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Acta Neuropathologica

, Volume 113, Issue 1, pp 81–86 | Cite as

Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy

  • Satoshi Orimo
  • Toshiro Kanazawa
  • Ayako Nakamura
  • Toshiki Uchihara
  • Fumiaki Mori
  • Akiyoshi Kakita
  • Koichi Wakabayashi
  • Hitoshi Takahashi
Original Paper

Abstract

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson’s disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.

Keywords

Cardiac sympathetic nerve MIBG myocardial scintigraphy Multiple system atrophy Sympathetic ganglia Lewy body pathology 

Notes

Acknowledgments

This work was supported in part by grants from the Research Committee on Neurodegenerative Diseases, Ministry of health, Labor and Welfare, Japan and the Japan Foundation for Neuroscience and Mental Health.

References

  1. 1.
    Amino T, Orimo S, Itoh Y, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathol 15:29–34PubMedCrossRefGoogle Scholar
  2. 2.
    Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedCrossRefGoogle Scholar
  3. 3.
    Braune S (2001) The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes. Clin Auton Res 11:351–355PubMedCrossRefGoogle Scholar
  4. 4.
    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 53:1020–1025PubMedGoogle Scholar
  5. 5.
    Daniel SE (1999) The neuropathology and neurochemistry of multiple system atrophy. In: Mathias CJ, Bannister SR (eds) Autonomic failure. Oxford University Press, Oxford p 321–328Google Scholar
  6. 6.
    Druschky A, Hilz MJ, Platsch G, Radespiel-Tröger M, Druschky 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 175:3–12PubMedCrossRefGoogle Scholar
  7. 7.
    Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (2002) α-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164PubMedCrossRefGoogle Scholar
  8. 8.
    Gray F, Vincent D, Hauw JJ (1988) Quantitative study of lateral horn cells in 15 cases of multiple system atrophy. Acta Neuropathol 75:513–518PubMedCrossRefGoogle Scholar
  9. 9.
    Kawasaki H, Shimada H, Tomonaga M (1988) Morphological study on the Lewy bodies in the sympathetic ganglia of the aged person (in Japanese). Jpn J Geriatr 25:282–291Google Scholar
  10. 10.
    Kennedy PGE, Duchen LW (1985) A quantitative study of intermediolateral column cells in motor neuron disease and the Shy-Drager syndrome. J Neurol Neurosurg Psychiatry 48:1103–1106PubMedGoogle Scholar
  11. 11.
    Nakajima R, Takahashi K, Nakamura H, Otomo E, Kameyama M (1981) A quantitative study on the intermediolateral cells of the thoracic cord in degenerative diseases of the nervous system. Clin Neurol 21:581–586Google Scholar
  12. 12.
    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 107:292–298PubMedCrossRefGoogle Scholar
  13. 13.
    Oppemheimer DR (1980) Lateral horn cells in progressive autonomic failure. J Neurol Sci 46:393–404CrossRefGoogle Scholar
  14. 14.
    Orimo A, Takahashi A, Uchihara A, Mori F, Kakita A, Wakabayashi K, Takahashi H (2006) Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson’s disease. Brain Pathol (in press)Google Scholar
  15. 15.
    Orimo S, Amino T, Ito Y, Takahashi A, Kojo T, Uchihara T, Tsuchiya K, Mori F, Wakabayashi K, Takahashi H (2005) Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109:583–588PubMedCrossRefGoogle Scholar
  16. 16.
    Orimo S, Amino T, Yokochi M, Kojo T, Uchihara T, Takahashi A, Wakabayashi K, Takahashi H, Hattori N, Mizuno Y (2005) Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2. Mov Disord 20:1350–1353PubMedCrossRefGoogle Scholar
  17. 17.
    Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999) 123I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194PubMedCrossRefGoogle Scholar
  18. 18.
    Sone M, Yoshida M, Hashizume Y, Hishikawa N, Sobue G (2005) α-Synuclein-immunoreactive structure formation is enhanced in sympathetic ganglia of patients with multiple system atrophy. Acta Neuropathol 110:19–26PubMedCrossRefGoogle Scholar
  19. 19.
    Taki J, Nakajima K, Hwang EH, 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 27:566–573PubMedCrossRefGoogle Scholar
  20. 20.
    Wakabayashi K (1989) Parkinson’s disease: the distribution of Lewy bodies in the peripheral autonomic nervous system (in Japanese). Brain Nerve 41:965–971PubMedGoogle Scholar
  21. 21.
    Wakabayashi K, Takahashi H (1997) Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 38(Suppl 2):2–7PubMedGoogle Scholar
  22. 22.
    Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy. Acta Neurol Scand 91:14–18Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Satoshi Orimo
    • 1
    • 2
  • Toshiro Kanazawa
    • 1
    • 2
  • Ayako Nakamura
    • 2
  • Toshiki Uchihara
    • 2
  • Fumiaki Mori
    • 3
  • Akiyoshi Kakita
    • 4
  • Koichi Wakabayashi
    • 3
  • Hitoshi Takahashi
    • 4
  1. 1.Department of NeurologyKanto Central HospitalTokyoJapan
  2. 2.Department of NeuropathologyTokyo Metropolitan Institute for NeuroscienceTokyoJapan
  3. 3.Department of NeuropathologyInstitute of Brain Science, Hirosaki University School of MedicineHirosakiJapan
  4. 4.Department of PathologyBrain Research Institute, University of NiigataNiigataJapan

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