Goto Masahide, Saito Yoshiaki, Honda Ryoko, Saito Takashi, Sugai Kenji, Matsuda Yuko, Miyatake Chiharu, Takeshita Eri, Ishiyama Akihiko, Komaki Hirofumi, Nakagawa Eiji, Sasaki Masayuki, Uto Chieko, Kikuchi Kenjiro, Motoki Takahiro, Saitoh Shinji
Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
Brain Dev. 2015 Feb;37(2):216-22. doi: 10.1016/j.braindev.2014.04.005. Epub 2014 May 3.
Neurological manifestations including psychomotor developmental delay and epilepsy in patients with Angelman syndrome caused by ubiquitin protein ligase E3A (UBE3A) mutations has been considered similar but is relatively milder than that in patients with deletion-type Angelman syndrome. This makes the diagnosis of the former subgroup often difficult. We here characterized epilepsy, specifically the types of tremulous movement, in 4 patients (age, 3-38years) with Angelman syndrome caused by UBE3A mutations.
Ictal electroencephalography was used to record episodic tremors in all study patients. Jerk-locked averaging was performed using digital electroencephalography and surface electromyogram data from patients who were monitored for 24h.
All patients had tremors in the limbs, head, and trunk, which resulted in 2 patients falling backward. These tremors lasted several seconds, and could emerge in clusters for hours in older patients. In addition, the tremors coincided with 7-8Hz rhythmic activity with a frontocentral predominance, diffuse spike-wave bursts, or no apparent change on electroencephalography. In 2 patients, these tremors were confirmed as cortical myoclonus using jerk-locked averaging. The other seizure types were isolated generalized myoclonus and tonic seizures. None of the patients experienced atypical absence seizures. Levetiracetam therapy was effective in controlling the myoclonic events in 2 of the 3 patients.
Semirhythmic myoclonus is common in patients with Angelman syndrome caused by UBE3A mutations, and such myoclonic events are often life disabling. The preserved expression of gamma-aminobutyric acid type A receptor subunit genes located proximal to UBE3A might explain the low prevalence of absence seizures in this population.
由泛素蛋白连接酶E3A（UBE3A）突变引起的天使综合征患者的神经学表现，包括精神运动发育迟缓及癫痫，一直被认为与缺失型天使综合征患者相似，但相对较轻。这使得前一亚组患者的诊断往往较为困难。我们在此对4例（年龄3至38岁）由UBE3A突变引起的天使综合征患者的癫痫，特别是震颤运动类型进行了特征描述。
采用发作期脑电图记录所有研究患者的发作性震颤。对监测24小时的患者，利用数字脑电图和表面肌电图数据进行抽搐锁定平均分析。
所有患者的四肢、头部和躯干均出现震颤，导致2例患者向后摔倒。这些震颤持续数秒，在老年患者中可能成簇出现数小时。此外，震颤与脑电图上7至8赫兹的节律性活动、额中央优势、弥漫性棘波爆发或无明显变化同时出现。在2例患者中，通过抽搐锁定平均分析证实这些震颤为皮质肌阵挛。其他发作类型为孤立性全身性肌阵挛和强直发作。所有患者均未出现非典型失神发作。左乙拉西坦治疗对3例患者中的2例控制肌阵挛发作有效。
半节律性肌阵挛在由UBE3A突变引起的天使综合征患者中很常见，且此类肌阵挛事件常使生活致残。UBE3A近端的γ-氨基丁酸A型受体亚基基因的保留表达可能解释了该人群中失神发作的低患病率。
