Clinical Research Directory

A Pilot Study to Evaluate the Efficacy and Safety of NaviFUS™ System Neuromodulating Treatment for Patients With Drug Resistant Epilepsy

This will be a prospective, pilot, open-label, two-arm, parallel-group, randomized study to evaluate the efficacy and safety of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant epilepsy (DRE).

Surgery as a Treatment for Medically Intractable Epilepsy

Background: \- Drug resistant epilepsy is the term used to describe epilepsy that cannot be controlled by medication. Many people whose seizures do not respond to medication will respond to surgical treatment, relieving seizures completely or almost completely in one-half to two-thirds of patients who qualify for surgery. The tests and surgery performed as part of this treatment are not experimental, but researchers are interested in using the data collected as part of routine standard epilepsy care to better understand epilepsy and its treatment. Objectives: \- To use surgery as a treatment for drug resistant epilepsy in children and adults. Eligibility: \- Children and adults at least 8 years of age who have simple or complex partial seizures (seizures that come from one area of the brain) that have not responded to medication, and who are willing to have brain surgery to treat their medically intractable epilepsy. Design: * Participants will be screened with a medical history, physical examination, and neurological examination. Imaging studies, including magnetic resonance imaging and computer-assisted tomography (CT), may also be conducted as part of the screening. Participants who do not need surgery or whose epilepsy cannot be treated surgically will follow up with a primary care physician or neurologist and will not need to return to the National Institutes of Health for this study. * Prior to the surgery, participants will have the following procedures to provide information on the correct surgical approach. * Video electroencephalography monitoring to measure brain activity during normal activities within a 24-hour period. Three to four 15-minute breaks are allowed within this period. * Electrodes placed directly in the brain or on the surface of the brain to measure brain activities and determine the part of the brain that is responsible for the seizures (seizure focus). * Participants will have a surgical procedure at the site of their seizure focus. Brain lesions, abnormal blood vessels, tumors, infections, or other areas of brain abnormality will be either removed or treated in a way that will stop or help prevent the spread of seizures without affecting irreplaceable brain functions, such as the ability to speak, understand, move, feel, or see. * Participants will return for outpatient visits and brain imaging studies 2 months, 1 year, and 2 years after surgery.

Investigating Epilepsy: Screening and Evaluation

Background: Epilepsy affects about 1 percent of the U.S. population. Most people with epilepsy respond well to medicine, but some do not. Researchers want people who have diagnosed or suspected epilepsy to participate in ongoing studies. They want to learn more about clinical care for epilepsy. They want fellows and residents to learn more about the care of people with epilepsy. Objectives: To learn more about seizures and find ways to best treat people with drug-resistant epilepsy. Eligibility: Adults and children ages 8 years and older with diagnosed or suspected epilepsy Design: Participants will be screened with: Physical exam Medical history Questionnaires Participants will have many visits. They may be admitted to the hospital for several weeks. Their medication might be stopped or changed. Participants will have many tests: Blood and urine tests EEG: Wires attached to the head with paste record brain waves. This may be videotaped. Thinking and memory tests MRI: Participants lie on a table that slides in and out of a tube. They perform simple tasks in the tube. MEG: Participants lie on a table and place their head in a helmet to record brain waves. PET scan: Participants lie on a table that slides into a machine. A small amount of radioactive dye is injected into their arm with an IV. For the IV, a small tube is inserted into the arm with a needle. Participants will stay enrolled in this study if they join other epilepsy-related studies. They may be contacted at intervals for follow-up. Their participation will end if they have not been seen clinically for their epilepsy for 3 years.

Localizing Epileptic Networks Using MRI and iEEG

Upon successful completion of this study, the investigators expect the study's contribution to be the development of noninvasive imaging biomarkers to predict IEEG functional dynamics and epilepsy surgical outcomes. Findings from the present study may inform current and new therapies to map and alter seizure spread, and pave the way for less invasive, better- targeted, patient-specific interventions with improved surgical outcomes. This research is relevant to public health because over 20 million people worldwide suffer from focal drug-resistant epilepsy and are potential candidates for cure with epilepsy surgical interventions.

A Phase 1/2 Study of NRTX-1001 Neuronal Cell Therapy in Drug-Resistant Bilateral Mesial Temporal Lobe Epilepsy (MTLE)

This is a multicenter, single arm, open label clinical trial that is designed to test the safety and preliminary efficacy of single administration inhibitory nerve cells called interneurons (NRTX-1001), into both temporal lobes of subjects with drug-resistant bilateral mesial temporal lobe epilepsy.

Evaluation of the NaviFUS System in Drug Resistant Epilepsy

Participants with drug-resistant epilepsy (DRE) enrolled in this study will receive focused ultrasound (FUS) treatment with the NaviFUS System, guided by the neuronavigation system to evaluate the safety and efficacy of using NaviFUS System. During the treatment, the FUS will electronically scan and target to the assigned zones on one or both of the hippocampi. The study consists of a 60-day screening period for baseline observation prior to treatment, a FUS treatment period of 2 weeks for Cohort 1 or 3 weeks for Cohort 2 with 2 FUS treatments per week using the NaviFUS System, and a safety follow-up period of 81 days.

Pre-operative Mapping of the Anterior Temporal Lobe Using Functional MRI Innovative Techniques in in Drug-resistant Epileptic Patients

Anterior temporal epilepsy is the most frequent form of focal epilepsy (more than 50% of focal epilepsies). The epilepsy is drug-resistant when epileptic seizures persist despite antiepileptic treatment (25% of cases). In this case, it is possible to offer a surgical solution to the patient: an anterior temporal lobectomy. This surgery consists of removing the entire portion of the temporal lobe responsible for epilepsy (epileptogenic zone), that is to say a major part of the temporal pole, the hippocampus and the ventral anterior temporal lobe (vATL). The goal of the surgery is to lead to a disappearance of the seizures while preserving the functions of the patient. This is why a pre-surgical assessment is systematically carried out in order to locate the epileptic focus and to predict the risks of neurological and cognitive deficits. The vATL is of particular interest because it is a highly functional region, involved in naming, semantic processing and face recognition. A resection of this region by anterior lobectomy can therefore impact these functions and lead to cognitive deficits (for example, up to 65% decline in naming), which can be disabling in the lives of patients, even if they are free from seizures. One of the major challenges of epilepsy surgery is therefore to predict the postoperative neuropsychological outcome. The prediction of the neuropsychological outcome of the post-surgery patient is largely based on the mapping of functional regions preoperatively, carried out by functional MRI (fMRI), or by electrical stimulation carried out during intracerebral exploration by StereoElectroEncephalography (SEEG). However, current techniques have drawbacks. Electrical stimulations are based on an invasive exploration (SEEG), are time-consuming and sometimes difficult to interpret. The fMRI sequences used in clinical routine do not make it possible to visualize the entire vATL region because of artifacts related to the auditory canal. Thus, the signal is strongly diminished in this region, rendering a large area of the vATL invisible. This results in insufficient visualization of activated vATL regions when performing tasks such as naming, semantic processing, and face recognition. Important functional regions can therefore be removed during surgery and negatively impact the patient's neuropsychological outcome. In the CARTA study, original methods are associated in order to increase the signal-to-noise ratio in vATL. On the one hand, the Multi-Band sequence, an innovative fMRI sequence, will be used. On the other hand, a particular method of presentation of visual stimuli will be used, called fast periodic visual stimulation (FPVS: Fast Periodic Visual Stimulation), during which the stimuli are presented periodically (fixed frequency). Individually, these methods improve vATL (signal enhancement) exploration. The investigators assume that the combination of the two methods may have a potentiating effect, compared to the standard SMS (Simultaneous Multi-Slice) sequence. fMRI exploration will not influence the surgical management of the patient included in the study because it is the beginning of the development of this technique, but could be used, in the longer term, to guide the surgeries of epileptic patients. Thus, the goal of this study is to precisely map the vATL, using innovative methods in fMRI. This mapping will make it possible to study the cerebral functions of the vATL involved in naming, semantic processing and face recognition, and ultimately improve the postoperative neuropsychological prognosis of epileptic patients.

Enhanced MRI Imaging in Healthy Participants and Participants With Epilepsy

Temporal lobe epilepsy (TLE) is a common type of epilepsy and one of the most likely to not be controlled by medication. For patients who do not respond to medication, surgery can result in a cure of seizures. Given the fact that around 50% of patients who undergo surgery are seizure free at 10 years there is a need to improve the understanding of what factors best predict surgical outcomes in order to improve our ability to select candidates for surgery. The demonstration of abnormalities in the temporal lobe on MRI is one of the best predictors of seizure free surgical outcomes. Recent studies suggest that changes in specific subregions of the hippocampus could be the strongest predictors of surgical success, however the small size of these regions, (millimeters) make them very difficult to study with standard clinical MRI. Recently new MRI methods have been developed at Wayne State University to image hippocampal blood vessels using ferumoxytol infusion. Feraheme (ferumoxytol) is a drug that is approved in the United States for the treatment of iron deficiency anemia and is currently being studied as an MRI contrast agent in 8 active clinical trials in the United States as well as a Parkinson's Disease study in Canada.

Pathophysiology, Psycho-emotional and Cognitive Functioning Associated With Tinnitus

the investigators have recently shown that patients with drug-resistant temporal lobe epilepsy who have undergone brain surgery targeting the medial temporal lobe structures were more likely to develop tinnitus postoperatively. This discovery of a vulnerability to tinnitus associated with medial temporal lobe surgery to eliminate drug-refractory epileptic seizures provides a new clinical model of tinnitus, targeting temporal lobe regions as generators or mediators of this hearing disorder. The objective of this project is to study the impact of tinnitus on the cognitive, emotional, psychoacoustic and cerebral functioning associated with this hearing disorder, and to clarify the pathophysiology of tinnitus by comparing different groups of individuals with tinnitus (surgical epileptic patients or non-surgical ORL patients) to matched tinnitus-free groups (surgical tinnitus-free cases and healthy controls volunteer).

Innovative MRI to Localize the Epileptic Zone

The goal of EPI-CATCHER is to outline the clinical potential of multiparametric quantitative MRI (mqMRI) and of GABA-edited magnetic resonance spectroscopy (GABA-MRS), combined with machine learning tools, as imaging biomarkers to localize and delineate the EZ.

Low-intensity Focused Ultrasound Pulsation (LIFUP) for Treatment of Temporal Lobe Epilepsy

We intend to use focused ultrasound to stimulate or suppress brain activity in patients with epilepsy. We hypothesize that focused ultrasound is capable of brain stimulation or suppression visible with functional MRI, and will not cause tissue damage.