Summary:Purpose: To evaluate the efficacy of the educational program MOSES (Modular Service Package Epilepsy). It was developed to improve patients' knowledge and understanding about their epilepsy, its treatment, and psychosocial consequences. The program intends to improve patients' coping with the disease, to strengthen self-esteem, and to support patients to become experts in managing their epilepsy.Methods: A controlled, randomized study design was used to examine the efficacy of MOSES. Patients from 22 epilepsy centers in Germany, Austria, and Switzerland were randomly allocated to either MOSES group (treatment group) or waitinglist group (control group). The 242 patients were aged from 16 to 80 years. The MOSES group (n ‫ס‬ 113) completed the questionnaires immediately before the educational course (T1) and 6 months later (T2), and the control group (n ‫ס‬ 129), 6 months before (T1) and immediately before (T2) the course. The questionnaires included generic instruments (SF-36, Rosenberg self-esteem Scale, von Zerssen Depression Scale), and epilepsy-specific scales (Restrictions in Daily Life, Epilepsy-Related Fears, Coping with Epilepsy and Adaptation). Depression was used as a moderator variable. Seizure frequency and satisfaction with therapy also were assessed. Multivariate analysis of variance (MANOVA) with repeated measurements and univariate analyses of variance were performed.Results: The MANOVA showed that participants of the educational program improved significantly. Univariate analyses revealed improvements in knowledge (p < 0.001) and coping with epilepsy (p ‫ס‬ 0.004), whereas important effects of MOSES on other epilepsy-specific measures and on generic questionnaires (SF-36, self-esteem) were not found. Participants of the MOSES program also improved in seizure outcome (p ‫ס‬ 0.041) and became more satisfied with the therapy [better tolerability of antiepileptic drug (AED) therapy, fewer side effects; p ‫ס‬ 0.014]. In addition, participants expressed being highly satisfied with the program.Conclusions: The study clearly indicates the need for patient education. Even patients with a long history of epilepsy and with additional handicaps or diseases benefitted from the MOSES program.

Oxcarbazepine is an antiepileptic drug with a chemical structure similar to carbamazepine, but with different metabolism. Oxcarbazepine is rapidly reduced to 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of oxcarbazepine. MHD has (S)-(+)- and the (R)-(-)-enantiomer, but the pharmacokinetics of the racemate are usually reported. The bioavailability of the oral formulation of oxcarbazepine is high (>95%). It is rapidly absorbed after oral administration, reaching peak concentrations within about 1-3 hours after a single dose, whereas the peak of MHD occurs within 4-12 hours. At steady state, the peak of MHD occurs about 2-4 hours after drug intake. The plasma protein binding of MHD is about 40%. Cerebrospinal fluid concentrations of MHD are in the same range as unbound plasma concentrations of MHD. Oxcarbazepine can be transferred significantly through the placenta in humans. Oxcarbazepine and MHD exhibit linear pharmaco-kinetics and no autoinduction occurs. Elimination half-lives in healthy volunteers are 1-5 hours for oxcarbazepine and 7-20 hours for MHD. Longer and shorter elimination half-lives have been reported in elderly volunteers and children, respectively. Mild to moderate hepatic impairment does not appear to affect MHD pharmacokinetics. Renal impairment affects the pharmacokinetics of oxcarbazepine and MHD. The interaction potential of oxcarbazepine is relatively low. However, enzyme-inducing antiepileptic drugs such as phenytoin, phenobarbital or carbamazepine can reduce slightly the concentrations of MHD. Verapamil may moderately decrease MHD concentrations, but this effect is probably without clinical relevance. The influence of oxcarbazepine on other antiepileptic drugs is not clinically relevant in most cases. However, oxcarbazepine appears to increase concentrations of phenytoin and to decrease trough concentrations of lamotrigine and topiramate. Oxcarbazepine lowers concentrations of ethinylestra-diol and levonorgestrel, and women treated with oxcarbazepine should consider additional contraceptive measures. Due to the absent or lower enzyme-inducing effect of oxcarbazepine, switching from carbamazepine to oxcarbazepine can result in increased serum concentrations of comedication, sometimes associated with adverse effects. The effect of oxcarbazepine appears to be related to dose and to serum concentrations of MHD. In general, daily fluctuations of MHD concentration are relatively slight, smaller than would be expected from the elimination half-life of MHD. However, relatively high fluctuations can be observed in individual patients. Therapeutic monitoring may help to decide whether adverse effects are dependent on MHD concentrations. A mean therapeutic range of 15-35 mg/L for MHD seems to be appropriate. However, more systematic studies exploring the concentration-effect relationship are required.

Introduction Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons. Patients and methods Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed. Patients were grouped according to the underlying pathology. Results A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis:

Switch of lateralization or bitemporal asynchrony in the ictal scalp EEG and bitemporal IED are most probably an index of bitemporal epileptogenicity in MTS and are associated with a worse outcome.

Compared with temporal or frontal resections, epilepsy surgery in the posterior cortex is rarely performed, and the literature concerning clinical predictors for the postoperative seizure outcome in this particular subgroup is sparse. The data of 42 patients with lesional focal epilepsies of the parieto-occipital lobe and the occipital border of the temporal lobe were evaluated retrospectively and related to the seizure outcome 2 years after epilepsy surgery. The investigated parameters included ictal semiology, pre- and postoperative EEG and neuroimaging, histological findings and demographic data. Postoperatively, seizure-free outcome was seen in: (i) 69% of patients with lateralizing auras, but only in 28% of patients without lateralizing auras (P = 0.01); and (ii) 57% of the patients with lateralizing seizures, but only in 17% of patients without lateralizing ictal semiology (P = 0.02). None of the patients with neither lateralizing auras nor lateralizing seizures achieved freedom from seizures (P < 0.01). The proportion of lateralizing seizures (P < 0.01) and auras (P = 0.02) in the total number of recorded seizures and auras was significantly related to the probability of a favourable surgical outcome. No patient with clinical lateralizing signs to the non-lesional hemisphere but 58% without such "false" lateralization achieved freedom from seizures (P = 0.02). The following parameters also proved to be predictive for a favourable seizure outcome: (i) tumoural aetiology; and (ii) absence of epileptiform discharges in the postoperative EEG. The presence and frequency of ictal semiology lateralizing to the lesional hemisphere and the absence of lateralizing signs to the non-lesional hemisphere are highly predictive of a favourable outcome after surgical treatment of epilepsy in the posterior cortex.

Our data confirm that ipsilateral PET hypometabolism may be an indicator for good postoperative outcome in presurgical evaluation of drug-resistant TLE, although the actual diagnostic added value remained questionable and unclear. PET does not appear to add value in patients localized by ictal scalp EEG and MRI. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation.

Summary:Purpose: To estimate the incidence rate of epilepsies and epileptic syndromes in German children and adolescents aged 1 month to <15 years, and to provide data on their classification.

Objective: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Methods: Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni-and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Results: Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. Interpretation: In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step.