Bilateral Anodal Cerebellar tDCS for Multidomain Dysfunctions in Patients With Multiple Sclerosis

Bilateral Anodal Cerebellar tDCS for Multidomain Dysfunctions in Patients With Multiple Sclerosis: A Randomized Controlled Trial Study

The goal of this clinical trial is to learn if brain stimulation can improve movement and daily function in people with multiple sclerosis (MS). The study will also look at how this treatment affects fatigue, sleep, memory and attention, and quality of life.

The main questions this study aims to answer are the following:

Does this treatment improve coordination and balance? Does it reduce fatigue and improve sleep and daily life? Does it change brain activity?

Researchers will compare active brain stimulation to sham stimulation (a look-alike treatment that does not deliver real stimulation) to see if the treatment works.

Participants will:

Receive brain stimulation sessions for two weeks Attend assessment sessions before and after treatment Return for a follow-up visit after four weeks Complete tests of movement, fatigue, sleep, and thinking

Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder characterized by demyelination and neurodegeneration within the central nervous system. Disruption of cerebro-cerebellar networks is a key feature of MS and contributes to impairments in motor coordination, balance, gait, fatigue, and cognitive performance. Cerebellar involvement is particularly associated with ataxia and postural instability, which significantly affect functional independence and quality of life.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique capable of modulating cortical and cerebellar excitability. Previous studies investigating cerebellar tDCS in MS have reported variable findings, which may be related to heterogeneity in stimulation protocols, the predominant use of unilateral stimulation approaches, and the frequent combination of stimulation with task-oriented rehabilitation. These factors limit the ability to isolate the independent effects of neuromodulation.

The cerebellum operates through bilateral cerebro-cerebellar loops, suggesting that bilateral stimulation may provide more comprehensive modulation of these distributed networks compared to unilateral approaches. In addition, the effects of tDCS are influenced by state-dependent factors, including concurrent motor activity. Delivering stimulation as a standalone intervention allows for clearer evaluation of its direct neuromodulatory effects without the confounding influence of concurrent rehabilitation.

This study is designed as a randomized, double-blind, sham-controlled trial to evaluate the effects of bilateral cerebellar tDCS on multidomain dysfunction in individuals with MS. Participants will be randomly assigned to receive either active or sham stimulation. The intervention consists of repeated sessions of bilateral cerebellar stimulation delivered over a two-week period using a standardized protocol.

The study aims to evaluate the effects of this intervention on motor and non-motor domains and to explore associated neurophysiological changes. By isolating the effects of bilateral cerebellar stimulation, this trial seeks to provide a clearer understanding of its therapeutic potential and to inform the development of targeted neuromodulation strategies in MS rehabilitation.

Inclusion Criteria:

• Confirmed diagnosis of Multiple Sclerosis according to the revised McDonald criteria
• Adult Age > 18 years
• Expanded Disability Status Scale (EDSS) score between 2.0 and 6.0
• Clinically stable disease status for at least 3 months prior to enrollment
• On stable disease-modifying therapy (DMT) for at least 3 months
• Ability to understand study procedures and provide informed consent
• Ability to ambulate independently or with assistive devices sufficient to complete motor assessments

Exclusion Criteria:

• Multiple sclerosis relapse within the past 3 months
• History of epilepsy or seizures
• Presence of implanted electronic devices (e.g., pacemaker, neurostimulator)
• Metallic implants in the head or skull incompatible with transcranial magnetic stimulation (TMS)
• Severe cognitive impairment preventing participation in assessments
• Pregnancy or planned pregnancy during the study period
• Other neurological or psychiatric disorders that may confound study outcomes
• Severe musculoskeletal or orthopedic conditions interfering with motor performance testing
• Contraindications to non-invasive brain stimulation or TMS