Incidence Of Multiple Sclerosis Research Articles

Analysis of potential microRNA biomarkers for multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating autoimmune neurodegenerative disorder for which no specific blood biomarker is available. MicroRNAs (miRNAs) have been investigated for their diagnostic potential in MS. However, MS-associated miRNAs are rarely replicated in different MS populations, thus impeding their use in clinical testing. Here, we evaluated the fold expression of seven reported MS miRNAs associated with MS incidence and clinical characteristics in 76 MS patients and 75 healthy control plasma samples. We found miR-23a-3p to be upregulated in relapsing-remitting MS (RRMS), while miR-326 was downregulated. MiR-150-5p and -320a-3p were significantly downregulated in secondary progressive MS (SPMS) patients compared to RRMS. High disability was associated with low miR-320a-3p, whereas low BDNF levels were associated with upregulation of miR-150-5p and downregulation of miR-326 expression in the total cohort. MiR-23a-3p and miR-326 showed significant diagnostic sensitivity, specificity, and accuracy for RRMS diagnosis. In addition, miR-150-5p and miR-320a-3p had comparable significant diagnostic test performance metrics distinguishing SPMS from RRMS. Therefore, there is potential for including miR-23a-3p and miR-326 in an RRMS diagnostic miRNA panel. Moreover, we have shown that miR-150-5p and miR-320a-3p could be novel RRMS conversion to SPMS biomarkers. The use of these miRNAs in MS diagnosis and prognosis warrants further investigation.

Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis

BackgroundDifferences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence. To address that, we conducted a gene expression analysis in female and male human spleen and identified the transmembrane protein CD99 as one of the most significantly differentially expressed genes with marked increase in men. CD99 has been reported to participate in immune cell transmigration and T cell regulation, but sex-specific implications have not been comprehensively investigated.MethodsIn this study, we conducted a gene expression analysis in female and male human spleen using the Genotype-Tissue Expression (GTEx) project dataset to identify differentially expressed genes between women and men. After successful validation on protein level of human immune cell subsets, we assessed hormonal regulation of CD99 as well as its implication on T cell regulation in primary human T cells and Jurkat T cells. In addition, we performed in vivo assays in wildtype mice and in Cd99-deficient mice to further analyze functional consequences of differential CD99 expression.ResultsHere, we found higher CD99 gene expression in male human spleens compared to females and confirmed this expression difference on protein level on the surface of T cells and pDCs. Androgens are likely dispensable as the cause shown by in vitro assays and ex vivo analysis of trans men samples. In cerebrospinal fluid, CD99 was higher on T cells compared to blood. Of note, male MS patients had lower CD99 levels on CD4+ T cells in the CSF, unlike controls. By contrast, both sexes had similar CD99 expression in mice and Cd99-deficient mice showed equal susceptibility to experimental autoimmune encephalomyelitis compared to wildtypes. Functionally, CD99 increased upon human T cell activation and inhibited T cell proliferation after blockade. Accordingly, CD99-deficient Jurkat T cells showed decreased cell proliferation and cluster formation, rescued by CD99 reintroduction.ConclusionsOur results demonstrate that CD99 is sex-specifically regulated in healthy individuals and MS patients and that it is involved in T cell costimulation in humans but not in mice. CD99 could potentially contribute to MS incidence and susceptibility in a sex-specific manner.

Proportion of Life Spent in Canada and the Incidence of Multiple Sclerosis in Permanent Immigrants.

While immigrants to high-income countries have a lower risk of multiple sclerosis (MS) compared with host populations, it is unknown whether this lower risk among immigrants increases over time. Our objective was to evaluate the association between proportion of life spent in Canada and the hazard of incident MS in Canadian immigrants. We conducted a population-based retrospective cohort study in Ontario, using linked health administrative databases. We followed immigrants, who arrived in Ontario between 1985 and 2003, from January 1, 2003, to December 31, 2016, to record incident MS using a validated algorithm based on hospital admission or outpatient visits. We derived proportion of life spent in Canada based on age at arrival and time since immigration obtained from linked immigration records. We used multivariable proportional hazard models, adjusting for demographics and comorbidities, to evaluate the association between proportion of life in Canada and the incidence of MS, where proportion of life was modelled using restricted cubic spline terms. We further evaluated the role of age at migration (15 or younger vs older than 15 years), sex, and immigration class in sensitivity analyses. We included 1.5 million immigrants (49.9% female, mean age 35.9 [SD 14.2] years) who had spent a median of 20% (Q1-Q3 10%-30%) of their life in Canada. During a mean follow-up of 13.9 years (SD 1.0), 934 (0.44/100,000 person-years) were diagnosed with MS. Compared with the median, a higher risk of MS was observed at higher values of proportion of life spent (e.g., hazard ratio [70% vs 20% proportion of life] 1.38; 1.07-1.78). This association did not vary by sex (p(sex × proportion of life) = 0.70) or immigration class (p(immigration class × proportion of life) = 0.13). The results did not vary by age at migration but were statistically significant only at higher values of proportion of life for immigrants aged 15 years or younger at arrival. The risk of incident MS in immigrants varied with the proportion of life spent in Canada, suggesting an acculturation effect on MS risk. Further work is required to understand environmental and sociocultural factors driving the observed association.

Trend control charts for multiple sclerosis case definitions

IntroductionThe validity of chronic disease case definitions for administrative health data may change over time due to changes in data quality. Trend control charts to identify out-of-control (OOC; i.e., unexpected) observations in a time series may indicate where disease estimates are influenced by changes in data quality. ObjectiveApply and compare trend control charts methods for multiple sclerosis (MS) incidence and prevalence estimates using previously-validated case definitions for Manitoba, Canada. MethodsEight case definitions were identified from published literature and applied to Manitoba administrative health data from January 1, 1972 to December 31, 2018. Incidence and prevalence trends were modeled using negative binomial and generalized estimating equation models, respectively. Trend control charts were used to plot predicted case counts against observed case counts. Control limits to identify OOC observations were calculated using two methods: predicted case count ±0.8*standard deviation (0.8*SD) and predicted case count ±2*standard deviation (2*SD). Differences in proportion of OOC observations across case definitions was assessed using McNemar's test. ResultsThe proportion of OOC observations ranged from 0.71 to 0.90 for incidence and 0.72 to 0.98 for prevalence when using the 0.8*SD control limits. A lower proportion of OOC observations (0.46 to 0.74 for incidence; 0.30 to 0.74 for prevalence) was observed for the 2*SD control limits. Neither method resulted in significant differences in OOC observations across case definitions. ConclusionsThe proportion of OOC observations in trend control charts varied with the control limit method adopted, but statistical significance did not. Trend control charts are a potentially useful tool for developing surveillance methods, but may benefit from disease-specific calibrated control limits.

Could ancient Yamnaya dairying explain the environmental component of multiple sclerosis?

On January 10th, 2024, Barrie et al. published a landmark paper identifying the ancestral European origin of the high-risk, multiple sclerosis (MS) allele, HLA-DRB1*15:01. The authors hypothesize that Bronze Age, Yamnaya migration to, and their population of Scandinavia and the British Isles, accounts for the high incidence of MS in these regions, stemming from the geographical spread of HLA-DRB1*15:01 as evidenced by their data. These data further indicate that this immune-related allele likely underwent positive-selection pressures, suggesting that HLA-DRB1*15:01 may have conferred increased immunological resistance to zoonotic pathogens that the Yamnaya would have been exposed to from a lifestyle of sheep, goat, and cattle herding, as well as from the prevalent consumption of dairy products harvested from these animals. We wish to expand the scope of the Barrie et al. hypothesis to include the other gene that emerged in their extensive genomic analysis; the lactase persistence allele, LCT/MCM6, which allows adults to consume milk beyond childhood without adverse physical effects. We propose that, in addition to the Yamnaya spread of HLA-DRB1*15:01, their spread of LCT/MCM6 engendered a cultural propensity for milk consumption that may play a significant role in the present-day, global distribution of MS. Specifically, we hypothesize that lactose tolerance, and the prominent dairy consumption it enables, may expose individuals to the enteric, dairy-animal pathogen, Clostridium perfringens type B/D and its Epsilon neurotoxin that targets the precise brain tissues damaged during each MS relapse.

An autoantibody signature predictive for multiple sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster in approximately 10% of PwMS who share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS. Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active preclinical period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid and serum, where it is highly specific for patients eventually diagnosed with MS. This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes.

Prevalence and incidence of multiple sclerosis in Turkey: A nationwide epidemiologic study.

Many studies on multiple sclerosis (MS) reveal different prevalence and epidemiologic results. In this study, we aimed to determine the epidemiologic profile of MS using official health records in Turkey. Patients diagnosed with MS from the official health data of the Ministry of Health, representing the entire population of Turkey, were included in the study. Prevalence and incidence calculations were performed using the data on gender, age, year of birth, city of residence, and year of diagnosis. As a result of the study, the number of patients with the ICD code G35 was determined as 201,061 and the number of patients with this code entered at least three times was determined as 82,225. The prevalence of MS in Turkey was calculated as 96.4 per 100,000 and the female/male ratio as 2.1/1. The incidence of MS in 2022 was 6.2 per 100,000 and the mean patient age was 43.1 ± 13.3 years (female: 43.0 ± 13.1 vs male: 43.2 ± 13.7) while the mean age at first diagnosis was 34.0 ± 13.0 (female: 33.6 ± 12.6 vs male: 34.9 ± 13.7). The research was conducted via Official Database of Turkey, which includes population of 85 million and provides valuable insights into the prevalence and incidence rates of this chronic disease.

Ethnic Disparities in the Incidence and Prevalence of Multiple Sclerosis (P4-6.018)

Ethnic Disparities in the Incidence and Prevalence of Multiple Sclerosis (P4-6.018)

Annual incidence of Multiple Sclerosis in a large Health Care System in the US from 2014 to 2020 (P11-6.003)

Annual incidence of Multiple Sclerosis in a large Health Care System in the US from 2014 to 2020 (P11-6.003)

Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review.

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

The burden of neurological conditions in north Africa and the Middle East, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019

The burden of neurological conditions in north Africa and the Middle East is increasing. We aimed to assess the changes in the burden of neurological conditions in this super-region to aid with future decision making. In this analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 data, we examined temporal trends of disability-adjusted life-years (DALYs; deaths and disabilities combined), deaths, incident cases, and prevalent cases of 14 major neurological conditions and eight subtypes in 21 countries in the north Africa and the Middle East super-region. Additionally, we assessed neurological DALYs due to 22 potentially modifiable risk factors, within four levels of classification, during the period 1990-2019. We used a Bayesian modelling estimation approach, and generated 95% uncertainty intervals (UIs) for final estimates on the basis of the 2·5th and 97·5th percentiles of 1000 draws from the posterior distribution. In 2019, there were 441·1 thousand (95% UI 347·2-598·4) deaths and 17·6 million (12·5-24·7) neurological DALYs in north Africa and the Middle East. The leading causes of neurological DALYs were stroke, migraine, and Alzheimer's disease and other dementias (hereafter dementias). In north Africa and the Middle East in 2019, 85·8% (82·6-89·1) of stroke and 39·9% (26·4-54·7) of dementia age-standardised DALYs were attributable to modifiable risk factors. North Africa and the Middle East had the highest age-standardised DALY rates per 100 000 population due to dementia (387·0 [172·0-848·5]), Parkinson's disease (84·4 [74·7-103·2]), and migraine (601·4 [107·0-1371·8]) among the global super-regions. Between 1990 and 2019, there was a decrease in the age-standardised DALY rates related to meningitis (-75·8% [-81·1 to -69·5]), tetanus (-88·2% [-93·9 to -76·1]), stroke (-32·0% [-39·1 to -23·3]), intracerebral haemorrhage (-51·7% [-58·2 to -43·8]), idiopathic epilepsy (-26·2% [-43·6 to -1·1]), and subarachnoid haemorrhage (-62·8% [-71·6 to -41·0]), but for all other neurological conditions there was no change. During 1990-2019, the number of DALYs due to dementias, Parkinson's disease, multiple sclerosis, ischaemic stroke, and headache disorder (ie, migraine and tension-type headache) more than doubled in the super-region, and the burden of years lived with disability (YLDs), incidence, and prevalence of multiple sclerosis, motor neuron disease, Parkinson's disease, and ischaemic stroke increased both in age-standardised rate and count. During this period, the absolute burden of YLDs due to head and spinal injuries almost doubled. The increasing burden of neurological conditions in north Africa and the Middle East accompanies the increasing ageing population. Stroke and dementia are the primary causes of neurological disability and death, primarily attributable to common modifiable risk factors. Synergistic, systematic, lifetime, and multi-sectoral interventions aimed at preventing or mitigating the burden are needed. Bill & Melinda Gates Foundation. For the Persian, Arabic and Turkish translations of the abstract see Supplementary Materials section.

Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003-2023.

Epstein-Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis. The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis. In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence. MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3-3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis. While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body's defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term.

Current opinion: Racial and ethnic health disparities in multiple sclerosis: considering the social determinants of health.

We discuss racial and ethnic disparities in multiple sclerosis (MS), outcomes, and social determinants of health (SDoH). We also provide essential considerations needed to bridge the gap in inequalities, including broader representation of racial and ethnic people in clinical trials and research in general and the inclusion of better measures of living conditions. The incidence and prevalence of MS have become more diverse in the USA. There is increased recognition that racial and ethnic health disparities and inequities exist due to adverse social conditions. Clinical trials have failed to be inclusive and diverse. Training in health disparity is an essential priority of funding sources, and designing clinical trials that consider the barriers these populations face can close significant gaps. The incidence, prevalence, and awareness of MS have seen an incline in diverse racial and ethnic populations. Health disparities exist in MS with Black, Hispanic, and indigenous populations appearing to have worse outcomes. SDoH play a significant role in causing these health disparities. Accessibility to clinical trials and treatment are barriers these populations face. Strategic and earnest interventions considering SDoH are critically needed to develop solutions that collectively improve health and MS care for all.

Inflammatory bowel disease is associated with an increase in the incidence of multiple sclerosis: a retrospective cohort study of 24,934 patients

BackgroundRecent data suggest a potential pathophysiological link between inflammatory bowel disease (IBD) and multiple sclerosis (MS), two immune-mediated diseases both of which can have a significant impact on patients' quality of life. In the present manuscript, we investigate the association between IBD and MS in a German cohort of general practice patients. These results may have important implications for the screening and management of patients with IBD, as well as for further research into the pathophysiological mechanisms underlying both disorders.Methods4,934 individuals with IBD (11,140 with Crohn’s disease (CD) and 13,794 with ulcerative colitis (UC)) as well as 24,934 propensity score matched individuals without IBD were identified from the Disease Analyzer database (IQVIA). A subsequent diagnosis of MS was analyzed as a function of IBD using Cox regression models.ResultsAfter 10 years of follow-up, 0.9% and 0.7% of CD and UC patients but only 0.5% and 0.3% of matched non-IBD pairs were diagnosed with MS, respectively (pCD = 0.002 and pUC < 0.001). Both CD (HR: 2.09; 95% CI 1.28–3.39) and UC (HR: 2.35; 95% CI 1.47–3.78) were significantly associated with a subsequent MS diagnosis. Subgroup analysis revealed that the association between both CD and UC and MS was more pronounced among male patients.ConclusionThe results of our analysis suggest a notable association between IBD and a subsequent MS diagnosis. These findings warrant further pathophysiological investigation and may have clinical implications for the screening of IBD patients in the future.

Epidemiological characteristics of multiple sclerosis in Stavropol region

Multiple sclerosis (MS) is a chronic autoimmune, infl ammatory and degenerative disease of the central nervous system and is the most common neurological disorder in young people.Purpose: to determine the clinical and epidemiological features of multiple sclerosis usig the example of the Stavropol region (SR).Materials and methods. A retrospective analysis of 655 medical records of patients for 2021–2022, hospitalized in the neurological department of a multidisciplinary hospital with a diagnosis of MS, was carried out. The age, gender, place of residence of the patient, age of onset of the disease, type of MS, degree of disability, and rate of disease progression were assessed. Statistical processing was carried out using Microsoft Excel and Statistica 10 software.Results. The incidence of MS during this period was 22.7 per 100,000 population. The share of women was 70.2%, men — 29.8%. Average age — 40.04 ± 10.8 years. The vast majority of cases of onset of MS (83.2%) occur between the ages of 21 and 50 years — 82.8% of women and 84% of men. When analyzing the severity of neurological defi cit, the average score on the extended Kurtzke scale of disability was 3.53 ± 1.7 points. The rate of progression was 1.21 ± 1.1 points per year, which corresponds to a fast pace. Among those hospitalized, 65.4% have a disability group: third — 41.9% (275 patients), second — 21.4% (140 patients), fi rst — 2.1% (14 patients).Conclusion. The Stavropol Territory is one of the regions with a moderate risk of developing multiple sclerosis. The results of the work may be useful in planning medical and social care in certain territories of this region.

Exploring Spinal Cord Changes in Multiple Sclerosis Patients Using MRI

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS). The diagnosis of MS is based on clinical signs and symptoms as well as findings in magnetic resonance imaging (MRI) sequences by demonstrating the spatial and temporal dispersion of white matter lesions, which are thought to be typical of MS in distribution, shape, extent, and signal abnormalities. Spinal cord MRI can identify asymptomatic lesions and rule out malignancies or spinal stenosis in patients for whom brain imaging is not helpful in making an MS diagnosis. This study examines the MRI features of Saudi Arabian patients clinically proven to have MS with typical lesions exclusively evident in the spinal cord. This retrospective cross-sectional study was carried out in 151 patients who are confirmed cases of MS based on clinical findings and MRI results. Patients’ MRI data were reviewed from the picture archiving and communication system (PACS). The study revealed that MS incidence was higher in females than males and that the number of people diagnosed with MS increased in middle age. Cervical cord plaques and cervical cord curve straightening were the most frequent changes (67% and 56%, respectively), indicating that MRI can complement and even replace clinical data in MS diagnosis, leading to earlier, more precise diagnoses and speedier starts to treatment.

The neurotropic schistosome vs experimental autoimmune encephalomyelitis: are there any winners?

The incidences of multiple sclerosis have risen worldwide, yet neither the trigger nor efficient treatment is known. Some research is dedicated to looking for treatment by parasites, mainly by helminths. However, little is known about the effect of helminths that infect the nervous system. Therefore, we chose the neurotropic avian schistosome Trichobilharzia regenti, which strongly promotes M2 polarization and tissue repair in the central nervous system, and we tested its effect on the course of experimental autoimmune encephalomyelitis (EAE) in mice. Surprisingly, the symptoms of EAE tended to worsen after the infection with T. regenti. The infection did not stimulate tissue repair, as indicated by the similar level of demyelination. Eosinophils heavily infiltrated the infected tissue, and the microglia number increased as well. Furthermore, splenocytes from T. regenti-infected EAE mice produced more interferon (IFN)-γ than splenocytes from EAE mice after stimulation with myelin oligodendrocyte glycoprotein. Our research indicates that the combination of increased eosinophil numbers and production of IFN-γ tends to worsen the EAE symptoms. Moreover, the data highlight the importance of considering the direct effect of the parasite on the tissue, as the migrating parasite may further tissue damage and make tissue repair even more difficult.

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.

Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07–1.55, P < 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5–7%, lowest risk quartile) to 41% (95%CI 33–49%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy.

COVID-19 and multiple sclerosis: is there a connection?

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which is based on inflammatory demyelination and neurodegeneration. Over the course of the COVID-19 pandemic, there has been a perception that the virus has an effect on the course of immune processes. The questions of whether the frequency of autoimmune diseases, including the nervous system, and their course has changed have been discussed. Aim of the study was to assess the clinical and epidemiological characteristics of MS during the COVID-19 pandemic from 01.01.2020 to 01.01.2023 in Novosibirsk. In the course of our work, we studied the incidence of MS and the features of the clinical picture of the debut of MS associated with COVID-19 infection. Material and methods. The study included 628 patients with MS living in Novosibirsk with the onset of the disease in the period before the pandemic from 01.01.2017 to 12/31/2019 (341 patients) and during the pandemic from 01.01.2020 to 01.1.2023 (287 patients). Results. The incidence rates of MS in Novosibirsk were calculated, it was 7.1 7.6 6.4 7.38 6.92 and 3.2 per 100 thousand population in 2017, 2018, 2019, 2020, 2021 and 2020, respectively. The average incidence of MS in the study period before the pandemic was 7.03 per 100 thousand population, during the pandemic – 5.83 per 100 thousand population (critical value of the Student’s t-test = 1.972, with a significance level of a = 0.05). When analyzing the association of clinical manifestations of the onset of MS with COVID-19, it was found that coordination disorders were observed in patients with moderate infection more often than in patients with mild infection (p &lt; 0.05; odds ratio 0.410, 95% confidence interval 0.162–1.035). No statistically significant correlation of clinical manifestations with the severity of infection was shown for patients with primary progressive MS, however, the predominance of the multi-focal nature of disease after a more severe course of COVID-19 was noted (40 %). After the first clinical demyelinating episode in the group of patients with relapsing-remitting MS, the chances of complete recovery in patients with mild infection are 2.8 times higher than in patients with moderate infection (p &lt; 0.05). Conclusions. Thus, as a result of the conducted study, the effect of COVID-19 on the change in the incidence of MS was not revealed. In the process of analyzing the clinical features of MS during the pandemic, it was found that COVID-19 infection can contribute to an unfavorable course of MS with worse recovery of neurological deficits after episodes of exacerbations, which leads to the accumulation of disability of patients.