Multiple system atrophy is a rare, rapidly progressive neurodegenerative disease characterized by variable combinations of parkinsonism, cerebellar ataxia, and autonomic dysfunction. Existing natural history studies from North America, Europe, and Japan suggest that clinical phenotypes and disease progression may differ across populations. However, comprehensive multicenter prospective data from Chinese patients with multiple system atrophy remain limited.

This prospective multicenter registry study aims to describe the clinical characteristics, longitudinal progression, and outcomes of Chinese patients with multiple system atrophy, to identify factors associated with disease progression and prognosis, and to establish a longitudinal cohort for future biomarker validation and clinical trial design.

Multiple system atrophy is an adult-onset, progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia, autonomic dysfunction, and variable non-motor manifestations. The disease is pathologically associated with alpha-synuclein accumulation and neuronal and glial degeneration in multiple brain regions. Due to its rarity, clinical heterogeneity, rapid progression, and poor prognosis, large-scale prospective studies are needed to better define its natural history and to support future therapeutic development.

This study is a prospective, observational, multicenter registry study conducted in China. Eligible participants will include patients with clinically established or clinically probable multiple system atrophy according to the 2022 Movement Disorder Society diagnostic criteria. Parkinson disease patients and healthy or non-neurodegenerative controls may also be enrolled for comparative analyses.

Data will be collected through in-person visits, medical record review, standardized clinical scales, neurological examinations, autonomic function testing, neuroimaging, laboratory tests, and biospecimen collection. Longitudinal follow-up will be performed at prespecified time points, including alternating in-person and telephone-based assessments when applicable. Clinical scales may include the Unified Multiple System Atrophy Rating Scale, Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale, non-motor symptom scales, autonomic symptom scales, and disability measures. Neuroimaging, autonomic function tests, electrophysiological or oculomotor evaluations, and biospecimen-based analyses may be performed according to the study protocol and local clinical practice.

The main objectives are to characterize the clinical features and longitudinal disease course of Chinese patients with multiple system atrophy, compare clinical characteristics between MSA-P and MSA-C subtypes, identify clinical and paraclinical factors associated with disease progression and prognosis, and establish a longitudinal platform for subsequent biomarker validation and clinical trial design.

Inclusion Criteria

1. Patients with clinically established or clinically probable multiple system atrophy according to the 2022 Movement Disorder Society diagnostic criteria; or
2. Patients with clinically established or clinically probable Parkinson disease according to the Movement Disorder Society diagnostic criteria; or
3. Healthy controls or controls without hereditary or neurodegenerative diseases who voluntarily agree to participate.
4. Age between 40 and 75 years.
5. Ability to provide informed consent or availability of a legally authorized representative when applicable.

Exclusion Criteria

1. Parkinsonism that cannot be classified as Parkinson disease or multiple system atrophy at the time of evaluation.
2. Clinical suspicion or diagnosis of other atypical parkinsonian syndromes, including progressive supranuclear palsy, dementia with Lewy bodies, or corticobasal syndrome.
3. Secondary parkinsonism due to intracranial space-occupying lesions, normal pressure hydrocephalus, drug-induced parkinsonism, or other identifiable causes.
4. Comorbid diseases that may substantially affect autonomic function, such as diabetic peripheral neuropathy or amyloidosis.
5. Refusal to participate in the study or refusal to undergo routine clinical evaluations for parkinsonian syndromes.
6. Psychiatric or behavioral abnormalities that preclude reliable clinical data collection or scale-based assessment.

Patients with MSA or PD who visited the outpatient department or wards of tertiary hospitals. Those who voluntarily participated, along with the family members of healthy individuals without neurodegenerative diseases, served as healthy controls.