Alonso-Nanclares L, Garbelli R, Sola R G, Pastor J, Tassi L, Spreafico R, DeFelipe J
Instituto Cajal, CSIC, Madrid, Spain.
Brain. 2005 Jan;128(Pt 1):158-73. doi: 10.1093/brain/awh331. Epub 2004 Nov 17.
Focal cortical dysplasia (FCD) is a pathology that is characterized by the abnormal development of the neocortex. Indeed, a wide range of abnormalities in the cortical mantle have been associated with this pathology, including cytoarchitectonic alterations and the presence of dysmorphic neurons, balloon cells and ectopic neurons in the white matter. FCD is commonly associated with epilepsy, and hence we have studied the ultrastructure of cortical tissue resected from three subjects with intractable epilepsy secondary to cortical dysplasia to identify possible alterations in synaptic circuitry, using correlative light and electron microscopic methods. While the balloon cells found in this tissue do not appear to receive synaptic contacts, the ectopic neurons in the white matter were abnormally large and were surrounded by hypertrophic basket formations immunoreactive for the calcium-binding protein parvalbumin. Furthermore, these basket formations formed symmetrical (inhibitory) synapses with both the somata and the proximal portion of the dendrites of these giant ectopic neurons. A quantitative analysis revealed that in the dysplastic tissue, the density of excitatory and inhibitory synapses was different from that of the normal adjacent cortex. Both increases and decreases in synaptic density were observed, as well as changes in the proportion of excitatory and inhibitory synapses. However, we could not establish a common pattern of changes, either in the same patients or between different patients. These results suggest that cortical dysplasia leads to multiple changes in excitatory and inhibitory synaptic circuits. We discuss the possible relationship between these alterations and epilepsy, bearing in mind the possible limitations that preclude the extrapolation of the results to the whole population of epileptic patients with dysplastic neocortex.
局灶性皮质发育不良（FCD）是一种以新皮质异常发育为特征的病理学情况。实际上，皮质层的广泛异常都与这种病理学情况相关，包括细胞构筑改变以及白质中存在发育异常的神经元、气球样细胞和异位神经元。FCD通常与癫痫相关，因此我们使用相关的光学和电子显微镜方法，研究了从三名因皮质发育不良继发难治性癫痫的患者切除的皮质组织的超微结构，以确定突触回路中可能存在的改变。虽然在这种组织中发现的气球样细胞似乎没有接受突触联系，但白质中的异位神经元异常大，并且被对钙结合蛋白小白蛋白免疫反应的肥大篮状结构所包围。此外，这些篮状结构与这些巨大异位神经元的胞体和树突近端形成了对称性（抑制性）突触。定量分析显示，在发育异常的组织中，兴奋性和抑制性突触的密度与正常相邻皮质不同。观察到突触密度既有增加也有减少，以及兴奋性和抑制性突触比例的变化。然而，无论是在同一患者中还是在不同患者之间，我们都无法确定一种共同的变化模式。这些结果表明，皮质发育不良会导致兴奋性和抑制性突触回路发生多种变化。我们讨论了这些改变与癫痫之间可能的关系，同时牢记可能存在的局限性，这些局限性妨碍了将结果外推至整个患有发育异常新皮质的癫痫患者群体。
