Blackmon Karen
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA; Center for Mind/Brain Sciences, University of Trento, Rovereto, Trento 38068, Italy.
Epilepsy Behav. 2015 Jun;47:172-82. doi: 10.1016/j.yebeh.2015.02.017. Epub 2015 Mar 24.
Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy".
自闭症谱系障碍（ASD）和癫痫之间高共病率的病因是诸多争论的主题。是癫痫导致了ASD，还是存在共同的潜在脑异常增加了患这两种疾病的风险？这篇综述总结了来自定量MRI研究的证据，表明脑结构异常不一定是ASD和癫痫的后果，而是疾病表现的前驱因素。在ASD发病前就存在灰质和白质体积异常，并且在小儿癫痫发病时也很明显。异常的脑生长轨迹在这两种疾病中也很常见，灰质成熟和白质成熟减弱就证明了这一点。尽管解释这些异常的病因尚不清楚，但灰质体积和白质微观结构的高遗传度估计表明遗传因素对脑结构有很强的影响。此外，对ASD和癫痫脑组织的组织病理学研究显示皮质发育畸形（MCDs）的发生率升高，如局灶性皮质发育不良和异位，这支持神经元迁移障碍是一个促成因素。虽然常规放射学分析在MRI上并不总是能看到MCDs，但定量MRI检测方法对癫痫中的细微畸形显示出高敏感性，并且有可能应用于ASD中的MCD检测。这种方法对于建立可用于基因研究的定量神经解剖内表型至关重要。在针对癫痫发作和自闭症症状的新兴药物治疗（如雷帕霉素和雷帕霉素类似物）的背景下，脑结构细微异常的体内神经影像标记物可以改善人类临床试验中的样本分层，并有可能扩大可能从治疗中受益的患者范围。本文是名为“自闭症与癫痫”的特刊的一部分。
