Departments of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Chalfont Centre for Epilepsy, Bucks, UK.
Epilepsia. 2021 Jun;62(6):1318-1328. doi: 10.1111/epi.16904. Epub 2021 May 4.
Sudden unexpected death in epilepsy (SUDEP) may arise as a result of autonomic dysfunction during a seizure. The central autonomic networks (CANs) modulate brainstem cardiorespiratory regulation. Recent magnetic resonance imaging (MRI) studies in SUDEP have shown cortical and subcortical volume changes and altered connectivity between CAN regions, but the pathological correlate is unknown. Because neuroinflammation is both a cause and a consequence of seizures and may relate to regional brain pathology, our aim was to evaluate microglial populations in CANs in SUDEP.
In 55 postmortem cases, including SUDEP, epilepsy controls without SUDEP and nonepilepsy controls, we quantified Iba1-expressing microglia in 14 cortical and thalamic areas that included known CAN regions.
Mean Iba1 labeling across all brain regions was significantly higher in SUDEP cases compared to epilepsy and nonepilepsy controls. There was significant regional variation in Iba1 labeling in SUDEP cases only, with highest labeling in the medial thalamus. Significantly higher labeling in SUDEP cases than epilepsy and nonepilepsy controls was consistently noted in the superior temporal gyrus. In cases with documented seizures up to 10 days prior to death, significantly higher mean Iba1 labeling was observed in SUDEP compared to epilepsy controls.
Our findings support microglial activation in SUDEP, including cortical and subcortical regions with known autonomic functions such as the thalamus and superior temporal gyrus. This may be relevant to cellular pathomechanisms underlying cardioregulatory failure during a seizure.
癫痫性猝死（SUDEP）可能是由于癫痫发作期间自主神经功能障碍引起的。中枢自主神经网络（CANs）调节脑干心肺调节。最近 SUDEP 的磁共振成像（MRI）研究表明皮质和皮质下体积变化以及 CAN 区域之间的连通性改变，但病理相关性尚不清楚。由于神经炎症既是癫痫发作的原因也是后果，并且可能与局部脑病理学有关，我们的目的是评估 SUDEP 中 CAN 中的小胶质细胞群体。
在包括 SUDEP、无 SUDEP 癫痫对照和无癫痫对照在内的 55 例死后病例中，我们在包括已知 CAN 区域在内的 14 个皮质和丘脑区域中量化了 Iba1 表达的小胶质细胞。
与癫痫和无癫痫对照组相比，所有脑区的平均 Iba1 标记在 SUDEP 病例中均显着升高。只有在 SUDEP 病例中观察到 Iba1 标记的显着区域变化，内侧丘脑的标记最高。在记录有死亡前 10 天内癫痫发作的病例中，SUDEP 病例中的平均 Iba1 标记明显高于癫痫对照组。
我们的发现支持 SUDEP 中小胶质细胞的激活，包括具有自主功能的皮质和皮质下区域，如丘脑和颞上回。这可能与癫痫发作期间心脏调节失败的细胞发病机制有关。
