Seizing the Neuroinflammatory Target: The Quest Continues

Abstract

Neuroinflammation in Neocortical Epilepsy Measured by PET Imaging of Translocator Protein Dickstein LP, Liow JS, Austermuehle A, et al. Epilepsia. 2019. doi:10.1111/epi.15967. Epub ahead of print. PMID: 31144767 Objectives: Neuroinflammation, implicated in epilepsy, can be imaged in humans with positron emission tomography (PET) ligands for translocator protein 18 kDa (TSPO). Previous studies in patients with temporal lobe epilepsy and mesial temporal sclerosis found increased [11C]PBR28 uptake ipsilateral to seizure foci. Neocortical foci present more difficult localization problems and more variable underlying pathology. Methods: We studied 11 patients with neocortical seizure foci using [11C]PBR28 or [11C] N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide 713 and 31 healthy volunteers. Seizure foci were identified with structural magnetic resonance imaging (MRI) and ictal video-electroencephalography monitoring. Six patients had surgical resections: 5 had focal cortical dysplasia type 2A or B and 1 microdysgenesis. Brain regions were delineated using FreeSurfer and T1-weighted MRI. We measured brain radioligand uptake (standardized uptake values) in the ipsilateral and contralateral regions, to compare calculated asymmetry indices (AIs; 200% *[ipsilateral − contralateral]/[ipsilateral + contralateral]) between patients with epilepsy and controls, as well as absolute [11C]PBR28 binding as the ratio of distribution volume to free fraction (VT/fP) in 9 patients (5 high-affinity and 4 medium-affinity binders) and 11 age-matched volunteers (5 high affinity and 6 medium affinity) who had metabolite-corrected arterial input functions measured. Results: Nine of 11 patients had AIs exceeding control mean 95% confidence intervals in at least one region consistent with the seizure focus. Three of the 9 had normal MRI. There was a nonsignificant trend for patients to have higher binding than volunteers both ipsilateral and contralateral to the focus in the group that had absolute binding measured. Significance: Our study demonstrates the presence of focal and distributed inflammation in neocortical epilepsy. There may be a role for TSPO PET for the evaluation of patients with suspected neocortical seizure foci, particularly when other imaging modalities are unrevealing. However, a complex method, inherent variability, and increased binding in regions outside seizure foci will limit applicability.