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

 -  Pregnancy

 -  Pre-existing Neurodegenerative Disorders

 -  Pre-existing epilepsy/seizure disorder

 -  Pre-existing dementia

 -  Isolated anoxic brain injury

 -  Incarceration present or pending

 -  Devastating cervical spine injury