Sarnat Harvey B, Philippart Michel, Flores-Sarnat Laura, Wei Xing-Chang
Department of Paediatrics, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Pathology (Neuropathology), University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada; Department of Clinical Neurosciences, University of Calgary Faculty of Medicine and Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.
David Geffen School of Medicine at UCLA, Los Angeles, California.
Pediatr Neurol. 2015 May;52(5):473-86. doi: 10.1016/j.pediatrneurol.2015.01.020. Epub 2015 Feb 9.
Timing is primordial in initiating and synchronizing each developmental process in tissue morphogenesis. Maturational arrest, delay, and precociousness all are conducive to neurological dysfunction and may determine different malformations depending on when in development the faulty timing occurred, regardless of the identification of a specific genetic mutation or an epigenetic teratogenic event. Delay and arrest are distinguished by whether further progressive development over time can be expected or the condition is static. In general, retardation of early developmental processes, such as neurulation, cellular proliferation, and migration, leads to maturational arrest. Retardation of late processes, such as synaptogenesis and myelination, are more likely to result in maturational delay. Faulty timing of neuronal maturation in relation to other developmental processes causes neurological dysfunction and abnormal electroencephalograph maturation in preterm neonates. Precocious synaptogenesis, including pruning to provide plasticity, may facilitate prenatal formation of epileptic circuitry leading to severe postnatal infantile epilepsies. The anterior commissure forms 3 weeks earlier than the corpus callosum; its presence or absence in callosal agenesis is a marker for the onset of the initial insult. An excessively thick corpus callosum may be due to delayed retraction of transitory collateral axons. Malformations that arise at different times can share a common pathogenesis with variations on the extent: timing of mitotic cycles in mosaic somatic mutations may distinguish hemimegalencephaly from focal cortical dysplasia type 2. Timing should always be considered in interpreting cerebral dysgeneses in both imaging and neuropathological diagnoses.
时间在组织形态发生过程中启动和同步每个发育进程方面至关重要。成熟停滞、延迟和早熟均有利于神经功能障碍，并且可能根据发育过程中错误时间出现的阶段而决定不同的畸形，无论是否识别出特定的基因突变或表观遗传致畸事件。延迟和停滞的区别在于随着时间的推移是否可以预期进一步的渐进性发育，或者病情是否静止。一般来说，早期发育过程如神经胚形成、细胞增殖和迁移的迟缓会导致成熟停滞。后期过程如突触发生和髓鞘形成的迟缓更有可能导致成熟延迟。与其他发育过程相关的神经元成熟时间错误会导致早产儿出现神经功能障碍和脑电图成熟异常。早熟的突触发生，包括为提供可塑性而进行的修剪，可能会促进产前癫痫回路的形成，导致严重的产后婴儿癫痫。前连合比胼胝体早3周形成；在胼胝体发育不全中其存在与否是初始损伤发生的标志。胼胝体过厚可能是由于短暂侧支轴突的回缩延迟。在不同时间出现的畸形可能具有共同的发病机制，只是在程度上有所不同：镶嵌体细胞突变中有丝分裂周期的时间可能会将半侧巨脑回与2型局灶性皮质发育不良区分开来。在影像学和神经病理学诊断中解释脑发育异常时，始终应考虑时间因素。
