PET measures of benzodiazepine receptors in progressive supranuclear palsy.
OBJECTIVE
To evaluate the integrity of neurons containing benzodiazepine receptors in metabolically affected regions of the brain in patients with clinically diagnosed progressive supranuclear palsy (PSP).


METHODS
The cerebral distribution of [11C]flumazenil (FMZ), a ligand that binds to the gamma-aminobutyric acid A (GABAA) receptor, and [18F]fluorodeoxyglucose (FDG), a measure of local cerebral glucose metabolism, was determined with PET in 12 patients with PSP and 10 normal control subjects. Tracer kinetic analysis was applied to quantify data and analysis was performed using three-dimensional stereotactic surface projections and stereotactically determined volumes of interest.


RESULTS
There was a global reduction in FMZ binding of 13%, with a reduction in the anterior cingulate gyrus of 20% (p = 0.004), where glucose metabolic rates also showed the greatest reduction.


CONCLUSIONS
PSP causes loss of benzodiazepine receptors in the cerebral cortex. Consistent with postmortem studies, the authors did not find significant changes in FMZ binding in subcortical nuclei that exhibit the most pathologic change. This study suggests that both loss of intrinsic neurons containing benzodiazepine receptors and deafferentation of the cerebral cortex from distant brain regions contribute to cerebral cortical hypometabolism in PSP.
Foster
N L
NL
Department of Neurology, University of Michigan at Ann Arbor, 48109-0316, USA. nlfoster@umich.edu
Minoshima
S
S
Johanns
J
J
Little
R
R
Heumann
M L
ML
Kuhl
D E
DE
Gilman
S
S
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18; D018757:GABA Modulators / Q000493:pharmacokinetics; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011963:Receptors, GABA-A / Q000502:physiology*; D012016:Reference Values; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D018757:GABA Modulators; D011963:Receptors, GABA-A; D019788:Fluorodeoxyglucose F18; D005442:Flumazenil