硫酸镁联合促肾上腺皮质激素治疗婴儿痉挛症开放性临床研究

An open-label clinical study on the efficacy and tolerability of magnesium sulfate combined with adrenocorticotropic hormone treatment on infantile spasm

研究背景婴儿痉挛症是一种以痉挛发作、脑电图高度失律和精神运动发育迟滞为特征的难治性癫癇,抗癫癇药物治疗效果欠佳。促肾上腺皮质激素作为一线治疗药物存在感染和高血压等不良反应,本研究旨在通过开放性临床试验评价硫酸镁联合促肾上腺皮质激素治疗婴儿痉挛症的疗效和耐受性。方法共计55例婴儿痉挛症患儿接受统一标准的硫酸镁联合促肾上腺皮质激素治疗,比较治疗前后痉挛发作频率和脑电图改变,治疗过程中通过监测患儿生命体征、实验室指标和药物不良事件评价药物耐受性。结果治疗2周后痉挛发作控制有效率为78.18%(43/55)、脑电图改善率为55.77%(29/52),其中无发作25例(45.45%)、脑电图恢复正常6例(11.54%)。不同发病年龄[≤4个月和>4个月(χ2=0.595,P=0.441)]、病程[≤2个月和>2个月(Fisher确切概率法:P=0.735)]和病因学[特发性或隐源性和症状性婴儿痉挛症(Fisher确切概率法:P=1.000)]对痉挛发作控制有效率,以及不同发病年龄(χ2=1.325,P=0.250)、病程(χ2=2.668,P=0.102)和病因学(χ2=2.215,P=0.145)对脑电图改善率之差异均无统计学意义;治疗期间无一例患儿发生高血压等不良事件。29例患儿经长期随访(治疗后1、3和12个月)无痉挛发作患儿比例基本维持不变(χ2=0.945,P=0.815)。结论硫酸镁联合促肾上腺皮质激素方案治疗婴儿痉挛症疗效肯定且耐受性良好。

Background Infantile spasm（IS） is characterized by spasm seizure, hypsarrhythmia in EEG, and psychomotor retardation. It is refractory to conventional antiepileptic drugs（AEDs）. As firstline therapy for IS, adrenocorticotropic hormone（ACTH） has side effects, such as infection and hypertension.This study aims to evaluate the efficacy and tolerability of magnesium sulfate combined with ACTH treatment by open-label clinical trial.Methods An open-label clinical study was designed. According to inclusion and exclusion criteria, objects were inpatients with IS. A total of 55 patients with IS were enrolled. After clinical data collection, standard magnesium sulfate combined with ACTH was given to the patients for 2 weeks. Efficacy and safety were assessed regularly. The evaluation parameters of efficacyincluded change of spasm seizure frequency and EEG after treatment. During administration process, vital signs were monitored, laboratory items were tested regularly, and adverse events were daily recorded by guardian.Results After treatment of magnesium sulfate combined with ACTH for 2 weeks, seizure control efficiency was 78.18%（43/55）, and the improvement rate of EEG was 55.77%（29/52）, wherein 25 patients（45.45%） acquired seizure free, 6 patients（11.54%） presented normal in EEG examination. There were no statistical differences of the effect of different onset ages（≤ 4 months, 〉 4 months） on seizure control efficiency rate（χ2= 0.595, P = 0.441） and EEG improvement rate（χ2= 1.325, P = 0.250）, the effect of different courses of disease（≤ 2 months, 〉 2 months） on seizure control efficiency rate（Fisher’s exact test：P = 0.735） and EEG improvement rate（χ2= 2.668, P = 0.102）, and the effect of different etiologies（idiopathic or cryptogenic IS, symptomatic IS） on seizure control efficiency rate（Fisher’s exact test： P =1.000） and EEG improvement rate（χ2= 2.215, P = 0.145）. No adverse events, such as hypertension,occurred. After long- term（1 month, 3 months and 12 months） follow- up for 29 patients, seizure free rate remained roughly unchanged（χ2= 0.945, P = 0.815）.Conclusions For patients with IS, magnesium sulfate combined with ACTH treatment is effective and well tolerated.