常规剂量与小剂量促肾上腺皮质激素治疗婴儿痉挛的对照研究

A comparative study of conventional dose and low dose adrenocorticotrophic hormone therapy for West syndrome

摘要:

目的：比较常规剂量与小剂量促肾上腺皮质激素（ACTH）治疗婴儿痉挛（West syndrome，WS）疗效及副作用的差异，寻找ACTH的最小有效剂量。方法：采用前瞻性随机对照研究，将30例WS（8例隐原性，22例症状性）随机分为常规剂量组（n=15）或小剂量组（n=15）。常规剂量组ACTH 50 IU/d×2周，随后2周减量至停药；小剂量组每日0.4 IU/kg×2周，若痉挛发作停止，随后2周减量至停药，若未完全控制或无效，加量至每日1 IU/kg 再用2周，随后用2周的时间逐渐减量至停药。比较ACTH两种不同剂量治疗WS的疗效及副作用。结果：常规剂量与小剂量治疗WS的近期疗效相似，有效率分别为53%及60%（P>0.05），治疗后脑电图变化、痉挛复发及复发时间两组间差异无显著性（P>0.05）。8例完成12个月以上随诊，长期疗效两组间也无差异。ACTH对隐原性WS的有效率及脑电图高峰失律消失例数均高于症状性组（P<0.05）。常规剂量组副作用发生率(93%，14/15)明显高于小剂量组(20%，3/15)，常规剂量组中1例出现轻度脑萎缩。结论：ACTH 50 IU/d与每日0.4 IU/kg两种剂量治疗WS的近期及远期疗效相似，对隐原性WS的疗效优于症状性，为避免副作用的发生，ACTH的使用应从小剂量（每日 0.4 IU/kg）开始。［中国当代儿科杂志，2009，11（6）：445-448］

Abstract:

OBJECTIVE: The efficacy and adverse effects of conventional dose and low dose adrenocorticotrophic hormone (ACTH) therapy for West syndrome (WS) were compared in order to identify a low effective dose with few adverse effects. METHODS: A prospective randomized controlled study was conducted. Thirty children with cryptogenic (n=8) or symptomatic (n=22) WS were enrolled. They were randomly assigned to receive either conventional dose or low dose ACTH therapy. For the conventional dose group, ACTH 50 IU per day was administered for 2 weeks and tapered to zero over the subsequent 2 weeks. For the low dose group, 0.4 IU/kg per day was injected for 2 weeks. After seizures were fully controlled, ACTH was tapered to zero over the subsequent 2 weeks. If there was an absence of an effective response in the low dose group, the dosage was increased to 1 IU/kg per day for the next 2 weeks and then tapered to zero over 2 weeks. Both effectiveness and adverse effects were compared between the two groups. RESULTS: There were no significant differences in the good initial responses between the conventional and the low dose groups, which were 53% and 60%, respectively (P>0.05). EEG findings after ACTH therapy, the rate of relapse of spasms, and the interval to relapse were not different between the two groups (P>0.05). The longterm outcomes were assessed in the initial 8 responders, and there were no significant differences between the two groups (follow-up duration>12 months). The rates of good efficacy and disappearance of the hypsarrhythmia were significantly higher in the cryptogenic WS group than in the symptomatic WS group (P<0.05). The incidence of ACTH therapy related-adverse effects in the conventional dose group (93%) was significantly higher than in the low dose group (20%) (P<0.01). The mild brain shrinkage was observed in one patient from the conventional dose group. CONCLUSIONS: The short-term and long-term therapeutic effects of ACTH between 50 IU/d and 0.4 IU/ ( kg?d) doses are similar. ACTH therapy is more effective for cryptogenic WS than symptomatic WS. To reduce adverse effects, ACTH therapy should start with a low dose (0.4 IU/ kg each day).［Chin J Contemp Pediatr, 2009, 11 (6):445-448］