period-cohort analysis. We performed a secondary comprehensive analysis of incidence, deaths, and DALYs of MS by calculating the estimated annual percentage change from 1990 to 2019 obtained from the Global Burden of Disease (GBD) 2019 study. The independent age, period, and birth cohort effects were evaluated by an age-period-cohort model. In 2019, there were 59,345 incident MS cases and 22,439 MS deaths worldwide. The global number of incidences, deaths, and DALYs of MS followed an upward trend, whereas the age-standardized rates (ASR) slightly declined from 1990 to 2019. High socio-demographic index (SDI) regions had the highest ASR of incidences, deaths, and DALYs in 2019, while the rate of deaths and DALYs in medium SDI regions are the lowest. Six regions which include high-income North America, Western Europe, Australasia, Central Europe, and Eastern Europe had higher ASR of incidences, deaths, and DALYs than other regions in 2019. The age effect showed that the relative risks (RRs) of incidence and DALYs reached the peak at ages 30-39 and 50-59, respectively. The period effect showed that the RRs of deaths and DALYs increased with the period. The cohort effect showed that the later cohort has lower RRs of deaths and DALYs than the early cohort. The global cases of incidence, deaths, and DALYs of MS have all increased, whereas ASR has declined, with different trends in different regions. High SDI regions such as European countries have a substantial burden of MS. There are significant age effects for incidence, deaths, and DALYs of MS globally, and period effects and cohort effects for deaths and DALYs.

Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces: A Population-Based Study.

Antitumor necrosis factor α (TNFα) agents are a class of biologic drugs used for the treatment of several immune-mediated conditions. An increased risk of multiple sclerosis (MS) with their use has been suggested, but studies have been limited. Relevant population-based epidemiologic data linking anti-TNFα to MS are scarce. The objective was to compare the risk of MS in anti-TNFα users with nonusers among patients with rheumatic disease (RD) or inflammatory bowel disease (IBD). A nested case-control study was conducted. Population-based health care-linked databases from 4 Canadian provinces were used. All patients with RD or IBD residing within a participating province between January 2000 and March 2018 were identified by validated case definitions. Any anti-TNFα dispensation in the 2 years before the index date (MS onset) was identified. Incident onset MS cases were ascertained using a validated algorithm. Up to 5 controls were matched to each MS case based on birth year ±3 years, disease duration, and health authority (based on region of residence). Conditional logistic regressions were used to calculate the incidence rate ratio (IRR) after adjusting for potential confounders. A meta-analysis was conducted to provide pooled estimates across provinces using random-effects models. Among 296,918 patients with RD patients, 462 MS cases (80.1% female, mean [SD] age, 47.4 [14.6] years) were matched with 2,296 controls (59.5% female, mean [SD] age, 47.4 [14.5] years). Exposure to anti-TNFα occurred in 18 MS cases and 42 controls. After adjusting for matching variables, sex, and the Charlson Comorbidity Index, the pooled IRR was 2.05 (95% CI, 1.13-3.72). Among 84,458 patients with IBD, 190 MS cases (69.5% female, mean [SD] age, 44.3 [12.3] years) were matched with 943 controls (54.1% female, mean [SD] age, 44.2 [12.2] years). Exposure to anti-TNFα occurred in 23 MS cases and 98 controls. The pooled adjusted IRR was 1.35 (95% CI, 0.70-2.59). The use of anti-TNFα was associated with an increased risk of MS compared with nonusers, especially among patients with RD. These findings could help clinicians and patients with RD to make more informed treatment decisions. Further studies are needed to validate these results for patients with IBD.

Bacillus Calmette-Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada.

The bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of multiple sclerosis (MS) through immunomodulation. Previous studies, presenting some limitations, reported no association. We re-examined this association in a large cohort focusing on relapsing-remitting MS (RRMS). The cohort included 400,563 individuals, and was linked with the Quebec provincial BCG vaccination registry and administrative health data. Individuals were followed up from 1983 to 2014 and then within Period 1 (1983-1996) and Period 2 (1997-2014), for the occurrence of MS. Incident MS cases were defined as those with ≥3hospital or physician claims for MS. Subjects with ≥1 drug reimbursement for MS disease-modifying therapies were classified as RRMS. Cox proportional hazards regression was used to estimate hazard ratios (HRs) over the follow-ups, adjusting for potential confounders. Possible effect modification due to sex was assessed. A total of 178,335 (46%) individuals were BCG vaccinated. There were 274 (0.06%) incident MS cases identified in 1983-1996, and 1433 (0.4%) in 1997-2014. No association was found with RRMS, either in Period 1 (adjusted HR [HRadj ]=0.96, 95% confidence interval [CI] = 0.63-1.45; 96 cases) or in Period 2 (HRadj =1.02, 95% CI = 0.85-1.23; 480 cases). The remaining MS cases, for whom the phenotype was unknown, were positively associated with BCG over the entire follow-up (HRadj =1.25, 95% CI = 1.10-1.41; 1131 cases) and in Period 2 (HRadj =1.33, 95% CI = 1.17-1.52; 953 cases). No interaction with sex was found. Findings suggest that BCG vaccination does not decrease the risk of RRMS, and that future studies should consider phenotypes of MS.

Low sun exposure acts synergistically with high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels in multiple sclerosis etiology.

Among multiple sclerosis (MS) patients, an association has been observed between low levels of vitamin D and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels. However, whether sun exposure/vitamin D moderates the role of Epstein-Barr virus (EBV) infection in MS etiology is unclear. We aimed to investigate potential synergistic effects between low sun exposure and elevated EBNA-1 antibody levels regarding MS risk. We used a population-based case-control study involving 2017 incident cases of MS and 2443 matched controls. We used logistic regression models to calculate the odds ratios of MS with 95% confidence intervals (CIs) in subjects with different sun exposure habits and EBNA-1 status. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Low sun exposure acted synergistically with high EBNA-1 antibody levels (AP 0.2, 95% CI 0.03-0.3) in its association to increased MS risk. The interaction was present regardless of HLA-DRB1*15:01status. Low sun exposure may either directly, or indirectly by affecting vitamin D levels, synergistically reinforce pathogenic mechanisms, such as aspects of the adaptive immune response, related to MS risk conveyed by EBV infection.

1321Marginal structural model of the causal role of hepatitis B vaccination in multiple sclerosis risk

Abstract Background There are conflicting reports regarding the association between uptake of recombinant vaccine against hepatitis B virus (HBV) and risk of multiple sclerosis (MS). Most cohort or case-control studies found no significant short- or long-term increase in MS risk after immunization. Whereas others reported a significant increase in MS risk within three years of HBV vaccination. The present matched case-control study was conducted to test the hypothesis whether recombinant HBV vaccination status is causally associated with MS risk using targeted maximum likelihood estimation (TMLE) that uses data-adaptive flexible machine learning algorithms to estimate the causal parameters. Methods Confirmed 110 MS incident cases and age (± 5 years), gender and nationality matched (1:1) 110 community controls were enrolled. A pre-tested structured questionnaire was used to collect the data on demographics, environmental factors, comorbidities, history of vaccinations through face-to-face interviews both from cases and controls. We implemented case-control-weighted TMLE – a double robust, multistep procedure to estimate causal relative risk (RR), marginal odds ratio (OR) and population attributable fraction. Results This study demonstrated a non-specific protective effect of HBV vaccine against MS risk as estimated by TMLE (causal RR 0.63, 95% CI: 0.45-0.90; p = 0.004; marginal OR 0.43; 95% CI: 0.18-0.67; p = 0.006). The population attributable fraction was 20% (95% CI: 6%, 34%; p = 0.014)) Conclusions Subject to inherent limitations of the case-control design, this study suggests a non-specific protective effect of recombinant HBV vaccination against MS risk. Future studies may contemplate to confirm these results. Key message Causal analysis showed a non-specific protective causal association between uptake of recombinant HBV vaccine and MS risk in the study population.

High prevalence of comorbidities at diagnosis in immigrants with multiple sclerosis

Background: Multiple sclerosis (MS) has been associated with certain comorbidities in general population studies, but it is unknown how comorbidity may affect immigrants with MS. Objective: To compare prevalence of comorbidities in immigrants and long-term residents at MS diagnosis, and in matched control populations without MS. Methods: We identified incident MS cases using a validated definition applied to health administrative data in Ontario, Canada, from 1994 to 2017, and categorized them as immigrants or long-term residents. Immigrants and long-term residents without MS (controls) were matched to MS cases 3:1 on sex, age, and geography. Results: There were 1534 immigrants and 23,731 long-term residents with MS matched with 4585 and 71,193 controls, respectively. Chronic obstructive pulmonary disease (COPD), diabetes, hypertension, ischemic heart disease, migraine, epilepsy, mood/anxiety disorders, schizophrenia, inflammatory bowel disease (IBD), and rheumatoid arthritis were significantly more prevalent among immigrants with MS compared to their controls. Prevalence of these conditions was generally similar comparing immigrants to long-term residents with MS, although COPD, epilepsy, IBD, and mood/anxiety disorders were less prevalent in immigrants. Conclusion: Immigrants have a high prevalence of multiple comorbidities at MS diagnosis despite the “healthy immigrant effect.” Clinicians should pay close attention to identification and management of comorbidity in immigrants with MS.

Multiple sclerosis incidence and prevalence in Poland: Data from administrative health claims

BackgroundThe detailed data concerning multiple sclerosis (MS) epidemiology in Poland are based on studies from few and less populated provinces. Therefore, we evaluated MS incidence and prevalence in Poland using electronic administrative health claims (AHCs) from the National Health Fund. MethodsWe retrospectively analyzed the AHC financial database collected from 2009 to 2019, encompassing all patients using public health resources. Three different algorithms for identification of MS cases were used: based on studies performed in German population (type 1), tested in the United States (type 2), and one created for the purpose of this study (type 3) that required at least 3 AHCs since 2009 with G35 ICD-10 diagnosis in outpatient specialist care, during hospitalization, and/or at rehabilitation service in any combination within maximally 3 years between the first and the last AHC, and provided that at least one AHC was either in neurological outpatient care or during hospitalization at a neurological ward or prescription of disease-modifying therapy. The American algorithm (type 2) required 3 AHCs within the analyzed year, while the German algorithm (type 1) required only one AHC in the analyzed year. ResultsAccording to the type 3 algorithm, age-adjusted MS incidence and prevalence in 2019 was 6.6 and 131.2 / 100,000 inhabitants, respectively. From 2014 to 2019, the significant trend in increasing prevalence and decreasing incidence of MS was observed (p<0.001). Median age of prevalent MS patients was 50 years (interquartile range, IQR 39-61) whereas median age of incident MS cases was 37 years (IQR 28-48). Female-to-male ratio in MS patients was 2.4. According to the type 1 algorithm, age-adjusted MS incidence and prevalence in 2019 was 11.6 and 244.9 / 100,000 inhabitants, respectively. Use of the type 2 algorithm resulted in estimated age-adjusted MS incidence and prevalence values in 2019 of 6.2 and 120.1 / 100,000 inhabitants, respectively. ConclusionsMultiple sclerosis incidence and prevalence in Poland are higher than previously reported and similar to the numbers shown for central European countries.

The epidemiology of multiple sclerosis in the Scottish Highlands: Prevalence, incidence and time to confirmed diagnosis and treatment initiation

IntroductionAlthough multiple sclerosis (MS) is frequent in the northern hemisphere, there have not been recent epidemiological studies in the Scottish Highlands about MS. ObjectivesTo get updated data regarding MS prevalence, incidence and mortality in the Highlands. Time between symptom onset and MS diagnosis was also evaluated in incident MS cases and the pattern of use of disease-modifying therapies (DMTs) was analysed. MethodsStudy population was people with MS under the care of the Highland Health and Social Care Partnership. The catchment area included North area (Wick, Thurso, Brora, Invergordon), Center (Inverness, Aviemore, Nairn, Fort William), and West coast (Ullapool, Skye). Data were obtained from the MS database at Raigmore hospital (prevalence, midyear 2017) and the prospective hospital-register based study (diagnosis) that was carried out over a 12-month period, in 2016. The 2010 McDonald criteria for diagnosis of new MS cases were used. Crude prevalence and incidence and 95% confidence interval (CI) were calculated for the MS adult onset population, and data was standardised to the European standard population 2013; cause-specific mortality rate was analysed. Pattern of use of DMTs during the first year of diagnosis was also registered. Results745 patients were registered in the MS database. 75.4% (562 cases) were females, and female/male ratio was 3:1. Mean age of population was 54.1 ± 14.1 years (range: 15-95 years). Mean number of years since diagnosis was 8.5 ± 4.6 years. Estimated prevalence for the population aged 15 and older was 376 cases per 100,000 inhabitants (95% CI: 354-399). 36 incident MS cases were registered in 2016 (88.8% females; mean age 40.4 ± 12.1 years). Annual incidence in Highlands was 18.2 per 100,000 inhabitants (95% CI: 14-24). The mean period of time from symptom onset to diagnosis was 38.8 ± 43.2 months. 47.2% (17/36) did not take any DMT during the first year after the diagnosis. ConclusionPrevalence and incidence of MS in the Scottish Highlands is high. Although the gap period between symptom onset and diagnosis is moderate, a significant proportion of recently diagnosed MS patients were not keen to start a DMT the first year after the diagnosis.

Joinpoint Regression Analysis of Trends in Multiple Sclerosis Incidence in Kuwait: 1980–2019

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown precise etiology. Temporally, a tendency for increasing MS incidence has been recorded worldwide. This cross-sectional cohort study sought to quantify trends in the age-standardized incidence rates (ASIRs) (per million person-years) of MS in Kuwait from 1980 to 2019, overall and by subcohorts defined by age at MS onset, sex, and nationality. Methods: MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry (KNMSR). Using midyear relevant Kuwait population as denominator and the World Standard Population as a reference, MS ASIRs overall and by subcohorts defined by age at onset (0–19, 20–39, and 40+ years), sex (male and female), and nationality (Kuwaiti and non-Kuwaiti) were computed. Joinpoint regression analysis was conducted to estimate average annual percent change (AAPC) and its 95% confidence interval (CI) overall and by subcohorts. Results: During 1980–2019, a total of 1,764 MS incident cases of 95.6 million person-years at-risk were diagnosed and registered in KNMSR. The overall MS ASIR (per million person-years) during the study period was 34.1 (95% CI: 16.1, 52.1). Between 1980 and 2010, in the total cohort, ASIRs of MS significantly increased by 13% (AAPC = 13.0; 95% CI: 10.8, 15.3; p < 0.001), followed by statistically nonsignificant declining trend during the ensuing period (AAPC = −3.8; 95% CI: −14.8, 8.8; p = 0.522). Joinpoint regression analysis revealed that 2 subcohorts of Kuwaiti females each with one joinpoint had significant increasing trends in MS ASIRs (0- to 19-year-old Kuwaiti females, AAPC: 1980–2009, 81.0; 95% CI: 58.2, 107.0; p = 0.001; 20- to 39-year-old Kuwaiti females, AAPC: 1980–1999, 131.7; 95% CI: 26.9, 322.8; p = 0.021). Additionally, of remaining 10, 6 subcohorts had significantly (p < 0.05) increasing trends in MS ASIRs from 1980 to 2019. Conclusions: From 1980 to 2010, Kuwait has an overall significantly increasing trend in MS ASIRs followed by a nonsignificant declining drift in the ensuing period. The increasing trend in MS risk appeared to be driven by increased risk among Kuwaiti females younger than 40 years. The underlying factors modulating MS risk in Kuwait need further studies.

Stressful life events are associated with the risk of multiple sclerosis.

Background and purposeUnexpected stressful life events may alter immune function and affect susceptibility to autoimmune diseases including multiple sclerosis (MS). Current results from epidemiological investigations examining the role of stress in MS remain inconsistent. The aim was to conduct the hitherto largest population‐based case–control study on this topic.MethodsExtensive questionnaire information collected on lifestyle environmental factors available for 2930 incident MS cases and 6170 controls were used to assess the association of 10 major life events that had occurred before disease onset with the risk of MS by unconditional logistic regressions, adjusting for potential confounders. Stratified analyses were also performed by sex and time.ResultsCompelling evidence was found for a link between major life events and risk of MS – most events significantly increased disease risk by 17%–30%. It was further observed that women were affected to a greater extent than men under certain stressful scenarios, and that most events that happened recently (≤5 years prior to MS onset) had significant effects on MS, indicating a critical window in disease development.ConclusionStressful life events may have an adverse effect on the risk of MS. Research into the mechanisms of this observation may give important clues to triggering pathogenetic events in MS.

Health service utilization in immigrants with multiple sclerosis.

Access to neurology specialty care can influence outcomes in individuals with multiple sclerosis (MS), but may vary based on patient sociodemographic characteristics, including immigration status. To compare health services utilization in the year of MS diagnosis, one year before diagnosis and two years after diagnosis in immigrants versus long-term residents in Ontario, Canada. We identified incident cases of MS among adults aged 20-65 years by applying a validated algorithm to health administrative data in Ontario, Canada, a region with universal health insurance and comprehensive coverage. We separately assessed hospitalizations, emergency department (ED) visits, outpatient neurology visits, other outpatient specialty visits, and primary care visits. We compared rates of health service use in immigrants versus long-term residents using negative binomial regression models with generalized estimating equations adjusted for age, sex, socioeconomic status, urban/rural residence, MS diagnosis calendar year, and comorbidity burden. From 2003 to 2014, there were 13,028 incident MS cases in Ontario, of whom 1,070 (8.2%) were immigrants. As compared to long-term residents, rates of hospitalization were similar (Adjusted rate ratio (ARR) 0.86; 95% CI: 0.73-1.01) in immigrants the year before MS diagnosis, but outpatient neurology visits (ARR 0.93; 95% CI: 0.87-0.99) were slightly less frequent. However, immigrants had higher rates of hospitalization during the diagnosis year (ARR 1.20, 95% CI: 1.04-1.39), and had greater use of outpatient neurology (ARR 1.17, 95% CI: 1.12-1.23) but fewer ED visits (ARR 0.86; 95% CI: 0.78-0.96). In the first post-diagnosis year, immigrants continued to have greater numbers of outpatient neurology visits (ARR 1.16; 95% CI: 1.10-1.23), but had fewer hospitalizations (ARR 0.79; 95% CI: 0.67-0.94). Overall, our findings were reassuring concerning health services access for immigrants with MS in Ontario, a publicly funded health care system. However, immigrants were more likely to be hospitalized despite greater use of outpatient neurology care in the year of MS diagnosis. Reasons for this may include more severe disease presentation or lack of social support among immigrants and warrant further investigation.

Hospital diagnosed pneumonia before age 20 years and multiple sclerosis risk

IntroductionRespiratory inflammation has been proposed as a risk factor for MS. This study aims to determine if hospital-diagnosed pneumonia in adolescence (before age 20 years) is associated with subsequent multiple...

Race, ethnicity, and cognition in persons newly diagnosed with multiple sclerosis.

To determine whether black or Hispanic patients with newly diagnosed multiple sclerosis (MS) are more likely to have cognitive impairment than white patients when compared to controls matched on age, sex, and race/ethnicity. Whether black or Hispanic patients have a more aggressive MS disease course than white patients remains unclear. No prior studies have examined differences in early cognitive impairment. The oral Symbol Digit Modalities Test (SDMT) is sensitive to early cognitive impairment in MS but normative data in nonwhite patients are limited. We studied 1,174 adults who enrolled in the MS Sunshine Study. SDMT and verbal fluency were measured in 554 incident cases of MS or clinically isolated syndrome (CIS) and 620 matched controls. Multivariable regression was used to examine correlates of abnormal SDMT in the entire cohort. The strongest independent predictors of lower oral SDMT scores in rank order were having MS/CIS, lower educational attainment, and being black or Hispanic. Black and Hispanic patients and controls had lower SDMT scores than white participants even after controlling for age, sex, and education. However, no interaction between race/ethnicity and MS case status on SDMT scores was detected. Easy-to-use reference scores stratified by age and educational attainment for black and Hispanic patients are provided. Persons with newly diagnosed MS/CIS are more likely to have subtly impaired cognitive function than controls regardless of race/ethnicity. Lower absolute SDMT scores among black and Hispanic patients compared to white patients highlight underlying US population differences rather than differences in MS disease severity.