The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.

We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n=8), thalamocapsular hemorrhage (n=6), or pure thalamic stroke (n=7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia. (Stroke 1990^21:519-524)

SUMMARY The dopamine D2 receptors were investigated in vivo in eight neuroleptic-free patients with persistent tardive dyskinesia using positron emission tomography and 76Br-bromospiperone. The striatal receptor density, estimated by the striatum/cerebellum radioligand concentration ratio, was not elevated in patients as compared with age-matched controls but was positively correlated with the severity of orofacial dyskinesia assessed with the Abnormal Involuntary Movement Rating Scale. These results indicate that tardive dyskinesia is associated with normal levels of striatal D2 receptors but the severity of orofacial movements may depend on the relative density of striatal D2 receptors.Tardive dyskinesia (TD) is a protracted, sometimes permanent, complication of long-term neuroleptic treatment, affecting 13% to 31% of treated schizophrenic patients.'2 It is a distressing condition as the involuntary movements affect the orofacial musculature and often do not respond to therapy save for reintroduction or increased dosage of neuroleptics. There is no established preventive measure other than restricting prescription, and limiting both dosage and duration, of neuroleptic treatment as much as possible.3Brain dopamine receptor hypersensitivity is the most widely accepted hypothesis for the development of TD: it resembles levodopa-induced dyskinesia; it is both caused and controlled by dopaminergic antagonists and aggravated by dopaminergic agonists; during and following chronic neuroleptic treatment, rodents show increased behavioural responses to dopaminergic agonists with correlated increase in dopamine D2 receptor density in the striatum.4 Until now, however, no direct evidence for this role of striatal D2 receptors has been obtained in prospectively selected TD patients. We have evaluated striatal D2 receptors in TD patients in vivo using positron emission tomography (PET) and 76Br-bromospiperone to investigate the following hypothesis: (1) the striatal D2 receptors are increased in TD, and (2) the D2 receptor density is correlated to the severity of TD. Eight dyskinetic patients were studied after giving informed consent (table 1). The eight TD patients (7 women and I man, mean age 64-3 years, SD 4 7) were compared with eight agematched controls (3 women and 5 men, mean age 63 5, SD 2 6). The diagnosis of TD was established when abnormal involuntary movements (AIMS) (of a choreic nature), without other neurological abnormalities, had been permanent for the past 3 months, affecting in all cases the oro-linguofacial area and sometimes also the limbs or trunk, and had begun following a minimum of 3 months of exposure to neuroleptics, persisting at least 9 days after withdrawal of the neuroleptics (the type of which not being relevant). Neuroleptics had been prescribed, sometimes for many years, by general practitioners for reasons not always clear, particularly in the six chronically depressed patients. The characteristics ofdyskinesia and the plasma concentration of prolactin (as an index of neuroleptic medicati...