Increased In Vivo Expression of an Inflammatory Marker in Temporal Lobe Epilepsy

Abstract

Animal studies and clinical observations suggest that epilepsy is associated with inflammation. Translocator protein (TSPO) (18 kDa), a marker of inflammation, is increased in vitro in surgical samples from patients with temporal lobe epilepsy. TSPO can be measured in the living human brain with PET and the novel radioligand 11C-PBR28. In this study, we sought to determine whether in vivo expression of TSPO is increased ipsilateral to the seizure focus in patients with temporal lobe epilepsy. Methods Sixteen patients with unilateral temporal lobe epilepsy and 30 healthy subjects were studied with 11C-PBR28 PET and MRI. Uptake of radioactivity after injection of 11C-PBR28 was measured from regions of interest drawn bilaterally onto MR images. Brain uptake from ipsilateral and contralateral hemispheres was compared using a paired-samples t test. Results We found that brain uptake was higher ipsilateral to the seizure focus in the hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and choroid plexus but not in other brain regions. This asymmetry was more pronounced in patients with hippocampal sclerosis than in those without. Conclusion We found increased uptake of radioactivity after injection of 11C-PBR28 ipsilateral to the seizure focus in patients with temporal lobe epilepsy, suggesting increased expression of TSPO. Studies in larger samples are required to confirm this finding and determine the clinical utility of imaging TSPO in temporal lobe epilepsy.

A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: Current state and future research opportunities

“…Increased neuroinflammation has been reported in temporal lobe epilepsy using [ 11 C]PBR-28 (Hirvonen et al, 2012), so that studies investigating TSPO binding need to account for that potential confound, for example by excluding individuals with autism and epilepsy. Future studies examining the interactions between neuronal and glial cells and their involvement in shaping social behaviors could help enhance our understanding of ASD pathophysiology.…”

Immunity and Inflammation in Epilepsy

“…A recent study reported an increased uptake of radioactivity after injection of 11C-PBR28 (a new tracer for the detection of TSPO) ipsilateral to the seizure focus (within the hippocampus) of TLE patients, particularly in patients with HS (Hirvonen et al 2012). Additional studies are, however, needed to determine the clinical utility of imaging TSPO, and to correlate increases in TSPO binding with the neuropathological finding in patients undergoing epilepsy surgery.…”

Biomarkers of Epileptogenesis: The Focus on Glia and Cognitive Dysfunctions

“…Recent evidence in animal models of epileptogenesis and in patients with pharmacoresistant seizures have demonstrated that both the extent and regional pattern of glial cell activation can be imaged non-invasively: astrocyte activation can be monitored by measuring specific metabolites using proton magnetic resonance spectroscopy ( 1 H-MRS) [26] or monoamine oxidase(MAO)-B by positron emission tomography (PET) [27][28][29], while microglia/macrophage activation can be measured by PET imaging of translocator protein 18 (TSPO) [30][31][32]. In particular, 1 H-MRS is an in vivo imaging technique which allows area-specific detection and quantification of myo-inositol (mIns), a sugar alcohol found predominantly in astrocytes [26], which represents a quantifiable indicator of reactive astrogliosis [33,34].…”