Some of our center's ongoing projects in both clinical and translational epilepsy research:
The Epilepsy Phenome/Genome Project (EPGP)
Dr. R. Kuzniecky, Dr. O. Devinsky
New York University and the University of California San Francisco were awarded NIH funding for The Epilepsy Phenome/Genome Project (EPGP), the most ambitious and complex study in epilepsy to date. EPGP will bring together 14 prominent epilepsy centers and 50 investigators throughout the United States. The $21 million grant will recruit more than 4000 epilepsy patients and control subjects to study the relationship between their clinical (phenome) and genetic (genome) data. This five-year study will use state-of-the-art techniques to manage and analyze huge volumes of data. EPGP will provide the infrastructure to discover more specific and effective therapies tailored to an individual’s seizure disorder. EPGP will help identify the gene mutations that explain drug-responsiveness as well as the genes that modify epilepsy susceptibility. Faces has provided the financial support for the 3-year planning phase leading to NIH funding. Please click here for more information.
Hybrid Neuroprosthesis (HNP) Study
Dr. N. Ludvig, Dr. G. Medveczky, S. Baptiste, J. John,
Dr. R. Kuzniecky, Dr. O. Devinsky
The NYU Epilepsy Center began working on the HNP project in April 2004. The goal was to develop an implantable device that will treat seizures by detecting them and delivering a drug to the epileptic region. This aims to concentrate the medicine in time and space around the seizure focus, and not expose other parts of the body and brain continuously to medicines that may only be needed <0.1% of the time, in a small portion of the brain. The device consists of several components including a mini-pump, detection software, and special delivery catheters. Over the past year, we have finalized studies in lab rats, testing several compounds that demonstrate the feasibility of this treatment.
We are beginning the next phase of these studies with new EEG software to recognize seizures, new pump design, monkey studies and “human proof of concept” studies. This project can have a great impact on therapy for epilepsy and other neurological disorders such as Alzheimer’s and Parkinson’s disease.
The Epilepsy Clinical Trials Consortium
Dr. J. French, Dr. O. Devinsky, Dr. B. Vasquez, Dr. R. Kuzniecky
The Epilepsy Clinical Trials Consortium is also funded by faces. The consortium includes the epilepsy centers at NYU, University of Pennsylvania, Columbia, Montefiore-Einstein, and Cornell. Clinical trial consortiums have been one of the most effective means to accelerate the development of new therapies, as exemplified by the prostate cancer, Alzheimer’s disease, and Parkinson’s disease study groups. This, however, is a novel approach in the field of epilepsy. The consortium will perform early (Phase I and II) clinical trials to test whether new drugs show promise in treating epilepsy. The consortium will take a leadership role in developing trial methodology and protocols. During 2006, the infrastructure was created and the consortium is now operational and beginning its first clinical trial in testing a new antiepileptic drug in early development. This project is a collaborative one with the Epilepsy Therapy Development Project.
Brain Cooling for the Treatment of Epilepsy
Dr. R. Kuzniecky, S. Seal, Dr. G. Medveczky, Dr. N. Ludvig
Brain cooling for epilepsy is based on the established concept that physiologic activity decreases with lowering body temperature. Experimental data suggest that brain cooling can decrease seizure activity in animals. Faces is supporting the development of the NYU brain cooling program. In 2006, we developed the experimental methods and probes for brain temperature measurements. This year, we will start cooling experiments to test their effectiveness in animals.
Bioimaging of Epilepsy
Dr. R. Kuzniecky, Dr. H. Hetherington, Dr. J. Pan
Magnetic Resonance Spectroscopy (MRS) uses a strong magnet and radio waves to generate signals that indicate quantities of critical brain chemicals. Our studies in collaboration with Yale University aim at understanding the brain biochemical changes in epilepsy. We are studying the ability of MRS to help localize the seizure focus and to investigate brain injury and recovery in epilepsy. Alterations in chemical concentrations provide a metabolic window of brain function and may permit us to better identify the area from which seizures arise.
MRS can detect disturbances in tissue well before any structural changes are evident on MRI. MRS can also study brain neurotransmitters such as GABA, the main inhibitory chemical in the brain, and glutamate, the major excitatory chemical. NIH has recently funded studies at NYU using bioimaging to study the effects of nutritional supplements on seizures.
Neurophysiology of Epilepsy Using Laminar Electrodes
Dr. T. Thesen, Dr. R. Kuzniecky, Dr. O. Devinsky, Dr. W. Doyle, Dr. C. Wang
The aim of this study is to better understand the micro-electrophysiology of normal and epileptogenic areas of the human brain. Recordings are carried out with microelectrodes that can record activity from each layer of the cerebral cortex (six layers). These findings may help us understand the circuitry in epilepsy and how brain cells communicate with each other. This study is supported by both the NIH and faces.
- Comparing epileptiform activity in generalized and partial epilepsy to establish criteria for distinguishing these disorders and understanding the underlying physiology.
- Establishing computational techniques to improve MEG studies in patients with implanted metallic devices, such as the vagal nerve stimulator.
- Comparing seizure foci localization by MEG and intracranial electrodes in epilepsy surgery patients to enhance the predictive value of MEG.
- Mapping sensory and motor functions to improve the safety of neurosurgical procedures.
- Utilizing MEG to identify language function in patients.
In addition to the clinical care, the TS Center is also a leader in TS research. Dr. Daniel Miles is currently representing the center as a protocol is developed to investigate the use of rapamycin the treatment of subependymal giant cell tumors. These tumors have the potential to enlarge and obstruct cerebrospinal fluid, leading to hydrocephalus. At present, treatment involves surgery to place a shut and remove the tumor. If supported by the NIH, the study will utilize rapamycin to shrink the tumors and avoid the need for surgery.
Other research studies in Tuberous Sclerosis Include:
- Multi-stage Surgery for TSC at NYU (published, Pediatrics).
- A multicenter study on the outcome of epilepsy surgery in TSC. (presented, American Epilepsy Society)
- Why and how often children with TSC have Autistic Spectrum Disorders.
- Rapamycin study for treating kidney angiomyolipomas in TSC.
- A study on the accuracy of the MP5 Nighttime Seizure Monitor. This monitor is used to detect nocturnal seizures and may help to prevent sudden death in epilepsy patients (SUDEP).
- Childhood Absence Epilepsy (CAE) Study. Development of an infrastructure that will help support NYU’s participation in an NIH research protocol investigating the efficacy of three drugs for CAE, and study their impact on cognition, behavior, and quality of life.
- Analysis of the largest group of patients with epilepsy and psychosis and its seizure-related, genetic, and other causes.
- Correlation of MRI features in the white matter with neuropsychological testing in temporal lobe epilepsy.
- Language mapping using fMRI and MEG
- Multistage epilepsy surgery: safety, efficacy, and utility of a novel approach in pediatric and adult extratemporal epilepsy
- Effects of seizures on autonomic and cardiovascular function
- Therapeutic outcomes of treating infantile spasms
- Group psychological education as treatment for psychogenic nonepileptic seizures
- Depression and quality of life in treatment-resistant epilepsy
