raclopride and Machado-Joseph-Disease

In spinocerebellar ataxias (SCAs), up to 30% of patients complain of restless legs syndrome (RLS). In primary RLS, a putative role of the dopaminergic system has been postulated. To assess dopaminergic function in SCA1, 2, and 3, dopamine D(2) receptor binding potential (BP) was assessed by [(11)C]raclopride positron emission tomography in 10 SCA patients, 4 of whom suffered from RLS as demonstrated by polysomnography. BP was compared to 9 age-matched control subjects. In 2 SCA patients, striatal BP was clearly reduced (<2 SD below the mean of controls). However, there were no significant group differences between SCA and controls, largely owing to a significantly higher variance of striatal BP in SCA. BP was negatively correlated with disease duration. The fit suggests an increased BP in early stages, followed by a moderate decline in all quantified regions (caudate, dorsal putamen, ventral striatum) presumably reflecting a progressive loss of D(2) receptors. RLS in SCA was not accompanied by a significant reduction of D(2) receptor availability in the striatum. This missing correlation may point to an extrastriatal origin of RLS.

Topics: Adult; Ataxin-1; Ataxin-3; Ataxins; Carbon Radioisotopes; Corpus Striatum; Female; Genotype; Humans; Machado-Joseph Disease; Male; Middle Aged; Nerve Tissue Proteins; Neurologic Examination; Nuclear Proteins; Occipital Lobe; Polysomnography; Positron-Emission Tomography; Raclopride; Receptors, Dopamine D2; Repressor Proteins; Restless Legs Syndrome; Spinocerebellar Ataxias

We performed [18F]6-fluoro-L-dopa (6-FD) and [11C]raclopride (RAC) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAC-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD.

Topics: Adolescent; Adult; Caudate Nucleus; Cerebellum; Dihydroxyphenylalanine; Dopamine Antagonists; Female; Humans; Machado-Joseph Disease; Male; Middle Aged; Parkinson Disease; Putamen; Raclopride; Reference Values; Salicylamides; Tissue Distribution; Tomography, Emission-Computed