Shurtleff Hillary, Barry Dwight, Chanprasert Sirisak, Firman Tim, Warner Molly, Saneto Russell P
Department of Neurology, University of Washington, Seattle, WA, USA; Seattle Children's Hospital, Seattle, WA, USA.
Seattle Children's Hospital, Seattle, WA, USA; Enterprise Analytics, Seattle Children's Hospital, Seattle, WA, USA.
Epilepsy Behav. 2018 Nov;88:235-243. doi: 10.1016/j.yebeh.2018.09.013. Epub 2018 Oct 11.
This retrospective descriptive study was undertaken to further define the intelligence profiles of children with mitochondrial disorders, in the context of seizures and age of symptom onset.
We retrospectively identified forty-nine pediatric patients with definitive mitochondrial disease diagnoses and complete intelligence or adaptive functioning testing data. Patients were 0-216 months at onset of symptoms and 61-250 months of age at testing. Twenty-four of 49 patients had seizures. Twenty-one of the 24 patients with seizures had medically intractable seizures. All patients had Wechsler Intellectual Quotient (IQ) testing, except nine patients with seizures who were unable to engage in IQ testing and were assessed with a structured parent interview measure, the Vineland Adaptive Behavior Scales. We used descriptive and exploratory data analysis methods to characterize test results.
Distribution of ages for patients with the Vineland assessment was younger than those given the Wechsler. The median overall score (combining Wechsler and Vineland summary scores) for all patients was 85 (interquartile range [IQR]: 50, 102), with the group without seizures obtaining a higher median Full Scale IQ (FSIQ) of 100 (IQR: 86, 109), compared to the group with seizures with a median FSIQ of 67 (IQR: 49.5, 89), a difference that is both statistically and clinically different (Δ = 33; 95% CI: 9, 52). The adaptive function measure was composed of patients only with intractable epilepsy and yielded the lowest overall median summary score of 43 (IQR: 37, 50). This general trend in differences between the FSIQ scores of the groups with and without seizures was also seen across all subscale measures analyzed-IQ index scores and two subtest scores, Digit Span and Coding-though differences were not always statistically different. Vargha-Delaney's A effect sizes ranged between 0.68 and 0.90, trends that mirrored those of distributional and median differences. Groups without versus with seizures differed most distinctly in Performance IQ (PIQ), with the group without seizures' median PIQ being 100 (IQR 94, 112) versus the group with seizures' median PIQ being 63 (IQR 54, 84), a difference of 37 points (95% CI).
Results suggest that patients with mitochondrial diseases with seizures and early onset disease represent a worse cognitive phenotype, as compared with those with no seizures, who can have average intelligence. Results are discussed in the context of current literature.
本回顾性描述性研究旨在结合癫痫发作情况和症状出现年龄，进一步明确线粒体疾病患儿的智力特征。
我们回顾性确定了49例确诊为线粒体疾病且有完整智力或适应性功能测试数据的儿科患者。患者症状出现时年龄为0至216个月，测试时年龄为61至250个月。49例患者中有24例有癫痫发作。24例有癫痫发作的患者中，21例患有药物难治性癫痫。除9例有癫痫发作无法进行智商测试的患者通过结构化家长访谈量表（文兰适应行为量表）进行评估外，所有患者均进行了韦氏智商测试。我们使用描述性和探索性数据分析方法来描述测试结果。
接受文兰评估的患者年龄分布比接受韦氏评估的患者年轻。所有患者的总体中位数得分（结合韦氏和文兰总结得分）为85（四分位间距[IQR]：50，102），无癫痫发作组的全量表智商（FSIQ）中位数较高，为100（IQR：86，109），而有癫痫发作组的FSIQ中位数为67（IQR：49.5，89），差异在统计学和临床上均有意义（Δ = 33；95%置信区间：9，52）。适应性功能测量仅包括患有难治性癫痫的患者，其总体中位数总结得分最低，为43（IQR：37，50）。在分析的所有子量表测量中，即智商指数得分以及数字广度和编码这两个子测试得分中，也观察到了有癫痫发作组和无癫痫发作组FSIQ得分之间的这种总体差异趋势，尽管差异并非总是具有统计学意义。瓦尔加 - 德莱尼A效应大小在0.68至0.90之间，与分布和中位数差异趋势一致。无癫痫发作组和有癫痫发作组在操作智商（PIQ）方面差异最为明显，无癫痫发作组的PIQ中位数为100（IQR 94，112），而有癫痫发作组的PIQ中位数为63（IQR 54，84），相差37分（95%置信区间）。
结果表明，与无癫痫发作且智力可处于平均水平的线粒体疾病患者相比，有癫痫发作且疾病早发的线粒体疾病患者代表了更差的认知表型。结合当前文献对结果进行了讨论。
