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01-08-2005 | Case Report

An autopsy case of early (“minimal change”) olivopontocerebellar atrophy (multiple system atrophy-cerebellar)

Authors: Koichi Wakabayashi, Fumiaki Mori, Makoto Nishie, Yoshinobu Oyama, Aiichiro Kurihara, Makoto Yoshimoto, Naohito Kuroda

Published in: Acta Neuropathologica | Issue 2/2005

Abstract

We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month duration. The patient developed dysarthria, followed by impaired balance of gait, mild limb ataxia, and saccadic eye movement. A postmortem examination performed after she was found dead in a bathtub revealed neuronal loss restricted to the olivopontocerebellar system, being more severe in the pontine nucleus. Mild neuronal loss was also found in the anterior vermis and inferior olivary nucleus. α-Synuclein immunohistochemistry demonstrated widespread occurrence of glial cytoplasmic inclusions in the central nervous system, which were more numerous in the pontine base and cerebellar white matter. In contrast, neuronal α-synuclein accumulation was confined to the pontine and inferior olivary nuclei. The number of neuronal intranuclear inclusions was much higher than that of neuronal cytoplasmic inclusions. Moreover, α-synuclein accumulation was more severe in the neurites than in the cytoplasm or nucleus. This case demonstrates the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar atrophy).

Arima K, Murayama S, Mukoyama M, Inose T (1992) Immunocytochemical and ultrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol 83:453–460

Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (1998) NACP/α-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol 96:439–444CrossRefPubMed

Braak H, Rüb U, Del Tredici K (2003) Involvement of precerebellar nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 29:60–76CrossRefPubMed

Brodal A (1981) Neurological anatomy in relation to clinical medicine, 3rd edn. Oxford University Press, New York

Brodal P, Bjaalie JG (1992) Organization of the pontine nuclei. Neurosci Res 13:83–118CrossRefPubMed

Dickson DW, Liu W-K, Hardy J, Farrer M, Mehta N, Uitti R, Mark M, Zimmerman T, Golbe L, Sage J, Sima A, D’Amato C, Albin R, Gilman S, Yen S-H (1999) Widespread alterations of α-synuclein in multiple system atrophy. Am J Pathol 155:1241–1251PubMed

Giasson BI, Mabon ME, Duda JE, Montine TJ, Robertson D, Hurtig HI, Lee VMY, Trojanowski JQ (2003) Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol 106:243–250

Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163:94–98CrossRefPubMed

Horimoto Y, Aiba I, Yasuda T, Ohkawa Y, Katayama T, Yokokawa Y, Goto A, Ito Y (2002) Longitudinal MRI study of multiple system atrophy—when do the findings appear, and what is the course? J Neurol 249:847–854CrossRefPubMed

10.

Inoue M, Yagishita S, Ryo M, Hasegawa K, Amano N, Matsushita M (1997) The distribution and dynamic density of oligodendroglial cytoplasmic inclusions (GCIs) in multiple system atrophy: a correlation between the density of GCIs and the degree of involvement of striatonigral and olivopontocerebellar systems. Acta Neuropathol 93:585–591

11.

Jellinger KA (2003) Neuropathological spectrum of synucleinopathies. Mov Disord 18 (Suppl 6):S2–12CrossRefPubMed

12.

Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: immunohistochemical and ultrastructural studies. Acta Neuropathol 79:584–594CrossRefPubMed

13.

Kawamoto Y, Akiguchi I, Nakamura S, Budka H (2002) Accumulation of 14-3-3 proteins in glial cytoplasmic inclusions in multiple system atrophy. Ann Neurol 52:722–731CrossRefPubMed

14.

Komori T, Ishizawa K, Arai N, Hirose T, Mizutani T, Oda M (2003) Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy. Acta Neuropathol 106:66–70

15.

Kume A, Takahashi A, Hashizume Y, Asai J (1991) A histometrical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy. J Neurol Sci 101:178–186CrossRefPubMed

16.

Kume A, Takahashi A, Hashizume Y (1993) Neuronal cell loss of the striatonigral system in multiple system atrophy. J Neurol Sci 117:33–40CrossRefPubMed

17.

Lin WL, DeLucia MW, Dickson DW (2004) α-Synuclein immunoreactivity in neuronal nuclear inclusions and neurites in multiple system atrophy. Neurosci Lett 354:99–102CrossRefPubMed

18.

Matsuo A, Akiguchi I, Lee GC, McGeer EG, McGeer PL, Kimura J (1998) Myelin degeneration in multiple system atrophy detected by unique antibodies. Am J Pathol 153:735–744PubMed

19.

Mori F, Piao YS, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K (2003) α-Synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy. J Neuropathol Exp Neurol 62:812–819PubMed

20.

Nakazato Y, Suzuki S (1996) Oligodendroglial microtubular tangles in multiple system atrophy. Neuropathology 16:145–150

21.

Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamaguchi H (1990) Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 49:521–530PubMed

22.

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 107:292–298CrossRefPubMed

23.

Nishie M, Mori F, Yoshimoto M, Takahashi H, Wakabayashi K (2004) A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy. Neuropathol Appl Neurobiol 30:546–554CrossRefPubMed

24.

Ozawa T, Paviour D, Quinn NP, Josephs KA, Sangha H, Kilford L, Healy DG, Wood NW, Lees AJ, Holton JL, Revesz T (2004) The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain 127:2657–2671CrossRefPubMed

25.

Papp MI, Lantos PL (1992) Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci 107:172–182CrossRefPubMed

26.

Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100CrossRefPubMed

27.

Piao Y-S, Mori F, Hayashi S, Tanji K, Yoshimoto M, Kakita A, Wakabayashi K, Takahashi H (2003) α-Synuclein pathology affecting Bergmann glia of the cerebellum in patients with α-synucleinopathies. Acta Neuropathol 105:403–409

28.

Probst-Cousin S, Rickert CH, Schmid KW, Gullotta F (1998) Cell death mechanisms in multiple system atrophy. J Neuropathol Exp Neurol 57:814–821PubMed

29.

Takei Y, Mirra SS (1973) Striatonigral degeneration: a form of multiple system atrophy with clinical parkinsonism. In: Zimmerman HM (ed) Progress in Neuropathology, vol II. Grune & Stratton, New York, pp 217–251

30.

Tsuchiya K, Watabiki S, Sano M, Iobe H, Shiotsu H, Taki K, Hashimoto K (1998) Distribution of cerebellar cortical lesions in multiple system atrophy: a topographic neuropathological study of three autopsy cases in Japan. J Neurol Sci 155:80–85CrossRefPubMed

31.

Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM-Y (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α-synuclein. Ann Neurol 44:415–422CrossRefPubMed

32.

Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182CrossRefPubMed

33.

Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, Takahashi H (1998) Accumulation of α-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol 96:445–452CrossRefPubMed

34.

Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, Aiba I, Abe Y, Tamakoshi A, Doyu M, Hirayama M, Sobue G (2002) Progression and prognosis in multiple system atrophy. An analysis of 230 Japanese patients. Brain 125:1070–1083CrossRefPubMed

35.

Wenning GK, Jellinger KA (2005) The role of α-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 109:129–140

36.

Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP (1994) Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 117:835–845PubMed

37.

Wenning GK, Quinn N, Magalhaes M, Mathias C, Daniel SE (1994) “Minimal change” multiple system atrophy. Mov Disord 9:161–166CrossRefPubMed

38.

Wenning GK, Tison F, Elliott L, Quinn NP, Daniel SE (1996) Olivopontocerebellar pathology in multiple system atrophy. Mov Disord 11:157–162CrossRefPubMed

Title: An autopsy case of early (“minimal change”) olivopontocerebellar atrophy (multiple system atrophy-cerebellar)
Authors: Koichi Wakabayashi
Fumiaki Mori
Makoto Nishie
Yoshinobu Oyama
Aiichiro Kurihara
Makoto Yoshimoto
Naohito Kuroda
Publication date: 01-08-2005
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 2/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-005-1029-1

At a glance: The STEP trials

Springer Medicine

An autopsy case of early (“minimal change”) olivopontocerebellar atrophy (multiple system atrophy-cerebellar)

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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