Guillaume Lamotte1, Courtney Holmes2, Tianxia Wu3, David S Goldstein4. 1. Clinical Neurosciences Program (CNP), Division of Intramural Research (CNP), National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike 10/8C260, Bethesda, MD, 20892, USA; Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike 10/8C260, Bethesda, MD, 20892, USA. Electronic address: guillaume.lamotte@nih.gov/. 2. Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike 10/8C260, Bethesda, MD, 20892, USA. Electronic address: holmesc@ninds.nih.gov. 3. Clinical Trials Unit, NINDS, 9000 Rockville Pike 10/2A23B, Bethesda, MD, 20892, USA. Electronic address: wuti@mail.nih.gov. 4. Clinical Neurocardiology Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike 10/8C260, Bethesda, MD, 20892, USA. Electronic address: goldsteind@ninds.nih.gov.
Abstract
INTRODUCTION: Parkinson disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are characterized by intra-cerebral deposition of the protein alpha-synuclein and are termed synucleinopathies. Lewy body synucleinopathies involve decreased cardiac sympathetic innervation and functional abnormalities in residual noradrenergic terminals. This observational, retrospective, cohort study describes long-term trends in indices of cardiac sympathetic innervation and function in synucleinopathies. METHODS: Patients with PD (N = 31), PAF (N = 9), or MSA (N = 9) underwent repeated 18F-dopamine positron emission tomography (median follow-up 3.5 years). Interventricular septal 18F-dopamine-derived radioactivity 8 min after tracer injection (8' Radioactivity) was used as an index of sympathetic innervation and the slope of mono-exponential decline of radioactivity between 8 and 25 min (k8'-25') as an index of intraneuronal vesicular storage. Healthy volunteers (HVs) (N = 33) and individuals at high risk of PD (N = 15) were controls. RESULTS: Upon initial evaluation the groups with PD and orthostatic hypotension (OH), PAF, or PD and no OH had low mean 8' Radioactivity compared to HVs (p < 0.0001, p = 0.0002, p = 0.006) and had elevated k8'-25' (p = 0.0007, p = 0.007, p = 0.06). There was no significant difference between MSA and HVs. In PD 8' Radioactivity decreased by a median of 4% per year and did not decrease in MSA. k8'-25' values did not change during follow-up in any group. CONCLUSIONS: Neuroimaging evidence of decreased vesicular uptake in cardiac sympathetic nerves is present upon initial evaluation of patients with Lewy body synucleinopathies and may provide a biomarker of catecholaminergic dysfunction early in the disease process. Published by Elsevier Ltd.
INTRODUCTION:Parkinson disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) are characterized by intra-cerebral deposition of the protein alpha-synuclein and are termed synucleinopathies. Lewy body synucleinopathies involve decreased cardiac sympathetic innervation and functional abnormalities in residual noradrenergic terminals. This observational, retrospective, cohort study describes long-term trends in indices of cardiac sympathetic innervation and function in synucleinopathies. METHODS:Patients with PD (N = 31), PAF (N = 9), or MSA (N = 9) underwent repeated 18F-dopamine positron emission tomography (median follow-up 3.5 years). Interventricular septal 18F-dopamine-derived radioactivity 8 min after tracer injection (8' Radioactivity) was used as an index of sympathetic innervation and the slope of mono-exponential decline of radioactivity between 8 and 25 min (k8'-25') as an index of intraneuronal vesicular storage. Healthy volunteers (HVs) (N = 33) and individuals at high risk of PD (N = 15) were controls. RESULTS: Upon initial evaluation the groups with PD and orthostatic hypotension (OH), PAF, or PD and no OH had low mean 8' Radioactivity compared to HVs (p < 0.0001, p = 0.0002, p = 0.006) and had elevated k8'-25' (p = 0.0007, p = 0.007, p = 0.06). There was no significant difference between MSA and HVs. In PD 8' Radioactivity decreased by a median of 4% per year and did not decrease in MSA. k8'-25' values did not change during follow-up in any group. CONCLUSIONS: Neuroimaging evidence of decreased vesicular uptake in cardiac sympathetic nerves is present upon initial evaluation of patients with Lewy body synucleinopathies and may provide a biomarker of catecholaminergic dysfunction early in the disease process. Published by Elsevier Ltd.
Entities:
Keywords:
Fluorodopamine; Multiple system atrophy; Parkinson disease; Pure autonomic failure; Sympathetic nervous system
Authors: William J Burke; Vijaya B Kumar; Neeraj Pandey; W Michael Panneton; Qi Gan; Mark W Franko; Mark O'Dell; Shu Wen Li; Yi Pan; Hyung D Chung; James E Galvin Journal: Acta Neuropathol Date: 2007-10-27 Impact factor: 17.088