Military Injuries - Understanding Post-Traumatic Epilepsy (MINUTE): Bioinformatics with Big Data to Examine Multimodal PTE Biomarkers
Abstract
Background: Epilepsy is a neurological disorder arising from abnormal electrical activity in the brain. It affects 1 in 26 Americans, and is marked by recurrent episodes of sudden sensory disturbance, loss of consciousness, or convulsions. Epilepsy can arise from a brain injury, in which case it is considered post-traumatic epilepsy (PTE). Since traumatic brain injury (TBI) can affect any part of the brain, it can progress in many different ways, and there are numerous biological mechanisms involved in seizure progression after TBI. Recent advances in neuroimaging, blood-based biomarkers, and clinical assessment are providing insights into PTE mechanisms, but researchers tend to analyze each type of data separately. This research suggests that patient symptoms and conditions, such as depression, anxiety, and seizure patterns may be key to understanding which biological processes govern PTE, non-traumatic epilepsy (NTE), and treatment-resistant epilepsy (TRE) health trajectories. We propose to combine many sources of data, including health system records, patient-reported outcomes, blood-based biomarkers, neuroimaging, and neuropsychological assessment data in order to produce a complete picture of Veteran’s health trajectories. We will use this multifaceted data to build a model that can better understand the progression of epilepsy. We will also include Veterans with psychogenic non-epileptic seizures (PNES) and non-seizure (no epilepsy and no PNES) controls (NSC) to identify specific variables most strongly associated with the emergence and outcomes of PTE across all levels of TBI severity. We will use established statistics alongside state-of-the-art bioinformatics on the data to address four aims. Aim 1: Develop longitudinal health trajectories for Veterans with epilepsy, and matched Veterans with PNES and NSC using longitudinal health system, survey and experience sampling data. Aim 2: Identify features of neuroimaging data that are most strongly associated with epilepsy, PTE, PNES, and/or mood disorders. Aim 3: Identify features of blood-based brain-related biomarkers that are most strongly associated with epilepsy, PTE, PNES, and/or mood disorders. Aim 4: Correlate and associate the informative variables identified in Aims 1-3 across domains, to uncover new relationships between self-reported symptoms, biomarkers, and imaging/physiologic markers of PTE. We hypothesize: 1) Veterans with epilepsy (PTE, NTE, TRE) will have different health needs and trajectories compared to similar (matched) Veterans with PNES and NSCs; 2) the trajectories (particularly of epilepsy) will be associated with change in blood-based biomarkers, neuroimaging findings, and differences between biomarkers (current vs. pre-injury/deployment); and 3) combined biomarker/neuroimaging findings will vary by epilepsy phenotype (i.e., PTE, NTE, TRE], and will differ from matched PNES and NSC Veterans. Research Strategy: We will obtain data from two existing Epilepsy Research Program-funded PTE/PNES projects, which provide a foundation for our longitudinal cohort. The first data source is a PTE study comprised of a cohort of over 2000 Veterans who have agreed to be re-contacted for future research. The PNES study provides a cohort of approximately 900 individuals who have been identified as having definite, or probable PNES based on expert assessment. We will invite individuals with PTE and NTE to participate. For those who consent and complete a short survey, we will identify similar individuals with regard to age, sex, and TBI from the survey respondent pool without seizure history (NSC), and the PNES cohort. We will invite 50 Veterans from each of the six groups (PTE, NTE, PNES+TBI, PNES-no TBI, NSC+TBI, NSC-no TBI) who respond and complete experience sampling (e.g., respond to prompts such as “rate your stress levels right now”) to undergo clinical evaluation, neuropsychological testing, neuroimaging, and blood draw for biomarker ana
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110327
Entities
People
- Mary Jo V Pugh
Organizations
- George E. Wahlen Department of VA Medical Center
- United States Army