Comprehensive Epilepsy Center Research
At NYU Langone’s Comprehensive Epilepsy Center, we are dedicated to research and continually seek to expand our efforts to understand epilepsy, seizure disorders, and their treatment. Current research topics include new drug development, sudden unexplained death in epilepsy (SUDEP), the genetics of epilepsy, tuberous sclerosis and epilepsy, autism and epilepsy, sleep and memory, neurostimulation, women and pregnancy, and the identification of biomarkers that predict epilepsy outcome. Many of our research initiatives are supported by Finding a Cure for Epilepsy and Seizures (FACES).
The Comprehensive Epilepsy Center currently has 16 research coordinators and more than 30 active research studies. Our research initiatives include the following.
Human Epilepsy Project
Most patients are started on an antiepileptic drug (AED) regimen after an epilepsy diagnosis, yet doctors have no way to predict who will be among the one third of patients who continue to have seizures as a result of AED treatment resistance, or what causes that resistance.
The Human Epilepsy Project (HEP) 1 is a large, 10-year prospective study designed to identify biomarkers that predict epilepsy progression, treatment response, and outcomes in people with recently diagnosed focal epilepsy. HEP1 is a partnership among 33 international academic centers, foundations, and industries led by the Comprehensive Epilepsy Center. HEP1 researchers have collected blood samples and high-resolution MRI and electroencephalogram (EEG) data from more than 400 people with epilepsy who track their seizures in a digital diary. Each person is followed for three to six years. HEP1 also collects information on memory, mood, and drug adverse effects over time, which allows investigators to determine whether there is any progressive disturbance in these areas that are so important to quality of life.
Another aim of the project is the creation of an open data repository of clinical information and biologic samples that allows researchers to determine how all of these elements are related. Data gathered so far reveal important insights into the likelihood of mood problems, the association between specific abnormalities in brain imaging and treatment resistance, and the likelihood of response to different medications.
HEP2 is a 2-year prospective observational study of 200 treatment-resistant patients with focal epilepsy. NYU Langone researchers are spearheading this study in conjunction with the Epilepsy Study Consortium and the Epilepsy Foundation. We are studying the natural history of the disorder to determine the likelihood of improvement, remission, or worsening. We also assess comorbidities, such as mood disorders, and whether there are biomarkers of disease severity.
The Comprehensive Epilepsy Center led the initial open-label study and two of the three randomized controlled trials of cannabidiol (Epidiolex®) to treat children and young adults with Dravet syndrome and Lennox-Gastaut syndrome. These trials showed clinically and statistically significant improvement in seizure frequency and supported the recent U.S. Food and Drug Administration (FDA) approval of Epidiolex® for the treatment of these devastating epilepsy syndromes. Ongoing collaborations with Richard Tsien, PhD, at NYU Langone’s Neuroscience Institute are focused on identifying the mechanism of action of cannabidiol on synapses in neural circuits to understand how it affects seizures.
The center is also involved in pilot trials of cannabinoids to treat symptoms of autism spectrum disorder. Trials using cannabidiol, in collaboration with NYU Langone’s Child Study Center, and cannabidivarin—another cannabis-derived compound—with the Albert Einstein College of Medicine, are now in progress.
New Antiepileptic Drugs
Our center has been a longstanding leader in clinical trials in epilepsy. Our faculty have contributed to the completion of numerous successful clinical trials, which led to the FDA approval of new antiepileptic drugs such as perampanel and cannabidiol. The approval and availability of new effective drugs in epilepsy have positively impacted the lives of many patients not tolerating or responding to older drugs.
New targets for epilepsy drugs and methods of delivering drugs are regularly discovered through laboratory research. The next step is to test drugs aimed at those new targets by studying their effects on people with epilepsy in a clinical trial. Clinical trials offer patients the opportunity to contribute to the epilepsy community by enabling that essential step from the laboratory to FDA approval and may enable access to new antiepileptic drugs before approval.
Clinical trials at NYU Langone are enrolling patients with different types of epilepsy not responding to approved antiepileptic drugs, ranging from focal epilepsy to absence epilepsy. If patients are considered eligible for a clinical trial after screening, they receive regular evaluation by research staff for the duration of the study to monitor the efficacy and safety of the treatment. In some studies, everyone receives the study medication right away. In others, there may be a “blinded” phase, during which neither the patient nor the study staff know whether the patient is receiving the new drug or a placebo (sugar pill). In these trials, all patients have the opportunity to continue into an extension of the study during which everyone receives the drug.
In addition to clinical trials, we are involved in studies in which eligible patients are followed to determine the patient characteristics that may predict whether they will respond to a particular drug or develop side effects.
Sudden Unexpected Death in Epilepsy
We are researching the risk factors, mechanisms, epidemiology, neuropathology, and genetics of SUDEP. The Comprehensive Epilepsy Center launched the North American SUDEP Registry in 2011, and collaborates with neurologists, epidemiologists, genetics researchers, imaging researchers, and neuropathologists at NYU Langone and around the world.
We have initiated the largest international study of SUDEP by studying patients with seizures that were recorded in epilepsy-monitoring units in the United States, Canada, Europe, and Australia, comparing characteristics of those who later died from SUDEP with those in subjects who are living. The goal is to identify biomarkers and risk factors that can help inform the development and assessment of preventive strategies.
In addition, clinicians at the Comprehensive Epilepsy Center are also interested in developing strategies to prevent SUDEP, including behavioral interventions to improve disease self-management and devices to detect seizures.
Seizure Detection Devices
The Comprehensive Epilepsy Center has long been involved in studies to test noninvasive devices to detect convulsive seizures and alert caregivers. Improving the ability of family members and caregivers to provide basic first aid during and immediately after a tonic-clonic seizure is thought to be a possible way to lower the risk of seizure-related injury and death. Noninvasive and easy-to-use sensors that detect seizure-related movements, muscle activity, and changes in autonomic function can be used for seizure detection.
The center has been involved in studies examining the accuracy of these sensors, including the MP5 mattress movement monitor, the Brain Sentinel SPEAC surface EMG sensor, and the Empatica Embrace watch. Two of these devices, the SPEAC device and the Empatica Embrace, were recently approved by the FDA and are now available to patients to aid in seizure monitoring.
The center is now involved in studies in collaboration with Epitel to validate a novel, small EEG patch (Epilog) intended for long-term seizure monitoring and counting in the home through grants from the Epilepsy Foundation and the National Institutes of Health.
Faculty member Daniel Friedman, MD, is involved in this research.
Sudden Unexplained Death in Childhood
The Sudden Unexplained Death in Childhood Registry and Research Collaborative (SUDCRRC) is a multisite collaboration between NYU Langone, Columbia University, and the Mayo Clinic that works to increase the understanding of the characteristics, circumstances, medical histories, and pathologies of children between 11 months and 18 years of age who have died suddenly, often without explanation. Over 40 percent of the children enrolled had a history of febrile seizures during their lifetime. The SUDCRRC analyzes cases of sudden unexpected deaths in these children to understand risk factors, causes, and develop preventive measures.
To date, the SUDCRRC has enrolled 155 families into the SUDCRRC from across the United States, Canada, and the United Kingdom. The goal is to study 300 families.
The study does the following:
- performs a comprehensive family interview regarding the child’s history, their family history, and first-person accounts of the circumstances of death
- reviews the child’s death and medical and family history through our study pathologists (including forensic, pediatric, cardiac, and neuropathologists) to determine whether a possible, probable, or definite cause of death can be identified; pursues additional studies when indicated to assist in determining a specific cause of death
- performs neuroimaging and neuropathology evaluations as well as genetic analysis (whole-exome sequencing platform) on the child who died; undertakes additional genetic analyses for biological parents and symptomatic family members
- examines the risks that lead to sudden deaths in children
- identifies at-risk individuals and establishes prevention strategies to reduce the incidence of sudden unexplained death in childhood
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Women and Epilepsy
NYU Langone is a leader in studies of women with epilepsy, with a particular focus on the care of these women during their childbearing years. Katherine S. Inoyama, MD, directs the Program for Women with Epilepsy. We were one of three centers to conduct the Women with Epilepsy: Pregnancy Outcomes and Delivery (WEPOD) study. The study compared women with epilepsy who were attempting pregnancy with matched controls, and demonstrated for the first time that women with epilepsy do not have specific problems with fertility and that the rate of miscarriage is no higher in women with epilepsy than in women without epilepsy.
NYU Langone is also involved in the ongoing multicenter Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study and contributes to its administrative core. This controlled trial provides vital information about risks to women with epilepsy during pregnancy, including risks of pregnancy complications, and monitors children born to women with epilepsy for as long as six years to determine whether they experience any particular developmental issues.
We also collaborate with other researchers to investigate issues and complications related to the use of specific antiepileptic drugs during pregnancy.
Memory and Stimulation Studies
Research on memory and stimulation focuses on how the brain makes and stores memories, and how these processes may be disrupted in patients with epilepsy. One important line of investigation examines how sleep supports the long-term stabilization of memories and how perturbed sleep activity in patients with epilepsy may contribute to memory dysfunction.
In collaboration with György Buzsáki, MD, PhD, at NYU Langone’s Neuroscience Institute, our faculty members are pursuing ongoing studies of how neurostimulation—including transcranial electrical stimulation, acoustic stimulation, and direct electrical stimulation—may help restore and enhance key sleep rhythms to support memory function. Several active research projects combine cognitive testing, neurophysiology (scalp EEG and intracranial EEG), and neurostimulation in epilepsy patients and healthy controls. We work closely with basic neuroscientists, cognitive neuroscientists, and biomedical engineers.
The intracranial EEG program is a multidisciplinary group of researchers and clinicians dedicated to advancing our understanding of the human brain and improving the health of people with neurological disorders. Nearly one third of people with epilepsy have seizures that cannot be sufficiently controlled with medication. For many of these drug-resistant patients, treatment requires invasive surgical procedures to study the activity of their neural networks and/or resect pathological tissue.
Electrocorticography (ECoG), or intracranial EEG, is the practice of using invasive electrodes implanted inside or on the surface of patients’ brains during clinical procedures to record electrical activity from the cortex and other brain regions both for diagnosis of epilepsy networks and for palliative treatment of seizures such as with a responsive neurostimulation (RNS) device. Our group is actively engaged in clinical research initiatives to develop safer and more effective ECoG electrode technologies to advance clinical care for people with epilepsy. We are also running ongoing experiments aimed at understanding how the ECoG signals recorded during clinical procedures can be used to further our understanding of seizure networks and predict cortical stimulation mapping and postoperative outcomes.
Patients undergoing clinical procedures can also consent to participate in cognitive neuroscience experiments. The ECoG recordings obtained during these experiments enable researchers to examine the underlying neural mechanisms and networks involved in human cognitive processing, including speech and language, sensory perception, memory, and decision making.
The ECoG group is based in the Comprehensive Epilepsy Center, although faculty from a number of departments and institutes across NYU Langone and NYU, including the Neuroscience Institute, Department of Neurology, Department of Neurosurgery, NYU Center for Neural Science, and Department of Psychology, are involved in the research. We also partner with several external groups, including researchers and clinicians at Harvard University, Princeton University, Columbia University, Duke University, University of California at Davis, and the Max Planck Institute for Empirical Aesthetics. The group is led by Adeen Flinker, PhD, and Sasha Devore, PhD.
Healthful Behavioral Changes
People with epilepsy (PWE) are commonly affected by mood disorders such as depression that negatively impact quality of life. Yet little is known about how mood disorders are best managed in different ethnic populations. Moreover, among the 30 to 50 percent of PWE that do not take their medication as prescribed, nonadherence is higher among ethnic minority and lower socioeconomic status groups.
Researchers at the Comprehensive Epilepsy Center together with colleagues in the Department of Population Health are studying a variety of behavioral interventions aimed at improving physical and mental health, quality of life, and medication adherence in at-risk populations.
For example, a study currently in progress suggests that higher levels of daily stress are associated with a higher risk of nonadherence to epilepsy medication prescriptions. This finding suggests that stress management may provide a promising approach to managing nonadherence in at-risk populations, which in turn may decrease risk of injury and death as well as healthcare costs. Another ongoing study, funded by the U.S. Centers for Disease Control and Prevention, is developing and testing group mindful-based cognitive behavioral therapy interventions that can be delivered by phone to Spanish-speaking PWE to improve mood symptoms and quality of life.
These types of studies tackle important social issues related to quality of life in ethnically diverse PWE and will inform the development of culturally tailored behavioral intervention strategies. The ultimate goal of this program of research is to identify and disseminate effective nonpharmacological interventions to improve outcomes in all PWE.
CDKL5 Deficiency Disorder
NYU Langone has one of six CDKL5 Deficiency Disorder (CDD) Centers of Excellence in the United States approved by the International Center for CDKL5 Research, offering a wide range of neurological, genetic, neurodevelopmental, and specialty services for children with this disorder.
In addition to providing state-of-the-art medical care, our center is also actively collaborating with the Loulou Foundation and several companies to develop novel therapies for children with CDD. NYU Langone has already undertaken clinical trials of cannabidiol for CDKL5 deficiency disorder and ataluren for CDD caused by premature stop codons. We are now initiating trials with both ganaxolone and Ovid935 to treat seizures associated with CDD. Our center personnel have also been involved with Tevard, Mia Med, and Rettco, companies developing new therapeutics that could benefit patients with CDD.
Investigators involved in this research include Orrin Devinsky, MD, and Erin Conway, MS, RN, CPNP.
NYU Langone has one of nine Dup15q Centers of Excellence in the United States approved by the Dup15q Alliance, offering a wide range of neurological, genetic, neurodevelopmental, and specialty services for children with this disorder. In addition to providing state-of-the-art medical care, our center is also actively collaborating with partners in academics and industry to develop novel therapies for children with Dup15q.
NYU Langone has already undertaken clinical trials of cannabidiol for Dup15q and Ovid935 to treat seizures associated with CDD. Our center’s personnel have been actively involved in scientific research to develop biomarkers for Dup15q and to better understand how to improve seizure control, cognitive and behavioral development, and quality of life in these children.
NYU Langone’s Angelman Syndrome Clinic opened in 2018 with the support of the Angelman Syndrome Foundation. The clinic is based at the Comprehensive Epilepsy Center but is multidisciplinary in nature, with representatives from pediatric subspecialties including neuropsychology, gastroenterology, rehabilitation medicine, and genetics. The clinic provides consultative services and ongoing care including treatment of epilepsy, developmental delays, and eating and behavioral disorders.
The clinic works in close collaboration with other clinics supported by the Angelman Syndrome Foundation on both clinical and basic science research, and focuses on providing comprehensive diagnostic and therapeutic interventions in treatment of patients’ epilepsy.
The pediatric epilepsy program is the focal point of care for people with Sturge-Weber syndrome at NYU Langone. The Comprehensive Epilepsy Center, along with specialists in dermatology, ophthalmology, and radiology, has been designated as a Center of Excellence by the Sturge-Weber Foundation. The program involves both clinical care of patients with epilepsy, glaucoma, and port wine birthmarks, as well as participation in a multicenter research protocol supported by a National Institutes of Health grant investigating the natural course of the disorder.
Faculty member Daniel K. Miles, MD, is involved in this research.
Autism and Epilepsy
The Comprehensive Epilepsy Center has a long-standing and extensive program in the clinical care and research for children and adults who have both autism and epilepsy. We help to coordinate neurological, genetic, neurodevelopmental, and specialty services for children with autism, and are a core site of the Autism and Developmental Neuroscience Center (ADNC).
In addition to pioneering studies on cannabidiol for epilepsy, we are collaborating with the ADNC in a trial of cannabidiol for autism and with another center in a trial of cannabidivarin for autism. We are initiating a collaboration with epilepsy centers to study brain tissue removed during epilepsy surgery to better understand the genetic and cellular changes underlying epilepsy and autism, and how these relate to biomarkers in our blood and microbiome.
Our research has led to a better understanding of the shared genes that can underlie both autism and epilepsy, neuroimaging biomarkers of autism and epilepsy, and precision genetic approaches to treating these disorders.
Orrin Devinsky, MD, is involved in this research.
Research in neuroimaging uses MRI and related techniques such as magnetic resonance spectroscopy to investigate how brain structure and function are affected in epilepsy. Advanced imaging methods help us assess focal and network-level brain changes, with a focus on improving clinical outcomes in both newly diagnosed and patients with chronic epilepsy.
Imaging methods we use include high-resolution structural imaging using both clinical and high-field 7T MRI scanners, diffusion imaging to create imaging patterns of white matter connections throughout the brain, functional MRI to image brain function both at rest and during cognitive and motor tasks, and spectroscopy to assess brain metabolites. Our researchers have an active interest in the application of advanced statistical modeling techniques to identify subtle brain changes in epilepsy, including big data approaches, which can include thousands of participants, and cloud-based methods for image analysis and modeling.
We have ongoing collaborations with the wider NYU community and many epilepsy research groups across the United States and the rest of the world. Current projects include the Human Epilepsy Project, the ENIGMA-Epilepsy consortium, and the Neural Markers of Quality of Life in Epilepsy study.
Neuroinflammation and Autoimmunity
Neuroinflammation and autoimmunity are increasingly recognized players in the development of epilepsy and the perpetuation of seizures. We care for patients who have a proven or suspected autoimmune cause of epilepsy, including for those who may not be responding to antiepileptic drugs and may need a diagnostic workup and treatment plan targeted at an underlying autoimmune cause.
Led by Claude Steriade, MD, CM, NYU Langone conducts research to determine appropriate disease markers for accurate diagnosis and treatment response of autoimmune epilepsy, with the collaboration of other centers in the United States, Spain, and Australia. We also have ongoing collaborations with the Department of Psychiatry at NYU Langone to investigate the role of neuroinflammation in mediating the relationship between epilepsy and behavioral comorbidities like depression and psychosis.
Other Rare Epilepsies and Precision Medicine
Clinicians at the Comprehensive Epilepsy Center treat patients with rare genetic forms of epilepsy. Using modern sequencing technologies, investigators are able to identify the precise mutations associated with these rare epilepsies, and research efforts are underway to develop precision therapies including direct gene editing approaches—in collaboration with Chengzu Long, PhD, in the Department of Medicine—and viral delivery techniques.
Rapid chemical screening approaches are being developed by collaborators at the University of Tromso to identify novel drug treatments. The Comprehensive Epilepsy Center also collaborates with a number of external partner labs to study the molecular, cellular, and network mechanisms in these rare genetic epilepsies. Collaborating institutions include Columbia University, Indiana University, University of Tromso, Weizmann Institute of Science, and Hanyang University.
In addition to the development of precision treatments, our clinicians are working to develop patient and caregiver resources. They also engage with the global clinical community to identify additional patients with these rare genetic forms of epilepsy.
Intensive Care Unit Neurology and Status Epilepticus
The Comprehensive Epilepsy Center is actively engaged in research to improve outcomes of patients with refractory seizures, including subclinical seizures, of varying etiologies and treatment methods over a prolonged duration of time and analyze the contribution of EEG patterns to the management, assessment of treatment efficacy, and prognosis. We are part of the Critical Care EEG Monitoring Consortium, a collaborative effort of 50 institutions worldwide to advance research and improve the standard of care of critically ill patients on EEG.
Our ability to monitor neurological intensive care unit (ICU) patients continuously on video EEG increases our understanding of how seizures complicate other problems, such as brain hemorrhage, tumor, encephalitis, cardiac arrest, autoimmune disease, and traumatic brain injury, and how to accurately diagnose and provide state-of-the art care.
Faculty member Manisha G. Holmes, MD, is involved in this research.