Natural history of pure autonomic failure: A United States prospective cohort

on behalf of the Autonomic Disorders Consortium

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Objective: To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. Methods: One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy-four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests. Results: At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow-up, 25 of 74 subjects (34%) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell. Interpretation: Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis. Ann Neurol 2017;81:287–297.

Original languageEnglish (US)
Pages (from-to)287-297
Number of pages11
JournalAnnals of Neurology
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2017

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Pure Autonomic Failure
Smell
Multiple System Atrophy
Lewy Body Disease
REM Sleep Behavior Disorder
Parkinson Disease
Central Nervous System
Age of Onset
Norepinephrine
Sleep
Urinary Bladder
Biomarkers
Heart Rate
Odds Ratio

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Natural history of pure autonomic failure : A United States prospective cohort. / on behalf of the Autonomic Disorders Consortium.

In: Annals of Neurology, Vol. 81, No. 2, 01.02.2017, p. 287-297.

Research output: Contribution to journalArticle

on behalf of the Autonomic Disorders Consortium 2017, 'Natural history of pure autonomic failure: A United States prospective cohort', Annals of Neurology, vol. 81, no. 2, pp. 287-297. https://doi.org/10.1002/ana.24877
on behalf of the Autonomic Disorders Consortium. / Natural history of pure autonomic failure : A United States prospective cohort. In: Annals of Neurology. 2017 ; Vol. 81, No. 2. pp. 287-297.
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abstract = "Objective: To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. Methods: One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy-four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests. Results: At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow-up, 25 of 74 subjects (34{\%}) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell. Interpretation: Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis. Ann Neurol 2017;81:287–297.",
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