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Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and 18 F-Fluorodeoxyglucose-positron emission tomography, [ 18 F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs). PET imaging with radioligands targeting the18-kDa translocator protein (TSPO), a marker of glial activation, may aid EZ localization. This study investigates the correlation between TSPO-PET imaging and SEEG iHFOs in DRFE to determine the utility of TSPO-PET in pre-surgical assessments, especially in complex or non-lesional cases., Methods: Patients with DRFE and inconclusive phase 1 assessments were recruited from Bicêtre Hospital (AP-HP) for a prospective study (Eudract 2017-003381-27). They underwent SEEG and [ 18 F]DPA-714 (N,N-diethyl-2-(2-(4-(2-(fluoro- 18 F)ethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) (TSPO radioligand) PET imaging. Statistical parametric mapping (SPM) techniques analyzed significant [ 18 F]DPA-714-PET uptake (TSPO-map) and generated epileptogenicity maps (EM-map). Correlation analyses at regional and voxel-of-interest (VOI) levels assessed the relationship between TSPO-map and EM-map., Results: We were able to obtain and analyze both maps in 12 of 17 patients recruited. A significant positive correlation between EM-map and TSPO-map in focal epilepsies was found regionally (r = .81, p < .00004) and at the VOI level (r = .79, p < .00003). Temporal, insular, parietal, and occipital regions showed particularly strong correspondence. In frontal epilepsies, TSPO-map was more focal than EM-map, suggesting increased specificity for SEEG planning. This study also demonstrated the benefit of the TSPO-map in identifying multiple foci in multifocal epilepsies, with or without lesions., Significance: These findings suggest that neuroinflammation may be a molecular substrate of the EZ in non-lesional focal epilepsy. Identifying the EZ inpatients with complex DRFE and inconclusive MRI/[ 18 F]FDG-PET imaging is essential to improve resective surgery outcomes. Combining TSPO-PET imaging with SEEG recordings may help bridge this gap., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with 18 F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS., Methods: The model was induced into the right dorsal hippocampus of male C57/Bl6 mice. Micro-PET/computed tomographic scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month, and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point., Results: TSPO PET uptake reached peak at 7 days and mostly related to microglial activation, whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO, reflected by a continuing increased PET uptake., Significance: TSPO-targeted PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor response to treatment., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Purpose: Posttraumatic epilepsy (PTE) occurs in a proportion of traumatic brain injury (TBI) cases, significantly compounding the disability, and risk of injury and death for sufferers. To date, predictive biomarkers for PTE have not been identified. This study used the lateral fluid percussion injury (LFPI) rat model of TBI to investigate whether structural, functional, and behavioral changes post-TBI relate to the later development of PTE., Methods: Adult male Wistar rats underwent LFPI or sham injury. Serial magnetic resonance (MR) and positron emission tomography (PET) imaging, and behavioral analyses were performed over 6 months postinjury. Rats were then implanted with recording electrodes and monitored for two consecutive weeks using video-electroencephalography (EEG) to assess for PTE. Of the LFPI rats, 52% (n = 12) displayed spontaneous recurring seizures and/or epileptic discharges on the video-EEG recordings., Key Findings: MRI volumetric and signal analysis of changes in cortex, hippocampus, thalamus, and amygdala, (18) F-fluorodeoxyglucose (FDG)-PET analysis of metabolic function, and behavioral analysis of cognitive and emotional changes, at 1 week, and 1, 3, and 6 months post-LFPI, all failed to identify significant differences on univariate analysis between the epileptic and nonepileptic groups. However, hippocampal surface shape analysis using large-deformation high-dimensional mapping identified significant changes in the ipsilateral hippocampus at 1 week postinjury relative to baseline that differed between rats that would go onto become epileptic versus those who did not. Furthermore, a multivariate logistic regression model that incorporated the 1 week, and 1 and 3 month (18) F-FDG PET parameters from the ipsilateral hippocampus was able to correctly predict the epileptic outcome in all of the LFPI cases. As such, these subtle changes in the ipsilateral hippocampus at acute phases after LFPI may be related to PTE and require further examination., Significance: These findings suggest that PTE may be independent of major structural, functional, and behavioral changes induced by TBI, and suggest that more subtle abnormalities are likely involved. However, there are limitations associated with studying acquired epilepsies in animal models that must be considered when interpreting these results, in particular the failure to detect differences between the groups may be related to the limitations of properly identifying/separating the epileptic and nonepileptic animals into the correct group., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Hippocampal sclerosis (HS) is the most frequent lesion found in mesial temporal lobe epilepsy (mTLE). MR imaging is considered to be the most sensitive and specific method to detect HS. Despite extensive studies performed on humans and except in a recent study, the morphologic pattern of HS is usually analyzed when the disease has already fully developed, thus not allowing any insight into the mapping of the progressive morphologic changes inducing the development of mTLE. We have recently characterized a model of mTLE that reproduces the unilateral pattern of HS, induced by intrahippocampal injection of low doses of kainate (KA) in mice., Methods: In this study, we monitored the temporal evolution of the development of HS in this model of mTLE by using T2-weighted sequence, T2-relaxation time measurements, and T1-weighted spin-echo technique after injection of gadolinium, from 1 h to 120 days after KA injection., Results: HS induced by intrahippocampal KA injection occurred in two phases. First, we observed a transient hyperintense T2-weighted signal in the cortex above the injected hippocampus, most likely indicative of vasogenic edema partly due to the neurotoxic effect of KA. The concomitant increase in the T2 signal in the injected hippocampus and ipsilateral amygdala likely reflects the phase of cytotoxic edema occurring probably in relation to the excitotoxic consequences of both KA and seizure activity. Second, from 15 days on, a persistent unilateral increased T2 signal was detected in the hippocampus, which most probably reflects gliosis., Conclusions: Our findings indicate that longitudinal follow-up would permit a better understanding of the mechanisms underlying the constitution of HS in humans and eventually development of prevention strategies.