Different phenoconversion pathways in pure autonomic failure with versus without Lewy bodies

ObjectiveTo determine predicting factors and frequency of phenoconversion from pure autonomic failure (PAF) into a synucleinopathy with motor or cognitive involvement of multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB).MethodsWe performed a retrospective review of all patients with PAF from 2001 to 2011 evaluated at Mayo Clinic, Rochester. Clinical follow-up and patient telephone calls were used to assess for development of symptoms and diagnosis of MSA, PD, or DLB. Clinical and laboratory variables were extracted with factors predictive of evolution assessed using group comparison, odds ratio, and logistical regression.ResultsAmong 275 patients with PAF at presentation, 67 (24%) phenoconverted to a synucleinopathy with motor or cognitive involvement; 34 met criteria for MSA, while 33 met criteria for PD or DLB. Age at onset was younger in MSA phenoconverters. Clinical features at presentation influenced phenoconversion: severe bladder symptoms were more common in MSA phenoconverters; subtle motor signs were more frequent in MSA and PD/DLB phenoconverters. MSA phenoconverters were more likely to have higher supine norepinephrine levels and preganglionic pattern of anhidrosis. Presentation variables predicting MSA phenoconversion included subtle motor signs, supine norepinephrine levels, severe bladder symptoms, and dream enactment behavior. Presentation variables predictive of PD/DLB phenoconversion included subtle motor signs, dream enactment behavior, and constipation.ConclusionsOur findings suggest that at least a quarter of patients with PAF phenoconvert to MSA, PD, or DLB. Presentation features determine patients at risk for evolution with specific patterns indicative of phenoconversion to MSA vs PD/DLB.Classification of evidence:This study provides Class II evidence that several presentation variables including subtle motor signs, severe bladder symptoms, and dream enactment behavior are associated with an increased risk of developing a synucleinopathy with motor or cognitive involvement.

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The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature

Acta Neuropathologica ◽

10.1007/s004010050693 ◽

1997 ◽

Vol 94 (2) ◽

pp. 192-196 ◽

Cited By ~ 120

Author(s):

K. Hague ◽

P. Lento ◽

S. Morgello ◽

S. Caro ◽

H. Kaufmann

Keyword(s):

Autonomic Failure ◽

Lewy Bodies ◽

Pure Autonomic Failure ◽

Review Of The Literature ◽

Autopsy Findings

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Pure autonomic failure

Neurology ◽

10.1212/wnl.0000000000003737 ◽

2017 ◽

Vol 88 (12) ◽

pp. 1129-1136 ◽

Cited By ~ 43

Author(s):

Wolfgang Singer ◽

Sarah E. Berini ◽

Paola Sandroni ◽

Robert D. Fealey ◽

Elizabeth A. Coon ◽

...

Keyword(s):

Bladder Dysfunction ◽

Autonomic Failure ◽

Lewy Bodies ◽

Pure Autonomic Failure ◽

Cns Involvement ◽

Sweat Loss ◽

Mild Degree ◽

Several Variables ◽

Laboratory Variables

Objective:Based on the observation that a subset of patients originally diagnosed with pure autonomic failure (PAF) eventually develops extrapyramidal or cerebellar involvement consistent with multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB), we aimed to identify predictors of progression of PAF to more sinister synucleinopathies.Methods:In this retrospective cohort study, we reviewed patients seen at Mayo Clinic Rochester by autonomic specialists between 2001 and 2011 and during initial evaluation diagnosed with orthostatic hypotension consistent with PAF (possible PAF). In order to assess for the presence or absence of progression, we identified patients with 3 years or more of in-person follow-up (stable PAF) or documented progression to another synucleinopathy (converters). To identify predictors of conversion, we assessed odds of conversion based on clinical, autonomic, and laboratory variables.Results:Among 318 patients fulfilling criteria for possible PAF, we identified 41 with stable PAF and 37 (12%) converters. Of those who evolved, 22 developed MSA, 11 developed PD/DLB, and 4 remained indeterminate. Several variables were identified to predict conversion to MSA: (1) mild degree of cardiovagal impairment, (2) preganglionic pattern of sweat loss, (3) severe bladder dysfunction, (4) supine norepinephrine >100 pg/mL, and (5) subtle motor signs at first presentation. Separate variables were found to predict conversion to PD/DLB. Composite conversion scores were generated based on individual predictors.Conclusions:Over 10% of patients originally diagnosed with PAF eventually evolve to develop CNS involvement, most commonly MSA. A combination of variables allows for prediction of conversion.

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