Early Seizures and Temporal Lobe Trauma Predict Post-Traumatic Epilepsy: A Longitudinal Study

CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe Traumatic Brain Injury (TBI), 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of Post-Traumatic Epilpesy (PTE), 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

OBJECTIVE: Injury severity after TBI is a well-established risk factor for the development of PTE. However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE.

METHODS: We assessed early seizure incidence (n?=?90) and longitudinal development of PTE (n?=?46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2?years post-injury.

RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n?=?90). Within the cohort of subjects who had evidence of early seizures (n?=?24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n?=?46), 45.7% of patients developed PTE within a minimum of 2?years post-injury. Within the cohort of subjects who developed PTE (n?=?21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n?=?21) were more likely than patients who did not develop PTE (n?=?25) to have a hemorrhagic temporal lobe injury (p?<?0.001), worse functional recovery (p?=?0.003), and greater temporal lobe atrophy (p?=?0.029).

CURE Discovery: Preventing Post-Traumatic Epilepsy with 2-Deoxy-D-Glucose Treatment

The latest results from a CURE-funded grant represent a promising advance in the quest to prevent post-traumatic epilepsy. Dr. Thomas Sutula from the University of Wisconsin and his team have found that the administration of 2-Deoxy-D-Glucose (2DG) following a traumatic brain injury can significantly reduce the subsequent development of post-traumatic epilepsy in a rodent model.

The finding that 2DG can prevent the development of post-traumatic epilepsy in rats is exciting for several reasons. 2DG is a sugar-like molecule that has been proposed to mimic the ketogenic diet – a diet that is highly effective in the treatment of difficult-to-treat epilepsies. Therefore, like the ketogenic diet, 2DG may also have therapeutic effects for individuals that have already developed epilepsy (in this case, post-traumatic epilepsy). 2DG is also already being used in the treatment of other illnesses, including cancer, and can likely progress rapidly to a clinical trial for post-traumatic epilepsy. Furthermore, with this research, Dr. Sutula and his team have successfully utilized a novel rat model that more readily develops a post traumatic-epilepsy-like syndrome with frequent seizures following traumatic brain injury, providing a great research tool in the quest for treatments and a cure for post-traumatic epilepsy.

Post-traumatic epilepsy is a type of epilepsy that develops following a traumatic brain injury such as a bump or blow to the head. Post-traumatic epilepsy accounts for nearly 20% of all symptomatic epilepsies in the general population, and is one of the most common causes of acquired epilepsy. Post-traumatic epilepsy can be particularly devastating because no known prevention or cure for the disorder currently exists.

Because post-traumatic epilepsy can develop months or even years after an initial traumatic brain injury, there is a critical window of time during which the development of post-traumatic epilepsy might be prevented, if only a preventative measure were in existence. For these reasons, Dr. Sutula’s finding that 2DG significantly reduces the development of post-traumatic epilepsy in his novel breed of rat within this critical window is an important one.

In the future, Dr. Sutula and his team plan on taking strategic steps to push their research forward towards an Investigational New Drug trial to test the effectiveness of this drug in the prevention of post-traumatic epilepsy in humans. In this way, Dr. Sutula hopes that his research will impact the lives of individuals suffering from post-traumatic epilepsy, or those with the potential to develop post-traumatic epilepsy, as soon as possible.

Clinical Trial: Neuroimaging Biomarker for Seizures

Brief Summary: This multi-site study will examine patients with epilepsy (ES) following head injury [i.e., posttraumatic epilepsy (PTE)] and posttraumatic psychogenic Non-epileptic seizures (PNES) and will compare them to patients with traumatic brain injury (TBI) who do not have seizures using functional neuroimaging.

Detailed Description: Numerous Veterans and civilians have seizures, which can be epileptic or nonepileptic in nature. Epileptic seizures are caused by abnormal brain cell firing. Nonepileptic seizures appear similar to epileptic seizures, but are associated with traumatic experiences and underlying psychological stressors. Both types of seizure are common and disabling, and many patients with seizures do not have adequate control resulting in loss of quality of life.

Impact: This grant application for the first study investigating mechanisms of PNES and PTE will provide increased understanding of neural circuitry in PTE and PNES, which can inform PTE and PNES treatments and could change clinical neurologic and psychiatric practice for PTE and PNES.

Anticipated study start date: March 1, 2018
Primary completion date: March 2021
Estimated study completion date: September 2011

Eligibility Criteria

Inclusion Criteria:

Inclusion criteria for PNES, ES and TBI (w/o PNES or ES) participants

  • Individuals with history of documented TBI (any severity).
  • Males and Females ages 18-60 years .
  • Women of child bearing potential, if currently using appropriate contraception.


Inclusion criteria of PNES and ES participants

  • Diagnosed by video/EEG with lone PNES or by EEG with lone ES.
  • Patients must have at least 1 PNES or 1 ES during the year prior to enrollment.


Exclusion Criteria:

Exclusion Criteria of PNES, ES and TBI (w/o PNES or ES) participants

  • Current or past year self-injurious behavior.
  • Current suicidal intent (BDI suicide question 9 score of >1).
  • Current or past year psychosis.
  • Pending litigation or current application for long term disability.
  • Active substance or alcohol use disorder (dependence), in past 3 months.
  • Serious illness requiring systemic treatment or hospitalization; the participant either completes therapy or is clinically stable on therapy, for at least 30 days prior to study entry.
  • Inability to fill out the self-report surveys.
  • Women who are or/are attempting to become pregnant during the study.
  • Ineligible or unwilling to complete MRI imaging.
  • Inability to document TBI.


Exclusion Criteria for PNES and ES participants

  • Inability or unwillingness to participate in CBT and assigned homework.
  • Currently enrolled in cognitive therapy aimed at PNES (Current CBT or other psychotherapy may be administered).
  • Concurrent mixed ES/PNES or equivocal video/EEG findings in discerning between ES and PNES will not be enrolled.

Amendment Passes Senate to Continue DOD Medical Research Funding

WASHINGTON, D.C.— Two provisions in the National Defense Authorization Act threatened to affect important medical research funded by the Department of Defense (DOD). Thanks to the efforts of Senator Dick Durbin (D-IL) and the voices of advocates like CURE through the Research, Not Red Tape initiative, an amendment passed in the Senate in early June to protect this funding so it can continue to support breakthrough research for active service members, military families, and veterans.

This is especially important as it applies to the new, multidisciplinary, team science initiative CURE is developing in collaboration with the DOD to advance the understanding of epilepsy as a result of traumatic brain injuries, the signature wound of the wars in Iraq and Afghanistan.

CURE To Expand Work With Veterans’ Epilepsy Thanks To Department Of Defense Grant

Chicago, IL- Citizens United for Research in Epilepsy today announced that it will create a new research program and focus with a grant of approximately 10 million dollars over 5 years to go toward epilepsy research in veterans with traumatic brain injury. The grant was awarded by the Department of Defense, Psychological Health and Traumatic Brain Injury Research Program, award number W81XWH-15-2-0069.

The grant will support a team approach to researching the prevention and treatment of Post-Traumatic Epilepsy (PTE). The incidence of epilepsy in active service members increased by an alarming 52 percent from 2006 to 2010.Approximately 8 percent of those afflicted have been diagnosed with traumatic brain injury (TBI) , making it the most common predisposing condition. Twenty-four percent of military-related epilepsy is associated with prior TBI.

“Our veterans deserve much better after serving our country,” said Susan Axelrod, founding chair of CURE.  “In the wars in Iraq and Afghanistan the “signature wound” was traumatic brain injury. Those who suffer severe TBI face up to a 50 percent chance of developing Post-Traumatic Epilepsy (PTE), with the symptoms of epilepsy (seizures) manifesting themselves immediately or even up to fifteen years post-injury.   At CURE we are committed to exploring the complex underlying mechanisms of post-traumatic epilepsy and ways to treat it more effectively and one day even prevent it entirely.”

“CURE applauds the U.S. Department of Defense for dedicating this significant amount of resources to epilepsy research,” said Robin Harding, Chief Executive Officer. “We are grateful to those who back our effort to find a cure for this disease through research and by increasing awareness of epilepsy’s prevalence and devastating consequences for patients and their families.  Investing in research is the cornerstone of discovery and an ultimate cure.”

“The next great breakthrough is not going to come from a single researcher working in isolation,” said Julie Milder, PhD, Associate Research Director at CURE and Program Officer for the DOD grant. “We strongly believe in the power of collaboration and its ability to move science forward faster.  We are incredibly grateful for this opportunity to move team science into the area of post-traumatic epilepsy– one that is desperate for greater understanding.”

Next steps for the program include convening a meeting of key opinion leaders in epilepsy, traumatic brain injury and veterans’ health to determine opportunities of biggest impact over the next five years. The outcomes of the meeting will serve as the basis for the development of a targeted team science research program which will be announced through a request for applications in late spring.