Phenotypes of Epilepsy Etiology and Drug Resistance (PEER)
Abstract
Post-traumatic epilepsy (PTE) refers to epilepsy that emerges and persists for more than 7 days after a traumatic brain injury (TBI). The likelihood of PTE depends on the severity of the brain injury, and there is normally a significant duration of time, often years, between a brain injury and the onset of recurring seizures. The delay between injury and epilepsy may offer a clinical window of opportunity since it represents a period of time prior to the emergence of epilepsy where we can affect change for those at higher risk for epilepsy following TBI. For example, if we compiled the right information together in the right ways, like the severity of brain injury, relevant medical history, and medications, it may be possible to infer who will develop epilepsy after brain injury. Very high accuracy is not required for this to be useful. For example, if we estimated the top one thousand Service Members we think are at risk of epilepsy after TBI, and only one hundred of them go on to develop epilepsy, then we will still have given some advanced warning to a hundred people that they are going to have a serious life-changing disease in the future. This means they can be allocated resources, targeted for interventions or trials before epilepsy emerges, and they can begin to prepare for different eventualities. However, a simple model that looks at the medical history of Veterans and tries to guess who will be diagnosed with epilepsy in the future may not work for a few reasons. First, reporting rates of head injury are very low, and injury information from before military service or elsewhere may not be available. We propose to solve this problem directly by using the responses of thousands of Veteran volunteers with epilepsy and TBI who were asked about the dates and details of their epilepsy and history of lifetime head trauma in a study conducted by project co-investigator Dr. Mary Jo Pugh. We have agreements to reuse this data, which also documents measures of quality of life, medication use, combat exposure, and many other factors. Combined with decade-long medical histories, we can use this data offered by Veterans to greatly improve our model timing and event date accuracies. Aside from event timing, there is another challenge. There is no guarantee that prior medical conditions and demographics contain enough information to make good future predictions. The strongest warning signs that come before an epilepsy diagnosis are often subjective, like unexplained fatigue, absent mindedness, spacing out, or changes in behavior. To capture these valuable pre-diagnostic warning signs, we propose to examine multimodal data. We will capture this information by proxy by analyzing big data repositories that detail how people use health services over time, dates, and dosages of medications that are administered, what health problems emerge, and what services are used and how frequently. A core feature of this study is that we believe the order of all these things combined might add a lot of predictive power. Whether a medication is prescribed in the presence or absence, or before or after certain medical diagnosis is informative. Little work has explored whether specific health comorbidities interact with injury characteristics to increase risk for PTE, and military health questions of interest to the Department of Defense remain unanswered. We propose to enact the solutions to these hurdles we have described and specifically focus on medication differences and outcomes in our first aim. In our second aim, we will develop risk scores for PTE and drug-resistant epilepsy (DRE) following TBI. We want to try and exploit the delayed window of time between TBI and epilepsy diagnosis for detection and to buy time to prepare. The right preceding information could provide a summary measure of epilepsy risk following TBI, which could offer new opportunities for intervention and health care planning. The causal nature of epilepsy acquisi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310221
Entities
People
- Eamonn Kennedy
Organizations
- United States Army
- University of Utah