Epilepsy Research Benchmarks

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Advance, Challenges, Opportunities 2007 Epilepsy Research Benchmarks Dan Lowenstein, UCSF (Benchmarks Chair) Interagency Collaborative to Advance Research in Epilepsy March 23, 2010

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Epilepsy Research Benchmarks: history and improvement March 2000 - Curing Epilepsy: Focus on the Future Conference united researchers, mind suppliers, and pioneers of willful associations Developed the primary arrangement of objectives for the expansive epilepsy explore group Benchmarks Stewards advance and track advance March 2007 - Curing Epilepsy:  Translating Discoveries into Therapies Updated the first Benchmarks in light of advance rolled out and improvements in research bearings

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2007 Epilepsy Research Benchmarks Area I: Prevent epilepsy and its movement Area II: Develop new restorative methodologies and streamline flow ways to deal with cure epilepsy Area III: Prevent, point of confinement, and turn around the co-morbidities connected with epilepsy and its treatment www.ninds.nih.gov/inquire about/epilepsyweb/2007_benchmarks.htm

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Epilepsy Research Benchmarks: Area I Prevent epilepsy and its movement Identify up 'til now unrecognized reasons for epilepsy (e.g., hereditary, immune system and irresistible) Identify hidden components of epileptogenesis. Recognize biomarkers for epileptogenesis Identify ways to deal with forestall epilepsy or its movement Develop new creature models to concentrate on epileptogenesis Test the viability of avoidance methodologies

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Epilepsy Research Benchmarks: Area I Identify up 'til now unrecognized reasons for epilepsy Gene disclosure Many known qualities influence particle channels or neurotransmitter flagging New discoveries indicate different procedures Synaptic vesicle discharge Cadherin superfamily (improvement of neuronal network) Interneuron (inhibitory) advancement New pieces of information from qualities connected to mental health or different issue connected with epilepsy Immune or fiery hazard components Acute seizures connected with H1N1 and RSV contaminations Maternal genitourinary diseases and expanded seizure chance in posterity Case examine reporting autoantibody-interceded encephalitis Interactions amongst hereditary and natural hazard elements?

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Epilepsy Research Benchmarks: Area I Targeting the instruments of epileptogenesis Hypoxic-ischemic (H-I) encephalopathy Most incessant reason for neonatal seizures Role for expanded articulation of glutamate receptor subunits In rodent demonstrate, drugs that piece AMPA receptors lessen H-I seizures and intellectual deficiencies mTOR flagging pathway Over-enacted by changes that cause Tuberous Sclerosis (TSC) Also dysregulated in other epilepsy creature models and human epilepsies Rapamycin (mTOR inhibitor) has hostile to epileptogenic impact in mouse models of TSC and worldly projection epilepsy (TLE)

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Epilepsy Research Benchmarks: Area I New creature models of epilepsy and epileptogenesis Childhood epilepsies Multiple new models produced for Infantile Spasms (IS), a staggering epileptic encephalopathy Epileptogenesis in maturing Increased rate of seizures in Alzheimer's illness hAPP mouse display has non-convulsive cortical seizures Acquired epilepsy Theiler's murine encephalomyelitis infection (TMEV) as mouse model for intense symptomatic seizures and post-contamination procured epilepsy

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Epilepsy Research Benchmarks: Area I Challenges and Opportunities Ongoing necessities Animal models of epilepsy advancement and movement for unthinking and intercession explore Biomarkers that anticipate movement in new onset epilepsy or the improvement of epilepsy in those at hazard Genetics Advancing hereditary advances show openings all inclusive familial and extensive scale affiliation contemplates Application of entire genome sequencing to known loci Need for coordinated effort crosswise over studies utilizing distinctive patient associates Acquired epilepsies H1N1 and RSV diseases exhibit normal examinations for concentrating on insusceptible related epilepsy New clinical trials continuous or starting for post-traumatic epilepsy

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Epilepsy Research Benchmarks: Area II Develop new helpful techniques and upgrade ebb and flow ways to deal with cure epilepsy Identify essential systems of ictogenesis (seizure era) that will prompt to the improvement of cures Develop devices that encourage the recognizable proof and approval of a cure Optimize existing treatments and grow new treatments and advances for curing epilepsy

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Epilepsy Research Benchmarks: Area II Seizure era, engendering and end Advancing innovations for recording system action High-thickness intracranial EEG and microelectrode recording Graph hypothesis , utilitarian availability investigation of seizure action Could mediations that objective "center" cells in epileptogenic tissue take out seizure action without loss of system capacity? Cell flagging pathways Astrocyte systems coupled through hole intersections keep up epileptiform action The corrosive detecting particle channel ASIC1a adds to seizure end Opens in light of diminished pH, which happens amid seizure Increases movement of inhibitory interneurons

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Epilepsy Research Benchmarks: Area II New methodologies for focused treatments Brain incitement Some trials have indicated decreased seizure recurrence No vast scale, randomized trials yet demonstrate opportunity from seizures Gene treatment and different biologics Neuropeptide frameworks (NPY, galanin) and GABA flagging pathway are most well known target Focal restorative conveyance Adenosine Suppresses seizures, yet cardiovascular symptoms confine clinical application Adenosine-discharging networks or cell inserts Other methodologies under scrutiny incorporate central cooling, catheter conveyance

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Epilepsy Research Benchmarks: Area II Optimizing results for surgical intercession Surgical mediation remains a decent alternative for patients with an epileptogenic center that can be obviously restricted evacuated without useful misfortune exceeding advantages of lessened seizure recurrence Improving the limitation of epileptic foci Application of propelling imaging and recording innovations (e.g. HFOs) Better comprehension of useful systems required in dialect and memory may enhance surgical arranging and capacity to anticipate and maintain a strategic distance from useful shortfalls

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Epilepsy Research Benchmarks: Area II Challenges and Opportunities Despite new anticonvulsant drugs, 25-35% of individuals with epilepsy need satisfactory seizure control Challenges in treatment advancement Drugs, quality treatment, biologics, central medication conveyance Need for particular focusing on, durable impacts Brain incitement Effective incitement conventions will require better comprehension of circuits required in various epilepsies Challenges confronting clinical trials Epilepsy Study Consortium, NINDS Common Data Elements

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Epilepsy Research Benchmarks: Area III Prevent, point of confinement, and turn around the co-morbidities connected with epilepsy and its treatment Identify and describe the full range and age specificity of co-morbidities in individuals with epilepsy Identify indicators and basic components that add to co-morbidities Determine the ideal medicines for the neuropsychiatric and subjective co-morbidities in individuals with epilepsy Prevent or farthest point other unfavorable outcomes happening in individuals with epilepsy Develop compelling strategies for analysis, treatment and aversion of non-epileptic seizures (NES)

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Epilepsy Research Benchmarks: Area III Cognitive and behavioral comorbidities of epilepsy Community-based and populace considers report expanded: Depression and self-destructive ideation/endeavor Anxiety Cognitive deficiencies Behavioral issues Reported weakness, weakness related practices (e.g., smoking, idleness) What are the relative commitments of Chronic seizures and their treatment? Covering organic systems basic comorbidities and the advancement of epilepsy?

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Epilepsy Research Benchmarks: Area III Risk elements for subjective and behavioral comorbidities Young period of onset Duration of epilepsy Symptomatic or cryptogenic etiology Presence of intellectual/behavioral shortfalls at onset Brain imaging and neural movement corresponds Many studies have indicated connections amongst basic as well as utilitarian irregularities and psychological/behavioral deficiencies in epilepsy Further advance foreseen from methodologies that look crosswise over entire systems or apply numerous imaging/recording modalities

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Epilepsy Research Benchmarks: Area III Animal models indicate components In a rodent model of febrile seizures, MRI anomalies display after prompted seizure anticipate later memory shortages Spatial memory shortages in a rodent model of TLE watched not long after incited status epilepticus and preceding the advancement of incessant seizures connected with electrophysiological changes in the hippocampus … and to potential medicines Inhibition of Interleukin-1 β (IL-1 β ) flagging enhanced depressive side effects in rodent model of TLE In a rodent model of nonattendance epilepsy, ethosuximide averted spike-wave releases and enhanced measures of sadness

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Epilepsy Research Benchmarks: Area III Other comorbidities connected with epilepsy Sudden Unexplained Death in Epilepsy (SUDEP) Increased danger of unexpected passing with a few epilepsies, particularly if seizures are not well controlled  Advances in comprehension the instruments of SUDEP Mouse model of cardiovascular Long QT disorder joins one particle channel to both epilepsy and heart arrhythmias prompting to sudden demise Naturally happening SUDEP in primates (possibly new creature demonstrate) Further portrayal of unfriendly respiratory impact of seizures American Epilepsy Society and Epilepsy Foundation Joint Task Force and 2008 NINDS workshop Research and instruction/exceed needs

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Epilepsy Research Benchmarks: Area III Reproductive results in ladies with epilepsy Healthy Outcomes for Pregnancies in Epilepsy (HOPE) discussion American Academ