Understanding Of Epilepsy Research Articles

PatientsLikeMe® Online Epilepsy Community: Patient characteristics and predictors of poor health-related quality of life.

The online PatientsLikeMe® Epilepsy Community allows patients with epilepsy to record, monitor, and share their demographic, disease, and treatment characteristics, providing valuable insights into patient perceptions and understanding of epilepsy. The objective of this retrospective analysis was to characterize the profile of users and their disease and identify factors predictive of poor health-related quality of life (HRQoL), while assessing the platform's potential in providing patient-reported data for research purposes. Data recorded (January 2010-November 2011) by Epilepsy Community members, with an epilepsy diagnosis and who reported >1 seizure, included the following: sociodemographic and disease characteristics, treatments, symptoms, side effects perceived as medication-related, seizure occurrence, and standardized questionnaires (Quality of Life in Epilepsy Inventory [QOLIE-31/P], EuroQoL 5-Dimensions Scale, 3 Levels [EQ-5D-3L], and Hospital Anxiety and Depression Scale [HADS]). Univariate and multivariate logistic regressions were conducted to identify predictors of poor HRQoL. During the study period, the Epilepsy Community comprised 3073 patients, of whom 71.5% were female, had a mean age of 37.8years, and had a mean epilepsy duration of 17.7years. The most frequently reported moderate/severe symptoms (n=2135) included memory problems (60.2%), problems concentrating (53.8%), and fatigue (50.0%). Medication-related side effects (n=639) included somnolence (23.2%), fatigue (17.2%), and memory impairment (13.8%). The QOLIE-31/P scores (n=1121) were significantly worse in patients who experienced a recent seizure. For QOLIE-31/P, highly predictive factors for poor HRQoL included the following: mild/moderate problems concentrating, depression, memory problems, treatment side effects, occurrence of tonic-clonic seizures, and epilepsy duration ≤1year. For EQ-5D-3L, highly predictive factors for poor HRQoL included the following: pain, depression, and comorbidities. Patients on newer AEDs were less likely to report poor HRQoL (QOLIE-31/P). These findings move further towards supporting the feasibility and usefulness of collecting real-world, anonymized data recorded by patients online. The data provide insights into factors impacting HRQoL, suggesting that a holistic treatment approach beyond seizure control should be considered in epilepsy.

Total Variation Based Multi Feature Model for Epilepsy Detection Using Support Vector Machine

ABSTRACTEpilepsy is a critical brain disease which occurs primarily based on changes or connectivity issues between two neurons. Electroencephalography (EEG) is an efficient modality for capturing brain signals with respect to stimuli. Total variation (TV) is an energy based feature which helps to discriminate epilepsy from normal pattern. This paper proposes an efficient epileptic detection system based on TV model. Existing methods use single feature for classification, whereas, combination of multiple relevant features helps for better understanding of epilepsy. This paper also discusses combined multi feature model with TV for efficient detection and classification of EEG signal subbands (gamma, beta, alpha, theta, and delta) using support vector machine. Results show 100% delta band based classification accuracy for combination of features such as TV and sample entropy. This research also shows that combination of multi features such as, Shannon, spectral, TV, and linear predictor coefficient gives good classification accuracy for most of the subbands.

WITHDRAWN: Psychological treatments for epilepsy.

BACKGROUND: Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. OBJECTIVES: To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency or leads to a better quality of life (QOL), or both. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (11 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2010) and MEDLINE (1948 to December 2010). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. MAIN RESULTS: We found three small trials (total 50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency.Two trials found cognitive behavioural therapy (CBT) to be effective in reducing depression among people with epilepsy and a depressed affect, whilst another did not. Two trials of CBT found improvements in QOL scores. One trial of group cognitive therapy found no significant effect on seizure frequency while another trial found a statistically significant reduction in seizure frequency as well as seizure index (product of seizure frequency and seizure duration in seconds) among participants treated with CBT.One small trial compared CBT with yoga and found similar rates of seizure freedom and 50% responder rates at the end of one year. Compared to pretest scores, the CBT group showed an improvement in the World Health Organization quality of life instrument, short version (WHO QOL-BREF) (P ≤ 0.01) while the yoga group had an improvement in their QOL according to the satisfaction with life scale (SWLS) (P ≤ 0.05).Two trials of combined relaxation and behaviour therapy, one of electroencephalographic (EEG) bio-feedback and four of educational interventions did not provide sufficient information to assess their effects on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency.Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve cognitive and motor functions in individuals with the greatest seizure reduction. Educational interventions were found to be beneficial in improving knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies.Two trials investigated the effects of a self management program on QOL measures. One found no significant differences in overall QOL except for an improvement in the QOL in persons with epilepsy (QOLIE-89) role limitations - emotional score. The other study found no significant benefits in any of the outcomes studied except for more positive attitudes about the outcomes associated with taking medications. AUTHORS' CONCLUSIONS: In view of methodological deficiencies and the limited number of individuals studied, we have found no reliable evidence to support the use of psychological treatments and further trials are needed. Since the last version of this review, none of the new relevant studies have provided additional information to change the conclusions. Language: en

Epilepsy: Is there hope?

Epilepsy is a highly prevalent chronic neurologic disorder and leads to social, behavioural, health and economic consequences. ‘Treatment gap’ varies from 10 per cent in developed countries to 75 per cent in low-income countries. Stigma and discrimination related to epilepsy are prevalent worldwide. Electroencephalography (EEG) is considered the most important tool for evaluating the patient with epilepsy. Video-EEG monitoring is an important tool for confirming the seizure type and estimating the epileptogenic zone in the brain. Neuroimaging evaluation is important to determine the aetiology of the epilepsies. Genetic testing has increased the probability of identifying the causes of some types of epilepsies. Epilepsy can be treated in an affordable way with low-cost medications. Refractory epilepsies occur in approximately one-third of recently diagnosed patients with epilepsy. For this group of patients, there are options of surgical treatment, diets and neurostimulation to improve seizure control and quality of life. In poorly organized societies, there is a lack of prioritization of epilepsy in national health policies, limited resources for trained personnel and a shortage of basic antiepileptic medications. There is evidence of improvement in the understanding of epilepsy and a clear progress in the management of epileptic seizures in recent times.

Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI

Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches.Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as ‘ON’ blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG.BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas.In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum.

Public attitudes and knowledge toward epilepsy in ismailia governorate

Objective This study was conducted to find out knowledge and attitudes toward epilepsy among a sample of people living in Ismailia governorate in Egypt. Patients and methods A cross-sectional survey was conducted by using a face-to-face interview; 840 respondents were included, among whom 420 were from an urban area − Sheikh Zayed district − and 420 were from a rural area − Abu-Sultan village. The survey instrument was a 26-item questionnaire in Arabic form that was designed to evaluate knowledge and attitudes with respect to epilepsy. Results Of the 840 respondents, 91.2% had heard of or read about epilepsy, 24.8% knew someone with epilepsy, and 30.7% had witnessed a seizure. According to the respondents, the main cause of epilepsy was psychological disease (63.7%), followed by evil spirits (Jinn) (49.5%) and a form of insanity (47.4%). Approximately 70% of the respondents (70.7%) agreed that the intelligence of an epileptic patient is below average. About three-quarters of the respondents (74.6%) believed that epilepsy cannot be cured. More than 50% of the respondents believed that an epileptic patient could not get married (57.5%), nor have a child (58.7%). About 80% of the respondents refused to marry an epileptic patient (77.7%) or to marry their child to an epileptic patient (83.0%). Fifty-nine percent of the respondents would not offer a job to a person with epilepsy, and 41.1% refused working with an epileptic patients. The negative attitudes toward an epileptic person were more common among rural, female, less-educated, and elderly respondents. Conclusion Public perception of epilepsy is lacked and needs attention. The study revealed that practices and knowledge toward epilepsy were limited, especially with respect to epilepsy’s cause, manifestation, and management. Continuing effective educational interventions would be needed to improve the appropriate understanding of epilepsy, and to ameliorate the social discrimination and misconceptions against epilepsy.

Advancing epilepsy treatment through personalized genetic zebrafish models.

With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts.

Molecular genetics of idiopathic generalized epilepsies

Most of idiopathic generalized epilepsies (IGEs) follow a complex genetic inheritance, with only a few rare, large families presenting with an autosomal dominant inheritance. During the past 20 years many genes associated with IGE were discovered, most of which encode ion channels or neurotransmitter receptors, but the question about the total number of existing genes is still unanswered. Novel technologies have resulted in the expansion of knowledge of normal variations in the human genome and enabled progress in the area of the molecular basis of IGE. New generation sequencing has become affordable and exom sequencing well established standard technology. The main result achieved was identification of copy number variations associated with IGE. But these rare variants could not be identified with genome-wide significance suggesting that genetic architecture of IGE is much more heterogeneous. The other achievement was identification of common genetic variants or Single Nucleotide Polymorphisms associated with IGE through genome-wide association studies, but not only in genes encoding the ion channels, moving the field of IGE genetics beyond the channelopathies. True measure of the success of these researches will be the possibility to translate genetic discoveries into a deeper mechanistic understanding of epilepsy in order to develop effective therapy.

A review of 'medical' knowledge of epilepsy amongst isiZulu-speaking patients at a regional hospital in KwaZulu-Natal.

BackgroundEpilepsy is a common disorder in South Africa and the literature indicates that many patients do not access treatment. The reasons are complex and include a poor knowledge about causes, symptoms, diagnosis and treatment (medical knowledge). This study aimed to assess the medical knowledge of isiZulu-speaking people with epilepsy (PWE) who attend a combination regional and district hospital in the eThekwini district in KwaZulu-Natal Province.MethodThis was a prospective, cross-sectional, descriptive study. Data were collected using a validated data collection tool for assessing the medical knowledge of PWE and analysed descriptively.ResultsThe questionnaires were completed by 199 PWE, with the general level of schooling being low and half being unemployed. Knowledge around causes, symptoms, diagnosis and treatments was good, but there were significant gaps in knowledge that may affect morbidity and mortality.DiscussionThe findings will serve as a useful guide to develop both preventive and educational interventions to enhance knowledge around the causes and treatment of epilepsy in this population. It is important that such interventions also consider family and healthcare providers.ConclusionThere were considerable gaps in the medical knowledge of isiZulu-speaking PWE's, indicating the need for an educational intervention to improve their understanding of epilepsy. Further research is needed-using a range of tools to ensure that the data is reliable and valid–if the results are to be generalisable to the rest of the province and South Africa.

Responding to the needs of people with intellectual disability and epilepsy: Shared priorities

The primary objective of this paper is to present recent advances in our understanding of epilepsy and to discuss the implications of these advances to optimise health and social care supports for people with epilepsy and intellectual disability (ID). The high prevalence and impact of epilepsy among people with ID has been well described. Similarly well described are the considerable barriers epilepsy imposes on people with ID experiencing a fulfilling, prolonged, and healthy life. Recent advances in our understanding of epilepsy may reduce these barriers, in particular approaches to reduce sudden unexpected death in epilepsy, to reduce epilepsy-related hospitalisation, and to improve the social experience of people with ID. We propose a number of draft actions in response to recent developments in each of these three areas.

CE

As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.

The Role of Culture in Temporal Lobe Epilepsy and Criminality: A Case Series from Malaysia

Culture still plays an important role in the understanding of epilepsy among non-western developing nations. As a result, many patients are left undiagnosed and untreated until a serious incident such as an accident or a crime occurs, leading to medical attention. This case series gives two examples of patients who were sent for forensic psychiatric assessment after allegedly committing a crime in Malaysia. Both had temporal lobe epilepsy but diagnoses were delayed because of cultural beliefs, and ultimately they were acquitted using insanity as a defence. Implications from these cases include the need for improving public awareness of temporal lobe epilepsy as a treatable medical condition in view of the prevalent cultural belief of ‘possession states’, and the need for more streamlined and precise forensic services that would include an automatism defence.

CE: Epilepsy Update, Part 1: Refining Our Understanding of a Complex Disease.

Epilepsy is a serious, common neurologic disease that affects people of all ages. As underscored in the 2012 Institute of Medicine report Epilepsy Across the Spectrum: Promoting Health and Understanding, the millions of people living with epilepsy in the United States face the challenges of seeking out high-quality, coordinated health care and community services; overcoming epilepsy misinformation and stigma; and finding understanding and support in their communities. This article, the first in a two-part series, discusses new research that has increased our understanding of epilepsy's etiology and pathophysiology, new definitions that are changing the ways we evaluate and treat this disease, conditions that frequently present with epilepsy, and psychosocial challenges faced by people with epilepsy. Part 2, which will appear in next month's issue, reviews comprehensive nursing care and evidence-based treatment for epilepsy and presents resources for people with epilepsy and their families.

A brain slice experimental model to study the generation and the propagation of focally-induced epileptiform activity

The early cellular events that in a brain network lead to seizure generation and govern seizure propagation are probably based on different cellular mechanisms. Experimental models in which these events can be separately studied would contribute to improve our understanding of epilepsy. We recently described an in vitro model in entorhinal cortex slices from young rats in which focal seizure-like discharges (SLDs) can be induced in spatially defined regions and at predictable times by local NMDA applications performed in the presence of 4-amimopyridine (4-AP) and low extracellular Mg2+. Through the use of single-dual cell patch-clamp and field potential recordings, and Ca2+ imaging from large ensembles of neurons, interneurons and astrocytes, we here extend this model to entorhinal and temporal cortex slices of rat and mouse brain, providing evidence that multiple SLDs exhibiting the typical tonic–clonic discharge pattern can be also evoked in these cortical regions by successive NMDA applications. Importantly, the temporal cortex is more accessible to viral vector injections than the entorhinal cortex: this makes it feasible in the former region the selective expression in inhibitory interneurons or principal neurons of genetically encoded Ca2+ indicators (GECI) or light-gated opsins. In this model, an optogenetic approach allows to activate specific neuronal types at spatially defined locations, i.e., the focus or the propagating region, and at precise time, i.e., before or during SLD. The NMDA/4-AP model can, therefore, represent a valuable tool to gain insights into the role of specific cell populations in seizure generation, propagation and cessation.

Commentary: international epilepsy day.

Seizure disorders are widely misunderstood by the general population, yet most people know someone who has been diagnosed with epilepsy. Treatment and quality of life can be enhanced through improved awareness and understanding of epilepsy—or “the epilepsies”—by those affected by recurrent seizures and by their friends, family, health care providers, teachers, colleagues at work, and strangers met in restaurants or on sidewalks. Epilepsy does not respect international borders. To this end, a day to raise awareness of epilepsy around the world can have meaningful impact. The tuberous sclerosis complex (TSC) community understands the consequences of misunderstanding and the impact of increased understanding. TSC is a rare genetic disorder affecting roughly 50,000 individuals in the United States and 1 million worldwide. TSC causes nonmalignant tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin, and lungs. The aspects of TSC that most strongly impact quality of life are generally associated with the brain: seizures, developmental delay, intellectual disability, and autism. Thus, TSC can be considered one of “the epilepsies” in the sense that approximately 85% of those affected by TSC will experience seizures during their lifetime—most commonly in early childhood when the developmental consequences can be severe. Everyone with TSC is affected somewhat differently, much in the way that no two people with epilepsy have identical experiences, which makes it all the more important to make others aware of how such a disorder does or does not affect one's life. Since 2012, TSC organizations around the world have celebrated TSC Global Awareness Day annually on May 15. Through various activities on social media, a radio media tour, a Congressional briefing, face-to-face gatherings, and lighting Niagara Falls “TSC blue,” more people become aware of TSC each year. Equally important, those affected by TSC and their loved ones have become more empowered to advocate for themselves. There is no single best way to care for someone with TSC; not everyone has access to the same types of medical care, and not everyone is affected by the disorder in the same way. TSC Global Awareness Day brings basic education to the general population and provides those affected by TSC with specific information to help them advocate for themselves and their loved ones in their own way, and in their own language, to best meet their own needs. An International, Global, or World Epilepsy Day to empower those with epilepsy and to educate the global population can make a difference. The epilepsies know no calendars, no religious traditions, and no languages. The choice of date and title should be made rapidly by representatives of the major international epilepsy organizations so that the educational process can begin as soon as possible. The TSC community is eager to participate in a worldwide day for epilepsy education and advocacy to improve the lives of those affected by seizure disorders everywhere. I have no conflicts of interest to disclose. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Steve Roberds is Chief Scientific Officer, Tuberous Sclerosis Alliance.

Ellen R. Grass Lecture: Extraordinary EEG

ABSTRACT.The electroencephalogram (EEG) is a unique measure of the electrical function of the brain. Cerebral sources of EEG potentials expressed by the human brain have been recorded on the surface of the scalp for almost 100 years. With the advances in digital technology, present day EEG has evolved to include specialized techniques that offer new capabilities never realized before. Refined intracranial recording techniques and multi-channel systems now permit access to regions of the brain that have previously been off limits to conventional EEG recording. Extraordinary biorhythms beyond 1 to 35 Hz that have been typically used in routine EEG are now exploring extreme band-widths that may disclose epileptogenic regions and their yield causative networks involved in generating seizures. These spectral frequencies ranging from infraslow activity to high frequency oscillations have far reaching implications for people with uncontrolled seizures. Micro-EEG recordings are now shedding light on electrophysiological recordings of single columns of neuronal activity in clinical research expanding our understanding of epilepsy to the cellular level. Beyond the routine application of EEG analyzed for clinical use, special EEG techniques now provide a window to reveal detailed information about the seizure onset zone in patients with epilepsy, as well as advance our understanding of the functional processes of the brain itself. These breakthroughs will allow EEG-based treatment alternatives.

Childhood Epilepsy: An Update on Diagnosis and Management

Within the past few years there is a rapid expansion in our understanding of epilepsy. The development of new anti-epileptic drugs and refinements to epilepsy surgery are widening the therapeutic options for epilepsy. In addition, the classification of the epilepsies continues to evolve based on an increased understanding of the molecular genetics of the condition and this includes the recognition of possible novel epilepsy syndromes. This review considers some of these exciting developments, as well as addressing the essential features of the diagnosis, investigations, management and impact of epilepsy in childhood.

Changing name of epilepsy in Korea; cerebroelectric disorder (noi‐jeon‐jeung,뇌전증,腦電症)

Public misconception of epilepsy may lead to significant stigma to the disease itself, thereby causing impaired quality of life in people with epilepsy. Traditionally, epilepsy has been considered to be the consequence of evanescent spiritual forces, and even demonic possession (in many countries). The names of epilepsy in some East Asian countries originated from China, and include madness in their meaning. We recently changed the Korean name of epilepsy, gan-jil (간질, : a crazy, convulsive disease having meaning similar to ), to a neutral and scientifically explainable name: noi-jeon-jeung (뇌전증; ; cerebroelectric disorder). We expect that changing the stigmatized name of epilepsy to a neutral and scientific term with the meaning of cerebroelectric disorder will reduce the social stigma by understanding of epilepsy as one of the neurologic disorders.

Chapter 3 - Mutant GABAA receptor subunits in genetic (idiopathic) epilepsy

The γ-aminobutyric acid receptor type A (GABAA receptor) is a ligand-gated chloride channel that mediates major inhibitory functions in the central nervous system. GABAA receptors function mainly as pentamers containing α, β, and either γ or δ subunits. A number of antiepileptic drugs have agonistic effects on GABAA receptors. Hence, dysfunctions of GABAA receptors have been postulated to play important roles in the etiology of epilepsy. In fact, mutations or genetic variations of the genes encoding the α1, α6, β2, β3, γ2, or δ subunits (GABRA1, GABRA6, GABRB2, GABRB3, GABRG2, and GABRD, respectively) have been associated with human epilepsy, both with and without febrile seizures. Epilepsy resulting from mutations is commonly one of following, genetic (idiopathic) generalized epilepsy (e.g., juvenile myoclonic epilepsy), childhood absence epilepsy, genetic epilepsy with febrile seizures, or Dravet syndrome. Recently, mutations of GABRA1, GABRB2, and GABRB3 were associated with infantile spasms and Lennox-Gastaut syndrome. These mutations compromise hyperpolarization through GABAA receptors, which is believed to cause seizures. Interestingly, most of the insufficiencies are not caused by receptor gating abnormalities, but by complex mechanisms, including endoplasmic reticulum (ER)-associated degradation, nonsense-mediated mRNA decay, intracellular trafficking defects, and ER stress. Thus, GABAA receptor subunit mutations are now thought to participate in the pathomechanisms of epilepsy, and an improved understanding of these mutations should facilitate our understanding of epilepsy and the development of new therapies.

Systems biology of human epilepsy applied to patients with brain tumors

Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many "systems" in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both.