Cardioselective peripheral noradrenergic deficiency in Lewy body synucleinopathies.

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Citation: Annals of Clinical & Translational Neurology. 7(12):2450-2460, 2020 12.PMID: 33216462Institution: MedStar Washington Hospital CenterDepartment: NeurologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Dopamine/pk [Pharmacokinetics] | *Heart/dg [Diagnostic Imaging] | *Lewy Body Disease/me [Metabolism] | *Multiple System Atrophy/me [Metabolism] | *Myocardium/me [Metabolism] | *Norepinephrine/me [Metabolism] | *Parkinson Disease/me [Metabolism] | *Pure Autonomic Failure/me [Metabolism] | *Sympathetic Nervous System/me [Metabolism] | Aged | Autopsy | Female | Fluorine Radioisotopes | Heart Septum/dg [Diagnostic Imaging] | Heart Septum/me [Metabolism] | Heart Ventricles/dg [Diagnostic Imaging] | Heart Ventricles/me [Metabolism] | Heart/ir [Innervation] | Humans | Lewy Body Disease/dg [Diagnostic Imaging] | Male | Middle Aged | Multiple System Atrophy/dg [Diagnostic Imaging] | Parkinson Disease/dg [Diagnostic Imaging] | Positron-Emission Tomography | Pure Autonomic Failure/dg [Diagnostic Imaging] | Sympathetic Nervous System/dg [Diagnostic Imaging]Year: 2020ISSN:
  • 2328-9503
Name of journal: Annals of clinical and translational neurologyAbstract: INTERPRETATION: By in vivo sympathetic neuroimaging and postmortem neurochemistry peripheral noradrenergic deficiency in LB synucleinopathies is cardioselective. MSA does not involve peripheral noradrenergic deficiency. Copyright (c) 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.METHODS: 18 F-DA-derived radioactivity in the heart, liver, spleen, pancreas, stomach, kidneys, thyroid, and submandibular glands were analyzed from 145 patients with LB synucleinopathies (112 PD, 33 PAF), 74 controls, and 85 MSA patients. In largely separate cohorts, postmortem tissue norepinephrine data were reviewed for heart, liver, spleen, pancreas, kidney, thyroid, submandibular gland, and sympathetic ganglion tissue from 38 PD, 2 PAF, and 5 MSA patients and 35 controls.OBJECTIVE: Lewy body (LB) synucleinopathies such as Parkinson's disease (PD) entail profound cardiac norepinephrine deficiency. The status of sympathetic noradrenergic innervation at other extracranial sites has been unclear. Although in vivo neuroimaging studies have indicated a cardioselective noradrenergic lesion, no previous study has surveyed peripheral organs for norepinephrine contents in LB diseases. We reviewed 18 F-dopamine (18 F-DA) positron emission tomographic images and postmortem neurochemical data across several body organs of controls and patients with the LB synucleinopathies PD and pure autonomic failure (PAF) and the non-LB synucleinopathy multiple system atrophy (MSA).RESULTS: Interventricular septal 18 F-DA-derived radioactivity was decreased in the LB synucleinopathy group compared to the control and MSA groups (P < 0.0001 each). The LB and non-LB groups did not differ in liver, spleen, pancreas, stomach, or kidney 18 F-DA-derived radioactivity. The LB synucleinopathy group had markedly decreased apical myocardial norepinephrine, but normal tissue norepinephrine in other organs. The MSA group had normal tissue norepinephrine in all examined organs.All authors: Goldstein DS, Holmes C, Lamotte G, Lenka A, Sullivan POriginally published: Annals of Clinical & Translational Neurology. 2020 Nov 20Fiscal year: FY2021Fiscal year of original publication: FY2021Digital Object Identifier: Date added to catalog: 2020-12-31
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Journal Article MedStar Authors Catalog Article 33216462 Available 33216462

INTERPRETATION: By in vivo sympathetic neuroimaging and postmortem neurochemistry peripheral noradrenergic deficiency in LB synucleinopathies is cardioselective. MSA does not involve peripheral noradrenergic deficiency. Copyright (c) 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

METHODS: 18 F-DA-derived radioactivity in the heart, liver, spleen, pancreas, stomach, kidneys, thyroid, and submandibular glands were analyzed from 145 patients with LB synucleinopathies (112 PD, 33 PAF), 74 controls, and 85 MSA patients. In largely separate cohorts, postmortem tissue norepinephrine data were reviewed for heart, liver, spleen, pancreas, kidney, thyroid, submandibular gland, and sympathetic ganglion tissue from 38 PD, 2 PAF, and 5 MSA patients and 35 controls.

OBJECTIVE: Lewy body (LB) synucleinopathies such as Parkinson's disease (PD) entail profound cardiac norepinephrine deficiency. The status of sympathetic noradrenergic innervation at other extracranial sites has been unclear. Although in vivo neuroimaging studies have indicated a cardioselective noradrenergic lesion, no previous study has surveyed peripheral organs for norepinephrine contents in LB diseases. We reviewed 18 F-dopamine (18 F-DA) positron emission tomographic images and postmortem neurochemical data across several body organs of controls and patients with the LB synucleinopathies PD and pure autonomic failure (PAF) and the non-LB synucleinopathy multiple system atrophy (MSA).

RESULTS: Interventricular septal 18 F-DA-derived radioactivity was decreased in the LB synucleinopathy group compared to the control and MSA groups (P < 0.0001 each). The LB and non-LB groups did not differ in liver, spleen, pancreas, stomach, or kidney 18 F-DA-derived radioactivity. The LB synucleinopathy group had markedly decreased apical myocardial norepinephrine, but normal tissue norepinephrine in other organs. The MSA group had normal tissue norepinephrine in all examined organs.

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