Multiple Sclerosis Research Research Articles

Quality of life differences between African Americans and Hispanic Americans with multiple sclerosis

BackgroundIn comparison to non-minority patients with multiple sclerosis, minority research in multiple sclerosis continues to be only a few percent of the literature. Often, the comparator group is with the Caucasian populations of the world, who themselves comprise of non-ubiquitous groups. Comparisons between minority groups have not been done as they relate to quality of life, partly because the populations are smaller. Our study will compare the quality life differences between two minority populations living in the same geographic and urban area.MethodsThis study utilized cross-sectional data from an observational prospective cohort study. A total of 28 minority patients were included in this study. All patients were on a disease modifying therapy. Demographic information was obtained. The primary outcome measure was the MSQLI and all scores were derived from the MSQLI user’s manual.ResultsThe MSQLI scores of the Mental Health Index were lower in all areas for Hispanic White MS patients as compared to Non-Hispanic African American patients, but 3 of 5 were statistically significant: MHI total score, MHI anxiety, and MHI behavioral control subscores (all p < 0.05). When investigating if EDSS associated with MSQLI measures, independent of minority group, the only noted difference was between the mild (EDSS< or = 3) and the moderate group (EDSS 3.5–5.5) in the Physical Components Score and Health Transition Score (p = 0.028 and p < 0.05).ConclusionThe study begins to elucidate differences in quality life measures between minorities with multiple sclerosis potentially leading to culturally competent care.

Semaphorin 4A as a biomarker of multiple sclerosis and neuromyelitis optica spectrum disorder

AbstractSelecting appropriate treatment from the early stage of the disease is important for a better prognosis for patients with multiple sclerosis (MS). Although various disease‐modifying drugs have been approved for MS, there is no appropriate biomarker to predict treatment responsiveness. We have recently identified serum semaphorin 4A (Sema4A) as a biomarker for predicting the treatment efficacy of interferon‐β therapy. One‐third of patients with MS show high serum Sema4A levels. These patients tend to have a higher Expanded Disability Status Scale score, and possess immune characteristics of Th17‐skewing condition. Interestingly, these patients do not respond effectively to interferon‐β therapy. However, retrospective analysis of our MS cohort showed that those with high serum Sema4A levels show a favorable response to fingolimod (FTY) therapy. Efficacy of FTY was observed even in patients who later switched to FTY due to recurrent attacks under interferon‐β therapy. Our observations suggest that FTY could be a better candidate for managing the disease activity of MS patients with high Sema4A levels. Considering the fact that the efficacy of other various disease‐modifying drugs still remains elusive among MS patients with varying Sema4A profile, further investigation is required to clarify the role of serum Sema4A as a biomarker in making an appropriate decision regarding various disease‐modifying drug choices. For patients with neuromyelitis optica spectrum disorder, we found that a certain proportion of patients show high levels of serum Sema4A. In the present review, we discuss the current advances in the field of MS research focusing on the role of Sema4A, and further present the clinical features of neuromyelitis optica spectrum disorder patients with high Sema4A levels.

Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study.

BackgroundThe Clinical Understanding and Research Excellence in ME/CFS group (CureME) at the London School of Hygiene & Tropical Medicine has supported and undertaken studies in immunology, genetics, virology, clinical medicine, epidemiology and disability. It established the UK ME/CFS Biobank (UKMEB), which stores data and samples from three groups: participants with ME/CFS, Multiple Sclerosis (MS) and healthy controls. Patient and public involvement have played a central role from its inception.AimTo explore the views of participants with ME/CFS and MS on CureME research findings, dissemination and future biomedical research priorities.MethodFive ME/CFS and MS focus groups were conducted at two UK sites. Discussions were transcribed and analysed thematically.ResultsA total of 28 UKMEB participants took part: 16 with ME/CFS and 12 with MS. Five themes emerged: (a) Seeking coherence: participants’ reactions to initial research findings; (b) Seeking acceptance: participants explore issues of stigma and validation; (c) Seeking a diagnosis: participants explore issues around diagnosis in their lives; (d) Seeking a better future: participants’ ideas on future research; and (e) Seeking to share understanding: participants’ views on dissemination. Focus groups perceived progress in ME/CFS and MS research in terms of “putting together a jigsaw” of evidence through perseverance and collaboration.ConclusionThis study provides insight into the emotional, social and practical importance of research to people with MS and ME/CFS, suggesting a range of research topics for the future. Findings should inform biomedical research directions in ME/CFS and MS, adding patients’ voices to a call for a more collaborative research culture.

Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis.

In the majority of patients multiple sclerosis starts with a relapsing remitting course (RRMS), which may at later times transform into secondary progressive disease (SPMS). In a minority of patients the relapsing remitting disease is skipped and the patients show progression from the onset (primary progressive MS, PPMS). Evidence obtained so far indicate major differences between RRMS and progressive MS, but no essential differences between SPMS and PPMS, with the exception of a lower incidence in the global load of focal white matter lesions and in particular in the presence of classical active plaques in PPMS. We suggest that in MS patients two types of inflammation occur, which develop in parallel but partially independent from each other. The first is the focal bulk invasion of T- and B-lymphocytes with profound blood brain barrier leakage, which predominately affects the white matter, and which gives rise to classical active demyelinated plaques. The other type of inflammation is a slow accumulation of T-cells and B-cells in the absence of major blood brain barrier damage in the connective tissue spaces of the brain, such as the meninges and the large perivascular Virchow Robin spaces, where they may form aggregates or in most severe cases structures in part resembling tertiary lymph follicles. This type of inflammation is associated with the formation of subpial demyelinated lesions in the cerebral and cerebellar cortex, with slow expansion of pre-existing lesions in the white matter and with diffuse neurodegeneration in the normal appearing white or gray matter. The first type of inflammation dominates in acute and relapsing MS. The second type of inflammation is already present in early stages of MS, but gradually increases with disease duration and patient age. It is suggested that CD8+ T-lymphocytes remain in the brain and spinal cord as tissue resident cells, which may focally propagate neuroinflammation, when they re-encounter their cognate antigen. B-lymphocytes may propagate demyelination and neurodegeneration, most likely by producing soluble neurotoxic factors. Whether lymphocytes within the brain tissue of MS lesions have also regulatory functions is presently unknown. Key open questions in MS research are the identification of the target antigen recognized by tissue resident CD8+ T-cells and B-cells and the molecular nature of the soluble inflammatory mediators, which may trigger tissue damage.

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Stockholm, Sweden - September 11-13, 2019

35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Stockholm, Sweden - September 11-13, 2019

Validity of the Marshall Sitting Questionnaire in people with multiple sclerosis

ABSTRACTThis study examines the validity of the Marshall Sitting Questionnaire (MSQ) in people with multiple sclerosis (MS) and presents a prediction model to improve the accuracy of the MSQ estimates. Participants (n = 63 [15M and 48F], age: 56.6 ± 7.3 years) wore an accelerometer on the hip for a 7-day period and completed the MSQ. Sedentary behaviour (SB) estimates were computed as min/day for both the MSQ and accelerometer. Associations between the two methods were examined using the Pearson correlation and agreement was assessed using a Bland-Altman plot. A linear prediction model was developed to improve the accuracy of the MSQ estimates using a selection of predictor variables routinely collected in MS research. There was a moderate correlation between MSQ and accelerometer SB estimates (r = 0.34, p < 0.01). The Bland-Altman plot indicated that the MSQ overestimated SB (mean bias: 80.54 min/day, 95% limits of agreement: −410.5 to 571.5 min/day). The prediction model improved the MSQ estimates by 39% and virtually eliminated measurement bias (mean bias:-0.21 min/day; 95% limits of agreement:-109.8 to 109.4 min/day). The results indicate preliminary evidence for the validity of the MSQ in people with MS, and support the application of an alternative prediction model to improve the accuracy of the MSQ estimates.Abbreviations: SB = sedentary behaviour; MS = multiple sclerosis; MSQ = Marshall Sitting Questionnaire; PA = physical activity; EDSS = Expanded Disability Status Scale; LPA = light physical activity; MVPA = moderate-to-vigorous physical activity; GLTEQ = Godin Leisure Time Exercise Questionnaire; PDDS = Patient-Determined Disease Steps; RMSE = root mean square error.

Power and hegemony in research supervision: A critical discourse analysis

&lt;p align="center"&gt;&lt;em&gt;This qualitative case study research aimed to investigate the notions of power and hegemony in research consultations around the construct of language ideologies. The study employed purposive sampling by selecting two MS (Education) research supervisees with their supervisors. It identified a social wrong of power and hegemony in research supervision practices and with a transformative spirit, hoped to bring about awareness and modifications in research supervision. Methodically, the study followed the analytical approach of Norman Fairclough’s Critical Discourse Analysis (CDA) (1989; 2003). The data were collected through observations and transcriptions of research consultation meetings and interviews of the participants. The textual analysis of case one revealed how language became a source of establishing asymmetrical power relations between the participants. Contrastingly, in case two the consultations were not hinged on language aspects and had more equality and homogeneity between the partners. The finding of the study indicated that language ideologies played a very important role in sustaining the dominant position of the powerful agent, that is, the supervisor. Based on the findings, it is hoped that this research would lead to more democratic styles of supervision and equity and emancipation in supervision as a social practice.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords: &lt;/strong&gt;critical discourse analysis, power and hegemony, language ideologies, research supervision&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Multiple sclerosis in 2018: new therapies and biomarkers

2018 has been a year of substantial progress in multiple sclerosis research, with breakthroughs in experimental medicine and translational research. Advances have ranged from successful clinical trials to new reports of promising biomarkers and improved understanding of the pathophysiology of multiple sclerosis.

Health Outcomes and Lifestyle in a Sample of People With Multiple Sclerosis (HOLISM): Longitudinal and Validation Cohorts.

Objective: To report the methodology and summary data of the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) longitudinal and validation cohorts. We report (1) data on participation, socio-demographics, disease characteristics, medication use, modifiable lifestyle risk factor exposures, and health outcomes of the HOLISM longitudinal cohort 2.5-years post enrolment; (2) attrition at this 2.5-year wave; and (3) baseline characteristics of the associated HOLISM validation cohort.Methods: The HOLISM longitudinal study recruited people internationally with self-reported diagnosed multiple sclerosis (MS) through web 2.0 platforms and MS society newsletters. Participants, first recruited in 2012, were invited 2.5-years later to participate in a follow-up survey. At both time points, participants completed a comprehensive online questionnaire of socio-demographics, modifiable lifestyle exposures, and health outcomes using validated and researcher-designed tools. The same methodology was used to recruit a new sample: the HOLISM validation cohort. Characteristics were explored using summary measures.Results: Of 2,466 people with MS at baseline, 1,401 (56.8%) provided data at 2.5-year follow-up. Attrition was high, likely due to limited amount of contact information collected at baseline. Completion of the 2.5-year wave was associated with healthier lifestyle, and better health outcomes. Participants completing follow-up had diverse geographical location, were predominantly female, married, unemployed or retired. At 2.5-year follow-up, nearly 40% were overweight or obese, most were physically active, non-smokers, consumed little alcohol, used vitamin D/omega-3 supplements, and 42% reported current disease-modifying drug use. Thirty percentage of reported cane or gait disability, while 13% relied on major mobility supports (Patient Determined Disease Steps). Approximately half the respondents reported a comorbidity, 63% screened positive for clinically significant fatigue (Fatigue Severity Scale), and 22% screened positive for depression (Patient Health Questionnaire-9). The validation cohort's characteristics were mostly consistent with previously reported HOLISM baseline data.Conclusions: Exploring prospective associations of modifiable environmental/behavioral risk factors with health outcomes in this international longitudinal sample of people with MS will be beneficial to MS research. Impacts of attrition and selection bias will require consideration. The validation cohort provides opportunity for replication of previous findings, and also for temporal validation of predictive models derived from the HOLISM cohort.

The International Multiple Sclerosis Visual System Consortium: Advancing Visual System Research in Multiple Sclerosis.

The International Multiple Sclerosis Visual System Consortium (IMSVISUAL) was formed in November 2014 with the primary goal of improving research, care, and education regarding the role of the visual system in multiple sclerosis (MS) and related disorders. In this review, we describe the formation, goals, activities, and structure of IMSVISUAL, as well as the relationship of IMSVISUAL with the Americas Committee for Treatment and Research in MS (ACTRIMS). Finally, we provide an overview of the work IMSVISUAL has completed to date, as well as an outline of research projects ongoing under the auspices of IMSVISUAL. IMSVISUAL has 140 members worldwide and continues to grow. Through IMSVISUAL-related research, optical coherence tomography (OCT)-derived peripapillary retinal nerve fiber layer (pRNFL) thinning has been established as a predictor of future disability in MS. IMSVISUAL has also developed guidelines for reporting OCT studies in MS. Moreover, a systematic review performed by IMSVISUAL found that not only are pRNFL and ganglion cell + inner plexiform layer (GCIPL) thicknesses reduced in patients with MS (particularly in eyes with prior optic neuritis [ON]), but that inner nuclear layer measures may be higher among MS ON eyes, relative to healthy control eyes. Currently, there are several ongoing IMSVISUAL projects that will establish a role for visual outcomes in diagnosing MS and quantifying the effects of emerging therapies in clinical trials. The development of IMSVISUAL represents a major collaborative commitment to defining the role of visual outcomes in high-quality, large-scale studies that generate definitive and instructive findings in the field of MS. As a consortium, IMSVISUAL has completed several international collaborative projects, is actively engaged in numerous ongoing research studies, and is committed to expanding the role of vision research in MS and related disorders.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET

BackgroundOver the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with high affinity to the 18-kDa translocator-protein (TSPO), which is mainly expressed on activated microglia. The aim of this proof of concept study was to evaluate this in vivo marker of neuroinflammation in primary and secondary progressive MS.MethodsAll subjects were genotyped for the rs6971 polymorphism within the TSPO gene, and low-affinity binders were excluded from participation in this study. Eight patients with progressive MS and seven age and genetic binding status matched healthy controls underwent a 60 min dynamic PET scan using [18F]DPA714, including both continuous on-line and manual arterial blood sampling to obtain metabolite-corrected arterial plasma input functions.ResultsThe optimal model for quantification of [18F]DPA714 kinetics was a reversible two-tissue compartment model with additional blood volume parameter. For genetic high-affinity binders, a clear increase in binding potential was observed in patients with MS compared with age-matched controls. For both high and medium affinity binders, a further increase in binding potential was observed in T2 white matter lesions compared with non-lesional white matter. Volume of distribution, however, did not differentiate patients from healthy controls, as the large non-displaceable compartment of [18F]DPA714 masks its relatively small specific signal.ConclusionThe TSPO radioligand [18F]DPA714 can reliably identify increased focal and diffuse neuroinflammation in progressive MS when using plasma input-derived binding potential, but observed differences were predominantly visible in high-affinity binders.

Ozanimod for the treatment of relapsing remitting multiple sclerosis

ABSTRACT Introduction Ozanimod is a selective sphingosine 1-phosphate receptor 1 and 5 modulator under development by Celgene, for the treatment of relapsing remitting multiple sclerosis. Extensive clinical experience has become available for the related compound fingolimod, favoring the sphingosine 1-phosphate therapeutic concept. Off-target effects have been attributed to its low receptor specificity and have prompted the development of next generation sphingosine 1-phosphate receptor modulators. Areas covered The authors evaluate the literature of ozanimod, using the PubMed database as well as repositories of the European Committee for Treatment and Research in Multiple Sclerosis and the American and European Academy of Neurology. Specifically, the authors cover and discuss the preclinical data on ozanimod, pharmacokinetics and dynamics, and data on efficacy and safety from the pivotal trials. Expert opinion Superiority of ozanimod over intramuscular interferon β-1a with regard to reduction in annualized relapse rate and magnetic resonance imaging outcomes has been shown in two phase III trials. The beneficial effect on brain volume and gray matter loss are encouraging and in line with data on other newer immunomodulators. Ozanimod is a valuable contribution to the therapeutic armamentarium in MS, although the effect on disability progression is unclear and requires further investigations.

European and American Guidelines for Multiple SclerosisTreatment.

The management and treatment of multiple sclerosis (MS) is becoming more and more complex as many medications are now available, with different routes of administration, mechanisms of action, and effectiveness and safety profiles. The decision-making process to choose the right medication is a complex task requiring a careful evaluation of the results of clinical and post-marketing studies, and the capability to translate data from clinical studies to patients in everyday clinical practice. Two European neurological societies, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and European Academy of Neurology (EAN), and the American Academy of Neurology (AAN) have recently delivered guidelines for MS treatment, helping neurologists to address the most common clinical issues related to this topic. The two guidelines offer a similar view and similar recommendations for the most relevant and common questions of clinical practice. For some aspects of MS treatment the statements are slightly different, in particular regarding pregnancy management in relation to treatments, the use of mitoxantrone, and the treatment of secondary progressive MS (SP-MS).

Expanded disability status scale progression assessment heterogeneity in multiple sclerosis according to geographical areas.

Using placebo data from 3 randomized multiple sclerosis (MS) trials with uniform inclusion criteria, we investigated heterogeneity of Expanded Disability Status Scale (EDSS) progression by geographical areas. Our analysis revealed a significantly lower EDSS progression in Eastern European countries (10.8%) compared with Western Europe (13.1%) or the USA/Canada (21.4%, p < 0.001); EDSS improvement behaved the same way. This heterogeneity is not explained by differences of baseline variables. No differences were detected on more easily quantifiable measures, the Timed 25-Foot Walk or the Multiple Sclerosis Functional Composite. At a time when disease progression represents the target for future interventions in MS, establishment of more quantitative and objective outcomes remains a key priority of MS research. Ann Neurol 2018;84:621-625.

Prophylactic treatment against GM-CSF, but not IL-17, abolishes relapses in a chronic murine model of multiple sclerosis.

The pathogenic role of IL-17 and GM-CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP139-151 ) to trigger EAE-relapses (EAE-II) in SJL mice that had recovered from a primary-EAE episode (EAE-I). This procedure resulted in severe and irreversible disease that, unlike EAE-I, was not abolished by anti-IL-17-mAb. In contrast, prophylactic anti-GM-CSF-mAb treatment prevented EAE-I and -II. Strikingly, the expression of T-cell transcription factors and cytokines/chemokines in mice treated with anti-GM-CSF during both EAE episodes was silenced. Anti-GM-CSF-mAb treatment administered only during EAE-II did not completely prevent relapses but mice ultimately reached full recovery. Anti-GM-CSF treatment also strongly impaired and ultimately resolved monophasic MOG35-55 -induced EAE in C57Bl/6 mice. In such protected mice, anti-GM-CSF treatment also prevented a further relapse induced by MOG-revaccination. These results underscore the critical role of GM-CSF on pro-inflammatory mediator production. Furthermore, we observed a strong preventive and curative effect of anti-GM-CSF neutralisation in two EAE models, relapsing and chronic. Altogether these findings are relevant for further MS research.

Promoting remyelination through cell transplantation therapies in a model of viral-induced neurodegenerative disease.

Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Several United States Food and Drug Administration-approved therapies exist that impede activated lymphocytes from entering the CNS thereby limiting new lesion formation in patients with relapse-remitting forms of MS. However, a significant challenge within the field of MS research is to develop effective and sustained therapies that allow for axonal protection and remyelination. In recent years, there has been increasing evidence that some kinds of stem cells and their derivatives seem to be able to mute neuroinflammation as well as promote remyelination and axonal integrity. Intracranial infection of mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in immune-mediated demyelination and axonopathy, making this an excellent model to interrogate the therapeutic potential of stem cell derivatives in evoking remyelination. This review provides a succinct overview of our recent findings using intraspinal injection of mouse CNS neural progenitor cells and human neural precursors into JHMV-infected mice. JHMV-infected mice receiving these cells display extensive remyelination associated with axonal sparing. In addition, we discuss possible mechanisms associated with sustained clinical recovery. Developmental Dynamics 248:43-52, 2019. © 2018 Wiley Periodicals, Inc.

Multiple sclerosis: pregnancy and women's health issues

BackgroundThe course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. AimsTo analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease. MethodsWe conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for ‘multiple sclerosis’, ‘MS’, ‘EAE’, ‘pregnancy’, ‘hormonal factors’, ‘treatment’, and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts. Results and conclusionsWe provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, foetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data.

The Swiss Multiple Sclerosis Registry (SMSR): study protocol of a participatory, nationwide registry to promote epidemiological and patient-centered MS research

BackgroundMultiple sclerosis (MS) is one of the most frequently observed neurological conditions in Switzerland, but data sources for country-wide epidemiological trend monitoring are lacking. Moreover, while clinical and laboratory MS research are generally well established, there is a gap in patient-centered MS research to inform care management, or treatment decisions and policy making not only in Switzerland but worldwide.MethodsIn light of these research gaps, the Swiss Multiple Sclerosis Society initiated and funded the Swiss Multiple Sclerosis Registry (SMSR) an open-ended, longitudinal and prospective, nationwide, patient-centered study.The SMSR recruits adult persons with a suspected or confirmed MS diagnosis who reside or receive care in Switzerland. The SMSR has established a governance structure with clear rules and guidelines. It follows a citizen-science approach with direct involvement of persons with MS (PwMS), who contribute actively to registry development, operations, and research. Main scientific goals entail the study of MS epidemiology in Switzerland, health care access and provision, as well as life circumstances and wellbeing of persons with MS.The innovative study design (“layer model”) offers several participation options with different time commitments. Data collection is by means of regular surveys and medical record abstraction. Survey participation is offered in different modes (web, paper & pencil) and in the three main national languages (German, French, Italian). Participants also receive regular data feedbacks for personal use and self-monitoring, contextualized in the whole population of study participants. Data feedbacks are also used to solicit data corrections of key variables from participants.DiscussionThe SMSR combines the advantages of traditional and novel research methods in medical research and has recruited over 1600 PwMS in its first year. The future-oriented design and technology will enable a response not only to future technological innovations and research trends, but also to challenges in health care provision for MS.Trial registrationClinicalTrials.gov NCT02980640; December 6, 2016; retrospectively registered.

Validation of the preference-based multiple sclerosis index

Background: Preference-based measures of health-related quality of life (HRQL) are used as primary or secondary endpoints in multiple sclerosis (MS) research. Objective: The purpose of this paper was to evaluate the structural, convergent, and known-groups validity of the preference-based multiple sclerosis index (PBMSI) of HRQL in people with MS. Methods: Participants were recruited from three MS clinics in Montreal. Structural validity was assessed using polychoric correlation coefficients and factor analysis. To assess convergent validity, hypotheses were formulated about the strength of correlations between the PBMSI and other HRQL measures. Known-groups validity was assessed against different measures of disability. Results: The average age of the sample was 46 and 77% were women. Factor analysis supported the structural validity of the PBMSI; the items collectively were measuring one underlying construct. The PBMSI showed convergent validity against generic measures of HRQL, and known-groups validity between persons with different levels of disability. Conclusion: The results of this study support the construct validity of the PBMSI as an outcome measure of HRQL in MS. The PBMSI overcomes limitations observed with currently used HRQL measures in MS and may be used to contrast different interventions for people with MS.