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Related Experiment Video

Updated: Jul 2, 2025

Measuring Cardiac Autonomic Nervous System ANS Activity in Children
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Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study.

Patricio Millar Vernetti1, Lucy Norcliffe-Kaufmann1, Jose-Alberto Palma1

  • 1Department of Neurology, New York University Grossman School of Medicine, New York, NY 10016, USA.

Brain : a Journal of Neurology
|February 17, 2024
PubMed
Summary

Pure autonomic failure (PAF) patients phenoconverting to Parkinson's disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) showed early clinical markers. These include autonomic, motor, and swallowing issues, predicting progression of alpha-synuclein neurodegeneration.

Keywords:
Lewy body diseaseatypical parkinsonismautonomic dysfunctionautonomic failurenatural historyprospective

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Area of Science:

  • Neurology
  • Autonomic Neuroscience
  • Neurodegenerative Diseases

Background:

  • Pure autonomic failure (PAF) is a synucleinopathy precursor.
  • Identifying early markers for phenoconversion is crucial for neurodegenerative disease prediction.

Purpose of the Study:

  • To identify clinical features of PAF patients that predict phenoconversion to alpha-synuclein-associated neurodegeneration.
  • To establish predictive markers for Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) in PAF patients.

Main Methods:

  • Longitudinal observational cohort study of 209 PAF patients.
  • Detailed assessments of autonomic, motor, sleep, olfactory, and cognitive functions.
  • Prospective follow-up for up to 10 years to identify phenoconversion events.

Main Results:

  • 33% of participants phenoconverted within a mean of 3 years.
  • Faster phenoconversion linked to urinary/sexual dysfunction, subtle motor signs, dysphagia, and speech changes.
  • Specific markers identified for PD (handwriting), DLB (utensil handling), and MSA (younger onset, preserved olfaction, anhidrosis, urinary issues).
  • Blunted heart rate response during tilt-table test predicted PD.
  • Annual phenoconversion risk to CNS synucleinopathy estimated at 12%.

Conclusions:

  • Clinical features at PAF diagnosis can predict phenoconversion to specific alpha-synucleinopathies.
  • Early identification of predictive markers aids in understanding neurodegenerative disease progression.
  • Autonomic dysfunction severity and specific symptoms are key indicators for phenoconversion risk.