摘要目的 探讨系统化疗基础上间断应用大剂量丙种球蛋白(HD-IVIG)冲击联合泼尼松免疫治疗控制神经母细胞瘤(NB)患儿阵挛症状的可行性.方法 回顾性分析2011年5月至2017年2月首都医科大学附属北京儿童医院收治的8例合并阵挛症状的NB患儿的临床资料,包括一般资料、肿瘤情况、神经系统症状、治疗及预后等.随访截止至2017年3月1日.结果 8例患儿中男3例,女5例;起病年龄10.0 ～35.5个月(中位年龄17.5个月);出现阵挛症状至确诊后开始治疗时间为1.25 ～ 6.50个月(中位时间为3.60个月).本组8例NB患儿均出现躯干及肢体阵挛等神经系统副肿瘤综合征表现,其中合并眼阵挛肌阵挛综合征(OMS)5例.患儿均初次就诊于首都医科大学附属北京儿童医院或当地医院神经科.原发瘤灶位于双侧肾上腺、骶前区各1例,单侧肾上腺、腹膜后、纵隔各2例.影像学检查显示仅1例原发瘤灶直径＞5 cm.除1例存在肿瘤局部椎体侵犯外,其他7例均未见远处转移.病初神经元特异性烯醇化酶(NSE)升高4例;尿香草扁桃酸(VMA)升高1例;乳酸脱氢酶(LDH)升高5例,但均＜500 IU/L.8例患儿中,6例肿瘤病理类型为NB,其中分化型4例,分化差型2例;节细胞性神经母细胞瘤(GNB)2例,其中结节型1例,混杂型1例.肿瘤N-MYC均无扩增.临床分期:Ⅱ期5例,Ⅲ期3例.临床分组:中危组7例,低危组1例.除1例患儿因经济原因诊治不规律,阵挛症状未见明显改善,目前除失访外,其余患儿均在系统化疗基础上给予间断HD-IVIG冲击及泼尼松口服的免疫治疗:HD-IVIG在整体系统化疗6～8疗程期间多次冲击治疗(每疗程2 g/kg,每月1次),应用丙种球蛋白的同时,给予患儿口服泼尼松,自足量开始口服,疗程1.0 ～5.5个月,平均3个月,后开始缓慢减量,随访至今,已停用激素者4例,总疗程8～12个月,平均10个月.4例患儿于治疗后1个月即阵挛症状好转,5～12个月症状消失;2例分别于治疗后3个月及停药后半年阵挛好转,其中1例治疗后1年症状完全消失,1例随访至今仍有轻度阵挛症状.除1例失访患儿外,其余患儿原发病定期瘤灶评估提示病情均处于稳定状态.结论 系统规律化疗基础上间断应用HD-IVIG冲击联合泼尼松免疫治疗可有效控制NB患儿的阵挛症状.阵挛症状干预时间越早,神经系统症状恢复时间越快.

abstractsObjective To explore the feasibility of immunotherapy intermittently with high dose intravenous immunoglobulin(HD-IVIG)impact therapy combined with prednisone on the basis of systematic chemotherapy to control the clonic symptoms of children with neuroblastoma(NB).Methods A retrospective analysis was made based on the clinical data of 8 NB children with combined clonus,who were admitted in Beijing Children's Hospital,Capital Medical University from May 2011 to February 2017.And analysis and summary were also made according to patients' clinical data,neurological symptoms,therapy methods and prognosis.The follow-up visiting was ended on March 1,2017.Results Eight patients were investigated,3 male and 5 female,with onset age ranged from 10.0 to 35.5 months (the median age was 17.5 months),and the period from occurrence of clonic symptoms to a definite diagnosis and starting treatment was 1.25 to 6.50 months (the median time was 3.60 months).All patients developed kinds of neurological syndrome clinically,such as clonus on the trunk and limbs,and 5 cases of them were involved in combined opsoclonus-myoclonus syndrome (OMS).All patients went for their first-time consultancy at the Neurology Department of Beijing Children's Hospital,Capital Medical University or local hospitals.The primary tumor focus was found in unilateral adrenal gland in 2 cases,1 case in bilateral adrenal glands,2 case in retroperitoneal region,2 cases in mediastinum and 1 cases in presacral region.The image examination indicated 1 case with a tumor focus,the diameter of it more than 5 cm.Except for 1 case involved in the local invasion of tumor in vertebral body,the images examination of all other patients showed the focus in the primary location,without visible distant metastasis or no abnormality was seen by head magnetic resonance imaging (MRI) examination.Initially,four cases had normal neuronal specific enolase (NSE) and 4 had higher NSE;one case had higher urine vanillylmandelic acid (VMA) and 7 normal;3 cases had higher urine homovanillic acid(HVA) and 5 normal.Among 8 patients,the pathological pattern of 6 cases was NB,in which 4 cases were of differentiated type and 2 cases of poorly differentiated type;the pathological pattern of 2 cases was ganglion cell NB,in which 1 case was of nodular type and 1 case of mixed type.N-MYC was not amplified.Clinical staging:5 cases of stage Ⅱ and 3 cases of stage Ⅲ.Clinical grouping:7 cases of intermediate risk group and 1 case of low risk group.So far,1 case lost follow-up in that the child didn't receive regular diagnosis and treatment due to economic problem,so significant improvement of clonic symptoms was not seen,all other patients were given the immunotherapy with intermittent HD-IVIG impact therapy and oral administration of prednisone based on systematic chemotherapy:immunoglobulin was applied respectively before,during and after chemotherapy in multiple impact treatments;3 cases received 4 courses of treatment,2 cases received 3 courses of treatment and 2 cases received 2 courses of treatment.Prednisone was given orally during the application of immunoglobulin,from the full dose and with the course of treatment of 1.0 to 5.5 months,3 months on average;then the dose was gradually reduced.With the follow-up up to now,hormone was discontinued in 4 cases and the total course of treatment was 8 to 12 months,10 months on average.One month after the treatment of patients in 4 cases,the clonic symptoms were improved or disappeared in 5 to 12 months;the clonus of patients in 2 cases was improved respectively 3 months after treatment and half a year after drug withdrawal,in which the symptoms of 1 case disappeared completely 1 year after treatment and the slight clonic symptoms of 1 case still existed by the update follow-up.Except for 1 case of patient lost to follow-up,the regular primary tumor focus of all patients indicated that the disease conditions were in a stable state.Conclusions The immunotherapy intermittently applied with HD-IVIG impact therapy in combination with prednisone based on regular systematic chemotherapy can effectively control the clonic symptoms of children with NB.The earlier the intervene treatment for clonic symptoms is recommended,so that the faster recovery of symptoms can be achieved.Early diagnosis and early treatment play a helpful role in the recovery of children with neurological symptoms.