The Effects of High-Intensity Interval Training on Gait, Balance, and Cognitive Functions in Individuals With Multiple Sclerosis

Individuals with MS aged 18 and older, with an EDSS score of 0-4, no relapse in the past three months, and medically stable condition will be randomized into two groups using a sealed-envelope method. Group 1 will receive MICT on a cycle ergometer (twice weekly, 8 weeks); Group 2 will receive low-volume HIIT with the same frequency. Both groups will receive an individualized physiotherapy program after each aerobic session. Outcomes include gait (TUG, T25FW, DGI), balance (Mini-BESTest, mCTSIB), cognitive function (BICAMS: SDMT, CVLT-II, BVMT-R), exercise capacity (ISWT), and blood biomarkers (BDNF, VEGF) assessed via ELISA.

• Moderate-Intensity Continuous Training (MICT) (Behavioral): Cycle ergometer-based exercise, twice weekly for 8 weeks. Starting intensity at 60% of peak workload, progressing to 80%. Each session includes 5-min warm-up, 20-30 min continuous exercise, and 5-min cool-down, followed by 30-min individualized physiotherapy program.
• High-Intensity Interval Training (HIIT) (Behavioral): Cycle ergometer-based exercise, twice weekly for 8 weeks. Each session includes 5-min warm-up (40% peak workload), 10 × 1-min intervals at 90% peak workload with 1-min active recovery (60% peak workload) between each interval, and 5-min cool-down. Total aerobic exercise duration: \~20 min, followed by 30-min individualized physiotherapy program.

Primary outcomes

• Timed Up and Go Test (TUG) [Baseline and 8 weeks]: Timed Up and Go Test (TUG). Participants are asked to rise from a standard chair, walk 3 meters, turn around, walk back, and sit down as fast as safely possible. Measured in seconds. Lower values indicate better functional mobility and balance.

Secondary outcomes

• Timed 25-Foot Walk Test (T25FW) [Baseline and 8 weeks]: Timed 25-Foot Walk Test (T25FW). Participants are instructed to walk 7.62 meters (25 feet) as quickly and safely as possible. Measured in seconds. Lower values indicate better walking speed.
• Dynamic Gait Index (DGI) [Baseline and 8 weeks]: Dynamic Gait Index (DGI). Assesses the ability to maintain balance while walking under varied conditions across 8 tasks. Minimum score: 0, Maximum score: 24. Higher scores indicate better dynamic gait balance.
• Incremental Shuttle Walk Test (ISWT) [Baseline and 8 weeks]: Incremental Shuttle Walk Test (ISWT). Participants walk between two cones placed 9 meters apart at increasing speeds guided by audio signals until they can no longer maintain the required pace. Measured in meters walked. Higher values indicate better functional exercise capacity.
• Mini Balance Evaluation Systems Test (Mini-BESTest) [Baseline and 8 weeks]: Mini Balance Evaluation Systems Test (Mini BESTest). Assesses dynamic balance across 14 items in 4 subsections: anticipatory postural control, reactive postural control, sensory orientation, and dynamic gait. Minimum score: 0, Maximum score: 28. Higher scores indicate better balance performance.
• Modified CTSIB (mCTSIB) - Static Posturography [Baseline and 8 weeks]: Modified Clinical Test of Sensory Interaction and Balance (mCTSIB). Assesses static postural stability under 4 conditions: eyes open/closed on firm and foam surfaces. Postural sway is measured in degrees per second. Lower values indicate better static balance.
• Serum BDNF levels (ELISA) [Baseline and 8 weeks]
• Serum VEGF levels (ELISA) [Baseline and 8 weeks]
• Symbol Digit Modalities Test (SDMT) [Baseline and 8 weeks]: Part of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery. Assesses information processing speed in neurological conditions. Participants are asked to match symbols with corresponding digits within 90 seconds. Minimum score: 0, Maximum score: 110. Higher scores indicate better cognitive processing speed.
• California Verbal Learning Test-II (CVLT-II) [Baseline and 8 weeks]: Part of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery. Assesses auditory and verbal memory. A list of 16 words across 4 categories is read aloud and recalled over 5 trials. Minimum score: 0, Maximum score: 80. Higher scores indicate better verbal learning and memory.
• Brief Visuospatial Memory Test-Revised (BVMT-R) [Baseline and 8 weeks]: Part of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery. Assesses visuospatial memory. Six geometric figures are presented and participants are asked to reproduce them from memory. Minimum score: 0, Maximum score: 36. Higher scores indicate better visuospatial memory.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosed with Multiple Sclerosis by a neurologist (Hacettepe University Hospitals, Neurology Outpatient Clinic)
* Age 18 years and older
* EDSS score between 0 and 4
* Score of 24 or above on the Standardized Mini Mental State Examination
* No relapse in the past 3 months
* Medically stable for at least 6 months

Exclusion Criteria:

• Any additional cardiopulmonary, neurological, or systemic disease other than MS

• Yeliz SALCI, Principal investigator, Hacettepe University