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Epilepsy Clinical Research
Clinical Research OverviewPatient-oriented epilepsy research at Yale has led to major advances in the diagnosis and treatment of epilepsy. Yale was one of the first centers in the world to perform epilepsy neurosurgery, and remains at the forefront in developing innovative brain imaging methods, deep brain stimulation, other neurosurgical techniques, medication trials, and additional novel approaches. Ongoing projects are listed below. Please consider joining our effort by enrolling in a clinical trial or making a gift today! 
Long-term Outcome of Epilepsy SurgeryThis project is a prospective multimodal outcome study funded by NIH and based at Yale which includes 6 other sites, and follows the seizure, quality of life, cognitive and psychiatric outcomes of resective epilepsy surgery with standard interventions and instruments to measure those aspects of patient response. Ongoing analyses will focus on the interplay between these outcomes, predictors of outcomes, differences in procedures involving various cerebral locations, and other questions that can be addressed using this remarkable database. Individual diagnostic methods, for example MRI with standardized interpretation, or SPECT with ictal injection and coregistration and subtraction processing are part of the diagnostic evaluation, and their interpretation, interrater reliability, correlation with other localizing studies, and predictive value for pathology and outcome can be examined in this large contemporary surgical population.
Seizure Awareness StudyThis ongoing study examines the extent to which patients are aware of their seizures, through questionnaire and interview methods and videotape review of seizure events in hospitalized epilepsy patients. The work is collaborative between all the epilepsy faculty, fellows and patients and a Yale Medical student who is coordinating the data collection and analysis. The observations have key importance for our treatment and diagnosis at every stage of the epileptic process.
Computational Neurophysiology LaboratoryThe long-term goal of the Computational Neurophysiology Laboratory (CNL) is to understand seizure generation. The tools we employ towards this are the visual and quantitative analysis of the scalp and intracranial EEG. Members of the CNL are also engaged in innovative collaborative research with colleagues in the Yale Epilepsy Research Program. These collaborative projects seek to combine information from multiple modalities including EEG, microdialysis, SPECT, PET, MRI, fMRI and magnetic resonance spectroscopy (MRS) to further our understanding of epilepsy. Contact: Hitten Zaveri, PhD
Anticipating Seizures in Epileptic NetworksThis project involves investigations of advanced analysis of intracranial EEG data in adult and pediatric epilepsy patients for "Anticipating Seizures in Epileptic Networks." Contacts: Hitten Zaveri, PhD
NeuroPace Responsive Neurostimulator (RNS™) SystemThe Yale Epilepsy Program is participating in a clinical trial of responsive electrical stimulation of the brain as a treatment for intractable partial epilepsy using an implanted medical device. NeuroPace, Inc is sponsoring this investigational device study of their Responsive Neurostimulator (RNS™) system. The study is open to patients 18 years of age or older with partial onset seizures that are resistant or hard to treat using two or more antiepileptic medications. Candidates will continue to receive their epilepsy medications while participating in the trial. Contact: Robert B. Duckrow, MD Other links: Neuropace The NeuroPace RNS™ is designed to detect abnormal electrical activity in the brain and to deliver small amounts of electrical stimulation to suppress seizures before there are any seizure symptoms.
MR Imaging of EpilepsyThis project involves the investigation of MR imaging of epilepsy; ie, MR imaging features of epileptogenic anomalies, with emphasis on cortical dysplasia. Using a systematic approach developed for interpretation of MR scans of seizure patients, we are performing prospective studies that will correlate MR imaging features with clinical and surgical characteristics. Contact: Richard Bronen, MD
Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics StudyThis is a multicenter study of new onset childhood absence epilepsy. Contacts: Candy Cardoza, RN - Study coordinator Other links: Government Clinical Trials: Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
Long-term Outcomes of Childhood-Onset EpilepsyWe are engaged in a longitudinal study of children with newly diagnosed epilepsy, started in 1993. The first phase of the study concerned the prediction of remission, relapse, and intractability early in the course of the disorder. Recently we addressed several issues concerning the mid-term (5-10 years) seizure outcomes, mortality, status epilepticus, as well as developmental, and educational outcomes. Over the next several years, we hope to provide information regarding two sets of issues: 1) Occurrence of later-appearing intractable epilepsy and the association with hippocampal volumetric measurements. 2) Social, educational, behavioral, psychiatric and quality of life outcomes in young adults with childhood onset epilepsy: their relation to seizure outcome. This information will be central to informing evaluation, treatment, management, and counseling approaches for children with epilepsy and their families. Contacts: Susan Levy, MD Other links: Connecticut Study of Epilepsy
Absence Epilepsy, Attention, & fMRIThe mechanisms for impaired attention in absence epilepsy are not known. To determine how human brain networks are affected by absence seizures we perform simultaneous fMRI and EEG recordings in children during absence seizures. To determine which brain regions are crucial for maintaining normal attention we repeat these measurements during attention tasks. We then test whether brain regions activated during the task show altered activity when performance is disrupted by an absence seizure. Contacts: Hal Blumenfeld, MD, PhD
Nuclear Medicine Imaging in EpilepsyOur nuclear imaging analysis team has developed novel methods for analyzing single photon emission computed tomography (SPECT) and positron emission tomography (PET) images in epilepsy patients. Improved methods of analyzing blood flow during seizures with SPECT has helped pinpoint seizure onset for surgical planning. The latest method developed by our group is Ictal-interictal SPECT Analyzed by SPM (ISAS). In addition, our group has developed novel methods for detecting the uncoupling of blood flow and metabolism in seizure generating regions of the brain using SPECT/PET ratio imaging. Contacts: Hal Blumenfeld, MD, PhD
Epileptogenic Tissue Localization using EEG-fMRIThis proposal is aimed at further developing and understanding combined electroencephalography and functional magnetic resonance imaging (EEG-fMRI). The experiments are designed to improve our understanding of the relationship between MR measures of neuronal activity in the presence of epileptiform activity, and neuronal signatures of activity based on surface or depth recorded EEG. Contacts: Robert Todd Constable, PhD
Functional MRI for Neurosurgical Planning in EpilepsyFunctional MR imaging (fMRI) has the potential to replace, or significantly enhance, the current methods used in Neurosurgical planning. It is noninvasive and has been shown to be able to localize cortical activity. Contacts: Robert Todd Constable, PhD
Bioimaging and Intervention in Neocortical EpilepsyMagnetic resonance functional and spectroscopic imaging (fMRI, MRS) of the brain provides tremendous opportunities in the study and treatment of epilepsy. We will develop high resolution MRS and fMRI at 4T and advanced analysis and integration methods to better define the epileptogenic tissue and surrounding regions, and enhance our understanding of the biochemical mechanisms underlying the dysfunction in neocortical epilepsy. Contacts: James Duncan, PhD
Energy and Metabolism in Temporal Lobe EpilepsyA variety of metabolic imaging studies, including FDG PET and MRS, have suggested metabolic and energy deficiencies in epileptogenic regions of certain symptomatic epilepsies. Contacts: Dennis Spencer, MD
Multimodal Clinical Image Coregistration in EpilepsyBioImage Suite is an integrated image analysis software suite developed at Yale. It uses a combination of C++ and Tcl in the same fashion as that pioneered by the Visualization Toolkit (VTK) and it leverages both VTK and the Insight Toolkit. It has extensive capabilities for both neuro/cardiac and abdominal image analysis and state of the art visualization. Contacts: Xenios Papademetris, PhD Other links: Yale Bioimage Suite
Brain Microdialysis and Stimulation in EpilepsyMajor goal in our laboratory is to elucidate the neurochemical mechanisms underlying epilepsy using brain microdialysis, intracranial electrode recording and stimulation in conscious neurosurgical epilepsy patients. We are also interested in the neurochemical and electrophysiological changes during cognitive processing, sleep, and in the effects of sex steroids on brain neurochemistry. HPLC is used to analyze the microdialysate samples obtained from the human brain for several neurotransmitters and neurometabolites. Another line of research is to study the effects of direct brain stimulation on neurotransmitter dynamics and brain excitability in order to develop better treatments for brain disorders such as refractory epilepsy and depression. The work involves close collaboration between the Departments of Neurosurgery, Neurology and Psychiatry. Contact: Idil Cavus, MD, PhD
Virtual Reality to Test Driving Safety in EpilepsyOur research study uses virtual reality driving simulation during video/EEG monitoring to learn more about driving safety in patients with epilepsy. One of the most devastating aspects of epilepsy is its effects on patients’ ability to drive. Some suffer motor vehicle accidents when they have seizures, and many others are prevented from driving for months or years at a time by state laws, doctors’ advice or fear of crashing. The goal of our research is to determine how epileptic seizures affect driving performance, and to learn which brain regions lead to impaired driving safety during and following seizures. In addition, the types of seizures which cause impaired driving safety will be investigated. Our hope is that this research will provide useful information for clinicians when discussing driving risk with their patients. Knowledge of the brain networks affected when driving safety is impaired can also lead to treatments which prevent this problem. This will enhance safety, prevent injuries, and improve the quality of life for patients with epilepsy. Contacts: Hal Blumenfeld, MD, PhD Other links: Driving Study
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