Cardiac sympathetic denervation from the early stage of Parkinson's disease: clinical and experimental studies with radiolabeled MIBG.

Abstract

UNLABELLED: 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.