Imaging of Glial Activation and Risk for Posttraumatic Epilepsy
Abstract
Survivors of traumatic brain injury (TBI) often suffer from neurologic, cognitive, psychologic, and social impairment that can be challenging to overcome. One of the more common and challenging impairments is post-traumatic epilepsy (PTE), which can occur in approximately 1 in 5 patients with a severe TBI and can be quite debilitating. We do not know why some patients develop PTE and others do not; however, animal models of both TBI and epilepsy suggest that inflammation in the brain (neuroinflammation) is common in both diseases. Given this commonality, neuroinflammation may be an important cause of PTE, and we hypothesize that higher degrees of neuroinflammation are associated with an increased risk for developing epilepsy. However, measuring the degree of neuroinflammation is challenging in humans, as it does not show up on routine imaging of the brain or in routine blood work. Encouragingly though, positron emission tomography (PET) can be used to measure the degree of active neuroinflammatory cells in the brain, which can be used as a surrogate for neuroinflammation. A PET scan is an imaging study that allows doctors to check to see how well organs and tissues are functioning by administering a radioactive drug (tracer) that shows this activity. Several of these tracers are able to bind to the translocator protein (TSPO), a protein that is not present in large amounts in a healthy human brain. However, TSPO is present in much higher concentrations in the injured brain, and this correlates with higher concentrations of activated neuroinflammatory cells. Thus, using PET with a TSPO tracer, we can measure the degree of activated inflammatory cells in the injured brain. In our proposed study, we plan to scan patients with TBI with a TSPO PET study to: (1) assess increased TSPO binding in the injured brain, (2) determine if increased TSPO binding is associated with increased risk for early seizures and PTE, and (3) evaluate the association between increased TPSO binding and patient outcome. In this study, we plan to enroll patients with moderate and severe TBI who have bruising of the brain involving the frontal and temporal lobes. Patients will be admitted to the intensive care unit and monitored with continuous electroencephalography (cEEG), which measures electrical brain waves, for the detection of seizures, and will undergo a magnetic resonance image (MRI) of the brain. Blood work will also be done to develop biomarkers of PTE. In addition, patients will undergo a TSPO PET scan at 2 weeks and 2 months following injury to measure the degree of neuroinflammation. Patients will be followed intermittently for 1-year post-injury to determine which patients develop PTE and what their functional outcome is. Then, the TSPO PET studies will be analyzed, and the relationship between cEEG data, serum biomarkers, MRI, and the PTE will be assessed. We predict that post-traumatic neuroinflammation will be significantly increased in the injured brain on TSPO PET and that these changes will correlate with increased risk for early seizures, PTE, and functional outcome. Such findings will allow us to better understand the mechanisms for how PTE develops in some individuals following brain trauma, allowing early risk stratification of patients and innovative targets for therapeutic interventions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910510
Entities
People
- Ryan Martin
Organizations
- United States Army
- University of California, Davis