? PROJECT 3 ? BIOMARKERS OF HUMAN EPILEPTOGENESIS AFTER TRAUMATIC BRAIN INJURY The mechanisms underlying human acquired epileptogenesis remain poorly understood and a novel multimodal approach to study the process from inception to manifest clinical epilepsy is needed. We have selected Post-Traumatic Epilepsy (PTE) as a model to pursue this understanding because the timing of the potential epileptogenic insult is known and the period of epileptogenesis can be determined. The EpiBioS4Rx Scientific Premise is Epileptogenesis after TBI can be prevented with specific treatments; the identification of relevant biomarkers and performance or rigorous preclinical trials will permit the future design and performance of economically feasible full-scale clinical trials of antiepileptogenic therapies. In Project 3, we plan to perform a multicenter, multidisciplinary observational study of early epileptogenesis after moderate-severe TBI in 300 subjects with the specific injury phenotype of temporal and/or frontal lobe hemorrhagic contusional injury that matches the experimental injury models in animal Projects 1 and 2. We plan four specific aims that feature determining measuring the presence of early electroencephalographic, MRI and blood biomarkers of epileptogenesis.
In aim 4, we plan to create the ideal clinical trial network and trial design informed by our animal Project 2 as well as shared data from large biomarkers trials in both adults (TRACK, CENTER) and children (ADAPT) with TBI. In the Public Engagement Core, we have recruited an outstanding multidisciplinary team of consumers, consumer advocates and key opinion leaders in TBI, PTE, and Epilepsy Clinical Trials to work in this project. We plan a highly integrated and adaptive study design across all 3 Projects and 3 Cores of EpiBioS4Rx to enable a rigorous experimental design for robust and unbiased results. Integration is demonstrated by injury type, methodology, mechanistic investigation, shared analysis and methods, shared public engagement core, and shared DSMB The ultimate goal is to develop a personalized medicine approach for a future definitive clinical trial for an antiepileptogenic drug for PTE.

Public Health Relevance

? PROJECT 3 ? BIOMARKERS OF HUMAN EPILEPTOGENESIS AFTER TRAUMATIC BRAIN INJURY This Project is aimed at understanding and evaluating post-traumatic epilepsy, a serious health problem that accounts for 5% of all epilepsy worldwide. We propose to study a sizeable patient population known to be susceptible to such epilepsy, and assess them over time. Through this process, in close concert with basic science researchers targeting the identical issues, we aim to provide the complete scientific basis across multiple physiological, neurological, neurochemical and neuroimaging parameters for design and execution of a future clinical trial by a highly trained and well-equipped consortium of neuroscience specialists.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
Correa, Daniel J; Kwon, Churl-Su; Connors, Susan et al. (2018) Applying participatory action research in traumatic brain injury studies to prevent post-traumatic epilepsy. Neurobiol Dis :
Vakharia, Vejay N; Duncan, John S; Witt, Juri-Alexander et al. (2018) Getting the best outcomes from epilepsy surgery. Ann Neurol 83:676-690
Engel Jr, Jerome; Bragin, Anatol; Staba, Richard (2018) Nonictal EEG biomarkers for diagnosis and treatment. Epilepsia Open 3:120-126
Engel Jr, Jerome (2018) The current place of epilepsy surgery. Curr Opin Neurol 31:192-197
Schnakers, Caroline; Lutkenhoff, Evan S; Bio, Branden J et al. (2018) Acute EEG spectra characteristics predict thalamic atrophy after severe TBI. J Neurol Neurosurg Psychiatry :
Perucca, Piero; Smith, Gregory; Santana-Gomez, Cesar et al. (2018) Electrophysiological biomarkers of epileptogenicity after traumatic brain injury. Neurobiol Dis :
Ono, Tomonori; Wagenaar, Joost; Giorgi, Filippo S et al. (2018) A companion to the preclinical common data elements and case report forms for rodent EEG studies. A report of the TASK3 EEG Working Group of the ILAE/AES Joint Translational Task Force. Epilepsia Open 3:90-103
Semple, Bridgette D; Zamani, Akram; Rayner, Genevieve et al. (2018) Affective, neurocognitive and psychosocial disorders associated with traumatic brain injury and post-traumatic epilepsy. Neurobiol Dis :
Brady, Rhys D; Casillas-Espinosa, Pablo M; Agoston, Denes V et al. (2018) Modelling traumatic brain injury and posttraumatic epilepsy in rodents. Neurobiol Dis :
Salar, Seda; Moshé, Solomon L; Galanopoulou, Aristea S (2018) Metabolic etiologies in West syndrome. Epilepsia Open 3:134-166

Showing the most recent 10 out of 39 publications