Day 2 :
Keynote Forum
Tatiana Falcone
Cleveland Clinic, USA
Keynote: Suicide risk in patients with Epilepsy
Time : 10:00-10:40
Biography:
Tatiana Falcone has graduated from Medical School, Epidemiology and Psychiatry from Universidad Pontificia Bolivariana Colombia. She continued her Psychiatry, Child and Adolescent Psychiatry Training and Neurophysiology at Cleveland Clinic for the last 7 years. She is the Director of Project CARE (Coordination Access Resources and Education for Children with Epilepsy, a federally funded initiative to improve quality of care and life in children of epilepsy. She is a Fellow of the APA, an active Member of the Physically Child committee at the AACAP and the Psychosocial Comorbidities committee at AES.
Abstract:
In 2010, 38,364 Americans of all ages committed suicide which translates to one death every 13.7 minutes. Suicide rates are high among young people, suicide accounts for 13% of all adolescent deaths annually. The reported rate of suicide in patients with epilepsy is around 12% compared to 1.1-1.2% in the general population. Death by suicide has been reported in 5% of adult patients with epilepsy compared to 1.4% in the general population. There is a 5-fold increase in the rate of suicide among patients with epilepsy and up to 25-fold higher in people with temporal lobe epilepsy. Results from meta-analyses also indicate that patients with epilepsy have an increased risk of suicidal ideation and behavior. In a study analyzing 76 cohorts of people with epilepsy (N=60,846), 13 of the cohorts were made up of children. Among the child cohorts, the overall percent of death by suicide was 1.3%. Overall, the standardized mortality ratio for epilepsy patients was 3.3 (95% CI 2.8-3.7), 190 deaths were observed compared with the 58.4 expected. Some of the risk factors associated with suicide are mood disorders, psychotic disorders, personality disorders, substance abuse, previous suicide attempts and critical life events. Other epilepsy specific risk factors are stigma of epilepsy and peri-ictal mood dysphoria. Epilepsy patients who commit suicide tend to have early onset epilepsy, high seizure frequency, AED polytherapy and history of MDD. The severity of depression is probably the most important risk factor. Early screening is important to identify patients with epilepsy at risk for suicide.
Keynote Forum
Ana Maria Sebastiao
University of Lisbon, Portugal
Keynote: Adenosine modulation of signaling at the tripartite synapse: Implications for Epilepsy
Time : 10:40-11:20
Biography:
Ana M Sebastião has completed his PhD in 1987 from the Gulbenkian Institute of Science and the New University of Lisbon. She is the Director of the Institute of Pharmacology and Neuroscience, Medical School, University of Lisbon, and of the Mind-Brain College of the University of Lisbon, Portugal. She has published more than full 140 papers quoted more than 4600 times, and has been serving as an Editorial Board Member of several journals. She also served as President of the Portuguese Neuroscience and Portuguese Pharmacological Societies as well as in the Executive Council of the Federation of European Pharmacological Societies.
Abstract:
Adenosine is an endogenous anti-epileptic substance, known for its ability to inhibit excitatory synaptic transmission. I will focus on recent work by our group aiming to elucidate how high affinity A1 (A1R) and A2A (A2AR) adenosine receptors affect not only excitatory but also inhibitory transmission at the hippocampus. A2ARs can directly interfere with the life-span of GABA at synapses, since GABA transport is facilitated by A2ARs in nerve endings and astrocytes, where A1R and A2AR act as tetramers to fine tune GABA uptake. A1R inhibits the function of GABAA receptors localized at perisynaptic/extrasynaptic compartments in excitatory and a subset of inhibitory neurons, being involved in the control of persistent tonic GABAergic responses. A2A Rs influence the GABAergic input to a subset of inhibitory neurons and promote synchronous pyramidal cell firing in hyperexcitable conditions. In addition, A2ARs enhance extrasynaptic AMPA receptor mediated responses, allow the sustained recruitment of calcium-permeable AMPA receptors after ischemia, leading to a long-lasting facilitation of excitatory synaptic transmission and trigger neurotrophic factor actions upon synaptic plasticity. These actions of adenosine contribute to fine-tune neuronal activity and to set the stage for plasticity, eventually influencing seizure-induced aberrant plasticity.
- Epileptic Seizures and its Syndromes, Prevention and Management of Epilepsy
Location: Frederick Douglass
Chair
Nick Kane
North Bristol NHS Trust, UK
Co-Chair
Radcliffe Durodami Lisk
Allied Health Sciences in the University of Sierra Leone, UK
Session Introduction
Durodami Lisk
Allied Health Sciences in the University of Sierra Leone, UK
Title: The Challenges of Managing Epilepsy is resource poor countries in Africa- Experience from Sierra Leone
Time : 11:40-12:00
Biography:
D R Lisk later worked in the College of Medicine and Allied Health Sciences at the University of Sierra Leone and was Associate Professor and Head of department of Medicine. In 1991-2 he was Visiting Professor of Neurology and the stroke fellow at the University of Texas Health Science Centre in Houston. He returned to England in 2002 and was Consultant Neurologist and epilepsy lead at Basildon University Hospital. He won a National Health Service Gold award for his work on epilepsy in Basildon. He is now directing a link project on epilepsy between Basildon and Sierra Leone.
Abstract:
In developed countries, epilepsy is accepted as a medical condition and patients submit themselves to the various method of treatment available. Sierra Leone is a small West African country with poor infrastructure and health services.56% of people with epilepsy believe that epilepsy is caused by demons and witchcraft and seek treatment from traditional healers. It is also widely believed that epilepsy is transferable.We have looked at knowledge, attitudes, and practices of health workers towards epilepsy as well as the impact of epilepsy on school attendance of affected children. We further investigated the co-morbidities of depression and anxiety in our patients. Education, awareness raising and sensitization are important strategies in changing the attitudes of the community and improving service uptake. We have used innovative methods as well as standard media such as radio, television and posters in getting our primary messages across that epilepsy is a manageable medical condition and it is not transferable. With the use of basic antiepileptic drugs and outreach clinics, we have been able to reach thousands of patients throughout the country but a lot more needs to be done.
Guy Bar-Klein
Ben-Gurion University of the Negev, Israel
Title: Magnetic resonance imaging of blood-brain barrier dysfunction as a biomarker for Epileptogenesis
Time : 12:00-12:20
Biography:
Guy Bar-Klein has completed his PhD from Ben-Gurion University of the Negev and is currently a Postdoctoral Associate at the Howard Hughes Medical Institute. He has a B.Sc. in biophysics and M.Med.Sc in neurophysiology. In his research, Guy focuses on in-vivo electrophysiological recordings and molecular assays of epileptogenic processes and pathologies associated with blood-brain barrier (BBB) dysfunction. Studying the mechanisms regulating BBB permeability and the following effects, will hopefully lead to potential therapeutic treatments for BBB-related processes, emphasizing on post-traumatic epilepsy and other epileptogenic syndromes.
Abstract:
Acquired epilepsy is frequently followed brain insults. Interestingly, these insults are frequently associated with dysfunctional blood-brain barrier (BBB). We recently showed that BBB injury lead to albumin-mediated activation of transforming growth factor β (TGF-β) signaling in astrocytes, astrogliosis, local inflammatory response followed by epileptiform discharges and delayed seizures. Importantly, the FDA-approved AT1 antagonist, losartan, blocked albumin-induced TGF-β signaling and prevents epileptogenesis. Here we performed a longitudinal study in rats exposed to paraoxon to induce status epilepticus (SE) and epileptogenesis and executed repeated magnetic resonance imaging (MRI) to quantitatively monitor BBB integrity. Continuous video-electrocorticographic (ECoG) recordings were acquired to monitor for seizures. Analysis of the ECoG signals revealed that 13 out of 22 of the rats presented ≥2 spontaneous seizures and therefore were defined as epileptic. Signal analysis in 13 defined brain regions using logistic regression and forward selection suggested that focal BBB breakdown in olfactory structures increases the likelihood of a rat to become epileptic while diffuse damage decreases this likelihood. We thus were able to predict epilepsy with high sensitivity and specificity (92.3% and 77.8% respectively) with 12 out of 13 epileptic rats classified correctly and only 2 out of 9 non-epileptics falsely classified as epileptic. Our results demonstrate that increased BBB permeability in specific brain regions may serve as a reliable biomarker for SE-induced epileptogenesis and together with our findings showing losartan as anti-epileptogenic drug, highlight the potential of specific anti-epileptogenic treatment for patients identified with high risk to develop epilepsy.
- Epilepsy in Women and Inborn, Impact of the Epilepsies on daily life and Epilepsy Imitators
Location: Frederick Douglass
Session Introduction
Nick Kane
North Bristol NHS Trust, UK
Title: The Occurrence of Non-Epileptic Events (NEE) in a Pediatric Population with Medically Intractable Epilepsy enrolled on a Pediatric Epilepsy Surgery Program
Time : 12:20-12:40
Biography:
Nick Kane MBChB, MSc, MD (Hons), FRCS, FRCP (by election) trained in Neurophysiology at the Burden Neurological Institute, the National Hospital for Neurology and Neurosurgery and Great Ormond Street Hospital for Children in Londona full time NHS Consultant Clinical Neurophysiologist, Honorary Senior Clinical Lecturer at Bristol University and current President of the British Society for Clinical Neurophysiology. He is a former winner of the International Jubilee Gower Epilepsy prize and has 20 publications in peer reviewed Journals.
Abstract:
Over a 5 year period (2008 to 2014) 150 consecutive pediatric patients (age range 6 months to 17 years, mean 10.3 years, 76 males) were enrolled in our Pediatric Epilepsy Surgery program. Patients had been diagnosed with epilepsy on clinical and routine EEG grounds, and were deemed pharmaco-resistant based on their failure to respond to 2 or more anti-epileptic drugs at adequate doses for 6 months or more. As part of their pre-surgical work-up patients were admitted for 3 to 5 days of Video EEG (VEEG) monitoring. We prospectively identified epileptic seizures in 124 children (83%), confirming the clinical diagnosis, and/or stereotypic non-epileptic events (NEE) without electrographic changes in 82 (55%). The videoed NEE were reviewed with the patient’s parents or carers, confirmed as habitual and erroneously attributed to ictal activity. This gave a VEEG-confirmed co-existence of epileptic seizures and NEE 50%, compared to 10% to 50% in the Non-Epileptic Attack Disorder literature. We conclude that it is common to encounter concurrent epileptic and non-epileptic events in pediatric patients with medically intractable epilepsy. Our figure of 50% is higher than the reported occurrence of psychogenic nonepileptic seizures in recent retrospective VEEG series of pediatric populations, when the clinical question was the differential diagnosis of epilepsy (33%), including pre-surgical evaluations (19%) Whilst not a contra-indication to epilepsy surgery per se the co-existence of NEE (or PNES) should be borne in mind when managing and counselling pediatric patients.
Shripad Hebbar
Manipal University, India
Title: Epilepsy and Oral Hormonal Contraception - Indian Perspective
Time : 12:40-13:00
Biography:
Shripad Hebbar has completed his Masters in Obstetrics & Gynaecology at the age of 28 years from Karnataka University, India. He is currently working as Additional Professor of Obstetrics and Gynaecology a Kasturba Medical College, Manipal, University, one of the top recognized universities in India. He has authored several text books, research articles (more than 50) and has special interest in undergraduate and postgraduate teaching.
Abstract:
There are about 50 million people with epilepsy in the world and a quarter of them are in the reproductive age group. These women like others are highly fertile and frequently need to adopt effective and safe contraceptive measures to avoid unplanned pregnancy. There are several concerns regarding the efficacy and safety of natural methods or barrier methods in women who are taking antiepileptic drugs (AED), failure of which poses a great risk to the developing fetus as most of the AEDs have teratogenic effect. Oral hormonal pills are prescribed to epileptic women not only for birth control but also in certain situations such as polycystic ovaries, irregular menstruation, acne and dysfunctional uterine bleeding. There are major bidirectional interactions between reproductive hormones and antiepileptic drugs which the physician should be aware of while dealing with these women. This extensive review focusses upon potential drug interactions between constituents of various oral pills and anti-epileptic drugs, the formulations available in India with special note on ormeloxifene which is exclusively marketed for birth control in Rural India.
Sara Eyal
The Hebrew University of Jerusalem, Israel
Title: Effects of Anti-epileptic drugs on carriers for drugs, hormones and nutrients: Implications for foetal exposure
Time : 14:00-14:20
Biography:
Sara Eyal has completed her PhD from the Hebrew University and Postdoctoral studies from The University of Washington. She is a Senior Lecturer at the Hebrew University's Institute for Drug Research and the Head of Research of the University's Pharm D program. She has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of Frontiers in Pharmacology: Drug Metabolism and Transport.
Abstract:
Our aim is to explore a novel mechanism of potential teratogenicity of antiepileptic drugs (AEDs), altered expression of placental and systemic carriers for hormones, nutrients and medications. We have recently demonstrated that AEDs affect the expression of folate placental uptake carriers (reduced folate carrier-RFC, folate receptor α-FRα) and efflux transporters (breast cancer resistance protein-BCRP and multidrug resistance protein 2) and thyroid hormones uptake transporters (L-type amino acid transporter-LAT1 and organic anion transporting polypeptides-OATPs) in a human placental cell line. Our findings from studies in mice provide further evidence for additional effects of AEDs on fetal exposure to xenobiotics through modification of their systemic pharmacokinetics. Identification of AED effects on the placental barrier and fetal exposure to xenobiotics and endogenous compounds could be a first step towards a more rational pharmacotherapy and supplemental therapy in pregnant women with epilepsy.
Mahnaz Asgharpour
Azad university, Iran
Title: A New Bifurcation Parameter in a Modified Huber-Braun Model
Time : 14:20-14:40
Biography:
Mahnaz Asgharpour received the B.S. in biomedical engineering from Jondishapoor University of Medical Sciences, Ahwaz, Iran and the M.S. degree in biomedical engineering from the Department of Biomedical Engineering of the Science and Research branch of Azad University, Tehran, Iran. She is a Ph.D. candidate in electrical engineering, control and system design at the department of electrical engineering, Tehran Science and Research branch of Azad University. She has been a lecturer at the Technical and Engineering Department of Azad University for up to four years. Her research interests include computational neuroscience, nonlinear dynamics and chaos.
Abstract:
Thermally sensitive neurons represent a bursting-spiking activity which is characterized by fast repetitive spiking trains of action potentials followed by quiescent periods. Synchronization of this activity in a network of coupled spiking neurons such as the epileptogenic zone in the brain may cause some neurological disorders such as epileptic seizures. The aim of this paper is to introduce a new algorithm for prediction the spiking onset in a model of an epileptic neuron and we try to use some parameters for feature extraction in our simulations which are potentially applicable in the non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS). In this regard, a modified Huber-Braun model of a thermally sensitive neuron exposed to external rTMS-induced voltages is presented. Applying the Chaos theory, the bifurcation diagram of a modified Huber-Braun model with a novel bifurcation parameter has been represented. Then we used the time at which the period doubling bifurcation is started in order to approximate the seizure onset in the modified model.
Saeideh Salehpour
Lorestan University of Medical Science, Iran
Title: Neural pathway damage of retrograde memory in Epileptic patients with older Anti-epileptic drugs
Time : 14:40-15:00
Biography:
Saeideh Saleh Pour has completed her Diploma at the age of 18 years. She is an Intern of Medicine at Lorestan University of Medical Science (LUMS). She is interested in research specially in Neurology.
Abstract:
Introduction: Memory is a very important field of cognitive function. Retrograde memory is the past memory that makes the information treasure of life for every person. With regard to the importance of memory, it seems that the evaluation of it in patients with risk of memory deficit is necessary. Epileptic patients are at a high risk of memory decline. Methods: In this study, our subjects were thirty grand mal epileptic patients under treatment with the older generation of epileptic drugs (carbamazepine or valproate sodium or phenobarbital). The types of memory are evaluated by Persian version of Addenbrook’s cognitive examination. Result & Discussion: In the study, all types of memory are definitely damaged but they have the variety of 20 until 100 percent of our subjects. Only one type of memory that has a decline for 100% of subjects was retrograde memory. Prefrontal and temporal cortex is two essential sites for that. It seems that the pathway between the prefrontal cortex and the hippocampus involve some kind of disconnection. Researchers in this study have some suggestions for the future study of epileptic patients who have taken older antiepileptic drugs. These suggestions will be discussed in this congress.
- Symposium
Location: Frederick Douglass
Session Introduction
Sloka Iyengar
Northeast Regional Epilepsy Group, USA
Title: Exploring Synaptic Plasticity in the Epileptic hippocampus in Epilepsy
Time : 15:00-15:40
Biography:
Sloka Iyengar received her PhD from the University of South Carolina, School of Medicine where she used electrophysiology to study synaptic plasticity in epilepsy. During her Postdoctoral work at the Nathan Kline Institute in New York, she studied the role of adult neurogenesis in seizures. Presently, she works as a Clinical Researcher and manages the brain tumor-related epilepsy research consortium. She is also a Science Writer and Advocate and regularly writes articles to make basic science more accessible to non-scientists.
Abstract:
Temporal lobe epilepsy (TLE) is a neurological disorder that can be caused due to stroke, traumatic brain injury or meningitis and is characterized by spontaneous, recurrent seizures. Medications used to treat TLE are called anti-epileptic drugs (AEDs) and can be associated with side-effects and refractoriness. It is important to better understand the changes that place in the brain that enable and sustain epileptic seizures in order to provide better therapies for people with epilepsy. The process by which a normal brain becomes ‘epileptic’ is called epileptogenesis and I have been studying epileptogenesis using experimental rodent models for the past ten years. All my studies have focused on the temporal lobe mainly the hippocampus because of its role in seizure generation and propagation. Using electrophysiology, we found differential regulation of synaptic plasticity by a neurotrophic factor called neuregulin (NRG) in the epileptic brain as compared to the non-epileptic brain. In another project, we focused on a process called adult neurogenesis in the hippocampus. Using mice, we found that a reduction in adult neurogenesis increased susceptibility to seizures. Currently used AEDs are associated with substantial side-effects because they act on both the healthy non-diseased tissue and the epileptic tissue. Exploring differences between the epileptic and non-epileptic circuitry could ultimately lead to development of more efficacious therapies for people with epilepsy.
- Video Presentation
Location: Frederick Douglass
Session Introduction
Abbas Alnaji
Al Sadir Medical City, Iraq
Title: Dormant and sub-clinical bacterial infections of brain may be the cause behind all epilepsies including that due to post-traumatic or associated with space occupying lesion SOL
Time : 16:00-16:30
Biography:
Abbas Alnaji completed his Degree in Neurosurgery FICMS NS from University of Baghdad 1999. He is interested in research work and have twelve papers published in the field of Surgical Pathology Causations.
Abstract:
As neurosurgeon, I had an ambition to open unit for surgical treatment of epilepsy in our department like those in other parts of the world. I started my personal efforts to make myself more and deeper knowledgeable in this field. This maneuver yielded in interpretation of a fact that epilepsy simply is a Global Brain Dysfunction (GBD), the burden of it may be more in this or that part of the brain to be presented as a certain mode we term it with some known clinical entity. As results to this fact, epilepsy to be launched clinically it needs: A time to reach or exceeds certain threshold by this it had been called idiopathic and or it needs an added precipitating factors like head trauma by this it termed post traumatic. This GBD has other potential (needs added factor like motion sickness) or overt central clinical signs and symptoms if we put them in our consideration this fact will become clear or explains why patients with epilepsy suffers from chronic head ache, vertigo, memory impairment, weakness in concentration and many others. In short, I want to say epilepsy is not the only one who sits on the sofa it over-rides the other manifestations both socially and clinically. Another fact, this GBD is a complication or secondary to a chronic general systemic illness GSI. Again, as a result to this fact, you may find 1 history of signs and symptoms refered to a systemic chronic or sub-acute infectious disease. The patient may had been treated for systemic review referring to a general chronic health problems. Thorough physical examination picks up what refers to some long standing sufferings however, mild. 4 investigations are of some controversy, like PCR in this study which is positive 33% for blood, 66% for CSF and 66% for tissue in 15 patients all had been treated successfully with anti-neurobrucellosis whom being diagnosed clinically according to the above criteria. So, we have two interdigitated diseases; neurobrucellosis and epilepsy, one disease is a complication to the other (epilepsy is a complication of the neurobrucellosis). What’s new in this issue is, if we forget about the 15 patients with PCR study for Brucella as causation for epilepsy treated in Iraq, 2015. I had more than 100 patients over the period of 2006-2014 of all age groups and both genders treated in Iraq, Jordan and Libya for all what can be termed as modalities of idiopathic epilepsy (details for post traumatic and due to SOL in the full text), these patients either newly diagnosed by me or come with different anti-epileptic/s but uncontrolled, not forgetting a boy of nine years old presented to my private clinic with a troublesome un-controlled grand mal in spite of the three anti epileptics in maximum doses. I say those 100 patients had been treated depending on the above criteria for neurobrucellosis as a cause for their seizure modalities with excellent success whatever the duration of their affection. This was prior to PCR era at least in the aforementioned countries. The group with no antiepileptic/s starts to have a noticeable gradual improvement over the beginning 10-15 days both quantitatively and qualitatively (with care for precipitating factors). While those come already on antiepileptic/s but uncontrolled, they kept on their regimens and withdrawn gradually as they getting better on the same upper principle. Due to the poor long lasting follow up. Only 30% witnessed their full recovery until these words being written, May 2015. In conclusion; epilepsy, if we put the above facts in our consideration, we find that epilepsy is one manifestation of a chronic systemic infectious disease, the others are precipitating or co-factors, in my career this chronic systemic disease is mostly chronic Brucellosis.