CURE is committed to advancing epilepsy research by bringing together great minds from around the world.
Frontiers in Research Seminar Series
With the support of the Nussenbaum-Vogelstein family, the goal of this program is to expose young researchers and clinicians to exciting epilepsy research, and to provide opportunities for young investigators to interact with a senior level epilepsy researcher.
Critical Care EEG Monitoring: A Practical Update
Friday, January 5, 2018
Stony Brook Medicine
Speaker: Lawrence Hirsch, MD (Yale University)
Host: Louis N. Manganas, MD, PhD
Talk Summary: Dr. Hirsch will provide an update in diagnosing and managing seizures, including nonconvulsive ones, and related EEG patterns in critically ill patients. This talk will benefit any member of the health care team involved in inpatient care of patients with altered mental status, including MDs, nurses, PA’s, APRNs, and EEG technologists.
• To learn which patients are at risk of nonconvulsive seizures and warrant EEG monitoring
• To learn how to understand EEG reports and which findings require urgent or aggressive treatment
• To learn how to treat clinical and nonconvulsive seizures in the critically ill most effectively.
Status Epilepticus Research: My Adventures
Tuesday, January 9, 2018
University of Colorado
Speaker: Jaideep Kapur, MD, PhD (University of Virginia)
Host: Manisha Patel, PhD
Talk Summary: Goal of this talk is to highlight importance of novel scientific approaches and team science in epilepsy research. Changing focus from the role GABA -mediated inhibition to AMPA mediated excitatory transmission allowed us to use novel brain mapping techniques and genetic tools to gain novel insights into pathophysiology of status epilepticus.
In an effort to improve patient care, we organized a large, 60 -site clinical trial to investigate treatment of benzodiazepine-refractory status epilepticus, called Established Status Epilepticus Treatment Trial ( ESETT). Organization and execution of such a large study required participation of a multidisciplinary team consisting of adult and pediatric ED physicians, adult and pediatric neurologists, trial design experts, biostatisticians , database experts, pharmacists and pharmacologists, and most importantly clinical research coordinators. Team science is critical to improving patient outcomes.
The Indisputable Dawn of Precision Medicine in Epilepsy
Friday, February 9, 2018 - 12:00pm to 1:00pm
Philadelphia College of Osteopathic Medicine
Speaker: Dan Lowenstein, MD (University of California, San Francisco)
Host: Jocelyn Lippman-Bell, PhD
Talk Summary: Despite remarkable advances in basic and clinical neuroscience, and the introduction of many new pharmacological treatments, the overall impact of care for patients with epilepsy has not significantly changed for the past 50 years. Until now. Our increasing ability to define the “Knowledge Network” that includes the multi-layered determinants of health and disease in large populations is beginning to translate into more and more precise, individualized diagnostics and therapeutics. In epilepsy, genetics is leading the way, but this is only the dawn of what will, thankfully, be a new era in our ability to treat and eventually cure patients with epilepsy and other brain network disorders.
Preventing SUDEP (Sudden and Unexpected Death in Epilepsy) and How to Build Research Around SUDEP
Wednesday, February 28, 2018 - 10:15am to 12:00pm
Monash University Malaysia
Speaker: Prof. Ley Sander, MD, PhD, FRCP (University College London Insitute of Neurology)
Host: Mohd. Farooq Shaikh, PhD
Talk Summary: Individuals with epilepsy, particularly those with uncontrolled epilepsy, are at a much greater risk of premature death than those without. In fact, the standardized mortality ratio in those with epilepsy is between 2 and 3. In the UK, the most common cause of epilepsy-related death is due to Sudden Unexpected Death in Epilepsy (SUDEP), which accounts for up to one-fifth of deaths in some series. SUDEP is more common in those with frequent convulsive seizures (particularly nocturnal seizures) and in those with drug-resistant epilepsy. While the causes of SUDEP are unknown, the most commonly suggested underlying mechanisms are cardiac arrhythmias, respiratory depression and “cerebral shutdown”. Because no preventative measures currently exist, an understanding of SUDEP risk factors, potential mechanisms and the effectiveness of preventative measures is essential. To this end, there are a multitude of opportunities available in the field of SUDEP research and these opportunities will be interactively discussed during the presentation.
Thalamocortical Tonic Inhibition, Absence Epilepsy and Sleep
Wednesday, April 11, 2018 - 12:00pm to 1:00pm
Johns Hopkins University School of Medicine
Speaker: Mathew Jones, PhD (University of Wisconsin - Madison)
Host: Frank Bosmans, PharmD, PhD
Talk Summary: Absence epilepsy is characterized by EEG spike-and-wave discharges (SWDs) and behavioral arrests. Previous studies in several rodent models proposed that enhanced GABAergic thalamic tonic inhibition is "necessary and sufficient" to cause typical absence epilepsy. In contrast, here we show that knock-in mice expressing a human absence epilepsy mutation in the GABA-A receptor (γ2R43Q) have typical absence seizures but have a complete loss, rather than enhancement, of tonic inhibition in principal cells of both thalamus and cortex. Furthermore, pharmacological blockade of tonic inhibition in wild type mice is sufficient to provoke SWDs, whereas pharmacological rescue of tonic inhibition in mutant mice suppresses SWDs by ~60%. Like many humans with various epilepsies, γ2R43Q knock-in mice also have disrupted sleep cycles, with SWDs occurring preferentially within minutes after abrupt transitions from NREM to Wake stages. This sleep/seizure linkage appears to be reduced by rescue of tonic inhibition. Together with previous results, these data suggest that an optimal level of GABAergic tonic inhibition throughout the thalamocortical circuit is required for normal function and that deviation from this optimum in either direction results in pathological thalamocortical function including absence seizures and sleep disruptions. Pharmacological rescue of tonic inhibition is thus a potential treatment for certain subtypes of absence epilepsy and associated sleep disruption.
Integrating Brain Implants with Local and Distributed Computing Devices: A Next Generation Epilepsy Management System
Tuesday, May 1, 2018 - 9:30am to 10:30am
Gladstone Institutes, San Francisco
Speaker: Greg Worrell, MD, PhD (Mayo Clinic)
Host: Jeanne Paz, PhD
Talk Summary: Brain stimulation has emerged as an effective treatment for a wide range of neurological and psychiatric diseases. Interfacing implantable brain devices with local and cloud computing resources has the potential to improve electrical stimulation efficacy, disease tracking and management. Epilepsy, in particular, is a neurological disease that might benefit from integration of implanted devices with off-the-body computing for tracking disease and therapy. Recent studies have demonstrated seizure forecasting, seizure detection, and therapeutic electrical stimulation in patients with focal epilepsy. In this talk, Dr Worrell will review progress on his Brain Initiative public-private-partnership with Medtronic Inc. to develop a next generation epilepsy management system in which low demand analytics requiring fast response times are embedded in the implanted device and more complex algorithms are implemented in off¬-the¬-body local and distributed cloud computing environments.
Instability in epileptic networks: initiation, termination, interruption
Tuesday, May 15, 2018
University of Bonn, Germany
Speaker: John Huguenard, PhD (Stanford University)
Host: Laura Ewell, PhD
Talk Summary: Historically, neuroscience research has provided mechanistic insights regarding ways in which neural circuitry may become dysfunctional in the context of epileptic seizures. For example, a rich history of studies in isolated rodent brain slices has provided a window into neural function during seizure-like events, but these studies are often artificially produced in vitro (out of the living organism). These in vitro studies allow for easier access to intracellular recordings and other advanced neurophysiological approaches whose results support roles for individual neurons and synapses in provoking and preventing seizure states. Now, advances in scientific methods allow for real-time modulation of specific neural activity in behaving animals experiencing seizures. In this talk I will present recent in vivo (live animal) studies from our laboratory and others that validate some, but not all, of the mechanistic models obtained from simple ex vivo approaches and discuss how an integrated in vitro/in vivo approach may lead to a powerful translational path.
Cannabinoids in Epilepsy
Tuesday, June 12, 2018 - 8:00am to 9:00am
George Washington University
Speaker: Eric Marsh MD, PhD (Children’s Hospital of Philadelphia)
Host: Mohamad Koubeissi, MD
Talk Summary: Using cannabinoids in the treatment of epilepsy is an area that is controversial, yet holds much promise. This talk will review the biology of cannabis – both the botany and human cannabinoid system – and then review the preclinical data on cannabidiol (CBD) and other cannabinoids. An overview of the neurological uses of cannabis will be presented, with a focus on the current data for the use of CBD and other cannabinoid preparations in epilepsy. The talk will then end with a summary of the current data and future directions regarding epilepsy in the cannabinoid space.
Combining Human iPSC and Animal Models to Study Genetic Epileptic Encephalopathies
Thursday, June 21, 2018 - 11:00am to 12:00pm
Boston Children's Hospital
Speaker: Jack Parent, MD (University of Michigan)
Host: Phillip Pearl, MD
Talk Summary: Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an unparalleled approach for neurological disease modeling using patient-derived neurons. My laboratory has applied the iPSC approach in combination with genetically modified mice to model severe childhood genetic early infantile epileptic encephalopathies (EIEEs) with patient-derived cells. More recently, we developed other rodent genetic EE models by combining in utero electroporation with CRISPR gene editing (IUE-CRISPR). The talk will describe our findings using these models to study three different EIEEs cause by mutations in SCN8A, SPTAN1 and STRADA. Our studies of mouse and patient iPSC models of EIEE13 due to de novo dominant SCN8A mutations show gain-of-function increased persistent or resurgent sodium current leading to neuronal hyperexcitability. We modeled EIEE5 SPTAN1-associated epilepsy with embryonic rat IUE-CRISPR and found that Sptan1 deletion altered cortical pyramidal cell morphology with loss of inhibitory innervation. Similar morphological defects were seen with overexpression of human mutant SPTAN1 and in EIEE5 patient iPSC-derived neurons. In the last part of the talk, I will discuss our recent studies of PMSE (polyhydramnios, megalencephaly and symptomatic epilepsy) caused by autosomal recessive STRADA mutations, using patient-derived iPSCs grown in 2-D cultures and as cortical organoids. Taken together, our work suggests that combining human iPSC and animal models of EIEEs offers great promise for mechanistic understanding of these severe childhood genetic epilepsies, and should provide useful platforms to identify novel therapies.
CURE sponsors conferences taking place globally in the field of epilepsy research. We are dedicated to engaging the research community, promoting collaboration and increasing epilepsy’s visibility with the goal of finding a cure.
Partners Against Mortality in Epilepsy (PAME)
Thursday, June 14, 2018 to Saturday, June 16, 2018
Chair(s): PAME Leadership
Overview: The fourth PAME conference will again bring together healthcare providers, researchers, public health officials, patient advocates, caregivers, families, and patients living with epilepsy. This diverse group of stakeholders will focus on the shared goal of improving our understanding of mortality in epilepsy, including Sudden Unexpected Death in Epilepsy (SUDEP).
PAME 2018 Conference Objectives:
• Critically evaluate the incidence, risk factors, and prevention strategies for mortality in epilepsy
• Describe the progress made and future directions for research regarding mortality in epilepsy
• Provide opportunities for collaborations among stakeholders, including people with epilepsy, researchers, families, clinicians, and advocates
• Gain skills in advocacy to build public awareness and impact public policy regarding epilepsy mortality
Gordon Research Seminar (GRS) on the Mechanisms of Epilepsy and Neural Synchronization
Saturday, August 18, 2018 to Sunday, August 19, 2018
Mount Snow, VT
Chair(s): Amanda Hernan, PhD and Tristan Shuman, PhD
Overview: The Gordon Research Seminar (GRS) is a unique forum for graduate students, post-docs, and other junior scientists to present new, unpublished data and discuss cutting-edge ideas amongst peers. The meeting is held in conjunction with the "Mechanisms of Epilepsy and Neuronal Synchronization" Gordon Research Conference (GRC), which is the preeminent basic science conference focused on epilepsy. The GRS exclusively features posters and talks by graduate student and postdoc-level researchers as well as a keynote lecture from a leading epilepsy basic researcher and a mentorship session designed to provide trainees with established mentors willing to help guide their careers. Together, this makes for a rare platform to promote young epilepsy researchers, integrate trainees into the epilepsy research community, and impact their career trajectory.
Gordon Research Conference (GRC) on the Mechanisms of Epilepsy and Neural Synchronization
Sunday, August 19, 2018 to Friday, August 24, 2018
Mount Snow, VT
Chair(s): Amy Brooks-Kayal, MD and Christophe Bernard, PhD
Overview: The overall aim of this Gordon Research Conference (GRC) is to bring together established and early career researchers, students, and postdoctoral fellows for 5 days in an intensive, interactive environment to present and discuss state-of-the-art, unpublished findings related to basic mechanisms of epilepsy, current translational studies and synchronization of neuronal activity in cerebral networks. The conference is designed to involve extensive discussion, and the environment is specifically geared towards fostering interactions between graduate students/post-docs and established researchers, and to facilitate intense in-depth discussions and generate collaborations between investigators in the interest of furthering the field. The specific theme of this GRC is “Translating mechanisms into therapies” and the conference will focus on how basic science discoveries can be effectively utilized to develop new therapies to prevent, better treat and cure epilepsy. Epilepsy research is inherently interdisciplinary, and the conference will bring together geneticists, molecular biologists, developmental neuroscientists, neuroanatomists, electrophysiologists, clinician-scientists and computational neuroscientists working on the full spectrum of epilepsy research from studies of basic mechanisms through preclinical and human research.