Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Seizures and Antiepileptic Drugs: From Pathophysiology to Clinical Practice

Recurrent, spontaneous seizure activity caused by abnormal neuronal firing in the brain is a hallmark of epilepsy, a common chronic neurological disorder. Recent research that has expanded the knowledge of the cellular and molecular mechanisms that modulate neuronal excitability and network activity in the brain provides the development and discovery of antiepileptic drugs (AEDs). AED therapy starts with the selection of the most appropriate drug for individual patient according to a strategic decision based on the risk-benefit ratio. Beyond three generations of AEDs developed over the last 40 years, more effective, better tolerated, disease-modifying pharmacological therapies are still needed to improve seizure outcome and reduce the safety burden. In this review, we aim to provide a special focus on epilepsy with an overview of underlying pathophysiological mechanisms that may contribute to seizure generation and propagation. Besides, knowledge of principle pharmacological properties of current AEDs which are essential for rational drug therapy is considered. Limited safety data are available especially for recent AEDs, we also discussed their safety profiles concerning major adverse effects, teratogenicity and their use in pregnancy and lactation. Epilepsy is a chronic disorder which needs special knowledge and experience during AED treatment with meticulous follow-up of patients to avoid short and long-term adverse effects with the best possible seizure controlled outcome and high quality of life

Epilepsy and Sport

Epilepsy is a commonly encountered disorder in Turkey and throughout the world. It is widely believed that exercise enhances seizures, and that traumas and accidents occur more frequently in epileptic patients. This belief has created a stigma, restricting the daily lives of patients with epilepsy. Epileptic children and adolescents are socially isolated and prevented from engaging in sports and similar activities in developing countries. The aim of the present article is to demonstrate that exercise, including sports, is not a precipitating factor for seizures, and that this type of activity may be used to control and prevent epilepsy

Immuno- and antiinflammatory therapies in epileptic disorders

P>Several experimental and clinical studies demonstrated an immunologic basis for different forms of epilepsy. A wide range of immune abnormalities have been reported suggesting the existence of various subtypes of epileptic syndromes with different immunopathogenetic mechanisms. This evidence gives rise to the development of immunologic and immunomodulatory treatments such as usage of steroids, plasmapheresis, and intravenous immunoglobulins, which will be discussed briefly in this article

Reflex epilepsy: triggers and management strategies

Reflex epilepsies (REs) are identified as epileptic seizures that are consistently induced by identifiable and objective-specific triggers, which may be an afferent stimulus or by the patient's own activity. RE may have different subtypes depending on the stimulus characteristic. There are significant clinical and electrophysiologic differences between different RE types. Visual stimuli-sensitive or photosensitive epilepsies constitute a large proportion of the RE and are mainly related to genetic causes. Reflex epilepsies may present with focal or generalized seizures due to specific triggers, and sometimes seizures may occur spontaneously. The stimuli can be external (light flashes, hot water), internal (emotion, thinking), or both and should be distinguished from triggering precipitants, which most epileptic patients could report such as emotional stress, sleep deprivation, alcohol, and menstrual cycle. Different genetic and acquired factors may play a role in etiology of RE. This review will provide a current overview of the triggering factors and management of reflex seizures

Catamenial Epilepsy

When seizures occur in clusters during certain stages of the menstrual cycle (perimenstrual and periovulatory stages), it is defined as catamenial epilepsy. The prevalence varies between 10% and 70%. There are 3 patterns of catamenial epilepsy: perimenstrual (most common), periovulatory, and seizures in the insufficient luteal phase. In the pathophysiology of this occurrence, the neuroactive properties of the reproduction-associated steroid hormones (direct membrane-associated short-term effect and intracellular receptor/genomic-related long-term effect) and their cyclic changes in serum levels play a role in the susceptibility of the epileptogenic area to neuroactive steroids. Among steroid hormones, while progesterone and neurosteroids are known as anticonvulsants, estrogen, the best known proconvulsant, has been found in recent studies to also have anticonvulsant effects related to Neuropeptide Y. Hormonal (medroxyprogesterone acetate, clomiphene, triptorelin, leuprolide, progesterone, goserelin), non-hormonal (acetazolamide, clobazam, lamotrigine, levetiracetam), and neurosteroid-based therapies (ganaxolone) are used in the treatment of catamenial epilepsy. Seizure control and menstrual cycle maintenance, measurement of the blood level of antiepileptic drugs before and after menstruation and adjustment of the drug dosage as required, intermittent benzodiazepine administration, acetazolamide, or hormonal treatments such as oral contraceptives during menstruation are among the treatment strategies for catamenial epilepsy

Convulsive syncope: a condition to be differentiated from epilepsy

The clinical presentation of epilepsy and syncope can be confusingly similar. We present a patient with reflex syncopal episodes that mimic seizures using video-EEG recordings. During the episodes, head/eye deviations, automatisms and dystonic movements, suggesting an epileptic seizure, were observed. The EEG revealed diffuse slow waves when the patient lost consciousness and complete cessation of the cerebral activity occurred when the dystonic movements started. On ECG recordings, bradycardia, followed by complete asystolia lasting for 40 seconds, was observed. We conclude that the differential diagnosis of epilepsy and syncope can be quite misleading and clinical features may not always be reliable. In cases where diagnosis is uncertain, circulatory and cardiac causes should always be kept in mind and video-EEG with simultaneous cardiac recordings are mandatory for accuracy of diagnosis. [ Published with video sequences

Convulsive syncope: a condition to be differentiated from epilepsy

The clinical presentation of epilepsy and syncope can be confusingly similar. We present a patient with reflex syncopal episodes that mimic seizures using video-EEG recordings. During the episodes, head/eye deviations, automatisms and dystonic movements, suggesting an epileptic seizure, were observed. The EEG revealed diffuse slow waves when the patient lost consciousness and complete cessation of the cerebral activity occurred when the dystonic movements started. On ECG recordings, bradycardia, followed by complete asystolia lasting for 40 seconds, was observed. We conclude that the differential diagnosis of epilepsy and syncope can be quite misleading and clinical features may not always be reliable. In cases where diagnosis is uncertain, circulatory and cardiac causes should always be kept in mind and video-EEG with simultaneous cardiac recordings are mandatory for accuracy of diagnosis. [ Published with video sequences

Outcomes of low-dose valproic acid treatment in patients with juvenile myoclonic epilepsy

Purpose: There are conflicting data regarding the drug dose that is sufficient to achieve seizure control as well as the parameters of seizure remission in juvenile myoclonic epilepsy (JME). The present study aimed to identify factors that contribute to seizure control in JME and to evaluate factors associated with JME remission and the efficacy of low-dose valproic acid (VPA) therapy

Misdiagnosis due to gastrointestinal symptoms in an adolescent with probable autonomic status epilepticus and Panayiotopoulos syndrome

Panayiotopoulos syndrome is a common benign epilepsy affecting otherwise healthy children that present with autonomic seizures, in which nausea, retching, and vomiting are particularly common and prominent. Because of the unusual ictal symptoms and lengthy manifestations, misdiagnosis is a common major problem. We describe a young girl with intractable and lengthy vomiting attacks, several admissions to hospitals, and extensive gastroenterological workup for several years from early childhood. On all previous occasions the diagnosis varied from psychosomatic disease, to functional dyspepsia. to cyclic vomiting syndrome. The possibility of autonomic epileptic seizures and Panayiotopoulos syndrome, though likely, was not considered. (c) 2009 Elsevier Inc. All rights reserved