Decreased striatal monoaminergic terminals in olivopontocerebellar atrophy and multiple system atrophy demonstrated with positron emission tomography.
We used [11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter (VMAT2), with positron emission tomography to study striatal monoaminergic presynaptic terminals in 4 patients with multiple system atrophy, 8 with sporadic olivopontocerebellar atrophy, and 9 normal control subjects. Specific binding in the striatum was significantly reduced in the multiple system atrophy patients as compared with the normal control group, with average reductions of 61% in the caudate nucleus (p = 0.002) and 58% in the putamen (p = 0.009). Smaller reductions were found in the sporadic olivopontocerebellar atrophy group, averaging 26% in the caudate nucleus (p = 0.05) and 24% in the putamen (p = 0.11). Mean blood-to-brain [11C]dihydrotetrabenazine transport (K1) was significantly different between groups only in the cerebellum, with values for the sporadic olivopontocerebellar atrophy group diminished compared with the normal control group. Cerebellar K1 was not significantly decreased in the multiple system atrophy group. The finding of reduced striatal VMAT2 in sporadic olivopontocerebellar atrophy patients suggests nigrostriatal pathology, indicating that some may later develop symptomatic extrapyramidal disease.
Gilman
S
S
Department of Neurology, University of Michigan, Ann Arbor 48109-0316, USA.
Frey
K A
KA
Koeppe
R A
RA
Junck
L
L
Little
R
R
Vander Borght
T M
TM
Lohman
M
M
Martorello
S
S
Lee
L C
LC
Jewett
D M
DM
Kilbourn
M R
MR
D000328:Adult; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D001692:Biological Transport; D002526:Cerebellar Diseases / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009479:Neuropeptides; D009849:Olivopontocerebellar Atrophies / Q000000981:diagnostic imaging* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000032:analysis; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine