Participants' perspectives of "NeuroSask: Active and Connect"-a virtual chronic disease management program for individuals with a neurological condition.

Introduction: Neurological conditions account from more than half of Canadians requiring chronic care. Both physical activity and the development of a self-management skillset are critical components supporting individuals with chronic health conditions. "NeuroSask: Active and Connected" is a virtual chronic disease management program offering twice weekly neuro-physiotherapist directed "active" exercise sessions, followed by weekly knowledge-exchange "connect" sessions with invited guest experts. NeuroSask was launched April 2020 in response to the restricted services and supports for people with neurological conditions. The program aimed to provide seated physical activity, social interaction, and access to expertise in neurological conditions and neurorehabilitation. A program evaluation of NeuroSask was conducted to gain participants' perspectives. Methods: All participants registered for the NeuroSask program were invited to complete optional online surveys (SurveyMonkey) circulated by email at 3 occasions post-program launch: 10 weeks, 1 year, and 2 years. Participants could complete any one or all of the surveys, at their discretion. The number of potential respondents changed dependent on the total number of participants registered for NeuroSask at the time the survey was circulated. Questions were co-designed by multi-stakeholder team members. Descriptive statistics were used for closed-ended questions and a reflexive thematic analysis was completed with coding conducted in NVivo 12 Plus for open-ended text. Results: Response rates (participants/registrants) were as follows: 10-week survey 260/793, one year survey 326/1224, and 2-year survey 434/1989. 90% of participants reported being in either the age categories of 40-59 years or above 60 years. 75% of both survey respondents and program registrants were female. 70% of both survey respondents and program registrants reported a diagnosis of multiple sclerosis and 30% reported other neurological conditions. Survey respondents were from all ten Canadian provinces, with 45% reporting living outside of large cities. Respondents reported preferring online vs. in person format for this type of programming. Three main themes, and eight corresponding subthemes were identified highlighting the perceived impact and key components of the NeuroSask program: Theme 1 "together in a positive and encouraging environment" (subthemes 1a: connection, 1b: empowerment); Theme 2 "access to enthusiastic qualified leaders from home" (subthemes 2a: leader characteristics, 2b: accessibility, 2c: program logistics); Theme 3 "being able to enjoy everyday life" (subthemes 3a: symptom benefits and beyond, 3b: carry-over, 3c: keep going, please do not cancel). Conclusion: NeuroSask is an example of an accessible and meaningful virtual approach to providing ongoing support for some individuals with neurological conditions. It was perceived as beneficial for fostering community and connection in a positive environment with perceived benefits extending beyond symptom management to participant reported improvements in function, daily life, and disease experience.

Physiotherapist and participant perspectives from a randomized-controlled trial of physiotherapist-supported online vs. paper-based exercise programs for people with moderate to severe multiple sclerosis.

PURPOSE: There is a gap in research on how best to support exercise in moderate to severe MS. The objective of this study is to share perspectives of people living with MS and physiotherapists on their experiences in a randomized clinical trial of online physiotherapy vs. an active comparator. METHODS: Semi-structured exit interviews were conducted with volunteer participants from the online and comparator arms of the trial, and focus groups were held with study physiotherapists. Transcripts were analyzed using reflexive thematic analysis. RESULTS: Perspectives from participants with MS yielded three themes: usability of their program, utility of their program, and motivation to participate. Visual and dexterity impairments limited the usability of the online program. Having an opportunity "to be pushed" was valued by participants in both trial arms. Motivation to exercise was variable, and participants desired periodic face-to-face contact with their physiotherapists. Perspectives from trial physiotherapists yielded similar and complementary findings concerning usability and utility. CONCLUSIONS: Participants with MS and physiotherapists found the online physiotherapy platform useful for supporting exercise, yet they identified some limitations. As the appeal of online platforms has increased since the pandemic, it will be important to consider the needs of people with moderate to severe MS. TRIAL REGISTRATION NUMBER: NCT03039400.IMPLICATIONS FOR REHABILITATIONPeople with moderate-to-severe MS and physiotherapists involved in a clinical trial found online physiotherapy useful for supporting exercise. Physiotherapists and participants using the online program desired improved platform accommodations for people living with MS with visual and dexterity impairments.Physiotherapists and people living with MS from both the online exercise program and comparator groups perceived a need for more face-to-face contact and opportunities to build therapeutic alliance.Perspectives from prescribing physiotherapists and people living with MS about supporting exercise online may have practice implications during and post-pandemic.

Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age.

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a 'sub-proteome', such as the 'metalloproteome', defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1-1) isoform in 15% of the population.

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.

Magnetic Resonance Imaging of Spinal Cord Lesions in Patients with Multiple Sclerosis in Saskatchewan, Canada.

BACKGROUND: Spinal cord lesions (SCLs) contribute to disability in multiple sclerosis (MS). Data in Saskatchewan, Canada, concerning SCLs and their association with disability levels in patients with MS are lacking. The study objectives were to identify clinicodemographic profiles of patients with MS with respect to spinal cord magnetic resonance imaging (MRI) involvement; determine the frequency of individuals with MRI SCLs; and explore differences between patients with MS with and without SCLs with respect to disability and disease-modifying therapy status. METHODS: A monocentric, cross-sectional, retrospective review of prospectively collected data from 532 research-consented patients seen at Saskatoon MS Clinic was performed. Data were collected from a database and electronic medical records. RESULTS: Of the 356 patients (66.9%) with an SCL, 180 (50.6%) had only cervical cord lesions. Median Expanded Disability Status Scale (EDSS), ambulation, and pyramidal scores of patients with SCLs were higher than those of patients without SCLs. Of patients with EDSS scores of at least 6, those with SCLs were younger than those without SCLs (P = .01). Patients with SCLs were 55% less likely to have been on continuous disease-modifying therapy since diagnosis than patients without SCLs (adjusted odds ratio, 0.45; 95% CI, 0.25-0.81; P = .008). CONCLUSIONS: Prevalence and association with disability of SCLs in patients with MS are comparable with existing literature. Patients with MS with SCLs have higher levels of disability and attain EDSS scores of at least 6 at a younger age.

Adherence to Physiotherapy-Guided Web-Based Exercise for Persons with Moderate-to-Severe Multiple Sclerosis: A Randomized Controlled Pilot Study.

BACKGROUND: Options to support adherence to physical activity in moderate-to-severe multiple sclerosis (MS) are needed. The primary aim was to evaluate adherence to a Web-based, individualized exercise program in moderate-to-severe MS. Secondary aims explored changes in 29-item Multiple Sclerosis Impact Scale, Hospital Anxiety and Depression Scale (HADS), grip strength, Timed 25-Foot Walk test, and Timed Up and Go (TUG) results. METHODS: Participants were randomized (2:1) to a physiotherapist-guided Web-based home exercise program or a physiotherapist-prescribed written home exercise program. The primary outcome was adherence (number of exercise sessions over 26 weeks). Secondary outcomes were described in terms of means and effect sizes. RESULTS: There were 48 participants: mean ± SD age, 54.3 ± 11.9 years; disease duration, 19.5 ± 11.0 years; and Patient-Determined Disease Steps scale score, 4.4 ± 1.6. There was no significant difference in mean ± SD adherence in the Web-based group (38.9 ± 28.1) versus the comparator group (34.6 ± 40.8; U = 198.5, P = .208, Hedges' g = 0.13). Nearly 50% of participants (23 of 48) exercised at least twice per week for at least 13 of the 26 weeks. Adherence was highest in the Web-based subgroup of wheelchair users. Medium effect sizes were found for the HADS anxiety subscale and in ambulatory participants for TUG. There were no adverse events. CONCLUSIONS: There was no difference in exercise adherence between the Web-based and active comparator groups. There was no worsening of secondary outcomes or adverse events, supporting the safety of Web-based physiotherapy. More research is needed to determine whether wheelchair users might be most likely to benefit from Web-based physiotherapy.

The Dilemma of When to Stop Disease-Modifying Therapy in Multiple Sclerosis: A Narrative Review and Canadian Regional Reimbursement Policies.

BACKGROUND: Disease-modifying therapy (DMT) has changed the landscape of multiple sclerosis (MS) care. However, there is lack of consensus on the duration of treatment and the selection of individuals most likely to benefit from continued treatment. Current evidence, practice guidelines, health policy, and ethical considerations presented together may further inform challenging clinical decision making and future directions. The objectives of this study were to conduct a narrative review of original research and practice guideline recommendations on discontinuation of DMTs in MS; to collect information regarding Canadian regional reimbursement policies for DMT coverage in MS; and to present ethical considerations applicable to such decision making. METHODS: A literature review was conducted of the MEDLINE/PubMed, OneFile (GALE), Scopus (Elsevier), and ProQuest Biological Science Collection databases. Data regarding Canadian regional reimbursement policies for DMT coverage in MS were collected from the ministry/government websites. Ethical considerations were reviewed in the context of the identified evidence, guidelines, and policies. RESULTS: The literature lacks evidence from prospective randomized controlled trials that directly addresses the issue of discontinuation of DMTs in MS. Current practice guidelines advocate the vital role of patient choice in decision making. There are regional variations in Expanded Disability Status Scale criteria scores for continuing MS DMT coverage among Canadian provinces/territories. CONCLUSIONS: In the absence of strong evidence on discontinuation of DMTs, shared decision making and consideration of the ethical complexities could help in the decision-making process.

Predictors of hospitalization in a Canadian MS population: A matched cohort study.

OBJECTIVE: Hospitalizations are the most costly component of healthcare in Canada, and hospitalization rates are higher in the multiple sclerosis (MS) population compared to the general population. This study aimed to examine predictors of hospitalizations in the MS population in Saskatchewan, Canada. METHODS: This retrospective cohort study used population-based health administrative data from Saskatchewan, Canada from 1996 to 2016. Subjects with MS were identified using a validated definition (≥3 hospital, physician, or drug claims for MS). Up to five general population controls were identified for each MS case and matched on sex, age, and geographical location. The rate of hospitalizations and reason for admission were determined for each case and control. Negative binomial (hospitalization rate) and binary logistic (reason for admission) regression models fitted with generalized estimating equations were used to test the following potential predictors: sex, age, median household income, calendar year, prior hospitalizations, and comorbidity status. RESULTS: We identified 4,878 MS cases (11,744 hospitalizations), and 23,662 matched controls (32,541 hospitalizations). Higher comorbidity burden, older age, and prior hospital admissions were associated with an increased rate of all-cause hospitalizations for both cohorts. Males were more likely to be hospitalized than females for all-cause (adjusted rate ratio: 1.20; 95% CI: 1.07 - 1.34) and MS-specific (adjusted odds ratio: 1.34; 95% CI 1.15 - 1.55) hospitalizations. The rate of MS-specific hospitalizations decreased with age, and there was no association with comorbidity or prior hospitalizations. A diagnosis of MS was associated with decreased odds of hospitalization due to neoplasms, diseases of the circulatory system, and mental health and behavioural disorders. CONCLUSION: Increased age, comorbidity, and prior hospital admissions are predictors of all-cause hospitalizations. Conversely, MS-related hospitalizations decreased as subjects aged, and there was no association with comorbidity. Our results highlight that reasons for hospitalizations can differ by age, and clinicians should consider this when managing patients, as they make efforts to reduce hospitalizations in the MS population.

Perspectives on walking from people with multiple sclerosis and reactions to video self-observation.

Purpose: People with multiple sclerosis (MS) rank walking among the most challenging aspects of their condition. A greater understanding of people's perspectives concerning their walking may help to prioritize walking outcomes and strategies for optimizing walking. The purpose was to explore perceptions of walking in people with MS and to describe their reactions after observing themselves walk on video.Materials and methods: An interpretive thematic analysis study using face-to-face, semi-structured interviews was conducted with 14 people who self-identified a change in their walking due to MS. Participants were video-recorded walking and watched their video during the interview.Results: Four themes were identified: "awareness," "acceptance," "constant change," and "increased effort." People with MS develop awareness of how their walking performance looks and awareness of constantly-changing internal factors and external factors which impact their walking. Awareness of change in fatigue, temperature, terrain, and the use of aids in particular are perceived relevant to walking and to impact the effort required to walk. People with MS also describe differences in their acceptance of how others view their walking and the changes related to walking. An analogy with a marionette performing describes how people perceive walking as no longer automatic; instead walking requires the person to consciously pull the strings to walk. An increase in both the physical and cognitive effort is required to walk and an awareness and acceptance of a variety of changes in oneself and the lived world may help or hinder walking. People with MS are willing to watch themselves walk on video and are not surprised by what they observe.Conclusions: People with MS develop a learned self-awareness with variable levels of acceptance about their walking function and what it looks like. The perceptions on walking from persons with MS suggest that focusing on reducing the effort to walk and minimizing the constantly-changing variables may help to optimize walking.Implications for rehabilitationPeople with multiple sclerosis are challenged by the increased effort and constant change required to walk in their day-to-day lives.A focus on minimizing both the effort to walk and the changing variables (i.e., fluctuating symptoms and environmental factors) is warranted.People with multiple sclerosis develop a learned awareness of how they walk and how their walking looks.Acceptance of loss of walking function is variable.Video self-observation is a feasible tool which warrants further exploration for enhancing acceptance of walking function and accommodating strategies.

Individualised behaviour change strategies for physical activity in multiple sclerosis (IPAC-MS): protocol for a randomised controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system. Because of the long-term and unpredictable nature of the disease, the burden of MS is significant from both a patient and societal perspective. Despite a recent influx of disease-modifying therapies to treat MS, many individuals continue to experience disability that negatively affects productivity and quality of life. Previous research indicates that physical activity has a positive impact on walking function in individuals with MS, in addition to the usual beneficial effects on overall health. However, most people with MS are not active enough to gain these benefits, and a lack of support to initiate and maintain physical activity has been identified as a major barrier. This study will evaluate the impact of a novel intervention involving individualised behaviour change strategies delivered by neurophysiotherapists on increasing physical activity levels in individuals with MS who are currently inactive. METHODS/DESIGN: This single-blind, parallel-group, randomised controlled trial will be conducted in Saskatchewan, Canada. Eligible participants include individuals with MS who are ambulatory but identified as currently inactive by the self-reported Godin Leisure-Time Exercise Questionnaire (GLTEQ). The intervention will be delivered by neurophysiotherapists and includes individualised behaviour change strategies aimed at increasing physical activity over a 12-month period. The control group will receive usual care during the 12-month study period. The primary outcome is the change in physical activity level, as measured by the change in the GLTEQ score from baseline to 12 months. Secondary outcomes include the change in patient-reported outcome measures assessing MS-specific symptoms, confidence and quality of life. DISCUSSION: Physical activity has been identified as a top research priority by the MS community. Findings from this novel study may result in new knowledge that could significantly impact the management and overall health of individuals with MS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04027114. Registered on 10 July 2019.

Establishing the Incidence and Prevalence of Multiple Sclerosis in Saskatchewan.

OBJECTIVE: To validate a case definition of multiple sclerosis (MS) using health administrative data and to provide the first province-wide estimates of MS incidence and prevalence for Saskatchewan, Canada. METHODS: We used population-based health administrative data between January 1, 1996 and December 31, 2015 to identify individuals with MS using two potential case definitions: (1) ≥3 hospital, physician, or prescription claims (Marrie definition); (2) ≥1 hospitalization or ≥5 physician claims within 2 years (Canadian Chronic Disease Surveillance System [CCDSS] definition). We validated the case definitions using diagnoses from medical records (n=400) as the gold standard. RESULTS: The Marrie definition had a sensitivity of 99.5% (95% confidence interval [CI] 92.3-99.2), specificity of 98.5% (95% CI 97.3-100.0), positive predictive value (PPV) of 99.5% (95% CI 97.2-100.0), and negative predictive value (NPV) of 97.5% (95% CI 94.4-99.2). The CCDSS definition had a sensitivity of 91.0% (95% CI 81.2-94.6), specificity of 99.0% (95% CI 96.4-99.9), PPV of 98.9% (95% CI 96.1-99.9), and NPV of 91.7% (95% CI 87.2-95.0). Using the more sensitive Marrie definition, the average annual adjusted incidence per 100,000 between 2001 and 2013 was 16.5 (95% CI 15.8-17.2), and the age- and sex-standardized prevalence of MS in Saskatchewan in 2013 was 313.6 per 100,000 (95% CI 303.0-324.3). Over the study period, incidence remained stable while prevalence increased slightly. CONCLUSION: We confirm Saskatchewan has one of the highest rates of MS in the world. Similar to other regions in Canada, incidence has remained stable while prevalence has gradually increased.

Prevalence of Extracranial Venous Narrowing on Magnetic Resonance Venography Is Similar in People With Multiple Sclerosis, Their Siblings, and Unrelated Healthy Controls: A Blinded, Case-Control Study.

PURPOSE: The study sought to assess and compare the prevalence of narrowing of the major extracranial veins in subjects with multiple sclerosis and controls, and to assess the sensitivity and specificity of magnetic resonance venography (MRV) for describing extracranial venous narrowing as it applies to the chronic cerebrospinal venous insufficiency theory, using catheter venography (CV) as the gold standard. METHODS: The jugular and azygos veins were assessed with time-of-flight MRV in this assessor-blinded, case-control study of subjects with multiple sclerosis, their unaffected siblings, and unrelated controls. The veins were evaluated by diameter and area, and compared with CV. Collateral vessels were also analyzed for maximal diameter, as a potential indicator of compensatory flow. RESULTS: A high prevalence of extracranial venous narrowing was demonstrated in all study groups, collectively up to 84% by diameter criteria and 90% by area, with no significant difference between the groups when assessed independently (P = .34 and .63, respectively). There was high interobserver variability in the reporting of vessel narrowing (kappa = 0.32), and poor vessel per vessel correlation between narrowing on MRV and CV (kappa = 0.064). Collateral neck veins demonstrated no convincing difference in maximum size or correlation with jugular narrowing. CONCLUSION: There is a high prevalence of narrowing of the major extracranial veins on MRV in all 3 study groups, with no significant difference between them. These findings do not support the chronic cerebrospinal venous insufficiency theory. Although MRV has shown a high sensitivity for identifying venous narrowing, time-of-flight imaging demonstrates poor interobserver agreement and poor specificity when compared with the gold standard CV.

Total knee arthroplasty in multiple sclerosis.

We present a case report of total knee arthroplasty complicated by spasticity and contractures in a patient with multiple sclerosis (MS). Four previous case reports in the literature describe adverse outcomes after total knee arthroplasty in persons with MS secondary to severe spasticity. Preoperative, intraoperative, and postoperative considerations for persons with MS, which may help to improve functional outcomes, are discussed. Prospective research is needed among persons with MS to help determine the timing and selection of persons for arthroplasty and to minimize complications related to spasticity.

The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results.

OBJECTIVE: People with multiple sclerosis (MS) are living longer so strategies to enhance long-term health are garnering more interest. We aimed to create a profile of ageing with MS in Canada by recruiting 1250 (5% of the Canadian population above 55 years with MS) participants and focusing data collection on health and lifestyle factors, disability, participation and quality of life to determine factors associated with healthy ageing. DESIGN: National multicentre postal survey. SETTING: Recruitment from Canadian MS clinics, MS Society of Canada chapters and newspaper advertisements. PARTICIPANTS: People aged 55 years or older with MS symptoms more than 20 years. OUTCOME MEASURES: Validated outcome measures and custom-designed questions examining MS disease characteristics, living situation, disability, comorbid conditions, fatigue, health behaviours, mental health, social support, impact of MS and others. RESULTS: Of the 921 surveys, 743 were returned (80.7% response rate). Participants (mean age 64.6±6.2 years) reported living with MS symptoms for an average of 32.9±9.5 years and 28.6% were either wheelchair users or bedridden. There was only 5.4% missing data and 709 respondents provided optional qualitative information. According to data derived from the 2012 Canadian Community Health Survey of Canadians above 55 years of age, older people with MS from this survey sample are about eight times less likely to be employed full-time. Older people with MS were less likely to engage in regular physical activity (26.7%) compared with typical older Canadians (45.2%). However, they were more likely to abstain from alcohol and smoking. CONCLUSIONS: Despite barriers to participation, we were able to recruit and gather detailed responses (with good data quality) from a large proportion of older Canadians with MS. The data suggest that this sample of older people with MS is less likely to be employed, are less active and more disabled than other older Canadians.

Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study.

BACKGROUND: Chronic cerebrospinal venous insufficiency has been proposed as a unique combination of extracranial venous blockages and haemodynamic flow abnormalities that occurs only in patients with multiple sclerosis and not in healthy people. Initial reports indicated that all patients with multiple sclerosis had chronic cerebrospinal venous insufficiency. We aimed to establish the prevalence of venous narrowing in people with multiple sclerosis, unaffected full siblings, and unrelated healthy volunteers. METHODS: We did an assessor-blinded, case-control, multicentre study of people with multiple sclerosis, unaffected siblings, and unrelated healthy volunteers. We enrolled the study participants between January, 2011 and March, 2012, and they comprised 177 adults: 79 with multiple sclerosis, 55 siblings, and 43 unrelated controls, from three centres in Canada. We assessed narrowing of the internal jugular and azygous veins with catheter venography and ultrasound criteria for chronic cerebrospinal venous insufficiency proposed by Zamboni and colleagues. Catheter venography data were available for 149 participants and ultrasound data for 171 participants. FINDINGS: Catheter venography criteria for chronic cerebrospinal venous insufficiency were positive for one of 65 (2%) people with multiple sclerosis, one of 46 (2%) siblings, and one of 32 (3%) unrelated controls (p=1·0 for all comparisons). Greater than 50% narrowing of any major vein was present in 48 of 65 (74%) people with multiple sclerosis, 31 of 47 (66%) siblings (p=0·41 for comparison with patients with multiple sclerosis), and 26 of 37 (70%) unrelated controls (p=0·82). The ultrasound criteria for chronic cerebrospinal venous insufficiency were fulfilled in 35 of 79 (44%) participants with multiple sclerosis, 17 of 54 (31%) siblings (p=0·15 for comparison with patients with multiple sclerosis) and 17 of 38 (45%) unrelated controls (p=0·98). The sensitivity of the ultrasound criteria for detection of greater than 50% narrowing on catheter venography was 0·406 (95% CI 0·311-0·508), and specificity was 0·643 (0·480-0·780). INTERPRETATION: This study shows that chronic cerebrospinal venous insufficiency occurs rarely in both patients with multiple sclerosis and in healthy people. Extracranial venous narrowing of greater than 50% is a frequent finding in patients with multiple sclerosis, unaffected siblings, and unrelated controls. The ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography. The significance of venous narrowing to multiple sclerosis symptomatology remains unknown. FUNDING: MS Society of Canada, Saskatoon City Hospital Foundation, Lotte and John Hecht Memorial Foundation, Vancouver Coastal Health Foundation, and the Wolridge Foundation.

Placebo power.

A variable placebo response has been previously described in the multiple sclerosis (MS) literature and in sham surgical trials involving other patient populations. Conditioning and expectancy models are proposed to explain the biological mechanisms of a placebo response. Possibly, when neuroimmune mechanisms are involved in the disease process, placebo and treatment responses interact. The measurement of a placebo response related to endovascular procedures in MS may be scientifically and ethically challenging. Based on the factors associated with larger placebo responses, it is estimated that a significant placebo response may be associated with these procedures. The factors and mechanisms associated with marked placebo responses should be considered in the design of future studies related to the investigation of endovascular procedures for MS.