Translingual neurostimulation combined with physical therapy to improve walking and balance in multiple sclerosis (NeuroMSTraLS): Study protocol for a randomized controlled trial.

INTRODUCTION: Physical rehabilitation restores lost function and promotes brain plasticity in people with Multiple Sclerosis (MS). Research groups worldwide are testing the therapeutic effects of combining non-invasive neuromodulation with physical therapy (PT) to further improve functional outcomes in neurological disorders but with mixed results. Whether such devices enhance function is not clear. We present the rationale and study design for a randomized controlled trial evaluating if there is additional benefit to the synergistic pairing of translingual neurostimulation (TLNS) with PT to improve walking and balance in MS. METHODS AND ANALYSIS: A parallel group [PT + TLNS or PT + Sham], quadruple-blinded, randomized controlled trial. Participants (N = 52) with gait and balance deficits due to relapsing-remitting or progressive MS, who are between 18 and 70 years of age, will be recruited through patient registries in Newfoundland & Labrador and Saskatchewan, Canada. All participants will receive 14 weeks of PT while wearing either a TLNS or sham device. Dynamic Gait Index is the primary outcome. Secondary outcomes include fast walking speed, subjective ratings of fatigue, MS impact, and quality of life. Outcomes are assessed at baseline (Pre), after 14 weeks of therapy (Post), and 26 weeks (Follow Up). We employ multiple methods to ensure treatment fidelity including activity and device use monitoring. Primary and secondary outcomes will be analyzed using linear mixed-effect models. We will control for baseline score and site to test the effects of Time (Post vs. Follow-Up), Group and the Group x Time interaction as fixed effects. A random intercept of participant will account for the repeated measures in the Time variable. Participants must complete the Post testing to be included in the analysis. ETHICS AND DISSEMINATION: The Human Research Ethics Boards in Newfoundland & Labrador (HREB#2021.085) & Saskatchewan (HREB Bio 2578) approved the protocol. Dissemination avenues include peer-reviewed journals, conferences and patient-oriented communications.

Use of natalizumab in persons with multiple sclerosis: 2022 update.

BACKGROUND: Natalizumab is a humanized monoclonal antibody used for treatment of highly active relapsing-remitting multiple sclerosis (MS). With more than 15 years of post-marketing experience with natalizumab in Canada, several real-world studies have shown the long-term efficacy and safety of natalizumab. In addition, risk stratification/mitigation strategies for progressive leukoencephalopathy (PML), an adverse effect associated with natalizumab based on the John Cunningham virus (JCV) index; treatment duration beyond 24 months; and prior exposure to immunosuppressant drugs have been developed. METHODS: A group of neurologists from various MS clinics across Canada met in September 2021 to update the 2015 Canadian practice recommendations for the use of natalizumab in persons with MS (PwMS). RESULTS: The recommendations focused on the long-term efficacy and safety data from real-world studies, patient selection according to JCV index criteria, risk management strategies for PML (including extended interval dosing), and options for switching to currently available disease-modifying therapies for MS. CONCLUSIONS: The recommendations of clinical neurologists seek to optimize the management of PwMS who may benefit from treatment with natalizumab.

Prolonged cortical silent period is related to poor fitness and fatigue, but not tumor necrosis factor, in Multiple Sclerosis.

OBJECTIVE: Poor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown. METHODS: MS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP). RESULTS: Sixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable. CONCLUSION: Low fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue. SIGNIFICANCE: MS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks.

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.