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Disease Progression in Multiple System Atrophy: The ASPIRE Multi-Modal Biomarker Study.

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Early multiple system atrophy (MSA) shows rapid neuroimaging changes within six months. Higher neurofilament light chain (NfL) levels predict increased mortality and dropout risk in MSA patients.

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Area of Science:

  • Neurology
  • Biomarker Research
  • Neurodegenerative Diseases

Background:

  • Multiple system atrophy (MSA) is a progressive neurodegenerative disorder.
  • Early diagnosis and understanding disease progression are crucial for patient management.
  • Candidate biomarkers require characterization in early-stage MSA.

Purpose of the Study:

  • To characterize changes in candidate biomarkers in early multiple system atrophy (MSA).
  • To identify baseline predictors of faster disease progression in MSA.
  • To assess the utility of neuroimaging and plasma NfL in early MSA.

Main Methods:

  • A 1-year prospective, multicenter study involving early MSA patients and healthy controls.
  • Assessed clinical scores (UMSARS), 3T-MRI, DaT-SPECT, and plasma NfL.
  • Analyzed changes from baseline to 6 and 12 months using mixed linear regression.

Main Results:

  • Significant worsening of UMSARS scores and increased brainstem/cerebellar atrophy observed within 6 months.
  • Decreased striatal specific binding ratio (SBR) was noted, with distinct patterns in MSA-P and MSA-C subtypes.
  • Baseline brainstem/pons volume and SBR predicted clinical worsening; higher plasma NfL correlated with dropout and mortality risk.

Conclusions:

  • Neuroimaging changes are detectable within 6 months in early MSA.
  • Plasma NfL is a significant predictor of mortality and dropout risk in MSA.
  • Longitudinal biomarker assessment offers valuable insights into MSA progression.