Multiple Sclerosis In Individuals Research Articles

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.

Impact of adult-onset multiple sclerosis on MRI-based intracranial volume: A study in clinically discordant monozygotic twins

ObjectiveIntracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. MethodsFSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. Results54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10−5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). ConclusionWe offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.

Podcast on Identifying and Understanding Barriers to Care in Underserved Populations With MS in the United States.

Multiple sclerosis (MS) can affect people from all racial and ethnic backgrounds, but, historically, the incidence of MS in the United States was thought to be highest in White individuals. More recent data suggest that the incidence of MS in Black or African American individuals is comparable to that in White individuals. In Hispanic or Latino individuals, incidence of MS is lower, but age of onset may be earlier compared with White individuals. Additionally, there are important differences in MS disease severity, disease progression, and mortality in Black or African American and Hispanic or Latino populations. Compared with their White counterparts, individuals from these underrepresented groups are more likely to be affected by MS in specific areas of the nervous system, such as accelerated loss of retinal and brain tissue in Black or African American individuals and optic neuritis in Hispanic individuals. Additionally, Black or African American individuals with MS tend to have an aggressive disease course, earlier disability, and higher risk of requiring ambulatory assistance. Although these differences may be attributed to genetic factors, systemic racism and biases and barriers to accessing care may perpetuate health disparities. Moreover, non-White communities remain broadly underrepresented in clinical trials; however, it is vital that these populations are appropriately represented so that any potential differences in drug efficacy or safety implications are detected. Thus, it is important to increase awareness of MS in these populations. In this podcast, the authors discuss characteristics of MS in Black or African American and Hispanic or Latino populations, identify barriers to care, and propose solutions to improve access to MS care in these populations. MP4 (358385 KB).

On possible practical applications of the gut microbiome research in the prevention, diagnosis, assessment of, and treatment modification for multiple sclerosis in patients from risk groups

Research into the gut microbiota (GM) in multiple sclerosis (MS) has the potential to lead to a number of practical applications in the prevention, diagnosis, assessment of, and treatment modification for, MS. Four most promising areas include biomarkers, treatment personalization, drug development as well as disease prevention and mitigation. Changes in the GM have been observed in individuals with MS; analysis of the GM composition may help to identify individuals at risk of developing the disease or to monitor disease progression. Dietary interventions aimed at improving gut health could be used as a complementary approach to traditional MS treatments in order to reduce inflammation thereby potentially improving MS symptoms and lessening disease progression. Differences in the GM between individuals with MS suggest that personalized treatment approaches based on an individual's microbiome composition could be effective. Manipulating the GM could therefore be a potential avenue for drug development in MS. In addition, the exploration of bacteria or bacterial metabolites as therapeutic agents to modulate the immune system and reduce inflammation is also promising. Such explorations may even help identify strategies for preventing the development of MS in at-risk individuals. Overall, practical applications of gut microbiome research in MS are still in the early stages and further research is needed to fully understand the mechanisms underlying the relationship between the gut microbiome and MS and to determine the most effective interventions for improving gut health in individuals with the disease.

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome

Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. To determine the time to onset of symptoms consistent with MS. From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. ClinicalTrials.gov Identifier: NCT03122652.

Childbirth delivery mode and the risk of multiple sclerosis: a prospective population-based study

BackgroundCaesarean section (CS) may affect the risk of developing multiple sclerosis (MS) in the offspring, possibly through changes in gut microbiota composition, but findings from previous studies are inconsistent. We...

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.

Advanced central nervous system imaging biomarkers in radiologically isolated syndrome: a mini review.

Radiologically isolated syndrome is characterised by central nervous system white-matter hyperintensities highly suggestive of multiple sclerosis in individuals without a neurological history of clinical demyelinating episodes. It probably represents the pre-symptomatic phase of clinical multiple sclerosis but is poorly understood. This mini review summarises our current knowledge regarding advanced imaging techniques in radiologically isolated syndrome that provide insights into its pathobiology and prognosis. The imaging covered will include magnetic resonance imaging-derived markers of central nervous system volumetrics, connectivity, and the central vein sign, alongside optical coherence tomography-related metrics.

Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region

Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources. To calculate the US prevalence of MS in Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White individuals (hereafter referred to as White) stratified by age, sex, and region. A validated algorithm was applied to private, military, and public (Medicaid and Medicare) administrative health claims data sets to identify adult cases of MS between 2008 and 2010. Data analysis took place between 2019 and 2022. The 3-year cumulative prevalence overall was determined in each data set and stratified by age, sex, race, ethnicity, and geography. The insurance pools included 96 million persons from 2008 to 2010. Insurance and stratum-specific estimates were applied to the 2010 US Census data and the findings combined to calculate the 2010 prevalence of MS cumulated over 10 years. No exclusions were made if a person met the algorithm criteria. Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution. A total of 744 781 persons 18 years and older were identified with MS with 564 426 cases (76%) in females and 180 355 (24%) in males. The median age group was 45 to 54 years, which included 229 216 individuals (31%), with 101 271 aged 18 to 24 years (14%), 158 997 aged 35 to 44 years (21%), 186 758 aged 55 to 64 years (25%), and 68 539 individuals (9%) who were 65 years or older. White individuals were the largest group, comprising 577 725 cases (77%), with 80 276 Black individuals (10%), 53 456 Hispanic individuals (7%), and 33 324 individuals (4%) in the non-Hispanic other category. The estimated 2010 prevalence of MS per 100 000 US adults cumulated over 10 years was 161.2 (95% CI, 159.8-162.5) for Hispanic individuals (regardless of race), 298.4 (95% CI, 296.4-300.5) for Black individuals, 374.8 (95% CI, 373.8-375.8) for White individuals, and 197.7 (95% CI, 195.6-199.9) for individuals from non-Hispanic other racial and ethnic groups. During the same time period, the female to male ratio was 2.9 overall. Age stratification in each of the racial and ethnic groups revealed the highest prevalence of MS in the 45- to 64-year-old age group, regardless of racial and ethnic classification. With each degree of latitude, MS prevalence increased by 16.3 cases per 100 000 (95% CI, 12.7-19.8; P < .001) in the unadjusted prevalence estimates, and 11.7 cases per 100 000 (95% CI, 7.4-16.1; P < .001) in the direct adjusted estimates. The association of latitude with prevalence was strongest in women, Black individuals, and older individuals. This study found that White individuals had the highest MS prevalence followed by Black individuals, individuals from other non-Hispanic racial and ethnic groups, and Hispanic individuals. Inconsistent racial and ethnic classifications created heterogeneity within groups. In the United States, MS affects diverse racial and ethnic groups. Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers.

Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.

Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of ∼500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.

Epstein-Barr virus and multiple sclerosis: moving from questions of association to questions of mechanism.

The link between Epstein-Barr virus (EBV) and multiple sclerosis (MS) has puzzled researchers since it was first discovered over 40 years ago. Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS. Early MS disease is characterised by episodic neuroinflammation and focal lesions in the central nervous system (CNS) that over time develop into progressive neurodegeneration and disability. Risk of MS is vanishingly low in EBV seronegative individuals, history of infectious mononucleosis (acute symptomatic primary infection with EBV) significantly increases risk and elevated antibody titres directed against EBV antigens are well-characterised in patients. However, the underlying mechanism - or mechanisms - responsible for this interplay remains to be fully elucidated; how does EBV-induced immune dysregulation either trigger or drive MS in susceptible individuals? Furthermore, deep understanding of virological and immunological events during primary infection and long-term persistence in B cells will help to answer the many questions that remain regarding MS pathogenesis. This review discusses the current evidence and mechanisms surrounding EBV and MS, which have important implications for the future of MS therapies and prevention.

Quantitative Meta-analyses of Cognitive Abilities in Children With Pediatric-onset Multiple Sclerosis.

Pediatric-onset multiple sclerosis (POMS), is the manifestation of multiple sclerosis in individuals before 18years of age. About a third of children with POMS show some form of lower cognitive performance. The purpose of this study is to examine using quantitative meta-analyses the effect size of altered performance between children with and without POMS on overall intelligence quotient (IQ), information processing speed, and language functions. We searched the literature for studies that reported scores on cognitive tests administered to children with and without POMS. Studies were systematically reviewed using PRISMA guidelines. We analyzed data from 14 studies that examined 1283 children with and without POMS when cognitive categories consisted of five or more studies. Effect sizes, publication bias and potential confounds were considered. Significant cognitive differences are revealed for all categories with the strongest effect observed for overall IQ. A moderate effect is observed for information processing speed, and small effects for verbal fluency and verbal memory. Cognitive abilities present differently in children with POMS and a better understanding of this manifestation will inform intervention and remediation tools that can improve clinical and educational practice for the benefit of children with POMS.

The health effects of vitamin D supplementation: evidence from human studies.

Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration <30 nmol/l) should be corrected, whereas most guidelines recommend serum 25OHD concentrations of >50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected.

Clinical predictors of the benign course of multiple sclerosis in a medically underserved population

Benign multiple sclerosis (MS) is characterized by little disability accumulation over the disease course. The majority of contributions to understanding the predictors of benign MS come from high-income areas; it is unknown whether the same predictors can be derived from the resource-limited populations that have limited access to proper diagnostics and management. We aimed to study clinical predictors of benign MS in individuals with relapsing-remitting (RR) course coming from underserved areas.

Evaluation of Month of Birth in Neuromyelitis Optica Spectrum Disorders (NMSOD) and Multiple Sclerosis (MS).

Introduction Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMO) are chronic immune-mediated diseases in the central nervous system (CNS). Environmental factors such as month of birth can be a trigger for these diseases. Therefore, we conducted this study to compare the months of birth in MS and NMOSD patients with the control group. Methods In this cross-sectional study, 2345 patients with MS, 220 NMOSD patients, and 2174 healthy subjects were enrolled. Demographic information such as age, sex, month of birth, and education in three groups was extracted from the database. The associations between month of birth and MS were studied by binary logistic regression with adjusting for the year of birth. Results There was a reduced birth rate in September-October in NMOSD (OR = 0.309, 95% CI: 0.150-0.636; p < 0.001) and MS patients (OR = 0.470, 95% CI: 0.374-0.591; p < 0.001) compared to the general population. The birth rate in March-April in MS was higher than the control group (OR = 1.613, 95% CI: 1.324-1.964; p < 0.001). There was no difference in the birth month distribution between the NMOSD and MS patients. No significant difference in MOB among different MS types was found. Conclusion Our findings showed a decreasing risk of NMOSD and MS in individuals born in the autumn months and an increasing MS risk in spring. More studies are required to elucidate the association between the month of birth and risk of MS and NMOSD and the seasonality factors.

Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans

Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.

Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis.

Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS. This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6years. The primary outcome measure was the conversion to MS. During clinical follow-up of 46 (26-58) months (median, 25%-75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow-up. Individuals with a pRNFL of 99µm or lower or a GCIP of 1.99mm3 or lower were at a 7.5- and 8.0-fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1µm decline in pRNFL. Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision-making in individuals with RIS.

Epidemiology of Pediatric-Onset Multiple Sclerosis: A Systematic Review of the Literature.

Multiple sclerosis onset in youth is increasingly recognized. A systematic review was conducted to assess incidence and prevalence of pediatric-onset multiple sclerosis, focusing on occurrence by age subgroups and disease course. A literature search for the period 1965-2018 was carried out, selecting population-based studies of multiple sclerosis in individuals aged 19 years and younger. Nineteen studies met inclusion criteria. One pediatric neurologist extracted the data. Overall incidence ranged from 0.05 (95% confidence interval 0.03-0.08) to 2.85 (95% confidence interval 2.83-2.86) per 100 000 children and overall prevalence from 0.69 (95% confidence interval 0.58-0.80) to 26.92 (95% confidence interval 26.61-27.23) per 100 000 children. Incidence increased with age. The female-male ratio increased from 1.2:1 in children <12 years old to 2.8:1 in children ≥12 years old. Ten studies (n=521 children) reported disease course. Seven studies found only relapsing-remitting disease and 3 studies found primary-progressive disease in 3.0% to 6.7%. Two secondary-progressive disease cases were identified. Epidemiologic data aid in understanding the magnitude of multiple sclerosis and its clinical phenotypes, for planning for new disease-modifying therapies in the pediatric population.

Association between polymorphisms of a folate - homocysteine - methionine - SAM metabolising enzyme gene and multiple sclerosis in a Polish population.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune disease with a still unknown aetiology. The main initial mechanism of demyelination and injury to the central nervous system (CNS) appears to be inflammation. Neurotoxicity induced by homocysteine (Hcy) may be a factor affecting this process. 5,10-methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in Hcy metabolism. It leads to Hcy remethylation to methionine. In the present study, we aimed to investigate a possible association between two variants of MTHFR gene in patients with MS in Poland and healthy individuals. In this study, we genotyped 174 relapsing-remitting MS patients and 186 healthy controls using the TaqMan technique. It was found that, regardless of the presence of a specific allele, the gender of MS patients affects age at the time of the clinical onset of the disease: in rs1801133 for the C allele and T, the average age was 35 years for women and 29 for men (p = 0.0004; p = 0.034 respectively). Similarly for the second polymorphism rs1801131 for the A allele and C, the average age was 35 years for women and 29 for men (p = 0.001; p = 0.01 respectively). No significant allelic / genotypic frequency differences have been observed between the studied groups (c.677C > T, CT/TT p = 0.719, p = 0.262; c.1298A > C, AC/CC of p = 0.686; p = 0.66). We found no association between polymorphisms of a folate-homocysteine-methionine-SAM metabolising gene enzyme and multiple sclerosis in a Polish population.

Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome.

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS.