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Michelle Ploughman,1 Chelsea Harris,1 Stephen H Hogan,1 Cynthia Murray,2 Michelle Murdoch,3 Mark W Austin,1 Mark Stefanelli4 1Recovery and Performance Laboratory, Faculty of Medicine, 2School of Nursing, Memorial University, 3Coalition of Persons with Disabilities, 4Department of Neurology, Faculty of Medicine, Memorial University, St John’s, NL, Canada Background: The debate within the multiple sclerosis (MS) community initiated by the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis and the subsequent liberation procedure placed some people with MS at odds with health care professionals and researchers.Objective: This study explored decision making regarding the controversial liberation procedure among people with MS.Subjects and methods: Fifteen people with MS (procedure, n=7; no procedure, n=8) participated in audiotaped semistructured interviews exploring their thoughts and experiences related to the liberation procedure. Data were transcribed and analyzed using an iterative, consensus-based, thematic content-analysis approach.Results: Participants described an imbalance of motivating factors affirming the procedure compared to hesitating factors that provoked the participant to pause or reconsider when deciding to undergo the procedure. Collegial conversational relationships with trusted sources (eg, MS nurse, neurologist) and ability to critically analyze the CCSVI hypothesis were key hesitating factors. Fundraising, family enthusiasm, and the ease of navigation provided by medical tourism companies helped eliminate barriers to the procedure.Conclusion: Knowledge of factors that helped to popularize the liberation procedure in Canada may inform shared decision making concerning this and future controversies in MS. Keywords: alternative medicine, CCSVI, decision making, liberation, multiple sclerosis, qualitative

Abstract: The optimal amount of endurance exercise required to elevate proteins involved in neuroplasticity during stroke rehabilitation is not known. This study compared the effects of varying intensities and durations of endurance exercise using both motorized and voluntary running wheels after endothelin-I-induced focal ischemia in rats. Hippocampal levels of brain-derived neurotrophic factor, insulin-like growth factor I and synapsin-I were elevated in the ischemic hemisphere even in sedentary animals suggesting an intrinsic restorative response 2 weeks after ischemia. In the sensorimotor cortex and the hippocampus of the intact hemisphere, one episode of moderate walking exercise, but not more intense running, resulted in the greatest increases in levels of brain-derived neurotrophic factor and synapsin-I. Exercise did not increase brain-derived neurotrophic factor, insulin-like growth factor I or synapsin-I in the ischemic hemisphere. In voluntary running animals, both brain and serum insulin-like growth factor I appeared to be intensity dependent and were associated with decreasing serum levels of insulin-like growth factor I and increasing hippocampal levels of insulin-like growth factor I in the ischemic hemisphere. This supports the notion that exercise facilitates the movement of insulin-like growth factor I across the blood–brain barrier. Serum corticosterone levels were elevated by all exercise regimens and were highest in rats exposed to motorized running of greater speed or duration. The elevation of corticosterone did not seem to alter the expression of the proteins measured, however, graduated exercise protocols may be indicated early after stroke. These findings suggest that relatively modest exercise intervention can increase proteins involved in synaptic plasticity in areas of the brain that likely subserve motor relearning after stroke. [Copyright &y& Elsevier]

Objective: To investigate sensorimotor integration by quantifying short-latency afferent inhibition (SAI) in people with MS who experience manual dexterity problems compared to controls., Methods: 22 people with MS with self-reported manual dexterity problems and 10 sex and age-matched controls were assessed using various upper extremity clinical tests. SAI was assessed by a transcranial magnetic stimulation pulse over the primary motor cortex preceded by peripheral nerve stimulation to the median nerve at 6 interstimulus intervals 2 - 8 ms longer than individualized N20 latencies., Results: Although within normal limits, persons with MS exhibited significantly slower Nine Hole Peg Test performance and pinch strength in the dominant hand. They also exhibited greater sensory impairment (monofilament test) in the dominant hand. Persons with MS showed significantly greater disinhibition of SAI in the dominant hand compared to controls, which was significantly correlated with weaker pinch strength., Conclusion: Reduced SAI in people with MS, particularly in the dominant hand, signifies disruptions in cortical cholinergic inhibitory activity and is associated with lower pinch strength., Significance: Evaluating changes in SAI may offer insight into the disrupted cortical cholinergic inhibitory activity that contributes to sensorimotor disintegration, potentially advancing disease management in persons with MS., Competing Interests: Conflicts of interest statement None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 International Federation of Clinical Neurophysiology. All rights reserved.)

Objective: Investigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability., Methods: Participants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition., Results: Participants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS<3). This resulted in lower E/I ratios in the higher disability group. Individuals with higher disability presented with asymmetrical E/I ratios between brain hemispheres, a pattern not present in the group with lower disability. In regression analyses controlling for demographics, lowered TMS-probed E/I ratio predicted variance in disability (R 2  = 0.37, p < 0.001), upper extremity function (R 2  = 0.35, p < 0.001), walking speed (R 2  = 0.22, p = 0.005), and cognitive performance (R 2  = 0.25, p = 0.007). Receiver Operating Characteristic curve analysis confirmed 'excellent' discriminative ability of the E/I ratio in distinguishing high and low disability. Finally, excitation superiorly correlated with the E/I ratio than overall inhibition in both hemispheres (p ≤ 0.01)., Conclusion: The E/I ratio is a potential neurophysiological biomarker of disability level in MS, especially when assessed in the hemisphere corresponding to the weaker body side. Interventions aimed at increasing cortical excitation or reducing inhibition may restore E/I balance potentially stalling progression or improving function in MS., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michelle Ploughman reports financial support was provided by The Canadian Institutes for Health Research. Michelle Ploughman reports financial support was provided by Newfoundland and Labrador Research and Development Corporation. Michelle Ploughman reports financial support was provided by Canada Foundation for Innovation. Michelle Ploughman reports financial support was provided by Canada Research Chairs Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Mobility impairment is common in multiple sclerosis (MS); however, agility has received less attention. Agility requires strength and neuromuscular coordination to elicit controlled propulsive rapid whole-body movement. Grip strength is a common method to assess whole body force production, but also reflects neuromuscular integrity and global brain health. Impaired agility may be linked to loss of neuromuscular integrity (reflected by grip strength or corticospinal excitability)., Objectives: We aimed to determine whether grip strength would be associated with agility and transcranial magnetic stimulation (TMS)-based indices of corticospinal excitability and inhibition in persons with MS having low disability. We hypothesized that low grip strength would predict impaired agility and reflect low corticospinal excitability., Methods: We recruited 34 persons with relapsing MS (27 females; median [range] age 45.5 [21.0-65.0] years) and mild disability (median [range] Expanded Disability Status Scale 2.0 [0-3.0]), as well as a convenience sample of age- and sex-matched apparently healthy controls. Agility was tested by measuring hop length during bipedal hopping on an instrumented walkway. Grip strength was measured using a calibrated dynamometer. Corticospinal excitability and inhibition were examined using TMS-based motor evoked potential (MEP) and corticospinal silent period (CSP) recruitment curves, respectively., Results: MS participants had significantly lower grip strength than controls independent of sex. Females with and without MS had weaker grip strength than males. There were no statistically significant sex or group differences in agility. After controlling for sex, weaker grip strength was associated with shorter hop length in controls only (r = 0.645, p < .05). Grip strength did not significantly predict agility in persons with MS, nor was grip strength predicted by corticospinal excitability or inhibition., Conclusions: In persons with MS having low disability, grip strength (normalized to body mass) was reduced despite having intact agility and walking performance. Grip strength was not associated with corticospinal excitability or inhibition, suggesting peripheral neuromuscular function, low physical activity or fitness, or other psychosocial factors may be related to weakness. Low grip strength is a putative indicator of early neuromuscular aging in persons with MS having mild disability and normal mobility., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls., Methods: We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score)., Results: In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks., Conclusions: Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Baldasso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The link between moderate- to vigorous-intensity physical activity (MVPA) and cardiorespiratory fitness in individuals with multiple sclerosis (MS) remains unclear. This study examined the relationship between self-reported MVPA and objectively assessed cardiorespiratory fitness, emphasizing sex differences., Methods: 107 adults with MS (77 females), aged (mean ± standard deviation) 47.2 ± 10.2 years, were recruited from a local MS clinic. Fitness was measured as maximal oxygen uptake (V̇O 2max ) during a graded maximal exercise test using a recumbent stepper. MVPA (24-hour recall) was estimated as the duration of activities ≥ 3 MET (metabolic equivalent of task). MET-minutes were calculated by multiplying MET by duration. We explored sex differences in self-reported MVPA, cardiorespiratory fitness, and disability; examined sex differences in associations between these variables; and investigated whether MET-minutes of MVPA predicted V̇O 2max in females and males., Results: Mean V̇O 2max was 24.79 mL·kg -1 ·min -1 , indicating poor cardiorespiratory fitness levels, despite high levels of self-reported MVPA (mean = 412.5 MET-minutes). Fifty-three percent of males and 40% of females had V̇O 2max levels below the 20 th age- and sex-standardized population percentile, indicating poor cardiorespiratory fitness. There were statistically significant associations between MVPA and V̇O 2max (Rho = 0.27, p = .01), as well as disability and V̇O 2max (Rho = -0.35, p = .02), in females but not males. A regression model using sex, age, body mass, disability, and MVPA to estimate V̇O 2max was valid in predicting V̇O 2max values that were statistically equivalent to those measured in the laboratory in females but not males. However, the inclusion of MVPA did not add to the predictive value of this equation., Conclusions: Despite reporting high levels of MVPA, people with MS had poor cardiorespiratory fitness. MVPA, fitness, and disability were associated in females only, indicating that sex differences should be considered in fitness appraisal. Self-reported MVPA did not predict fitness, suggesting 24-hour recall may not be representative of true activity or fitness levels in persons with MS. Future work should examine sex differences in associations between MVPA and fitness using objective measures such as accelerometry., Competing Interests: The authors have no competing interests to declare., (Copyright © 2024 Syamala Buragadda et al.)

Background: Rehabilitative treatments that promote neuroplasticity are believed to improve recovery after stroke. Animal studies have shown that cardiovascular exercise (CE) promotes neuroplasticity but the effects of this intervention on the human brain and its implications for the functional recovery of patients remain unclear. The use of biomarkers has enabled the assessment of cellular and molecular events that occur in the central nervous system after brain injury. Some of these biomarkers have proven to be particularly valuable for the diagnosis of severity, prognosis of recovery, as well as for measuring the neuroplastic response to different treatments after stroke., Objectives: To provide a critical analysis on the current evidence supporting the use of neurophysiological, neuroimaging, and blood biomarkers to assess the neuroplastic response to CE in individuals poststroke., Results: Most biomarkers used are responsive to the effects of acute and chronic CE interventions, but the response appears to be variable and is not consistently associated with functional improvements. Small sample sizes, methodological variability, incomplete information regarding patient's characteristics, inadequate standardization of training parameters, and lack of reporting of associations with functional outcomes preclude the quantification of the neuroplastic effects of CE poststroke using biomarkers., Conclusion: Consensus on the optimal biomarkers to monitor the neuroplastic response to CE is currently lacking. By addressing critical methodological issues, future studies could advance our understanding of the use of biomarkers to measure the impact of CE on neuroplasticity and functional recovery in patients with stroke., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease that involves attacks of inflammatory demyelination and axonal damage, with variable but continuous disability accumulation. Transcranial magnetic stimulation (TMS) is a noninvasive method to characterize conduction loss and axonal damage in the corticospinal tract. TMS as a technique provides indices of corticospinal tract function that may serve as putative MS biomarkers. To date, no reviews have directly addressed the diagnostic performance of TMS in MS. The authors aimed to conduct a critical narrative review on the diagnostic performance of TMS in MS., Methods: The authors searched the Embase, PubMed, Scopus, and Web of Science databases for studies that reported the sensitivity and/or specificity of any reported TMS technique compared to established clinical MS diagnostic criteria. Studies were summarized and critically appraised for their quality and validity., Results: Seventeen of 1,073 records were included for data extraction and critical appraisal. Markers of demyelination and axonal damage-most notably, central motor conduction time (CMCT)-were specific, but not sensitive, for MS. Thirteen (76%), two (12%), and two (12%) studies exhibited high, unclear, and low risk of bias, respectively. No study demonstrated validity for TMS techniques as diagnostic biomarkers in MS., Conclusions: CMCT has the potential to: (1) enhance the specificity of clinical MS diagnostic criteria by "ruling in" true-positives, or (2) revise a diagnosis from relapsing to progressive forms of MS. However, there is presently insufficient high-quality evidence to recommend any TMS technique in the diagnostic algorithm for MS., Competing Interests: Michelle Ploughman is an Academic Editor for PeerJ., (© 2024 Snow et al.)

Background: As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established., Objective: Establish recommendations for future mechanistic exercise studies in MS., Methods: In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research., Results: We concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. Consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies., Conclusion: The resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cognitive impairment is a disabling and underestimated consequence of multiple sclerosis (MS), with multiple determinants that are poorly understood., Objectives: We explored predictors of MS-related processing speed impairment (PSI) and age-related mild cognitive impairment (MCI) and hypothesized that cardiorespiratory fitness and corticospinal excitability would predict these impairments., Methods: We screened 73 adults with MS (53 females; median [range]: Age 48 [21-70] years, EDSS 2.0 [0.0-6.5]) for PSI and MCI using the Symbol Digit Modalities Test and Montréal Cognitive Assessment, respectively. We identified six persons with PSI (No PSI, n  = 67) and 13 with MCI (No MCI, n  = 60). We obtained clinical data from medical records and self-reports; used transcranial magnetic stimulation to test corticospinal excitability; and assessed cardiorespiratory fitness using a graded maximal exercise test. We used receiver operator characteristic (ROC) curves to discern predictors of PSI and MCI., Results: Interhemispheric asymmetry of corticospinal excitability was specific for PSI, while age was both sensitive and specific for MCI. MS-related PSI was also associated with statin prescriptions, while age-related MCI was related to progressive MS and GABA agonist prescriptions. Cardiorespiratory fitness was associated with neither PSI nor MCI., Discussion: Corticospinal excitability is a potential marker of neurodegeneration in MS-related PSI, independent of age-related effects on global cognitive function. Age is a key predictor of mild global cognitive impairment. Cardiorespiratory fitness did not predict cognitive impairments in this clinic-based sample of persons with MS., Competing Interests: We have no competing interests to declare., (© 2023 The Authors. Published by Elsevier Ltd on behalf of International Brain Research Organization.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was supported by an Independent Investigator –led Grant from Helius Medical, the company that makes the PoNS units. They and their employees had no involvement in the design and conduct of this study. Helius Medical technologies provided the PoNS™ (both TLNS and sham) devices. They have no involvement in data collection, analysis or reporting., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Community-based exercise programs delivered through healthcare-community partnerships (CBEP-HCPs) are beneficial to individuals with balance and mobility limitations. For the community to benefit, however, these programs must be sustained over time., Purpose: To identify conditions influencing the sustainability of CBEP-HCPs for people with balance and mobility limitations and strategies used to promote sustainability based on experiences of program providers, exercise participants, and caregivers., Methods: Using a qualitative collective case study design, we invited stakeholders (program providers, exercise participants, and caregivers) from sites that had been running a CBEP-HCP for people with balance and mobility limitations for ≥4 years; and sites where the CBEP-HCP had been discontinued, to participate. We used two sustainability models to inform development of interview guides and data analysis. Qualitative data from each site were integrated using a narrative approach to foster deeper understanding of within-organization experiences., Results: Twenty-nine individuals from 4 sustained and 4 discontinued sites in Ontario ( n  = 6) and British Columbia ( n  = 2), Canada, participated. Sites with sustained programs were characterized by conditions such as need for the program in the community, presence of secure funding or cost recovery mechanisms, presence of community partners, availability of experienced and motivated instructors, and the capacity to allocate resources towards program marketing and participant recruitment. For sites where programs discontinued, diminished participation and/or enrollment and an inability to allocate sufficient financial, human, and logistical resources towards the program affected program continuity. Participants from discontinued sites also identified issues such as staff with low motivation and limited experience, and presence of competing programs within the organization or the community. Staff associated the absence of referral pathways, insufficient community awareness of the program, and the inability to recover program cost due to poor participation, with program discontinuation., Conclusion: Sustainability of CBEP-HCPs for people with balance and mobility limitations is influenced by conditions that exist during program implementation and delivery, including the need for the program in the community, and organization and community capacity to bear the program's financial and resource requirements. Complex interactions among these factors, in addition to strategies employed by program staff to promote sustainability, influence program sustainability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Aravind, Graham, Cameron, Ploughman and Salbach.)

Objectives: Heat sensitivity (HS) describes a temporary worsening of multiple sclerosis (MS) symptoms with increased body temperature. The pathophysiology may relate to central nervous system conduction deficits and autonomic dysfunction. We conducted deep clinical phenotyping of a cohort of persons with MS to identify predictors of HS., Methods: We recruited 59 MS participants with HS or No HS. Participants self-reported symptom severity (Hospital Anxiety and Depression Scale, Multiple Sclerosis Impact Scale, and fatigue visual analog scale) and underwent maximal exercise and transcranial magnetic stimulation testing to characterize autonomic and corticospinal function. We examined associations with HS using binomial logistic regression., Results: People with HS (36/59) had significantly greater disability, depression, fatigue, and physical and psychological functional effects of MS. They also had significantly lower corticospinal excitability but not conduction. After controlling for disease-modifying therapy (DMT), disability, and disease type, self-reported difficulty using hands in everyday tasks was significantly associated with a large increase in the odds of HS. Autonomic and corticospinal dysfunction were not associated with HS. Lack of DMT use alone was also associated with a large increase in the odds of HS., Discussion: Following a comprehensive assessment of plausible contributors to HS, HS was most strongly associated with lack of a DMT prescription and self-reported hand dysfunction. Surprisingly, objective measurement of autonomic and corticospinal integrity did not contribute to HS., Competing Interests: Declaration of Competing Interest We have no competing interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Persons with multiple sclerosis (MS) frequently report pain that negatively affects their quality of life. Evidence linking pain and corticospinal excitability in MS is sparse. We aimed to (1) examine differences in corticospinal excitability in MS participants with and without pain and (2) explore predictors of pain., Methods: Sixty-four participants rated their pain severity on a visual analog scale (VAS). Transcranial magnetic stimulation (TMS) and validated clinical instruments characterized corticospinal excitability and subjective disease features like mood and fatigue. We retrieved information on participants' prescriptions and disability status from their clinical records., Results: Fifty-five percent of participants reported pain that affected their daily functioning. Persons with pain had significantly greater fatigue and lower area under the excitatory motor evoked potential (MEP) recruitment curve (eREC AUC), a measure of total corticospinal excitability. After controlling for age, disability status, and pain medications, increased fatigue and decreased eREC AUC together explained 40% of the variance in pain., Discussion: Pain in MS is multifactorial and relates to both greater fatigue and lesser corticospinal excitability. Future work should better characterize relationships between these outcomes to develop targeted pain interventions such as neuromodulation., Summary: We examined pain in MS. Individuals with pain had higher fatigue and lower corticospinal excitability than those without pain. These outcomes significantly predicted self-reported pain., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Background: Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose., Objectives: To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS., Methods: We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain)., Results: The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability., Discussion: TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Machine learning can discern meaningful information from large datasets. Applying machine learning techniques to raw sensor data from instrumented walkways could automatically detect subtle changes in walking and balance. Multiple sclerosis (MS) is a neurological disorder in which patients report varying degrees of walking and balance disruption. This study aimed to determine whether machine learning applied to walkway sensor data could classify severity of self-reported symptoms in MS patients. Ambulatory people with MS ( n = 107) were asked to rate the severity of their walking and balance difficulties, from 1-No problems to 5-Extreme problems, using the MS-Impact Scale-29. Those who scored less than 3 (moderately) were assigned to the "mild" group ( n = 35), and those scoring higher were in the "moderate" group ( n = 72). Three machine learning algorithms were applied to classify the "mild" group from the "moderate" group. The classification achieved 78% accuracy, a precision of 85%, a recall of 90%, and an F1 score of 87% for distinguishing those people reporting mild from moderate walking and balance difficulty. This study demonstrates that machine learning models can reliably be applied to instrumented walkway data and distinguish severity of self-reported impairment in people with MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Combden, Jiang, Buragadda, Newell, Williams, Critch and Ploughman.)

Objective: Physical fitness and preserved cognitive function may provide neuroprotection in multiple sclerosis (MS), but few studies have examined their role in symptom progression over time. Dual-task paradigms can be useful to detect subtle impairment among people with MS in early stages of the disease. The present study investigated whether higher aerobic fitness or greater cognitive function could predict performance in dual-task walking 1-2 years later among people with mild or no MS-related walking impairment., Method: Participants ( n = 50) performed dual-task walking (walking while serially subtracting 7's from 100), completed the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and a fitness test (VO 2max ). They were tested at two time points (T1 and T2), approximately 1 year apart. Walking speed, MoCA, SDMT, and VO 2max at baseline (T1) were examined as predictors of dual-task walking speed at T2., Results: MoCA (higher score), but not SDMT or fitness, was significantly correlated with percentage decrease in dual-task walking and was a significant predictor of dual-task-walking speed at T2, accounting for additional 6.1% of its variance. Cognitive impairment (MoCA < 26) at baseline corresponded to a 12 cm/s unit decrease in dual-task-walking speed at T2., Conclusions: Our results provide longitudinal evidence that better cognitive function, specifically global MoCA score, may protect against decline in dual-task walking ability over the years. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: As more people are surviving stroke, there is a growing need for services and programs that support the long-term needs of people living with the effects of stroke. Exercise has many benefits; however, most people with stroke do not have access to specialized exercise programs that meet their needs in their communities. To catalyze the implementation of these programs, our team developed the Stroke Recovery in Motion Implementation Planner, an evidence-informed implementation guide for teams planning a community-based exercise program for people with stroke., Objective: This study aimed to conduct a user evaluation to elicit user perceptions of the usefulness and acceptability of the Planner to inform revisions., Methods: This mixed methods study used a concurrent triangulation design. We used purposive sampling to enroll a diverse sample of end users (program managers and coordinators, rehabilitation health partners, and fitness professionals) from three main groups: those who are currently planning a program, those who intend to plan a program in the future, and those who had previously planned a program. Participants reviewed the Planner and completed a questionnaire and interviews to identify positive features, areas of improvement, value, and feasibility. We used descriptive statistics for quantitative data and content analysis for qualitative data. We triangulated the data sources to identify Planner modifications., Results: A total of 39 people participated in this study. Overall, the feedback was positive, highlighting the value of the Planner's comprehensiveness, tools and templates, and real-world examples. The identified areas for improvement included clarifying the need for specific steps, refining navigation, and creating more action-oriented content. Most participants reported an increase in knowledge and confidence after reading the Planner and reported that using the resource would improve their planning approach., Conclusions: We used a rigorous and user-centered process to develop and evaluate the Planner. End users indicated that it is a valuable resource and identified specific changes for improvement. The Planner was subsequently updated and is now publicly available for community planning teams to use in the planning and delivery of evidence-informed, sustainable, community-based exercise programs for people with stroke., (©Jessica Reszel, Joan van den Hoek, Tram Nguyen, Gayatri Aravind, Mark T Bayley, Marie-Louise Bird, Kate Edwards, Janice J Eng, Jennifer L Moore, Michelle L A Nelson, Michelle Ploughman, Julie Richardson, Nancy M Salbach, Ada Tang, Ian D Graham. Originally published in JMIR Formative Research (https://formative.jmir.org), 29.07.2022.)

Background: The Stroke Recovery in Motion Implementation Planner guides teams through the process of planning for the implementation of community-based exercise programs for people with stroke, in alignment with implementation science frameworks., Objective: The purpose of this study was to conduct a field test with end users to describe how teams used the Planner in real-world conditions; describe the effects of Planner use on participants' implementation-planning knowledge, attitudes, and activities; and identify factors influencing the use of the Planner., Methods: This field test study used a longitudinal qualitative design. We recruited teams across Canada who intended to implement a community-based exercise program for people with stroke in the next 6 to 12 months and were willing to use the Planner to guide their work. We completed semistructured interviews at the time of enrollment, monitoring calls every 1 to 2 months, and at the end of the study to learn about implementation-planning work completed and Planner use. The interviews were analyzed using conventional content analysis. Completed Planner steps were plotted onto a timeline for comparison across teams., Results: We enrolled 12 participants (program managers and coordinators, rehabilitation professionals, and fitness professionals) from 5 planning teams. The teams were enrolled in the study between 4 and 14 months, and we conducted 25 interviews. We observed that the teams worked through the planning process in diverse and nonlinear ways, adapted to their context. All teams provided examples of how using the Planner changed their implementation-planning knowledge (eg, knowing the steps), attitudes (eg, valuing community engagement), and activities (eg, hosting stakeholder meetings). We identified team, organizational, and broader contextual factors that hindered and facilitated uptake of the Planner. Participants shared valuable tips from the field to help future teams optimize use of the Planner., Conclusions: The Stroke Recovery in Motion Implementation Planner is an adaptable resource that may be used in diverse settings to plan community-based exercise programs for people with stroke. These findings may be informative to others who are developing resources to build the capacity of those working in community-based settings to implement new programs and practices. Future work is needed to monitor the use and understand the effect of using the Planner on exercise program implementation and sustainability., (©Jessica Reszel, Joan van den Hoek, Tram Nguyen, Gayatri Aravind, Mark T Bayley, Marie-Louise Bird, Kate Edwards, Janice J Eng, Jennifer L Moore, Michelle L A Nelson, Michelle Ploughman, Julie Richardson, Nancy M Salbach, Ada Tang, Ian D Graham. Originally published in JMIR Formative Research (https://formative.jmir.org), 29.07.2022.)

Background: Bipedal hopping has the potential to detect subtle multiple sclerosis (MS)-related impairments, especially among patients who "pass" typical movement tests. In this narrative review, we outline the biomechanics of bipedal hopping and propose its usefulness as a novel outcome measure for people with MS having mild disability., Methods: We summarize articles that (1) examined the biomechanics of jumping or hopping and (2) tested the validity and/or reliability of hopping tests. We consolidated consistencies and gaps in research and opportunities for future development of the bipedal hop test., Results: Bipedal hopping requires immense power, coordination, balance, and ability to reduce co-contraction; movement components typically affected by MS. These impairments can be measured and differentiated by examining specific variables, such as hop length (power), symmetry (coordination), center of pressure (balance), and coefficient of variability (co-contraction/spasticity). Bipedal hopping challenges these aspects of movement and exposes sensorimotor impairments that may not have been apparent during walking., Conclusions: Testing of bipedal hopping on an instrumented walkway may detect and monitor sensorimotor control in people with MS who do not currently present with clinical deficits. Early measurement is imperative for precise rehabilitation prescription to slow disability progression prior to onset of measurable gait impairment.Implications for rehabilitationJumping and hopping tests detect lower limb and balance impairments in children, athletes, and older adults.Bipedal hop test measures multiple domains: power, coordination, balance, and muscle timing.Bipedal hop test may expose subtle sensorimotor impairments in people with multiple sclerosis.Multiple variables measured can discern type of sensorimotor impairment to direct personalized rehabilitation programs.

Background: Using embedded sensors, instrumented walkways provide clinicians with important information regarding gait disturbances. However, because raw data are summarized into standard gait variables, there may be some salient features and patterns that are ignored. Multiple sclerosis (MS) is an inflammatory neurodegenerative disease which predominantly impacts young to middle-aged adults. People with MS may experience varying degrees of gait impairments, making it a reasonable model to test contemporary machine leaning algorithms. In this study, we employ machine learning techniques applied to raw walkway data to discern MS patients from healthy controls. We achieve this goal by constructing a range of new features which supplement standard parameters to improve machine learning model performance., Results: Eleven variables from the standard gait feature set achieved the highest accuracy of 81%, precision of 95%, recall of 81%, and F1-score of 87%, using support vector machine (SVM). The inclusion of the novel features (toe direction, hull area, base of support area, foot length, foot width and foot area) increased classification accuracy by 7%, recall by 9%, and F1-score by 6%., Conclusions: The use of an instrumented walkway can generate rich data that is generally unseen by clinicians and researchers. Machine learning applied to standard gait variables can discern MS patients from healthy controls with excellent accuracy. Noteworthy, classifications are made stronger by including novel gait features (toe direction, hull area, base of support area, foot length and foot area)., (© 2022. The Author(s).)

Several putative neurorestorative therapies in multiple sclerosis (MS) have recently failed; this includes high-dose biotin, bexarotene, a retinoic acid receptor gamma agonist, and opicinumab (anti-LINGO-1). Are these failures biological or due to poor trial design? We argue that the failure to include exercise in these trials and selecting participants without the capacity for repair may explain these disappointing results. We propose the need for mapping the biological mechanisms of recovery within trials, understanding the critical window when remyelination/repair occurs in terms of targeting interventions at the right time and selecting subjects who are capable of repair. We also make the case for testing combinations that include other pro-repair interventions such as exercise, Nrf2 inducers and possibly neurostimulation. The MS community can't afford for any more treatments to fail because of poor trial design and ignoring biology., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background . The COVID-19 pandemic attributable to the severe acute respiratory syndrome virus (SARS-CoV-2) has had a significant and continuing impact across all areas of healthcare including stroke. Individuals post-stroke are at high risk for infection, disease severity, and mortality after COVID-19 infection. Exercise stroke rehabilitation programs remain critical for individuals recovering from stroke to mitigate risk factors and morbidity associated with the potential long-term consequences of COVID-19. There is currently no exercise rehabilitation guidance for people post-stroke with a history of COVID-19 infection. Purpose . To (1) review the multi-system pathophysiology of COVID-19 related to stroke and exercise; (2) discuss the multi-system benefits of exercise for individuals post-stroke with suspected or confirmed COVID-19 infection; and (3) provide clinical considerations related to COVID-19 for exercise during stroke rehabilitation. This article is intended for healthcare professionals involved in the implementation of exercise rehabilitation for individuals post-stroke who have suspected or confirmed COVID-19 infection and non-infected individuals who want to receive safe exercise rehabilitation. Results . Our clinical considerations integrate pre-COVID-19 stroke (n = 2) and COVID-19 exercise guidelines for non-stroke populations (athletic [n = 6], pulmonary [n = 1], cardiac [n = 2]), COVID-19 pathophysiology literature, considerations of stroke rehabilitation practices, and exercise physiology principles. A clinical decision-making tool for COVID-19 screening and eligibility for stroke exercise rehabilitation is provided, along with key subjective and physiological measures to guide exercise prescription. Conclusion . We propose that this framework promotes safe exercise programming within stroke rehabilitation for COVID-19 and future infectious disease outbreaks.

Multiple Sclerosis (MS) is a neurodegenerative disease in which pathophysiology and symptom progression presents differently between the sexes. In a cohort of people with MS (n = 110), we used transcranial magnetic stimulation (TMS) to investigate sex differences in corticospinal excitability (CSE) and sex-specific relationships between CSE and cognitive function. Although demographics and disease characteristics did not differ between sexes, males were more likely to have cognitive impairment as measured by the Montreal Cognitive Assessment (MoCA); 53.3% compared to females at 26.3%. Greater CSE asymmetry was noted in females compared to males. Females demonstrated higher active motor thresholds and longer silent periods in the hemisphere corresponding to the weaker hand which was more typical of hand dominance patterns in healthy individuals. Males, but not females, exhibited asymmetry of nerve conduction latency (delayed MEP latency in the hemisphere corresponding to the weaker hand). In males, there was also a relationship between delayed onset of ipsilateral silent period (measured in the hemisphere corresponding to the weaker hand) and MoCA, suggestive of cross-callosal disruption. Our findings support that a sex-specific disruption in CSE exists in MS, pointing to interhemispheric disruption as a potential biomarker of cognitive impairment and target for neuromodulating therapies., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Abstract: Health administrative data provide a potentially robust information source regarding the substantial burden chronic pain exerts on individuals and the health care system. This study aimed to use health administrative data to estimate comorbidity prevalence and annual health care utilization associated with chronic pain in Newfoundland and Labrador, Canada. Applying the validated Chronic Pain Algorithm to provincial Fee-for-Service Physician Claims File data (1999-2009) established the Chronic Pain (n = 184,580) and No Chronic Pain (n = 320,113) comparator groups. Applying the Canadian Chronic Disease Surveillance System coding algorithms to Claims File and Provincial Discharge Abstract Data (1999-2009) determined the prevalence of 16 comorbidities. The 2009/2010 risk and person-year rate of physician and diagnostic imaging visits and hospital admissions were calculated and adjusted using the robust Poisson model with log link function (risks) and negative binomial model (rates). Results indicated a significantly higher prevalence of all comorbidities and up to 4 times the odds of multimorbidity in the Chronic Pain Group (P-value < 0.001). Chronic Pain Group members accounted for 58.8% of all physician visits, 57.6% of all diagnostic imaging visits, and 54.2% of all hospital admissions in 2009/2010, but only 12% to 16% of these were for pain-related conditions as per recorded diagnostic codes. The Chronic Pain Group had significantly higher rates of physician visits and high-cost hospital admission/diagnostic imaging visits (P-value < 0.001) when adjusted for demographics and comorbidities. Observations made using this methodology supported that people identified as having chronic pain have higher prevalence of comorbidities and use significantly more publicly funded health services., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: The COVID-19 pandemic has likely had a negative impact on rehabilitation and quality of life (QoL) research in multiple sclerosis (MS)., Method: We explored perceived barriers to research among 87 researchers, representing 18 countries, both prior to and since COVID-19., Results: A 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)., Conclusions: Implications for the future landscape of rehabilitation research in MS are discussed., (© The Author(s) 2021.)

Objective: To evaluate the safety and feasibility of performing treadmill aerobic exercise in moderate normobaric hypoxia among chronic hemiparetic stroke survivors., Design: Observational study using convenience sampling., Setting: Research laboratory in a tertiary rehabilitation hospital., Participants: Chronic hemiparetic stroke survivors who could walk at least 10-m with or without assistance and had no absolute contraindications to exercise testing., Intervention: Participants (three male and four female) were asked to complete three normobaric hypoxia exposure protocols within a single session. First, they were passively exposed to normobaric hypoxia through gradual reductions in the fraction of inspired oxygen (F I O 2 = 20.9, 17.0, and 15.0%) while seated (5-min at each level of F I O 2 ). Participants were then exposed to the same reductions in F I O 2 during constant-load exercise performed on a treadmill at 40% of heart rate reserve. Finally, participants completed 20-min of exercise while intermittently exposed to moderate normobaric hypoxia (5 × 2-min at F I O 2 = 15.0%) interspaced with 2-min normoxia intervals (F I O 2 = 20.9%)., Outcome Measures: The primary outcome was occurrence of adverse events, which included standardized criteria for terminating exercise testing, blood oxygen saturation (S p O 2 ) <80%, or acute mountain sickness score >2. The increased cardiovascular strain imposed by normobaric hypoxia exposure at rest and during exercise was evaluated by changes in S p O 2 , heart rate (HR), blood pressure, and rating of perceived exertion (RPE)., Results: One participant reported mild symptoms of nausea during exercise in normobaric hypoxia and discontinued participation. No other adverse events were recorded. Intermittent normobaric hypoxia exposure was associated with reduced S p O 2 (MD = -7.4%, CI: -9.8 to -5.0) and increased HR (MD = 8.2, CI: 4.6 to 11.7) compared to intervals while breathing typical room air throughout the 20-min constant-load exercise period. The increase in HR was associated with a 10% increase in relative effort. However, reducing F I O 2 had little effect on blood pressure and RPE measurements., Conclusion: Moderate normobaric hypoxia appeared to be a safe and feasible method to increase the cardiovascular strain of submaximal exercise in chronic hemiparetic stroke survivors. Future studies evaluating the effects of pairing normobaric hypoxia exposure with existing therapies on secondary prevention and functional recovery are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kelly, Basset, McCarthy and Ploughman.)

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disorder. Interleukin-1 receptor antagonist (IL-1RA) is an endogenous soluble antagonist of the IL-1 receptor and blocks the pro-inflammatory effects of IL-1β known to contribute to MS pathology. The objectives of this study were to determine whether IL-1RA is associated with disability in MS and how this correlates with neurofilament light (NfL) levels in cerebrospinal fluid (CSF)., Methods: Peripheral blood and CSF were collected from consenting MS patients. Patient demographic and clinical variables, including past relapse activity, were also collected. Circulating levels of IL-1RA, IL-18, and IL-1β were measured in plasma; IL-1RA and NfL were measured in the CSF via Bio-plex multiplex immunoassay kits and ELISA, respectively. IL-1RA expression was investigated in vitro using primary human macrophages and microglia, and in situ using post-mortem MS tissue., Results: Following a multiple regression analysis, IL-1RA levels in plasma correlated with expanded disability status scale score independent of all other variables. In a separate cohort, CSF IL-1RA significantly correlated with NfL. In vitro, induction of the NLRP3 inflammasome, a pathological hallmark within MS lesions, led to increased release of IL-1RA from primary human microglia and macrophages. In the CNS, IL-1RA + macrophages/microglia were present at the rim of mixed active/inactive MS lesions., Conclusions: Results presented in this study demonstrate that IL-1RA is a novel exploratory biomarker in relapsing-remitting MS, which correlates with disability and provides mechanistic insights into the regulatory inflammatory responses within the demyelinated CNS., (Copyright © 2021. Published by Elsevier B.V.)

Background: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention., Objective: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation., Methods: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS., Results: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy., Conclusions: This coordinated call to action-to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them-is an important step in addressing gaps in rehabilitation research for people affected by progressive MS.

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period ( p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min -1 kg -1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min -1 kg -1 CI: -0.38 to 1.62). Pre to post changes in C-reactive protein (-0.9 mg/L; p =0.017), short-term glycemia (+14.7 mol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min -1 ; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose-response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery.

We propose a method for calculating standard spatiotemporal gait parameters from individual human joints with a side-view depth sensor. Clinical walking trials were measured concurrently by a side-view Kinect and a pressure-sensitive walkway, the Zeno Walkway. Multiple joint proposals were generated from depth images by a stochastic predictor based on the Kinect algorithm. The proposals are represented as vertices in a weighted graph, where the weights depend on the expected and measured lengths between body parts. A shortest path through the graph is a set of joints from head to foot. Accurate foot positions are selected by comparing pairs of shortest paths. Stance phases of the feet are detected by examining the motion of the feet over time. The stance phases are used to calculate four gait parameters: stride length, step length, stride width, and stance percentage. A constant frame rate was assumed for the calculation of stance percentage because time stamps were not captured during the experiment. Gait parameters from 52 trials were compared to the ground truth walkway using Bland-Altman analysis and intraclass correlation coefficients. The large spatial parameters had the strongest agreements with the walkway (ICC(2, 1) = 1.00 and 0.98 for stride and step length with normal pace, respectively). The presented system directly calculates gait parameters from individual foot positions while previous side-view systems relied on indirect measures. Using a side-view system allows for tracking walking in both directions with one camera, extending the range in which the subject is in the field of view.

Physical sedentarism is linked to elevated levels of circulating cytokines, whereas exercise upregulates growth-promoting proteins such as brain-derived neurotrophic factor (BDNF). The shift towards a 'repair' phenotype could protect against neurodegeneration, especially in diseases such as multiple sclerosis (MS). We investigated whether having higher fitness or participating in an acute bout of maximal exercise would shift the balance of BDNF and interleukin-6 (IL-6) in serum samples of people with progressive MS ( n = 14), compared to matched controls ( n = 8). Participants performed a maximal graded exercise test on a recumbent stepper, and blood samples were collected at rest and after the test. We assessed walking speed, fatigue, and maximal oxygen consumption (V·O2max). People with MS achieved about 50% lower V·O2max ( p = 0.003) than controls. At rest, there were no differences in BDNF between MS and controls; however, IL-6 was significantly higher in MS. Higher V·O2max was associated with a shift in BDNF/IL-6 ratio from inflammation to repair (R = 0.7, p = 0.001) when considering both groups together. In the MS group, greater ability to upregulate BDNF was associated with faster walking speed and lower vitality. We present evidence that higher fitness indicates a shift in the balance of blood biomarkers towards a repair phenotype in progressive MS.

Transcranial magnetic stimulation (TMS) is a non-invasive method used to investigate neurophysiological integrity of the human neuromotor system. We describe in detail, the methodology of a single pulse TMS protocol that was performed in a large cohort of people ( n = 110) with multiple sclerosis (MS). The aim was to establish and validate a core-set of TMS variables that predicted typical MS clinical outcomes: walking speed, hand dexterity, fatigue, and cognitive processing speed. We provide a brief and simple methodological pipeline to examine excitatory and inhibitory corticospinal mechanisms in MS that map to clinical status. Delayed and longer ipsilateral silent period (a measure of transcallosal inhibition; the influence of one brain hemisphere's activity over the other), longer cortical silent period (suggestive of greater corticospinal inhibition via GABA) and higher resting motor threshold (lower corticospinal excitability) most strongly related to clinical outcomes, especially when measured in the hemisphere corresponding to the weaker hand. Greater interhemispheric asymmetry (imbalance between hemispheres) correlated with poorer performance in the greatest number of clinical outcomes. We also show, not surprisingly, that TMS variables related more strongly to motor outcomes than non-motor outcomes. As it was validated in a large sample of patients with varying severities of central nervous system dysfunction, the protocol described herein can be used by investigators and clinicians alike to investigate the role of TMS as a biomarker in MS and other central nervous system disorders.

Objective . To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants . The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process . Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results . Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions . The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.

Background: Most prevalence estimates of chronic pain are derived from surveys and vary widely, both globally (2%-54%) and in Canada (6.5%-44%). Health administrative data are increasingly used for chronic disease surveillance, but their validity as a source to ascertain chronic pain cases is understudied., Aim: The aim of this study was to derive and validate an algorithm to identify cases of chronic pain as a single chronic disease using provincial health administrative data., Methods: A reference standard was developed and applied to the electronic medical records data of a Newfoundland and Labrador general population sample participating in the Canadian Primary Care Sentinel Surveillance Network. Chronic pain algorithms were created from the administrative data of patient populations with chronic pain, and their classification performance was compared to that of the reference standard via statistical tests of selection accuracy., Results: The most performant algorithm for chronic pain case ascertainment from the Medical Care Plan Fee-for-Service Physicians Claims File was one anesthesiology encounter ever recording a chronic pain clinic procedure code OR five physician encounter dates recording any pain-related diagnostic code in 5 years with more than 183 days separating at least two encounters. The algorithm demonstrated 0.703 (95% confidence interval [CI], 0.685-0.722) sensitivity, 0.668 (95% CI, 0.657-0.678) specificity, and 0.408 (95% CI, 0.393-0.423) positive predictive value. The chronic pain algorithm selected 37.6% of a Newfoundland and Labrador provincial cohort., Conclusions: A health administrative data algorithm was derived and validated to identify chronic pain cases and estimate disease burden in residents attending fee-for-service physician encounters in Newfoundland and Labrador., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: Currently, there is a paucity of research describing physiotherapy services for individuals with multiple sclerosis (MS) in Canada. Using qualitative methods, we aimed to develop a survey to examine physiotherapy practice patterns for people with MS receiving services in Canada. Method: We began by conducting a review of the current literature and combining participatory action research methods with the expertise of registered physiotherapists and individuals with MS. Semi-structured interviews were conducted with 10 participants to obtain their input into survey development. The interviews were then transcribed verbatim and analyzed thematically. Results: Five key themes emerged from the thematic analysis: (1) provide additional answer options, (2) reformat or clarify questions, (3) ensure that questions or options are appropriate, (4) ensure good readability and flow, and (5) determine the appropriate length of the survey. After a final revision, the survey consisted of 24 items in the following domains: demographics, MS programme and patient population, interdisciplinary care, and programme and service barriers. Conclusions: This survey is the first of its kind in Canada and is the first step toward improving the quality of health of people living with MS and the effectiveness of current physiotherapy practices for them., (© Canadian Physiotherapy Association.)