title: Neurocirculatory and nigrostriatal abnormalities in Parkinson disease from LRRK2 mutation.
abstract: BACKGROUND
  Patients with Parkinson disease (PD) often have cardiac sympathetic denervation and failure of neurocirculatory regulation by baroreflexes. Familial PD caused by mutation of the gene encoding alpha-synuclein or by alpha-synuclein gene triplication also features cardiac sympathetic denervation and baroreflex failure.
  
  
  METHODS
  Here we report results of cardiac sympathetic neuroimaging by 6-[(18)F]fluorodopamine PET, baroreflex testing based on beat-to-beat hemodynamic responses to the Valsalva maneuver, and nigrostriatal neuroimaging using 6-[(18)F] fluorodopa PET in a proband with mutation of the gene encoding leucine-rich repeat kinase 2 (LRRK2), the most common genetic abnormality identified so far in familial PD.
  
  
  RESULTS
  The patient had no detectable 6-[(18)F] fluorodopamine-derived radioactivity in the left ventricular myocardium, a progressive fall in blood pressure during the Valsalva maneuver and no pressure overshoot after release of the maneuver, and decreased 6-[(18)F] fluorodopa-derived radioactivity bilaterally in the putamen and substantia nigra.
  
  
  CONCLUSIONS
  This patient with Parkinson disease (PD) caused by LRRK2 mutation had evidence of cardiac sympathetic denervation, baroreflex-sympathoneural and baroreflex-cardiovagal failure, and nigrostriatal dopamine deficiency, a pattern resembling that in the sporadic disease. The results fit with the concept that in LRRK2 PD, parkinsonism, cardiac sympathetic denervation, and baroreflex failure can result from a common pathogenetic process.
authors.affiliation: Clinical Neurocardiology Section, National Institutes on Neurological Disorders and Stroke, National Institute on Aging, NIH, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: R
authors.initials: R
authors.lastname: Imrich
authors.forename: E
authors.initials: E
authors.lastname: Peckham
authors.forename: C
authors.initials: C
authors.lastname: Holmes
authors.forename: G
authors.initials: G
authors.lastname: Lopez
authors.forename: C
authors.initials: C
authors.lastname: Crews
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: A
authors.initials: A
authors.lastname: Singleton
authors.forename: M
authors.initials: M
authors.lastname: Hallett
mesh_terms: D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017704:Baroreflex / Q000235:genetics; D004252:DNA Mutational Analysis; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012021:Reflex, Abnormal / Q000235:genetics; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D014636:Valsalva Maneuver / Q000235:genetics
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases