Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurogenerative disease caused by combined genetic susceptibilities and environmental exposures. Identifying and validating these exposures are of paramount importance to modify disease risk. We previously reported that persistent organic pollutants (POPs) associate with ALS risk and survival and aimed to replicate these findings in a new cohort. METHOD: Participants with and without ALS recruited in Michigan provided plasma samples for POPs analysis by isotope dilution with triple quadrupole mass spectrometry. ORs for risk models and hazard ratios for survival models were calculated for individual POPs. POP mixtures were represented by environmental risk scores (ERS), a summation of total exposures, to evaluate the association with risk (ERSrisk) and survival (ERSsurvival). RESULTS: Samples from 164 ALS and 105 control participants were analysed. Several individual POPs significantly associated with ALS, including 8 of 22 polychlorinated biphenyls and 7 of 10 organochlorine pesticides (OCPs). ALS risk was most strongly represented by the mixture effects of OCPs alpha-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor and cis-nonachlor and an interquartile increase in ERSrisk enhanced ALS risk 2.58 times (p<0.001). ALS survival was represented by the combined mixture of all POPs and an interquartile increase in ERSsurvival enhanced ALS mortality rate 1.65 times (p=0.008). CONCLUSIONS: These data continue to support POPs as important factors for ALS risk and progression and replicate findings in a new cohort. The assessments of POPs in non-Michigan ALS cohorts are encouraged to better understand the global effect and the need for targeted disease risk reduction strategies.

Flavonoid intake and risk of Parkinson's disease.

BACKGROUND: Flavonoids have been proposed to reduce the risk of Parkinson's disease (PD). However, results from epidemiological studies have been inconclusive. OBJECTIVE: To prospectively examine the association between the intake of flavonoids and their subclasses and the risk of PD and how pesticides may confound or modify that association. METHODS: The study population comprised 80 701 women (1984-2016) and 48 782 men (1986-2016) from two large US cohorts. Flavonoid intake was ascertained at baseline and every 4 years thereafter using a semiquantitative Food Frequency Questionnaire. We conducted multivariable-adjusted Cox regression models to estimate HRs and 95% CIs of PD according to quintiles of baseline and cumulative average intakes of flavonoids and subclasses. We repeated the analyses, adjusting for intakes of high-pesticide-residue fruits and vegetables (FVs) and stratifying by servings/day of high-pesticide-residue FV intake. RESULTS: We identified 676 incident PD cases in women and 714 in men after 30-32 years of follow-up. Higher total flavonoid intake at baseline was not associated with a lower PD risk, neither in men (HR comparing highest to lowest quintile: 0.89, 95% CI: 0.69 to 1.14) nor in women (HR comparing highest to lowest quintile: 1.27, 95% CI: 0.98 to 1.64). Similar results were observed for cumulative average intakes and flavonoid subclasses. Results remained similar after adjustment for and stratification by high-pesticide-residue FV and when analyses were restricted to younger PD cases. CONCLUSION: These results do not support a protective effect of flavonoid intake on PD risk. Pesticide residues do not confound or modify the association.

Effect of long-term Tai Chi training on Parkinson's disease: a 3.5-year follow-up cohort study.

BACKGROUND: Tai Chi has shown beneficial effects on the motor and non-motor symptoms of Parkinson's disease (PD), but no study has reported the effect of long-term Tai Chi training. OBJECTIVE: To examine whether long-term Tai Chi training can maintain improvement in patients with PD. METHODS: Cohorts of patients with PD with Tai Chi training (n=143) and patients with PD without exercise as a control group (n=187) were built from January 2016. All subjects were assessed at baseline and in November 2019, October 2020 and June 2021. A logarithmic linear model was used to analyse rating scales for motor and non-motor symptoms. The need to increase antiparkinsonian therapies was presented as a Kaplan-Meier plot and as a box plot. The bootstrap method was used to resample for statistical estimation. RESULTS: Tai Chi training reduced the annual changes in the deterioration of the Unified Parkinson's Disease Rating Scale and delayed the need for increasing antiparkinsonian therapies. The annual increase in the levodopa equivalent daily dosage was significantly lower in the Tai Chi group. Moreover, patients benefited from Tai Chi training in motor symptoms, non-motor symptoms and complications. CONCLUSION: Tai Chi training has a long-term beneficial effect on PD, with an improvement in motor and non-motor symptoms and reduced complications. TRIAL REGISTRATION NUMBER: NCT05447975.

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60.

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

Emulating randomised clinical trials in relapsing-remitting multiple sclerosis with non-randomised real-world evidence: an application using data from the MSBase Registry.

BACKGROUND: To mimic as closely as possible a randomised controlled trial (RCT) and calibrate the real-world evidence (RWE) studies against a known treatment effect would be helpful to understand if RWE can support causal conclusions in selected circumstances. The aim was to emulate the TRANSFORMS trial comparing Fingolimod (FTY) versus intramuscular interferon ß-1a (IFN) using observational data. METHODS: We extracted from the MSBase registry all the patients with relapsing-remitting multiple sclerosis (RRMS) collected in the period 2011-2021 who received IFN or FTY (0.5 mg) and with the same inclusion and exclusion criteria of the TRANSFORMS RCT. The primary endpoint was the annualised relapse rate (ARR) over 12 months. Patients were 1:1 propensity-score (PS) matched. Relapse-rate ratio (RR) was calculated by mean of a negative binomial regression. RESULTS: A total of 4376 patients with RRMS (1140 in IFN and 3236 in FTY) were selected. After PS, 856 patients in each group were matched. The ARR was 0.45 in IFN and 0.25 in FTY with a significant difference between the two groups (RR: 0.55, 95% CI: 0.45 to 0.68; p<0.001). The result of the emulation was very similar and fell within the 95% CI of that observed in the RCT (RR: 0.49, 95% CI: 0.37 to 0.64; p<0.001) with a standardised difference of 0.66 (p=0.51). CONCLUSIONS: By applying the same inclusion and exclusion criteria used in the RCT and employing appropriate methodology, we successfully replicated the RCT results with only minor discrepancies. Also, even if the confounding bias cannot be fully eliminated, conducting a rigorous target trial emulation could still yield valuable insights for comparative effectiveness research.

Prognostic factors for disease activity in newly diagnosed teriflunomide-treated patients with multiple sclerosis: a nationwide Danish study.

BACKGROUND: Clinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This study evaluates how these factors, along with age and sex, influence prognosis during treatment with teriflunomide (TFL). METHODS: We conducted a nationwide cohort study using data from the Danish Multiple Sclerosis Registry.Eligible participants had relapsing-remitting MS or clinically isolated syndrome and initiated TFL as their first treatment between 2013 and 2019. The effect of age, pretreatment relapses, T2L and EDSS scores on the risk of disease activity on TFL were stratified by sex. RESULTS: In total, 784 individuals were included (57.4% females). A high number of pretreatment relapses (≥2) was associated with an increased risk of disease activity in females only (OR and (95% CI): 1.76 (1.11 to 2.81)). Age group 50+ was associated with a lower risk of disease activity in both sexes (OR females=0.28 (0.14 to 0.56); OR males=0.22 (0.09 to 0.55)), while age 35-49 showed a different impact in males and females (OR females=0.79 (0.50 to 1.23); OR males=0.42 (0.24 to 0.72)). EDSS scores and T2L did not show any consistent associations. CONCLUSION: A high number of pretreatment relapses was only associated with an increased risk of disease activity in females, while age had a differential impact on the risk of disease activity according to sex. Clinicians may consider age, sex and relapses when deciding on TFL treatment.

Future Burden of Ischemic Stroke in Australia: Impact on Health Outcomes between 2019 and 2038.

BACKGROUND: Projections of the future burden of ischemic stroke (IS) has not been extensively reported for the Australian population; the availability of such data would assist in health policy planning, clinical guideline updates, and public health. METHODS: First, we estimated the lifetime risk of IS (from age 40 to 100 years) using a multistate life table model. Second, a dynamic multistate model was constructed to project the burden of IS for the whole Australian population aged between 40 and 100 years over a 20-year period (2019-2038). Data for the study were primarily sourced from a large, representative Victorian linked dataset based on the Victorian Admitted Episode Dataset and National Death Index. The model projected prevalent and incident cases of nonfatal IS, fatal IS, and years of life lived (YLL) with and without IS. The YLL outcome was discounted by 5% annually; we varied the discounting rate in scenario analyses. RESULTS: The lifetime risk of IS from age 40 years was estimated as 15.5% for males and 14.0% for females in 2018. From 2019 to 2038, 644,208 Australians were projected to develop incident IS (564,922 nonfatal and 79,287 fatal). By 2038, the model projected there would be 358,534 people with prevalent IS, 35,554 people with incident nonfatal IS and 5,338 people with fatal IS, a 14.2% (44,535), 72.9% (14,988), and 106.3% (2,751) increase compared to 2019 estimations, respectively. Projected YLL (with a 5% discount rate) accrued by the Australian population were 174,782,672 (84,251,360 in males and 90,531,312 in females), with 4,053,794 YLL among people with IS (2,320,513 in males, 1,733,281 in females). CONCLUSION: The burden of IS was projected to increase between 2019 and 2038 in Australia. The outcomes of the model provide important information for decision-makers to design strategies to reduce stroke burden.

Incidence of Multiple Sclerosis in Uruguay: A Prospective Population-Based Study.

BACKGROUND: The worldwide incidence of multiple sclerosis (MS) is estimated at 0.5-10 cases per 100,000 person-years and is probably increasing. In 2014, a previous study estimated the incidence of multiple sclerosis in Uruguay at 1.2 cases per 100,000 person-years. OBJECTIVES: We conducted an observational, prospective, population-based study to determine MS incidence from diagnosis in Uruguay. METHODS: The population studied included people older than 18 years of age who were living in Uruguay between July 1, 2019, and June 30, 2021. The diagnosis was based on 2017 McDonald criteria. Multiple data sources were employed including neurologists, magnetic resonance imaging centers, laboratories performing oligoclonal band testing, neurophysiology laboratories, neurorehabilitation centers, the institution Fondo Nacional de Recursos, and the MS Patients' Association of Uruguay (EMUR). The capture-recapture method was used to estimate incidence. RESULTS: 155 new MS cases were confirmed after review. The median age was 35 (range 18-62). Thirteen patients (8.38%) were diagnosed with late-onset MS. The crude incidence rate was 2.89 cases per 100,000 person-years, 3.95 among females, and 1.72 among male patients. The incidence rate estimated using the capture-recapture method was 3.18 (95% CI: 3.02-3.34). CONCLUSIONS: According to the Atlas of MS, Uruguay has a low incidence rate (2.0-3.99), even though it is one of the highest in Latin America. Our country aligns with the global trend of increasing incidence. Age and sex distribution were similar to other studies, with a high incidence of patients with late-onset multiple sclerosis. The capture-recapture method confirms the exhaustivity of our investigation.

Two Decades of Stroke in the United States: A Healthcare Economic Perspective.

INTRODUCTION: Stroke is a leading cause of morbidity and mortality in the USA and has implications on the financial health of patients, families, and healthcare systems. The objective of this study aimed to determine the economic perspective of stroke on the national healthcare system for the past 2 decades. METHODS: This retrospective study of inpatient subjects from 2000 to 2020 with stroke was collected from the Healthcare Cost and Utilization Project (HCUP). We queried patients admitted primarily for ischemic or hemorrhagic stroke. Patients were evaluated for demographics, length of stay (LOS), mortality, and hospital charges. Statistical Z-testing with a significance of p < 0.05 was conducted for the analysis. RESULTS: During the study period, 12,158,747 stroke subjects were studied, with 51.9% female and a mean age of 70.08 (±0.16) years old. The mean rate of stroke discharges per 100,000 persons was 187.71 (±3.44), decreasing from 200 to 193 during the study (p = 0.16). The mean percentage of deaths was 8.78% (±0.17), which decreased from 10.96% to 6.81% (p = 0.00). The mean LOS was 6.28 days (±0.08), which increased from 6.70 to 7.15 (p = 0.00). During the study period, the aggregated national bill was USD 725 billion. The mean hospital charges per patient were USD 57,178 (±1,504), increasing from USD 19,647 to USD 121,765 per person during the study period (p = 0.00), while mean hospital costs per stay were USD 15,781 (±330). These data closely conform to an exponential growth pattern, and forecasting per patient charges for the next 10 years demonstrates a cost of USD 287,836 by 2030. CONCLUSIONS: Our data show that the rate and mortality of stroke have decreased, but its charges and costs are increasing. The improvement in outcomes could be multifactorial such as establishment of comprehensive stroke centers and evolving treatment modalities. Ironically, the charges per patient increased more than sixfold with a national bill almost equal to the annual Medicare budget. Thus, the significance of preventive medicine, such as controlling hypertension, diabetes, and smoking cessation, cannot be understated. With such a dramatically increasing financial burden, improvements in mitigating risk factors, educational programs, and access to care may be a more cost-effective option.

Prevalence and genotypic associations of epilepsy in Prader-Willi Syndrome: A systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS). METHODS: A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed. RESULTS: Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures. CONCLUSIONS: The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed.

Subjective cognitive decline and cognitive change among diverse middle-aged and older Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: The potential utility of subjective cognitive decline (SCD) as an early risk marker of Alzheimer's disease and related dementias is under consideration. We examined associations between SCD and cognitive change among middle-aged and older Hispanic/Latino adults living in the United States. METHODS: The short-form Everyday Cognition Scale (ECog-12) was assessed to generate global, executive function, and memory-related SCD scores. We used survey generalized regressions to model the change in learning, memory, verbal fluency, executive function, and global cognitive performance over 7 years as a function of SCD (at Visit 2). RESULTS: The mean age was 56.37 ± 8.10 years at Visit 1 (n = 6225). Higher ECog-12 was associated with greater decline in global cognitive performance (ECog-12 global: B = -0.17, standard error [SE] = 0.02; ECog-12 executive: B = -0.15, SE = 0.02; ECog-12 memory: B = -0.14, SE = 0.02, p's < 0.001). DISCUSSION: These results support the link between subjective reports of cognitive decline and objectively measured 7-year cognitive decline in community-dwelling, middle-aged, and older Hispanic/Latino adults. HIGHLIGHTS: We found that nearly two-thirds of diverse middle-aged and older Hispanics/Latinos reported cognitive concerns in a large and representative population study. Self-reported subjective experiences of cognitive decline reflect objective cognitive decline in US Hispanics/Latinos. The relationship is stronger among men compared to women. The relationship between subjective and objective changes to memory are stronger in those with cognitive concerns, and remain even in cognitively healthy individuals.

Association between early treatment of multiple sclerosis and patient-reported outcomes: a nationwide observational cohort study.

BACKGROUND: Timing of disease-modifying therapy affects clinical disability in multiple sclerosis, but it is not known whether patient reported outcomes are also affected. This study investigates the relationship between treatment timing and patient-reported symptoms and health-related quality of life. METHODS: This was a nationwide observational cohort study of adults with relapsing multiple sclerosis, with disease onset between 2001 and 2016, and commenced on disease-modifying treatment within 4 years from disease onset. Patients commencing treatment within 0-2 years were compared with patients commencing treatment at 2-4 years. Indication bias was mitigated by propensity matching. Outcomes were patient-reported symptoms and health-related quality of life as measured by the Multiple Sclerosis Impact Scale (MSIS-29) and EuroQol-5 Dimensions-3 Level (EQ-5D). The follow-up period was 4-10 years from disease onset. RESULTS: There were 2648 patients (69% female, median age 32.8) eligible for matching. Mean follow-up time was 3.7 years. Based on 780 matched patients, each year of treatment delay was associated with a worse MSIS physical score by 2.75 points (95% CI 1.29 to 4.20), and worse MSIS psychological score by 2.02 points (95% CI 0.03 to 3.78), in the adjusted models.Among 690 matched patients, earlier treatment start was not associated with EQ-5D score during the follow-up. CONCLUSIONS: Earlier commencement of disease-modifying treatment was associated with better patient-reported physical symptoms when measured using a disease-specific metric; however, general quality of life was not affected. This indicates that other factors may inform patients' overall quality of life.

Timing of physical activity across adulthood on later-life cognition: 30 years follow-up in the 1946 British birth cohort.

BACKGROUND: To assess how timing, frequency and maintenance of being physically active, spanning over 30 years in adulthood, is associated with later-life cognitive function. METHODS: Participants (n=1417, 53% female) were from the prospective longitudinal cohort study, 1946 British birth cohort. Participation in leisure time physical activity was reported five times between ages 36 and 69, categorised into: not active (no participation in physical activity/month); moderately active (participated 1-4 times/month); most active (participated 5 or more times/month). Cognition at age 69 was assessed by tests of cognitive state (Addenbrooke's Cognitive Examination-III), verbal memory (word learning test) and processing speed (visual search speed). RESULTS: Being physically active, at all assessments in adulthood, was associated with higher cognition at age 69. For cognitive state and verbal memory, the effect sizes were similar across all adult ages, and between those who were moderately and most physically active. The strongest association was between sustained cumulative physical activity and later-life cognitive state, in a dose-response manner. Adjusting for childhood cognition, childhood socioeconomic position and education largely attenuated these associations but results mainly remained significant at the 5% level. CONCLUSIONS: Being physically active at any time in adulthood, and to any extent, is linked with higher later-life cognitive state, but lifelong maintenance of physical activity was most optimal. These relationships were partly explained by childhood cognition and education, but independent of cardiovascular and mental health and APOE-E4, suggestive of the importance of education on the lifelong impacts of physical activity.

Huntington's Disease in Chile: Epidemiological and Genetic Aspects.

INTRODUCTION: Huntington's disease (HD) is a neurodegenerative, autosomal dominant disabling condition due to an expansion of the CAG trinucleotide in the HTT gene. Motor, psychiatric, and cognitive disorders characterize it. Chilean reports on HD in the era of molecular diagnosis were wanted. METHODS: This is a retrospective analysis of a prospective cohort of patients with HD seen at the Center for Movement Disorders (CETRAM) in Chile between 2013 and 2019. Sociodemographic, genotype, and neuropsychiatric features were investigated. RESULTS: One hundred three probands with HD were identified. The majority (63.1%) were born in the metropolitan region, followed by the VIII and V regions with 8.73% and 7.76%, respectively. When pedigrees were analyzed, ninety unrelated families encompassing 1,007 individuals were identified; among relatives, other 35 manifested HD, and 106 died of HD. Besides, five hundred seventy-nine individuals were at genetic risk. The minimum estimated prevalence of HD in Chile in 2019 was 0.72 × 100,000 inhabitants. The mean CAG repeats (CAGR) of 47.2 ± 10.74 for the expanded allele and 17.93 ± 2.05 for the normal allele. The mean age of onset was 41.39 ± 13.47 years. Juvenile cases represented 7.8% of this cohort, and 4.9% had a late onset. There was a negative correlation between the age of onset and the CAGR of the expanded allele (r =-0.84 p < 0.0001). Besides, 79.6% had a family history of HD. CONCLUSIONS: This is the first report characterizing genetics, motor, and neuropsychiatric features in patients with HD in Chile. The mean length of CAGR expansion of the abnormal allele was similar to previous reports in North America (i.e., Mexico and Canada) and higher than that reported in the neighboring country of Argentina. According to previous estimations, the minimal prevalence of HD in Chile may be lower than expected.

Obstetrical Outcomes of Patients with Epilepsy in a Canadian Tertiary Care Center (2014-2020).

BACKGROUND: There is a paucity of data on the obstetrical outcomes of Canadian pregnant patients with epilepsy, which may differ from the average Canadian pregnancy and from other populations of pregnant patients with epilepsy. METHODS: Pregnant patients with epilepsy were identified from a prospectively collected database of patients seen at the maternal-fetal medicine obstetrics program of Mount Sinai Hospital (Toronto, Canada) between January 1, 2014, and November 20, 2020. Pregnancy, delivery, and neonatal outcome data were retrieved from this database and described using 95% binomial confidence intervals. Comparisons of obstetrical outcomes over the same period among the Canadian population average, obtained from publicly available national health data, were done using one-proportion Z-tests for nominal variables and one-sample t-tests for continuous variables. RESULTS: In total, 282 pregnancies, from 224 patients, were included, which resulted in 274 live births. Mean maternal age was 32.8 years (s.d. = 4.6; population average [µ] = 30.9; p < 0.01), and 53% were primiparous (CI95% = 49%-61%; µ = 43%; p < 0.01). The observed rates of obstetrical complications were gestational hypertension 9% (CI95%=6%-13%; µ=7%; p=0.19), gestational diabetes 5% (CI95% = 3%-8%; µ = 9%; p = 0.02), cesarean section 44% (CI95% = 38%-50%; µ = 28%; p < 0.01), postpartum hemorrhage 5% (CI95% = 3%-8%; µ = 0.5%; p < 0.01), stillbirth 1% (CI95% = 0%-2%; µ=1%; p > 0.99), and prematurity 9% (CI95% = 6%-13%; µ = 8%; p = 0.44). CONCLUSION: In this cohort of Canadian pregnant patients with epilepsy from an urban tertiary care center, observed rates of obstetrical complications were rare and no higher than in the Canadian population over the same period, with the exception of cesarean section and postpartum hemorrhage. Future prospective studies that include primary care and rural settings are needed to increase the generalizability of those results.

Mortality and cause of death in multiple sclerosis in western Norway 1950-2021: a registry-based linkage study.

BACKGROUND: Persons with multiple sclerosis (pwMS) have higher risk of mortality compared with the general population. Longitudinal studies are important for understanding the evolution of survival in pwMS. OBJECTIVE: Examine changes in mortality among pwMS during the past seven decades. METHODS: We followed pwMS from Hordaland and Møre and Romsdal in Western Norway, with disease onset from before 1950, identified from population-based epidemiological surveys and the Norwegian MS Registry and Biobank, until 1 January 2021. Data were linked to the Norwegian Cause of Death Registry to obtain underlying cause of death. We examined all-cause, and cause-specific mortality using standardised mortality ratios (SMR) and excess death rates (EDR). We calculated life expectancies and assessed survival stratified by sex, age and disease phenotype at onset. We compared hazard ratios (HRs) for mortality, in pwMS diagnosed before and after the era of disease-modifying treatment (DMT). RESULTS: Of 3624 pwMS, 964 (55.5% women) had died, predominantly of multiple sclerosis (49.0%). Median life expectancy for pwMS was 74.3 years (95% CI 73.3 to 75.3), compared with 83.1 years for the general population (p<0.001). From disease onset, pwMS survived 14.6 years shorter than the general population (p<0.001). Overall, SMR was 2.3 (95% CI 2.13 to 2.42) and EDR was 6.8 (95% CI 6.42 to 7.09) for pwMS. Treatment-eligible pwMS diagnosed in the DMT era had the lowest risk of mortality, HR 0.49 (95% CI 0.34 to 0.70,p<0.001). CONCLUSION: Excess mortality among pwMS declined during the past seven decades, possibly due to improved diagnostics, better symptomatic treatment and access to DMTs.

Risk of stroke in multiple sclerosis and neuromyelitis optic spectrum disorder: a Nationwide cohort study in South Korea.

BACKGROUND: People with multiple sclerosis (MS) are more likely to develop stroke than those without. However, little is known about the association between neuromyelitis optica spectrum disorder (NMOSD) and the risk of stroke. We aimed to estimate the risk of stroke in patients with MS and NMOSD in South Korea. METHODS: Data from the Korean National Health Insurance between January 2010 and December 2017 were analysed. A total of 1541/1687 adult patients with MS/NMOSD, who were free of stroke were included. Matched controls were selected based on age, sex and the presence of hypertension, diabetes mellitus and dyslipidaemia. RESULTS: The risk of developing stroke was 2.78 times higher (adjusted HR (aHR), 95% CI 1.91 to 4.05) in patients with MS compared with controls matched by age, sex, hypertension, diabetes mellitus and dyslipidaemia. The risk of stroke in NMOSD was also higher than that in matched controls (aHR=1.69, 95% CI 1.10 to 2.61) and not statistically different from that of MS (p=0.216). The patients with MS had a higher risk for either of ischaemic or haemorrhagic stroke (HR=2.63 and 2.93, respectively), whereas those with NMOSD had a higher risk for ischaemic stroke (HR=1.60) with marginal statistical significance. CONCLUSIONS: The risk of stroke is increased in patients with MS and NMOSD and seemed comparable between the two conditions. This is the first study that estimates the risk of stroke in patients with MS and NMOSD within the same population.

Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: a two-phase study.

OBJECTIVE: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD). METHODS: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria. RESULTS: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD. CONCLUSIONS: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.

Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis.

OBJECTIVE: To quantify sex differences in activity and severity of multiple sclerosis (MS) and how it depends on disease duration and time since clinical onset. METHODS: All Danish citizens with onset of relapsing MS since 1996 who have received disease-modifying therapy have been followed with annual or biannual control visits with mandatory notification of the Danish Multiple Sclerosis Registry. Men and women were compared by the inverse probability of being female. Relapse rates and changes in the Expanded Disability Status Scale (EDSS) scores were analysed with weighted general linear models, and we used weighted Cox regression for HRs between men and women for different EDSS endpoints. RESULTS: We included 3028 men and 6619 women. The weighted female:male relapse rate ratio was 1.16 (95% CI: 1.10 to 1.22) but after age 50 years, the difference disappeared. The annualised increase in EDSS was 0.07 in men (95% CI: 0.05 to 0.08) and 0.05 in women (95% CI: 0.04 to 0.06); p=0.017. With women as reference, the HR for reaching EDSS 4 was 1.34 (95% CI: 1.23 to 1.45; p<0.001), and for reaching EDSS 6 it was 1.43 (95% CI: 1.28 to 1.61; p<0.001). The diagnostic delay did not differ significantly between the sexes. CONCLUSION: Women have more inflammatory disease activity in terms of relapses than men up to the age of menopause indicating that sex hormones may play a role. Men are more subject to the neurodegenerative component of MS than women, particularly after the age of 45 years.

Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry.

BACKGROUND: Early recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time. OBJECTIVE: To identify early predictors of rapid disability accrual in patients with paediatric-onset MS. METHODS: Using the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data. RESULTS: 672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15-17) years. Older age at symptom onset (exp(ß)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)). CONCLUSIONS: A relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening.