title: Pure autonomic failure without synucleinopathy.
abstract: Pure autonomic failure is a rare form of chronic autonomic failure manifesting with neurogenic orthostatic hypotension and evidence of sympathetic noradrenergic denervation unaccompanied by signs of central neurodegeneration. It has been proposed that pure autonomic failure is a Lewy body disease characterized by intra-neuronal deposition of the protein alpha-synuclein in Lewy bodies and neurites. A middle-aged man with previously diagnosed pure autonomic failure experienced a sudden, fatal cardiac arrest. He was autopsied, and tissues were harvested for neurochemical and immunofluorescence studies. Post-mortem microscopic neuropathology showed no Lewy bodies, Lewy neurites, or alpha-synuclein deposition by immunohistochemistry anywhere in the brain. The patient had markedly decreased immunofluorescent tyrosine hydroxylase in sympathetic ganglion tissue without detectable alpha-synuclein even in rare residual nests of tyrosine hydroxylase-containing ganglionic fibers. In pure autonomic failure, sympathetic noradrenergic denervation can occur without concurrent Lewy bodies or alpha-synuclein deposition in the brain or sympathetic ganglion tissue.
authors.affiliation: Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Risa
authors.initials: R
authors.lastname: Isonaka
authors.affiliation: Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Holmes
authors.affiliation: Naval Medical Center, Portsmouth, VA, USA.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Cook
authors.affiliation: Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD, 20892-1620, USA.
authors.forename: Patti
authors.initials: P
authors.lastname: Sullivan
authors.affiliation: Tel Aviv University Sackler Faculty of Medicine, Tel HaShomer, Israel.
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Sharabi
authors.affiliation: Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 5N220, Bethesda, MD, 20892-1620, USA. goldsteind@ninds.nih.gov.
authors.forename: David S
authors.initials: DS
authors.lastname: Goldstein
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D054970:Pure Autonomic Failure / Q000097:blood* / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014636:Valsalva Maneuver / Q000502:physiology*; D051844:alpha-Synuclein / Q000097:blood*
chemical_list: D051844:alpha-Synuclein
keywords: Catecholamine; Norepinephrine; Pure autonomic failure; Sympathetic; Synuclein