Epilepsy and Autism Severity: A Study of 6,975 Children
Epilepsy and Autism Severity: A Study of 6,975 Children
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DOI：
10.1002/aur.2132
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发表时间：
2019-08-01
期刊：
影响因子：
4.7
通讯作者：
Lipkin, Paul H.
中科院分区：
文献类型：
--
作者：
Ewen, Joshua B.;Marvin, Alison R.;Lipkin, Paul H.
众所周知，癫痫在自闭症谱系障碍（asd）患者中所占的比例高于预期。先前对这种异质性疾病的研究表明，智商（IQ）可能推动了这种关系。由于智力障碍（ID）独立于ASD，是癫痫的一个危险因素，目前的文献对ASD和癫痫之间长期理解的独特关系提出了质疑。其次，关于自闭症谱系障碍的发育倒退是否与癫痫有关的数据尚不清楚。使用来自在线研究注册的两个队列，共计6,975名ASD儿童，我们检查了四种ASD严重程度指标在驱动癫痫关系中的独立作用：ID，语言障碍，核心ASD症状严重程度和运动功能障碍，控制两个已知的相关因素：年龄和性别。我们还研究了发育倒退和癫痫是否有独立的统计联系。所有四个ASD严重程度因素在一个队列中显示出与癫痫的独立统计关联，在另一个队列中显示出三个。ID在两个队列中显示出最大的相对风险（RR）。效应量是适度的。回归同样显示了与癫痫的独立统计关联，但效应量较小。与之前的研究类似，ID对ASD患儿癫痫的RR贡献最大。然而，其他ASD严重程度标志物显示出统计学相关性，表明ASD-癫痫的相关性不受ID的影响。文献的不一致可能是由于研究力度不足，但在进行更大规模的研究时，临床意义和科学相关性可能取决于效应大小，而不仅仅是统计意义。孤独症杂志，2019,12:1251-1259。(c) 2019年国际自闭症研究学会，Wiley期刊公司众所周知，癫痫在自闭症谱系障碍（asd）患者中比在一般人群中更常发生。自闭症谱系障碍和癫痫之间的联系之所以引起人们的兴趣，是因为将这两种疾病结合起来研究可能有助于提高我们对这两种疾病的遗传、分子和细胞机制以及治疗方法的理解。最近的研究表明，ASD患者的智商（IQ）可能是癫痫患病率增加的原因。然而，我们的方法是观察与ASD相关的一系列严重因素，并在两个大的ASD儿童样本中寻找每个严重因素与癫痫之间的相关性。总之，我们发现每一个严重因素——智力残疾的存在、语言非典型的存在、asd特异性症状的严重程度和运动问题的存在——都独立地预测了癫痫风险的小幅增加，反驳了智商单独是一个风险因素的观点。我们还研究了癫痫是否与发育倒退有关。虽然已知严重的癫痫综合征如Landau-Kleffner综合征在发育退化后会引起自闭症样症状，但对于其他形式的癫痫是否与许多幼儿癫痫患者更常见的发育退化有关仍存在争议。事实上，我们发现癫痫和发育退化之间有很小的联系。
Epilepsy is known to occur in a higher-than-expected proportion of individuals with autism spectrum disorders (ASDs). Prior studies of this heterogeneous disorder have suggested that intelligence quotient (IQ) may drive this relationship. Because intellectual disability (ID) is, independently of ASD, a risk factor for epilepsy, current literature calls into question the long-understood unique relationship between ASD and epilepsy. Second, data have been unclear about whether developmental regression in ASD is associated with epilepsy. Using two cohorts from an online research registry, totaling 6,975 children with ASD, we examined the independent role of four ASD severity measures in driving the relationship with epilepsy: ID, language impairment, core ASD symptom severity, and motor dysfunction, controlling for two known relevant factors: age and sex. We also examined whether developmental regression and epilepsy have an independent statistical link. All four ASD severity factors showed independent statistical associations with epilepsy in one cohort, and three in the other. ID showed the largest relative risk (RR) in both cohorts. Effect sizes were modest. Regression similarly showed an independent statistical association with epilepsy, but with small effect size. Similar to previous work, ID showed the greatest contribution to RR for epilepsy among children with ASD. However, other ASD severity markers showed statistical associations, demonstrating that the ASD-epilepsy association is not reducible to the effect of ID. Inconsistencies in the literature may be due to underpowered studies, yet moving forward with larger-n studies, clinical significance and scientific relevance may be dictated by effect size and not merely statistical significance. Autism Res 2019, 12: 1251-1259. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Epilepsy is known to occur more often in individuals with autism spectrum disorders (ASDs) than is the case in the general population. The association between ASD and epilepsy is of interest because studying the two disorders in combination may help advance our understanding of genetic, molecular, and cellular mechanisms-as well as therapies-for both. Recent studies have suggested that intelligence quotient (IQ) alone in individuals with ASD may account for the increased prevalence of epilepsy. However, our approach was to look at a range of severity factors relevant to ASD and to look for correlations between each severity factor and epilepsy, within two large samples of children with ASD. In summary, we found that each severity factor-presence of intellectual disability, presence of language atypicalities, ASD-specific symptoms severity, and presence of motor issues-independently predicted a small increased risk for epilepsy, countering the argument that IQ alone is a risk factor. We also examined whether epilepsy is associated with developmental regression. Although severe epilepsy syndromes such as Landau-Kleffner syndrome are known to cause autistic-like symptoms following developmental regression, there is controversy about whether other forms of epilepsy are associated with the more common developmental regression seen in many young children with epilepsy. Indeed, we found a small association between epilepsy and developmental regression.