Intermittent Theta-Burst Stimulation for Lower-Limb Spasticity and Pain in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. Lower-limb spasticity and neuropathic pain can substantially impair mobility, daily functioning, and quality of life. Current symptomatic treatments include oral antispastic medication and targeted botulinum toxin type A injections, but their effects may be incomplete or time-limited. Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation protocol with the potential to modulate cortical and corticospinal excitability. The study will determine whether active iTBS applied over the primary motor cortex produces a greater reduction in lower-limb spasticity and neuropathic pain than sham iTBS in patients with MS. This is a randomized, two-arm, parallel-group, sham-controlled, assessor-blinded clinical study conducted at the Multiple Sclerosis Centre of the 2nd Department of Neurology, Faculty of Medicine, Comenius University Bratislava and University Hospital Bratislava. Eligible participants will be randomized to active iTBS or sham iTBS. Stimulation will target the primary motor cortex contralateral to the more affected lower limb and the cortical representation of the muscle group corresponding to the dominant spastic pattern, identified using motor-evoked potentials and neuronavigation. Participants will undergo five sessions on consecutive weekdays. The active protocol comprises 1,200 pulses per day, delivered as two 600-pulse blocks separated by a 15-minute inter-block interval. Clinical and neurophysiological assessments will be performed at baseline and at Weeks 2 and 4 after the intervention by an assessor blinded to treatment allocation. Assessments include the Tardieu Scale, pain measures, MS-specific quality-of-life and symptom questionnaires, and the H/M ratio measured by electromyography. Participants with a persistent clinical indication after completion of the four-week follow-up may receive botulinum toxin type A as standard-of-care rescue treatment.