Individualized Transcranial Magnetic Stimulation in Parkinsonian Disorders

Parkinsonian disorders, including Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy, are characterized by heterogeneous motor and non-motor manifestations that may respond incompletely to conventional pharmacological and rehabilitative treatments. Repetitive transcranial magnetic stimulation may provide a noninvasive approach to modulating dysfunctional brain networks. This study aims to evaluate the feasibility, safety, and potential clinical effects of individualized, network-guided repetitive transcranial magnetic stimulation in patients with parkinsonian disorders.

This is an ongoing, single-center, single-group, open-label interventional study comprising disease-specific cohorts of participants with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Individualized stimulation targets are identified using structural and functional magnetic resonance imaging, with particular attention to sites within the somato-cognitive action network. Participants receive intermittent theta burst stimulation according to the stimulation protocol specified in the intervention section of this record.

Clinical, neuroimaging, and neurophysiological assessments are performed before treatment, immediately after completion of treatment, and at the prespecified follow-up visit. Clinical assessments evaluate motor function, mobility, balance, ataxia, non-motor symptoms, autonomic symptoms, orthostatic blood pressure regulation, and urinary function, as applicable to each disease cohort. Magnetic resonance imaging and electroencephalography are used to explore treatment-related changes in brain network function. Medications and rehabilitation regimens are maintained as stable as clinically feasible during the treatment period.

An initial cohort of eight participants with multiple system atrophy was evaluated as an early, disease-specific pilot and exploratory analysis of the ongoing parent study. This analysis was conducted to assess treatment feasibility, safety, and preliminary clinical changes in the multiple system atrophy cohort. These participants form part of the overall study population and do not constitute a separate clinical trial. Recruitment and follow-up of the parent study are ongoing.

Inclusion criteria

• Diagnostic Criteria Clinically established or clinically probable Parkinson's Disease (PD) according to the 2015 International Parkinson and Movement Disorder Society (MDS) diagnostic criteria; Clinically established or clinically probable Multiple System Atrophy (MSA) according to the 2022 MDS diagnostic criteria; Clinically probable or clinically possible Progressive Supranuclear Palsy (PSP) according to the 2017 MDS diagnostic criteria.
• Demographics Aged 30 to 80 years, inclusive; no gender restrictions.
• Disease Severity and Staging PD: Modified Hoehn and Yahr (H-Y) stage 2-4; MSA: Unified Multiple System Atrophy Rating Scale (UMSARS) Part IV stage 1-4; PSP: Modified Rankin Scale (mRS) grade 2-4.
• Informed Consent and Compliance Ability to understand and comply with the study requirements and provide written informed consent.

Exclusion criteria

• Contraindications to TMS Presence of intracranial metallic implants or other foreign bodies, including but not limited to cochlear implants, cardiac pacemakers, or internal metallic/magnetic fragments.
• Contraindications to EEG and MRI EEG: Known allergy to conductive paste or other EEG-related contraindications. MRI: History of claustrophobia, presence of MRI-incompatible implants, or extensive tattoos.
• Concurrent Physical Therapies Currently receiving Transcranial Magnetic Stimulation (TMS) or other therapeutic physical modalities, such as Transcranial Direct Current Stimulation (tDCS).
• Unstable Medical Conditions Presence of unstable systemic diseases requiring urgent pharmacological or surgical intervention.
• Neurological and Psychiatric History Personal or family history of epilepsy; History of moderate-to-severe psychiatric or psychological disorders; Chronic insomnia or regular use of sedative-hypnotics; Current use of medications that significantly alter central nervous system excitability.