Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio <1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studie

Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study

The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40–65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary, there is evidence of accelerated brain ageing in severe chronic epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy

Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio <1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies

Epilepsy and stigma: An approach to understanding through the life and works of the Brazilian writer Machado de Assis (1839-1908)

Machado de Assis (1839-1908)-novelist, short story writer, essayist, and poet-is a fascinating personality. Had he written in French, English, German, or Italian, he would have achieved universal fame and would be in the same company as Balzac, Tolstoy, Dickens, and Dostoevsky. This article discusses stigma in epilepsy through Machado de Assis' life, literary work, and letters to other Brazilian writers. Founder of the Brazilian Academy of Letters, Machado offers an insoluble enigma to psychologists and essayists. Born in stark poverty, feeble, and ugly, he had to fight the taint of epilepsy. the documentation of epilepsy in Machado de Assis' texts and letters and the testimony of his contemporaries is unique, allowing the comprehension of scientific concepts and stigma related to epilepsy in the 19th century, when the positivist ideas of the Italian neuropsychiatrist Cesare Lombroso (1835-1909) permeated nascent Brazilian neuropsychiatry. Much of the stigma associated with epilepsy we witness today emerged from these concepts. Even today in Brazil, when barbaric crimes are committed, headlines in newspapers produced by forensic psychiatrists often attribute the conduct of the criminal to epileptic behavior. (C) 2011 Elsevier Inc. All rights reserved.Universidade Federal de São Paulo UNIFESP, Dept Neurol & Neurosurg, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Neurol & Neurosurg, São Paulo, BrazilWeb of Scienc

An appraisal to Hans Berger by the time of his 150^th birthday: the human EEG and tales of blood flow, heat and brain waves

More than 100 years of research have passed by and still the human electroencephalogram (EEG) remains a puzzle to be solved. Starting from his studies on plethysmography until his theories on brain thermodynamics, Hans Berger was able to refine his method of recording cortical signs with the apparatus at his disposal in an ordinary neuropsychiatric yard towards an early account of human EEG. This review is an appraisal of his contribution to the field of modern neurophysiology

The relevance of electroencephalogram as a follow-up test in Hashimoto encephalopathy course after corticosteroids therapy

Universidade Federal de São Paulo, Dept Neurol, BR-04023900 São Paulo, BrazilHIAE, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, BR-04023900 São Paulo, BrazilWeb of Scienc