Department of Psychiatry & Behavioral Sciences, University of Louisville, Louisville, KY 40202, USA.
Acta Neuropathol Commun. 2013 Oct 11;1:67. doi: 10.1186/2051-5960-1-67.
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.
先前的报告表明，自闭症谱系障碍（ASD）患者的大脑存在组织学异常，提示存在发育不良过程。在这项研究中，我们确定了 ASD 个体大脑皮层中异常的皮质变薄区域，并通过计算机图像分析检查了相同区域的神经元形态计量学异常。
该研究分析了 7 名自闭症（ADI-R 诊断）和 7 名年龄/性别匹配的神经典型个体的细胞素包埋和尼氏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计量学分析。我们的研究结果表明，在我们的 ASD 人群中，存在局限性的皮质宽度减小焦点，这些焦点在受影响个体中的位置和总体大小上存在差异，额叶特别涉及。空间统计学表明，受影响区域内神经元的大小减小。粒度学证实了较小的锥体神经元的存在，并提示中间神经元的总数减少。
神经病理学与局灶性皮质发育不良（FCD）的诊断一致。来自医学文献（例如，异位）和我们自己的研究的结果表明，这种皮质畸形的发生似乎源于室周生殖细胞的异时性分裂。最终结果是，在皮质发生过程中，放射状迁移的神经母细胞（未来的锥体神经元）在其发育过程中与那些遵循切线途径（中间神经元）的神经母细胞不同步。在表现出类似自闭症表型的不同情况下可能存在共同的病理机制，这支持将 ASD 视为“序列”而不是综合征的观点。ASD 中的局灶性皮质发育不良可能有助于解释该患者群体中癫痫发作和感觉异常的高患病率。
