Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
Translational Neuroimaging Laboratory, McGill University, Montréal, Québec, Canada.
Epilepsia. 2021 Jul;62(7):1559-1568. doi: 10.1111/epi.16952. Epub 2021 May 31.
Previous positron emission tomography (PET) studies using [ C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [ C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes.
We obtained magnetic resonance imaging (MRI) and [ C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [ C]ABP688 nondisplaceable binding potential (BP ) values were averaged across each subfield, and Z-scores were calculated. Subfield [ C]ABP688-BP was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [ F]fluorodeoxyglucose (FDG) uptake in each clinical group.
MTLE [ C]ABP688-BP was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [ C]ABP688-BP and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [ C]ABP688-BP was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [ C]ABP688-PET+[ F]FDG-PET showed no between-group significant difference in [ F]FDG uptake, whereas CA1-3 [ C]ABP688-BP remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21).
Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [ C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [ C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.
先前使用 [C]ABP688 的正电子发射断层扫描 (PET) 研究表明，内侧颞叶癫痫 (MTLE) 患者致痫海马体中代谢型谷氨酸受体 5 (mGluR5) 变构结合位点的可用性降低。然而，mGluR5 异常与术后结果之间的联系仍不清楚。在这里，我们测试了 CA 区域（更易受到谷氨酸兴奋性毒性影响）中减少的 [C]ABP688 PET 结合是否与手术结果相关。
我们从 31 名单侧 MTLE 患者和 30 名健康对照者中获得了磁共振成像 (MRI) 和 [C]ABP688-PET。使用 FreeSurfer 对 MRI 海马亚区进行分割。为了尊重较低的 PET 特殊分辨率，将 MRI 衍生的解剖亚区合并为 CA1-3、CA4/齿状回和 Subiculum。在每个亚区中平均计算了经过部分体积校正的 [C]ABP688 不可置换结合潜能 (BP) 值，并计算了 Z 分数。比较了无癫痫发作和有癫痫发作患者之间的亚区 [C]ABP688-BP。此外，我们还评估了每个临床组的亚区体积和 [F]氟脱氧葡萄糖 (FDG) 摄取。
与对照组相比，MTLE 的 [C]ABP688-BP 在同侧（致痫）CA1-3 和 CA4/齿状回 (p <.001，95%置信区间 [CI] =.29-.51) 中降低，而 Subiculum 中没有差异。在无癫痫发作患者 (Engel IA，n = 13) 和有癫痫发作患者 (Engel IC-III，n = 10) 之间比较了 [C]ABP688-BP 和亚区体积。仅在同侧 CA1-3 中，无癫痫发作患者的 [C]ABP688-BP 低于有癫痫发作患者 (p =.012，95% CI = 1.46-11.0)，与体积无关。对 12 名接受 [C]ABP688-PET+[F]FDG-PET 检查的患者进行了亚组分析，两组间 [F]FDG 摄取无显著差异，而在 12 名无癫痫发作患者中的 7 名患者中，CA1-3 的 [C]ABP688-BP 仍然显著降低 (p =.03，95% CI = -3.13 至 -.21)。
通过 [C]ABP688-PET 在体内测量的海马体 CA1-3 中 mGluR5 变构结合位点的可用性降低，与手术后无癫痫发作有关，与萎缩或低代谢无关。源自海马体 CA1-3 [C]ABP688-PET 的信息是一种有前途的成像生物标志物，可能对 MRI 阴性/PET 阴性 MTLE 患者的手术决策产生影响。
