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Positron emission tomography measures of benzodiazepine receptors in Huntington's disease
Author(s) -
Holthoff Vjera A.,
Koeppe Robert A.,
Frey Kirk A.,
Penney John B.,
Markel Dorene S.,
Kuhl David E.,
Young Anne B.
Publication year - 1993
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410340114
Subject(s) - putamen , flumazenil , caudate nucleus , benzodiazepine , medicine , endocrinology , positron emission tomography , gabaa receptor , huntington's disease , receptor , chemistry , nuclear medicine , disease
We performed positron emission tomographic (PET) measurements of the regional distribution volume of benzodiazepine receptors and regional glucose metabolism in 6 drug‐free patients with early Huntington's disease following injection of [ 11 C] flumazenil, a nonsubtype selective central benzodiazepine receptor antagonist, and 18 F‐2‐fluoro‐2‐deoxy‐ D ‐glucose, respectively. Flumazenil data were analyzed with a recently developed two‐compartment, two‐parameter tracer kinetic model. Benzodiazepine receptor density is related to distribution volume for flumazenil. In comparison with a group of healthy volunteers, benzodiazepine receptor density was significantly decreased in the caudate nucleus. Glucose metabolism was significantly reduced not only in the caudate nucleus but also in the putamen and thalamus. The changes in benzodiazepine receptor density observed in the caudate nucleus are commensurate with data obtained in postmortem autoradiographic studies of receptor density. Based on such postmortem studies we also anticipated changes in putamen and thalamic benzodiazepine receptor density. However, relatively little is known on receptor changes in early Huntington's disease, because the autoradiographic data available were obtained mostly in patients with advanced disease. The decreased glucose metabolism in the caudate and putamen agrees well with previously published results of PET studies, whereas metabolic impairment of the thalamus has not yet been described in Huntington's disease. The present study suggests that regional metabolism and γ‐aminobutyric acid (GABA)‐benzodiazepine receptor changes in subcortical structures of patients with early Huntington's disease do not occur with the same time course: Caudate benzodiazepine receptor density is already severely impaired when other subcortical structures reveal only minor abnormalities. Impairment of neuronal metabolism seems to predate GABA/benzodiazepine receptor changes since the putamen and thalamus demonstrate metabolic impairment without detectable loss of benzodiazepine receptor density.