Js. Perlmutter et al., DECREASED [F-18] SPIPERONE BINDING IN PUTAMEN IN IDIOPATHIC FOCAL DYSTONIA, The Journal of neuroscience, 17(2), 1997, pp. 843-850
In this study we have investigated the pathophysiology of two idiopath
ic focal dystonias: hand cramp with excessive cocontractions of agonis
t and antagonist hand or forearm muscles during specific tasks, such a
s writing, and facial dystonia manifested by involuntary eyelid spasms
(blepharospasm) and lower facial and jaw spasms (oromandibular dyston
ia). We used positron emission tomography (PET) to measure the in vivo
binding of the dopaminergic radioligand [F-18]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 a
nd blood volume in each subject as well as the radiolabeled metabolite
s of [F-18]spiperone in arterial blood. A stereotactic method of local
ization, independent of the appearance of the images, was used to iden
tify the putamen in all of the PET images. We analyzed the PET and art
erial blood data with a validated nonsteady-state tracer kinetic model
representing the in vivo behavior of the radioligand. An index of bin
ding called the combined forward rate constant was decreased by 29% in
dystonics, as compared with normals (p < 0.05). There were no signifi
cant differences between dystonics and normals in regional blood flow,
blood volume, nonspecific binding, permeability-surface area product
of [F-18]spiperone or the dissociation rate constant. These findings a
re consistent with a decrease of dopamine D-2-like binding in putamen
and are the first demonstration of a receptor abnormality in idiopathi
c dystonia. These results have important implications for the pathophy
siology of dystonia as well as for function of the basal ganglia.