Focal cortical dysplasias in autism spectrum disorders.
Focal cortical dysplasias in autism spectrum disorders.
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DOI：
10.1186/2051-5960-1-67
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发表时间：
2013-10-11
影响因子：
7.1
通讯作者：
Switala AE
中科院分区：
文献类型：
--
作者：
Casanova MF;El-Baz AS;Kamat SS;Dombroski BA;Khalifa F;Elnakib A;Soliman A;Allison-McNutt A;Switala AE
先前的报告表明，自闭症谱系障碍（ASD）患者的大脑中存在组织学异常，提示发育不良过程。在这项研究中，我们在ASD个体的大脑皮层中确定了异常皮质变薄的区域，并通过计算机图像分析检查了相同的神经元形态测量异常。该研究分析了7名自闭症患者（诊断为ADI-R）和7名年龄/性别匹配的神经典型患者的纤维蛋白包埋和nissl染色的连续全冠状脑切片。在使用拉普拉斯方程测量皮质宽度之前，对切片进行扫描和手动分割。然后对确定的区域进行神经元形态分析。我们的研究结果表明，在我们的ASD人群中存在皮质宽度减小的局限性病灶，在受影响的个体中，无论是在位置还是总体大小上都有所不同，尤其是额叶。空间统计表明，受影响区域内的神经元大小减少。颗粒测定证实了更小的锥体细胞的存在，并提示中间神经元总数减少。神经病理学符合局灶性皮质发育不良（FCD）的诊断。医学文献（如异位）和我们自己的研究结果表明，这种皮质畸形的发生似乎与心室周围生发细胞的异速分裂有关。最终的结果是，在皮质发生过程中，径向迁移的神经母细胞（未来的锥体细胞）与沿着切向路线（中间神经元）的神经母细胞的发育不同步。在表达自闭症样表型的不同条件中可能存在一种共同的病理机制，这有利于将ASD视为一种“序列”而不是一种综合征。ASD的局灶性皮质发育不良可能解释了该患者群体中癫痫发作和感觉异常的高患病率。
Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis. The study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons. The neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a “sequence” rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.
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影响因子：
14.5
作者：
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通讯作者：
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