Multiple Sclerosis Research Research Articles

A Tripartite Knowledge Translation Program: Innovative Patient-Centered Approach to Clinical Research Participation for Individuals with Multiple Sclerosis.

Background Knowledge translation (KT) models that represent an individual's perspective are a sign of effective KT. Some common challenges in KT include participant engagement, organization of the team, and time demands of the participants. We implemented a unique tripartite KT program to (1) share current research, (2) inform persons living with multiple sclerosis (pwMS) about the clinical research process, and (3) invite pwMS to immediately participate in clinical research. The primary aim was to determine participants' perspectives on the value and acceptability of an experiential research program offered at a patient and family educational conference. Methods A team of researchers identified factors that would impact the logistics of hosting an experiential research program at a conference and designed a unique tripartite KT program. The local multiple sclerosis (MS) society was engaged to select an appropriate location and invite stakeholders to the conference. A survey to determine participants' perspectives on the value and acceptability of the experiential research program was developed and analyzed. Results 65 pwMS attended the conference, and 44 (67.7%) participated in the on-site experiential research program. 72.7% of the participants completed the survey, of which 93.8% stated that they strongly agree or agree with the following statements: “Did you feel like participating in research today was a valuable experience to you?” and “Did you feel like you were contributing to MS research?” 100% of the participants agreed or strongly agreed when asked “would you like to see more research activities taking place at these kinds of events?” Conclusions This paper describes the logistics and challenges of conducting an experiential KT program, which proved to be rewarding for pwMS. The majority of pwMS attending the conference agreed to participate in the on-site experiential research program and an overwhelming majority of participants felt the experience was valuable.

A smartphone sensor-based digital outcome assessment of multiple sclerosis

Background: Sensor-based monitoring tools fill a critical gap in multiple sclerosis (MS) research and clinical care. Objective: The aim of this study is to assess performance characteristics of the Floodlight Proof-of-Concept (PoC) app. Methods: In a 24-week study (clinicaltrials.gov: NCT02952911), smartphone-based active tests and passive monitoring assessed cognition (electronic Symbol Digit Modalities Test), upper extremity function (Pinching Test, Draw a Shape Test), and gait and balance (Static Balance Test, U-Turn Test, Walk Test, Passive Monitoring). Intraclass correlation coefficients (ICCs) and age- or sex-adjusted Spearman’s rank correlation determined test–retest reliability and correlations with clinical and magnetic resonance imaging (MRI) outcome measures, respectively. Results: Seventy-six people with MS (PwMS) and 25 healthy controls were enrolled. In PwMS, ICCs were moderate-to-good (ICC(2,1) = 0.61–0.85) across tests. Correlations with domain-specific standard clinical disability measures were significant for all tests in the cognitive (r = 0.82, p < 0.001), upper extremity function (|r|= 0.40–0.64, all p < 0.001), and gait and balance domains (r = −0.25 to −0.52, all p < 0.05; except for Static Balance Test: r = −0.20, p > 0.05). Most tests also correlated with Expanded Disability Status Scale, 29-item Multiple Sclerosis Impact Scale items or subscales, and/or normalized brain volume. Conclusion: The Floodlight PoC app captures reliable and clinically relevant measures of functional impairment in MS, supporting its potential use in clinical research and practice.

Research interrupted: The impact of the COVID-19 pandemic on multiple sclerosis research in the field of rehabilitation and quality of life.

BackgroundThe COVID-19 pandemic has likely had a negative impact on rehabilitation and quality of life (QoL) research in multiple sclerosis (MS).MethodWe explored perceived barriers to research among 87 researchers, representing 18 countries, both prior to and since COVID-19.ResultsA Wilcoxon signed-rank test found that significantly more researchers reported experiencing barriers to research since the onset of the pandemic compared to pre-COVID-19 (p < .001), with 78% of respondents reporting at least some barriers since COVID-19. The most commonly-cited barriers related to participant access (n = 38) and interruptions/delays to projects (n = 19). Although no gender differences were found in the number of barriers reported, female respondents were more likely to cite time or competing demands as barriers to research. Females were also more likely to perceive being negatively impacted by the pandemic compared to other genders (p = .007).ConclusionsImplications for the future landscape of rehabilitation research in MS are discussed.

Hypertension and hypertension severity in Hispanics/Latinx with MS

Background: Vascular comorbidities (VCs) including hypertension (HTN) are associated with worse multiple sclerosis (MS) outcomes. HTN is common in Latinx, but the prevalence and relationship with disability are unknown in Latinx with MS. Methods: Latinx (n = 451) from the Alliance for Research in Hispanic MS (ARHMS) seen between 2007 and 2019 were included. HTN, diabetes (DM), hyperlipidemia (HLD), ischemic events, and smoking were considered VC. Blood pressures (BPs) were classified using the American Heart Association (AHA) criteria. Logistic regression determined associations between VC and ambulatory disability accounting for age, sex, and disease duration. Results: Medical comorbidities were found in 41.9% and VC in 24.2%. Smoking (13.6%) and HTN (7.3%) were the most common. HTN was the most common over the age of 40 (12.6%). The odds of having severe disability were three times higher for those with HTN (odds ratio [OR], 3.12; 95% confidence interval (CI), 1.37–7.12). Stage II HTN according to AHA also tripled the odds (OR, 2.89; 95%CI, 1.11–7.55). AHA BP confirmed HTN in 27.5% (compared to 7.3% with established diagnosis). Conclusion: HTN diagnosis and stage II HTN defined by AHA were independently associated with severe ambulatory disability in Latinx with MS. HTN was underdiagnosed. Future studies should assess whether HTN treatment control would prevent disability in MS.

Performance of highly cited multiple sclerosis publications in the Science Citation Index expanded: A scientometric analysis

BackgroundThe present study aims to identify and analyze the characteristics of highly cited publications on Multiple sclerosis in the Science Citation Index Expanded. MethodsDocuments that had 100 citations or more were considered as the highly cited documents. Highly cited publications were analyzed in the distribution of document types, languages, publication years, Web of Science categories, and journals as well as publication performance of countries, institutions, and authors. The six and five publication indicators were applied to compare publications of the countries and the institutes respectively. Highly cited authors were analyzed by Y-index. ResultsIn general, articles spent about 12 years to be highly cited articles. The USA dominated the production by the six publication indicators. Harvard University was the most active in research on multiple sclerosis while the University of California, Los Angeles in the USA shows the most independent research. M. Filippi was recognized as the most productive author who had the most articles as the corresponding author. ConclusionThe findings may be of interest to multiple sclerosis researchers and policymakers all around the world.

Barriers and motivators for tobacco smoking cessation in people with multiple sclerosis

IntroductionSmoking is a key modifiable risk factor for health outcomes of people with multiple sclerosis (MS). Little evidence exists on whether the information and support needs of people with MS who smoke are met. This study aimed to explore knowledge, attitudes and beliefs about smoking and quitting, and quitting support needs in Australian people with MS. MethodsCurrent and recent smokers were recruited for phone interviews through social media and newsletters. Interview data were analysed in NVivo using framework analysis. ResultsWe interviewed 25 people with MS (20 current and five recent smokers). Many participants had little knowledge about the risks of smoking on MS progression. Some reported perceived benefits from smoking on MS symptoms, while others perceived smoking worsening their symptoms. Similarly, quitting was believed to have health benefits, but concerns about withdrawal symptoms and the impact on MS symptoms and relapses were common. Participants reported ambivalence discussing smoking with clinicians; some wanting more information and support, while also feeling shame or guilt. Many participants were asked about their smoking status by MS clinicians, however, the provision of evidence-based information, and referrals to quitting support services was very infrequent. General practitioners were often found helpful and supportive, but participants gave more weight to quit advice from MS clinicians. ConclusionOur results are the first to indicate that smoking cessation needs of Australian people with MS are not met. These findings should be confirmed in a larger sample, but there is potential to investigate whether implementing routine provision of brief advice in MS care, as a coordinated effort between MS researchers, practitioners, consumer advocates and behavioural intervention services, may meet these needs. Further, developing targeted resources and training quit counsellors to provide appropriate information and support specific to people with MS may improve smoking cessation success in people with MS.

Status of the neuromyelitis optica spectrum disorder in Latin America

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. ObjectivesTo determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. MethodsThe Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti­ AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. ResultsWe identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. ConclusionsThis is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Contribution of common risk variants to multiple sclerosis in Orkney and Shetland

Orkney and Shetland, the population isolates that make up the Northern Isles of Scotland, are of particular interest to multiple sclerosis (MS) research. While MS prevalence is high in Scotland, Orkney has the highest global prevalence, higher than more northerly Shetland. Many hypotheses for the excess of MS cases in Orkney have been investigated, including vitamin D deficiency and homozygosity: neither was found to cause the high prevalence of MS. It is possible that this excess prevalence may be explained through unique genetics. We used polygenic risk scores (PRS) to look at the contribution of common risk variants to MS. Analyses were conducted using ORCADES (97/2118 cases/controls), VIKING (15/2000 cases/controls) and Generation Scotland (30/8708 cases/controls) data sets. However, no evidence of a difference in MS-associated common variant frequencies was found between the three control populations, aside from HLA-DRB1*15:01 tag SNP rs9271069. This SNP had a significantly higher risk allele frequency in Orkney (0.23, p value = 8 × 10–13) and Shetland (0.21, p value = 2.3 × 10–6) than mainland Scotland (0.17). This difference in frequency is estimated to account for 6 (95% CI 3, 8) out of 150 observed excess cases per 100,000 individuals in Shetland and 9 (95% CI 8, 11) of the observed 257 excess cases per 100,000 individuals in Orkney, compared with mainland Scotland. Common variants therefore appear to account for little of the excess burden of MS in the Northern Isles of Scotland.

Research priorities in multiple sclerosis in Latin America: A multi-stakeholder call to action to improve patients care: Research priorities in MS in LATAM

As human and economic resources are limited, especially in Latin America (LATAM), it is important to identify research priorities to improve multiple sclerosis (MS) patients care in the region. The objective was to generate a multidisciplinary consensus on research priorities in MS for patients care in LATAM by involving healthcare professionals and MS patient associations. METHODS: consensus was reached through a four-step modified Delphi method designed to identify and rate research priorities in MS in LATAM. The process consisted of two qualitative assessments, a general ranking phase and a consensus meeting followed by a more detailed ranking phase RESULTS: a total of 62 participants (35 neurologists, 4 nurses, 12 kinesiologists, 7 neuropsychologists and 4 patient association members) developed the process. At the final ranking stage following the consensus meeting, each participant provided their final rankings, and the top priority research questions were outlined. 11 research priorities were identified focusing on healthcare access, costs of the disease, physical and cognitive evaluation and rehabilitation, quality of life, symptoms management, prognostic factors, the need of MS care units and patient's management in emergencies like COVID-19. CONCLUSION: this work establishes MS research priorities in LATAM from multiple perspectives. To pursue the actions suggested could launch the drive to obtain information that will help us to better understand the disease in our region and, especially, to better care for affected patients.

Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications. 18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.

Motor Impairment in Multiple Sclerosis: Analysis from the North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) (4731)

Motor Impairment in Multiple Sclerosis: Analysis from the North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) (4731)

ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis.

Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.

The Evolution of Neurofilament Light Chain in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune, inflammatory neurodegenerative disease of the central nervous system characterized by demyelination and axonal damage. Diagnosis and prognosis are mainly assessed through clinical examination and neuroimaging. However, more sensitive biomarkers are needed to measure disease activity and guide treatment decisions in MS. Prompt and individualized management can reduce inflammatory activity and delay disease progression. Neurofilament Light chain (NfL), a neuron-specific cytoskeletal protein that is released into the extracellular fluid following axonal injury, has been identified as a biomarker of disease activity in MS. Measurement of NfL levels can capture the extent of neuroaxonal damage, especially in early stages of the disease. A growing body of evidence has shown that NfL in cerebrospinal fluid (CSF) and serum can be used as reliable indicators of prognosis and treatment response. More recently, NfL has been shown to facilitate individualized treatment decisions for individuals with MS. In this review, we discuss the characteristics that make NfL a highly informative biomarker and depict the available technologies used for its measurement. We further discuss the growing role of serum and CSF NfL in MS research and clinical settings. Finally, we address some of the current topics of debate regarding the use of NfL in clinical practice and examine the possible directions that this biomarker may take in the future.

Assessment of Comprehensibility of Industry Conflicts of Interest and Disclosures by Multiple Sclerosis Researchers at Medical Conferences

This cross-sectional study uses length of disclosure slide display times and slide word counts to assess the comprehensibility of industry conflicts of interest (COI) disclosures by researchers presenting at the world’s largest multiple sclerosis (MS) conference.

Quality of life measures in pediatric multiple sclerosis: a systematic review and meta-analysis.

To identify generic measures used to measure quality of life (QoL) in pediatric multiple sclerosis research, estimate an overall score of children and adolescents with pediatric multiple sclerosis, and compare the scores to scores of typically developing children and adolescents. A systematic search was conducted on four databases. All studies were included if: the sample was children with pediatric demyelinating disorders; self-reported QoL/health-related quality of life (HRQoL) measures or results were reported; and the mean age of the sample was below 21 years. Quality of the included articles was appraised using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and the Mixed Methods Appraisal Tool checklist. A meta-analysis was also conducted. A total of 12 full-text articles were included. Content analysis showed that many components of QoL were not included in the measures. Seven studies were included in the meta-analysis. The meta-analyzed score was 75.7 (95% confidence interval 71.2-80.3) with a pooled standard deviation of 16.6. Scores of typically developing children and children with pediatric multiple sclerosis were similar. Most measures assessed HRQoL and not QoL. Development of a condition-specific measure of QoL for children and adolescents with pediatric multiple sclerosis would make an important contribution to the field. What this paper adds Health-related quality of life (HRQoL) measures were used to measure quality of life in pediatric multiple sclerosis. HRQoL scores in pediatric multiple sclerosis were similar to typically developing children and adolescents.

Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment. Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

PART 2: Mouse models for multiple sclerosis research.

Lower urinary tract symptoms and dysfunction (LUTS/LUTD) contribute to loss of quality of life, morbidity, and need for medical intervention in most patients with multiple sclerosis (MS). Although MS is an inflammatory neurodegenerative disease, clinical manifestations including continence control disorders have traditionally been attributed to the loss of neural signaling due to neurodegeneration. Clinical approaches to MS-LUTS/LUTD have focused on addressing symptoms in the context of urodynamic dysfunctions as pathophysiologic understandings are incomplete. The mouse model provides a useful research platform for discovery of more detailed molecular, cellular, and tissue-level knowledge of the disease and its clinical manifestations. The aim of this two-part review is to provide a state-of-the-art update on the use of the mouse model for MS research, with a focus on lower urinary tract symptoms. Part I presents a summary of current understanding of MS pathophysiology, the impact on lower urinary tract symptoms, and briefly introduces the types of mouse models available to study MS. Part II presents the common animal models that are currently available to study MS, their mechanism, relevance to MS-LUTS/LUTD and their urinary pathophysiology, advantages and disadvantages.

The Effect of Different National Treatment Strategies on Disability Outcome in Relapsing-Remitting Multiple Sclerosis: A Propensity Score Adjusted Comparison between Denmark and Sweden

Background: Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The objective was to investigate the influence of such differences on disease modifying treatment (DMT) and disability outcome. Methods: Patients with RRMS commencing their first DMT 2013-2016 were retrospectively included from the Swedish and Danish MS registries. Time to the 24-week confirmed disability worsening (CDW, primary outcome) and 24-week confirmed disability improvement (CDI, secondary outcome) and milestone expanded disability status scale (EDSS) score 3 and 4 end-points (secondary outcomes) were analyzed using Inverse Probability of Treatment Weighting (IPTW)-based Cox regression models with robust standard errors. The IPTW model used a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the two countries. Findings: A total of 2700 patients from the Swedish registry and 2161 patients from the Danish MS registry commencing a first DMT between 2013 and 2016 were included in the analysis and observed for an average of 4 years. The proportion of patients initiating with a low-moderate as compared to highly effective DMT was 92.4% (teriflunomide 42%) and 7.6% in Denmark and 62.4% (teriflunomide 2.4%) and 35% in Sweden, respectively. Swedish patients were associated with a 29% reduction in the rate of post-baseline 24-week CDW relative to Danish patients (IPTW HR 0.71; 95% CI 0.57-0.90; p=0.004). The Swedish cohort was associated with a 27% and 26% reduction in the rate of reaching EDSS 3 and 4 respectively, relative to Danish patients (HR 0.73; 95% CI 0.62-0.85; p<0.001; and 0.74; 95% CI 0.59-0.93; p=0.009, reference = Denmark). Interpretation: We show for the first time that differences in treatment strategies of RRMS have an impact on disability outcomes at a national level. Escalation of treatment efficacy seemed inferior to using more efficacious DMT as initial treatment. Funding Statement: This study was supported by the Swedish Research Council, the Swedish Brain foundation, the Karolinska University Hospital & the Patient-Centered Outcomes Research Institute (PCORI), the Swedish Multiple Sclerosis Research Foundation, the Swedish Federal Government (LUA/ALF Agreement ALFGBG-722081), the Swedish Association of Persons with Neurological Disabilities, the Research Foundation of the Multiple Sclerosis Society of Gothenburg, the Edit Jacobson Foundation, and NEURO Sweden. Declaration of Interests: TS has received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis. MM has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. FP has received research grants from Biogen and Novartis. AS reports no conflicts of interest FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. PVR has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, and Alexion, has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, has received support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. MK reports no conflicts of interest HJ has received honoraria for participating in advisory board from Biogen. JH has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis and speaker’s fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, BiogenIdec, Merck- Serono, TEVA, Sanofi-Genzyme and Bayer-Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain foundation JL has received travel support and/or lecture honoraria from Biogen, Novartis, Merck, Alexion, Roche and SanofiGenzyme; has served on scientific advisory boards for Biogen, Novartis, Merck, Roche, BSM and SanofiGenzyme; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, and Novartis. Ethics Approval Statement: The study was approved by the The Swedish Ethical Review Authority (Dnr: 2019-00839/1199-18), and The Danish Data Protection Authority (Org. number 202100 2973).

Animal modeling of lower urinary tract dysfunction associated with multiple sclerosis: Part I: Justification of the mouse model for MS research.

Lower urinary tract symptoms and dysfunction(LUTS/LUTD) contribute to loss of quality of life, morbidity, and need for medical intervention in most patients with multiple sclerosis (MS). Although MS is an inflammatory neurodegenerative disease, clinical manifestations including continence control disorders have traditionally been attributed to the loss of neural signaling due to neurodegeneration. Clinical approaches to MS-LUTS/LUTD have focused on addressing symptoms in the context of urodynamic dysfunctions as pathophysiologic understandings are incomplete. The mouse model provides a useful research platform for the discovery of more detailed molecular, cellular, and tissue-level knowledge of the disease and its clinical manifestations. The aim of this two-part review is to provide a state-of-the-art update on the use of the mouse model for MS research, with a focus on lower urinary tract symptoms. Part I presents a summary of the current understanding of MS pathophysiology, the impact on lower urinary tract symptoms, and briefly introduces the types of mouse models available to study MS. Part II presents the common animal models that are currently available to study MS, their mechanism, relevance to MS-LUTS/LUTD and their urinary pathophysiology, advantages, and disadvantages.

Telehealth in Multiple Sclerosis Clinical Care and Research.

Purpose of ReviewThe COVID-19 pandemic has provided us with a unique opportunity to experiment with telehealth and evaluate its benefits and limitations. This review discusses the impact of telehealth on multiple sclerosis (MS) care and research in adults and children.Recent FindingsTelehealth visits for MS patients have been shown to reduce missed workdays and costs for patients. Brief telephone-based counseling may be associated with better adherence to disease-modifying therapy, although results of multiple home-based tele-rehabilitation for people with MS have been equivocal. Overall, patients and providers have reported high levels of satisfactions with telehealth. Several remote disability measures and numerous other technological tools have emerged for use in remote MS research and care. Major challenges of telehealth include limitations to performing a complete neurologic exam and disparities in access to telehealth amongst vulnerable populations with limited access to virtual platforms.SummaryFollowing the rapid expansion of telehealth during the pandemic, it is highly likely that we will continue to embrace the benefits of this valuable tool. Future directions for improving telehealth should include more evidence-based research on the diagnostic accuracy in neuroimmunology and reducing disparities in the access to telehealth.