Intensive Aerobic Cycling Is Feasible and Elicits Improvements in Gait Velocity in Individuals With Multiple Sclerosis: A Preliminary Study.

BACKGROUND: Aerobic exercise (AEx) has many potential benefits; however, it is unknown whether individuals with multiple sclerosis (MS) can attain the optimal intensity and duration to harness its effects. Forced-rate exercise (FE) is a novel paradigm in which the voluntary pedaling rate during cycling is supplemented to achieve a higher exercise intensity. The aim of this pilot trial was to investigate the feasibility and initial efficacy of a 12-week FE or voluntary exercise (VE) cycling intervention for individuals with MS. METHODS: Twenty-two participants with MS (Expanded Disability Severity Scale [EDSS] 2.0-6.5) were randomly assigned to FE (n = 12) or VE (n = 10), each with twice weekly 45-minute sessions at a prescribed intensity of 60% to 80% of maximum heart rate (HR). RESULTS: Eighteen individuals (FE = 11; VE = 7) completed the intervention, however, adaptations were required in both groups to overcome barriers to cycling. Overall, participants exercised for an average of 42.2 ± 2.3 minutes at an aerobic intensity of 65% ± 7% of maximum HR and a pedaling cadence of 67.3 ± 13.3 RPM. Cycling led to improved treadmill walking speed (0.61 to 0.68 m/sec, P = .010), with somewhat greater improvement with FE compared to VE (increase of 0.09 vs 0.03 m/s, respectively, P = .17) post intervention. Notably, the participant with the highest disability level (EDSS 6.5) tolerated FE but not VE. CONCLUSIONS: Aerobic exercise is feasible for individuals with MS, although those with increased disability may require novel paradigms such as FE to achieve targeted intensity. Further trials are warranted to investigate the effects of FE across the MS disability spectrum.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

An 8-week Forced-rate Aerobic Cycling Program Improves Cardiorespiratory Fitness in Persons With Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To examine the cardiorespiratory effects of a forced-rate aerobic exercise (FE) intervention among individuals with chronic stroke compared with an upper extremity repetitive task practice (UE RTP) control group. DESIGN: Secondary analysis of data from a randomized controlled trial. SETTING: Research laboratory. PARTICIPANTS: Individuals with chronic stroke (N=60). INTERVENTIONS: Participants completed 24 sessions of FE followed by RTP (FE+RTP, N=30) or time matched RTP alone (N=30). The FE+RTP group was prescribed exercise at 60%-80% of heart rate reserve on a motorized stationary cycle ergometer for 45 minutes followed by 45 minutes of RTP. The control group completed 90 minutes of RTP. MAIN OUTCOME MEASURES: Metabolic exercise stress tests on a cycle ergometer were conducted at baseline and post-intervention. Outcomes included peak oxygen consumption (peak V̇o2) and anaerobic threshold (AT). RESULTS: Fifty participants completed the study intervention and pre/post stress tests. The FE+RTP group demonstrated significantly greater improvements in peak V̇o2 from 16.4±5.7 to 18.3±6.4 mL/min/kg compared with the RTP group (17.0±5.6 to 17.2±5.6 mL/min/kg, P=.020) and significantly greater improvements in AT from 10.3±2.8 to 11.5±3.6 mL/min/kg compared with the RTP group (10.8±3.9 to 10.4±3.2 mL/min/kg, P=.020). In analyzing predictors of post-intervention peak V̇o2, the multivariable linear regression model did not reveal a significant effect of age, sex, body mass index, or beta blocker usage. Similarly, bivariate linear regression models for the FE group only did not find any exercise variables (aerobic intensity, power, or cycling cadence) to be significant predictors of peak V̇o2. CONCLUSIONS: While the aerobic exercise intervention was integrated into rehabilitation to improve UE motor recovery, it was also effective in eliciting significant and meaningful improvements in cardiorespiratory fitness. This novel rehabilitation model may be an effective approach to improve motor and cardiorespiratory function in persons recovering from stroke.

The Utilization of Forced-Rate Cycling to Facilitate Motor Recovery Following Stroke: A Randomized Clinical Trial.

BACKGROUND: The potential for aerobic exercise (AE) to enhance neuroplasticity post-stroke has been theorized but not systematically investigated. Our aim was to determine the effects of forced-rate AE (FE) paired with upper extremity (UE) repetitive task practice (FE + RTP) compared to time-matched UE RTP (RTP only) on motor recovery. METHODS: A single center randomized clinical trial was conducted from April 2019 to December 2022. Sixty individuals ≥6 months post-stroke with UE hemiparesis were randomized to FE + RTP (N = 30) or RTP only (N = 30), completing 90-minute sessions, 3×/week for 8 weeks. The FE + RTP group underwent 45-minute of FE (5-minute warm-up, 35-minute main set, and 5-minute cool down) followed by 45-minute of UE RTP. The RTP only group completed 90-minute of RTP. Primary outcomes were the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). The 6-minute Walk Test (6MWT, secondary outcome) assessed walking capacity. RESULTS: Sixty individuals enrolled and 56 completed the study. The RTP only group completed more RTP in terms of repetitions (411.8 ± 44.4 vs 222.8 ± 28.4, P < .001) and time (72.7 ± 6.7 vs 37.8 ± 2.4 minutes, P < .001) versus FE + RTP. There was no significant difference between groups on the FMA (FE + RTP, 36.2 ± 10.1-44.0 ± 11.8 and RTP only, 34.4 ± 11.0-41.2 ± 13.4, P = .43) or ARAT (FE + RTP, 32.5 ± 16.6-37.7 ± 17.9 and RTP only, 32.8 ± 18.6-36.4 ± 18.5, P = .88). The FE + RTP group demonstrated greater improvements on the 6MWT (274.9 ± 122.0-327.1 ± 141.2 m) versus RTP only (285.5 ± 160.3-316.9 ± 170.0, P = .003). CONCLUSIONS: There was no significant difference between groups in the primary outcomes. The FE + RTP improved more on the 6MWT, a secondary outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03819764.

Utilizing the arts to improve health, resilience, and well-being (HeRe We Arts®): a randomized controlled trial in community-dwelling individuals with chronic medical conditions.

Background: Healthcare workers are concerned with promoting behavior changes that enhance patients' health, wellness, coping skills, and well-being and lead to improved public health. The purpose of this randomized controlled trial was to determine if participation in an 8-week arts-based program leads to improved mood, health, resilience, and well-being in individuals with chronic health conditions as compared to a wait list control group. Methods: Self-report questionnaires for well-being, mental health, physical health, overall health, social health, mood, coping, and resilience were administered at baseline, Week 8 (end of program), and Week 16 (8-week follow-up). Results: Statistically significant improvements were noted in all outcome measures for the treatment group, as well as in most areas compared to the control group. Many of the positive results at Week 8 were either maintained or further improved at Week 16. Discussion: These results suggest that arts-based programming can have a positive effect on the mood, health, resilience, and well-being of individuals with chronic health conditions. Therefore, arts-based programming should be utilized more frequently in the management of chronic conditions in community-dwelling individuals. These benefits should be further assessed in larger clinical trials.

Palliative Care Knowledge and Attitudes Among Patients With Neuroinflammatory Diseases.

Background: Neuroinflammatory diseases are progressive leading to loss of function and disability. Although palliative care (PC) utilization has increased globally, it has scarcely increased in neurology. Objectives: To explore PC attitudes and knowledge among patients with neuroinflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: A cross-sectional 1-year study was conducted using the Palliative Care Knowledge Scale (PaCKS) and the PC Health Information National Trends Survey (HINTS). Murray's transition theory guided this study, which integrates palliative services including decision making, communication, and coordinated care. Results: The majority of study patients were female (69%) (N = 86) and White (79%). Forty-two percent indicated that they had never heard about PC, 46% said that they knew a little bit about PC, and 12% said that they knew a lot about PC. Fifty percent of patients knew the goals of PC and had knowledge about PC services. Forty-four percent to 60% agreed that PC goals include helping friends and family to cope with a patient's illness, offering social and emotional support, and managing pain and other symptoms. Patients who self-reported being familiar with PC performed significantly better on the PaCKS than those unfamiliar with PC (p < 0.001), and those who self-reported moderate or severe memory loss performed significantly worse on the PaCKS than those with mild memory loss (p = 0.027). There was an association between higher education and PC knowledge and between patients' PaCKS scores and their self-reported HINTS PC knowledge. Conclusions: Patients have partial PC knowledge. Patients require education about PC early in their disease along their illness trajectory.

Aerobic cycling reduces fatigue and improves pain in persons with multiple sclerosis: A preliminary study.

Fatigue and pain are prevalent in persons with multiple sclerosis (PwMS), negatively impacting quality of life (QoL). Clinical management is challenging due to their multiple underlying causes. Aerobic exercise elicits central and peripheral effects, which may effectively manage MS-related symptoms. Our aim was to determine the effects of an aerobic cycling intervention on symptoms impacting QoL. Eighteen participants completed a 12-week moderate- to high-intensity aerobic cycling intervention. Participants reported significant improvements in physical fatigue, overall fatigue, pain intensity, and pain interference. Aerobic exercise should be considered as part of a multi-faceted approach to improve fatigue and pain in PwMS.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Development of an integrated conceptual model of multiple sclerosis spasticity.

PURPOSE: Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity. METHODS: A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step. RESULTS: Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature. CONCLUSIONS: This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician-patient dialogue, research, and patient care.

Many people with multiple sclerosis (MS) have spasticity, generally in the lower limbs, but this symptom is complex and multidimensional and therefore difficult to characterize.MS spasticity may be influenced by moderators, triggers, modifiers, and treatment, all of which can affect objective measures and the subjective experience of spasticity.MS spasticity can have physical, functional, social, and emotional/psychological impacts as well as long-term consequences that can affect rehabilitation and ultimately reduce health-related quality of life for people with MS.Given that people with MS may view spasticity differently than their rehabilitation providers, providers should ask patients about their spasticity, including their moderators, triggers, modifiers, experience, impacts, long-term consequences, and effects on quality of life.This conceptual model provides a framework to improve clinician-patient dialogue, research, and rehabilitation for MS spasticity.

Increased Comfortable Gait Speed Is Associated With Improved Gait Biomechanics in Persons With Chronic Stroke Completing an 8-Week Forced-Rate Aerobic Cycling Intervention: A Preliminary Study.

ABSTRACT: Task-specific gait training is recommended to improve locomotor function after stroke. Our objective was to determine the effects of a forced-rate aerobic exercise intervention on gait velocity and biomechanics in the absence of task-specific gait training. Individuals with chronic stroke ( N = 14) underwent 24 sessions of forced-rate aerobic exercise, at a targeted aerobic intensity of 60%-80% of their heart rate reserve. Change in comfortable walking speed in addition to spatiotemporal, kinematic, and kinetic variables were measured using three-dimensional motion capture. Overground walking capacity was measured by the 6-min walk test. To determine gait biomechanics associated with increased walking speed, spatiotemporal, kinematic, and kinetic variables were analyzed separately for those who met the minimal clinically important difference for change in gait velocity compared with those who did not. Participants demonstrated a significant increase in gait velocity from 0.61 to 0.70 m/sec ( P = 0.004) and 6-min walk test distance from 272.1 to 325.1 meters ( P < 0.001). Those who met the minimal clinically important difference for change in gait velocity demonstrated significantly greater improvements in spatiotemporal parameters ( P = 0.041), ground reaction forces ( P = 0.047), and power generation ( P = 0.007) compared with those who did not. Improvements in gait velocity were accompanied by normalization of gait biomechanics.

Stimulation of the Premotor Cortex Enhances Interhemispheric Functional Connectivity in Association with Upper Limb Motor Recovery in Moderate-to-Severe Chronic Stroke.

Background: Transcranial direct current stimulation (tDCS) targeting the primary motor cortex is modestly effective for promoting upper-limb motor function following stroke. The premotor cortex (PMC) represents an alternative target based on its higher likelihood of survival and dense motor-network connections. Objective: The objective of this study was to determine whether ipsilesional PMC tDCS affects motor network functional connectivity (FC) in association with reduction in motor impairment, and to determine whether this relationship is influenced by baseline motor severity. Methods: Participants with chronic stroke were randomly assigned to receive active-PMC or sham-tDCS with rehabilitation for 5 weeks. Resting-state functional magnetic resonance imaging was acquired to characterize change in FC across motor-cortical regions. Results: Our results indicated that moderate-to-severe participants who received active-tDCS had greater increases in PMC-to-PMC interhemispheric FC compared to those who received sham; this increase was correlated with reduction in proximal motor impairment. There was also an increase in intrahemispheric dorsal premotor cortex-primary motor cortex FC across participants regardless of severity or tDCS group assignment; this increase was correlated with a reduction in proximal motor impairment in only the mild participants. Conclusions: Our findings have significance for developing targeted brain stimulation approaches. While participants with milder impairments may inherently recruit viable substrates within the ipsilesional hemisphere, stimulation of PMC may enhance interhemispheric FC in association with recovery in more impaired participants. Trial Registration: ClinicalTrials.gov Identifier: NCT01539096; Registration date: February 21, 2012.

Effects of Vibration Training on Cognition and Quality of Life in Individuals With Multiple Sclerosis.

Background: Multiple sclerosis (MS) detrimentally affects cognition and quality of life (QOL). Interventions that can improve cognitive deficit and QOL in individuals with MS are desired. This pilot study investigated the possible effects of vibration training on improving cognition and QOL in individuals with MS. Methods: Eighteen adults with MS were randomized into 2 groups: training and control. The training group underwent 6 weeks of vibration training, and the control group maintained their normal lifestyle throughout the study. In both groups, before and after the training course, the disability status was evaluated by the Patient Determined Disease Steps scale and the Multiple Sclerosis Functional Composite (MSFC), cognitive function was assessed by the Behavior Rating Inventory of Executive Function-Adults (BRIEF-A) and the Buschke Selective Reminding Test (SRT), and QOL was gauged by the 36-item Short Form Health Survey (SF-36). Results: The training was well accepted by the participants, and no major adverse event was reported. All participants finished the entire protocol. Compared with the control group, the training group showed greater improvements in MSFC score, Metacognition Index score of the BRIEF, SRT score, and physical domain score of the SF-36. Conclusions: These results suggest that vibration training could be an effective alternative training paradigm to enhance cognition and QOL in individuals with MS, and they provide an encouraging base to conduct a large-scale clinical trial.

Patient Versus Clinician Proxy Reliability of the AM-PAC "6-Clicks" Basic Mobility and Daily Activity Short Forms.

OBJECTIVE: The purpose of this study was to test the reliability of the Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" mobility and activity short forms between patients and therapist proxies. As a secondary aim, reliability was examined when patients completed their self-report before versus after the therapist evaluation. METHODS: Patients being seen for an initial physical therapist (N = 70) or occupational therapist (N = 71) evaluation in the acute care hospital completed the "6-Clicks" mobility short form (if a physical therapist evaluation) or activity short form (if an occupational therapist evaluation). Whether patients completed their self-assessment before or after the evaluation was randomized. Patient- and therapist-rated "6-Clicks" raw scores were converted to AM-PAC T-scores for comparison. Reliability was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots, and agreement was assessed with weighted kappa values. RESULTS: The ICCs for the "6-Clicks" mobility and daily activity short forms were 0.57 (95% CI = 0.42-0.69) and 0.45 (95% CI = 0.28-0.59), respectively. For both short forms, reliability was higher when the patient completed the self-assessment after versus before the therapist evaluation (ICC = 0.67, 95% CI = 0.47-0.80 vs ICC = 0.50, 95% CI = 0.26-0.67 for the mobility short form; and ICC = 0.52, 95% CI = 0.29-0.70 vs ICC = 0.34, 95% CI = 0.06-0.56 for the activity short form). CONCLUSION: Reliability of the "6-Clicks" total scores was moderate for both the mobility and activity short forms, though higher for the mobility short form and when patients' self-report occurred after the therapist evaluation. IMPACT: Reliability of the AM-PAC "6-Clicks" short forms is moderate when comparing scores from patients with those of therapists responding as proxies. The short forms are useful for measuring participants' function in the acute care hospital; however, it is critical to recognize limitations in reliability between clinician- and patient-reported AM-PAC scores when evaluating longitudinal change and recovery.

Safety and efficacy of transcranial direct current stimulation in upper extremity rehabilitation after tetraplegia: protocol of a multicenter randomized, clinical trial.

STUDY DESIGN: A multisite, randomized, controlled, double-blinded phase I/II clinical trial. OBJECTIVE: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI). SETTING: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey. METHODS: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up. PRIMARY OUTCOME MEASURE(S): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM). SECONDARY OUTCOME MEASURES: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated. TRIAL REGISTRATION: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.