title: Pure autonomic failure: Predictors of conversion to clinical CNS involvement.
abstract: 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.
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Singer
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Berini
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Paola
authors.initials: P
authors.lastname: Sandroni
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fealey
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Coon
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Mariana D
authors.initials: MD
authors.lastname: Suarez
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN.
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Benarroch
authors.affiliation: From the Department of Neurology, Mayo Clinic, Rochester, MN. low@mayo.edu.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001833:Body Temperature Regulation; D002490:Central Nervous System / Q000000981:diagnostic imaging; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006339:Heart Rate; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000503:physiopathology; D009460:Neurologic Examination; D010300:Parkinson Disease / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D054970:Pure Autonomic Failure / Q000503:physiopathology*; D055815:Young Adult