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Published online before print August 6, 2008, doi:10.1212/01.wnl.0000316192.52731.77)
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Received October 16, 2007
Accepted February 26, 2008

Reduced striatal D1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy

M. Fedi MD, S. F. Berkovic MD, FRACP, I. E. Scheffer MD, FRACP, G. O'Keefe PhD, C. Marini MD, PhD, R. Mulligan PhD, S. Gong PhD, H. Tochon-Danguy PhD, and D. C. Reutens MD, FRACP*

From the Department of Medicine (M.F., S.F.B., I.E.S., D.C.R.), The University of Melbourne; Centre for PET (M.F., G.O., R.M., S.G., H.T.-D., D.C.R.), Austin Health, Heidelberg, Victoria; Department of Paediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia; Neurogenetics Laboratory (C.M.), Istituto di Neuropsichiatria Infantile (INPE), IRCSS Fondazione Stella Maris, Pisa, Italy; and Department of Medicine (M.F., D.C.R.), Southern Clinical School and Monash University, Clayton, Victoria, Australia.


* To whom correspondence should be addressed. E-mail: David.Reutens{at}med.monash.edu.au.

Background: Mutations of the neuronal nicotinic acetylcholine (nACh) receptor identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) lead to increased sensitivity to ACh. As activation of presynaptic nicotinic receptors augments the release of dopamine in the striatum and the prefrontal regions, we tested the hypothesis that that the {alpha}4-Ser248Phe mutation affects dopaminergic transmission.

Methods: We measured D1 receptor binding using [11C]-SCH23390 and PET in 12 subjects with the {alpha}4-Ser248Phe mutation (3 men, mean age 41 ± 16 years) and 19 controls (8 men, mean age 36 ± 13 years) matched for gender, smoking status, and age. Parametric images were produced using the simplified reference region method. Both MRI-based regions of interest and voxel based analyses were used.

Results: Reduced striatal [11C]-SCH23390 binding occurred with the mutation (controls 1.1 ± 0.1; ADNFLE 0.97 ± 0.2; p < 0.01). Statistical parametric mapping confirmed a region of reduced [11C]-SCH23390 binding in the right putamen in {alpha}4-Ser248Phe subjects compared to controls (309 voxels, local maxima 20 16 -2 mm; Zscore 3.57, p < 0.05).

Conclusions: Reduced D1 receptor binding may represent increased extracellular dopamine levels or, more likely, receptor downregulation. Alterations in mesostriatal dopaminergic circuits may contribute to nocturnal paroxysmal motor activity in autosomal dominant nocturnal frontal lobe epilepsy.




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S. R. Haut and R. L. Albin
Dopamine and epilepsy: Hints of complex subcortical roles
Neurology, September 9, 2008; 71(11): 784 - 785.
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