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

Cheng-Cheng Fan1, Chao Han2, Xue-Mei Wang3

  • 1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Journal of Parkinson'S Disease
|July 20, 2024
PubMed
Summary

This study identified four distinct clinical profiles in multiple system atrophy (MSA), revealing that malignant diffuse and rigid akinetic subtypes significantly worsen prognosis and increase the risk of becoming bedbound compared to other MSA phenotypes.

Keywords:
Multiple system atrophynon-motor symptomsprognosissubtypessurvival

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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.