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ARTICLE

Cardiac Sympathetic Denervation in Parkinson Disease

David S. Goldstein, MD, PhD; Courtney Holmes, CMT; Sheng-Ting Li, MD; Simon Bruce, MD; Leo Verhagen Metman, MD; and Richard O. Cannon, III, MD

5 September 2000 | Volume 133 Issue 5 | Pages 338-347

Background: In Parkinson disease, orthostatic hypotension can result from L-dopa treatment or from sympathetic neurocirculatory failure. The latter is detected by abnormal blood pressure responses to the Valsalva maneuver and can be associated with loss of functional cardiac sympathetic nerve terminals.

Objective: To determine the frequency of cardiac sympathetic denervation in Parkinson disease, with or without sympathetic neurocirculatory failure, and its association with disease duration, severity, and L-dopa treatment.

Design: Intergroup comparisons in resting patients.

Setting: National Institutes of Health Clinical Center, Bethesda, Maryland.

Patients: 29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers.

Measurements: Beat-to-beat blood pressure responses to the Valsalva maneuver, interventricular septal 6-[¹⁸F]fluorodopamine–derived radioactivity, cardiac extraction fraction of [³H]norepinephrine, appearance rate of norepinephrine in coronary sinus plasma (cardiac norepinephrine spillover) and venous–arterial differences in levels of dihydroxyphenylglycol (DHPG) and endogenous L-dopa.

Results: Of the 29 patients with Parkinson disease, 9 with sympathetic neurocirculatory failure and 11 without had low septal 6-[¹⁸F]fluorodopamine–derived radioactivity (2861 ± 453 Bq/mL per MBq/kg and 5217 ± 525 Bq/mL per MBq/kg, respectively). All 6 patients with Parkinson disease and decreased 6-[¹⁸F]fluorodopamine–derived radioactivity who underwent right-heart catheterization had a decreased cardiac extraction fraction of [³H]norepinephrine and virtually no cardiac norepinephrine spillover or venous–arterial increments in plasma levels of DHPG and L-dopa. Sympathetic neurocirculatory failure and decreased 6-[¹⁸F]fluorodopamine–derived radioactivity were unrelated to disease duration, disease severity, or L-dopa treatment.

Conclusions: Many patients with Parkinson disease—including all those with sympathetic neurocirculatory failure—have evidence of cardiac sympathetic denervation. This suggests that loss of catecholamine innervation in Parkinson disease occurs in the nigrostriatal system in the brain and in the sympathetic nervous system in the heart.

Author and Article Information

From the National Institutes of Health, Bethesda, Maryland; and Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.

Acknowledgments: The authors thank Marjorie Gillespie, RN; Patricia Woltz, RN; Sandra Brentzel, RN; the cardiac catheterization nurses of the Cardiology Branch, National Heart, Lung, and Blood Institute; and the technicians of the National Institutes of Health Positron Emission Tomography Department.

Requests for Single Reprints: David S. Goldstein, MD, PhD, Building 10, Room 6N252, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

Current Author Addresses: Drs. Goldstein, Li, and Bruce: Building 10, Room 6N252, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620.

Ms. Holmes: Building 10, Room 6N250, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620.

Dr. Verhagen Metman: Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Suite 1606, 1725 West Harrison Street, Chicago, IL 60612.

Dr. Cannon: Building 10, Room 7B15, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892.

Author Contributions: Conception and design: D.S. Goldstein.

Analysis and interpretation of the data: D.S. Goldstein, C. Holmes, S. Li, S. Bruce, R.O. Cannon.

Drafting of the article: D.S. Goldstein.

Critical revision of the article for important intellectual content: R.O. Cannon.

Provision of study materials or patients: L. Verhagen Metman.

Administrative, technical, or logistic support: C. Holmes, S. Bruce, L. Verhagen Metman, R.O. Cannon.

Collection and assembly of data: D.S. Goldstein, C. Holmes, S. Li, S. Bruce, R.O. Cannon.

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