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Volume 17, Number 2,
Issue of January 15, 1997
pp. 843-850
Copyright ©1997 Society for Neuroscience
Decreased [18F]Spiperone Binding in Putamen
in Idiopathic Focal Dystonia
Received June 17, 1996; revised Oct. 15, 1996; accepted Nov. 5, 1996.
Joel S. Perlmutter1, 5,
Mikula K. Stambuk4,
Joanne Markham6,
Kevin J. Black1, 2, 5,
Lori McGee-Minnich1,
Joseph Jankovic7, and
Stephen M. Moerlein3, 5
Departments of 1 Neurology and Neurological Surgery,
2 Psychiatry, and 3 Medicinal Chemistry,
4 Division of Biology and Biomedical Sciences,
5 Mallinckrodt Institute of Radiology, and the
6 Biomedical Computing Laboratory, Washington University
School of Medicine, St. Louis, Missouri 63110, and
7 Department of Neurology, Baylor College of Medicine,
Houston, Texas 77030
In this study we have investigated the pathophysiology of two
idiopathic focal dystonias: hand cramp with excessive cocontractions of
agonist and antagonist hand or forearm muscles during specific tasks,
such as writing, and facial dystonia manifested by involuntary eyelid
spasms (blepharospasm) and lower facial and jaw spasms (oromandibular
dystonia). We used positron emission tomography (PET) to measure the
in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two
focal dystonias and compared the findings with those from 13 normals.
We measured regional cerebral blood flow and blood volume in each
subject as well as the radiolabeled metabolites of
[18F]spiperone in arterial blood. A stereotactic method
of localization, independent of the appearance of the images, was used
to identify the putamen in all of the PET images. We analyzed the PET
and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the
radioligand. An index of binding called the combined forward rate
constant was decreased by 29% in dystonics, as compared with normals
(p < 0.05). There were no significant
differences between dystonics and normals in regional blood flow, blood
volume, nonspecific binding, permeability-surface area product of
[18F]spiperone or the dissociation rate constant. These
findings are consistent with a decrease of dopamine D2-like
binding in putamen and are the first demonstration of a receptor
abnormality in idiopathic dystonia. These results have important
implications for the pathophysiology of dystonia as well as for
function of the basal ganglia.
Key words:
dystonia;
PET;
spiperone;
D2-like receptors;
putamen;
blepharospasm;
hand cramp
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