Abstract
Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer’s disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antibody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.
Similar content being viewed by others
References
Algotsson A, Viitanen M, Winblad B, Solders G (1995) Autonomic dysfunction in Alzheimer’s disease. Acta Neurol Scand 91:14–18
Amino T, Orimo S, Ihoh Y, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 15:29–34
Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lücking CH (1998) Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson’s disease with autonomic failure. Acta Neurol Scand 97:307–314
Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH (1999) Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 53:1020–1025
Druschky A, Hilz MJ, Platsch G, Radespiel-Tröger M Drushky K, Kuwert T, Neundörfer B (2000) Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT. J Neurol Sci 175:3–12
Giubilei F, Strano S, Imbimbo BP, Tisei P, Calcagnini G, Lino S, Frontoni M, Santini M, Fieschi C (1998) Cardiac autonomic dysfunction in patients with Alzheimer disease: possible pathogenetic mechanisms. Alzheimer Dis Assoc Disord 12:356–361
Goldstein DS, Holmes C, Li S-T, Bruce S, Metman LV, Cannon RO III (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347
Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, McKee A, Tabaton M, Litvan I (1994) Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 44:2015–2019
Horimoto Y, Matsumoto M, Akatsu H, Ikari H, Kojima K, Yamamoto T, Otsuka Y, Ojika K, Ueda R, Kosaka K (2003) Autonomic dysfunctions in dementia with Lewy bodies. J Neurol 250:530–533
Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H, Satoh A, Seto M, Tsujihata M, Takahashi H (1999) Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases. Neurology 52:1269–1271
Kawano H, Okada R, Yano K (2003) Histological study on the distribution of autonomic nerves in the human heart. Heart Vessels 18:32–39
Kimber J, Mathias CJ, Lees AJ, Bleasdale-Barr K, Chang HS, Churchyard A, Watson L (2000) Physiological, pharmacological and neurohormonal assessment of autonomic function in progressive supranuclear palsy. Brain 123:1422–1430
Konno H, Yamamoto T, Iwasaki Y, Iizuka H (1986) Shy-Drager syndrome and amyotrophic lateral sclerosis: cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 73:193–204
Kosaka K (1990) Diffuse Lewy body disease in Japan. J Neurol 237:197–204
Matthews MR (1992) Autonomic ganglia in multiple system atrophy and pure autonomic failure. In: Bannister R, Mathias CJ (eds) Autonomic failure: a textbook of clinical disorders of the autonomic nervous system. Oxford University Press, New York, pp 593–621
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s disease (CERAD). Part ll. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486
Nishie M, Mori F, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2004) Accumulation of phosphorylated α-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. Acta Neuropathol 107:292–298
Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999)123I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194
Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, Wakabayashi K, Takahashi H (2001) Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA. Neurology 57:1140–1141
Orimo S, Oka T, Miura H, Tsuchiya K, Mori F, Wakabayashi K, Nagao T, Yokochi M (2002) Sympathetic cardiac denervation in Parkinson’s disease and pure autonomic failure but not in multiple system atrophy. J Neurol Neurosurg Psychiatry 73:776–777
Orimo S, Ozawa E, Nakade S, Hattori H, Tsuchiya K, Taki K, Takahashi A (2003) [123I]MIBG myocardial scintigraphy differentiates corticobasal degeneration from Parkinson’s disease. Intern Med 42:127–128
Polinsky RJ, Kopin IJ, Ebert MH, Weise V (1981) Pharmacologic distinction of different orthostatic hypotension syndromes. Neurology 31:1–7
Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, Sawabe M, Arai T, Nagura H, Yamanouchi H, Hasegawa M, Iwatsubo T, Murayama S (2003) Accumulation of phosphorylated alpha-synuclein in aging human brain. J Neuropathol Exp Neurol 62:644–654
Satoh A, Serita T, Seto M, Tomita I, Satoh H, Iwanaga K, Takashima H, Tsujihata M (1999) Loss of123I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 40:371–375
Schatz IJ, Bannister SR, Freeman RL (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 46:1470
Taki J, Nakajima K, Hwang E-H, Matsunari I, Komai K, Yoshita M, Sakajiri K, Tonami N (2000) Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. Eur J Nucl Med 27:566–573
Wakabayashi K, Takahashi H, Ohama E, Takeda S, Ikuta F (1993) Lewy bodies in the visceral autonomic nervous system in Parkinson’s disease. In: Narabayashi H, Nagatsu N, Yanagisawa N, Mizuno Y (eds) Advances in Neurology. Lippincott-Raven, New York, pp 609–612
Watanabe H, Ieda T, Katayama T, Takeda A, Akiba I, Doyu M, Hirayama M, Sobue G (2001) Cardiac123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 70:781–783
Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155:60–67
Yoshita M, Taki J, Yamada M (2001) 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 71:583–588
Acknowledgements
We thank Dr. Iwatsubo for providing the phosphorylated α-synuclein antibody, and Ms. Yamada and Ms. Nakamura for their technical assistance. This work was supported in part by a grant from the Japan Foundation for Neuroscience and Mental Health (Tama Nakagawa Foundation).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Orimo, S., Amino, T., Itoh, Y. et al. Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109, 583–588 (2005). https://doi.org/10.1007/s00401-005-0995-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00401-005-0995-7