The Neurophysiology of Post-Traumatic Epilepsy: Unraveling Epileptogenesis Signals (NEPTUNE)
Abstract
Focus Area: (1) Markers and Mechanisms and (2) Innovative Research. Objectives and Rationale: Post-traumatic epilepsy (PTE) affects 20% of civilians and near half of military Service Members with severe traumatic brain injury (TBI). Seizures and other brain activity following acute injury are likely contributing to PTE in humans; however, the specific early changes in brain wave characteristics that emerge before epilepsy starts are unknown. In this Idea Development Award proposal, Dr. Amorim will test whether quantitative analysis of brain waves can help predict seizures within 7 days and PTE diagnosis 6 months after TBI. The central hypothesis is that evolution in shapes and features of brain waveforms soon after TBI reflect the biology of epilepsy. Dr. Amorim already collected data from 85 patients with TBI who had electrodes placed on the brain’s surface to record seizures during life-saving TBI surgery, and he plans to recruit 60 additional patients. Effects of anti-seizure medications (ASM) given in the hospital will be connected to the brain wave data to determine which ASM better prevent early seizures and their association with PTE risk. Dr. Geoffrey Manley, Professor of Neurosurgery at the University of California, San Francisco (UCSF), and Dr. Lowenstein, Professor of Neurology at UCSF, are world-renowned leaders in the field of TBI and epilepsy who are committed to Dr. Amorim’s project and his career development. This project is expected to discover new knowledge about brain activity after TBI that may: (1) help future studies select patients most likely to benefit from interventions to prevent seizures and PTE and (2) help select the right medication for the right patient to prevent seizure recurrence and prevent side effects. This research opportunity will ideally position Dr. Amorim to lead studies to prevent PTE and advance treatments. Applications and Benefits: A successful project will expand our knowledge about PTE biology and guide the care of patients with TBI to (1) improve survival without disability from seizures or PTE and (2) improve selection and dosing of ASM. - What populations will it help, and how will it help them? This work will have immediate impact to patients and military Service Members with TBI who are at highest risk for PTE: patients with moderate to severe TBI or penetrating injuries. The overarching goal is to create patient-specific treatment strategies to avoid PTE from developing early on after TBI. - What are the potential applications, benefits, and risks? This study will support point-of-care applications for acute seizure diagnosis after TBI, early predictors of PTE, and individualized ASM use. Importantly, this information will support future studies testing interventions to prevent epilepsy in patients at highest risk. Participants in this study may benefit from epilepsy evaluation with experts in PTE. This study has limited risks as there are no interventions; however, it may involve a small risk of loss of privacy as patient information will be collected. - What are the likely contributions of the proposed research project to advancing PTE research, patient care, and/or quality of life? Understanding the specific biological changes in brain activity that predict epilepsy after TBI will help clinicians educate patients and families about epilepsy risk and select interventions for studies to stop acute seizures and PTE. Side effects from ASM are common in PTE; therefore, ASM selection to maximize effectiveness and prevent side effects could have a big impact in a patient’s quality of life. Timeline: We plan to complete this project in 24 months. We will enroll patients and pursue brain wave analysis for 18 months and complete the needed PTE follow-up by 24 months. In the last 6 months of the project, we plan to submit a proposal for a study in PTE prevention that uses brain wave responses to ASM within days from TBI to guide medication selection. If this
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310242
Entities
People
- Edilberto Amorim De Cerqueira Filho
Organizations
- United States Army
- University of California, San Francisco