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.

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations. Objective: This study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations. Methods: A Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination. Results: A total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3-120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died. Conclusion: This systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis.

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations.

A Predictive Autoantibody Signature in Multiple Sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, 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 of PwMS that 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 prodromal period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid (CSF) 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.

Ultrasound measures of muscle morphology in people with multiple sclerosis are associated with muscle performance and functional mobility.

BACKGROUND: Neurologically-based muscle weakness is a common symptom in people with multiple sclerosis MS (MS), who may also exhibit muscle morphology changes and intrinsic muscle dysfunction. Diagnostic ultrasound (sonography) is a non-invasive, inexpensive, and clinically feasible method to measure muscle morphology. The purpose of this study was to investigate possible asymmetries in lower limb muscle morphology and performance in people with MS, and to assess the relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. METHODS: This cross-sectional study was conducted at the Washington, DC Veterans Affairs Medical Center. The study participants were 29 Veterans with MS (52% female, 79% African-American, 48.6 ± 11.2 years old, Mean Expanded Disability Status Scale: 3.6 ± 1.4) who completed seated knee extension isokinetic strength and power tests, functional assessments (Timed 25-Foot Walk - T25FW, 5-Times Sit-to-Stand - 5STS), and quantitative B-mode ultrasound image acquisition of the rectus femoris muscle to derive morphology measures (thickness and echogenicity). The limb with weaker knee extension strength was identified as the more-involved limb. Differences between the more and less-involved limb were quantified using a t-test for all muscle morphology and muscle performance measures. Relationships between muscle morphology and patient characteristics, muscle performance, and functional mobility were evaluated using bivariate and multivariate analyses. RESULTS: The rectus femoris thickness from the more-involved limb was lower (p<0.001) than that of the less-involved limb, whereas echogenicity was not different between the two limbs (p=0.147). Rectus femoris thickness of the more-involved limb was directly related to age (r=-0.63, p<0.001), muscle strength (r=0.53, p=0.003) and power (r=0.53, p=0.003), and gait speed (r=0.42, p=0.024); whereas its echogenicity was positively associated only with muscle strength (r=-0.46, p=0.013) and power (r=-0.50, p=0.006). Together rectus femoris thickness and echogenicity of the more involved limb explained 44% and 48% of the variance in muscle strength and power, respectively (p<0.001). CONCLUSION: This study supports the ability of sonography to measure muscle morphology in people with MS, identify asymmetries, and quantify associations with important clinical correlates. Compared with more invasive and costly alternatives, sonography is a clinically feasible, relatively low-cost tool that can be used to assess muscle morphology in people with MS. Further research is warranted to determine the potential clinical utility of sonographic measures of muscle morphology in evaluating changes due to disease progression or therapeutic interventions in this population.

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

Importance: Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measurements: Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution. Results: 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. Conclusions and Relevance: 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.

Use of Telemedicine Among People with Multiple Sclerosis Before and During the COVID-19 Pandemic.

Introduction: Multiple sclerosis (MS) is the most common progressive neurological condition with onset in young adulthood. Because people with MS (PwMS) are often separated from specialty care by distance or disability, telemedicine can help alleviate that burden by removing obstacles to accessing care. Methods: We surveyed 762 PwMS in the iConquerMS research network about their use of in-person and telemedicine services prepandemic (January-February 2020) and during the coronavirus disease 2019 (COVID-19) pandemic (September-November 2020). The survey asked PwMS about their use of in-person and telemedicine services, technology access, perceptions and preferences of telemedicine, their most recent telemedicine encounter, and reasons for not using telemedicine. Results: Prepandemic, the most cited reason for not using telemedicine was providers not offering remote visits. During the pandemic, there was a decrease in the use of in-person health care (100% to ∼78%) and an increase in telemedicine utilization (25% to ∼80%). Most participants had access to telemedicine-enabling technologies and a large portion indicated a preference for using telemedicine for some or most/all of their MS health care (41-57%). Before the pandemic, telemedicine utilization was highest for primary care, while during the pandemic, utilization of telemedicine was greatest for general MS care. Mental health telemedicine encounters increased during the pandemic. Discussion: The dramatic increase in telemedicine utilization during the COVID-19 pandemic has provided access for PwMS to multispecialty care. Maintaining the policy changes that enabled remote health care to expand during the pandemic will be critical for sustained access to MS specialty care for this vulnerable population.

A Qualitative, Multiperspective Inquiry of Multiple Sclerosis Telemedicine in the United States.

BACKGROUND: Telemedicine has expanded access to high-quality, appropriate, and affordable health care for people with multiple sclerosis (MS). This study explored how the expansion of MS telemedicine is perceived and experienced by people with MS, health care providers (HCPs), and payers and policy experts (PYs). METHODS: Forty-five semistructured interviews with 20 individuals with MS, 15 HCPs, and 10 PYs were conducted between September 2020 and January 2021. The interviews were recorded on a televideo platform, transcribed, and analyzed for themes using qualitative data software. RESULTS: Interviews revealed the following 4 themes. Technology: Telemedicine increases access and convenience. Technical challenges were the most cited downside to telemedicine. Clinical encounters: Confidence in MS care via telemedicine varies. Virtual "house calls" have clinical benefits. Financing and infrastructure: Reimbursement parity is critical to utilization and expansion of telemedicine. Stakeholders are hopeful and fearful as infrastructure and business models begin to shift. Shifting expectations: The familiar structure of the office visit is currently absent in telemedicine. Telemedicine visits need more intentionality from both providers and patients. CONCLUSIONS: Telemedicine is an efficient, convenient way to deliver and receive many aspects of MS care. To expand telemedicine care, many HCPs need more training and experience, people with MS need guidance to optimize their care, and PYs in the United States need to pass legislation and adjust business models to incorporate benefits and reimbursement for telemedicine health in insurance plans. The future is promising for the ongoing use of telemedicine to improve MS care, and stakeholders should work to preserve and expand the policy changes made during the COVID-19 pandemic.

Telemedicine and Multiple Sclerosis: A Survey of Health Care Providers Before and During the COVID-19 Pandemic.

BACKGROUND: Telemedicine provides a gateway to specialty care that, otherwise, patients with multiple sclerosis (MS) could have difficulty accessing. Studies have shown that telemedicine provides a valid alternative to in-person visits. There are limited data on the strengths and limitations of telemedicine from the perspective of MS providers. METHODS: After reviewing the literature and pilot testing questions about telemedicine in provider focus groups, a 34-question survey was created on the Qualtrics web platform. A stratified sample of MS providers throughout the United States was recruited to participate. The survey initiated in November 2019 and closed in November 2020. RESULTS: Survey participants (N = 94) included neurologists (43.0%), advanced practice providers (28.0%), nurses (14.0%), mental health providers (7.0%), social workers (3.0%), rehabilitation providers (4.0%), and pharmacists (1.0%). Clinical video telemedicine (CVT) was the most commonly used platform, and 76.6% of respondents indicated that they used telemedicine to care for patients with MS. As a result of the COVID-19 pandemic, the rate of telemedicine use increased from 44.4% to 84.2%. Most health care providers (93.0%) were "very satisfied" or "somewhat satisfied" with their most recent telemedicine visit, and 94.4% of providers reported a desire to continue using telemedicine, although 84.6% found it difficult to perform a full examination. CONCLUSIONS: There was a large uptick in the use of telemedicine when the COVID-19 pandemic forced clinics to cease in-person visits. Providers predominantly used CVT; store-and-forward telemedicine and remote patient monitoring have fewer technical issues than CVT and seem to be underused.

Telemedicine Utilization Among Patients With Multiple Sclerosis in the US Veterans Health Administration, 2010-2020.

Background and Objectives: Telemedicine may help to bridge the specialty care access gap for patients with MS (PwMS) restricted by distance or disability. The objective of this study is to assess the frequency and longitudinal patterns of telemedicine utilization among PwMS and controls. Methods: We conducted a population-based nested case-control study within the Veterans Health Administration (VHA) from January 1, 2010, to December 31, 2020. MS cases and controls were individually matched on sex, age, and Veterans Affair (VA) service region (Veterans Integrated Service Network). MS case and control participants sample sizes by year included 2010: 19,387/86,379; 2016: 19,752/88,535; and 2020: 16,451/78,315. Telemedicine encounter codes were used to identify telemedicine utilization among MS cases and controls in the VHA for 2010, 2016, and 2020. Telemedicine encounters were categorized according to mode (video, phone, and supplementary remote) and type of care provided. Results: Patients in the VHA have had increasing utilization of telemedicine over the past decade. Among PwMS, mean telemedicine encounters increased steadily from 2010 to 2020 (5.6-10.5 encounters/patient, respectively). Across all years, MS cases were significantly more likely than controls to use telemedicine. The odds ratios (ORs) (95% confidence interval [CI]) of any telemedicine utilization comparing MS cases with controls in 2010, 2016, and 2020, respectively, were 1.5 (CI: 1.3-1.5), 1.9 (CI: 1.8-2.0), and 1.7 (CI: 1.6-1.8). Compared with non-Hispanic White veterans, non-Hispanic Black veterans were more likely to use telemedicine (adjusted OR = 1.5; [CI: 1.40-1.60]). The most common and least common modes of telemedicine among cases and controls were telephone and supplementary remote, respectively. Comparing 2010 with 2020, the largest increases in telemedicine utilization exhibited among MS cases were among primary care, specialty care, specialty neurology care, and other types of health care. States with the highest increases in telemedicine utilization were AL, CA, CO, FL, GA, KS, IL, NY, and SC. PwMS tended to live in counties with more adverse social determinants of health compared with controls. Discussion: PwMS were significantly more likely to use telemedicine than their matched controls. There were significant increases in telemedicine utilization between 2010 and 2020. The VHA has a robust telemedicine system of care that has grown to supplement in person care more so than other US health care systems. Future work is needed to assess the determinants of telemedicine utilization.

Harmonizing Magnetic Resonance Imaging Protocols for Veterans With Multiple Sclerosis.

Background: Magnetic resonance imaging (MRI) assists with the diagnosis of multiple sclerosis (MS), allows for timely therapeutic intervention, and for the evaluation of disease progression, treatment effect, and safety. An international task force including representatives from the Veterans Health Administration worked together to update guidelines for imaging the brain, spinal cord, and optic nerve in people with MS. Observations: This commentary communicates the core message of the 2021 MAGNIMS-CMSC-NAIMS Consensus Recommendations on the Use of MRI in Patients With Multiple Sclerosis as part of the MS Center of Excellence effort to align with contemporary guidelines, apply the highest scientific standards, and achieve consistent outcomes for veterans with MS. To implement and disseminate these proposed recommendations within the Veterans Health Administration, a workgroup was formed at the end of 2020, which discussed a modified version of the 2021 MRI Guidelines to accommodate US Department of Veterans Affairs medical centers that had fewer imaging resources as well as veterans' needs. Conclusions: Standardized MRI protocols are fundamental for the care of veterans with MS. Mitigating interscan variabilities is recognized as a priority by scientific and clinical expert committees.

The Economic Burden of Multiple Sclerosis in the United States: Estimate of Direct and Indirect Costs.

BACKGROUND AND OBJECTIVES: A recent report estimated that approximately 1 million adults were living with multiple sclerosis (MS) in the United States. Although MS is rarely the direct cause of death, its debilitating effects on normal body functions can result in considerable disruption to daily living and life roles including work, physical independence, mobility, social interaction, and participation in leisure activities. This study estimated the total economic burden of MS in the United States in 2019. METHODS: This study used a prevalence-based approach to estimate the national economic burden of MS. Claims from 3 sources (Medicare Current Beneficiary Survey, Medicare Standard Analytical File, and Optum de-identified Normative Health Information System) were used to obtain direct costs and a survey was developed to collect indirect costs (e.g., labor market productivity losses, costs of paid and unpaid caregivers, home modification) from 946 patients with MS (PwMS). Direct medical costs reflected the difference in the total average annual amount paid for PwMS vs matched controls without MS. Future earnings loss due to premature death attributable to MS was calculated using Centers for Disease Control and Prevention mortality data and Medicare claims data. RESULTS: The estimated total economic burden was $85.4 billion, with a direct medical cost of $63.3 billion and indirect and nonmedical costs of $22.1 billion. Retail prescription medication (54%); clinic-administered drugs, medication, and administration (12%); and outpatient care (9%) were the 3 largest components of the direct costs. The average excess per-person annual medical costs for PwMS was $65,612; at $35,154 per person, disease-modifying therapies (DMTs) accounted for the largest proportion of this cost. The cost per DMT user ranged from $57,202 to $92,719, depending on sex-age strata. The average indirect and nonmedical costs were $18,542 per PwMS and $22,875 per PwMS if caregivers' costs were included. Lost earnings due to premature death, presenteeism, and absenteeism losses were the largest indirect cost components. DISCUSSION: MS is a costly chronic disease, with direct costs of prescription drugs and indirect productivity loss being important cost drivers. Our findings suggested that the burden of MS in the United States has been underestimated.

Impact of comorbid post traumatic stress disorder on multiple sclerosis in military veterans: A population-based cohort study.

BACKGROUND: Very little is known regarding the impact of post traumatic stress disorder (PTSD) on the course of multiple sclerosis (MS). OBJECTIVES: To explore the impact of pre-existing PTSD on MS relapses, magnetic resonance imaging (MRI) activity, and disability in a large population-based cohort. METHODS: Military Veterans with MS and PTSD prior to symptom onset (MSPTSD, n = 96) were identified using the Department of Veterans Affairs MS databases. MSPTSD cases were matched to MS controls without PTSD (n = 95). Number of relapses, number of new T2 lesions and new gadolinium lesions on brain MRI, and neurological disability were abstracted between 2015 and 2019. RESULTS: The mean annualized relapse rate was greater in the MSPTSD group versus controls (0.23 vs 0.06, respectively; p < 0.05), as was the annualized mean number of new T2 and gadolinium-enhancing lesions on brain MRI (0.52 vs 0.16 and 0.29 vs 0.08, respectively; p < 0.05). Disability accrual (time to Disability Status Scale 6.0) was more rapid (23.7 vs 29.5 years, p < 0.05) in relapsing MS patients with PTSD. CONCLUSION: Patients with MSPTSD have higher disease activity and reach disability endpoints more rapidly than controls. This is the first study to show PTSD as a potentially modifiable risk factor for MS relapses, MRI activity, and disability.

Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans.

BACKGROUND: We previously reported that the single nucleotide polymorphism (SNP) rs9282860 in serine threonine kinase 11 (STK11) gene which codes for liver kinase B1 (LKB1) has higher prevalence in White relapsing-remitting multiple sclerosis (RRMS) patients than controls. However it is not known if this SNP is a risk factor for MS in other populations. METHODS: We assessed the prevalence of the STK11 SNP in samples collected from African American (AA) persons with MS (PwMS) and controls at multiple Veterans Affairs (VA) Medical Centers and from a network of academic MS centers. Genotyping was carried out using a specific Taqman assay. Comparisons of SNP frequencies were made using Fisher's exact test to determine significance and odds ratios. Group means were compared by appropriate t-tests based on normality and variance using SPSS V27. RESULTS: There were no significant differences in average age at first symptom onset, age at diagnosis, disease duration, or disease severity between RRMS patients recruited from VAMCs versus non-VAMCs. The SNP was more prevalent in AA than White PwMS, however only in secondary progressive MS (SPMS) patients was that difference statistically significant. AA SPMS patients had higher STK11 SNP prevalence than controls; and in that cohort the SNP was associated with older age at symptom onset and at diagnosis. CONCLUSIONS: The results suggest that the STK11 SNP represents a risk factor for SPMS in AA patients, and can influence both early (onset) and later (conversion to SPMSS) events.

Multiple sclerosis in Kenya: Demographic and clinical characteristics of a registry cohort.

BACKGROUND: Multiple Sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. There is limited literature regarding the burden of MS in sub-Saharan Africa (SSA). OBJECTIVE: To describe the demographic and clinical characteristics of patients with MS (PwMS) presenting to a tertiary referral hospital in Nairobi. METHODS: We conducted a retrospective descriptive study for PwMS presenting to Aga Khan University Hospital, Nairobi from 2008-2018. RESULTS: 99 cases met the diagnostic criteria for MS with a male to female ratio of 1:4. Majority (68.7%) of PwMS were indigenous Africans with a mean age of onset of 30.7 years. Mean duration from symptom onset to first neuro-imaging was 5.04 years. Only 33% of patients had sensory symptoms at onset whereas 54.5% had vitamin D deficiency/insufficiency. Majority (79.5%) had relapsing remitting MS (RRMS) and 56.6% were initiated on disease modifying therapy (DMT). Only 21.2% of patients on DMT were non-compliant. Patients with RRMS were more likely to be initiated on DMT at our hospital (p < 0.001). CONCLUSION: Clinical characteristics of these patients largely resemble those of other SSA cohorts and African American patients. There was a delay between symptom onset and neuroimaging. There were also issues with DMT compliance.

COVID-19 Vaccine in Veterans with Multiple Sclerosis: Protect the Vulnerable.

Older veterans with progressive MS and associated comorbidities are at higher risk of death should they be infected by COVID-19 and we urge health care providers to educate every veteran about the benefits of being vaccinated against COVID-19.

Disease-modifying therapy prescription patterns in people with multiple sclerosis by age.

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for their ability to reduce disease activity, namely clinical relapses and signal changes on magnetic resonance imaging (MRI). Disease activity appears age dependent. Thus, the greatest benefit would be expected in younger people with MS (PwMS) whereas benefits in the elderly are uncertain. METHODS: Real-world data were obtained from PwMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR). RESULTS: 6948 PwMS were surveyed from NARCOMS, and the MSSR had 1719 participants. In younger adult PwMS 40-years old or less, 183 (61.4%) in NARCOMS and 179 (70.5%) in the MSSR were prescribed DMTs. Among PwMS over age 60, 1575 (40.1%) in NARCOMS and 239 (36.3%) in the MSSR were prescribed DMTs. More PwMS in the age group of 31-40 (p = 0.035) and 41-50 (p = 0.001) in the MSSR were using DMTs compared with PwMS of the same age groups in NARCOMS. CONCLUSION: These findings suggest that DMTs are under-utilized in the younger population and continue to be commonly prescribed in the elderly. Broader access may explain the higher prescription rate of DMTs in US veterans.

MS and Disability Progression in Latin America, Africa, Asia and the Middle East: A Systematic Review.

BACKGROUND: There is evidence of an increased prevalence and disease burden of Multiple Sclerosis (MS) in parts of the world where the risk was once considered low, such as Latin America (LA), Sub-Saharan Africa, Asia and the Middle East-North Africa (MENA). Despite the growing number of clinical reports, the phenotype and course of MS in these regions remains understudied compared with Europe and North America. We aimed to investigate MS phenotypes and long-term clinical outcomes across these regions. METHOD: A Boolean search of the medical literature was conducted between January 1980 and April 30, 2020. PubMed, SCOPUS, Global Health, and the Cochrane databases, were used to identify all relevant citations. Articles were collated and managed on Covidence® software. We independently appraised the articles for meeting study criteria and for quality using the Critical Appraisal Skills Program (CASP) and the Specialist Unit for Review Evidence (SURE) system. RESULTS: A total of 1,639 studies were imported for screening. After removing 545 duplicates, two authors assessed 1,094 abstracts and selected 515 for full-text screening. 72 articles met study criteria, including 19 studies from LA, 4 from sub-Saharan Africa, 24 from Asia and 25 from MENA. The overall sex ratio was 2.5:1 (female: male). Disability was assessed using the Expanded Disability Status Scale (EDSS). Longitudinal disability progression and time to standard endpoints was compared by region and with relevant Western reports. Patients with MS living in the MENA region appear to reach disability milestones faster than those in the Western world, although this finding is not uniform. South Asia shows distinct disability features compared with East Asia, more closely resembling those of the West. Disease morbidity in East Asia appears more benign than in the West after careful exclusion of neuromyelitis optica spectrum disorder cases. Populations in LA tend to have similar MS features to the Western world, but some exceptions exist, including African descendants that reach disability milestones earlier. Using all studies with appropriate survival analysis, the mean time to EDSS 6.0 was 16.97 years with a heterogeneity index of 24.59. CONCLUSION: The clinical phenotypes and disability progression of MS in LA, Africa, Asia and the MENA region have similarities to Western MS. In some regions and subpopulations there is evidence of a more aggressive course, possibly due to a combination of genetic and environmental factors. More population-based longitudinal data are needed, particularly in Sub-Saharan Africa.

Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition.

BACKGROUND: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support advocacy efforts. OBJECTIVES: The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country, regional and global levels. METHODS: Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis. Regional analyses and comparisons with 2013 data were conducted. RESULTS: A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population). MS prevalence has increased in every world region since 2013 but gaps in prevalence estimates persist. The pooled incidence rate across 75 reporting countries is 2.1 per 100,000 persons/year, and the mean age of diagnosis is 32 years. Females are twice as likely to live with MS as males. CONCLUSIONS: The global prevalence of MS has risen since 2013, but good surveillance data is not universal. Action is needed by multiple stakeholders to close knowledge gaps.

An International Standardized Magnetic Resonance Imaging Protocol for Diagnosis and Follow-up of Patients with Multiple Sclerosis: Advocacy, Dissemination, and Implementation Strategies.

Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.