Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study.
Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and beta-CIT as well as IBZM. Age-matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of beta-CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.
Boesch
Sylvia M
SM
Department of Neurology, University of Innsbruck, Austria. sylvia.boesch@uibk.ac.at
Donnemiller
Eveline
E
Müller
Jörg
J
Seppi
Klaus
K
Weirich-Schwaiger
Helga
H
Poewe
Werner
W
Wenning
Gregor K
GK
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000503:physiopathology; D001549:Benzamides; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000503:physiopathology; D003042:Cocaine / Q000031:analogs & derivatives*; D050483:Dopamine Plasma Membrane Transport Proteins; D020821:Dystonic Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012016:Reference Values; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D001549:Benzamides; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D003042:Cocaine