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Cardiac and Extracardiac Sympathetic Denervation in Parkinson’s Disease with Orthostatic Hypotension and in Pure Autonomic Failure

Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

The uptake of 6-¹⁸F-fluorodopamine by cardiac noradrenergic nerves enables visualization of the sympathetic innervation of the left ventricular myocardium by PET. Patients with Parkinson’s disease (PD) and orthostatic hypotension (OH) (PD+OH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-¹⁸F-fluorodopamine–derived radioactivity, consistent with cardiac sympathetic denervation, a phenomenon that neurochemical, neuropharmacologic, and, most recently, postmortem neuropathologic studies have confirmed. In this study, we examined whether 6-¹⁸F-fluorodopamine can visualize sympathetic innervation in extracardiac organs and, if so, whether patients with PD+OH or PAF have neuroimaging evidence of extracardiac noradrenergic denervation. Methods: To validate the method, healthy volunteers underwent 6-¹⁸F-fluorodopamine scanning of the head, thorax, and abdomen, with or without treatment with desipramine to block sympathoneural uptake of catecholamines. ¹³N-Ammonia scanning was used to address possible group differences in 6-¹⁸F-fluorodopamine delivery by blood perfusion. Results: Desipramine treatment was associated with decreased 6-¹⁸F-fluorodopamine–derived radioactivity in the heart, renal cortex, and thyroid gland but not in the liver, spleen, renal pelvis, or salivary glands. Both the PD+OH group and the PAF group had decreased 6-¹⁸F-fluorodopamine–derived radioactivity in the heart (P < 0.0001) and renal cortex (P = 0.02 and P = 0.005, respectively). The PD+OH group also had decreased radioactivity in the thyroid gland (P = 0.01). Neither group had decreased radioactivity in the other organs, after correction for ¹³N-ammonia–derived radioactivity. Conclusion: 6-¹⁸F-Fluorodopamine scanning visualizes sympathetic innervation in the heart, renal cortex, and thyroid gland. Both PD+OH and PAF involve decreased noradrenergic innervation that is most prominent in the heart but is also detectable in extracardiac organs.

Key Words: fluorodopamine • ammonia • pure autonomic failure • Parkinson’s disease • PET

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