Walking fatigability (WF) is a common and disabling feature of people with multiple sclerosis (pwMS), yet its neural underpinnings are poorly understood. Here, we investigated real-time cortical activity during the 6-min walk test (6MWT) and its relationship with changes in gait speed and quality. PwMS with and without WF (n = 42), and healthy controls (HC, n = 25), completed a 6MWT. Using functional near-infrared spectroscopy, cortical activity was measured in the prefrontal, premotor and motor cortices. Concomitantly, inertial measurement units measured gait speed and quality on a minute-by-minute basis. PwMS with WF (Expanded Disability Status Scale-EDSS = 6 [2.62]) showed marked declines in speed and gait quality, accompanied by altered patterns of cortical activation throughout the 6MWT. While HC and pwMS without WF (EDSS = 3[1.75]) dynamically modulated activity across frontal (p < .004), premotor (p < .043) and motor (p < .032) regions to respond to the task demands, pwMS with WF exhibited sustained reliance on frontal cortical regions and limited engagement of the broader walking network. Across all groups and cortical regions, an overall cortical activity pattern was observed. Specifically, cortical activity peaked during the first minute, stabilised during minutes 2-4, and increased during minutes 5-6. In both HC and pwMS, correlation analyses (rho:324-597) indicate that greater increases in cortical activity were associated with better gait speed/quality. Nevertheless, while these associations suggest that HC can recruit a broader walking control network, pwMS demonstrated an executive-driven pattern of brain-gait control. These findings suggest that walking fatigability can be partly driven by impaired ability to flexibly recruit cortical resources during prolonged walking.

BackgroundStudies show that beat-based cues from music and metronomes benefit gait in persons with progressive multiple sclerosis (PwPMS) during short walking. While useful for controlled assessment, prolonged walking better reflects real-world function. Adaptive beat-alignment algorithms using biofeedback may enhance synchronization and benefit gait dynamics but their effects in PwPMS remain unknown.AimsTo investigate the effect of walking with and without an adaptive beat-alignment algorithm on synchronization consistency during 8 minutes of walking compared to walking in silence, and its effects on gait. We also examined how clinical factors like dynamic balance and cognition affect synchronization consistency during walking with music and metronomes, with and without adaptive beat alignment.MethodsHealthy controls (HCs) and PwPMS walked for 8 minutes under 5 conditions: silence, music, and metronomes, with or without adaptive beat alignment, at their preferred pace. The algorithm adjusted phase and tempo in real time to restore baseline cadence. We measured synchronization, gait parameters, dynamics, and clinical outcomes.ResultsTwenty-one PwPMS and 18 HCs participated. Adaptive beat-alignment improved synchronization consistency and gait dynamics compared to fixed-tempo walking. Cognitive flexibility and working memory explained 10% of variance in the non-adaptive and 6% in the adaptive conditions, while dynamic balance (40%) impaired synchronization across both algorithms. Auditory cues resulted in slower walking and shorter strides compared to silence.ConclusionThis study demonstrates the feasibility of adaptive beat-alignment strategies enhancing synchronization consistency and gait dynamics in PwPMS; however, cognitive flexibility, working memory, and dynamic balance influenced synchronization performance.

Background. RehaCom, a computerized cognitive rehabilitation program for people with multiple sclerosis (PwMS), has been studied primarily in relation to treatment "dose" (duration, frequency, and adherence), with less focus on which training modules drive improvement or which participant factors predict responsiveness. This secondary analysis of the CogEx trial investigated whether progression within specific RehaCom modules was associated with processing speed improvement, measured by the SDMT, and whether baseline characteristics predicted response in participants with progressive MS. Methods. A total of 153 participants completed 12 weeks of RehaCom training across 5 attention-based modules. Cognition was assessed at baseline, 12 weeks, and 6 months using the SDMT. Correlation and regression analyses evaluated associations between module progression and cognitive outcomes. Results. Progression correlated significantly with SDMT improvement in 4 modules, with the strongest effects for Attention/Concentration (r = .37, P < .001) and Divided Attention-2 (r = .36, P < .001). Higher baseline SDMT, higher premorbid IQ, older age, and greater module progression independently predicted better SDMT performance at12-weeks (adjusted R-2 = .73). At 6 months, higher baseline SDMT, greater progression in Attention/Concentration and Divided Attention-2, older age, and female sex predicted better SDMT performance (adjusted R-2 = .71). Conclusion. Processing speed gains in progressive MS were related to both module-specific progression and participant characteristics, supporting a precision approach to cognitive rehabilitation that tailors training content to individual cognitive profiles. This study is a secondary analysis of the CogEx trial (ClinicalTrials.gov Identifier: NCT03679468; https://clinicaltrials.gov/ct2/show/NCT03679468).

BACKGROUND AND PURPOSE:Pain is a frequent symptom of multiple sclerosis (MS). Algometry as a method to measure pressure pain threshold (PPT) has not yet been validated for test-retest reliability and construct validity in persons with MS (pwMS). This research aims to investigate the test-retest reliability and construct validity of the pressure algometry for pain in MS. METHODS:Sixty pwMS with pain were included (mean age: 51.08 ± 11.61, Expanded Disability Status Scale [IQR]: 3.75 [3.3]). The reliability (test-retest, measurement error) and construct validity (hypothesis testing) were analyzed. A digital algometer (Somedic Sales AB, Hörby, Sweden) was applied perpendicularly and bilaterally on the trapezius muscle, thumbnails, low back, and quadriceps muscle to assess local PPTs. Three trials were performed on each body site, and the mean of the trials was used for statistical analysis. To investigate test-retest reliability, participants repeated the testing at 3- to 8-day intervals. RESULTS:PPTs obtained by algometry showed good to excellent test-retest reliability (ICC [95% CI]: 0.82 [0.70-0.89]-0.91 [0.85-0.95]) in 4 different body parts. PPT measures had significant negative moderate correlations with pain outcome measures (the Neuropathic Pain Scale, Neuropathic Pain Symptom Inventory, Brief Pain Inventory-Short Form, Douleur Neuropathique en 4, and painDETECT) (Spearman's rho = -0.265 to -0.456) and the Modified Fatigue Impact Scale (Spearman's r = -0.281 to -0.392). Weak nonsignificant correlations were found between PPT measures and clinical variables (Spearman's r = -0.201 to 0.227). DISCUSSION AND CONCLUSIONS:PPT measurement can reliably assess pain in MS with weak to moderate validity in the neck, thumbnails, lower back, and legs.

Functional neuroplasticity likely occurs following cognitive rehabilitation (CR) and aerobic exercise (EX) in progressive multiple sclerosis (PMS). We explored network resting state (RS) functional connectivity (FC) changes and associations with cognitive measure modifications in CogEx study participants. Patients with PMS were randomly assigned to four groups and underwent 12 weeks of treatment with a combination of CR and EX or sham therapies. Cognitive and fMRI assessments were performed at baseline, immediately post-intervention (week-12) and 6 months post-intervention (month-9). RS FC within the main cognitive brain networks was extracted and compared between groups at whole-network and voxel-wise levels and correlated with cognitive changes. We included 87 PMS patients with moderate-to-severe disability (Expanded Disability Status Scale score 4.0–6.5). There were no differences in whole-network RS FC between the four groups. When comparing patients performing CR vs CR-S, we found increased salience (p = 0.01) and default-mode network (p = 0.02) RS FC at week-12, and increased left (p = 0.05) and right frontoparietal network (p = 0.04) RS FC at month-9 in CR compared with CR-S groups. Increased default-mode network RS FC correlated weakly with increased verbal memory in CR (rho = 0.27, p = 0.06). At voxel-wise level, we found increased RS FC in most analyzed networks in CR groups (p < 0.001, uncorrected) and decreased RS FC in CR-S groups at week-12 (p < 0.05, family-wise error corrected). CR modulated RS FC in cognitive networks of patients with PMS, suggesting treatment-related functional plasticity of large-scale networks even in late, disabling MS phases. These network-level changes may reflect neural processes that support cognitive improvement following CR.

OBJECTIVES:To identify, categorize, and appraise rehabilitation-specific quality indicators (QIs) with generic applicability for evaluating interprofessional rehabilitation care. DATA SOURCES:Peer-reviewed literature was searched through PubMed and Web of Science. Gray literature was retrieved through Google Scholar, websites on professional quality standards and national QI repositories, reference tracking and expert consultation. STUDY SELECTION:Two reviewers independently screened 4423 records following predefined eligibility criteria. Seventy-nine sources explicitly reporting QIs for rehabilitation were included (52 from peer-reviewed literature and 27 from gray literature). DATA EXTRACTION:Two reviewers independently extracted data on 1070 QIs, including indicator characteristics and development processes. Methodological quality was appraised by 3 reviewers using the Appraisal of Indicators through Research and Evaluation(AIRE) instrument. DATA SYNTHESIS:All extracted QIs were assessed on their generic applicability and measurability. After duplicate removal, 23 indicator sets were retained with 177 QIs. Only 5 indicator sets demonstrated a strong methodological foundation based on domain 1 to 3 ≥50% of the AIRE instrument. These 5 sets included 77 QIs of which 46 were identified as rehabilitation-specific and mapped to the World Health Organization (WHO) quality domains, predominantly people-centered (n=19) and effective (n=16), followed by integrated (n=6), with minimal representation of safe (n=2), timely (n=2), and efficient (n=1). According to the Donabedian framework, most rehabilitation-specific QIs were process indicators (n=42), whereas only 4 were outcome indicators. CONCLUSIONS:This review provides the first overview of rehabilitation-specific QIs with generic applicability and a strong methodological foundation. These findings can inform the selection and implementation of meaningful indicators to enhance the quality of interprofessional rehabilitation care. As such, these rehabilitation-specific QIs can serve as a starting point for quality improvement initiatives, including audit and feedback and benchmarking.

Background:People with MS (pwMS) present changes in gait speed and quality during a 6-min walking test (6MWT). It is unknown whether these changes are clinically meaningful. Objective:To examine the relationships between pwMS-perceived changes in gait speed and quality with walking fatigability indices. Methods:Forty-five pwMS (EDSS: 4.0; 51 ± 11 years) performed the 6MWT. Sensor-based fatigability indices were calculated by comparing gait quality and the distance walked between the first/last minute of the 6MWT. Perceived changes in speed, smoothness, balance, ankle, knee and hip movement, attention, spasticity and pain were reported after the 6MWT using a questionnaire (Likert-type). The minimal important change (MIC) was calculated using an anchor-based approach. Spearman's rank correlations (pwMS-perceived changes x fatigability indices) were calculated. Results:More than half of pwMS reported changes in speed, smoothness, balance, or ankle position after the 6MWT. Significant MICs were found for most gait quality fatigability indices, as well as significant correlations with perceived changes, particularly for distance, speed, cadence, stride length, double support, step duration variability, and toe-off angle. Conclusion:PwMS perceived changes in gait speed and quality. The MIC values complement existing cut-off scores, facilitating the identification of walking fatigability and its use in clinical trials.

BACKGROUND:To optimize the care of people with multiple sclerosis in Europe, the European Multiple Sclerosis Platform aimed to gather vital evidence from people with multiple sclerosis to understand prevalence, burden, and symptom management. METHODS:An online survey was distributed by 24 European Multiple Sclerosis Platform-associated multiple sclerosis organizations across 22 countries. Descriptive statistics were applied. RESULTS:Data from 17,151 people with multiple sclerosis revealed a mean of 13.7 symptoms. The five most prevalent symptoms included fatigue, sensory problems, sleep disturbances, cognitive impairment, and balance problems (range = 75%-93%). Respondents utilized a mean of 5.6 concurrent care modalities/strategies for symptom management, and 86% of them received disease-modifying drugs. They consulted a mean of 4.2 healthcare professionals for symptom management, with 50% experiencing coordination of care. Overall, 50% of respondents expressed satisfaction with their symptom management. However, satisfaction levels varied depending on the specific symptom: people with multiple sclerosis were twice as likely to report satisfaction with managing mobility, bladder control, and spasticity compared to managing sexual problems, fatigue, and cognitive impairment. CONCLUSION:This survey provides evidence of the high prevalence, burden, and impact of symptoms in people with multiple sclerosis, highlighting the need for multifaceted care strategies. The results call for a change in healthcare policies and practices.

ObjectiveCognitive capacity tests can measure cognitive fatigability (CF) in persons with multiple sclerosis (pwMS). This study investigated test-retest reliability of CF measures using Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT).MethodsCF index (CFI%) comparing the last and first thirds and delta scores of SDMT and PASAT were assessed in 49 pwMS (EDSS:3-6.5) and 23 healthy controls. Tests were performed twice 5-7 days apart.ResultsBoth groups showed a performance decline (-2 to -21%). CFI and delta showed poor reliability in both groups (ICC range = 0.04-0.36).ConclusionsCF measures exhibited low reliability in pwMS.

INTRODUCTION:Brain structure deteriorates with aging as well as with neurodegenerative diseases such as multiple sclerosis (MS). While these brain changes are accompanied by deterioration of motor function, the association between brain structures and motor function in older people with MS (pwMS) has been scarcely investigated, especially across a broad range of outcomes. OBJECTIVE:To investigate the association between a broad range of brain structures and motor function outcomes in older pwMS as well as in older, healthy controls (HC). METHODS:The present cross-sectional study included n = 41 older pwMS (≥60 years) and n = 27 age- and sex-matched HC. Assessments included volume and diffusivity of brain structures (evaluated via magnetic resonance imaging) and lower extremity motor function including neuromuscular function (muscle strength evaluated via leg press dynamometry; muscle power via chair rise test) and physical function (walking capacity evaluated via tests of walking speed, endurance, and balance/coordination). RESULTS:Associations between brain volumes and motor function were observed (generally weak, although moderate for lesion load), with more frequent and pronounced associations for walking capacity compared to neuromuscular function. Regarding brain diffusivity, associations were observed (generally weak-to-moderate), again with more frequent and pronounced associations for walking capacity compared to neuromuscular function. CONCLUSION:Neurodegeneration - specifically the changes in brain volumes and diffusivity - remains a primary driver of motor decline in older pwMS (as well as in age- and sex-matched HC). This appears particularly evident for lesion load and brain diffusivity, being critically linked to various motor outcomes, most notably walking capacity.

Background Pain is a frequent and disabling symptom of multiple sclerosis (MS), highlighting the need for valid patient-reported outcome measures (PROMs) to assess pain in both clinical practice and research. Although pain PROMs demonstrated good reliability in MS, their validity remains unknown. Objectives This study investigated the construct validity of Douleur Neuropathique en 4 (DN4), painDETECT, Neuropathic Pain Scale (NPS), Neuropathic Pain Symptom Inventory (NPSI), and Brief Pain Inventory-Short Form (BPI-SF). Methods 110 persons with MS participated (mean age 45±13 years, Expanded Disability Status Scale (EDSS) = 3 [Interquartile range (IQR):2.6]. was performed to evaluate. Construct validity was evaluated by structural validity using confirmatory factor analysis (CFA) and by hypothesis testing. Results Confirmatory factor analysis (CFA) indicated that almost all pain PROMs achieved an acceptable limit of goodness of fit. DN4 and painDETECT, as well as NPS and NPSI, showed a strong correlation with each other (Spearman rho= 0.657, 0.788, respectively). Weak-to-moderate correlations were found with self-report questionnaires (perceived stress, depression, anxiety, sleep, and fatigue) (Spearman rho from 0.109 to 0.427), and weak to nonsignificant correlations with cognitive information processing speed, manual dexterity, walking speed, spasticity, muscle strength, and activity level (Spearman rho ranging from -0.028 to 0.248). Conclusions Patient-reported outcome measures for pain (PROMs) are valid for assessing pain in MS. They are strongly correlated with each other but show weak to moderate correlations with psychosocial factors and non-significant correlations with physical and functional measures.

OBJECTIVE:To evaluate the reliability and validity of the dual-tasking questionnaire (DTQ), dual-task screening list (DTSL), and dual-task impact on daily life activities questionnaire (DIDA-Q). DESIGN:Multicenter, cross-sectional study SETTING: Persons with multiple sclerosis (pwMS) were recruited from 7 multiple sclerosis centers across 6 countries (Belgium, Chile, Italy, Israel, Spain, and Turkey). PARTICIPANTS:A total of 356 pwMS (mean age 47.5±11.5y, expanded disability status scale, 3.79±1.83) were enrolled. INTERVENTIONS:Not applicable MAIN OUTCOME MEASURES: The reliability (internal consistency, test-retest, and measurement error) and construct validity (structural and convergent) were assessed. RESULTS:The DTQ, DTSL, and DIDA-Q demonstrated excellent test-retest reliability (intraclass correlation coefficients [95% CI], 0.84 [0.80-0.87] to 0.90 [0.87-0.92]) and internal consistency (Cronbach α: 0.86-0.96). As hypothesized, the 3 questionnaires showed a strong correlation with each other, moderate-to-strong correlations with other self-report questionnaires (perceived walking difficulties, fatigue, and fear of falling), and low-to-moderate correlations with cognitive information processing speed, manual dexterity, and dual-task walking performance (walking with word list generation task), showing convergent validity. The DIDA-Q exhibited systematically superior properties. These results were also verified in subsets from 6 different countries. In the structural validity analysis, all questionnaires displayed 2 main factors, allocated as "motor-driven" and "cognitive-driven" subscales. CONCLUSIONS:The DTQ, DTSL, and DIDA-Q have good-to-excellent measurement properties, with the highest properties observed in DIDA-Q. The use of these self-reported questionnaires can be used in research and clinical practice to assess the effect of dual-task difficulties on the daily life of ambulatory pwMS.

Background There is limited understanding of adherence and compliance rates for exercise training(ET) in people with progressive multiple sclerosis(PMS). Objectives This secondary, exploratory data analysis examined rates of adherence and compliance for continuous, moderate intensity training and high-intensity interval training(HIIT) and possible correlates among people with PMS from the CogEx trial. Methods CogEx was a multi-site, multi-arm, randomized, double-blinded, and sham-controlled trial undertaken by 11 sites in six different countries. Participants(N=311) were randomized into one of four conditions with different combinations of ET and cognitive rehabilitation, including respective sham conditions, delivered twice weekly over 12 weeks. The analysis focused on adherence and compliance rates and correlates for participants in the pooled ET intervention conditions who received and attempted the ET intervention(n=152). Results The rates of adherence and compliance overall(combined for both training stimuli) were 94% and 66%, respectively. The rates of adherence and compliance for continuous, moderate-intensity exercise were 95% and 73%, respectively, and for HIIT were 92% and 58%, respectively. The multivariable regression indicated that better 6MWT performance predicted higher compliance(particularly with HITT), whereas better CVLT-II performance predicted higher adherence and compliance with continuous training in PMS. Conclusion Our results highlight worse compliance than adherence with ET, particularly for HIIT, in PMS. We further highlight cognitive and physical function as correlates of adherence and compliance for consideration in future clinical trials of ET in PMS.

OBJECTIVE:To investigate the prevalence and magnitude of dual-task (DT) difficulties and the discriminative ability of 3 questionnaires evaluating perceived DT difficulties: the Dual-Tasking Questionnaire (DTQ), Dual-Task Screening List (DTSL), and Dual-task Impact on Daily life Activities Questionnaire (DIDA-Q). DESIGN:Multicenter, cross-sectional study. SETTING:Persons with multiple sclerosis (pwMS) and those without multiple sclerosis were recruited from 7 centers across 6 countries. PARTICIPANTS:A total of 540 participants (N=540): 175 with mild disability (mean Expanded Disability Status Scale, 2.1; mean age, 42.9), 181 with moderate-to-severe disability (mean Expanded Disability Status Scale, 5.3; mean age, 51.9), and 184 of those without multiple sclerosis (mean age, 44.8). INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:The cutoff scores of the DTQ, DTSL, and DIDA-Q and prevalence of DT difficulties were calculated. The effect size (ES) was calculated to determine the magnitude of the differences between groups (pwMS vs those without multiple sclerosis). The discriminative properties were identified by the area under the receiver operating characteristic curve (AUC). Cutoff values were estimated as the mean survey score plus 2 SDs of those without multiple sclerosis. RESULTS:Prevalence ranged from 49%-87% in the moderate-to-severe disability and 25%-45% in the mild disability group. The cutoff scores were 45 of 100 for DTQ, 25 of 100 for DTSL, and 14 of 76 for DIDA-Q. The DTQ (ES, 0.61), DTSL (ES, 0.73), and DIDA-Q (ES, 0.80) demonstrated discriminative ability with a moderate-to-large ES, showing greater perceived DT difficulties in pwMS compared with those without multiple sclerosis. The DIDA-Q had the largest AUC (0.904) compared with DTSL (0.866), and DTQ (0.802). CONCLUSIONS:The DT difficulties were already perceived in almost half of the mildly disabled patients and increased with disability severity. The DTQ, DTSL, and DIDA-Q show discriminative ability, with the highest AUC and ES observed in DIDA-Q. The DTQ, DTSL, and DIDA-Q can clearly be used in pwMS for clinical and research purposes.

BACKGROUND:Optimizing moderate to severe upper limb recovery is likely to require a higher dose of rehabilitation training than is currently delivered, but the feasibility and acceptability of higher dose regimes is unclear in the early-stage post stroke. Objective: To determine the maximum time spent on upper limb rehabilitation in people with moderate to severe impairment in acute and early sub-acute stage of stroke, in a phase I dose-escalation study. METHODS:Participants were recruited using a 3+3 study design from 2 stroke units and rehabilitation centers in Belgium. Patients received standard care plus escalating doses of upper limb motor training at 4 dose time-on-task levels: 1 (40 minutes), 2 (67 minutes), 3 (100 minutes) and 4 (133 minutes). Treatment was provided for 3 daily sessions, starting with 3 participants at level 1 and if dose was completed based on dose-limiting toxicity criteria, it was escalated to the next level with 3 new participants. RESULTS:Eighteen participants were recruited (median days post-stroke: 7.5 [Q1:5; Q3: 23.3]) with a mean Fugl Meyer Assessment Upper Extremity score of 29.4 (SD: 11.2). The maximum tolerated time-on-task of upper limb rehabilitation was, 100 minutes per day, with an additional 35 minutes of routine upper limb therapy provided as part of standard care. Level of fatigue and rate of perceived exertion were highest at dose level 4, resulting in participants not completing the dose of 133 minutes. CONCLUSIONS:Confirmative with existing literature using a different intervention, individuals with moderate to severe impairment in the early-stage of stroke, can tolerate higher doses of upper limb rehabilitation than those typically administered in standard care. These findings support future investigation into phase I/IIa dose-finding clinical trials exploring long-duration, high-intensity upper limb rehabilitation programs in the early post-stroke period. REGISTRATION:NCT04973553 (July 22, 2021). https://classic. CLINICALTRIALS:gov/ct2/show/NCT04973553.

Background: People with multiple sclerosis (MS) have an increased risk of falls, which are often associated with changes in movement direction and preceded by head rotation (HR). We aimed to investigate the effects of HR on postural control and gait temporal parameters in people with MS compared with controls (Cs) and to quantify the number of strides required to correct gait after HR. Methods: Eighteen people with MS (44.4 ± 9.9 years; 3.1 ± 1.5 Expanded Disability Scale Score) and 10 Cs (43.6 ± 10.3 years) participated. Postural control during a standing task on a force plate was assessed and quantified by center of pressure displacement. Gait was assessed by 2D sagittal video analysis and analyzed with Kinovea. After30 seconds of unperturbed walking on a treadmill, participants were instructed to turn their head to the left and walk on, followed by a right HR. The 10 strides after the HR were compared with the mean of normal walking strides. Inter- and intragroup comparisons were performed using a mixed model for repeated measurements. Hierarchical testing was used for stride analysis. Results: While standing, people with MS performed worse in all conditions and increased center of pressure displacement after HR in comparison with Cs (P ≤ .05). While walking, both groups increased the relative stance phase after HR (P ≤ .05); however, people with MS reduced stride times (P ≤ .05), and Cs maintained them. After HR, people with MS needed 3 strides to normalize stride times back to baseline, versus 1 to none for Cs. Conclusions: People with MS have higher transient imbalance while walking and standing after an HR compared with Cs.

BACKGROUND:High-intensity interval training (HIIT) has emerged as a potentially effective exercise promoting functional recovery post-stroke. OBJECTIVE:This study examined the efficacy of adding HIIT cycling vs. combining unloaded cycling (SHAM) to conventional physiotherapy on exercise capacity, functional ability, disability level, and health-related quality of life (HRQoL) early post-stroke. METHODS:Forty-four acute stroke survivors were randomly assigned to the HIIT cycling or SHAM group for 6 weeks of exercise training, 3 days/week. The primary outcome was exercise capacity (peak work load [WRpeak]) measured by a maximal exercise test. Secondary outcomes included balance: Berg Balance Scale, walking ability: 6-minute and 10-meter walk tests (6MWT and 10mWT), lower-extremity muscle strength: 5-Repetition Sit-To-Stand test, disability level: modified Rankin Scale (mRS), and HRQoL by EuroQOL 5-dimension questionnaire. RESULTS:The 2-way factorial analysis of variance showed a significant interaction of time × group on WRpeak (P < .001), 6MWT (P < .001), 10mWT (P < .001), and mRS (P = .012). The significant interaction indicates that the change in WRpeak (mean +17.7 W [95% CI, 10.2-25.1]), 6MWT (mean +126.8 m [77.9-175.7]), 10mWT (mean +0.5 m/s [0.3-0.7]), and mRS (mean -0.7 point [-1.2 to -0.2]) after 6-week of training was significantly greater for HIIT cycling versus SHAM. These changes are also significantly greater in the HIIT group vs the SHAM group up to 6 months (P < .001) post-training. CONCLUSIONS:In individuals with acute stroke, individuals, combining HIIT cycling with conventional physiotherapy significantly maximizes recovery of exercise capacity and walking ability, and reduces the level of disability early post-stroke, compared to SHAM.Protocol Registration number:NCT06179173.