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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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