Multiple sclerosis (MS) is a chronic autoimmune central nervous system disease characterized by inflammation, demyelination, and neurodegeneration, resulting in motor, cognitive, speech-language, psychological, and cardiac autonomic impairments.
This double-blind, randomized, controlled crossover trial investigates the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex (Cz) and left dorsolateral prefrontal cortex (F3), combined with virtual reality (VR)-based exercise (MoveHero platform) and conventional physiotherapy, in 30 individuals with MS (EDSS 1.0-6.5).
Participants are randomized to Active-then-Sham or Sham-then-Active sequence groups. Each phase consists of 10 consecutive weekday rTMS sessions, followed by at least four weeks washout before crossover. Both targets use a circular coil at 10 Hz. Cz is stimulated at 90% resting motor threshold (30 trains, 50 pulses/train) and F3 at 110% resting motor threshold (40 trains, 50 pulses/train). The sham condition replicates the procedure with the coil inverted at 10% intensity. On six of ten intervention days, rTMS is followed by VR exercise and balance-focused physiotherapy.
Outcomes assessed at baseline and post-intervention include cardiac autonomic modulation (heart rate variability), balance, functional mobility, manual dexterity, fatigue, quality of life, depression, attention, executive function, working memory, psychological well-being, verbal fluency, and speech-language function (aphasia, dysphagia, dysarthria, voice quality). Follow-up reassessments are conducted at six months and one year.