Experimental Epilepsy Research, Department of Neurosurgery, University of Freiburg, Breisacherstr, 64, Freiburg 79106, Germany.
Acta Neuropathol Commun. 2013 Aug 8;1:47. doi: 10.1186/2051-5960-1-47.
Focal cortical dysplasias (FCD) are local disturbances of neocortical architecture and a common cause of pharmaco-resistant focal epilepsy. Little is known about the pathomechanisms leading to architectural abnormalities associated with FCD.
In the present study we compared 52 FCD cases originating from the frontal or temporal lobe with or without Ammon's horn sclerosis (AHS) with regard to structural and molecular differences. We applied layer-specific (ER81, RORß, SMI32, TLE4) and interneuron (calbindin, parvalbumin) markers by means of immunohistochemistry, in situ hybridization (ISH), and real time RT-PCR and correlated our findings with clinical parameters. We found that: (1) Structural abnormalities were most prominent in layers III-VI including changed morphology of individual neurons or dispersion, blurring and thinning of layers. These alterations were most pronounced in isolated frontal FCD, whereas the most homogeneous group was FCD IIIa. (2) Numbers of calbindin- and parvalbumin-positive interneurons varied considerably within the different FCD groups, but were not generally reduced. A significant decrease was only found for calbindin-positive interneurons in frontal FCD, and for parvalbumin-positive interneurons in FCD IIIa. (3) Interestingly, FCD IIIa presented with significant changes in the numbers of calbindin- or TLE4-positive neurons when compared to isolated FCD or controls. (4) Correlations between clinical and cellular parameters strongly depended on FCD localisation and age of the patients.
In summary, our data suggest that late cortical development is disturbed in FCD, yet most likely by different causes depending on brain region, FCD type and FCD severity.
局灶性皮质发育不良（FCD）是皮质结构的局部紊乱，是药物难治性局灶性癫痫的常见原因。导致与 FCD 相关的结构异常的病理机制知之甚少。
在本研究中，我们比较了 52 例起源于额叶或颞叶的 FCD 病例，这些病例有无 Ammon 角硬化（AHS），并比较了它们的结构和分子差异。我们应用了层特异性（ER81、RORβ、SMI32、TLE4）和中间神经元（钙结合蛋白、钙调蛋白）标志物，通过免疫组织化学、原位杂交（ISH）和实时 RT-PCR，将我们的发现与临床参数相关联。我们发现：（1）结构异常最明显的是 III-VI 层，包括单个神经元的形态改变或分散、层的模糊和变薄。这些改变在孤立性额叶 FCD 中最为明显，而最均匀的组是 FCD IIIa。（2）不同 FCD 组中钙结合蛋白和钙调蛋白阳性中间神经元的数量差异很大，但总体上并未减少。仅在前额叶 FCD 中发现钙结合蛋白阳性中间神经元数量显著减少，而在 FCD IIIa 中发现钙调蛋白阳性中间神经元数量显著减少。（3）有趣的是，与孤立性 FCD 或对照组相比，FCD IIIa 中钙结合蛋白或 TLE4 阳性神经元的数量有显著变化。（4）临床和细胞参数之间的相关性强烈依赖于 FCD 的定位和患者的年龄。
总之，我们的数据表明，FCD 中晚期皮质发育受到干扰，但最可能是由于不同的原因，取决于脑区、FCD 类型和 FCD 严重程度。
