Substantial thalamostriatal dopaminergic defect in Unverricht-Lundborg disease

Purpose: Unverricht-Lundborg disease (ULD) is currently classified as progressive myoclonus epilepsy. Myoclonus, the characteristic symptom in ULD, suggests that dopamine neurotransmission may be involved in the pathophysiology of ULD. Our purpose was to examine brain dopaminergic function in ULD patients. Methods: Four genetically and clinically diagnosed ULD patients and eight healthy controls were scanned with [¹¹C]raclopride-PET. PET images were coregistered to individual 1.5T MR images and region-of-interest analysis was performed for the striatum and thalamus. Standardized uptake values and individual voxel-wise binding potential maps of the patients and controls were also analyzed. Results: ULD patients had markedly higher (31-54%) dopamine D2-like receptor availabilities than healthy controls in both the striatum and the thalamus. The proportionally highest binding potentials were detected in the thalamus. There were no significant differences in the cerebellar uptake of [¹¹C]raclopride in ULD patients versus healthy controls. Voxel-based results were in accordance with the region-of-interest analysis. Conclusions: These results suggest that dopaminergic modulation at the level of the striatum and thalamus could be a crucial factor contributing to the symptoms of ULD. In the light of our data, we propose that ULD with dopamine dysfunction and dyskinetic symptoms shares certain pathophysiological mechanisms with classical movement disorders. Future studies are therefore warranted to study the effect of dopaminergic pharmacotherapy in ULD.