Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6.
BACKGROUND
The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome.


OBJECTIVE
To identify impairments of the dopaminergic system and regional changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6.


METHODS
We used [11C]d-threo-methylphenidate and [18F]fluorodeoxyglucose positron emission tomography to identify cerebral dopamine terminal loss and specific regional metabolic patterns in SCA1, SCA2, SCA3, and SCA6.


RESULTS
The binding potential of [11C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in contrast to patients with Parkinson disease, no increased susceptibility of the putamen was evident. Decreased regional cerebral glucose metabolism was found in the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A trend toward increased regional cerebral glucose metabolism was found in the temporal cortex of all patients with SCA, pronounced in SCA6.


CONCLUSIONS
Specific biochemical patterns point to different mechanisms of neuronal dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in SCA2 but distinct from Parkinson disease.
Wüllner
Ullrich
U
Department of Neurology, University of Bonn, Bonn, Germany. wuellner@uni-bonn.de
Reimold
Michael
M
Abele
Michael
M
Bürk
Katrin
K
Minnerop
Martina
M
Dohmen
Bernd-Michael
BM
Machulla
Hans-Juergen
HJ
Bares
Roland
R
Klockgether
Thomas
T
D000328:Adult; D001667:Binding, Competitive / Q000502:physiology; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008774:Methylphenidate; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology
D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019788:Fluorodeoxyglucose F18; D008774:Methylphenidate; D005947:Glucose; D004298:Dopamine