Abstracts

Rationale: Neuroinflammation has been implicated in epilepsy and can be measured in vivo using PET imaging of translocator protein with [11C]PBR28. Common structural lesions in epileptic patients, including focal cortical dysplasia, have been associated with activation of inflammatory pathways (Iyer 2010). Previous studies in patients with mesial temporal lobe epilepsy have shown increased [11C]PBR28 uptake ipsilateral to seizure foci relative to the contralateral hemisphere (Hirvonen et al 2012) as well as widespread, bilateral increases compared to healthy controls (in press). It is not yet known whether patients with epilepsy due to structural lesions outside of the mesial temporal lobe have similar increases in TSPO expression.Methods: We analyzed [11C]PBR28 scans of 9 epilepsy patients with seizure foci outside of the mesial temporal lobe, and 11 healthy controls. Eight patients and all controls had concurrent arterial blood sampling during PET scans. Four patients had surgical resections with histopathology findings of focal cortical dysplasia. Brain regions were delineated using FreeSurfer and T1-weighted MRI. For each patient, three regions were selected based on the seizure focus, localized using EEG, MRI, and/or surgical tissue pathology. First, we compared brain uptake of each radioligand (standardized uptake values, SUVs) in ipsilateral and contralateral regions, and calculated asymmetry indices [AIs, 200% *(ipsilateral-contralateral)/(ipsilateral+contralateral]. Second, we compared asymmetry indices in the selected regions between epilepsy patients and controls. Third, we compared absolute [11C]PBR28 binding as the ratio of distribution volume to free fraction (VT/fP) between patients and controls.Results: All 9 patients had AIs that exceeded the 95% confidence interval of the control mean in at least one region consistent with the seizure focus, but only three patients had two or more abnormal regions. Asymmetry did not differ based on the presence of dysplasia in surgical tissue samples. No significant differences were found between ipsilateral and contralateral SUVs or between patient and control VT/fP values in ipsilateral (F1,17=2.4, p =0.1) or contralateral (F1,17=2.3, p =0.1) regions.Conclusions: We found that epilepsy patients with lesions outside of the mesial temporal lobe had asymmetry of [11C]PBR28 uptake in some but not all affected regions. In cases of bilateral inflammation, asymmetry of TSPO may be minimized. In addition, the lack of significant group differences in this sample is in contrast to significant TSPO increases previously reported in mesial temporal lobe epilepsy patients, probably because of the variability in focus localization. This study highlights the challenges in studying epilepsy patients with varied seizure foci.