Kilmer Jennifer, Rodrigo Sebatian, Petrescu Ana-Maria, Aghakhani Nozar, Herbrecht Anne, Leroy Claire, Tournier Nicolas, Bottlaender Michel, Taussig Delphine, Bouilleret Viviane
Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Université Paris-Saclay, CEA, CNRS, Inserm, Orsay, France.
Neurophysiology and Epileptology Department, Hôpital Bicêtre, Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Orsay, France.
Epilepsia. 2025 Feb;66(2):430-443. doi: 10.1111/epi.18182. Epub 2024 Dec 16.
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 F-Fluorodeoxyglucose-positron emission tomography, [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.
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 [F]DPA-714 (N,N-diethyl-2-(2-(4-(2-(fluoro-F)ethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) (TSPO radioligand) PET imaging. Statistical parametric mapping (SPM) techniques analyzed significant [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.
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.
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/[F]FDG-PET imaging is essential to improve resective surgery outcomes. Combining TSPO-PET imaging with SEEG recordings may help bridge this gap.
药物难治性局灶性癫痫（DRFE）的切除性手术需要进行广泛评估以定位致痫区（EZ）。当非侵入性的第一阶段评估（脑电图，EEG；磁共振成像，MRI；以及氟代脱氧葡萄糖正电子发射断层扫描，[F]FDG-PET）对于EZ定位尚无定论时，立体脑电图（SEEG）等侵入性检查是必要的。致痫性图谱（Ems）利用SEEG识别的发作期高频振荡（iHFOs）来可视化EZ。使用靶向18 kDa转位蛋白（TSPO）（一种胶质细胞激活标志物）的放射性配体进行PET成像可能有助于EZ定位。本研究调查了DRFE中TSPO-PET成像与SEEG iHFOs之间的相关性，以确定TSPO-PET在术前评估中的效用，尤其是在复杂或无病灶的病例中。
从比塞特尔医院（AP-HP）招募DRFE且第一阶段评估尚无定论的患者进行一项前瞻性研究（欧盟临床试验注册号2017-003381-27）。他们接受了SEEG和[F]DPA-714（N,N-二乙基-2-(2-(4-(2-(氟-F)乙氧基)phenyl)-5,7-二甲基吡唑并[1,5-a]嘧啶-3-基)乙酰胺）（TSPO放射性配体）PET成像。统计参数映射（SPM）技术分析显著的[F]DPA-714-PET摄取（TSPO图谱）并生成致痫性图谱（EM图谱）。在区域和感兴趣体素（VOI）水平进行相关性分析，以评估TSPO图谱与EM图谱之间的关系。
在招募的17例患者中，有12例能够获得并分析两种图谱。在局灶性癫痫中，EM图谱与TSPO图谱在区域水平（r = 0.81，p < 0.00004）和VOI水平（r = 0.79，p < 0.00003）均发现显著正相关。颞叶、岛叶、顶叶和枕叶区域显示出特别强的对应关系。在额叶癫痫中，TSPO图谱比EM图谱更具局灶性，这表明对SEEG规划的特异性增加。本研究还证明了TSPO图谱在识别多灶性癫痫中的多个病灶方面的益处，无论有无病灶。
这些发现表明神经炎症可能是非病灶性局灶性癫痫中EZ的分子基础。在复杂DRFE且MRI/[F]FDG-PET成像尚无定论的患者中识别EZ对于改善切除性手术结果至关重要。将TSPO-PET成像与SEEG记录相结合可能有助于弥合这一差距。
