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

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.

Address correspondence and reprint requests to Dr. David C. Reutens, Department of Medicine, Level 5, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia 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 4-Ser248Phe mutation affects dopaminergic transmission.

Methods: We measured D₁ receptor binding using [¹¹C]-SCH23390 and PET in 12 subjects with the 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 4-Ser248Phe subjects compared to controls (309 voxels, local maxima 20 16 –2 mm; Z_score 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.

Abbreviations: ADNFLE = autosomal dominant nocturnal frontal lobe epilepsy; BP = binding potential; DLPFC = dorsolateral prefrontal cortex; MPFC = mesial prefrontal cortex; nACh = nicotinic acetylcholine; ORBF = orbitofrontal cortex; ROI = region of interest.

Editorial, page 784

See also page 788

e-Pub ahead of print on August 6, 2008, at www.neurology.org.

Disclosure: The authors report no disclosures.

Received October 16, 2007. Accepted in final form February 26, 2008.

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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. [Full Text] [PDF]