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In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).

We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 × 10 −8 ). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.Idiopathic generalized epilepsies (IGE) are common seizure disorders accounting for up to one-third of all epilepsies 1 . The vast majority of individuals with IGE have a complex genetic etiology2, for which the underlying genetic alterations remain largely unknown. Recently, a 15q13.3 microdeletion syndrome has been identified in 0.2-0.3% of individuals Correspondence should be addressed to T.S. (sandert@uni-koeln.de). Note: Supplementary information is available on the Nature Genetics website. AUTHOR CONTRIBUTIONST.S. and E.E.E. initiated and designed the study; I.H., H.M., S.v.S., I.S., A.A.K.-L., V.G., B.S., K.M.K., P.S.R., F.R., Y.W., H.L., F.Z., L.U., K.F., M. Feucht, F.V., G.-J.d.H., R.S.M., H.H., D. Luciano, C.R., D. Lindhout, C.E.E., U.S. and T.S. recruited and phenotyped the EPICURE sample; H.C.M., A.J.S., M.G., M. Fichera, C.B., P.G., P.T., A.M. and E.E.E. recruited and phenotyped the mixed IGE sample; A.F., M.W., M.N. and S.S. recruited and phenotyped the PopGen control sample; I.H., A.F., C.L., K.L.K., I.S., M.W., M.N., P.N. and T.S. performed the CNV analysis on SNP arrays; H.C.M., A.J.S., M. Fichera, C.B. and D. Luciano performed the qPCR screening; H.C.M., M. Fichera, C.B. and D. Luciano performed the screening using Illumina Genotyping BeadChips; H.C.M., A.J.S. and C.B. performed the confirmation using NimbleGen arrays; C.d.K., B.P.C.K. and D. Lindhout performed the confirmation using Illumina CNV BeadChips; I.H., H.C.M., A.J.S., M.G., M. Fichera, A.F., C.d.K., K.L.K., C.R., B.P.C.K., D. Lindhout, E.E.E. and T.S. coordinated the work and prepared the manuscript. Susceptibility loci for common idiopathic epilepsies, comprising benign epilepsy of childhood with centrotemporal spikes7 and common IGE syndromes8 ,9 , have also been mapped to the 15q13-q14 region. To test whether the 15q13.3 deletion increases risk of common epilepsies, we screened for structural variants within the 15q13.3 region in two independent samples of individuals with IGE and ancestrally matched controls. The first sample comprised 647 unrelated IGE cases of Western European ancestry (EPICURE sample) and 1,202 German controls (PopGen) genotyped using the Affymetrix GenomeWide Human SNP array 6.0. We identified the 15q13.3 microdeletion in 7 of 647 IGE cases ( Supplementary Fig. 1 online) with different IGE syndromes ( Supplementary Fig. 2 online). Thus, our results suggest that the 15q13.3 deletion only, and not the reciprocal duplication, represents a major risk factor for IGE. NIH Public AccessIn our stu...

Summary:Purpose: To determine the incidence and casefatality rate of status epilepticus (SE) in adults in Hessen, Germany, we performed a prospective, population-based study from July 1997 through June 1999.Methods: All adult patients residing within the zip-code area 35 (area-35) with SE were included. Area-35 had 743.285 adult inhabitants, including 123.353 adult inhabitants of the primary service area of the University Hospital Marburg (PS-area). Patients were reported by 16 hospitals in the area and were prospectively identified and carefully reviewed within 5 days by one of the authors. Based on the crude annual incidence of SE and a rate of underascertainment of 10% determined for the PS-area, the corrected, age-adjusted incidence of SE in area 35, more representative of the population of Germany, was calculated.Results: The crude annual incidence in the PS-area was 15.8/ 100,000 [95% confidence interval (CI), 11.2-21.6]. The calculated, corrected, age-adjusted incidence of SE in area 35 was 17.1/100,000. It was higher for men compared with women (26.1 vs. 13.7) and for those aged 60 years and older (54.5 vs. 4.2/100,000, p < 0.0001). The etiology was mainly remote symptomatic due to cerebrovascular disease. Epilepsy was previously diagnosed in only 50% of the patients. The case-fatality rate was 9.3%.Conclusions: Based on our data, at least 14,000 patients would be affected by SE in Germany, associated with ∼1,300 deaths annually. The incidence of SE in Germany is similar to that found in the white United States population. Furthermore, this study confirms the higher incidence of SE in male patients and in the elderly population. This may be due to a higher incidence of cerebrovascular disease in these subpopulations.

We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions.

Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2; chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7; P = 0.009). Including nine patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.

Summary:We propose an epileptic seizure classification based exclusively on ictal semiology. In this semiological seizure classification (SSC), seizures are classified as follows: The SSC identifies in detail the somatotopic distribution of the ictal semiology as well as the seizure evolution. The advantages of a pure SSC, as opposed to the current classification of the International League Against Epilepsy (ILAE), which is actually a classification of electroclinical syndromes, are discussed. Key Words: Seizure classification-Ictal semiology-Auras-Motor seizures-Paroxysmal events.The International League Against Epilepsy (ILAE) introduced a seizure classification in 1981 based on clinical semiology, interictal EEG findings, and ictal EEG patterns (1). The assumption behind such a classification, which is actually a classification of electroclinical features, is the existence of a strict one-to-one correlation between clinical-ictal semiology and interictalhctal EEG findings. Detailed analysis of clinical semiology and EEG findings shows, however, that this assumption is frequently incorrect (2), particularly for infants (3).

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