raclopride and Restless-Legs-Syndrome

Although D2/3 agonists have been used as a first-line medication for idiopathic restless legs syndrome (iRLS), findings on D2/3 receptors have been inconsistent. Here, we aimed to clarify the contribution of D2/3 receptor function to the clinical symptoms of iRLS by comparing the binding potential (BP(ND)) of [(11)C]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naïve, iRLS patients and eight age-matched healthy subjects were scanned with positron emission tomography (PET). After PET scans, all patients received pramipexole (0.125 mg) orally for 2 weeks. Patients were evaluated every day with several standardized clinical tests. The BP(ND) values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [(11)C]raclopride BP(ND) in the mesolimbic dopamine region (nucleus accumbens (NA) and caudate) was significantly lower in the iRLS group. No significant differences between groups were observed in the putamen. The NA [(11)C]raclopride BP(ND) levels correlated negatively with clinical severity scores and positively with the degree of posttreatment improvement in iRLS. The present results suggest that alterations in mesolimbic D2/3 receptor function reflect the pathophysiology of iRLS, and the baseline availability of D2/3 receptors may predict the clinical outcome after D2/3 agonist treatment.

Topics: Administration, Oral; Adult; Aged; Benzothiazoles; Caudate Nucleus; Dopamine Agonists; Dopamine Antagonists; Female; Humans; Male; Middle Aged; Nucleus Accumbens; Positron-Emission Tomography; Pramipexole; Raclopride; Radiography; Receptors, Dopamine D2; Receptors, Dopamine D3; Restless Legs Syndrome

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

To use PET to study striatal dopaminergic function in restless legs syndrome (RLS).. RLS is a common disorder experienced by as much as 5% of the population. It has been suggested that this condition is associated with a disturbance of dopaminergic transmission.. The authors measured nigrostriatal terminal dopamine storage with 18F-dopa and striatal D2 receptor binding with 11C-raclopride PET in 13 RLS patients, five of whom were receiving treatment with L-dopa at the time of scanning. RLS results were compared with those of age-matched control subjects.. Mean caudate and putamen 18F-dopa uptake were mildly reduced in the RLS patients compared with control subjects, and this reached significance (p = 0.04) in the putamen. Mean D2 binding was reduced in the caudate (p = 0.01) and the putamen (p = 0.008) in RLS patients compared with control subjects. Six of the 13 RLS patients had caudate and putamen D2 binding reduced below the control range. Three other RLS patients showed only reduced putamen D2 binding. There were no significant differences in striatal 18F-dopa uptake or D2 binding between L-dopa-naive and L-dopa-treated RLS patients.. These PET findings support the hypothesis of central dopaminergic dysfunction in RLS.

Topics: Aged; Carbon Radioisotopes; Corpus Striatum; Dihydroxyphenylalanine; Dopamine; Female; Humans; Kinetics; Male; Middle Aged; Raclopride; Restless Legs Syndrome; Salicylamides; Syndrome; Tomography, Emission-Computed