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SUMMARYTo elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients' seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient videoelectroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.

In this paper new concepts and developments are presented for structural analysis involving uncertain parameters. Based on a classi®cation of the uncertainties in structural analysis the uncertainty``fuzziness'' is identi®ed and its quanti®cation is demonstrated. On the basis of fuzzy set theory a general method for fuzzy structural analysis is developed and formulated in terms of the alevel optimization with the application of a modi®ed evolution strategy. Every known analysis algorithm for the realistic simulation of load-bearing behavior may be applied in the fuzzy structural analysis in the sense of a deterministic fundamental solution. By way of example, geometrically and physically nonlinear algorithms are adopted in the presented study as a deterministic fundamental solution for the analysis of steel and reinforced concrete structures. The paper also describes coupling between a-level optimization and the deterministic fundamental solution.

SUMMARYObjective: Hippocampal sclerosis (HS) is the major structural brain lesion in patients with temporal lobe epilepsy (TLE). However, its internal anatomic structure remains difficult to recognize at 1.5 or 3 Tesla (T) magnetic resonance imaging (MRI), which allows neither identification of specific pathology patterns nor their proposed value to predict postsurgical outcome, cognitive impairment, or underlying etiologies. We aimed to identify specific HS subtypes in resected surgical TLE samples on 7T MRI by juxtaposition with corresponding histologic sections. Methods: Fifteen nonsclerotic and 18 sclerotic hippocampi were studied ex vivo using an experimental 7T MRI scanner. T 2 -weighted images (T2wi) and diffusion tensor imaging (DTI) data were acquired and validated using a systematic histologic analysis of same specimens along the anterior-posterior axis of the hippocampus. Results: In nonsclerotic hippocampi, differences in MR intensity could be assigned to seven clearly recognizable layers and anatomic boundaries as confirmed by histology. All hippocampal subfields could be visualized also in the hippocampal head with threedimensional imaging and angulated coronal planes. Only four discernible layers were identified in specimens with histopathologically confirmed HS. All sclerotic hippocampi showed a significant atrophy and increased signal intensity along the pyramidal cell layer. Changes in DTI parameters such as an increased mean diffusivity, allowed to distinguish International League Against Epilepsy (ILAE) HS type 1 from type 2. Whereas the increase in T2wi signal intensities could not be attributed to a distinct specific histopathologic substrate, that is, decreased neuronal or increased glial cell densities, intrahippocampal projections and fiber tracts were distorted in HS specimens suggesting a complex disorganization of the cellular composition, fiber networks, as well as its extracellular matrix. Significance: Our data further advocate high-resolution MRI as a helpful and promising diagnostic tool for the investigation of hippocampal pathology along the anterior-posterior extent in TLE, as well as in other neurologic and neurodegenerative disorders.

Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS(®) LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer(®), which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to €285.1 Mio (median AED costs/patient: €158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.

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Lamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile.

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