부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1528-1167.2006.01370_3.x Byline: P Plouin (1), G Capovilla (2), A Covanis (3), M Koutroumanidis (4) Abstract: Monday, 9.sup.th July 200707:30 - 08:30Ballroom 1EUREPA SeminarEUREPA Seminar Series 1 - Discussion on Difficult Cases in Childhood Epilepsies Discussants: Plouin P .sup.1 Capovilla G .sup.2 Covanis A .sup.3 Koutroumanidis M .sup.4 , Hopital Necker Enfants Malades, France ; C. Poma Hospital, Italy ; The Children Hospital Agia Sophia, Greece ; St Thomas Hospital, UK Abstract: Monday, 9.sup.th July 200707:30 - 08:30TheatreEUREPA SeminarEUREPA Seminar Series 2 - Discussion on Difficult Cases in Adult Epilepsies Van Emde Boas W .sup.1 Velis Najm I .sup.2 Velis D .sup.3 Ozkara C .sup.4 (Stichting Epilepsie Instellingen Nederland (SEIN), Netherlands Cleveland Clinic Foundation, USA Epilepsie Instellingen Nederland (SEIN), Netherlands Universty of Istanbul,Turkey Abstract: Monday, 9.sup.th July 200707:30 - 08:30Room 209EUREPA SeminarEUREPA Seminar Series 3 - Discussion on Seizure Related Automatisms Tassinari C A .sup.1 Luders H O .sup.2 (University of Bologna, Italy University Hospitals Medical Group, USA) Abstract: Canevini M P .sup.1 (Regional Center for Epilepsy - S. Paolo Hospital -"Universita degli Studi") Differently to locomotion, chewing movements have a kinesiotopic representation in the sensorymotor cortex of some species. Nevertheless the basic pattern of chewing are present also in decerebrated animals and are controlled by a Central Pattern Generator (CPG) in the brainstem. Direct stimulation of many subcortical areas (amygdala among others) may evoke a chewing pattern. Amygdala has direct connections that end on masticatory motoneurons. Automatisms in the International Glossary are defined as: "A more or less coordinated, repetitive, motor activity usually occurring when cognition is impaired and for which the subject is usually amnesic afterward. This often resembles a voluntary movement and may consist of an inappropriate continuation of ongoing preictal motor activity" (1). Oroalimentary automatisms are: lip smacking, lip pursing, chewing, licking, tooth grinding or swallowing. The localizing effort for different ictal symptoms should always be contextualized into the individual seizure, but we could grossly subdivide in a localizing effort: - visceral-vegetative movements (suprasilvian region): swallowing (especially as an isolated symptom), spiting (for an excess of saliva), licking, chewing with more mechanical characteristics. -ictal chewing (food crushing and grinding) (amygdala) Oroalimentary automatisms may be present also as a post-ictal phenomenon. Recently Meletti et al.(2) reported a case of ictal rhythmic teeth grinding In particular, these data suggest that brainstem central pattern generators for masticatory activity can be set in motion in different conditions to generate rhythmic jaw muscle activities that share similar EMG and autonomic features. The trigger event can be an increased level of arousal, as occurs in sleep bruxism, or an epileptic discharge, as observed in this particular patient. Other patterns of involuntary chewing movements in different neurological conditions will be examined Abstract: Baumgartner C .sup.1 (Department of Neurology, Medical University of Vienna, Austria) Gestures can be defined as a motion of hands or body to emphasize or help to express a thought or feeling. Thus, gestures represent forms of non-verbal communication used instead of or in combination with verbal communication. The language of gestures is used to express a variety of feelings and thoughts, from contempt and hostility to approval and affection. Some ethnic groups use gestures more than others, and the amount of such gesturing that is considered culturally acceptable varies from one location to the next. Gestures during epileptic seizures are referred to as gestural automatisms. Gestural automatisms usually can be classified as de novo automatisms which begin with the or after the onset of the seizure, whereas they are rarely perseverative automatisms consisting of a mere continuation of a behavior starting already before the seizure. Gestural automatisms can be both reactive, i.e. responsive to external or internal stimuli, and released automatisms which include actions that are normally socially inhibited. Gestural automatisms can be further subdivided into simple and complex gestural automatisms. The former consist of rhythmical and discrete finger movements or simple movements of the legs. Complex gestural automatisms consist of complex motor behaviors and may sometimes appear violent. These latter automatisms are frequently reflexive induced by the intrusion of the patient's peripersonal space by others. Gestural automatisms are frequently accompanied by changes in facial expression including blank staring, expressions of fear, dread, smile, laughter or surprise. The anatomical basis of gestural automatisms is still uncertain, but several studies suggest that a dual - temporal and frontal - dysfunction may account for gestural automatisms. Furthermore, the relation of gestural automatisms to meaningful and meaningless gestures could be helpful to explore their underlying mechanisms. Abstract: Monday 9.sup.th July, 200708:30 - 09:30Hall 603Main Session (in collaboration with the Global Campaign Against Epilepsy)Issues In Developing Countries - The Three Gaps: Knowledge, Research and Treatment Lim S.H. .sup.1 (National Neuroscience Institute, Singapore) To provide optimal care for patients with epilepsy, clinicians must continuously acquire established & evolving knowledge in Epileptology, and apply such knowledge to patient care. Knowledge acquisition include making tacit knowledge explicit, identifying gaps in knowledge already held, and acquiring & integrating new information from multiple sources to fill these gaps. Traditional sources of epilepsy knowledge include textbooks, journals, and lecture notes which might be limited in developing countries. With Internet and World Wide Web (www.) that hyper-produce and hyper-distribute "free" information, clinicians can now acquire epilepsy knowledge via computers. E-learning initiative by academic epilepsy organization could further enhance knowledge acquisition. Literacy in computer & English languages and infrastructure for information & communication technology (ICT) are now crucial variables in knowledge acquisition. Superficially Internet appears to be the solution to the knowledge gap since it disseminates information widely and cheaply. However other issues arise. Vast quantities of epilepsy information are now available via www - too much to access by individual mind at any one time. The public also have unprecedented ability to access similar information and participate actively in evidence-based health care, pressurizing clinicians to stay updated. Determining the quality and reliability of accessible information is not easy, unless the information is from trusted sites such as ILAE or reputable academic institutions. Age, education and income influence the ability to access and sustain ICT, thus could impede the narrowing of the knowledge gap. Across the glob, technologically rich nations or cities tend to acquire information faster than technologically poor, further widening the knowledge gap between and within nations, and between members of social classes. Internet is still a great tool to bridge the knowledge gap and improve patient care. Local and international epilepsy organizations need to work with various governmental agencies to narrow the digital divide within each country. Abstract: Silberberg D .sup.1 (Department of Neurology, University of Pennsylvania, 3 W Gates Building 3400 Spruce Street, Philadelphia, USA) Despite the fact that epilepsy, almost uniquely among brain disorders, is eminently treatable with inexpensive medications, effective programs are lacking in most developing countries. 70-90% of individuals with active epilepsy - upwards of 30 million - go untreated. Inadequate health care systems, shortages of trained professionals, and the persistence of local belief systems contribute to the treatment gap. Estimates of the treatment gap range from 98% in rural Pakistan, to 75% in China. However, very little hard data exists for developing countries, for many of the same reasons that the treatment gap exists. Complex factors contribute to the treatment gap, alone or in combination: Epilepsy may not have been recognized, or properly diagnosed; there are often few or no neurologists; community health workers are usually untrained in dealing with neurological disorders; the person with epilepsy (PWE) may not know that treatment is available; the individual or family may not wish to acknowledge the problem. Thus, the PWE may not seek treatment. Perversely, high expectations for modern medicines may counter adherence. Preventive or biomedical treatment may not be seen as an option. Anti-epilepsy drugs (AED's) may not be available, at all, or on a continuing basis. The distance to travel to see a health worker may be too great. The health worker may prescribe the wrong medicine. Even the cost of Phenobarbital or Phenytoin may be too great. Fear of AED side effects may prevent treatment or result in failure of adherence. All of these factors represent components in a country's health care system; and epilepsy usually suffers from having a very low priority within the national system. The ways forward include research to better communicate the dimensions of the problem, studies to understand specifics of the etiology of the gap, country-by-country, and education at every level, from community health workers to health care policy leaders. Abstract: Avanzini G .sup.1 (Istituto Neurologico C. Besta, Laboratorio Di Neurofisiologia, Via Celoria 11, Milano, Italy) Abstract: Monday 9.sup.th July, 200710:00 - 11:30Hall 603Post Main SessionClosing The Three Gaps: Knowledge, Research And Treatment Kwan P .sup.1 (The Chinese University of Hong Kong, Division of Neurology, Department of Medicine & Therapeutics, Hong Kong) Abstract: Birbeck G .sup.1 (Michigan State University, #138 Service Road, A217, East Lansing, Michigan, USA) Anecdotal reports and some systematic data indicate that regions where the epilepsy treatment gap is greatest are the same areas with more severe and pervasive problems related to epilepsy-associated stigma. While all chronic diseases predispose to a decline in the affected person's socioeconomic status, for people with epilepsy (PWE) in developing regions the effects are extreme resulting in lower income, less wealth, poorer housing quality, less access to safe water, poorer options for public sanitation, greater food insecurity and less personal safety. If one examines closely factors that perpetuate a large treatment gap, stigma plays a significant role. Consider what is needed to decrease the treatment gap-(1) a reliable, affordable supply of effective AEDs, (2) healthcare providers willing and able to care for PWE, (3) a population of PWE who are aware that treatment is available and are able to access treatment sources. Behind of all these lies the underlying need for sufficient political will to facilitate the development and maintenance of these three key elements. Stigmatized persons are by the nature of their condition and position disempowered. This limits their access to education, employment, and social advancement. Deprivation occurs even within the household. And as a disempowered, underemployed, poorly educated, "devalued" group, PWE are less able to access existing public goods and services like healthcare. Health services for epilepsy are negatively impacted by courtesy or reflected stigma imposed upon healthcare workers who treat the condition and without vocal advocates epilepsy care receives little attention and low priority within the healthcare system. Poor services and care means increased medical morbidity and mortality related to the condition. And so the decline continues. The relationship between the treatment gap and epilepsy-associated stigma is an insidious one that requires explicit acknowledgement and directed efforts to decrease both. Abstract: Ali A .sup.1 (Epilepsy Centre of Jamaica, Andrews Memorial Hospital, 27 Hope Rd, Kingston, Jamaica) The protracted nature of epilepsy strains the affected individual's resources and interferes with their successful integration into normal life. Long entrenched societal stigma creates additional burdens, limiting education, employment, marriage and has led to restrictive legal regulations. For many patients psychosocial problems are therefore more disabling than the seizures themselves. In developing countries like Jamaica, these issues are brought into even sharper focus. Comprehensive epilepsy care must thus not only address diagnostic and therapeutic aspects but also manage these complex psychosocial issues. Patient care organisations can play an indispensable role in helping to support affected individuals. The Jamaican league of the ILAE (JLAE) was formed in 2001 and was followed in 2002 by the launch of the Jamaican Epilepsy Association (JEA), the local IBE chapter. These chapters were formed in recognition of the many difficulties patients and the island's health care system in general were facing. The chapters' principal mission has been to address the problem of societal stigma, and to improve knowledge of patients, their families and health workers of this condition. The JLAE now has 52 members in Jamaica and Barbados. The JEA is expanding its membership to include the business sector. Through fundraising, in 2004 the JLAE and JEA opened the only video-EEG Unit in the English-speaking Caribbean. Having permitted greater diagnostic precision and identification of the under-recognised entity of non-epileptic seizures, this Unit will soon facilitate surgical treatment of intractable epilepsy. The JEA and JLAE launched the first Annual Epilepsy Awareness Week in November 2006 addressing, among other issues, epilepsy in the workplace. This year the team has begun an outreach programme to educate the population in more remote communities. Current initiatives also include a mobile EEG unit, which will facilitate improved access to care for these communities. Abstract: Dumas M .sup.1 (Institut d'Epidemiologie Neurologique et de Neurologie Tropicale, Faculte de Medecine,2 rue du Dr Marcland, Limoges, Cedex, France) Epidemiology covers the distribution of diseases and studies the factors influencing diseases or their evolution, i.e. genetic or environmental factors. Epidemiological research is therefore crucial to set-up actions against the treatment gap, in particular in developing countries. Prevalence and incidence studies of epilepsy in a defined area allow first to estimate its frequency and to evaluate the cost-effectiveness of funding other studies, taking into account existing other diseases in the same area. Second, epidemiological studies will measure the treatment gap, its consequences and its causes: - economical factors, which are probably not so important, except for new drugs; sometimes the cost of a traditional treatment is more expensive than a modern one; - availability, accessibility and quality of drugs; - cultural factors with the multiple interpretations of the disease which are very often the main factors. The disease is considered as supernatural and then people consider that no physician can treat it; furthermore, the necessity of a long term treatment is an indirect proof of the incapacity to treat it. Epidemiological studies with adequate methodologies are the only possibility to quantify these factors and their interactions without biases. The overall elements could help to define strategies for a better management of the patients. Examples will be given to illustrate the contribution of epidemiology to fill the treatment gap in epilepsy. Abstract: Monday, 9.sup.th July 200710:00 - 11:30Ballroom 2Parallel SessionMulti-Level EEG Recordings In Epilepsy Surgery Elger C .sup.1 (Universitaet Bonn, Germany) Abstract: Najm I .sup.1 (Cleveland Clinic Foundation, USA) Abstract: Kahane P .sup.1 (Grenoble University Hospital, France) Abstract: Sakamoto A .sup.1 (University of Sao Paolo, Brazil) Abstract: Monday, 9.sup.th July 200710:00 - 11:30Ballroom 1Parallel SessionEvidence Based Imaging In Refractory Paediatric Epilepsy Harvey S .sup.1 (Royal Children's Hospital, Melbourne, Australia) Abstract: Chiron C .sup.1 (Hospital Necker, France) Abstract: Juhasz C .sup.1 (Children's Hospital of Michigan, USA) PET scanning has been applied for assisting localization of epileptic foci in children with chronic epilepsy for almost two decades. Still, the number of pediatric epilepsy PET studies remains limited with heterogeneous patient groups and diverse analytical approaches. Out of more than 20 studies published between 1990 and 2007, the majority reported on 2-deoxy-[18.sup.F]fluoro-D-glucose (FDG) PET results in children with intractable partial seizures. Findings from multiple centers consistently demonstrated focal hypometabolism on interictal FDG PET in the majority (60-95%) of such patients, with a good (up to 85%) concordance with EEG-defined epileptic foci or surgical resection sites. Importantly, PET showed localized abnormalities in about 2/3 of cases with non-localizing MRI. However, the overall number of reported cases is relatively small, considering that PET could be highly beneficial in MRI-negative pediatric epilepsy. In children with medically intractable cryptogenic infantile spasms, localized cortical hypometabolism can indicate an unsuspected cortical malformation (such as focal cortical dysplasia), which is often amenable for surgical resection resulting in seizure freedom. A few studies with intracranial EEG comparisons indicated that FDG PET can regionalize epileptic foci and guide intracranial electrode placement, but it may not be accurate in exactly localizing the epileptogenic zone in neocortical epilepsy. Initial results suggest that [11.sup.C]flumazenil PET (an imaging modality to study GABA.sub.A receptor binding) may be more accurate in this respect. In addition, increased uptake of alpha[11.sup.C]-methyl-L-tryptophan on PET is useful for identifying epileptogenic lesions in pediatric epilepsies, mainly those associated with tuberous sclerosis and malformations of cortical development. Altogether, these studies suggest that PET scanning with FDG and other, emerging PET tracers is clinically helpful in selected groups of children with chronic pediatric epilepsy. Further, prospective studies are needed to evaluate the effect of PET-assisted management of epilepsy on clinical outcome Abstract: Monday, 9.sup.th July 200710:00 - 11:30Ballroom 3Parallel SessionNon-Conventional Targets for Novel Antiepileptic Strategies Rogawski M A .sup.1 (Department of Neurology, University of California, Davis, Sacramento, California) Neurosteroids are steroid compounds that are synthesized locally within the brain and act in a non-classical fashion, that is, via cellular actions that do not involve nuclear hormone receptors. The most extensively studied neurosteroids are A-ring reduced metabolites of steroid hormones such as progesterone, deoxycorticosterone and testosterone whose neurosteroid derivatives are allopregnanolone, tetrahydrodeoxycorticosterone and androsterone. Such A-ring reduced neurosteroids are potent positive allosteric modulators of GABA-A receptors, with a preference for perisynaptic/extrasynaptic delta-subunit containing GABA-A receptors. These steroids protect against seizures in diverse animal models and they therefore represent "endogenous anticonvulsants." There is evidence that a fall in brain neurosteroids at the time of menstruation contributes to enhanced seizure susceptibility in catamenial epilepsy. Similarly, fluctuations in neurosteroid levels may contribute to seizure exacerbations at times of stress and reduced neurosteroids may play a role in poor seizure control in men with temporal lobe epilepsy. Evidence from animal models indicates that neurosteroid replacement may represent a novel therapeutic approach in epilepsy and may be of particular value in catamenial epilepsy and other conditions where fluctuations in neurosteroids contribute to the pathogenesis The neurosteroid analog ganaxolone (3alpha-hydroxy-3alpha-methyl-5alpha-pregnan-20-one) is being developed as a novel epilepsy therapeutic agent. Human trials indicate that ganaxolone is well tolerated and that it may be efficacious in the treatment of diverse forms of epilepsy in children and adults. Ganaxolone is currently undergoing clinical trials for the treatment of infantile spasms and adult partial epilepsy. Recent evidence in animal models have indicated that neurosteroids synthesized in the brain may retard temporal lobe epileptogenesis following status epilepticus. Consequently, it will be of interest to examine the potential of modulators of endogenous neurosteroid synthesis or exogenously administered neurosteroid analogs like ganaxolone as strategies to inhibit the development of epilepsy in individuals at risk. Abstract: Ravizza T .sup.1 (Mario Negri Institute For Pharamalogical Resesrch, Italy) Background: Interleukin (IL)-1[beta] and its signal transducing receptor (IL-1R1) are overexpressed in glia, neurons and endothelial cells of the blood-brain barrier in epileptic tissue from rodent brain and in patients with drug resistant epilepsies of different etiologies. Experimental findings in rodent models of seizures indicate that an increase in IL-1[beta] levels in the brain plays a crucial role in the maintenance of epileptic activity. Aim: We tested the hypothesis that effective seizure inhibition may be achieved by interfering with the IL-1[beta] system, using two different pharmacological approaches: (1) the blockade of IL-1RI using the endogenous receptor antagonist (IL-1Ra); (2) the inhibition of the endogenous production of IL-1[beta] using VX-765, a selective inhibitor of IL-1 converting enzyme (ICE), the enzyme producing the releasable and biologically active form of IL-1[beta]. Results: (1) Intracerebral injection of IL-1Ra or its endogenous overexpression in astrocytes potently inhibited behavioural and EEG seizures induced by chemoconvulsants in mice. Intracerebroventricular injection of IL-1Ra during status epilepticus induced by hippocampal electrical stimulation reduced behavioural seizures in rats, without altering the EEG activity in the hippocampus. (2) VX-765 (25-200 mg/kg intraperitoneally, i.p.) reduced in a dose-dependent manner the number and duration of kainate-induced EEG seizures in rats and delayed their time to onset by 2-fold. Repetitive injections of VX-765 (200 mg/kg, i.p.) prevented the development of rapid kindling without affecting the afterdischarge duration in the hippocampus. VX-765 (100 mg/kg/day, i.p.) after 4 days of treatment reduced up to 70% the frequency and duration of spontaneous EEG seizures occurring 2 months after intrahippocampal injection of kainic acid in mice. These seizures are refractory to several antiepileptic drugs. Conclusions: Pharmacological blockade of IL-1[beta] signaling represents a highly effective means to reduce acute and chronic seizures and appears to delay epileptogenesis. ICE inhibition may represent a novel strategy for developing effective antiepileptic treatments. Abstract: Friedman A .sup.1 (Ben-Gurion University, Israel) Common brain insults such as trauma, ischemia, infections and neurodegenerative diseases are associated with vascular perturbations, opening of the blood-brain barrier (BBB) as well as epileptogenesis. To challenge the hypothesis that BBB disruption may be involved in epileptogenesis, we established a model for a prolonged BBB opening in the rat neocortex. We show that several days following BBB disruption, hypersynchronized propagating epileptiform activity develops within the treated region. Epileptogenesis has also been found following direct exposure of the cortex to serum albumin. Co-immunoprecipitation experiments suggest that albumin binds to brain's TGF-[beta] receptors. Furthermore, albumin uptake was blocked by TGF-[beta] receptor antagonists. TGF-[beta] itself led to epileptiform activity in-vitro suggesting a molecular pathway activated by serum components under BBB opening leading to epileptogenesis. Albumin uptake was followed by increased expression of glial fibrillary acidic protein (GFAP) and decreased expression of astrocytic glutamate transporters together with the potassium inward-rectifying channel, KIR-4.1. These suggested reduced buffering of extracellular potassium ([K.sup.+].sub.o) and glutamate. Indeed, electrophysiological experiments 24hrs following BBB opening showed enhanced activity-dependent accumulation of [K.sup.+].sub.o together with NMDA-receptor mediated enhanced neuronal excitability. Treating rats with local perfusion of TGF-[beta] receptor antagonists together with serum albumin resulted in more than 50% reduction in the likelihood of epileptogenesis. Parallel brain imaging studies support the notion that BBB opening is common in human epileptic patients. In post-traumatic patients we found BBB opening more common in patients with post-traumatic epilepsy, compared to patients with similar brain lesions without seizures. Our results stress the potential significance of disruption of the BBB in epileptogenesis. We highlight a novel cascade of events following common brain insults leading to brain dysfunction, suggesting possible novel therapeutic targets. This work was supported by the Sonderforschungsbereich (SFB) 507 and TR3 and the German-Israeli Foundation for Scientific Research and Development (GIF). Abstract: Potschka H .sup.1 (Inst. of Pharmacology, Ludwig-Maximilians-University) In pharmacoresistant patients, overexpression of blood-brain barrier efflux transporters has been suggested to limit brain access and efficacy of antiepileptic drugs. Increasing evidence for an impact of these transporters on therapeutic success, promotes efforts to develop strategies to modulate transporter activity. Because the multidrug transporter P-glycoprotein (Pgp) seems to transport several antiepileptic drugs, efforts so far especially concentrate on this transporter. Mechanisms by which Pgp activity in the BBB can be modulated include direct inhibition, functional modulation, and transcriptional modulation. First and second generation Pgp inhibitors (e.g. verapamil) are hampered by additional pharmacodynamic effects or by effects on drug metabolism. The development of third generation Pgp inhibitors rendered selective modulators, such as tariquidar. As described in first case reports, coadministration of the unspecific Pgp inhibitor verapamil improved seizure control in pharmacoresistant patients. However, the case number so far is too low for general conclusions regarding efficacy of such an add-on treatment. In models of pharmacoresistant epilepsy, use of Pgp modulators including the specific inhibitor tariquidar, significantly improved the efficacy of antiepileptic drugs. One study, however, gave evidence that tolerance may occur with repeated administrations. Any modulation of transporter function has to consider the potential hazards. First, an influence on pharmacokinetics of the therapeutic will enhance drug concentrations not only in affected brain regions, thereby promoting side effect potentiation. Second, multidrug transporters such as Pgp serve a variety of physiological functions including the protection from xenobiotics. Xenobiotics may thus be more harmful in the presence of efflux transporter inhibitors. Furthermore Pgp and MRPs may protect brain parenchymal cells from apoptosis, and transporter inhibition may thus promote cell death. Nevertheless, transient inibition of efflux transporters by short-term administration of inhibitors may be a tolerable strategy to reverse or prevent drug resistance due to overexpression of transporters at the BBB. Abstract: Monday, 9.sup.th July 200710:00 - 11:30TheatreParallel SessionEpilepsy Genetics In The 21st Century (Part 1): Building Bridges From The Laboratory To Patient Care Scheffer I .sup.1 (University of Melbourne, Austin Health and Royal Children's Hospital) Monogenic epilepsies are rare; more than 15 genes have been identified through studies of large multiplex families. The majority of these genes encode ion channel subunits and have a range of mutations including missense, frameshift and truncation mutations. Truncation mutations usually result in a non-functional protein, whereas missense mutations alter protein function. Functional studies in vitro and in vivo provide important insights into the effects of mutations and aid in understanding genotype-phenotype correlations. In addition to the common types of intragenic mutations described above, the importance of copy number variation is becoming increasingly apparent. Copy number variation may be in the form of exonic deletion or duplication, or whole gene copy number variation. This new mechanism accounts for some cases with monogenic epilepsy who were previously mutation negative. The success of the discovery of the genes underlying Mendelian epilepsies does not readily translate to common epilepsies following complex inheritance. This is because variants in multiple susceptibility genes, each with a small effect, may be required to cause epilepsy with complex inheritance; environmental factors may also play a role. Different models have been proposed such as the Common disease-common variant model; however, the alternative Multiple rare variant-complex disease model may be more applicable with current data. There is emerging evidence that specific groups of genes are susceptibility alleles in complex epilepsies: calcium channel subunits, GABA.sub.A receptor subunits and the non-ion channel gene EFHC1. Functional effects of variants in specific genes may be highly variable with different mutations producing different molecular effects yet resulting in similar phenotypes. The challenge of understanding genotype-phenotype correlation shows that there are exciting times before us to unravel the genetics of the common epilepsies. Abstract: Escayg A .sup.1 (Department of Human Genetics, Emory University, USA) Voltage gated sodium channels play a critical role in generation of neuronal excitability by facilitating initiation and propagation of action potentials. Sodium channels contain a pore forming 260 kD alpha subunit and 1 to 4 accessory beta subunits ([beta]1 to [beta]4). In the mammalian genome there are ten paralogous alpha subunit genes of which four are primarily expressed in the central nervous system: SCN1A, SCN2A, SCN3A and SCN8A. SCN1A dysfunction has been established as an underlying cause of several subtypes of human epilepsy including Generalized Epilepsy with Febrile Seizure Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI or Dravet Syndrome). A mouse model of SMEI was recently described (Yu et al., Nature Neurosci. 2006). Heterozygous null mutants exhibit spontaneous seizures and premature lethality. Homozygous SMEI mice are ataxic and die at P15. Reduced levels of sodium currents were observed in hippocampal interneurons of SMEI mice, suggesting that reduced inhibition may play an important role in seizure generation. We have generated transgenic and targeted mutant mice that carry specific human GEFS+ mutations. Heterozygous mutants exhibit reduced seizure threshold and infrequent spontaneous seizures. Homozygous mutants exhibit spontaneous seizures and premature lethality. Electrophysiological findings were consistent with reduced excitability of hippocampal interneurons, suggesting that the phenotypically distinct SCN1A disorders GEFS+ and SMEI may share a common underlying mechanism. Abstract: Polack O .sup.1 (College De France, France) Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike-and-wave discharges (SWDs) on electroencephalographic recordings, concomitant with an alteration of consciousness. SWDs result from abnormal rhythmic oscillations within the corticothalamic loops, which would originate from a subscribed cortical region exhibiting an elevated propensity to generate paroxysmal activities. In childhood absence epilepsy (CAE), which provides the prototypic form of absence syndromes, the seizures start between 3 and 8 years of age (peak [proportional to]6-7 years) and most patients show spontaneous remission, often around adolescence. Analyses of twins and families with CAE suggest complex inheritance. Various susceptibility loci were reported and a mutation of the CLCN2 gene (coding for a voltage gated chloride channel) was identified. Recently, a new mutation in GABRA1 ([alpha]1 subunit of the GABA.sub.A receptor) was reported in a sporadic CAE. The establishment of the functional links between the genetic alterations and the physiopathology of absence seizures require the use of genetic models in which the neuronal mechanisms of epileptic discharges can be explored at different ages. The GAERS (genetic absence rats from Strasbourg) and WAG/Rij rat strains, well-characterized inbred models for CAE, spontaneously develop electrical paroxysms that resemble those of childhood absence seizures. In these rodent genetic models, the first seizures are observed at around 1-2 months and their incidence gradually increased to reach 100% at the age of 3 months. Three quantitative trait loci were found in GAERS and WAG/Rij rats controlling specific SWD variables, including frequency, amplitude, and severity of SWDs. Age was a major factor influencing the detection of genetic linkage to the various components of the SWDs. An alternative and promising strategy to elucidate the time-dependent expression of epileptogenesis will be to link, in the rodent genetic models, the age-dependent changes in intrinsic channels and/or synaptic networks with genetic alterations. Abstract: Monday 9.sup.th July, 200714:15 - 15:15Main SessionBallroom 2Prognosis In People With Epilepsy: Seizure Control, Remission And Intractability Brodie M.J. .sup.1 (Western Infirmary, Epilepsy Unit, Glasgow, Scotland, UK) Abstract: Berg A .sup.1 (Northern Illinois University, 429 Montgomery Hall, Illinois, USA) Intractable epilepsy is a concept that refers to epilepsy in which seizures are not fully controlled by standard pharmacologic treatments. Intractability is generally considered in the context of referral center populations. There the question is not whether someone's epilepsy is intractable but how best to treat it given a long history of repeated drug failures. Treatment of epilepsy once it is intractable is a tertiary prevention goal. Ideally, we would like to prevent epilepsy from becoming intractable in the first place (primary prevention) or maximize efforts to treat it as soon as it becomes intractable (secondary prevention). This requires identifying intractability when it first declares itself which, in turn, requires clear, unambiguous, robust, criteria that can be applied prospectively. Several definitions have been proposed and compared head-to-head. For the most part, there is reasonably good agreement among the definitions. Depending on the clinical or research purpose, (e.g. enrolment in a new drug trial versus surgery) different operational definitions may have relative strengths or weaknesses. There is an erroneous assumption that if epilepsy will be intractable, that fact can be ascertained soon after onset. This is not always the case. Whether epilepsy becomes intractable and when is largely a function of the underlying type of epilepsy (syndrome). The epileptic encephalopathies typically declare themselves intractable from the very outset with relentless onslaught of seizures and a clear immediate failure to respond to medications. Focal cortical epilepsies, by contrast, can follow an indolent, "stuttering" course making it very difficult to know when a drug has failed. Both careful delineation of the time course over which intractability unfolds in specific forms of epilepsy and recognition that predictors of intractability early in the course may differ from predictors later in the course are needed before we can improve early and meaningful identification of intractability. Abstract: French J .sup.1 (University of Pennsylvania, 3400 Spruce Street, Philadelphia, USA) Much of what is currently known about refractory epilepsy derives from studies in newly diagnosed patients. This may not be the only, or even the optimal population to study. Although it is tempting to look at epilepsy as a monophasic illness, in which patients can be easily categorized as drug resistant or drug sensitive early in their course, studies indicate that many people will alternate back and forth between these two states, and spontaneous remissions are not uncommon..sup.1 Recently, rather than identifying patients initiated on therapy, to determine who will be refractory, several studies have focused on patients who have established treatment resistance, to see who will remit. Randomized controlled trials of new AEDs in patients with refractory epilepsy have shown relatively low seizure free rates, even in the short term, ranging from 0-7.9%.sup.2 In another recent study specifically looking at short-term seizure freedom with the new drug pregabalin, estimates of seizure freedom for pregabalin were 5.5%, 1.3%, and 0.4% for baseline seizure frequencies of 5, 10, and 15 respectively, indicating that patients with a high baseline seizure frequency were less likely to remit. A study performed in 155 adult patients with therapy resistant epilepsy treated in a single practice demonstrated that 16% became seizure free for at least 6 months..sup.3 A second study followed 246 adult refractory patients for 3 years. The remission rate (at least 12 month) was 5%/year. .sup.4 Factors predicting continued seizures included a history of status epilepticus, younger age at intractability, number of drugs failed, and the presence of mental retardation. In summary, patients with seemingly refractory epilepsy can, indeed ultimately respond to therapy. Further study is needed to determine prognostic indicators for remission, and to see whether refractory patients who become seizure free will remain so long-term. 1.Sillanpaa M, Schmidt D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain. 2006;129:617-24. 2.Gazzola D, Balcer L, JA French. Seizure free Outcome in Randomized add-on Trials of the New Antiepileptic Drugs. Epilepsia 2007 In Press. 3. Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007. 4.Callaghan B, Anand K, Hauser W, French J. The Likelihood of Seizure Remission in an Adult Population with Refractory Epilepsy. Epilepsia. 2005;5(6C):S594. Abstract: Monday 9.sup.th July, 200715:45 - 17:15Ballroom 2Post Main SessionAcute Symptomatic Seizures: What Is The Frequency,The Prognosis And The Relation To Epilepsy Hauser A .sup.1 (Columbia University, 630 West 168th Street, New York, USA) Acute symptomatic seizures occur at the time of a systemic insult or in close temporal association with a documented brain insult. Acute symptomatic seizures differ from epilepsy in several important aspects: First, unlike epilepsy, these seizures have a clearly identifiable proximate cause, to extent that one can ever be certain of a causal association. When one considers the temporal sequence of acute symptomatic seizures (e.g., uremia, head injury, or stroke immediately preceding a seizure), the biologic plausibility (acute disruption of brain integrity or metabolic homeostasis) and in many cases the dose effect (severity of injury correlated with the risk for seizures) all quite compellingly indicate causation. There are few studies of the incidence of acute symptomatic seizures. The age-adjusted incidence for 1955 to 1984 in Rochester Minnesota was 39/100,000 and accounted for 40% of all cases of afebrile seizures identified in the community during the study period. This rate is somewhat higher than that reported in Gironde, Bordeaux, France, (29 per 100,000) but also accounted for 40% of afebrile seizures. In industrialized countries, the greatest proportion of acute symptomatic seizures is associated with stroke followed by trauma and infection. In developing countries, the distribution of causes is probably different. About 5% of people with brain trauma will have a seizure at the time of the insult. Between 3 and 5% of people with stroke will have acute symptomatic seizures. People with acute symptomatic seizures due to acute neurologic insults are also associated with an increased risk for subsequent epilepsy. Abstract: Beghi E .sup.1 (Istituto Mario Negri, Via Eritrea 62, Milano, Italy) Several acute and chronic metabolic and endocrine disorders may cause CNS dysfunction and provoke acute symptomatic seizures (ASS). However, in order for a metabolic or endocrine dysfunction to be epileptogenic, the abnormal findings can be associated with the seizure if documented within 24 hours of the event and specific cut offs must be identified. In the absence of standard values, temporary bounds for metabolic factors that may precipitate seizures can be obtained from classic textbooks (Plum & Posner, 1972). The following values may cause ASS: glucose 25 mmol/l associated with ketoacidosis (whether or not associated with long-standing diabetes); sodium < 115 mmol/l; calcium < 5.0 mg/dl (35.7 mmol/l); creatinine > 10.0 mg/dl (>884 micromol/l). Although alcohol is commonly thought to be associated with seizures, the validity of information on alcohol intake depends upon the source (interview vs. medical record) and the stigma associated with alcohol use and abuse. Alcohol-withdrawal seizures must be considered at the presence of a history of chronic alcohol abuse, current alcohol use with reduction in consumption, and symptoms of withdrawal such as tremors or delusions. Seizures must occur within 7-48 hours of the last drink. If there is a history of recent alcohol abuse without a known history of chronic alcohol abuse, then clinical judgment should determine whether or not the seizure was due to alcohol withdrawal. Other substances, including drugs and illicit compounds, have been associated with the risk of epileptic seizures. Illicit drugs such as cocaine, phencyclidine, amphetamines and heroin can also cause seizures. Past and present heroin use is a risk factor for acute symptomatic and unprovoked seizures. Drug overdose or very high level of therapeutic drugs can be associated with ASS. In contrast, for drugs given at therapeutic doses, finding a correlation between drug exposure and occurrence of seizures does not necessarily establish a causal association. Using an evidence-based approach, drugs can be classified according to their epileptogenic potential. Drugs with high epileptogenic potential include meperidine, sevoflurane, clozapine, phenothiazines and cyclosporine. Drugs with intermediate epileptogenic potential include propofol, maprotiline, tricyclic antidepressants and chlorambucil. Drugs with low epileptogenic potential include fluorquinolones, carbapenems, bupropion and iodinated contrast media. Abstract: Carpio A .sup.1 (University of Cuenca, Consultorios Sta. Ines, F.Proano Y D. Cordova (Esquina), PO Box 0101-719, Cuenca, Ecuador) Acute symptomatic seizure (ASS) is defined as a seizure in close temporal association with an acute CNS insult or transient systemic disturbance. Information regarding ASS is extremely scarce in developing countries and in the developed world as well. According to the available information, causation and prognosis of ASS are quite different from those of epilepsy. Patients with a first afebrile seizure were prospectively identified in a general hospital of Ecuador: 51 (34.7%) had unprovoked seizures and 97 (65.3%) provoked or ASS. Among the 97 patients with ASS, the median age was 15 y. (range: 1 month to 84 years); 69 % were children and 31% adults. Status epilepticus was present in 26% of patients and 18.6% patients died during hospitalization. The main causes were: CNS infections (20.6%); cerebrovascular diseases (13.4%); neurocysticercosis (NC) (9.3%); trauma (8.2%); and tumors (6.2%). Seventy two patients were followed-up by 2 years. Patients with ASS had less recurrence risk (5.6%) compared to patients with unprovoked seizures (16.7%). On multivariable analysis, age, gender, seizure type, family history of epilepsy, did not predict recurrence. Only CT abnormalities and etiology predicted recurrence. The major causes of ASS in developed countries are traumatic brain injury, drug withdrawal, cerebrovascular disease, and CNS infection; as is also the case in developing countries; however, in these countries NC is one of the most common causes of ASS. NC is a typical example of ASS. Although the risk of subsequent epilepsy may be initially increased in patients with NC, in general it does not entail expectancy of seizure recurrence, unless acute brain inflammation recurs due to degenerative cysts. Such patients usually do not need to be treated on a long term basis with antiepileptic drugs, although such treatment may be warranted on a short-term basis until the acute condition is resolved. Much of the ASS in the developing world results from preventable causes. Abstract: Monday, 9.sup.th July 200715:45 - 17:15Ballroom 1Parallel SessionMood Disorders, A Co-Morbidity in Children with Epilepsy Heyman I .sup.1 (Great Ormond Street Hospital For Children, UK) This presentation will review both historical, and recent, epidemiological evidence showing that children with epilepsy are at increased risk for mental health problems, including anxiety and depression. Comparison will be made with both the general population, and to those with chronic illnesses not involving the central nervous system (CNS), and involve a discussion of the factors assumed to increase risk for emotional disorders in the child with epilepsy. Children with both epilepsy and structural CNS abnormality are more likely than not to have psychopathology, and the evidence for this will be reviewed. The impact and burden of this psychiatric co-morbidity contributes significantly to the overall disability, and recent studies which measure impairment, in addition to presence of symptoms, will be considered. Children with epilepsy often receive inadequate assessment, detection and treatment of co-morbid psychiatric difficulties, and there will be discussion of why this might be. The most common child mental health problems, including anxiety and depression, occur at higher rates in children with epilepsy, but there are currently few studies which examine treatment responsiveness of these psychiatric disorders in the child with epilepsy. The literature in this area will be reviewed, with consideration given to the impact of seizure alleviation on emotional and behavioral problems, as well as issues regarding direct treatment of co-morbid mental health needs in the child with epilepsy. There will be consideration of how to use the best evidence-based psychological and pharmacological treatments for depression and anxiety, in the child with epilepsy. Abstract: Hesdorffer D .sup.1 (Columbia University, USA) Many studies show that mood disorders are comorbid with epilepsy. Most of these studies are cross-sectional and have been conducted in adults, not in children. The relative paucity of such studies in children likely occurs because there is controversy concerning the validity of a diagnosis of mood disorders in young children. This talk will review the concept of comorbidity and will consider methodological issues important to studies of epilepsy and mood disorders in general and specifically in children. The data on comorbidity of mood disorders in children with epilepsy will be discussed and suggestions made for further research in this critically important area. Abstract: Caplan R .sup.1 (Semel Institute for Neuroscience and Human Behavior, USA) Purpose: This study examined the rate of depression and anxiety in children with epilepsy compared to normal children using established instruments. It also determined the sensitivity and specificity of these tools for depression and anxiety in these children. Methods: A structured psychiatric interview, the Children's Depression Inventory (Kovacs, 1985) and Multidimensional Anxiety Scale for Children (March et al., 1997), as well as cognitive testing were administered to 84 children with epilepsy and 40 normal children, aged 5-16 years. Parents provided behavioral information on each child through a structured psychiatric interview and the Child Behavior Checklist (Achenbach, 1991). Results: Significantly (p < .02) more children with epilepsy (25%) had DSM-IV affective and anxiety disorder diagnoses than the normal group (7.5%) with higher rates of anxiety disorders than depression. They also had significantly higher CDI scores (p < .0001), MASC scores (p < .009) and CBCL anxiety/depression (A/D) factor score (p < .001) than the normal group. Using structured interview based DSM-IV diagnoses as the gold standard, the highest sensitivity was achieved with the MASC (84%) and highest specificity with the CBCL A/D factor score (91.7%). Conclusions: In addition to the high rate of depression and anxiety disorder diagnoses in children with epilepsy, these findings suggest that borderline/clinical MASC and parent CBCL A/D scores can be used to screen for children with these diagnoses. However, children with normal A/D scores and borderline/clinical MASC will require a psychiatric diagnostic interview to confirm these diagnoses. Funding supported by NINDS 32070 Abstract: Dunn D .sup.1 (Indiana University School of Medicine, USA) Though depression may affect one-fourth of adolescents with epilepsy, depression in children and adolescents with epilepsy is too often unrecognized and untreated. These patients may have reduced quality of life and are at risk for suicidal ideation. Specific intervention trials for children and adolescents with epilepsy and depression are not available. Thus, health care professions need to use standard psychotherapies and psychopharmacological interventions appropriate for children and adolescent with depression, modifying them for the patient with epilepsy. Therapy might start with psychoeducation, delivered in group settings or by innovative techniques such as conference calls or internet. Programs for parents and children have improved knowledge, reduced anxiety, and lessened worries and concerns. Individual and group psychotherapies that teach coping skills and relaxation techniques may reduce emotion-based precipitants that increase seizure frequency. Standard cognitive behavioral therapy for depression should be helpful though no trials in children with epilepsy were found. Psychopharmacologic treatment of depression may be beneficial though there are no randomized controlled trials in children or adolescents with epilepsy. In adults with epilepsy, sertraline, citalopram, reboxetine, and mirtazapine have been effective in reducing symptoms of depression without adverse effects on seizure control. Trials of sertraline and citalopram in children and adolescents with depression but no epilepsy have demonstrated improvement in symptoms of depression without excessive side effects. Therapeutic trials in children and adolescents with depression and epilepsy are warranted. Once started on SSRIs, children and adolescents should be assessed for potential drug side effects including gastrointestinal problems, lethargy, behavioral activation, akathesia, and suicidal ideation. Because of the SSRI induced inhibition of cytochrome P450 enzymes, serum levels of antiepileptic drugs must be monitored. Tricyclic antidepressants have not been effective in treating depressed children or adolescents. Bupropion might be helpful but lowers the seizure threshold at higher doses and must be used cautiously. Abstract: Monday, 9.sup.th July 200715:45 - 17:15Ballroom 3Parallel Session(In collaboration with the Global Campaign against Epilepsy)Addressing Epilepsy Knowledge And Research Gaps In Developing Countries Tan C T .sup.1 , Tan L K .sup.1 (University of Malaya, Malaysia) In contrast to print journals, the on-line journals have the advantages of efficiency in management of manuscripts; flexibility in numbers and length of articles, use of colored pictures, audios, videos, and readers feedback; searching and hyperlink of references; saving of shelving space; accessibility around the clock and in remote area; with no increased cost for printing and distribution for increased readership. There are also disadvantages: There are few subscribers except libraries with increased price of subscription. The fixed costs of electronic journal are quite similar to print journals with uncertainty in financial returns. The low starting cost leads to proliferation of journals, with problem of quality and sustainability. Many websites have disappeared with no one having a stored copy. The rapid change in technology results in tapes and disks that can no longer be read. Also, users must have computers and software to access. Neurology Asia (www.neurology-asia.org) and Biomedical Imaging and Interventional Journal (www.biij.org) are both on-line journals based in developing world by Asian regional medical societies, free for both authors and readers. Neurology Asia is focused on Asian Neurology, also with print version. Both journals enjoy large hits and visits, and operate on low-cost model depending largely on sponsors and voluntary efforts. Listing in PubMed is the main challenge to ensure its continuing growth. In conclusion, free on-line journal can have an important role in reducing knowledge and research gap in developing countries. Successful free on-line journals require clear roles, critical mass of authors and readers, long-term commitment and viable financial structure. Abstract: Mehndiratta M M .sup.1 (Department of Neurology, G. B. Pant Hospital, New Delhi-110002, India) Epilepsy is one of the major brain disorders worldwide. The mean number of people with epilepsy per 1000 population varies across region. While it is 12.59 and 11.29 in the Americas and Africa, respectively, it is 9.97 in South-East Asia, 9.4 in the Eastern Mediterranean, 8.23 in Europe, and 3.66 in the Western Pacific. The mean number of people with epilepsy per 1000 population ranges from 7.99 in the high-income countries to 9.50 in the low-income countries. The total estimated world population is around 6.5 billion and population of Asia is approximately 3.7 billion. The difficulties related to epilepsy faced by the low resources countries are: poor research, care infrastructure and facilities, including the treatment gap in rural area; lack of neurologists, paramedical personnel; and continuing education, referral system, research, nursing support, etc. Treatment gap is the percentage of persons with active epilepsy who at any one time are not receiving anticonvulsant treatment. Epilepsy is responsible for an enormous amount of suffering affecting about 50 million people around the world, yet in the developing countries the large majority of people with epilepsy remain excluded from receiving care and are consequently maintained in the shadow of the treatment gap. A comprehensive epilepsy program is one in which a multi-disciplinary team (physicians, psychologists, nurses, social workers, and specialized technical help) is brought together to provide an organized approach to the management of people with complex problems of epilepsy. A survey of country resources available for epilepsy care was conducted within the framework of the ILAE/IBE/WHO Global Campaign Against Epilepsy and the data collected confirmed that epilepsy care was grossly inadequate compared with the needs in most countries. In addition, large inequities exist across regions and income groups of countries, with low-income countries having extremely meager resources. It is possible to narrow the research gap as well as treatment gap in epilepsy with improved understanding of mechanism, better care, awareness and education. Abstract: Cavalheiro E .sup.1 (Universidade Federal De Sao Paulo, Brazil) Abstract: Monday, 9.sup.th July 200715:45 - 17:15TheatreParallel SessionEpilepsy Genetics In The 21st Century (Part 2): Building Bridges From The Laboratory To Patient Care Serratosa J .sup.1 (Epilepsy Unit, Fundacion Jimenez Diaz, Madrid) We have reached the times where human epilepsy gene discoveries have a significant impact on the diagnosis and counseling of patients and families with epilepsy. It is foreseen that in the future gene discoveries may also have a major impact on the treatment of patients with epilepsy. 1. Diagnosis During the last decade research efforts in genetics, have led to the delineation of new epilepsy syndromes. These syndromes must be considered when approaching a patient with epilepsy. Several genetic epilepsy syndromes for which the responsible gene has been identified can now be diagnosed using molecular genetic testing. Direct mutation tests can now be performed for the majority of the progressive myoclonus (several genes) epilepsies and Dravet syndrome (SCN1A). Genetic testing directed to the identification of allelic variants that contribute to the common epilepsies may be useful in the future in order to predict increased seizure risk and to select the most appropriate drug for each individual (highest efficacy with least side effects). 2. Prognosis-counseling Adequate and precise diagnosis based on genetic information can provide patients with key prognostic information such as disease evolution, remission index and response to specific treatments. For example, in the progressive myoclonus epilepsies the diagnosis of Unverricht-Lundborg disease implies an almost normal life span and mild or no dementia. In contrast, in other progressive myoclonus epilepsies (such as Lafora disease or the neuronal ceroid lipofuscinoses) the prognosis is very poor and patients invariably die after a few years of disease progression. 3. Therapy As epilepsy genes are discovered, new drug targets are being identified and tested in the development pipeline of AEDs. Finally, as DNA sequencing costs diminish in unpredicted orders of magnitude, it is becoming more feasible to perform large-scale genome sequencing of individuals for a reasonable cost. This will allow for the identification of genetic profiles associated with antiepileptic drug response. Abstract: Ottman R .sup.1 (Columbia University, USA) Substantial progress has been made in the identification of genes that influence risk for some forms of epilepsy. One of the most important potential applications of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk of developing epilepsy in the future (predictive testing). Currently no established guidelines are available for the use of genetic testing in the epilepsies. Such guidelines are needed because of the great complexity in assessing the potential benefits and harms of testing in particular situations, and because many (if not most) practicing epileptologists are unfamiliar with the types of tests available, how to access them, how to decide whether or not they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients if they are offered. Establishment of recommendations for genetic testing in the epilepsies as a whole would be extremely difficult because of the large number of different epilepsy syndromes and their different clinical contexts, genetic contributions, and social, familial, and individual ramifications. However, here we provide a framework for considering the utility of genetic testing that can be applied to many different syndromes and contexts. This framework consists of four components of evaluation: analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications. These four areas will be discussed with regard to selected examples in the epilepsies where testing appears to have high utility, and others where it appears less useful at the present time. Finally, we provide guidelines for the manner in which testing is carried out: informed consent and pre- and post-test genetic counseling are essential to maximize benefit and minimize harm. Abstract: Tan N .sup.1 (National Neuroscience Institute, Singapore) Genetic association studies are genetic case-control studies that aim to identify common polymorphisms that influence susceptibility to epilepsy. Unfortunately, association studies have given conflicting results, due to myriad factors. One key problem is that of inadequate sample size; many studies are underpowered to identify the small effect sizes believed to underlie disease susceptibility. Genetic meta-analyses may shed some light. Pooling the results of multiple studies may provide sufficient power to give reasonably narrow point estimates and confidence intervals of the effect size. However, heterogeneity, publication bias, choice of genetic model remain issues of concern, though these may be surmountable in the near future. Abstract: Monday, 9.sup.th July 200715:45 - 17:15Room 209Parallel SessionHuman Herpes Virus 6 And Epilepsy Jacobson S .sup.1 (USA) Abstract: Shinar S .sup.1 (Albert Einstein College of Medicine, USA) Abstract: Gaillard W D .sup.1 (Children's National Medical Centre, USA) The most common pathological finding in patients with temporal lobe epilepsy (TLE) is mesial temporal sclerosis (MTS). Most patients with TLE and MTS have seizure onset during childhood, with an average age of 8-14. The most common historical event in patients with MTS is a history of complex or simple febrile seizures, found in about 1/3 of patients. One third of patients prospectively identified have evidence of MTS before age five years. After febrile seizures (one third), 10% have evidence of dual pathology, 15% acute brain infection, and 6% a history of immune suppression or transplant organ rejection, and 6% a history of prematurity with stroke. Imaging studies with MRI, MRS, and FDG-PET in patients with TLE and pathological studies from surgical specimens provide evidence for an initial insult followed by slow progressive decline in HF volume regional metabolism and cell counts. 60% of our MTLE (n = 23) are HHV6B+, and none with extratemporal epilepsy (n = 14). Only half with MTS and febrile seizures are HHV6B+; one third without a febrile seizure history are positive. HHV6B is found primarily in astrocytes, and is associated with decreased glutamate transporter uptake. The association with febrile seizures, and evidence for progressive disease, lead to the hypothesis that a chronic non-inflammatory, or reactivated, viral infection may be present. Clinical and experimental data suggest that glutamate toxicity may be a final common pathway for CA1 and CA3 cell loss in HHV6B mediated TLE and other causes of MTS. The observations may also account for the prolonged latency period found in some patients after an apparent precipitating event early in life. Abstract: Bien C G .sup.1 (University of Bonn, Dept. of Epileptology, Germany) Emerging evidence indicates that the brain destruction in Rasmussen's encephalitis (RE) is mediated by cytotoxic T lymphocytes. Immunohistochemical studies on brain tissue of affected individuals show that granzyme B positive T cells attack and destroy neurons and astrocytes (but not oligodendrocytes or myelin). However, it is still unclear what initially triggers this inflammatory process. T cell cytotoxicity can occur in the context of tumor immunity, autoimmune diseases and the immune response to viral infection. Since RE is obviously no tumorous disorder, etiology is most likely either linked to autoimmunity or a viral infection. In his 1958 index paper on the condition, Rasmussen himself suggested a viral origin. Contrary to a common belief, subsequent research has by no means "excluded" this. The existing studies have just provided inconclusive and in part contradictory data regarding an infection with the well-known herpesviridae herpes simplex virus (HSV) 1/2, cytomegalovirus, Epstein-Barr-virus, and human herpesvirus 6. There has, however, been no research on the potential association between RE and any of the other virus families. The unihemispheric nature of RE is also no contradiction to the virus hypothesis: Interestingly, Epilepsia partialis continua (EPC), the typical seizure type of RE, was initially described by Kosevnikov in a population of Siberians in which later on the usually unihemispheric and EPC-associated tick-borne viral Russian spring-summer meningoencephalitis was detected. Finally, we have observed the nuclear presence of inclusion body-like heat shock protein 70-reactivity in brain specimens of RE patients but not in controls (J. Bauer and C. G. Bien, in preparation). This observation is well compatible with the assumption of a viral protein accumulation in the nucleus which may serve as an additional hint to a viral etiology of this disorder. Further research is needed to demonstrate the hypothesized viral agent triggering the immune process of RE. Abstract: Tuesday, 10.sup.th July 200707:30 - 08:30Ballroom 1EUREPA SeminarEUREPA Seminar Series 1 - Discussion On Difficult Cases In Childhood Epilepsies Discussants: Plouin P .sup.1 Capovilla G .sup.2 Covanis A .sup.3 Koutroumanidis M .sup.4 (Hopital Necker Enfants Malades, France ; C. Poma Hospital, Italy ; The Children Hospital Agia Sophia, Greece ; St Thomas Hospital, UK) Abstract: Tuesday, 10.sup.th July 200707:30 - 08:30TheatreEUREPA SeminarEUREPA Seminar Series 2 - Discussion On Difficult Cases In Adult Epilepsies Discussants: Avanzini G .sup.1 Van Emde Boas W .sup.2 Najm I .sup.3 Stefan H .sup.4 (Italy Netherlands USA Germany) Abstract: Tuesday, 10.sup.th July 200707:30 - 08:30Room 209EUREPA SeminarEUREPA Seminar Series 3 - Discussion On Seizure Related Automatisms Luders H O .sup.1 (University Hospitals Medical Group, USA) Abstract: Gardella E .sup.1 Francione S .sup.2 (Bellaria Hospital, Italy C. Munari Epilepsy Surgery Centre, Italy) Purpose: the aim of this contribute is to characterize the features of different patterns of ictal complex motor behaviours principally included in the wide range of hyperkinetic (HK) manifestations, with or without an emotional component. Methods: Among the series of patients having undergone a presurgical investigation in the last decade (Epilepsy Surgery Centre "C. Munari", Milan; Bellaria Hospital, Bologna; "S. Paolo" Hospital, Milan), we selected those patients presenting seizures with HK manifestations. We performed a clinical and kinematic study of video-EEG data, consisting in the estimation of displacement, speed and acceleration of body segments (Videopoint Computerized System). Ictal emotional modifications of the facial expression were studied by clinical and FACS (Facial Action Coding System) analysis. Clinical EEG/SEEG correlations has been investigated, evaluating also the possible localizing/lateralizing value of single behavioural manifestations. Results: We observed different clinical-kinematic subgroups of HK/bipedal behaviours. Together with a "symmetrical" HK pattern with bilateral movement of trunk and limbs, we observed also "focal" HK patterns (e.g. hemilateral pattern, due to dystonic posturing contralateral of the ictal discharge; hemivertical and axial pattern, prominently involving respectively lower limbs or trunk) or a fragmentary, arrhythmic HK pattern ("puppet" pattern). In 72% of the patients an emotional modification of the facial expression has been observed (mainly fear). In all patients the symptomatogenic zone, during HK/bipedal manifestations, was an extended fronto-mesial area including the gyrus cinguli, mostly involving the non dominant hemisphere. The former motor pattern (puppet) had prominent fronto-lateral ictal onset. A slower motor activity often characterized the seizures of patients already operated on in frontal lobe. Conclusions: Despite the relative homogeneity in the descriptions of frontal motor behaviors with HK features, we observed a significant interidividual variability of the clinical manifestations. Usually the patients refer to be an observer of his own ictal motor activity, experiencing an "urge to move", sometimes associated with "fear to falling down". In fact, stereotyped motor behaviors could be associated to a facial emotional modification. HK behaviors reflect the diffusion of the ictal discharge to a widespread fronto-mesial circuit, mainly in the non dominant hemisphere. Other cerebral areas are probably involved in the modulation of the rhythm and/or of the spatial distribution of the HK manifestations, giving rise to this clinical heterogeneity. Abstract: Kahane P .sup.1 (Grenoble University Hospital, France) Author Affiliation: (1)Hopital Necker Enfants Malades, France (2)C. Poma Hospital, Italy (3)The Children Hospital Agia Sophia, Greece (4)St Thomas Hospital, UK