Post-Traumatic Epilepsy: Models, Common Data Elements and Optimization

March 18, 2021


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Meeting Date(s)
Session 1: Thursday, March 18, 2021 from 2:00 pm – 4:00 pm EST
Session 2: Thursday, April 22, 2021 from 2:00 pm – 4:00 pm EST
Session 3: Thursday, May 20, 2021 from 2:00 pm – 4:00 pm EST
Session 4: Thursday, June 17, 2021 from 2:00 pm – 4:00 pm EST

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Photo of MRI showing brain injury

Sponsored By: National Institute of Neurological Disorders and Stroke

Traumatic brain injury (TBI) is a leading cause of acquired epilepsy, especially for persons aged 15-24 years. About 40 percent of individuals with post-traumatic epilepsy have onset within six months; 50 percent within one year; and about 80 percent within two years of head injury. However, post-traumatic epilepsy (PTE) may begin more than 15 years later. The delay in recurrent seizure development presents both a clinical window for treatment and a significant hurdle for clinical and pre-clinical studies. Therefore, to elucidate both the cellular and molecular pathways through which seizures are induced by TBI and the clinical course, precise, carefully controlled studies are needed.

The conference will set the stage to optimize preclinical and clinical research to prevent epileptogenesis following TBI. The results will help improve biomedical research in posttraumatic epilepsy. The goals of the conference are to:

  1. Improve communication and collaboration between TBI and epilepsy investigators to focus on the study of PTE.
  2. Optimize preclinical models and markers to reduce replication of efforts and to improve predictive value of preclinical models to the clinic.
  3. Identify gaps in the research that require additional efforts.
  4. Identify clinical markers for prevention of PTE.
  5. Identify the next steps toward pre-clinical and clinical development of treatment paradigms to prevent PTE.
  6. Develop protocols for handling and archiving large datasets.

To address a poorly studied area, the NIH sponsored a series of virtual workshops, entitled, "post-traumatic epilepsy: Models, common data elements and optimization." The overall objective of the workshops was to encourage and advance research into the mechanisms through which brain injury results in recurrent seizure activity, or post-traumatic epilepsy (See Workshop Webpage). To advance the PTE field, experts from both epilepsy and TBI were brought together to optimize preclinical animal studies, define common data elements unique to PTE and to establish needs to better translate preclinical findings to the clinic. The workshop was highly successful in initiating dialog between epilepsy and TBI researchers, as well as preclinical and clinical investigators. The importance of collaboration across fields and between preclinical and clinical researchers was highlighted throughout the conference. The workshops were recorded and have been added to the webpage for reference.

The major points discussed include:

  1. The need for standardized validation for animal models of PTE with improved measures of TBI severity and associated unconsciousness.
  2. The value of common data elements for more focused research on mechanisms underlying the latency between TBI and the emergence of recurrent seizure activity.
  3. It was noted that identifying mechanisms that current models appear to miss may necessitate the development of new models or further adaptation of current models.
  4. The identification of additional mechanisms of epileptogenesis in preclinical studies are necessary to help further clinical study design
  5. Clinical studies noted how different types of injuries lead to different phenotypes of PTE. The identification of common co-morbidities and predictors of PTE was addressed.
  6. Predictive biomarkers for PTE were deemed essential to further the field. Potential biomarkers such as high frequency oscillations on EEG, microRNAs, select proteins and brain imaging.
  7. The necessity for data sharing, machine learning and other big data approaches were discussed.
  8. It as noted in each session that infrastructure and mechanisms for interpretation and storage of large data sets, especially EEG and imaging, are needed.
  9. Harmonization of large data sets was also an area of need.
  10. During the last session it was noted that a lack of patient engagement has been an area of need and potential patient engagement strategies were discussed.

The partnership between preclinical and clinical investigators was a major topic to come out of the workshops. It was noted that communication between preclinical investigators and clinicians will help better develop mechanistic studies to more clearly delineate mechanisms of epileptogenesis and better inform clinical trials and patient care. This will reduce number of phase III clinical trials and help advance the field overall.