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Objective: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy., Methods: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥ 60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency., Results: Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0)., Significance: In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Purpose: 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)., Methods: 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., Results: 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., Discussion: 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., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)