Hikmat Omar, Eichele Tom, Tzoulis Charalampos, Bindoff Laurence A
Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway.
Department of Clinical Medicine (K1), University of Bergen, 5020 Bergen, Norway.
Int J Mol Sci. 2017 Aug 24;18(9):1845. doi: 10.3390/ijms18091845.
Epilepsy is common in polymerase gamma (POLG) related disease and is associated with high morbidity and mortality. Epileptiform discharges typically affect the occipital regions initially and focal seizures, commonly evolving to bilateral convulsive seizures which are the most common seizure types in both adults and children. Our work has shown that mtDNA depletion-i.e., the quantitative loss of mtDNA-in neurones is the earliest and most important factor of the subsequent development of cellular dysfunction. Loss of mtDNA leads to loss of mitochondrial respiratory chain (MRC) components that, in turn, progressively disables energy metabolism. This critically balanced neuronal energy metabolism leads to both a chronic and continuous attrition (i.e., neurodegeneration) and it leaves the neurone unable to cope with increased demand that can trigger a potentially catastrophic cycle that results in acute focal necrosis. We believe that it is the onset of epilepsy that triggers the cascade of damage. These events can be identified in the stepwise evolution that characterizes the clinical, Electroencephalography (EEG), neuro-imaging, and neuropathology findings. Early recognition with prompt and aggressive seizure management is vital and may play a role in modifying the epileptogenic process and improving survival.
癫痫在与聚合酶γ（POLG）相关的疾病中很常见，且与高发病率和死亡率相关。癫痫样放电通常最初影响枕叶区域，局灶性癫痫发作通常会演变为双侧惊厥性癫痫发作，这是成人和儿童中最常见的癫痫发作类型。我们的研究表明，神经元中线粒体DNA（mtDNA）的耗竭，即mtDNA的定量损失，是随后细胞功能障碍发展的最早和最重要因素。mtDNA的缺失导致线粒体呼吸链（MRC）成分的丧失，进而逐渐使能量代谢失效。这种至关重要的神经元能量代谢平衡导致慢性和持续性的消耗（即神经退行性变），并使神经元无法应对可能引发潜在灾难性循环并导致急性局灶性坏死的需求增加。我们认为是癫痫的发作引发了一系列损伤。这些事件可以在表征临床、脑电图（EEG）、神经影像学和神经病理学发现的逐步演变中得到识别。早期识别并及时积极地进行癫痫发作管理至关重要，可能在改变致痫过程和提高生存率方面发挥作用。
