title: Cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K mutation in the α synuclein gene.
abstract: OBJECTIVE
  The aim of this study was to analyze autonomic function and cardiac sympathetic innervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene (SNCA) mutation.
  
  
  METHODS
  Autonomic function tests were performed in six patients, four of whom were symptomatic carriers (ages: 46, 59, 52 and 28-years) and two who were asymptomatic carriers (ages: 52 and 29 years). Autopsy studies were performed on an additional two symptomatic carriers not eligible for autonomic testing. Patients completed the SCOPA autonomic questionnaire, and underwent the head-up tilt test accompanied by measurements of plasma norepinephrine. Valsalva maneuver and deep breathing tests, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy were carried out. Myocardial tissue sections removed from the two autopsied cases were subjected to routine histological staining and immunohistochemical processing with monoclonal antibodies against tyrosine hydroxylase and alpha-synuclein.
  
  
  RESULTS
  Both the four symptomatic and the older asymptomatic carriers reported abnormalities in the SCOPA questionnaire and had markedly diminished cardiac MIBG uptake. Plasma norepinephrine in the supine and tilted positions was normal in all subjects. Only one patient had significant orthostatic hypotension. There was a complete absence of tyrosine hydroxylase immunostaining in the myocardium of the two autopsied cases.
  
  
  CONCLUSIONS
  We have found imaging and histological evidence of cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene mutation. The sympathetic denervation appears to be organ-specific, with selective affectation of the heart given that plasma norepinephrine levels and blood pressure were normal.
authors.affiliation: Movement Disorders and Autonomic Unit, Neurology Service, Cruces University Hospital, Basque Health Service, Department of Neurosciences, University of the Basque Country, Spain. beatriz_tijero@hotmail.com
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tijero
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gómez-Esteban
authors.forename: Elena
authors.initials: E
authors.lastname: Lezcano
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-González
authors.forename: Johanne
authors.initials: J
authors.lastname: Somme
authors.forename: Verónica
authors.initials: V
authors.lastname: Llorens
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martínez
authors.forename: Nerea
authors.initials: N
authors.lastname: Foncea
authors.forename: Inés
authors.initials: I
authors.lastname: Escalza
authors.forename: Koldo
authors.initials: K
authors.lastname: Berganzo
authors.forename: M A
authors.initials: MA
authors.lastname: Aniel-Quiroga
authors.forename: Verónica
authors.initials: V
authors.lastname: Ruiz
authors.forename: Nuria
authors.initials: N
authors.lastname: Terán
authors.forename: Horacio
authors.initials: H
authors.lastname: Kaufmann
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Zarranz
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics; D005260:Female; D006321:Heart / Q000294:innervation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009638:Norepinephrine / Q000097:blood; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D013562:Sympathectomy / Q000379:methods; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014636:Valsalva Maneuver / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D009638:Norepinephrine