HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takatsu, H. Articles by Fujiwara, H. Search for Related Content PubMed PubMed Citation Articles by Takatsu, H. Articles by Fujiwara, H.

Cardiac Sympathetic Denervation from the Early Stage of Parkinson's Disease: Clinical and Experimental Studies with Radiolabeled MIBG

Second Department of Internal Medicine, Gifu University School of Medicine, Gifu
Departments of Neurology and Cardiology, Gifu Prefectural Hospital, Gifu, Japan

Correspondence: For correspondence or reprints contact: Hisato Takatsu, MD, Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500-8705, Japan.

ABSTRACT

Autonomic disorder is not infrequent in patients with akinetic-rigid syndromes, including idiopathic Parkinson's disease. In the advanced stage of Parkinson's disease, abnormal blood pressure responses, such as orthostatic hypotension and abnormal circadian blood pressure rhythm, may occur. Few cases of reduced ¹²³I-metaiodobenzylguanidine (MIBG) accumulation in the heart or limbs of Parkinson's disease patients have been reported. However, whether reduced accumulation is caused by damage to the postganglionic sympathetic nervous system or by central autonomic failure corresponding to abnormalities in blood pressure regulation is unknown. Methods: We evaluated sympathetic denervation in 32 Parkinson's disease patients using ¹²³I-MIBG cardiac scintigraphy and compared the findings with those for autonomic dysfunction detected by orthostatic hypotension and diurnal blood pressure variation. Cardiac ¹²⁵I-MIBG accumulation was also determined in an experimental model of Parkinson's disease using mice pretreated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Results: Cardiac ¹²³I-MIBG accumulation 15 min after injection and 4 h after injection was markedly reduced in the Parkinson's disease patients (heart-to-mediastinum ratio: 1.58 ± 0.37 and 1.33 ± 0.28, respectively) compared with 7 healthy volunteers (2.42 ± 0.27 and 2.60 ± 0.15, respectively). This reduction was observed even at the earlier stages of physical activity or disease duration and also in patients with normal blood pressure response and variation, indicating that the marked decrease in cardiac ¹²³I-MIBG accumulation may be a special feature of Parkinson's disease. Pretreatment with a total dose of 100 mg/kg MPTP, which is the standard dose used to destroy the dopaminergic neurons in models of Parkinson's disease, significantly reduced cardiac ¹²⁵I-MIBG accumulation in C57BL/6 mice. Interestingly, the reduction of ¹²⁵I-MIBG accumulation was still significant when MPTP was reduced to 5 mg/kg. These findings indicated that the postganglionic sympathetic nerves may be damaged by MPTP or unknown toxic substrates in experimental or human Parkinson's disease during the early stage, because dopaminergic neurons and sympathetic nerves are substantially similar in their plasma membrane transporters. Conclusion: Cardiac scintigraphy with ¹²³I MIBG may be used as a new imaging approach in the diagnosis and characterization of akinetic-rigid syndromes, especially Parkinson's disease.

Key Words: ¹²³I-MIBG • Parkinson's disease • orthostatic hypotension • autonomic disorder

This article has been cited by other articles:

				A. E. Lang The progression of Parkinson disease: A hypothesis Neurology, March 20, 2007; 68(12): 948 - 952. [Abstract] [Full Text] [PDF]

				D. M. Raffel, R. A. Koeppe, R. Little, C.-N. Wang, S. Liu, L. Junck, M. Heumann, and S. Gilman PET Measurement of Cardiac and Nigrostriatal Denervation in Parkinsonian Syndromes J. Nucl. Med., November 1, 2006; 47(11): 1769 - 1777. [Abstract] [Full Text] [PDF]

				H Nagayama, M Hamamoto, M Ueda, J Nagashima, and Y Katayama Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson's disease J. Neurol. Neurosurg. Psychiatry, February 1, 2005; 76(2): 249 - 251. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, S.-T. Li, C. Holmes, and K. Bankiewicz Sympathetic Innervation in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Primate Model of Parkinson's Disease J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 855 - 860. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, S. Pechnik, C. Holmes, B. Eldadah, and Y. Sharabi Association Between Supine Hypertension and Orthostatic Hypotension in Autonomic Failure Hypertension, August 1, 2003; 42(2): 136 - 142. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, C. Holmes, Y. Sharabi, S. Brentzel, and G. Eisenhofer Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension Neurology, April 22, 2003; 60(8): 1327 - 1332. [Abstract] [Full Text] [PDF]

				K Hamada, M Hirayama, H Watanabe, R Kobayashi, H Ito, T Ieda, Y Koike, and G Sobue Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, April 1, 2003; 74(4): 423 - 426. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, D. Robertson, M. Esler, S. E. Straus, and G. Eisenhofer Dysautonomias: Clinical Disorders of the Autonomic Nervous System Ann Intern Med, November 5, 2002; 137(9): 753 - 763. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, C. S. Holmes, R. Dendi, S. R. Bruce, and S.-T. Li Orthostatic hypotension from sympathetic denervation in Parkinson's disease Neurology, April 23, 2002; 58(8): 1247 - 1255. [Abstract] [Full Text] [PDF]

				M Yoshita, J Taki, and M Yamada A clinical role for [123I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies J. Neurol. Neurosurg. Psychiatry, November 1, 2001; 71(5): 583 - 588. [Abstract] [Full Text] [PDF]

				H Watanabe, T Ieda, T Katayama, A Takeda, I Aiba, M Doyu, M Hirayama, and G Sobue Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, June 1, 2001; 70(6): 781 - 783. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, C. Holmes, S.-T. Li, S. Bruce, L. V. Metman, and R. O. Cannon III Cardiac Sympathetic Denervation in Parkinson Disease Ann Intern Med, September 5, 2000; 133(5): 338 - 347. [Abstract] [Full Text] [PDF]