Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：颞叶癫痫可发生杏仁核增大，据报道，杏仁核体积也在癫痫猝死（SUDEP）中增加。杏仁核刺激可诱发呼吸暂停,惊厥性中枢神经性呼吸暂停(PCCA)和全身性癫痫发作都是已知的SUDEP危险因素.神经元取向分散和密度成像（NODDI）最近提供了有关SUDEP中杏仁核微观结构改变的其他信息。在一系列24例颞叶手术癫痫病例中，我们的目的是量化杏仁核细胞病理学参数，可以预测肿大，NODDI变化,和临时呼吸功能障碍。
方法：使用全片扫描自动定量图像分析方法，髓鞘的平行评估，轴突,树突,少突胶质细胞,小胶质细胞,星形胶质细胞,神经元，血清素能网络，杏仁核中的mTOR途径激活（pS6）和磷酸化tau（pTau;AT8，AT100，PHF），杏仁核皮质,和感兴趣的白质区域与杏仁核大小的术前磁共振成像数据进行比较，以及13例NODDI和Ital相关呼吸暂停的证据。
结果：我们观察到明显更高的胶质细胞标记（Iba1，胶质纤维酸性蛋白，杏仁核区域中的Olig2）与皮质相比，杏仁核中的Olig2和Iba1之间具有很强的正相关性。较大的杏仁核体积与较低的微管相关蛋白（MAP2），而较高的NODDI取向分散指数与较低的Olig2细胞密度相关。在记录PCCA的三个案例中，MAP2和pS6-235表达高于无.pTau与SUDEP危险因素无关，包括发作频率.
结论：杏仁核微结构的组织学定量可以揭示癫痫的扩大和扩散成像改变，以探索杏仁核功能障碍的可能机制。包括mTOR通路激活,这反过来可能会增加SUDEP的风险。
方法：使用全片扫描自动定量图像分析方法，髓鞘的平行评估，轴突,树突,少突胶质细胞,小胶质细胞,星形胶质细胞,神经元，血清素能网络，杏仁核中的mTOR途径激活（pS6）和磷酸化tau（pTau;AT8，AT100，PHF），杏仁核皮质,和感兴趣的白质区域与杏仁核大小的术前磁共振成像数据进行比较，以及13例NODDI和Ital相关呼吸暂停的证据。
结果：我们观察到明显更高的胶质细胞标记（Iba1，胶质纤维酸性蛋白，杏仁核区域中的Olig2）与皮质相比，杏仁核中的Olig2和Iba1之间具有很强的正相关性。较大的杏仁核体积与较低的微管相关蛋白（MAP2），而较高的NODDI取向分散指数与较低的Olig2细胞密度相关。在记录PCCA的三个案例中，MAP2和pS6-235表达高于无.pTau与SUDEP危险因素无关，包括发作频率.
结论：杏仁核微结构的组织学定量可以揭示癫痫的扩大和扩散成像改变，以探索杏仁核功能障碍的可能机制。包括mTOR通路激活,这反过来可能会增加SUDEP的风险。
