The Genetic Factor and Altered EEG Network in the Development of Post-Traumatic Epilepsy
Abstract
Post-traumatic epilepsy (PTE) is a type of acquired epilepsy resulting from the effects of traumatic brain injury (TBI). TBI occurs when brain tissue is damaged by an external physical force that injures the brain. TBI is a major cause of death and disability in the United States. For the Veteran population, an estimated 22% of all combat casualties are due to brain injury, with over 379,500 active duty Service members having sustained a TBI between 2000 and 2017. This number could underestimate mild TBIs, such as dizziness and headache after a blast injury, which makes up the vast majority of brain trauma diagnoses at around 83.3%. TBIs are usually classified from “mild” and “moderate” to “severe,” with increasing injury severity correlating with increased risk for developing PTE. Following a TBI, the resulting brain damage can give rise to a variety of neurological dysfunctions, ranging from behavioral changes and loss of coordination to seizures. If recurrent and unprovoked seizures occur four weeks after TBI, they are considered manifestations of post-traumatic epilepsy. Increased risk of developing PTE is associated with conditions such as cerebral bleeding at the time of injury, bruising of the brain, and age over 65 years old, etc. PTE also occurs with mild and moderate TBI without apparent and identifiable injuries on brain images; seemingly mild injuries can thus lead to a downward spiral of neurological, behavioral, and socioeconomic conditions. Hence, there are likely other unknown risk factors we need to identify to develop strategies to mitigate the development of PTE following mild and moderate TBI. Identifying these risk factors could help us develop strategies for screening, monitoring, and intervening early in the case of mild and moderate TBI, so that we may prevent the development of epileptic disorders that potentially cannot be controlled by medication. About one-third of all epilepsy patients cannot be controlled by medication alone. This means a life of uncontrollable and unpredictable seizures, attention deficits, mood instability, memory problems, etc. Aside from immediate prohibitions on driving, this can frequently result in individuals dropping out of school, joblessness, social isolation, and severe socioeconomic downturn. We think that PTE is genetically predisposed, which means people who carry the variant of epilepsy gene will be much more likely to develop PTE after TBI. To investigate the question of whether there is a genetic predisposition in PTE, we propose the formation of a Veterans Affairs (VA)-based research team to screen Veterans with PTE using genomic sequencing. Two key hypotheses will guide this research: Our first hypothesis is that there is a genetic predisposition in patients who develop PTE after TBI. Our objective is to determine whether there is a higher rate of detecting epilepsy gene variants in the cohorts with PTE when compared with TBI controls without epilepsy. The future confirmative study can be planned if we can find a statistically significant association between the PTE and epilepsy genes. Our second hypothesis is that electroencephalography (EEG), which is a clinical study for recording electrical brain waves, can be quantitatively processed using an algorithm called independent component analysis (ICA) to objectively represent the different type of PTE to provide a comparison with the genomic information. An in-depth understanding of the genetic risk factors and the ICA processing of EEG will probably provide the basis for developing clinical tools to screen, monitor, modify, and prevent the development of PTE in high-risk individuals.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010932
Entities
People
- Zhijian Chen
Organizations
- United States Army
- VA Greater Los Angeles Healthcare System