Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

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.

Incongruence between Cardiorespiratory Fitness and Subjective Reports of Physical Activity in Multiple Sclerosis: A Focus on Sex Differences.

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 (V̇O2max) 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 V̇O2max in females and males. Results: Mean V̇O2max 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 V̇O2max levels below the 20th age- and sex-standardized population percentile, indicating poor cardiorespiratory fitness. There were statistically significant associations between MVPA and V̇O2max (Rho = 0.27, p = .01), as well as disability and V̇O2max (Rho = -0.35, p = .02), in females but not males. A regression model using sex, age, body mass, disability, and MVPA to estimate V̇O2max was valid in predicting V̇O2max 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.

Transcranial magnetic stimulation enhances the specificity of multiple sclerosis diagnostic criteria: a critical narrative review.

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.

Measuring Neuroplasticity in Response to Cardiovascular Exercise in People With Stroke: A Critical Perspective.

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.

The MoxFo initiative-Mechanisms of action: Biomarkers in multiple sclerosis exercise studies.

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.

Age and asymmetry of corticospinal excitability, but not cardiorespiratory fitness, predict cognitive impairments in multiple sclerosis.

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.

Conditions and strategies influencing sustainability of a community-based exercise program incorporating a healthcare-community partnership for people with balance and mobility limitations in Canada: A collective case study of the Together in Movement and Exercise (TIME™) program.

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.

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.

Lower corticospinal excitability and greater fatigue among people with multiple sclerosis experiencing pain.

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.

Multiple sclerosis-related heat sensitivity linked to absence of DMT prescription and subjective hand impairment but not autonomic or corticospinal dysfunction.

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.

Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review.

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.

Machine learning corroborates subjective ratings of walking and balance difficulty in multiple sclerosis.

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.

How Community-Based Teams Use the Stroke Recovery in Motion Implementation Planner: Longitudinal Qualitative Field Test Study.

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.

The Stroke Recovery in Motion Implementation Planner: Mixed Methods User Evaluation.

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.

Better cognitive function predicts maintenance of dual-task walking ability over time among people with relapsing-remitting MS.

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 (VO2max). They were tested at two time points (T1 and T2), approximately 1 year apart. Walking speed, MoCA, SDMT, and VO2max 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).

Machine learning classification of multiple sclerosis patients based on raw data from an instrumented walkway.

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).

Remyelination trial failures: Repercussions of ignoring neurorehabilitation and exercise in repair.

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.

Bipedal hopping as a new measure to detect subtle sensorimotor impairment in people with multiple sclerosis.

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.

Exercise-Based Stroke Rehabilitation: Clinical Considerations Following the COVID-19 Pandemic.

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.

Sex-specific disruption in corticospinal excitability and hemispheric (a)symmetry in multiple sclerosis.

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.