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.

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.

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.

Toward a low-cost, in-home, telemedicine-enabled assessment of disability in multiple sclerosis.

BACKGROUND: Remote assessment of neurological disability in people with multiple sclerosis (MS) could improve access to clinical care and efficiency of clinical research. OBJECTIVE: To develop and validate a telemedicine-based MS disability examination that does not require an in-home examiner. METHODS: Adults with MS were recruited after a standardized in-person Expanded Disability Status Scale (EDSS) evaluation, and within 1 week underwent a blinded televideo-enabled EDSS examination with a different clinician. EDSS and tele-EDSS scores were compared. RESULTS: Overall, 41 adults participated (mean (standard deviation (SD)) age: 47.0 years (11.6); median EDSS: 2 (range: 0-7)); 37 required no in-home assistance for the tele-EDSS evaluation (e.g. help positioning camera). Mean difference between EDSS and tele-EDSS was 0.34 (95% confidence interval (CI): 0.07-0.61). For 88% of evaluations, tele-EDSS and EDSS scores were within 1 point (similar to reported in-person inter-rater differences). Unweighted kappa for agreement within 0.5 point was 0.72. Correlation for individual functional systems (FS) ranged from modest (vision: 0.37) to high (bowel/bladder: 0.79). Overall correlation between EDSS and tele-EDSS was 0.89 (p < 0.0001); and 0.98 (p < 0.0001) at EDSS range: 4-7. CONCLUSION: In this proof of principle study, disability evaluation in mild to moderate MS is feasible using telemedicine without an aide at the patient's location.

A systematic review of modifiable risk factors in the progression of multiple sclerosis.

BACKGROUND: The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. OBJECTIVE: To systematically review modifiable risk factors and exposures associated with MS progression. METHODS: We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence. RESULTS: In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = -0.22; confidence interval (CI) = -0.32, -0.12; 11 studies; I2 = 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2 = 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures. CONCLUSION: MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.

A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis.

BACKGROUND: Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention. OBJECTIVE: To systematically review the evidence for interventions targeting risk factors for MS progression. METHODS: We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461). RESULTS: In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE). CONCLUSION: We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation.

Remote cognitive assessments for patients with multiple sclerosis: a feasibility study.

BACKGROUND: measuring cognitive function in patients with multiple sclerosis (MS) can be challenging given the obstacles faced when traveling to testing centers. OBJECTIVE: the purpose of this study was to evaluate the feasibility of remote cognitive assessment in patients with MS using the automated neuropsychological assessment metrics (ANAM-MS) and the symbol digit modalities test (SDMT). METHODS: patients meeting the McDonald criteria for MS (n = 24) were randomized to complete the live-in-office condition or a remote-in-office condition first, with all patients completing both sessions. Patients (n = 20) then completed a final remote-in-home testing session. Both remote sessions were proctored by a psychologist using a secure telehealth connection. RESULTS: scores on the live SDMT differed from scores in the two remote settings F(2, 38) = 4.46, p = 0.018. However, summary scores on the ANAM-MS were similar across the three settings, F(2, 36) = 2.21, p = 0.124. Satisfaction with telehealth testing was high on the part of the examiner and patients. Each telehealth testing session saved more than $144.00 in travel costs and lost wages. CONCLUSION: this study demonstrated that valid results can be obtained when evaluating patients remotely using ANAM-MS. Some differences were noted for the SDMT that suggest that either specific norms or a different implementation approach may be needed for telehealth.

Multiple sclerosis in gulf war era veterans. 2. Military deployment and risk of multiple sclerosis in the first gulf war.

BACKGROUND: Concern has been raised that US veterans of the 1990-1991 Gulf War (GW1) may be at increased risk to develop neurologic disease. METHODS: An incident cohort of multiple sclerosis (MS) and other demyelinating disease (ODD) was assembled from the US military comprising the Gulf War era (1990-2007). Cases of MS and ODD meeting standard diagnostic criteria were matched to a database of all active duty personnel from the Department of Defense. Relative risk (RR) estimates for MS and all demyelinating disease based on onset, deployment status, and exposures were calculated. RESULTS: For GW1, a total of 1,841 incident cases of definite MS and ODD were identified, with 387 among 696,118 deployed and 1,454 among 1,786,215 nondeployed personnel. The RR for MS alone among those deployed compared to those nondeployed was 0.69 (confidence interval, CI: 0.61-0.78), with 0.72 (CI: 0.62-0.83) in men and 0.96 (CI: 0.75-1.22) in women. Deployment was also nonsignificant or protective as an MS risk factor across racial groups, all age groups, and each military service. RRs for MS by service were: Air Force 0.71 (CI: 0.53-0.96), Army 0.80 (CI: 0.67-0.96), Marines 0.96 (CI: 0.63-1.47), and Navy 0.56 (CI: 0.43-0.74). CONCLUSION: Military deployment to GW1 was not a risk factor for developing MS.

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.

The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service.

We characterize here a new nationwide incident cohort of multiple sclerosis from the US military-veteran population. This cohort provides an update to the only other US nationwide incidence study of multiple sclerosis performed during the 1970s. Medical records and data from the Department of Defense and Department of Veterans Affairs for cases of multiple sclerosis who served in the military between 1990, the start of the Gulf War era, and 2007 and who were service-connected for this disorder by the Department of Veterans Affairs from 1990 on, were reviewed. A total of 2691 patients were confirmed as having multiple sclerosis: 2288 definite, 190 possible, 207 clinically isolated syndrome and six neuromyelitis optica. Overall racial categories were White, Black and other, which included all Hispanics. There were 1278 White males and 556 females; 360 Black males and 296 females; and 200 others, 153 (77%) of whom were Hispanic. Mean age at onset of 30.7 years did not differ significantly by race or sex. Age at onset was 17-50 years in 99%, the same age range as 99% of the military. Average annual age specific (age 17-50 years) incidence rates per 100 000 for the entire series were 9.6 with 95% confidence interval of 9.3-10.0. Rates for Blacks were highest at 12.1 with confidence interval 11.2-13.1, Whites were 9.3 (interval 8.9-9.8) and others 6.9 (interval 6.0-7.9). For 83 Hispanics defined for 2000-07, the rate was 8.2 (interval 6.5-10.1). Much smaller numbers gave rates of 3.3 for Asian/Pacific Islanders and 3.1 for native Americans. Rates by sex for Whites were 7.3 and 25.8 male and female, respectively, for Blacks 8.4 and 26.3, and for Hispanics 6.6 and 17.0. Rates by service were high for Air Force (10.9) and Army (10.6), medium for Navy (9.1) and Coast Guard (7.9), and low for Marines (5.3). Relative risk of multiple sclerosis was 3.39 female:male and 1.27 Black:White. These new findings indicate that females of all races now have incidence rates for multiple sclerosis some three times those of their male counterparts and that among these groups, Blacks have the highest and others (probably including Hispanics) the lowest incidence rates regardless of sex or service. The low rate for Marines is unexplained. This Gulf War era multiple sclerosis cohort provides a unique resource for further study.

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.

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.

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.

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.

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.

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 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.