Alteration of dopamine D2/D3 receptor binding in patients with juvenile myoclonic epilepsy

Abstract

To quantify extrastriatal and striatal D2/D3 receptor binding in patients with juvenile myoclonic epilepsy (JME) using the high-affinity dopamine D2/D3 receptor positron emission tomography (PET) ligand (18) F-Fallypride ([(18) F]FP). Twelve patients with JME and 21 age-matched control subjects were studied. Dynamic images (180 min) were acquired after injection of [(18) F]FP. Patients had been seizure-free of all seizure types for at least 10 days before scanning. Parametric images of binding potential (BP) were created using the simplified reference tissue model. The images were stereotactically normalized using a ligand-specific template. We performed a voxel-based analysis with statistical parametric mapping (SPM2). Region of interest (ROI) analysis was done comparing the BP of the thalamus, caudate nucleus, anterior (ventral) and posterior (dorsal) putamen, ventral striatum, and temporal lobe. Compared to controls, patients with JME showed a significant decrease in [(18) F]FP BP (SPM analysis corr. p < 0.001 at cluster level) restricted to the bilateral posterior putamen. There was no significant alteration of [(18) F]FP binding in other brains regions. ROI analysis revealed a significant (p < 0.05) decrease of [(18) F]FP BP in the left (mean -14.8%) and right (mean -16.9%) posterior putamen, but not in the anterior putamen, caudate, ventral striatum, thalamus, or temporal lobe. Patients with JME showed a reduction in D2/3 receptor binding restricted to the bilateral posterior putamen, suggesting a specific alteration of the dopaminergic system. Whether these changes can be regarded as merely functional or whether they relate to the pathophysiology of juvenile myoclonic epilepsy still remains unclear.