The Department of Neurological Surgery is currently conducting the following studies in Epilepsy:
Focal Cooling as Prophylactic Treatment for Posttraumatic Epilepsy
Principal Investigator: Raimondo D'Ambrosio, PhD
Funded By: Citizens United for Research in Epilepsy (CURE)
Posttraumatic epilepsy (PTE) is a chronic neurological disorder that appears following head injury and for which there is no prophylactic treatment. In addition, PTE results in complex partial seizures which are a type of seizures more frequently resistant to currently available antiepileptic drugs (AED). Although many AEDs have been introduced in recent years, the proportion of patients failing to respond has not significantly changed.
In addition, none of the drugs tested in clinical trials has been found to be antiepileptogenic following central nervous system injury. Furthermore, the high incidence of traumatic brain injury (TBI) in the Iraq and Afghanistan wars also creates the urgent need to develop broad-spectrum and field-deployable therapeutic strategies to prevent and/or limit epileptogenesis. In a blind, randomized study just completed, focal cooling of the rat neocortex after fluid percussion injury (FPI) prevented the onset of neocortical PTE within one month postinjury. Seizures did not return during re-warming for six-eight hours.
This research is meant to 1) determine the duration of seizure suppression, 2) collect preliminary data to formulate robust hypotheses on the mechanisms of action, and 3) begin the evaluation of best strategies to cool a medically intractable epileptic focus in the human. These data will be crucial to subsequent optimization of the treatment and for its rapid translation to the clinic through partnership with industry.
Posttraumatic Epilepsy Induced by Fluid Percussion Injury in the Rat
Principal Investigator: Raimondo D'Ambrosio, PhD
Funded By: National Institutes of Health (NIH
The overall goal of this research is to begin the investigation of the mechanisms responsible for the genesis and progression of posttraumatic epilepsy (PTE) induced by fluid percussion injury (FPI), a relevant model of concussive closed head injury in the rat. In our most recent work we:
- Discovered and characterized different types of chronic spontaneous recurrent partial seizures (CSRPSs grade 1, 2 and 3) following rostral parasaggital FPI (rpFPI) in the rat
- Discovered that rpFPI-induced PTE is a progressive disorder that results, months after injury, in mesial-temporal lobe epilepsy (MTLE) with dual pathology. The present proposal will focus on defining the neural substrates of rpFPI-induced CSRPSs, on the mechanisms of heterogeneity of FPI-induced CSRPSs, and on their mechanisms of genesis and progression.
Specific Aims: to test the following hypotheses:
- Tthat the frontal-parietal neocortex at the site of rpFPI develops into the early epileptic focus, responsible for grade 1 and 2 seizures, while hippocampus and piriform cortex develop epileptic foci, responsible for grade 3 seizures, at later times.
- That the probability of developing PTE following FPI, as well as seizure type, frequency and duration, their underlying pathology, and their temporal progression, depends on the degree and location of the injury.
- That neuronal and synaptic activity within the incipient early epileptic focus is required for posttraumatic epileptogenesis to occur.
- That a kindling-like cellular phenomenon mediated by the early epileptic focus is responsible for hippocampal epileptogenesis.
- That the pharmacological responsiveness of FPI-induced epilepsy changes with time, as the disease progresses, as a function of seizure type and temporal lobe sclerosis.
In addition, we aim to develop a murine model of FPI-induced PTE to introduce the use of genetically engineered mice in the investigation of risk factors and basic mechanisms of PTE. Because of the unparalleled phenotypic and etiological similarities existing between this rodent model and human PTE the data collected will lead to the elucidation of more relevant mechanisms of genesis and progression of PTE, and to a better standardization of the model to the advantage of both basic and translational research efforts.
Flumazenil-PET and Decision Making in the Surgical Management of Non-lesional Epilepsy
Principal Investigator: Jeffrey Ojemann, MD
Funded By: Dana Foundation
This project tests the hypothesis that a newer imaging technique, flumazenil positron emission tomography (flumazenil-PET), will impact decision-making processes in the evaluation of patients for the surgical treatment of intractable epilepsy.
Electrocorticography of Speech Perception and Production
Principal Investigator: Jeffrey Ojemann, MD and Erik Edwards, PhD
Funded By: NIH National Research Service Award
This project aims to improve cortical mapping in neurosurgical patients, with a focus on speech and language function. Cortical mapping is necessary for surgical planning in epilepsy patients in order to avoid post-operative behavioral deficits that compromise the patient's quality of life. Currently, this is accomplished by electrical stimulation mapping (ESM), but this has a number of drawbacks. Epilepsy patients often have electrodes implanted on the cortical surface for purposes of seizure localization. Our goal is to use these for electrocorticography (ECoG) mapping that is passive and without additional risk to the patient.
The working hypothesis behind the proposed research is that the high-gamma band of the ECoG can be used to measure task-specific cortical activations with high spatial and temporal resolution. The proposed project aims to develop ECoG as a cortical mapping method, both as an alternative to ESM for neurosurgical planning and as a means of addressing fundamental questions in linguistic neuroscience. Methodological improvements must be realized before ECoG can realize its full potential as a mapping modality. Three specific methodological improvements are proposed as part of this NRSA. Our long-term goal is to develop a battery of tasks to allow rapid functional mapping of individual patients for surgical planning. A second long-term goal is to better understand the involvement of different cortical regions, including auditory and motor regions, in language function.