Project Details
Description
The goal of this project is to study how posttraumatic epilepsy (PTE) develops after brain injury. In the general population, PTE accounts for 5% of all epilepsy cases and 20% of symptomatic epilepsy. This number is understandably higher in the military population where almost 50% of traumatic brain injury (TBI) victims, more specifically those who sustain penetrating head injuries, go on to develop PTE. A unique feature of PTE is that seizure begins in a delayed fashion after TBI. In approximately 80% of cases, epilepsy develops within 2 years, but the elevated risk extends for longer than 10 years post-TBI. Studies have identified risk factors associated with PTE, which include but are not limited to severity of initial TBI, length of posttraumatic amnesia, presence of intracranial hemorrhage, penetrating head injuries, depressed skull fractures, retention of metal fragments, location of lesion(s), cerebral contusions, age, and comorbid chronic alcoholism. There have not been any identified biomarkers, however, that can reliably predict the development of PTE after TBI. This is partly due to the fact that the mechanism of how PTE develops is not well understood, which makes the prevention and treatment of PTE challenging. Recent discoveries have suggested that epilepsy is a disease of brain network. Even when the origin of the seizure begins at a focal area of the brain, seizure cannot be sustained if the brain network cannot facilitate the spread of seizure to the other parts of the brain. Therefore, in order to understand how PTE develops, one has to understand the brain network abnormalities associated with PTE. Advanced magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI) and resting state functional MRI (rsfMRI) have offered noninvasive means to study the changes of brain network architecture related PTE. DTI measures structural connectivity, which is related to white matter tracks in the brain, whereas rsfMRI infers functional connectivity by measuring the correlation of the blood flow patterns between two regions of the brain. Research has shown that after TBI, both structural and functional connectivity is altered as a result of injuries. We hypothesize that for some individuals, the injured brain does not return to its normal state: The structural connectivity remained low both at the site of injury and many other areas of brain, while, at the same time, the functional connectivity increases at a chaotic fashion. Some normal functional connectivity suffers disruption and become weakened or even lost. These changes take place in a gradual fashion, which may be the reason why PTE occurs in a delayed fashion after TBI. In this study, we proposed to compare these metrics obtain from MRI studies between participants with PTE and those who have no neurological diseases. We will compare the brain network characteristics between the two groups and identify the ones with significant difference between the two groups. In addition, we will enroll participants who suffered moderate and severe TBI and then follow them up with repeated MRI, electroencephalogram (EEG) and neuropsychological tests at three time points, within 3 month, between 6 and 9 months, and between 12 to 18 months. Our objective is to capture changes of brain network parameters over time and investigate whether the evolution of brain network metrics during the recovery phase of TBI differs between the two groups (i.e., the group who develops PTE and the one that does not). Finally, we will use mathematical models to evaluate whether a subset of the abnormal network metrics can predict the development of PTE.
Status | Active |
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Effective start/end date | 9/15/18 → … |
Funding
- U.S. Army: $721,641.00