Demonstration project on epilepsy in Brazil - WHO/ILAE/IBE Global Campaign Against Epilepsy - A foreword

In 2002, ASPE (Assistência à Saúde de Pacientes com Epilepsia)* initiated an Epilepsy Demonstration Project (DP) in Brazil as part of the Global Campaign Against Epilepsy "Epilepsy out of the Shadows", led by the World Health Organization (WHO), the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)1-4. Demonstration Projects have been carried out in several countries and their main aim is to develop treatment models for people with epilepsy in primary health care settings, improving the quality of life of people with epilepsy and their families5-9. The project in Brazil has targeted areas in Campinas and São José do Rio Preto municipalities, both in São Paulo State, in Southeastern region8. A task force has been established to assess strategies to expand this nationwide. The DP was carried out in six phases as shown in Figure 1. The Brazilian DP was officially closed during the IV Workshop of the WHO/ILAE/IBE Global Campaign Against Epilepsy "Epilepsy out of the Shadows", held on May 4-5th 2006, in Campinas. The workshop reviewed the results of the project and discussed the establishment of a National Epilepsy Policy. This supplement presents some results from all phases of the Brazilian DP which were discussed during the Workshop. In brief, we believe that the DP had an impact in our society and brought a new perspective on epilepsy. Awareness campaigns are now carried out on September 9th (Epilepsy Awareness Day) annually in many sites around the country. Regulations and Bills related to epilepsy have been proposed in several regions. Epilepsy has been officially adopted as a theme to be considered in elementary education by the Ministry of Education. Currently, a National Epilepsy Programme, endorsed by the main Brazilian non-governmental organizations in the field of epilepsy, is under review at the Ministry of Health. We hope that this will benefit some of the many people with epilepsy in the country and will eventually bring epilepsy out of the shadows in Brazil

Reduced neurosteroid potentiation of GABAA receptors in epilepsy and depolarized hippocampal neurons

OBJECTIVE: Neurosteroids regulate neuronal excitability by potentiating γ-aminobutyric acid type-A receptors (GABARs). In animal models of temporal lobe epilepsy, the neurosteroid sensitivity of GABARs is diminished and GABAR subunit composition is altered. We tested whether similar changes occur in patients with epilepsy and if depolarization-induced increases in neuronal activity can replicate this effect. METHODS: We determined GABAR α4 subunit expression in cortical tissue resected from pediatric epilepsy patients. Modulation of human GABARs by allopregnanolone and Ro15-4513 was measured in Xenopus oocytes using whole-cell patch clamp. To extend the findings obtained using tissue from epilepsy patients, we evaluated GABAR expression and modulation by allopregnanolone and Ro15-4513 in cultured rat hippocampal neurons exposed to high extracellular potassium (HK) to increase neuronal activity. RESULTS: Expression of α4 subunits was increased in pediatric cortical epilepsy specimens encompassing multiple pathologies. The potentiation of GABA-evoked currents by the neurosteroid allopregnanolone was decreased in Xenopus oocytes expressing GABARs isolated from epilepsy patients. Furthermore, receptors isolated from epilepsy but not control tissue were sensitive to potentiation by Ro15-4513, indicating higher expression of α INTERPRETATION: These findings suggest that seizure activity-induced upregulation of

Structural imaging biomarkers of sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies

Training medical students to improve the management of people with epilepsy

Purpose: To evaluate the knowledge, attitude and perception of medical students prior to and after a training course about epilepsy. Methods: We used a KAP questionnaire with sixty-one questions which assesses knowledge, attitude and practice of epilepsy. Questionnaires were completed by 185 medical students, before and after epilepsy training. We compared the answers to see whether the lecture had changed the knowledge, attitude and practice in epilepsy. Results: One hundred and six students completed the questionnaire before an eight hour course on epilepsy and 79 students completed the questionnaire one year after the course. Comparison of the knowledge scores prior to (mean=53.9, standard deviation=11.4) and after the course (mean=63.8, standard deviation=11.9) showed that students had improved knowledge after the course (t-test=5.6, p < 0.001). Discussion: Training course on epilepsy for medical students can promote improvement in the knowledge, attitudes and perception regarding epilepsy, which is maintained one year later. These results highlight the importance of continuous educational programs within the Medical Curriculum

Italian Wikipedia and epilepsy: an infodemiological study of online information-seeking behavior

Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017. We compared the views of the article on epilepsy with those of articles focusing on Alzheimer's disease, migraine, multiple sclerosis, syncope, and stroke and adjusted all results for crude disease prevalence. With the only exception of the article on multiple sclerosis, the adjusted views for the Italian Wikipedia article on epilepsy were higher than those for the other neurological disorders. The most viewed articles on seizure type were devoted to tonic-clonic seizure, typical absence seizure, tonic convulsive seizures, and clonic convulsive seizures. The most frequently accessed articles on epilepsy syndromes were about temporal lobe epilepsy and Lennox-Gastaut syndrome. The most frequently viewed articles on AEDs were devoted to valproic acid, carbamazepine, and levetiracetam. Wikipedia searches seem to mirror patients' fears and worries about epilepsy more than its actual epidemiology. The ultimate reasons for searching online remain unknown. Epileptologists and epilepsy scientific societies should make greater efforts to work jointly with Wikipedia to convey more accurate and up-to-date information about epilepsy

Dissecting the genetic basis of comorbid epilepsy phenotypes in neurodevelopmental disorders.

BACKGROUND:Neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability, developmental disability, and epilepsy are characterized by abnormal brain development that may affect cognition, learning, behavior, and motor skills. High co-occurrence (comorbidity) of NDDs indicates a shared, underlying biological mechanism. The genetic heterogeneity and overlap observed in NDDs make it difficult to identify the genetic causes of specific clinical symptoms, such as seizures. METHODS:We present a computational method, MAGI-S, to discover modules or groups of highly connected genes that together potentially perform a similar biological function. MAGI-S integrates protein-protein interaction and co-expression networks to form modules centered around the selection of a single "seed" gene, yielding modules consisting of genes that are highly co-expressed with the seed gene. We aim to dissect the epilepsy phenotype from a general NDD phenotype by providing MAGI-S with high confidence NDD seed genes with varying degrees of association with epilepsy, and we assess the enrichment of de novo mutation, NDD-associated genes, and relevant biological function of constructed modules. RESULTS:The newly identified modules account for the increased rate of de novo non-synonymous mutations in autism, intellectual disability, developmental disability, and epilepsy, and enrichment of copy number variations (CNVs) in developmental disability. We also observed that modules seeded with genes strongly associated with epilepsy tend to have a higher association with epilepsy phenotypes than modules seeded at other neurodevelopmental disorder genes. Modules seeded with genes strongly associated with epilepsy (e.g., SCN1A, GABRA1, and KCNB1) are significantly associated with synaptic transmission, long-term potentiation, and calcium signaling pathways. On the other hand, modules found with seed genes that are not associated or weakly associated with epilepsy are mostly involved with RNA regulation and chromatin remodeling. CONCLUSIONS:In summary, our method identifies modules enriched with de novo non-synonymous mutations and can capture specific networks that underlie the epilepsy phenotype and display distinct enrichment in relevant biological processes. MAGI-S is available at https://github.com/jchow32/magi-s

Ictal kissing: occurrence and etiology.

Ictal kissing is a rare semiological manifestation in patients with epilepsy. We tried to estimate its occurrence and characterize the underlying etiology. We retrospectively reviewed all video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004-2015) for the occurrence of the term kiss . We then searched the electronic database PubMed on September 21, 2016 using the following search terms in the English language: ictal OR seizure OR epilepsy AND kiss OR kissing . Relevant original studies were included. During the study period, 5133 patients were investigated in our epilepsy monitoring unit. One patient (0.02%) had one episode of documented ictal kissing. He had drug-resistant right mesial temporal lobe epilepsy. In total, five studies met the criteria for inclusion in the review. These studies described nine patients with drug-resistant focal epilepsy and ictal kissing behavior. Six out of ten patients with ictal kissing had hippocampal sclerosis. We add to the literature on ictal kissing by providing additional information on its frequency and etiology. The most common underlying etiology for ictal kissing is hippocampal sclerosis. However, this semiological ictal phenomenon is not pathognomonic for any etiology or localization

Effect of neurostimulation on cognition and mood in refractory epilepsy.

Epilepsy is a common, debilitating neurological disorder characterized by recurrent seizures. Mood disorders and cognitive deficits are common comorbidities in epilepsy that, like seizures, profoundly influence quality of life and can be difficult to treat. For patients with refractory epilepsy who are not candidates for resection, neurostimulation, the electrical modulation of epileptogenic brain tissue, is an emerging treatment alternative. Several forms of neurostimulation are currently available, and therapy selection hinges on relative efficacy for seizure control and amelioration of neuropsychiatric comorbidities. Here, we review the current evidence for how invasive and noninvasive neurostimulation therapies affect mood and cognition in persons with epilepsy. Invasive therapies include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Noninvasive therapies include trigeminal nerve stimulation (TNS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, current evidence supports stable cognition and mood with all neurostimulation therapies, although there is some evidence that cognition and mood may improve with invasive forms of neurostimulation. More research is required to optimize the effects of neurostimulation for improvements in cognition and mood

Epilepsy beyond seizures: a review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs

Epilepsy is one of the most common chronic neurological conditions in the dog, estimated to affect 0.6 to 0.75 per cent of dogs. Owners of dogs with epilepsy have previously indicated that their dog's quality of life (QoL) is of greatest importance to them above seizure frequency; however, much of the research into canine epilepsy to date has focussed on seizure frequency, and how to reduce it via antiepileptic drug treatment. In people, the impact of epilepsy upon QoL has been widely studied, exploring not only its impact on physical health, but also the psychological health and cognitive capabilities of affected individuals. This paper reviews the existing literature on canine epilepsy, identifies potential threats to QoL, and draws parallels from human epilepsy research. We suggest that canine epilepsy poses threats to both quality and quantity of life, with treatment interventions posing a fine balance of potential benefits and harms to the patient. At present, little is known about the neurobehavioural, emotional and cognitive effects of epilepsy upon affected dogs. Further studies are needed to establish the extent to which unknown QoL-inhibiting comorbidities exist in the dog, in order to avoid their undertreatment, and to objectively quantify the effects of epilepsy on canine QoL