Data-Driven Subtypes of Multiple System Atrophy and Their Implications for Prognosis

Area of Science:

• Neurology
• Clinical Phenotyping
• Disease Progression

Background:

• Multiple system atrophy (MSA) exhibits significant heterogeneity in motor and non-motor symptoms.
• The relationship between distinct clinical phenotypes and patient prognosis in MSA remains poorly understood.

Purpose of the Study:

• To employ a data-driven approach to define clinical phenotypes in MSA.
• To assess the impact of identified MSA phenotypes on patient survival and the likelihood of becoming bedbound.

Main Methods:

• Cluster analysis was used to categorize 193 MSA patients based on their clinical history, motor, and non-motor symptoms.
• Kaplan-Meier analysis, Cox regression, and logistic regression were utilized to evaluate survival and identify factors associated with survival and bedbound status in 95 followed-up patients.

Main Results:

• Four distinct MSA clinical profiles were identified: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse.
• The malignant diffuse and rigid akinetic-dominant clusters demonstrated a significantly higher risk of mortality and becoming bedbound compared to the sleep and mood disorder-dominant and cerebellar symptom-dominant clusters, respectively.
• Median survival for the overall MSA cohort was 7.75 years.

Conclusions:

• Beyond classical parkinsonism and cerebellar subtypes, malignant diffuse and sleep/mood disorder-dominant profiles were identified.
• Patients with rigid-akinetic motor profiles generally face a worse prognosis than those with cerebellar symptom-dominant profiles.
• Early identification of diffuse symptoms, particularly postural instability and cognitive changes, signals rapid functional decline and disease progression, potentially indicating diverse underlying pathologies.