Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.
OBJECTIVE
The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [(123)I]beta-CIT SPECT.


METHODS
Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson's disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V (3)''), which is proportional to the receptor density (B (max)), were generated. In order to objectively localise focal changes in beta-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V (3)'' values between groups, were transformed onto the individual V (3)'' image to obtain mean regional uptake values.


RESULTS
Both SCA2 and YOPD patients showed significant decreases in striatal [(123)I]beta-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [(123)I]beta-CIT uptake were localised with SPM.


CONCLUSIONS
Voxel-wise analysis of [(123)I]beta-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [(123)I]beta-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation.
Scherfler
Christoph
C
Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. christoph.scherfler@uibk.ac.at
Boesch
Sylvia M
SM
Donnemiller
Eveline
E
Seppi
Klaus
K
Weirich-Schwaiger
Helga
H
Goebel
Georg
G
Virgolini
Irene
I
Wenning
Gregor K
GK
Poewe
Werner
W
D000328:Adult; D000067528:Ataxins; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016022:Case-Control Studies; D003042:Cocaine / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019275:Radiopharmaceuticals; D020754:Spinocerebellar Ataxias / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D000067528:Ataxins; D007457:Iodine Radioisotopes; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine