脑脊液肿瘤细胞阳性视网膜母细胞瘤6例治疗观察

观察全身应用卡铂、替尼泊苷和长春新碱（CTV）方案化疗加鞘内注射治疗脑脊液细胞学检查肿瘤细胞阳性的视网膜母细胞瘤（RB）患儿的疗效。方法　6例患儿资料来自首都医科大学附属北京同仁医院2006年11月至2008年7月临床确诊为RB且治疗前行脑脊液细胞学检查发现肿瘤细胞者,对其进行6～9次CTV方案化疗加8～10次鞘内注射治疗,同时结合局部治疗,随访12～20个月,观察疗效。结果　6例患儿均完成治疗,病情稳定,复查脑脊液细胞学检查均未发现肿瘤细胞,无复发及死亡。结论　全身化疗加鞘内注射是对RB颅内转移有效的治疗方法,由于观察时间较短,长期疗效尚须行观察。     

脑脊液中找肿瘤细胞在视网膜母细胞瘤中的应用价值

目的探讨脑脊液中找肿瘤细胞对判断视网膜母细胞瘤(RB)转移及预后的价值。方法选取本院2006年11月-2008年7月临床确诊为RB的患儿256例。男154例,女102例;单眼患儿171例,双眼患儿85例。治疗前常规行腰椎穿刺,并在脑脊液中找肿瘤细胞,观察有无肿瘤细胞及其与预后的关系。对脑脊液中发现肿瘤细胞的患儿予6~9个周期的化疗和8~10次鞘内注射,化疗方案采用CTV(卡铂、替尼泊苷和长春新碱)方案,鞘内注射药物为阿糖胞苷、甲氨蝶呤和地塞米松。随访时间8~23个月,平均14.6个月。结果256例患儿中8例脑脊液中发现肿瘤细胞,其中1例脑膜弥散浸润性转移,死亡;1例发生颅内转移,进一步行大剂量化疗+自体外周血造血干细胞移植,目前病情稳定;余6例随访期间行眼球摘除,病理证实4例侵犯视神经,占67%(4/6例),其中2例累及视神经断端;6例均未发现其他转移证据。结论RB常见的途径是沿视神经向颅内转移;脑脊液检查找肿瘤细胞对于早期判断颅内转移、早期治疗及预后有重要意义。     

视网膜母细胞瘤中枢神经系统转移的诊疗现状

视网膜母细胞瘤(RB)是儿童最常见的眼内恶性肿瘤,占儿童恶性肿瘤的4%左右。RB1基因突变是最早被发现与RB发生有关的肿瘤抑制基因,常表现为点突变及RB1部分缺失。随着认识的深入以及诊治方法的改善,远处转移期尤其是中枢神经系统(CNS)转移的RB就诊率逐年增高。目前,CNS转移性RB主要通过对临床表现、影像学特征、脑脊液(CSF)细胞学检查、组织病理学检查、基因检测等综合分析而最终诊断,其治疗是目前的难点。虽然近年来针对性地应用了全身静脉化疗、腰穿鞘注化疗、全脑全脊髓放射疗法等手段,结合针对原发病灶的手术及局部治疗手段等进行综合治疗,患儿生存率未见明显提高。因此,全面认识目前CNS转移性RB的诊断、综合治疗及国内外研究进展,对于研究RB发生CNS转移的原因及机制、预后影响因素及发掘更加有效的治疗手段等工作十分必要。     

小儿中枢神经系统白血病45例临床分析

本文报告了 45例小儿中枢神经系统白血病 (CNSL) ,分析了CNSL的隐匿性及二次复发 ,提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液 (CSF)检查发现 1～ 2个幼稚细胞时 ,可观察 1～ 2周再做CSF检查 ,以确定治疗方案     

干扰素鞘内注射治疗病毒性脑炎及治疗前后脑脊液干扰素浓度测定

目的探讨鞘内注射干扰素治疗病毒性脑炎的疗效并观察脑脊液干扰素在鞘注前后的浓度变化情况。方法将76例病毒性脑炎患儿随机分为治疗组(38例)和对照组(38例)。治疗组除在常规治疗基础上采用鞘内注射干扰素，同时又分为大剂量组与小剂量组。治疗前后分别采集脑脊液，用微量细胞病变抑制法测定脑脊液干扰素浓度。结果治疗组与对照组比较在临床症状改善方面明显优于对照组，差异有显著性。结论两种不同剂量干扰素疗效比较，大剂量组临床症状的改善优于小剂量组，提示其脑脊液干扰素浓度的高低与临床疗效大小呈平行关系。     

自体外周血干细胞移植治疗儿童视网膜母细胞瘤伴广泛脑室内转移1例并文献复习

目的探讨自体外周血干细胞移植(ABSCT)联合持续侧脑室引流、脑室内给药对儿童视网膜母细胞瘤(RB)广泛脑室内转移的治疗效果。方法 1例RB广泛脑室内转移的7岁患儿,脑脊液病理可见肿瘤细胞满视野,行ABSCT治疗。预处理方案:卡铂+依托泊苷+环磷酰胺,同时予持续侧脑室引流,经引流管侧脑室给药(甲氨蝶呤+地塞米松)。0 d输入自体外周血造血干细胞。结果 +11 d始,脑脊液找瘤细胞持续转阴,+17 d,骨髓造血重建,+24 d,拔除侧脑室引流管,脑脊液神经元特异性烯醇化酶(NSE)及蛋白均降至正常,+36 d复查头颅增强MRI,颅内病灶消失。结论 ABSCT联合持续侧脑室引流脑室内给药治疗RB广泛脑室内转移,对于RB颅内转移患儿的治疗有一定借鉴作用。     

急性淋巴细胞白血病患儿脑脊液一氧化氮动态检测意义探讨

目的　了解单独化疗对急性淋巴细胞白血病 (ALL)患儿颅脑功能的影响。方法　该院 1 997年 6月至 1 999年 4月住院患儿 1 8例 ,其中男 1 0例 ,女 8例 ,年龄 1～ 8岁 ,均采用ALL -XH - 97方案进行治疗。对照组 1 2例 ,男 8例 ,女 4例 ,年龄 2～ 6岁 ,均为该院骨科选择性手术病例。ALL患儿在化疗前、化疗中、缓解后以及长期缓解期等不同时间段 ,在常规进行鞘内注射时取脑脊液 1 .5ml作一氧化氮 (NO)浓度测定。对照组于选择性手术行蛛网膜下腔麻醉时抽取 2ml脑脊液检测NO。结果　ALL化疗前组与对照组脑脊液中NO浓度比较 :ALL患儿脑脊液中NO浓度 1 3.87± 3.2 6mol/L较对照组 6 .79± 1 .4 6mol/L升高 ,差异有显著性 (P <0 .0 5 )。ALL患儿化疗不同阶段脑脊液中NO浓度比较 :与化疗前相比 ,化疗中为 1 4 .0 8± 7.78mol/L ,缓解后为 1 2 .6 4± 5 .5 8mol/L ,NO浓度比较 ,差异无显著性 (P >0 .0 5 ) ,但长期缓解患者NO浓度 7.84± 3.2 1mol/L下降 ,差异有显著性 (P <0 .0 5 )。结论　由于白血病及其治疗可使中枢神经系统内产生过量的NO ,从而引起对患儿认知功能的影响 ,但随着时间的延长 ,这种影响会逐渐消失 ,患者的认知功能也可以恢复。     

小儿中枢神经系统白血病45例临床分析

本文报告了45例小儿中枢神经系统白血病（CNSL），分析了CNSL的隐匿性及二次复发，提出鞘内注射仍是预防和治疗CNSL的有效手段。主张在仅有脑脊液（CSF）检查发现1－2个幼稚细胞时，可观察1－2周再做CSF检查，以确定治疗方案。     

MTX鞘内注射致严重神经毒性反应3例报告

鞘内注射MTX可致严重神经毒性反应,现报告3例。例1,男,4岁,因贫血1月,发热3天住院。体检:贫血貌,颈淋巴结肿大如蚕豆。心肺正常。肝肋下3cm,脾肋下4cm。经血细胞及骨髓细胞学检查,确诊为ALL_1,以VDP方案治疗。第3天鞘内注射MTX7.5mg、DX2mg,注射后8小时,患儿烦躁不安,频繁呕吐,体温39℃,10小时抽搐昏迷死亡。死后即做腰穿,脑脊液正常。例2为男性11     

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目的探讨大剂量甲氨蝶呤静滴+鞘内注射治疗急性淋巴细胞白血病(ALL)患儿时中枢神经系统损伤的监测指标。方法2003年1～12月在青岛大学医学院附属医院收治的42例标危ALL患儿中。在行大剂量甲氨蝶呤静滴+鞘内注射化疗前及化疗后15、30、45d腰穿留取脑脊液(CSF)各1mL,用双抗体夹心酶联免疫法测定CSF中神经元特异性烯醇化酶(NSE)的质量浓度。结果化疗后,CSF中NSE质量浓度升高,于第15天达峰值,化疗30dNSE质量浓度下降,与化疗前比较差异有统计学意义;化疗45d后NSE质量浓度与化疗前比较差异无统计学意义。结论CSF中NSE是ALL患儿行大剂量甲氨蝶呤静滴+鞘内注射化疗时,神经细胞急性损伤的一个有价值的预报因子。     

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??Objective To explore the differential diagnostic significance of cerebrospinal fluid??CSF?? detection with flow cytometry??FCM?? technology in children with acute lymphoblastic leukemia??ALL?? accompanied by central nervous system diseases. Methods Seven CSF samples of children with ALL were detected by FCM??cell morphology??CSF routine tests and biochemical examination in Department of Pediatrics??the First Affiliated Hospital??Sun Yat-sen University from February 2009 to February 2014. The children were treated and followed-up. The comparison between FCM and traditional methods in the diagnosis of ALL accompanied with encephalopathy was made. Results According to the traditional methods??only two patients were diagnosed reliably with CNSL??and in the other five patients??the initial diagnosis ??CNSL or non-CNSL?? was equivocal. But according to the results of FCM??four patients were diagnosed with CNSL??and three of them had acquired complete remission after systemic and intrathecal chemotherapy. One patient died because of disease progression. Two patients?? who were diagnosed with viral meningitis?? improved rapidly after treatment with acyclovir. One patient was finally diagnosed with reactive meningitis disease?? because the cerebrospinal fluid gradually returned to normal without treatment and the follow-up was uneventful. Conclusion FCM is a highly sensitive technique capable of accurately detecting malignant cells. It is an important supplement to CSF routine detections??and has significant application value in differential diagnosis of ALL children accompanied by central nervous system diseases.     

Intrathecal thiotepa: reappraisal of an established therapy

PURPOSE: Intrathecal thiotepa is recommended as a treatment of leptomeningeal metastases (LM) in children, although published data to support this approach are limited. The authors sought to determine the efficacy of intrathecal thiotepa for pediatric LM. PATIENTS AND METHODS: The authors reviewed all children treated with intrathecal thiotepa for LM at two tertiary children's hospitals, assessing outcome by cerebrospinal fluid cytology, neuroimaging, neurologic examination, and overall survival rate. RESULTS: Fifteen children with LM evidenced by malignant cells in the cerebrospinal fluid (mean age 7.3 years; five medulloblastoma, one anaplastic astrocytoma, one glioblastoma, one retinoblastoma, one neuroblastoma, two rhabdomyosarcoma, one non-Hodgkin lymphoma, two acute lymphoblastic leukemia, and one acute myelogenous leukemia) were treated with intrathecal thiotepa at 5 to 11.5 mg/m2 per dose for two to seven doses. Five children received concomitant craniospinal irradiation; 12 received simultaneous systemic or other intrathecal chemotherapy, or both. Four children experienced clearance of malignant cells from the spinal fluid, but this response was sustained in only two. All four children with cytologic response received concurrent radiotherapy, chemotherapy, or both. No patients showed partial or complete response on neuroimaging. Only one child had improvement on the neurologic examination; six were unchanged and eight had worsening neurologic signs. Median survival was 15.1 weeks, with a 1-year overall survival rate of 26.7% (standard error 11.4%). CONCLUSIONS: The unfavorable outcomes observed suggest that intrathecal thiotepa adds little to combination therapy for pediatric LM.     

Prospective evaluation of clinical and laboratory effects of intrathecal chemotherapy on children with acute leukemia

The objective of this prospective 18-month study was to evaluate the clinical and laboratory effects of repeated intrathecal injections of chemotherapy in children with acute leukemia. All procedures were performed under general anesthesia, and complications were prospectively recorded. Laboratory measurements included lumbar puncture opening pressure, cerebrospinal fluid (CSF) chemistry, and cell count and morphology. Central venous pressure and ophthalmologic examinations were also performed. Forty-seven children underwent 247 intrathecal injections of chemotherapy. Adverse effects (13.7% of the procedures) included nausea and vomiting, back pain, and headache. One child each had transient cauda equina syndrome, transient communicating hydrocephalus, and persistent sacral plexus injury. The mean lumbar puncture opening pressure was significantly higher after intrathecal therapy than before (22 +/- 8 vs. 15 +/- 9 cm H2O, P = 0.02) and higher than reported in age-matched children without leukemia. All CSF chemistries, cell count, and morphology were normal. The overall incidence of complications was 13.7%. Most were mild and resolved quickly, but significant neurologic complications did occur. Lumbar puncture opening pressure was significantly higher in children with acute leukemia after intrathecal chemotherapy.     

Primary intraspinal soft-tissue sarcoma in childhood: Report of two cases with a review of the literature

Two young children who presented with lower spinal cord dysfunction manifested by bilateral leg weakness and urinary retention were diagnosed with intraspinal soft-tissue sarcoma. Neither patient had a significant extradural mass. Both tumors had histochemical features of rhabdomyosarcoma. Temporary responses were noted after combination chemotherapy either with vincristine, actinomycin D, and cyclophosphamide or with ifosfamide/mesna and etoposide. However, both patients developed uncontrollable cerebrospinal fluid (CSF) dissemination of tumor and died within 6 months of diagnosis, despite intrathecal chemotherapy and irradiation for one and very high-dose intravenous methotrexate (33 g/m²) for the other. This rare tumor can respond to parenteral antisarcoma chemotherapy, but better strategies are needed to prevent CSF spread and ultimate demise. Early institution of intrathecal cytostatic agents may retard or prevent CSF dissemination and prolong survival. © 1994 Wiley-Liss, Inc.     

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??Objective??To explore the clinical characteristics of anti-N-methyl-D-aspartate receptor??anti-NMDAR??encephalitis in children. Methods??Between April 2015 and December 2015??fifteen children were diagnosed with this disorder at the Department of Neurology??Children’s Hospital of Fudan University. We retrospectively analyzed the data of clinical characteristics and laboratory examinations. Results????1??There were seven females and eight males??the median age of onset was 7 years old??ranging from 8 months to 12 years.??2??Clinical characteristics were as follows?? 3/15??20%?? had impaired consciousness along with convulsion?? and 4/15??26.7%?? had emotional and behavioral changes at the onset of disease. Seizures occurred in all the 15 children and status epilepticus in 3 cases. Facial and limb involuntary movements occurred in 12/15??80%??. Seven cases??46.7%?? demonstrated uroschesis. Three had hypoventilation. Two??13.3%?? were secondary to virus infection.??3??Imaging and laboratory examination showed that the white blood cell of cerebrospinal fluid??CSF?? in 5/15 cases??33.3%?? were moderately elevated. The protein of cerebrospinal fluid??CSF?? was obviously increased in 2 patient??13.3%??. IgG index was detected in 10 patients and increased in 4/10??40%??. All had cerebrospinal fluid antibodies. MRI was abnormal in 10/15??66.7%??. EEG typically showed diffuse background slowing??while no extreme delta brush was observed. One case??6.7%?? had a mass in ovary. All patients received intravenous methylprednisolone and immunoglobulins??IVIG??. One case??6.7%?? received plasma exchange. Follow-ups lasted for 1 to 6 months. The functional outcomes of 9 patients were favorable??mRS being 0 to 2. Conclusion??Due to the lack of specificity of clinical symptoms and laboratory examination??this disorder is difficult to diagnose at the onset. The disease can be diagnosed by the specific anti-NMDAR antibody in the cerebrospinal fluid. Tumors and delt brush are rarely found in children with anti-NMDAR encephalitis. Early diagnosis and timely initiation of immunosuppressive treatment will result in favorable outcome in the majority of the patients.     

Lumbar spinal fluid collections in children treated with intrathecal chemotherapy: elevated CSF protein as a diagnostic clue

Subdural fluid collections can interfere with the effective intrathecal administration of chemotherapy by lumbar puncture (LP). We detected this complication in six children who were treated for acute lymphoblastic leukemia (ALL) and presented with an elevated protein concentration of the cerebrospinal fluid (CSF) during routine LP. Contrary to expectation the lumbar fluid collections persisted in two cases and in one case required the insertion of an Ommaya reservoir to continue intrathecal chemotherapy. Awareness and detection of this complication by imaging is important because of its potential to interfere with effective CNS-directed chemotherapy of ALL.     

CTV化疗方案治疗视网膜母细胞瘤的不良反应及其防治

目的 观察CTV化疗方案治疗视网膜母细胞瘤的相关不良反应及其防治措施.方法 选取2008年1月至2008年12月临床确诊为视网膜母细胞瘤并化疗的患儿,共154例.采用CTV化疗方案(卡铂28 mg/kg、替尼泊苷8 mg/kg、长春新碱0.05 mg/kg),观察患儿化疗时及化疗后的不良反应.结果 未摘除眼球的眼内期患儿化疗后肿瘤明显缩小.化疗时及化疗后无任何不良反应者3例,占1.9%;有不良反应按WHO化疗不良反应分级为Ⅰ度者48例,占31.2%;Ⅱ度64例,占41.6%;Ⅲ度28例,占18.2%,Ⅳ度11例,占7.1%.不良反应主要为血液系统和消化系统症状、脱发,少数病例出现发热、过敏和周围神经症状;除脱发外,其余不良反应均恢复.结论 CTV化疗方案治疗视网膜母细胞瘤安全、有效.     

Response of Orbital and Central Nervous System Metastases of Retinoblastoma Following Treatment with Cyclophosphamide/Doxorubicin

A 3.5-year-old boy with orbital and central nervous system extension of unilateral retinoblastoma received chemotherapy consisting of intravenous cyclophosphamide and doxorubicin and intrathecal methotrexate. Complete shrinkage of orbital tumor, phthisis bulbi,'and disappearance of intracranial metastases occurred following chemotherapy. Response of the intra-cranial tumors reflected the combined effects of cyclophosphamide and doxorubicin; the contribution of each agent could not be assessed. Cerebrospinal fluid tumor cells persisted prior to delivery of craniospinal irradiation, and were detected again 6 weeks after completion of irradiation.