Imaging of Neuro-Inflammation and the Risk for Post-Traumatic Epilepsy

  • End date
    Aug 14, 2022
  • participants needed
  • sponsor
    University of California, Davis
Updated on 19 June 2021


This study plans to evaluate the time course of inflammation in the brain after a moderate to severe traumatic brain injury using positron emission tomography (PET) brain imaging. Patients will undergo PET scans of the brain at two weeks and two months after injury to measure neuro-inflammation. The results of the PET scans will be analyzed and correlated with the risk of post-traumatic epilepsy.


The development of post-traumatic epilepsy (PTE) is associated with neurobiological, cognitive, psychological, and social consequences that are far-reaching for the patient. Despite our keen awareness of this significant public health issue, little is known regarding the biological mechanisms leading to PTE. One plausible mechanism is that unchecked neuroinflammation, a process that occurs in animal and human models of both traumatic brain injury (TBI) and epilepsy, leads to altered synaptic transmission and neuronal excitability. However, the direct relationship between neuroinflammation and PTE has been difficult to ascertain from pre-clinical studies as they may not accurately reflect the human condition, as few animal models can induce the progression of PTE without a pharmacological enhancer and are predominately limited to studies of mild-to-moderate TBI given high animal mortality rates from more severe injuries. Measurements of neuroinflammation in human TBI and epilepsy has also proven difficult without invasive monitoring or post-mortem evaluations, and measurements of inflammatory mediators in blood or serum may not meaningfully reflect the extent of neuroinflammation.

Encouragingly though, positron emission tomography (PET) can be used to measure the degree of in vivo glial activation in the central nervous system through radiotracer binding of the translocator protein (TSPO), serving as a surrogate of neuroinflammation. Minimally expressed in the uninjured brain, TSPO binding is increased in a number of brain disorders associated with neuroinflammation, including Alzheimer's disease, ischemic stroke, recurrent head trauma in football, brain metastases, TBI, and epilepsy, and is expressed predominately by activated microglia, the main mediators of neuroinflammation. Currently, no pre-clinical or clinical study has analyzed the relationship between glia activation, as measured by TSPO PET, and the risk for developing PTE. Accordingly, we plan to use [18F]DPA-714 to characterize neuro-inflammation following moderate-to-severe TBI in order to better understand the temporal time course of neuro-inflammation following injury and its potential role in epileptogenesis.

Condition Post-traumatic epilepsy
Treatment [18F]DPA-714 Positron Emission Tomography Scan
Clinical Study IdentifierNCT03999164
SponsorUniversity of California, Davis
Last Modified on19 June 2021


Yes No Not Sure

Inclusion Criteria

Acute Traumatic Brain Injury (TBI)
Age 18-100 are eligible
Glasgow Coma Scale (GCS) 3-13 without continuous sedation at time of enrollment
Ability to enroll within 72 hours of injury
Hemorrhagic contusional injuries to frontal and/or temporal lobes
Polytrauma including long bone fractures, blunt trauma, abdominal trauma or similar will be allowed
Penetrating TBI if continuous electroencephalography (cEEG) is feasible and survival for 2 years is feasible, recognizing that MRI may not be feasible with some forms of penetrating trauma

Exclusion Criteria

Low-affinity TSPO binding profile
Ages 17 years or younger
Patients with diffuse axonal injury in the absence of hemorrhagic contusions or skull fracture, and isolated epidural hemorrhages that improve after evacuation
No planned continuous EEG monitoring during injury day 1-7
Inability to undergo MRI at 14 days ( 4 days) due to bullet, metal implant, or pacemaker
Pre-existing Neurodegenerative Disorders
Pre-existing epilepsy/seizure disorder
Pre-existing dementia
Isolated anoxic brain injury
Incarceration present or pending
Devastating cervical spine injury
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