Tarquinio Daniel C, Hou Wei, Berg Anne, Kaufmann Walter E, Lane Jane B, Skinner Steven A, Motil Kathleen J, Neul Jeffrey L, Percy Alan K, Glaze Daniel G
Emory University, Atlanta, GA, USA
Stony Brook University Medical Center, Stony Brook, NY, USA.
Brain. 2017 Feb;140(2):306-318. doi: 10.1093/brain/aww302. Epub 2016 Dec 21.
Epilepsy is common in Rett syndrome, an X-linked dominant disorder caused by mutations in the MECP2 gene, and in Rett-related disorders, such as MECP2 duplication. However, neither the longitudinal course of epilepsy nor the patterns of seizure onset and remission have been described in Rett syndrome and related conditions. The present study summarizes the findings of the Rett syndrome Natural History study. Participants with clinical Rett syndrome and those with MECP2 mutations without the clinical syndrome were recruited through the Rett Natural History study from 2006 to 2015. Clinical details were collected, and cumulative lifetime prevalence of epilepsy was determined using the Kaplan-Meier estimator. Risk factors for epilepsy were assessed using Cox proportional hazards models. Of 1205 participants enrolled in the study, 922 had classic Rett syndrome, and 778 of these were followed longitudinally for 3939 person-years. The diagnosis of atypical Rett syndrome with a severe clinical phenotype was associated with higher prevalence of epilepsy than those with classic Rett syndrome. While point prevalence of active seizures ranged from 30% to 44%, the estimated cumulative lifetime prevalence of epilepsy using Kaplan-Meier approached 90%. Specific MECP2 mutations were not significantly associated with either seizure prevalence or seizure severity. In contrast, many clinical features were associated with seizure prevalence; frequency of hospitalizations, inability to walk, bradykinesia, scoliosis, gastrostomy feeding, age of seizure onset, and late age of diagnosis were independently associated with higher odds of an individual having epilepsy. Aggressive behaviour was associated with lower odds. Three distinct patterns of seizure prevalence emerged in classic Rett syndrome, including those who did not have seizures throughout the study, those who had frequent relapse and remission, and those who had relentless seizures. Although 248 of those with classic Rett syndrome and a history of seizures were in terminal remission at last contact, only 74 (12% of those with a history of epilepsy) were seizure free and off anti-seizure medication. When studied longitudinally, point prevalence of active seizures is relatively low in Rett syndrome, although lifetime risk of epilepsy is higher than previously reported. While daily seizures are uncommon in Rett syndrome, prolonged remission is less common than in other causes of childhood onset epilepsy. Complete remission off anti-seizure medications is possible, but future efforts should be directed at determining what factors predict when withdrawal of medications in those who are seizure free is propitious.
癫痫在瑞特综合征中很常见，这是一种由MECP2基因突变引起的X连锁显性疾病，在瑞特相关疾病中也很常见，如MECP2重复综合征。然而，在瑞特综合征及相关病症中，癫痫的纵向病程以及发作起始和缓解模式均未得到描述。本研究总结了瑞特综合征自然史研究的结果。2006年至2015年期间，通过瑞特自然史研究招募了患有临床瑞特综合征的参与者以及携带MECP2突变但无临床综合征的参与者。收集了临床细节，并使用Kaplan-Meier估计器确定癫痫的累积终生患病率。使用Cox比例风险模型评估癫痫的危险因素。在参与该研究的1205名参与者中，922人患有典型瑞特综合征，其中778人接受了3939人年的纵向随访。具有严重临床表型的非典型瑞特综合征的诊断与癫痫患病率高于典型瑞特综合征患者有关。虽然活动性癫痫发作的时点患病率在30%至44%之间，但使用Kaplan-Meier估计的癫痫累积终生患病率接近90%。特定的MECP2突变与癫痫发作患病率或严重程度均无显著关联。相比之下，许多临床特征与癫痫发作患病率相关；住院频率、无法行走、运动迟缓、脊柱侧弯、胃造口喂养、癫痫发作起始年龄和诊断较晚均与个体患癫痫的较高几率独立相关。攻击性行为与较低几率相关。典型瑞特综合征出现了三种不同的癫痫发作患病率模式，包括在整个研究过程中未发作的患者、频繁复发和缓解的患者以及持续发作的患者。尽管248名有癫痫病史的典型瑞特综合征患者在最后一次随访时处于终末期缓解状态，但只有74人（占癫痫病史患者的12%）无癫痫发作且停用了抗癫痫药物。纵向研究时，瑞特综合征中活动性癫痫发作的时点患病率相对较低，尽管癫痫的终生风险高于先前报道。虽然瑞特综合征中每日发作并不常见，但长期缓解比儿童期起病癫痫的其他病因少见。停用抗癫痫药物后完全缓解是可能的，但未来的努力应致力于确定哪些因素可预测无癫痫发作患者何时停药是合适的。
