Substantial thalamostriatal dopaminergic defect in Unverricht-Lundborg disease.
OBJECTIVE
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 [(11)C]raclopride-PET. PET images were coregistered to individual 1.5 T 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 [(11)C]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.
Korja
Miikka
M
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
Kaasinen
Valtteri
V
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
Lamusuo
Salla
S
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
Parkkola
Riitta
R
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
Någren
Kjell
K
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
Marttila
Reijo J
RJ
Turku University Hospital, Turku, FinlandTurku PET Centre, Turku, FinlandSalo Regional Hospital, Salo, Finland.
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000706:statistics & numerical data; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D020891:Raclopride / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D020194:Unverricht-Lundborg Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology*
D017448:Receptors, Dopamine D2; D020891:Raclopride; D004298:Dopamine