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.

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.

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.

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.

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.

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.

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.

The Multiple Sclerosis Surveillance Registry: A Novel Interactive Database Within the Veterans Health Administration.

OBJECTIVE: To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS), we present the MS Surveillance Registry (MSSR) within the US Department of Veterans Affairs (VA). BACKGROUND: Disease specific databases can be helpful in the management of neurologic conditions but few are fully integrated into the electronic health record and linked to health system data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge. METHODS: Building the MSSR was initiated by an iterative process with an IT team and MS health care providers. A common registry platform shared by other VA disease specific registries (eg, traumatic brain injury and cancer) was used to develop the IT infrastructure. MS cases were entered online into the MS Assessment Tool at selected MS Centers of Excellence (MSCoE) clinics in the US. Other large VA databases linked to MSSR are reviewed. Patient demographic and clinical characteristics were compared and contrasted with the broader VA population and other US registry populations. RESULTS: We have enrolled 1,743 patients with MS in the MSSR through fiscal year 2019 from selected MS regional programs in the VA MSCoE network. The mean age of patients was 56.0 years, with a 2.7 male:female ratio. Among those with definite MS, the mean European Database for MS Disability Score was 4.7 and 75% had ever used an MS disease modifying therapy. A summary electronic dashboard was developed for health care providers to easily access demographic and clinical data for individuals and groups of patients. Data on comorbid conditions, pharmacy and prosthetics utilization, outpatient clinic visits, and inpatient admission were documented for each patient. CONCLUSIONS: The MSSR is a unique electronic database that has enhanced clinical management of MS and serves as a national source for clinical outcomes.

Telemedicine and multiple sclerosis: A comprehensive literature review.

INTRODUCTION: Patients with multiple sclerosis (pwMS) face barriers accessing specialty care for evaluation and treatment. Telemedicine, the practice of clinical care at a distance with the aid of technology, may be a potential bridge to close the access gap for pwMS separated by distance or disability. The objective of this review was to investigate the types of telemedicine being utilized and overall outcomes for pwMS and their providers. METHODS: A Boolean search of the medical literature was conducted between January 2000 and January 31, 2018. PubMed, EMBASE, PsycINFO and the Cochrane databases, were used to identify all relevant citations. Two reviewers independently appraised the articles for meeting study criteria and for study quality using the CASP system. Financial costs of the telemedicine applications were assessed. RESULTS: A total of 28 studies involving 3252 participants met criteria for inclusion. Telemedicine interventions were classified, and outcomes were assessed systematically by the following categories: general MS care; rehabilitation and exercise; and neuropsychology/mental health. Studies showed a range of outcomes with variable quality. Overall, remote clinical examinations, long-term telemedicine management interventions and telerehabilitation were shown to be beneficial, cost-effective and satisfactory for patients and providers. DISCUSSION: Telemedicine is a viable platform for delivering specialty MS care. Remote neurological assessments and several forms of therapy have been shown to be technically feasible. Optimal implementation and barriers to the use of telemedicine in the current healthcare system should be explored.

A new way to estimate neurologic disease prevalence in the United States: Illustrated with MS.

OBJECTIVE: Considerable gaps exist in knowledge regarding the prevalence of neurologic diseases, such as multiple sclerosis (MS), in the United States. Therefore, the MS Prevalence Working Group sought to review and evaluate alternative methods for obtaining a scientifically valid estimate of national MS prevalence in the current health care era. METHODS: We carried out a strengths, weaknesses, opportunities, and threats (SWOT) analysis for 3 approaches to estimate MS prevalence: population-based MS registries, national probability health surveys, and analysis of administrative health claims databases. We reviewed MS prevalence studies conducted in the United States and critically examined possible methods for estimating national MS prevalence. RESULTS: We developed a new 4-step approach for estimating MS prevalence in the United States. First, identify administrative health claim databases covering publicly and privately insured populations in the United States. Second, develop and validate a highly accurate MS case-finding algorithm that can be standardly applied in all databases. Third, apply a case definition algorithm to estimate MS prevalence in each population. Fourth, combine MS prevalence estimates into a single estimate of US prevalence, weighted according to the number of insured persons in each health insurance segment. CONCLUSIONS: By addressing methodologic challenges and proposing a new approach for measuring the prevalence of MS in the United States, we hope that our work will benefit scientists who study neurologic and other chronic conditions for which national prevalence estimates do not exist.

The prevalence of MS in the United States: A population-based estimate using health claims data.

OBJECTIVE: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. METHODS: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. RESULTS: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. CONCLUSION: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Validation of an algorithm for identifying MS cases in administrative health claims datasets.

OBJECTIVE: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets. METHODS: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population. RESULTS: The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%-96.0%), specificity (66.7%-99.0%), positive predictive value (95.4%-99.0%), and interrater reliability (Youden J = 0.60-0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%. CONCLUSIONS: The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

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.

Self-directed exercise in multiple sclerosis: Evaluation of a home automated tele-management system.

Introduction Physical rehabilitation is one of the few non-pharmaceutical therapies for maintaining or improving walking ability for patients with multiple sclerosis. However, travel distance to rehabilitation clinics, neurological disability and insurance coverage often limit access to specialised rehabilitation services. To address these issues, we utilised a web-based system to support a home-based self-directed exercise programme. Methods Patients ( n = 24) were randomised to either routine home rehabilitation or to the multiple sclerosis home automated tele-management system for a six-month period. The study group had a mean age of 50.4 years, 56% of patients were male, and 67% had progressive multiple sclerosis with an overall mean Patient Determined Disease Steps score of 4.4 (cane or crutch required for walking). Key outcomes included the timed 25-foot-walk, six-minute-walk and the Berg Balance Scale. Results There was no statistically significant difference in the change of the primary walking outcome measure, timed 25-foot-walk, at six months between the home automated tele-management intervention and control groups ( p = 0.44). Similarly, change scores for the six-minute-walk were not significantly different between the home automated tele-management or control groups at six months. Discussion Maintaining overall gait abilities in this group of predominantly progressive multiple sclerosis patients is notable. Exercise adherence was positively associated with higher multiple sclerosis disability and self-reported walking ability. Study engagement and participation in routine home-based exercise for the entire study period was challenging. Further research using clinical video telerehabilitation techniques that optimise patient involvement warrants further study.

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.