Decreased [¹⁸F]Spiperone Binding in Putamen in Idiopathic Focal Dystonia

Abstract

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.

Bilateral pallidotomy for generalized dystonia

“…Different reports suggest an increased activity in the direct pathway 20,37,39 . The level of activity in the indirect pathway is more controversial: physiological studies, based on the mean discharge rates suggest an increased activity also on this pathway; studies with dopamine ligand receptors suggest a reduced activity 20,39 .…”

“…Different reports suggest an increased activity in the direct pathway 20,37,39 . The level of activity in the indirect pathway is more controversial: physiological studies, based on the mean discharge rates suggest an increased activity also on this pathway; studies with dopamine ligand receptors suggest a reduced activity 20,39 . GPi firing rates(as well as GPe) are reduced in dystonic patients as compared to Parkinson's disease patients or parkinsonian primates, but slightly faster than reported in patients with hemiballismus 13,20,40,41 .…”

Spontaneous dyskinesia and familial liability to schizophrenia

“…For example, lesions involving the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, thalamus, and cerebellum have been associated with particular spontaneous dyskinesias in several studies using a variety of methodological techniques (e.g., Antonini et al, 1998;Dooling & Adams, 1975;Kim et al, 2002;Krystkowiak et al, 2000;Krystkowiak et al, 1998;LeDoux & Brady, 2003;Lehericy et al, 1996;Lenz et al, 2002;Lozza et al, 2002;Naumann et al, 1996;Perlmutter et al, 1997). Moreover, an array of structural and functional abnormalities have been observed in several of these regions in individuals with schizophrenia, although substantial variation in findings exists (e.g., Danos et al, 2002;Gunduz et al, 2002;Jernigan et al, 1991;Keshavan et al, 1998;Lang et al, 2001;Marcelis et al, 2003;McCreadie et al, 2002;Menon et al, 2001;Muller et al, 2002;Sigmundsson et al, 2001;Staal et al, 2000;Staal et al, 2001;Young et al, 2000).…”

Animal Models for Investigating Benign Essential Blepharospasm

“…Such an increased incidence of Parkinson’s disease, however, does not appear to occur in BEB patients [106]. The eye irritation environmental trigger, however, is consistent with the human data [36-39] and the evidence that changes in the basal ganglia plays a role in the predisposing condition is compelling [40, 97-99]. Thus, the Schicatano et al (1997) model [100] suggests an outline for abnormal neural circuit interactions that support BEB.…”

“…Abnormalities in the D 2 receptor, however, may set the stage for BEB. BEB patients show a decreased D 2 binding in the striatum, [40, 97] and animal models of generalized and hemidystonia exhibit altered D 2 binding [98, 99]. …”