We investigated whether the dopamine (DA) transporter system is impaired in sporadic olivopontocerebellar atrophy (sOPCA) patients without clinical parkinsonism using the DA transporter radiotracer [123I]β-CIT [2β-carboxymethoxy-3β-(4-iodophenyl)tropane] and single-photon emission computed tomography (SPECT). SPECT scans were acquired in 9 patients with sOPCA, 7 multiple system atrophy (MSA) patients with parkinsonism (MSA-P), and 7 age-matched healthy controls 20–24 h after the intravenous injection of [123I]β-CIT. [123I]β-CIT-specific binding in the striatum was determined as the radioactivity ratio of the striatum to the occipital cortex (specific binding ratio, SBR). In patients with sOPCA and MSA-P, SBRs in the right and left striatum and the mean SBR were significantly lower than those in controls (p < 0.05). The mean SBRs in patients with sOPCA and MSA-P were reduced to 69.0 and 60.7% of the control mean, respectively. However, there was no significant difference in SBRs between sOPCA and MSA-P patients. In sOPCA patients, the mean SBR was significantly correlated with the score of the clinical cerebellar function scale (r = –0.670, p = 0.024). These results indicate that even in the absence of clinical parkinsonism, the striatal dopaminergic system may be impaired in sOPCA. The DA transporter loss in sOPCA serves as another clue for sOPCA being a part of the spectrum of MSA.

Keywords:
Olivopontocerebellar atrophy, Multiple system atrophy, Dopamine transporter, [123I]β-CIT, SPECT, Parkinsonism
1.
Petito CK, Hart MN, Porro RS, Earle KM: Ultrastructural studies of olivopontocerebellar atrophy. J Neuropathol Exp Neurol 1973;32:503–522.
2.
Koeppen AH, Baron KD: The neuropathology of olivopontocerebellar atrophy; in Duvoison RC, Plaitakis A (eds): Olivopontocerebellar Atrophies. New York, Raven Press, 1984, pp 13–38.
3.
Klockgether T, Schroth G, Diener H-C, Dichigans J: Idiopathic cerebellar ataxia of late onset: Natural history and MRI morphology. J Neurol Neurosurg Psychiatry 1990;53:297–305.
4.
Berciano J: Olivopontocerebellar atrophy. A review of 117 cases. J Neurol Sci 1982;53:253–272.
5.
Quinn N: Multiple system atrophy – The nature of the beast. J Neurol Neurosurg Psychiatry 1989;special suppl:8–89.
6.
Wenning GK, Shlomo YB, Magalhaes, Daniel SE, Quinn NP: Clinical features and natural history of multiple system atrophy. Brain 1994;117:835–845.
7.
Adams RD, Van Boart L, Van Der Eecken: Striato-nigral degeneration. J Neuropathol Exp Neurol 1964;23:584–608.
8.
Staal A, Dejong JM: Non-familial olivopontocerebellar atrophy; in De Jong JMBV (ed): Handbook of Clinical Neurology: Systems Atrophies II. Amsterdam, North-Holland, 1991, vol 16 (60), pp 519–536.
9.
Stern MB, Braffman BH, Skolnick BE, Hurtig HI, Grossman RI: Magnetic resonance imaging in Parkinson’s disease and parkinsonian syndromes. Neurology 1989;39:1524–1526.
10.
Graham JG, Oppenheimer DR: Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 1969;32:28–34.
11.
Oppenheimer SE: Diseases of the basal ganglia, cerebellum and motor neurons; in Humes AJ, Corsellis JAN, Duchen LW (eds): Greenfields Neuropathology, ed 4. New York, Wiley, 1984, pp 699–747.
12.
Kume A, Takahashi A, Hashizume Y, Asai J: A histochemical and comparative study on Purkinje cell loss and olivary nucleus cell loss in multiple system atrophy. J Neurol Sci 1991;101:178–186.
13.
Perani D, Bressi S, Testa D, Grassi F, Cortelli P, Gentrini S, Savoiardo M, Caraceni T, Fazio F: Clinical/metabolic correlations in multiple system atrophy. Arch Neurol 1995;52:179–185.
14.
Antonini A, Leenders KL, Vontobel P, Maguire RP, Missimer J, Psylla M, Gunther I: Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease. Brain 1997;120:2187–2195.
15.
Schulz JB, Klockgether T, Peterson D, Jauch M, Muller-Schauenburg W, Spieker S, Voigt K, Dichigans J: Multiple system atrophy: Natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57:1047–1056.
16.
Rinne JO, Burn DJ, Mathias CJ, Dphil, Quinn NP, Marsden CD, Brooks DJ: Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy. Ann Neurol 1995;37:568–573.
17.
Nirenberg MJ, Vaughan RA, Uhl GR, Kuhar MJ, Pickel VM: The dopamine transporter is localized to dendritic and axonal plasma membranes to nigrostriatal dopaminergic neurons. J Neurosci 1996;16:436–447.
18.
Langston JW: Mechanism of MPTP toxicity: More answers, more questions. Trends Pharmacol Sci 1985;6:375–378.
19.
Gainetdinov RR, Fumagalli F, Jones SR, Caron MG: Dopamine transporter is required in vivo MPTP neurotoxicity: Evidence from mice lacking the transporter. J Neurochem 1997;69:1322–1325.
20.
Neumeyer JL, Wang S, Milius RA: Iodine-123-2-β-carbomethoxy-3-β-(4-iodophenyl) tropane (β-CIT): High affinity SPECT radiotracer of monoamine reuptake sites in brain. J Med Chem 1991;34:3144–3146.
21.
Innis RB, Seibyl JP, Laruelle M, Abi-Dargham A, Wallace E, Baldwin RM, Zea-Ponce Y, Zoghbi S, Gao Y, Neumeyer JL, Charney DS, Hoffer PB, Marek KL: Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci USA 1993;90:11965–11969.
22.
Kim SE, Lee WY, Choe YS, Kim JH: SPECT measurement of iodine-123-β-CIT binding to dopamine and serotonin transporters in Parkinson’s disease: Correlation with symptom severity. Neurol Res 1999;21:255–261.
23.
Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Smith EO, Charney DS, Hoffer PB, Innis RB: Decreased single-photon emission computed tomogaphic [123I]β-CIT striatal uptake correlates with symptoms severity in Parkinson’s disease. Ann Neurol 1995;38:589–598.
24.
Marek KL, Seibyl JP, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Fussell B, Charney DS, van Dyck C, Hoffer PB, Innis RB: [123I]β-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson’s disease. Neurology 1996;46:231–237.
25.
Yamaguchi S, Fukuyama H, Ogawa M, Yamauchi H, Harada K, Shigenobu N, Kimura J: Olivopontocerebellar atrophy studied by positron emission tomography and magnetic resonance imaging. J Neurol Sci 1994;125:56–61.
26.
Lou J-S, Goldfarb L, McShane L, Gatev P, Hallett M: Use of buspirone for treatment of cerebellar ataxia: An open label study. Arch Neurol 1995;52:982–988.
27.
Zea-Ponce Y, Baldwin RM, Laruelle M, Wang S, Neumeyer JL, Innis RB: Simplified multidose preparation of iodine-123-β-CIT: A marker for dopamine transporter. J Nucl Med 1995;36:525–529.
28.
Reith ME, Xu C, Chen N-H: Pharmacology and regulation of the neuronal dopamine transporter. Eur J Pharmacol 1997;324:1–10.
29.
Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Snyder SH, Ravert HT, Dannals RF: Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson’s disease. Ann Neurol 1993;34:423–431.
30.
Isacson O: Clinical and preclinical PET correlates of parkinsonism with 11C-WIN 35,428. Ann Neurol 1994;35:377–378.
31.
Kim H-J, Im J-H, Yang S-O, Moon DH, Ryu JS, Bong J-K, Nam K-P, Cheon J-H, Lee M-C, Lee H-K: Imaging and quantitation of dopamine transporters with iodine-123-IPT in normal and Parkinson’s disease subjects. J Nucl Med 1997;38:1703–1711.
32.
Kim SE, Lee WY, Chi DY, Choe YS, Lee KH, Choi Y, Oh SJ, Kim BT: SPECT imaging of dopamine transporter with [123I]β-CIT: A poteential tool in Parkinson’s disease. Korean J Nucl Med 1996;30:19–34.
33.
Laruelle M, Baldwin RM, Malison RT: SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: Pharmacological characterization of brain uptake in nonhuman primates. Synapse 1992;13:295–309.
34.
Gilman S, Koeppe RA, Junck L, Kluin KJ, Lohman M, St Laurent RT: Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy. Ann Neurol 1994;36:166–175.
35.
Papp MI, Kahn JE, Lantos PL: Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 1989;94:79–100.
36.
Kato S, Nakamura H: Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: Immunohistochemical and ultrastructural studies. Acta Neuropathol (Berl) 1990;79:584–594.
37.
Nakazato Y, Yamazaki H, Hirato J, Ishida Y, Yamamuchi H: Oligodendroglial microtubular tangles in olivopontocerebellar atrophy. J Neuropathol Exp Neurol 1990;49:521–530.
38.
Abe H, Yagishita S, Amano N, Iwabuchi K, Hasegawa K, Kowa K: Argyrophilic glial intracytoplasmic inclusions in multiple system atrophy: Immunohistochemical and ultrasound study. Acta Neuropathol 1992;84:273–277.
39.
Rinne OJ, Laihinen A, Nagren K, Routtinen H, Ruotsalainen, Rinne UK: PET examination of the monoamine transporter with [11C]β-CIT and [11C]β-CFT in early Parkinson’s disease. Synapse 1995;21:97–103.
40.
Brucke T, Asenbaum S, Pirker W, Djamshidian S, Wegner S, Wober C, Muller C, Podreka I: Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I]β-CIT and SPECT: Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy. J Neural Trans Suppl 1997;50:9–24.
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