Multimodal Autonomic Biomarkers Predict Phenoconversion in Pure Autonomic Failure

Area of Science:

• Neurology
• Autonomic Neuroscience
• Synucleinopathies

Background:

• Pure autonomic failure (PAF) is characterized by autonomic dysfunction without other neurological signs.
• A significant proportion of PAF patients develop central neurological features, meeting criteria for multiple system atrophy (MSA) or Lewy body diseases (LBD).
• Distinguishing between these conditions and predicting progression is crucial for patient management.

Purpose of the Study:

• To investigate multimodal autonomic biomarkers for differentiating PAF, MSA, and LBD.
• To identify predictors of phenoconversion from PAF to MSA or LBD.
• To assess the utility of non-invasive autonomic assessments in predicting disease trajectory.

Main Methods:

• An observational cohort study involving 391 patients with alpha-synucleinopathy.
• Comprehensive autonomic assessments including cardiovascular testing, plasma noradrenaline, pupillometry, and questionnaires.
• Logistic regression modeling to identify predictive autonomic biomarkers for phenoconversion in PAF patients.

Main Results:

• PAF patients exhibited more severe orthostatic hypotension, lower supine plasma noradrenaline, and sympathetic pupillary deficits compared to MSA and LBD.
• 26% of PAF patients phenoconverted to MSA or LBD over a median of 13 years.
• Normal pupillary function, heart rate response ≥ 10 bpm, and supine noradrenaline ≥ 200 pg/mL predicted phenoconversion; younger age and higher noradrenaline predicted MSA conversion.

Conclusions:

• Normal pupillary function, intact cardiovagal responses, and specific plasma noradrenaline levels are indicators of future phenoconversion in PAF.
• Younger patients with higher supine plasma noradrenaline levels are more prone to developing MSA.
• Multimodal autonomic assessment effectively differentiates alpha-synucleinopathies and predicts PAF phenoconversion.