Clinical Epilepsy Research Research Articles

Did pediatric drug development advance epilepsy treatment in young patients? It is time for new research goals.

Modern drugs have changed epilepsy, which affects people of all ages. However, for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people < 18 years of age drugs, including antiseizure medications (ASMs), need separate proof of efficacy and safety, overall called "pediatric drug development". For ASMs, this has changed to some degree. Authorities now accept that ASMs are effective in < 18 years as well, but they still require "extrapolation of efficacy," as if minors were another species. As a result, some of the pediatric clinical epilepsy research over the past decades was unnecessary. Even more importantly, this has hampered research on meaningful research goals. We do not need to confirm that ASMs work before as they do after the 18th birthday. Instead, we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs' uses. Herein we discuss how to proceed in this endeavor.

Health care utilization of Hispanic/Latino veterans with epilepsy: A national population-based study.

Hispanic/Latino people with epilepsy are a growing population that has been understudied in clinical epilepsy research. U.S. veterans are at a higher risk of epilepsy due to greater exposures including traumatic brain injury. Hispanic/LatinoVeterans with Epilepsy (HL-VWEs) represent a growing population; however the treatment utilization patterns of this population have been vastly understudied. HL-VWE were identified from administrative databases during fiscal year 2019. Variables compared between Hispanic and non-Hispanic VWEs included demographics, rurality, service era, utilization of clinical services/investigations, and service-connected injury. Chi-square and Student's t tests were used for comparisons. Among 56 556 VWEs, 3247 (5.7%) were HL. HL-VWEs were younger (59.2 vs 63.2 years; p < .01) and more commonly urban-dwelling (81.6% vs 63.2%, p < .01) compared to non-HL-VWEs. They were also more likely to have served in recent missions such as the Persian Gulf War and post- 9/11 wars (p < .01). HL-VWEs had a higher utilization of all neurology services examined including neurology clinic visits, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, electroencephalography (EEG), epilepsy monitoring, and comprehensive epilepsy care (p < .01 for all). HL-VWEs were more likely to visit an emergency room or have seizure-related hospitalizations (p < .01). HL-VWEs were more likely to have a service-connected disability greater or equal to 50% (p < .01). This study is one of the largest cohorts examining HL-VWEs. We found higher utilization of services in neurology, epilepsy, and neuroimaging by HL-VWEs. HL-VWE are younger, more commonly urban-dwelling, and more likely to have served during recent combat periods and have higher amounts of service-connected disability. Given that the proportion of Hispanic veterans is projected to rise over time, more research is needed to provide the best interventions and mitigate the long-term impact of epilepsy on this diverse patient group.

Intracranial electrophysiological recordings on a swine model of mesial temporal lobe epilepsy

To test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine. Intrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9-28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test-retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model. The KA dosage test suggested that a 10 μl (1.0 μg/μl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E- (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p < 0.05) compared to the baseline. But the E-showed no change or a decrease (in week 2, p = 0.43) compared to their baseline rate. The between-group comparison showed much higher HFO rates in E + vs. E - (F = 35, p < 0.01). The high ICC value [ICC (1, k) = 0.81, p < 0.05] quantified from the HFO rate suggested that this model had a stable measurement of HFOs during the four-week post-KA periods. This study measured intracranial electrophysiological activity in a swine model of KA-induced mesial temporal lobe epilepsy (mTLE). Using the clinical SEEG electrode, we distinguished abnormal EEG patterns in the swine brain. The high test-retest reliability of HFO rates in the post-KA period suggests the utility of this model for studying mechanisms of epileptogenesis. The use of swine may provide satisfactory translational value for clinical epilepsy research.

Central histaminergic signalling, neural excitability and epilepsy.

Epilepsy is a common neurological disorder characterized by repeated and spontaneous epileptic seizures and is not well controlled by current medication. Traditional theory suggests that epilepsy results from an imbalance of excitatory glutamate neurons and inhibitory GABAergic neurons. However, new evidence from clinical and preclinical research suggests that histamine in the CNS plays an important role in the modulation of neural excitability and in the pathogenesis of epilepsy. Many histamine receptor ligands have achieved curative effects in animal epilepsy models, among which the histamine H3 receptor antagonist pitolisant has shown anti-epileptic effects in clinical trials. Recent studies, therefore, have focused on the potential action of histamine receptors to control and treat epilepsy. In this review, we summarize the findings from animal and clinical epilepsy research on the role of brain histamine and its receptors. We also identify current gaps in the research and suggest where further studies are most needed.

Publications pattern of clinical epilepsy research in Saudi Arabia

Objective:To assess the progress in the field clinical epilepsy in Saudi Arabia, by analyzing in depth the research output productivity and publication pattern, and to identify the current situation of epilepsy research and offer solutions.Method:Literature search strategy was designed to retrieve accessible articles that are related to epilepsy utilizing PubMed, Google Scholar, and Embase. The retrieved articles were analyzed with several parameters, then evaluated using Oxford Center of Evidence Based Medicine level of evidence scale.Results:Of all identified articles, 90 were conducted in Kingdom of Saudi Arabia and therefore were included. The included articles had a frequency of only 3.5 publications per year, and growth of 24.4% between the periods of 1990-2003 and 2004-2016. Only 13.3% of the articles were related to surgical epilepsy but the majority (86.7%) were related to medical epilepsy. Many articles (53.3%) were level III studies. The most common study design was retrospective studies in 35.6%, and the citations number ranged from 1–289 (Mean=7).Conclusion:Pattern of publications in clinical epilepsy researches revealed a slow growth rate in the frequency and a lower significance in the quality throughout the past 26 years. Active institutional and national promotion of clinical research is needed to help assess and therefore improve the quality of the provided epilepsy services.

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine.

Electrocortical source imaging of intracranial EEG data in epilepsy.

Here we report first results of numerical methods for modeling the dynamic structure and evolution of epileptic seizure activity in an intracranial subdural electrode recording from a patient with partial refractory epilepsy. A 16-min dataset containing two seizures was decomposed using up to five competing adaptive mixture independent component analysis (AMICA) models. Multiple models modeled early or late ictal, or pre- or post-ictal periods in the data, respectively. To localize sources, a realistic Boundary Element Method (BEM) head model was constructed for the patient with custom open skull and plastic (non-conductive) electrode holder features. Source localization was performed using Sparse Bayesian Learning (SBL) on a dictionary of overlapping multi-scale cortical patches constructed from 80,130 dipoles in gray matter perpendicular to the cortical surface. Remaining mutual information among seizure-model AMICA components was dominated by two dependent component subspaces with largely contiguous source domains localized to superior frontal gyrus and precentral gyrus; these accounted for most of the ictal activity. Similar though much weaker dependent subspaces were also revealed in pre-ictal data by the associated AMICA model. Electrocortical source imaging appears promising both for clinical epilepsy research and for basic cognitive neuroscience research using volunteer patients who must undergo invasive monitoring for medical purposes.

Research priorities in epilepsy for the next decade—A representative view of the European scientific community: Summary of the ILAE Epilepsy Research Workshop, Brussels, 17–18 January 2008

Research priorities in epilepsy for the next decade—A representative view of the European scientific community: Summary of the ILAE Epilepsy Research Workshop, Brussels, 17–18 January 2008

Design and applications of a multimodality image data warehouse framework.

A comprehensive data warehouse framework is needed, which encompasses imaging and non-imaging information in supporting disease management and research. The authors propose such a framework, describe general design principles and system architecture, and illustrate a multimodality neuroimaging data warehouse system implemented for clinical epilepsy research. The data warehouse system is built on top of a picture archiving and communication system (PACS) environment and applies an iterative object-oriented analysis and design (OOAD) approach and recognized data interface and design standards. The implementation is based on a Java CORBA (Common Object Request Broker Architecture) and Web-based architecture that separates the graphical user interface presentation, data warehouse business services, data staging area, and backend source systems into distinct software layers. To illustrate the practicality of the data warehouse system, the authors describe two distinct biomedical applications--namely, clinical diagnostic workup of multimodality neuroimaging cases and research data analysis and decision threshold on seizure foci lateralization. The image data warehouse framework can be modified and generalized for new application domains.

Future aspects of epilepsy research.

This contribution in honour of Prof. Gerhard Pendl first reviews some recent studies on resected tissue, migrational disorders, and Rasmussen's Syndrome. These areas of basic research profit from recent advances of molecular biology and genetics. On the clinical side, some studies dealing with proton magnetic resonance spectroscopy are reviewed. In order to highlight the progress in clinical epilepsy research using modern methods of structural and functional imaging, functional outcome prediction is also reviewed. This kind of advanced clinical research is dealt with by discussing risk factor assessment associated with postsurgical decrements in memory. With regard to motor functions, we compare the yield of functional MR and intraoperative cortical stimulation in patients with lesions in or close to the Rolandic cortex. Progress in the field of advanced EEG analysis is reviewed in the context of "seizure prediction" and cognitive event-related potentials. Finally some of the new epilepsy treatment options, such as Gamma Knife treatment, where Prof. Pendl's group made pioneering contributions, are dealt with.

Semistructured Interview for Seizure Classification: Agreement with Physicians' Diagnoses

A semi-structured interview was developed for classification of seizures in accordance with the 1981 International League Against Epilepsy (ILAE) criteria. The interview was administered over the telephone by trained lay interviewers. Interview-based diagnoses for 50 patients were compared with independent diagnoses by neurologists who also use the ILAE system for seizure classification. Interview diagnoses agreed with those of physicians for broad seizure-type classifications (i.e., partial vs. generalized onset) in 88% of patients and for detailed combinations of seizure type in 64% of patients. Nonchance agreement between the two sources, assessed by the kappa statistic, was excellent for any partial onset (kappa = 0.83), secondarily generalized (kappa = 0.81), and primary generalized tonic-clonic (kappa = 0.76) seizures. Agreement was fair to good for any generalized onset (kappa = 0.70), simple partial (kappa = 0.56), complex partial (kappa = 0.54), and generalized nonconvulsive (kappa = 0.56) seizures. Sensitivity ranged from 0.60 to 1.0 for partial onset seizures, and from 0.43 to 0.67 for generalized onset seizures. Specificity ranged from 0.60 to 0.87 for partial onset seizures, and was 1.0 for generalized onset seizures. Positive predictive value was 0.95 for any partial onset and 1.0 for any generalized onset seizure. These results suggest that this interview can produce accurate diagnoses of major seizure categories. Use of this instrument for clinical epilepsy research should facilitate conduct of large studies at a significant saving of both time and money.

Recognizing and Classifying Epileptic Seizures and Epileptic Syndromes

The appropriate diagnosis of the patient with epilepsy is first dependent on a determination of the type of seizure. When the type of seizure has been determined, consideration must be given to the nature of the epileptic syndrome, including concerns regarding the etiology of the attacks. The gradual evolution of the various classification schemes of epileptic seizures and epileptic syndromes complicates the task of the physician but also affords evidence of the dynamism extant in clinical epilepsy research. Intensive monitoring will assist not only in the diagnosis of the individual patient but also in the long-term re-evaluation and revision of the empirical classifications.