Department of Clinical and Experimental Epilepsy, University College London (UCL) Queen Square Institute of Neurology, London, UK.
Division of Neuropathology, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College Hospitals NHS Foundation Trust, London, UK.
Epilepsia. 2024 Aug;65(8):2368-2385. doi: 10.1111/epi.18033. Epub 2024 Jun 5.
Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction.
Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR-pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal-associated apnea.
We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule-associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6-235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency.
Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.
杏仁核增大可发生于颞叶癫痫，而癫痫猝死（SUDEP）也有报道称杏仁核体积增加。杏仁核刺激可诱发呼吸暂停，而惊厥后中枢性呼吸暂停（PCCA）和全身性发作均为已知的 SUDEP 危险因素。神经丝取向分散和密度成像（NODDI）最近提供了 SUDEP 中杏仁核微结构改变的额外信息。在一系列 24 例手术性颞叶癫痫病例中，我们的目的是量化可预测增大、NODDI 改变和发作性呼吸功能障碍的杏仁核细胞病理学参数。
使用全切片扫描自动定量图像分析方法，平行评估杏仁核、周边皮质和白质感兴趣区的髓鞘、轴突、树突、少突胶质细胞、小胶质细胞、星形胶质细胞、神经元、5-羟色胺能网络、mTOR 通路激活（pS6）和磷酸化 tau（pTau；AT8、AT100、PHF），并与术前磁共振成像数据比较，评估杏仁核大小，在 13 例病例中还进行了 NODDI 和发作相关呼吸暂停的评估。
与皮质相比，我们观察到杏仁核区域的神经胶质标记物（Iba1、胶质纤维酸性蛋白、Olig2）明显升高，并且在杏仁核中 Olig2 与 Iba1 呈强正相关。更大的杏仁核体积与更低的微管相关蛋白（MAP2）相关，而更高的 NODDI 取向分散指数与更低的 Olig2 细胞密度相关。在记录到 PCCA 的三个病例中，MAP2 和 pS6-235 的表达高于无 PCCA 的病例。pTau 与包括癫痫发作频率在内的 SUDEP 危险因素均无相关性。
杏仁核微观结构的组织学定量可以阐明癫痫中的增大和扩散成像改变，以探索杏仁核功能障碍的可能机制，包括 mTOR 通路激活，这反过来可能增加 SUDEP 的风险。
