Day 1 :
Keynote Forum
Tomokatsu Hori
Director, Tokyo University, Japan
Keynote: Abnormal immature granule cells are specific to hippocampal sclerosis type 1
Time : 10:00-10:50
Biography:
Abstract:
ILAE task force proposed a simple histological classification of hippocampal sclerosis. Surgical results based on this classification are presented, and PSA-NCAM abnormal immature granule cells are detected in type 1 HS. Type 1 HS is found in 25 patients (61% ) and (1) types of HS doesn’t correlate with age at operation and duration of illness, suggesting that these types represent distinct pathology of MTLE, (2) the mean age of onset in patients with type 1 sclerosis tends to be younger than those at least with no HS but this is not statistically significant (Kruskal-Wallis test), (3) the history of initial precipitating injury is not correlated with histological subtypes or post-operative seizure outcome, and (4) type 1 sclerosis seems to correlate with better post- surgical seizure outcome than other types. The choice of the operative procedure is important factor affecting the seizure outcome and that lateral temporal structure is also involved in the epileptogenesis in a subset of patients with MTLE. In fact, SAH alone is effective in over 80% of patients with type 1 sclerosis (Fisher’s exact test, p<0.05) but not for patients with type 3 sclerosis. The remarkable feature of our study is the presence of bizarre immature PSA-NCAM positive neurons in HS type 1 hippocampus. This neuron has a peculiar irregular soma with abundant neurites and synapses. The absence of bona fide astrocytes, presence of abnormal PSA-NCAM immature neurons might be neuron-glia abnormality causing long-lasting intractable TLE.
Keynote Forum
Sara Eyal
The Hebrew University of Jerusalem, Israel
Keynote: Effects of antiepileptic drugs on the placental function as a protective barrier
Time : 11:10-12:00
Biography:
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 previously demonstrated that AEDs affect the expression and activity of placental uptake and efflux carriers for essential compounds, including folate and thyroid hormones,in a human placental cell line and in pregnant mice. This talk will present our recent findings on the effects of AEDs on the human placenta, with a focus on the most teratogenic AED, valproic acid. 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.
Keynote Forum
Alberto Musto
Eastern Virginia Medical School, USA
Keynote: Preventing neuronal network disruption following brain injuries
Time : 12:00-12:50
Biography:
Abstract:
Temporal lobe epilepsy (TLE), or limbic epilepsy, the most common form of epilepsy in adults, has no cure. The current medical treatments are not effective to control some limbic seizures. Patients with TLE are still at risk for early mortality and comorbidities such as cognitive dysfunctions, depression and anxiety disorders. They also have higher prevalence of systemic disorders that exacerbate adverse effects from anti-epileptic drugs. TLE also carries a social stigma and increases the costs of health care and community. TLE is characterized by spontaneous recurrent complex partial seizures (limbic seizures) that arise in the hippocampus, spread within limbic circuitry and to other brain regions. LE is a product of complex biological events denominated limbic epileptogenesis (LE). LE is associated with brain injuries that alter neuronal network connectivity, which is leading to hyper-excitable network and limbic seizure susceptibility. Brief hippocampal spontaneous epileptiform activity, or microseizures observed in LE reflect small epileptogenic generators related to strong depolarization from pyramidal layers associated with an increased hyper-excitability, thus reflecting a complex pathological microcircuit activity. Microseizures are related to spontaneous bursts of certain groups of neuronal networks that lead to robust neuronal reorganization in epilepsy (i.e., chronic epilepsy), contributed, in some way, by an impairment of altered GABAergic perisomatic interneurons suggesting a dynamic and complex pathophysiology for the neuronal network involved in LE. Also, pathological high frequency oscillations (pHFOs) might precede microseizures and it could contribute to the propagation of MEA. pHFOs may recruit and synchronize other aberrant neuronal networks, which then trigger spontaneous recurrent seizures. Those aberrant networks are related to modification of dendritic spines (DS), subcellular site of the formation of aberrant neuronal network in LE. DS, morphological signature of postsynaptic sites and excitatory synaptic transmission, play a critical role in neuronal network assemblies during epileptogenesis. Modulation of activated inflammatory pathways, voltage-gated sodium channels, and the mTOR pathway are proposed for anti-aberrant neuro-network plasticity in LE. Continued clinical and experimental research in LE is critical for the discovery of new therapies to prevent TLE and to reduce adverse effects and pharmaco-resistance. Overall, the challenge in epilepsy research is to evaluate promised interventions for epileptogenesis and at the same time to identify biological mechanisms that can prevent aberrant neural network dysfunction.
- Epilepsy|Epilepsy Therapeutics|Epilepsy Case Reports
Location: Diplomat
Session Introduction
Elizabeth de Lange
Leiden University, Netherlands
Title: Pharmacoresistance is not associated with changes in P-gp expression at the level of the blood-brain barrier
Time : 12:50-13:20
Biography:
Abstract:
Increased expression of P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in pharmacoresistant epilepsy has been reported. It is thought to cause insufficient antiepileptic drug brain concentrations, and thereby decreased seizure control. However, the question remains how BBB P-gp expression changes with time, and if it is a reliable indicator for changes in BBB P-gp function. In rats, the relationship between P-gp expression (ex-vivo by immunohistochemistry) and function (BBB transport of quinidine, with or without P-gp inhibition by tariquidar) was determined up to 3-5 weeks following kainate induced Status Epilepticus (SE). SE was induced by intraperitoneal injections (IP, group A) or unilateral intrahippocampal injection (IH, group B). In addition, IH injection was followed by in vivo bilateral hippocampal microdialysis experiments (IH, group C). Following SE, for all groups, an initial increase in P-gp expression was followed by a subsequent decline. Group C showed a lack of relation between BBB P-gp expression and BBB P-gp function in individual rats.In conclusion, there is no relationship between BBB specific P-gp expression and function, and pharmacoresistant epilepsy is related to temporal changes in BBB P-gp expression, but is not related to changes in BBB p-gp function, but merely at the brain parenchymal cell level.
Naoto Hoshi
University of California, USA
Title: Palmitoylation of neural proteins might be a link between lipid metabolism and anticonvulsant action
Biography:
Abstract:
We recently found that valproic acid suppresses palmitoylation of neural proteins including AKAP5 (AKAP79/150). Reduced AKAP5 palmitoylation disrupted regulation of the M-current, which is generated by neural Kv7 channel family. Various neurotransmitters that activate Gq-coupled receptors suppress M-current and increase neuronal excitability. We show that palmitoylation is required for receptor-induced M-current supprssion. Similar disruption of M-current suppression was observed by inhibition of acyl-CoA synthetase. These results might fill in a gap between lipid metabolism and its anti-convalsant action.
Biography:
Abstract:
Epilepsy is a group of neurological disorders in which neurons’ signaling is corrupted. This condition characterized by a long-term risk of recurrent seizures and affects up to 1% of the general population. There are various genetic and environmental factors such as neuromuscular disorders, brain injury and abnormal brain development that resulted in epilepsy. More than 20 single gene syndromes and conditions whose main feature is epilepsy, or at least epilepsy is one of the significant manifestation, have been described. These neonatal or childhood syndromes manifest neurodegenerative lesions and majority of them shows autosomal dominant pattern of inheritance. These syndromes are: Autosomal dominant partial epilepsy with variable foci, autosomal dominant nocturnal frontal lobe epilepsy, benign familial neonatal convulsions, benign infantile familial convulsions, familial temporal lobe epilepsy, generalized epilepsy with febrile seizures plus, progressive myoclonic epilepsies (PMEs)-group of progressive neurological deterioration together with myoclonus and epilepsy autosomal recessive disorders-, neurofibromatosis 1 (NF-1) as a result of neuronal migration abnormalities in which approximately up to 13% of patients -1 develop epilepsy, tuberous sclerosis a complex disorder in which about 80% of affected manifest epilepsy, X-linked fragile X syndrome which develop mental retardation in affected male and up to 40% of patents develop epilepsy, X-linked dominant Rett syndrome a neurodevelopmental disorder in which about 70% to 80% of cases develop epilepsy, leukodystrophies, acute intermittent porphyria, inherited metabolic conditions like mucopolysaccharidoses. All of the aforementioned conditions show epilepsy as one their symptom but their differences are specific manifestations and age of onset. Understanding and distinguish each condition leads to appropriate management, diagnosis and therapy.
- Diseases Associated with Epilepsy |Prevention and Management of Epilepsy
Location: Diplomat
Session Introduction
Seth Omari Mensah
Kharkov National Medical University, Ukraine
Title: Management of epileptic seizures in ghana: complications of putting a spoon into an epileptic seizure patient’s mouth to prevent biting of their tongue
Biography:
Abstract:
Bryony Wilkes
St George’s University Hospital, United Kingdom
Title: Screening for mental health conditions in children with epilepsy
Biography:
Abstract:
The Strengths and Difficulites Questionnaire (SDQ) was used to screen for those at risk of, or currently experiencing MH problems. We received 86 replies and, following exclusions, 64 patients data was analysed. The patient’s electronic notes were used to determine diagnoses and medications.56% of patients scored high or very high risk for having or developing MH difficulties. A chi- square test indicated a significant difference (p<0.001) in the proportion of children with epilepsy with clinically significant scores versus the proportion in the community samples. Peer and pro-social subdomains scored in the ‘high’ risk category whilst the other subdomains scored in ‘close to average’ risk. Patients not on anti-epileptic drugs have close to average scores. There is trend towards those on more than 1 Antiepileptic drug having higher scores. Developmental disorder increases that risk of having a high or very high score from 43% to 68%.Our results reflect similar prevalence to that demonstrated in the literature; children with epilepsy have a high risk of developing MH disorders. Our data highlights the need to improve identification, diagnosis, prevention and management of MH problems in children with epilepsy on both a national and local level.
- Impact of the Epilepsies on daily life |Epilepsy in Women and Inborn
Location: Diplomat
Session Introduction
Ali H Alwadei
National Neuroscience Institute, Saudi Arabia
Title: Loss-of-function mutation in RUSC2 causes intellectual disability and secondary microcephaly
Biography:
Ali H Alwadei currently works at Pediatric Neurology Department, National Neuroscience Institute, King Fahad Medical City, PO Box 59046, Riyadh 11525, Saudi Arabia.
Abstract:
Intellectual disability is seen in up to 1% to 3% of the general population, and is often dichotomized into syn- dromic and non-syndromic forms.1 A genetic aetiology accounts for about 25% to 50% of cases, with up to 700 monogenic mutations identified so far.2 Recent advances in genetic testing have allowed the identification of an ever- increasing repertoire of genes causing intellectual disabil- ity.2 Characterization of their protein products has shed light onto the diverse biological pathways affected in this important neurological disease that results in significant impairment in cognitive and adaptive behaviour, and which has important medical and social implications.3 Aberrancies in synaptic vesicular transport and intracel- lular protein trafficking have been highlighted among the various biological pathways reported to cause intellectual disability.3 Included in these are mutations in genes coding for Rab proteins (rabaptins), a group of small Ras GTPases that have been shown to play an important role at different levels of the cellular trafficking pathway.4–6 Although over 60 Rab proteins have been identified so far, only a few have been implicated in human disease, including in patients with intellectual disability with or without associ- ated brain malformations.7,8 RUSC2, officially known as RUN and SH3 domain con- taining-2, is a gene found on chromosome 9p13.3 (gene identifier [ID] 9853, Mendelian Inheritance in Man [MIM] 611053). RUSC2 codes for iporin, a ubiquitous protein with moderate to high expression in the human brain.9,10 The literature on the functions of iporin remains sparse, but there is some evidence that it interacts with Rab1b and Rab1-binding protein GM130,10 both of which are also expressed in the brain, with highest expression in dendritic spines where they appear to play an important role in synaptogenesis.
So far, no mutations in RUSC2 have ever been shown to cause human disease, and no animal models disrupting this gene have been described. However, to our knowledge for the first time, we describe the clinical presentations of three patients (two male siblings and one unrelated female) with severe intellectual disability and microcephaly. Through whole-exome sequencing, all three were found to have inherited homozygous nonsense mutations in RUSC2. This report adds to the expanding landscape of genetic causes of intellectual disability, and suggests that RUSC2, probably through its interactions with Rab proteins and their effector molecules, may play an important role.
Mootaz Salman
Shefield Hallam University, UK
Title: Validation of the aquaporin role as a novel drug targets in therapeutic mannitol action and resistance in cerebral oedema and stroke
Biography:
Mootaz Salman is a pharmacist and researcher PhD student at the Biomolecular Sciences Research Centre (BMRC) at Sheffield Hallam University, working with Prof. Nicola Woodroofe and Dr. Matthew Conner’s research group and a member of the multi-institute Aquaporin research collaboration. His research interest focus on the identification of new drug targets for brain oedema and epilepsy through his work on the special water channels called “Aquaporins”. Mootaz graduated with Outstanding Distinction in his MSc winning the Sheffield Hallam University prize for the most scientific contribution and ranked 1st in year. His PhD research requires the skilled use of numerous techniques ranging from standard biochemical and molecular biology to cutting edge micro-array and laser confocal microscopy. Mootaz is an international ambassador at Sheffield Hallam University, ambassador for British Society of Experimental Biology (SEB); and STEM ambassador since 2014. He has given four invited oral presentations and talks at major international conferences in Canada, Netherlands, Romania and Japan along with three talks at a national level. He is also an active member in a number of scientific societies nationally and internationally including USA, Canada and Japan. He has been selected to be an abstract reviewer at two major international conferences; Brain 2015 in Canada and also for the upcoming Brain 2017 in Berlin, along with being an abstract reviewer and a member of poster judgement panel during the North of England Postgraduate Conference (NEPG) which is the UK's largest annual postgraduate conference for medical biosciences. Mootaz has successfully participated in organising a number of national and international high profile conferences and also he has been selected to chair scientific sessions at two national events
Abstract:
In humans there are 13 established members of the aquaporin (AQP) membrane protein water channels (AQP0-12) with a further two possible members recently discovered (AQP 13 & 14). AQPs are distributed throughout a wide range of tissues and involved in many physiologies; they have been shown to play a role in diverse disorders and pathologies1. Consequently, AQPs have been highlighted as key drug targets2. AQPs mediate water influx during cerebral oedema following ischemia as a result of traumatic brain injury or stroke. A number of AQPs have been shown to be expressed in the brain with AQP1 and 4 the most abundant. This project aimed to identify and study the molecular tools that could manipulate the translocation of brain AQPs as promising drug targets and also understanding the mechanisms of action/resistance for mannitol; which is considered to be a mainstay and gold standard to treat brain edema in order improve its therapeutic effectiveness.
Microarray on primary rat astrocytes has been used to investigate the possible mechanisms involved in the process of oedema under hypoxic and/or normoxic conditions. qRT-PCR was used to confirm the transcriptional capacity of the genes of interest from the microarray data. Potential key proteins within suggested mechanistic pathways were identified through analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID).
Abbas Alnaji
Alsadir Teaching Hospital, Iraq
Title: Cefixime and Azothromycin are beneficial in uncontrolled seizures in pediatric age group with or without mental retardation
Biography:
Abstract:
According to what had been mentioned in an article to the conference of Epilepsy and treatment 2015 USA, which is due the whole issue of the epilepsies or seizures to a specific type of chronic active bacterial global encephalitis CABGE, in our study it was mostly due to Neurobrucellosis, however other bacteria did not excluded and we recommended wider screening especially to those of intracellular nature. This combination was tailored due to Doxycyclin is not preferred in those of less than six of age. It has been choosed from several regimens were used by us as a trial treatment for what can be chronic Brucellosis patients diagnosed on clinical basis only to hinder emergence of antibiotics resistance in long term eradication efforts which exceeds that of complicated Tb in the old days. Mental retardation in some of patients was the event which followed the phase of uncontrolled attacks in presence of the classical antiepileptics both quantitatively and qualitatively. The old or traditional teachings due this brain dysfunction to the cerebral trauma from repeated fits as anoxia or so. While, however it is correct, the major or the real event behind this mental retardation in our vision is the ongoing parenchyma destruction by the infective agent, where if this hypothesis is correct! (we say hypothesis in spite of presence of vast number of successfully treated patients +/- PCR results), antiepileptics do not stop destruction, and this explains why incremental doses of antiepileptics are needed like analgesics in headache. This can be considered as a trial treatment based on clinical facts plus some PCR positive cases to reveal the cause behind abnormal cerebral electric discharge. The nomenclatures as idiopathic, post traumatic and so the other conditions are precipitating or a triggering factors.