Research Investigations

Some of our center's ongoing projects in both clinical and translational epilepsy research:

Sudden Unexplained Death in Epilepsy (SUDEP)

SUDEP is a common – and in some studies the most common – cause of death among people with epilepsy. For older adolescents and adults whose tonic-clonic seizures are not fully controlled on antiepileptic drugs, the risk of SUDEP can exceed 10% over a decade. The NYU Comprehensive Epilepsy Center, with FACES support, is spearheading a series of studies on SUDEP to learn more about the disorder and develop strategies to prevent it. faces has also supported the development of two large Center Without Walls NIH Planning Grants to study SUDEP. This effort is linking more than 60 clinical and basic science investigators in the United States, Canada, and Europe. This is the first study in a long time which addresses high risk SUDEP markers during seizures in children, which will help us better understand possible mechanisms for the terminal event in this vulneravble population

A recent study in the journal Epilepsia attempts to find reasons for the cause of death in SUDEP.This is the first study in a long time which addresses high risk SUDEP markers during seizures in children, which will help us better understand possible mechanisms for the terminal event in this vulneravble population. The study PI, Sanjeev Kothare, MD  has recently relocated to the NYU Comprehensive Epilepsy Center and continues to work with the entire group at NYU to further enhance this area of research.

Autism and Epilepsy Initiative

We have started a genetic study of individuals with epilepsy and autism to identify shared mechanisms that underlie these disorders. A quarter of all patients with autism have epilepsy and many more have epilepsy waves on their EEG. In many it is difficult to control and severely affects their quality of life and exacerbates cognitive and behavioral problems. We will leverage our efforts by utilizing existing genetic data repositories (including EPGP) of people with only epilepsy or autism. By comparing the DNA profiles of patients with both epilepsy and autism to those with only epilepsy or autism, we hope to identify the genetic factors that contribute to each disorder. We are also studying the range of clinical epilepsy and cases with uncontrolled seizures to learn more about the neurobiology and drug responsiveness of epilepsy in people with autism. Finally, sudden death in epilepsy (SUDEP) is the most common cause of death individuals with autism, and we are partnering with Autism Speaks to study this problem.

Anti-inflammatory Therapy as a Treatment for Epilepsy

There is increasing evidence – from animal models of epilepsy as well as from surgical tissue removed from patients with uncontrolled seizures – that inflammation can cause epilepsy that persists despite treatment with antiepileptic drugs. This process may be a target for novel anti-epilepsy therapy. We are currently working with international collaborators to translate these important findings to accelerate new therapies. The first step is to identify and characterize inflammation in epilepsy We are looking at a potential blood test of brain inflammation in individuals with tuberous sclerosis and epilepsy. We are also doing special brain imaging tests (PK PET scans) that “light up” inflammation in the brain. Finally, we are carefully studying all tissue removed during epilepsy surgery to identify the molecular biology of inflammation. The first multi-center anti-inflammatory trial in focal epilepsy, with NYU as one of the sites, has completed enrollment.

Subdural Pharmacotheerapy Device (SPD)

The NYU Comprehensive Epilepsy Center continues to develop the SDP device in animal studies . This implantable device is designed to prevent seizures by delivering drugs onto the epileptic tissue directly rather than orally which affects the entire body and brain. In animals, we can terminate strong seizures by delivering small amounts of antiepileptic drugs onto the brain’s surface. The device consists of several components including a mini-pump, detection software and special delivery catheters. We implanted the SPD outside the skull in several primates with encouraging results . Human “proof of concept” studies in the operating room reveal that delivering drug onto the brain can stop epilepsy wave activity. Meetings with the FDA indicate that we are on target for proceeding towards human trials in a few years once safety data is collected. This past year we have implanted the device in monkeys, are doing safety studies, as well as testing the drug we believe is most likely to prevent seizures without producing any functional deficit. A large NIH grant was recently submitted to complete the work.

Computerized Cognitive Training and Pyschoeducation for Patients with Temporal Lobe Epilepsy

This study examines the use of new computer technology to improve cognitive and behavioral outcomes in persons with temporal lobe epilepsy. The study will compare the relative effectiveness of two memory rehabilitation programs that are among the most aggressively marketed software packages in the market (Brain Fitness Program, Posit Science vs. Lumosity Training Program). We predict that the computerized training condition, which will be conducted in familiar settings for the participants (i.e. at home), will result in greater gains than a clinic-based psychoeducation intervention, which includes lectures about the use, and appropriate selection of, specific memory-related strategies, on memory measures and other measures of cognitive and behavioral outcome. It is our hope that the information gained from this study will lead to the development of a more comprehensive cognitive training program that can be used to improve the everyday lives of individuals living with epilepsy.

Epilepsy Phenome Genome Project (EPGP)

New York University and the University of California San Francisco organized “The Epilepsy Phenome/Genome Project” (EPGP) in 2003 using seed money from faces. More than 25 major epilepsy centers and over 100 investigators and co-workers throughout the United States, Canada, and Australia are now collaborating to create a powerful database on epilepsy. EPGP has recruited over 3,000 epilepsy patients, family members and control individuals to study the relationship between clinical (phenome) and genetic (genome) data. This 5-year study will provide the infrastructure to discover more specific and effective therapies that can be tailored to an individual’s seizure disorder. EPGP will help identify the gene mutations that can answer important questions. For example, why do some patients respond to drugs, while others do not? The study has been enormously successful in recruiting patients and obtaining high quality data. We are now turn to answering the important questions. For more information..

Neurophysiology of Epilepsy Using Laminar Electrodes

The aim of this study is to better understand the micro-electric physiology of normal and epileptic areas of the human brain. We use small recording electrodes implanted within the brain’s gray matter to study how neurons in each cortical layer communicate with each other. Our findings are helping scientists understand the basic mechanisms with which neurons generate electrical activity, and discover the reasons for their dysfunction in epilepsy. This study is supported by NIH and faces. This past year, Science, the premier scientific journal in the world, and other journals published the results of this work.

Neocortical Epilepsy

The neocortex is the name for the thin layer of gray matter that covers the brain. Half of all seizures start in the neocortex. Epilepsy surgery is much less successful when foci are located here. Often, this is because the structural abnormalities are microscopic and difficult to find on tests such as MRI and even EEG. We developed a technique to analyze MRIs relative to statistical maps of normal age-matched controls to discover abnormal areas that represent the seizure focus. This new method can detect known epileptogenic brain areas better than existing methods. We will now search for very subtle lesions that went undetected during routine clinical inspection. We are also searching for better ways to: identify neocortical epilepsy on EEG, classify the types of neocortical epilepsy, and assess the scope of the problem using epidemiological techniques. We have been investigating the sensitivity of these sophisticated imaging analysis techniques to find small hidden lesions in the brain that may cause epilepsy.

Bioimaging and Mapping the Human Brain in Epilepsy

Magnetoencephalography (MEG), MRI and Functional MRI (fMRI) are powerful techniques used to study the brain. MRI provides anatomic information, MEG can detect minute magnetic fields in the brain, and fMRI can visualize blood flow changes. These techniques can help unravel the mechanisms by which neurons react to stimuli and help us to better understand brain function and neuronal organization in healthy individuals and patients with epilepsy. MEG and fMRI can help us locate language function in patients before surgery and thus help to minimize the side effects of surgery. Faces support has led to the recruitment of investigators in this area, has generated scientific publications and helped obtain grants for a 5 year research program funded by the National Institutes of Health (NIH).

Fertility in Women with Epilepsy

This year we launched a study looking at the ability of women with epilepsy to become pregnant. Some studies found lower fertility rates among women with epilepsy, but no good study has been done to confirm this. Along with our collaborators at Brigham and Women’s hospital and North Shore/ Long Island Jewish Medical Center, we will track seizures, menstrual cycling and time to pregnancy in 100 women with epilepsy and 100 control women, using an IPOD touch diary. We will also explore the impact of menstrual cycling on antiepileptic drug levels, and cycle regularity in women with epilepsy versus control subjects. For more information..

Epilepsy Study Consortium

Thanks to the support of faces, we are helping to bring new drugs to market through the Epilepsy Study Consortium. The Epilepsy Study Consortium is a group of scientific investigators from academic medical research centers. They are all dedicated to optimizing clinical trial research methodology and performing trials that will enhance the likelihood that the best drugs are brought to the people who need them. The centers currently include NYU, Einstein/Montefiore, Cornell, Columbia, Yale, the University of Pennsylvania, Jefferson, Johns Hopkins, the University of Miami, Rush Presbyterian Hospital, Beth Israel Hospital in Boston, and the University of Virginia. The Epilepsy Study Consortium has continued to be active this year. We have completed enrollment on an anti-inflammatory compound (see above) and are half-way through a trial of new study tools. This year, the consortium is preparing to double in size, expanding to sites around the United States. We continue to assess new, more patient-friendly trial designs. We are sponsoring an international conference on Antiepileptic trial design, and we are collaborating with the National Institutes of Health to organize another meeting on the same topic.

Other faces-Supported Research Projects

• Proteomics as biomarker for epilepsy
• Multi-stage epilepsy surgery: safety, efficacy, and utility of novel approaches
• Use of map sensory and motor areas to improve the safety of neurosurgical procedures
• Development of the first Epilepsy Surgery Prognostic Scale
• Cortical language mapping using intracranial EEG and stimulation
• Multi-stage surgery for tuberous sclerosis complex
• New methods for protein delivery and sampling in the brain
• Treatment of seizures in hospitalized patients
• Imaging Psychosis in Epilepsy
• Development of Home Seizure detection Devices.