Kawano Osamu, Egawa Kiyoshi, Shiraishi Hideaki
Department of Pediatrics, Hokkaido University Hospital, Japan.
Department of Pediatrics, Hokkaido University Hospital, Japan.
Brain Dev. 2020 May;42(5):389-392. doi: 10.1016/j.braindev.2020.02.007. Epub 2020 Mar 10.
Angelman syndrome (AS) is a neurodegenerative disorder caused by functional loss of the maternal ubiquitin-protein ligase 3A gene. Nonepileptic myoclonus, also described as tremulous movement, often occurs during puberty and increases in adulthood. The involuntary movement in AS has not been defined patho-physiologically and the drugs used such as levetiracetam and piracetam are not always effective. Recently, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, perampanel (PER), was used to alleviate myoclonus in progressive myoclonus epilepsy. Herein, we tested the efficacy of PER for nonepileptic myoclonus.
Four patients with AS, aged from 20 to 40 years at the beginning of treatment, were enrolled in our study. All patients reported disruption to their daily lives from the myoclonus movement. They experienced mild to moderate improvement with the starting dose of 2 mg. The dose was increased to 4 mg in one patient to achieve sufficient efficacy, while two had their dose reduced to 1 mg due to dizziness or possible exacerbation of myoclonus. The last patient continued to take the starting dose. Follow-up over 16-20 months revealed a significant reduction in the severity of nonepileptic myoclonus in all patients.
Our study suggests that PER could be one of the promising drugs for nonepileptic myoclonus in AS.
天使综合征（AS）是一种由母体泛素蛋白连接酶3A基因功能丧失引起的神经退行性疾病。非癫痫性肌阵挛，也被描述为震颤运动，常在青春期出现，并在成年期加重。AS中的不自主运动在病理生理学上尚未明确，使用的药物如左乙拉西坦和吡拉西坦并不总是有效。最近，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂吡仑帕奈（PER）被用于减轻进行性肌阵挛癫痫中的肌阵挛。在此，我们测试了PER对非癫痫性肌阵挛的疗效。
4例AS患者在治疗开始时年龄为20至40岁，被纳入我们的研究。所有患者均报告肌阵挛运动干扰了他们的日常生活。起始剂量2mg时，他们有轻度至中度改善。1例患者将剂量增加至4mg以达到足够疗效，而2例因头晕或肌阵挛可能加重将剂量减至1mg。最后1例患者继续服用起始剂量。16至20个月的随访显示，所有患者的非癫痫性肌阵挛严重程度均显著降低。
我们的研究表明，PER可能是治疗AS中非癫痫性肌阵挛的有前景的药物之一。
