Safety,tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30–60 IU) or oral zonisamide (4–25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.     

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

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］     

甲基泼尼松龙冲击治疗小儿激素敏感肾病综合征的临床随机对照研究

目的客观评价甲基泼尼松龙(甲泼尼龙)冲击与传统的口服足量泼尼松对小儿肾病综合征的疗效及不良反应,为临床应用提供可参考的证据。方法以原发性肾病综合征、激素敏感复发或初发初治的病例为研究对象,采用分层区组随机有效对照,开放试验,以甲泼尼龙冲击为治疗组,口服泼尼松治疗为对照组,比较两者的疗效及不良反应。结果甲泼尼龙组13例患儿中2例冲击治疗期间因感染停止治疗,11例完成治疗并缓解,尿蛋白转阴时间为3～7d,中位时间5d;泼尼松组11例患儿均完成治疗并缓解,尿蛋白转阴时间为5～28d,中位时间8d(P=0.0008);甲泼尼龙冲击治疗组患儿2周内的不良反应有感染、情绪改变、消化道症状和浮肿加重,不良反应的发生率较泼尼松组高;缓解后3个月内的再次复发两组无差别;治疗后3个月的体质量和皮下脂肪厚度,泼尼松组较治疗前增加,身高和骨密度两组治疗前后均无差别;全部患儿的肾上腺皮质功能治疗后2周均受到抑制,至治疗后3个月绝大多数仍未恢复。结论与口服足量泼尼松治疗相比,甲泼尼龙冲击治疗显示了可使激素敏感的原发性肾病综合征患儿尿蛋白更快转阴的趋势,但治疗期间可能出现感染等不良反应;甲泼尼龙冲击治疗不能减少缓解后3个月内的再次复发,对患儿体质量和皮下脂肪分布的影响可能更小。     

SLC35A2 基因突变致马凡综合征家系中West 综合征患儿1 例报告并文献复习

目的鉴定马凡综合征家系中1例West综合征患儿基因致病性突变,为家系遗传咨询提供依据。方法收集患儿及其家系成员的临床资料进行分析。提取患儿及其父母、外祖母、舅舅的外周血DNA,采用医学外显子二代测序加拷贝数变异检测,再进行Sanger测序验证。并复习相关文献。结果女性患儿,10月龄,反复抽搐发作7个月,表现为婴儿痉挛。患儿及其母亲、外祖母存在马凡综合征体征。患儿及其母亲、外祖母存在FBN1基因c.7240CT(p.R2414*)无义突变;患儿还存在SLC35A2基因c.601delG(p.A201Qfs*148)移码突变,其父母SLC35A2基因未见该变异,该基因变异既往未见报道。患儿行室间隔修补术,并予托吡酯、半乳糖治疗后癫痫及发育情况好转。检索到临床资料齐全的相关SLC35A2基因突变报道 16篇共 74例患者,涉及58个位点,其中错义突变最常见,患者可有不同的临床表型,以早期婴儿癫痫性脑病最常见。结论 SLC35A2基因c.601delG(p.A201Qfs*148)是马凡综合征家系中该患儿罹患West综合征的致病性变异。该研究扩大了基因突变谱,为该家系的遗传咨询提供了基础;半乳糖联合托吡酯治疗有助于控制癫痫发作和改善发育情况。     

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??Objective??To observe the efficacy and safety of multi-target immunosuppressive therapy in treatment of children with steroid-resistant nephritic syndrome??SRNS??. Methods??A total of 48 children with SRNS were enrolled in this multicenter prospective study. Based on the same comprehensive treatment??the children were randomly divided into two groups?? ??1??observation group?? they were orally given CSA??3??4 mg/??kg·d???? and MMF??20 mg/??kg·d???? multi-target immunosuppressive therapy????2??control group??they were orally given CSA??4??6 mg/??kg·d????. The side effects were closely observed. The plasma concentrations of CSA??urine protein to creatinine ratios??liver and kidney function??blood routine and urine β2-microglobulin were respectively compared between the two groups after 2 weeks??1 month??3 months and 6 months of treatment. Results??The average plasma concentrations of CSA in the observation group was ??88.86±16.94?? μg/L??and in the control group it was ??152.96±19.20?? μg/L??P??0.001??. The urine protein to creatinine ratios in the observation group after 1 month and 3 months of treatment were lower than the control group in the same time period??P??0.05??. The serum albumin in the observation group after 1 month and 3 months of treatment was higher than the control group in the same time period??P??0.05??. The urine β2-microglobulin in these two groups had no differences during the treatment??P??0.05??. The overall remission rate of the observation group was 88%??and in the control group it was 87%. The remission rate of the observation group after 2 weeks and 1 month of treatment was better than the control group??P??0.05??. The main side effect during therapy was infection??gastrointestinal reaction??crinosity??hypertension and leukocyte decrease. The side effect of the observation group was less than the control group??P??0.05??. Conclusion??The multi-target therapy in children with SRNS by CSA and MMF results in early remission and can keep long-term remission with mild side effect.     

Targeted therapy for infants with diencephalic syndrome: A case report and review of management strategies

Young children with emaciation caused by a hypothalamic glioma are considered to have diencephalic syndrome (DS), which is often poorly controlled with conventional treatment. We describe an infant with DS whose tumor progressed following chemotherapy. Biopsy was performed for molecular testing and demonstrated a BRAF fusion. Treatment with the MEK inhibitor trametinib for 18 months resulted in reduction of tumor size, normalization of his weight curve, and marked neurodevelopmental improvement. Our results build on earlier reports of using targeted agents for low‐grade glioma, and we review the evolving management strategy for such patients in the era of precision medicine.     

A case of Chediak‐Higashi syndrome presented with accelerated phase could be treated effectively by unrelated cord blood transplantation

CHS is a rare immunodeficiency syndrome with defects in the functions of cytotoxic cells and neutrophils. Approximately 85% of patients with CHS undergo an AP within the first decade, which is similar to FHLH. Chemotherapy could induce transient remission, but only allogeneic HCT could correct the underlying genetic defect and prevent relapse. We reported a case of CHS diagnosed at 19 months, who had an elder brother who had previously succumbed to the same disease. The little girl presented with severe AP manifestations including recurrent high fever, enlarged superficial lymph nodes, and extraordinary hepatosplenomegaly occupying the whole abdominal and pelvic cavity. Comprehensive therapies including HLH 2004 protocol, supportive care, and antibiotics, especially antituberculous agents, were given to her to induce remission. After remission, the patient received fully HLA‐matched UCBT. The transplantation course was uneventful, except for fluctuation of donor chimerism. The patient has been alive for 36 months without infection and neurologic manifestations and is under further follow‐up. Our result provides another case that UCBT can be effective for treating patients with CHS and remission before HCT is important for good prognosis.