A comparison of multiple sclerosis disease characteristics across three genetically diverse Asian racial groups in Singapore.

Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups-Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.

Familial vs sporadic multiple sclerosis in the Israeli population: Differences in ethnicity distribution and disease progression, with anticipation in successive generations.

BACKGROUND: Multiple Sclerosis (MS) may cluster in families, an entity known as familial MS (FMS), possibly due to aggregation of genetic and environmental factors. Though previous studies have characterized FMS in different populations, no study to the best of our knowledge has yet characterized FMS in the unique Israeli population, which is comprised of relatively endogamous ethnicities. Our goal in this study was to compare demographic and clinical characteristics between FMS and sporadic MS (SMS), and to search for intra-familial patterns. METHODS: In a retrospective study of 101 FMS patients and 508 SMS patients, ethnicity and sex distribution was assessed. Clinical aspects were compared between 172 paired FMS and SMS patients, matched for sex, age and ethnicity, and between generations of the FMS cohort. RESULTS: Females comprised 75.3 % of FMS and 67.5 % of SMS patients (p = 0.1). Ethnic distribution was significantly different between FMS and SMS (p = 0.014), with the former comprising a higher proportion of Christian-Arabs (15.4% vs. 5.1 %, p = 0.004) and lower proportion of Jews (60% vs. 74.2 %, p = 0.016). Age at disease onset or diagnosis, frequency of positive Oligoclonal bands and comorbidity of other autoimmune/inflammatory disease or chronic diseases was comparable between FMS and SMS, yet motor symptoms at onset were more prevalent in FMS (34% vs. 20 %, p = 0.02). Annualized relapse rates throughout 10 years from onset were comparable. Among FMS, mean Expanded-Disability-Status-Scale (EDSS) and slope of deterioration in EDSS over 20 years from diagnosis were higher (p = 0.0004 and p = 0.023, respectively), time to EDSS ≥ 3 was shorter (7.1 vs. 12.1 years, HR 1.6, p = 0.036) and MS-Severity-Score (MSSS) was higher (3.84 vs. 2.95, p = 0.04), compared to SMS. Following adjustment for smoking, which tended to be higher among FMS patients (P = 0.06), mean EDSS and slope of deterioration in EDSS over 20 years remained significantly higher (p = 0.0006 and p = 0.025, respectively) in FMS, time to EDSS ≥ 3 tended to be higher (HR 1.5, p = 0.06), while MSSS was comparable. An inter-generational analysis of the total FMS cohort, as well as an intra-familial analysis, both adjusted for year of diagnosis, revealed significantly earlier age of onset (p < 0.0001 and p < 0.0001) and diagnosis (p = 0.001 and p < 0.0001) in the younger compared to the older generations, respectively. CONCLUSION: In this Israeli cohort, the proportions of specific ethnicities differ between FMS and SMS, indicating that FMS has a population-specific prevalence pattern, and that further investigation for susceptibility genes is warranted. Disease progression is faster in FMS patients and anticipation is observed in families with multiple cases of MS. Closer surveillance and application of a pro-active induction or early highly-effective therapeutic strategy for FMS patients should be considered, to reduce high disease activity and fast disability progression.

Traumatic brain injury, race, ethnicity and cognition in newly diagnosed persons with multiple sclerosis.

We sought to determine whether a history of traumatic brain injury (TBI) could explain the lower symbol digit modalities test (SDMT) scores observed among newly diagnosed multiple sclerosis (MS) and control participants identifying as Black or Hispanic versus white in the MS Sunshine Study (n = 1172). 330 (29.2 %) participants reported a history of ≥1 TBI. Accounting for TBI did not explain the significant independent associations between having MS, being Black or Hispanic and lower SDMT. The pervasive effects of systemic racism in the United States remain the best explanation for the lower SDMT scores observed in Black and Hispanic participants.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Prevalence and disease disability in immigrants with multiple sclerosis in Malmö, southern Sweden.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system and the major non-traumatic cause of permanent disability in young adults. Several migration studies have been performed over the years suggesting a pattern of higher disease disability in certain ethnic groups. To our knowledge, differences in disease progression in immigrants have not been studied in Sweden before. Thus, the aims of our study were to estimate the prevalence of multiple sclerosis among first-generation immigrants in the City of Malmö and to compare differences in disease severity with the native population. METHODS: All persons with multiple sclerosis living in Malmö on prevalence day 31 Dec 2010 were included. Cases were classified according to the country of birth into Scandinavians, Western and non-Western. RESULTS: The crude prevalence was 100/100,000 (95% CI, 80-124) among first-generation immigrants, 154/100,000 (95% CI, 137-173) among individuals with Scandinavian background, 123/100,000 (95% CI, 94-162) in the Western group and 76/100,000 (95% CI, 53-108) in the non-Western group. The mean Multiple Sclerosis Severity Score (MSSS) value among Scandinavians was 4.2 (SD 3.5), whereas the figures in the immigrant group were 4.6 (SD 3.3) and 5.2 (SD 3.7) among Westerns respectively non-Westerns, which differences were not statistically significant. When adjusting for gender, age at onset and initial disease course, the mean MSSS difference between the non-Western and the Scandinavian individuals was 1.7 (95% CI 0.18-3.3, p = 0.030). There were no differences on time to diagnosis or the time from diagnosis to treatment initiation between the three groups. CONCLUSIONS: We found a lower prevalence among Western and non-Western first-generation immigrants compared to the Scandinavian population and a more severe disease in non-Western immigrants than in Scandinavians.

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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

The role of ethnicity and native-country income in multiple sclerosis: the Italian multicentre study (MS-MigIT).

OBJECTIVE: Multiple sclerosis (MS) is a complex disorder in which environmental and genetic factors interact modifying disease risk and course. This multicentre, case-control study involving 18 Italian MS Centres investigated MS course by ethnicity and native-country economic status in foreign-born patients living in Italy. METHODS: We identified 457 MS patients who migrated to Italy and 893 age- and sex-matched native-born Italian patients. In our population, 1225 (93.2%) subjects were White Europeans and White Northern Americans (WENA) and 89 (6.8%) patients were from other ethnical groups (OEG); 1109 (82.1%) patients were born in a high-income (HI) Country and 241 (17.9%) in a low-middle-income (LMI) Country. Medical records and patients interviews were used to collect demographic and disease data. RESULTS: We included 1350 individuals (973 women and 377 men); mean (SD) age was 45.0 (11.7) years. At onset, 25.45% OEG patients vs 12.47% WENA (p = 0.039) had > 3 STIR spine lesions. At recruitment, the same group featured mean (SD) EDSS score of 2.85 (2.23) vs 2.64 (2.28) (p = 0.044) reached in 8.9 (9.0) vs 12.0 (9.0) years (p = 0.018) and underwent 1.10 (4.44) vs. 0.99 (0.40) annual MRI examinations (p = 0.035). At disease onset, patients from LMI countries had higher EDSS score than HI patients (2.40 (1.43) vs 1.99 (1.17); p = 0.032). DISCUSSION: Our results suggested that both ethnicity and socio-economic status of native country shape MS presentation and course and should be considered for an appropriate management of patients. To the best of our knowledge, this is the first study reporting on the impact of ethnicity in MS at an individual level and beyond an ecological population-perspective.

Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial.

BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population. METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya. RESULTS: A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI. CONCLUSION: BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS. GOV IDENTIFIER: NCT04377555.

Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population.

The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.

Signaling through the S1P-S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment.

Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1-5 (S1PR1-5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut-brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P-S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.

Health Disparities, Inequities, and Social Determinants of Health in Multiple Sclerosis and Related Disorders in the US: A Review.

Importance: There is empirical evidence that social determinants of health (SDOH) impact health outcomes in Black and Hispanic and Latinx individuals in the US. Recently, SDOH have risen to the top as essential intervention targets that could help alleviate racial and ethnic disparities. Neuromyelitis optica spectrum disorder (NMOSD) disproportionately affects Black individuals, and multiple sclerosis (MS) has seen a recent shift in select racial groups. It is unclear to what degree SDOH have been investigated and contribute to racial and ethnic health disparities and inequities. Observations: This narrative review provides a contemporary synthesis of SDOH associated with racial and ethnic health disparities and inequities in MS, NMOSD, and other autoimmune disorders, such as myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. These immune-mediated neurological diseases were chosen for their capacity to be a high burden to society and because of complementary SDOH-associated challenges among minority populations. A paucity of research addressing inequities and the role of SDOH in MS and NMOSD was noted despite findings that Black individuals have a higher risk of developing MS or NMOSD and associated mortality compared with White individuals. Greater health disparities were also found for those with lower income and education, lower health literacy, and negative illness perceptions in MS. No studies in MOG-Ab disorders were found. Conclusions and Relevance: Increased efforts are needed to better understand the role of SDOH in racial and ethnic health disparities and inequities in MS, NMOSD, and emerging autoimmune disorders. This includes developing research frameworks aimed at understanding the magnitude and interrelationships of SDOH to better develop system-based multilevel interventions across the spectrum of care for these neurological conditions.

Association of Disease Severity and Socioeconomic Status in Black and White Americans With Multiple Sclerosis.

OBJECTIVE: To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BAs) and White Americans (WAs) and to evaluate the role of socioeconomic status. METHODS: We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics, including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit zip codes. RESULTS: Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or to be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs mild disability, 95% confidence interval [CI] 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, 95% CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96), and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BAs. CONCLUSION: We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors; developing optimal treatment strategies among BAs with MS is warranted.

Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population.

Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.

IFN-γ and TNF-α Gene Polymorphisms in Multiple Sclerosis Patients in Northwest Iran.

BACKGROUND: Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking a role in autoimmune diseases, including multiple sclerosis (MS), which may induce inappropriate immune responses. OBJECTIVE: The aim of this study was to investigate the allelic and genotypic frequencies of interferon gamma gene (IFN-γ) at +874A/T locus and tumor necrosis factor (TNF-α) at+308A/G locus in MS patients of Azeri population. METHODS: At first, a questionnaire was prepared for each of 240 healthy, non-relative, and 152 Azeri MS patients before obtaining the blood sample from all subjects. After DNA extraction, the frequency of alleles and genotypes of the IFN-γ and TNF-α genes at +874A/T and -308G/A loci, respectively, were determined by allele-specific PCR method. Finally, the frequencies were compared between control and MS patients by chi-square test (x2-test) and p<0.05 was considered significant. RESULTS: In the IFN-γ +874A/T gene single nucleotide polymorphism (SNP), the most allelic and genotypic frequencies in MS patients were the A allele, 55.26% (p=0.04) and the AT genotype, 52.63% (p=0.048). In healthy individuals, it was 65.42% for the A allele and 45.42% for the AA genotype. For the TNF-α 308 G/A SNP, the highest allelic and genotypic frequencies in MS patients were the G allele with 55.92% (p<0.001) and AG genotype with 61.84%, and in healthy subjects, the allelic and genotypic frequencies were 84.2% and 70.8% for the G allele and GG genotype, respectively. CONCLUSION: Head trauma, the infection with the herpes virus and Mycoplasma pneumonia, frequent colds and high consumption of canned foods provide grounds for MS. The T allele in the IFN-γ gene (+874) and the genotypes of AA and AG at the TNF-α gene (-308) at the position-308 were considered as potential risk factors for MS. Therefore, the polymorphisms in cytokine genes and following changes in their expression levels can be effective in susceptibility to MS.

Assessment of Racial/Ethnic Disparities in Volumetric MRI Correlates of Clinical Disability in Multiple Sclerosis: A Preliminary Study.

BACKGROUND AND PURPOSE: Although global and regional brain volume has been established as a relevant measure to define and predict multiple sclerosis (MS) severity, characterization of specific trends by race/ethnicity is currently lacking. We aim to (1) characterize racial disparities in disability-specific patterns of brain MRI volumetric measures between Hispanic and Caucasian individuals with MS and (2) explore the relevance of these measures as predictors of clinical disability progression. METHODS: Brain MRI scans from 94 Hispanic and 94 age- and gender-matched Caucasian MS patients were analyzed using automatic and manual segmentation techniques. Select global and regional volume measures were correlated to Expanded Disability Status Scale (EDSS) scores at baseline and subsequent follow-up visits. RESULTS: Hispanic patients had a higher baseline median EDSS score (interquartile range [IQR], 2.0; [1.0-3.5]) compared to Caucasians (median [IQR], 1.0 [.0-2.0]) and an increased risk of requiring ambulatory assistance (hazard ratio [HR], 9.7; 95% confidence interval [CI], 2.8-32.5). Normalized thalamic volume was moderately associated with EDSS scores (rs   = -.42,  P < .001 in Hispanics; rs   = -.32, P  = .002 in Caucasians) and was the best predictor of sustained disability worsening in both racial groups in a time-to-event analysis. CONCLUSIONS: The confounding impact of race on quantitative brain volume measures may affect the interpretation of outcome measures in MS clinical trials.

Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?

BACKGROUND: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. METHODS: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. RESULTS: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). CONCLUSION: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.

Interleukin 7 receptor T244I polymorphism and the multiple sclerosis susceptibility: a meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is recognized as the most prevalent chronic inflammatory neurological disorder diagnosed in young adults. Recent evidence suggests that the T244I polymorphism of the IL7Rα gene (rs6897932) May influence MS susceptibility; however, individual studies have provided conflicting and controversial results. Therefore, this meta-analysis was conducted to assess the association between the IL7R T244I polymorphism and the risk of MS. METHOD: An extensive search for published literature up to May 2019 was accomplished in the electronic databases, and 28 studies consisting of 16,260 MS patients and 18,335 controls were included. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to investigate the strength of association. RESULTS: The results of the present meta-analysis represented significant association between the IL7R T244I polymorphism and MS susceptibility. (recessive model: OR = 1.126, 95% CI 1.026-1.236, P = .012; dominant model: OR = 1.172, 95% CI 1.024-1.341, P = .021; homozygous model: OR = 1.213, 95% CI 1.038-1.417, P = .015; and allelic model: OR = 1.109, 95% CI 1.025-1.200, P = .010, respectively). In the subgroup analysis according to region, our findings showed significant association in Europe. However, no association was found in Middle East. CONCLUSION: The current meta-analysis demonstrated that the C allele of IL7R T244I polymorphism might be a risk factor for the MS susceptibility in Europe but not in Middle East.

Socioeconomic status and race are correlated with affective symptoms in multiple sclerosis.

OBJECTIVE: Investigate the relationship between socioeconomic status (SES) and race with self-reported fatigue, depression, and anxiety levels in multiple sclerosis (MS). METHODS: Cross-sectional review of the MS Partners Advancing Technology and Health Solutions (MS PATHS) database for adults with MS in the United States. We evaluated race and socioeconomic status (available markers: insurance, employment status, or level of education) as predictors of fatigue, depression, and anxiety sub-scores of the Neuro-QoL (Quality of life in neurological disorders), with particular interest between Caucasians/whites (CA) and African Americans/blacks (AA). Multivariate linear regression models included as covariates age, sex, disability status, smoking status, body mass index, and disease-modifying therapy. RESULTS: 7,430 individuals were included; compared to CA, AA tended to be younger, more female-predominant, and had a higher level of disability. AA had completed slightly less education, had a higher level of Medicaid coverage or uninsured status, and had higher rates of unemployed or disabled status. In the univariate model, markers of lower SES, by whichever definition we used, correlated with worse affective symptoms. In the multivariate model stratified by race, CA showed similar trends. In contrast, in AA, only lower SES by employment status was correlated with worse affective symptoms. In both CA and AA, moderate and severe level of disability correlated with worse affective symptoms. CONCLUSION: SES and race may influence affective symptoms reported by individuals with MS. The reasons for the correlation are likely multifactorial. Longitudinal studies should strive to identify factors associated with risk of affective symptoms in MS that may be modifiable.