Immunoglobulins in cerebrospinal fluid in central nervous system disorders

Immunoglobulins were estimated in the cerebrospinal fluid from 70 cases of nervous system diseases. Thirty childern with evidence of C.N.S. irritation without infection served as controls. The immunoglobulins were higher in cases with C.N. S infections. Within this group meningeal involvement (tubercular and pyogenic) resulted in a significant rise in IgG compared to viral encephalitis. The proportion of immunoglobulin in the CSF protein can be helpful in distinguishing TBM from PM.     

Interleukin-6 in cerebrospinal fluid of patients with central nervous system infections

Interleukin(IL)-6 levels were measured in cerebrospinal fluid (CSF) and serum samples from pediatric patients with central nervous system (CNS) infections by means of an enzyme-linked immunosorbent assay. Mean IL-6 concentrations in CSF samples from patients with bacterial meningitis (49017 44 730 pg/ml) were significantly higher than those in patients with aseptic meningitis (10761572 pg/ml) or encephalitis (409835 pg/ml). In aseptic meningitis and encephalitis, IL-6 levels in serum were within the lower ranges (< 100 pg/ml), in contrast with the highly elevated levels found in bacterial meningitis (14 33218 385 pg/ml). In 5 of the 15 patients with encephalitis, elevated levels of IL-6 were observed in the initial CSF samples despite normal findings of routine CSF examinations. Also, sequential CSF samples revealed that there was an increase in the CSF cell count in two of the five patients. These results validated the potential of measuring IL-6 in CSF samples for the purpose of providing additional information on routine laboratory test results. D Central nervous system infection, cerebrospinal fluid, children, enzyme-linked immunosorbent assay, interleukin-6.
M Narita, Department of Pediatrics, Hokkaido University School of Medicine, N 15 W 7, Kita-ku, Sapporo 060, Japan     

Elevation of cerebrospinal fluid sialic acid concentration in children with central nervous system leukemia

We studied sialic acid in the cerebrospinal fluid (CSF) of 52 children with leukemia and 51 children with non-leukemic diseases. The CSF sialic acid concentration in the children with central nervous system (CNS) leukemia was significantly higher than that in the children with acute lymphoblastic leukemia without CNS involvement, acute non-lymphocytic leukemia without CNS involvement, non-hemopoietic diseases, non-suppurative meningitis, epilepsy, and other neurologic diseases. Serial determinations revealed a rapid decline in the CSF sialic acid concentrations in the patients with CNS leukemia who responded well to the therapy and who were free from relapse of CNS leukemia. The simultaneously determined CSF beta 2 microglobulin concentration did not show any significant changes. These results suggest that the CSF sialic acid may be a good indicator of CNS leukemia.     

Enzymatic changes in the cerebrospinal fluid in patients with infections of the central nervous system

Enzymatic determinations in cerebrospinal fluid (CSF) of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), gammaglutamyl transpeptidase (GGT), creatine phosphokinase (CPK) and creatine kinase BB (CK-BB) were performed in 16 patients with aseptic meningitis (AM), in 25 children with bacterial meningitis (BM) and in 15 patients with meningism. The activity of AST and GGT was significantly higher in patients with BM on admission compared with those with AM and meningism (p < 0.05 and p < 0.005, respectively) and decreased with therapy. The highest concentration of AST and LDH appeared in patients with poor outcome as well as in those with ventriculomegaly on neurosonography (p < 0.05). The concentration of CK-BB increased in all patient groups on admission and remained higher on termination of therapy. The present study confirms the high activity of AST and GGT in BM patients in the CSF whereas the increased activity of AST and LDH reflects the extent of brain injury. Nevertheless, the prognosis for individual patients cannot be established on the basis of enzyme activity alone, but depends on several factors.□     

脑脊液细胞因子检测在小儿中枢神经系统感染鉴别诊断中的意义

目的　探讨脑脊液 (CSF)γ 干扰素 (IFN γ)、粒细胞集落刺激因子 (G CSF)、α肿瘤坏死因子 (TNF α)、白细胞介素 6 (IL 6 )及白细胞介素 8(IL 8)的变化在小儿中枢神经系统感染 (CNSI)中的诊断价值。方法　采用双抗体夹心ELISA法检测 14例化脓性脑膜炎 (PM)、30例病毒性脑膜炎 (VM)及2 2例非中枢神经系统感染患儿CSF中IFN γ、G CSF、TNF α、IL 6及IL 8水平。结果　PM组G CSF及IL 8[(132± 4 1)、(2 5 3± 0 5 6 ) μg/L]水平明显高于VM组 [(5 3± 2 2 )、(0 5 3± 0 4 6 ) μg/L](P <0 0 0 1) ;IFN γ在VM组 [(2 0± 0 4 ) μg/L]水平明显高于PM组 [(0 8± 0 5 ) μg/L](P <0 0 1) ;各脑膜炎组中TNF α及IL 6水平均高于对照组 (P <0 0 0 1) ,但各组间比较差异无显著性。G CSF及IL 8水平增高程度与CSF中性粒细胞计数呈正相关 ;IFN γ增高程度与CSF白细胞数及葡萄糖定量间无相关性。结论G CSF、INF γ及IL 8在CSF中显著增高有助于PM与非PM的鉴别诊断 ;TNF α、IL 6在感染性脑膜炎发病过程中的作用是非特异性的 ,其在CSF中的变化对感染性脑膜炎患儿鉴别诊断无临床意义     

Detection of MYCN DNA in the cerebrospinal fluid for diagnosing isolated central nervous system relapse in neuroblastoma

We present the case of a 1-year-old female with stage-4 neuroblastoma with MYCN amplification; she was treated with five chemotherapy courses, resulting in normalization of elevated serum levels of tumor markers. Complete remission was achieved after allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning. Nine months later, however, the tumor relapsed in the central nervous system (CNS). The serum and cerebrospinal fluid (CSF) levels of the tumor markers were normal, but the MYCN copy number was high only in the CSF DNA, suggesting an isolated CNS recurrence. The MYCN copy number in the CSF DNA was reflective of response to treatment.     

脑脊液游离轻链检测在儿童中枢神经系统感染中的应用

目的探讨脑脊液(CSF)游离轻链检测在儿童中枢神经系统感染中的应用价值。方法用BN-Ⅱ特定蛋白分析仪检测24例病毒性脑炎患儿、7例化脓性脑膜炎患儿及12例CSF正常患儿的血清及CSF中白蛋白(ALB)、免疫球蛋白G(IgG)、游离轻链;用免疫固定电泳检测IgG寡克隆区带;计算白蛋白商值(QALB)、IgG商值(QIgG)、Kappa商值(Qκ)、Lamda商值(Qλ),并进行对比分析。结果所有患儿CSF寡克隆区带均为阴性;病毒性脑炎组和化脓性脑膜炎组患儿的QALB、QIgG、Qκ、Qλ显著高于CSF正常对照组(P均<0.05),化脓性脑膜炎组QALB、QIgG显著高于病毒性脑炎组(P均<0.01),病毒性脑炎组Qκ、Qλ与化脓性脑炎组比较,差异均无统计学意义(P>0.05);QIgG、Qλ随血脑屏障损害程度的加深呈递增趋势(P均<0.05);所有研究对象的QALB与QIgG、QALB与Qκ、QALB与Qλ、QIgG与Qκ、QIgG与Qλ、Qκ与Qλ均有相关性(r=0.320～0.814,P均<0.05)。结论游离轻链检测对儿童化脓性脑膜炎和病毒性脑炎的诊断有较大帮助,且Qλ能较好的反映患儿血脑屏障的损伤程度。     

Human herpes virus type 7 DNA in the cerebrospinal fluid of children with central nervous system diseases

Human herpes virus type 7 (HHV-7) has been associated with unspecific febrile syndrome, exanthem subitum (ES), viral rashes and Epstein-Barr virus (EBV) like syndrome. Neurological complications such as hemiplegia or seizures have been described in a few children with ES. Whether HHV-7 may also affect the CNS in the absence of ES is unknown. In this study, we investigated CSF samples from children with different neurological diseases for the presence of HHV-7 specific DNA. A HHV-7 specific nested polymerase chain reaction (PCR) was established amplifying a 478 bp DNA sequence of the glycoprotein U23 of HHV-7 strain SB. 68 children with CNS diseases with inflammatory CSF findings (n=24), CNS diseases without inflammatory CSF findings (n=18) and febrile seizures (n=26) were examined. A total of 26 children with infectious diseases in the absence of neurological disease and 11 children without signs of a peripheral infection and without neurological disease served as controls. The CSF samples of six children from the study groups were HHV-7 PCR positive, but none from the controls. These children were diagnosed with aseptic meningitis (n=1), viral encephalitis/meningoencephalitis (n=2), facial palsy (n=1), vestibular neuritis (n=1) and febrile seizure (n=1). Conclusion These results indicate that human herpes virus type 7 infection is associated with central nervous system disease in children and should be considered in children whether inflammation in the cerebrospinal fluid is present or not. Received: 4 September 2000 and in revised form: 2 December and 23 December 2000 /  Accepted: 27 December 2000     

Electrical resistance of cerebrospinal fluid in inflammatory diseases of central nervous system in children (author's transl)]

The specific electrical resistance of the cerebrospinal fluid was measured by means of conductometry in 14 cases of meningitis purulenta, 17 cases of meningitis serosa, 10 cases of encephalitis and in 32 control subjects. The mean value was found to be significantly increased in meningitis purulenta in comparison to the control group. The differences between the average values of the electrical resistance concerning other groups studied were found to be unsignificant. In some cases the initially increased electrical resistance of cerebrospinal fluid observed in the acute state of the disease reached the normal levels at the time of clinical improvement. The presumable causes of these phenomena are discussed.     

中枢神经系统感染患儿脑脊液和血清胰岛素样生长因子Ⅱ水平的变化及意义

目的　探讨中枢神经系统 (CNS)感染患儿脑脊液 (CSF)中胰岛素样生长因子 Ⅱ (IGF Ⅱ )水平的变化及其与CSF中葡萄糖浓度、蛋白质浓度和白细胞计数的关系。方法　 45例CNS感染患儿分为 2组 ,其中细菌性脑膜炎 (BM) 2 4例、病毒性脑炎 (VE) 2 1例 ,取 15例无神经系统疾病患儿的CSF作为对照组。用免疫放射分析法 (IRMA)测定CSF中IGF Ⅱ的浓度。结果　 1.BM组CSF中IGF Ⅱ浓度 64 .5 6± 49.61ng/ml显著高于VE组 3 1.41± 7.16ng/ml(P <0 .0 1)和对照组 2 7.19± 6.85ng/ml(P <0 .0 1) ;2 .CSF中IGF Ⅱ浓度与CSF中葡萄糖浓度呈负相关 (r =- 0 .5 61　P <0 .0 1) ,与CSF中蛋白浓度呈正相关 (r =0 .83 9　P <0 .0 0 1)。结论　1.IGF Ⅱ参与CNS感染的病理生理过程 ;2 .IGF Ⅱ可能参与CNS感染时CSF中葡萄糖和蛋白浓度变化的调节 ;3 .测定CSF中IGF Ⅱ浓度可对BM和VE的鉴别诊断提供帮助。     

中枢神经系统疾病患儿血清和脑脊液髓鞘碱性蛋白的定量分析

目的　探讨小儿中枢神经系统（ＣＮＳ） 疾病脑脊液（ＣＳＦ） 和血清髓鞘碱性蛋白（ ＭＢＰ） 水平的改变及临床意义,寻找反映小儿ＣＮＳ损伤的生化指标。方法　证实为ＣＮＳ疾病的患儿８５ 例,其中男５８ 例,女２７ 例,年龄１ 月～１３ 岁。采用ＥＬＩＳＡ 法对病例血清及部分病例ＣＳＦ标本作ＭＢＰ定量测定。结果　疾病组中ＣＮＳ感染、颅内出血、及颅内占位性病变等病例中ＣＳＦ和血清ＭＢＰ均值都明显高于正常对照组。结论　任何原因导致ＣＮＳ髓鞘结构的破坏时,其ＭＢＰ在ＣＳＦ的水平升高,当血清ＭＢＰ含量也升高时,提示血脑屏障（ＢＢＢ） 破坏,通透性升高。结果显示对ＣＳＦ和血清ＭＢＰ的检测,可作为一项反映ＣＮＳ损伤的生化指标。     

中枢神经系统感染脑脊液肿瘤坏死因子及其意义

探讨化脓性脑膜炎、病毒性脑膜炎或脑炎患儿脑脊液肿瘤坏死因子（TNF）的临床意义。方法采用TNF放免药盒，测定化脑组21例、病毒脑28例、对照组20例的脑脊液TNF。结果化脑组脑脊液TNF阳性率显著高于病毒脑组，化脑组脑脊液肿瘤坏死因子升高的平均浓度显著高于病毒脑组，差异有高度统计学意义。结论对接受过抗生素治疗而诊断不明者，可行脑脊液TNF检测，高水平则提示化脓性脑膜炎。     

蛋白质组学在神经系统疾病中的应用

蛋白质组学的概念自提出以来 ,研究方法中双向凝胶电泳、质谱分析、计算机软件分析等技术的发展突飞猛进 ,研究范围不断扩展 ,目前已成为生物医学领域中极其活跃的学科。蛋白质组学为人类疾病的研究提供了崭新的思路和技术 ,在对中枢神经系统疾病的研究中 ,通过表达蛋白质组学和细胞图谱蛋白质组学揭示其发病机制 ,为寻找疾病特异性蛋白质协助诊断和寻找药物作用的专一靶点协助治疗等提供了一种有力的工具 ,国内外在这方面的研究已取得了一定的进步     

中枢神经系统感染血浆及脑脊液中心钠素水平与低钠血症的关系

目的　 探讨心钠素 (ANP)在中枢神经系统 (CNS)感染及合并低钠血症中所起的作用及意义。 方法 　应用放射免疫法检测 45例中枢神经系统感染患儿血浆及脑脊液中ANP的水平 ,同时检测血清钠的含量 ,并与 12例对照组比较。 结果 　(1)急性期患儿血浆ANP均高于对照组 (P <0 0 1) ,并发症组患儿升高更明显 (P <0 0 0 1) ;急性期儿脑脊液ANP均低于对照组(P <0 0 1) ,并发症组儿降低尤其明显 (P <0 0 0 1) ;(2 )中枢神经系统感染患儿血浆ANP与血清钠水平呈负相关 (r =-0 748,P<0 0 5 ) ,脑脊液ANP水平与血清钠无显著相关 (r =0 2 17,P >0 0 5 )。 结论 　 (1)中枢神经系统感染患儿血浆及脑脊液ANP水平反映脑损伤严重程度和预后 ;(2 )ANP参与低钠血症形成过程     

肠道病毒中枢神经系统感染患儿脑脊液中VP1序列的分子分型研究

目的 探讨肠道病毒(EV)中枢神经系统感染患儿脑脊液(CSF)中VP1序列分子分型研究的临床价值.方法 2003年1月至2005年12月青岛大学附属医院和滨州医学院附属医院采用通用引物和VP1段分子分型引物分别对63例无菌性脑膜炎和脑炎惠儿急性期和恢复期的CSF标本进行扩增,对VP1分型引物扩增阳性片段进行克隆、测序及分型研究.结果 采用通用引物经2次PCR检测急性期患儿的CSF标本共47例(47/63,74.6%)阳性,恢复期仅3例(3/57,5.3%)阳性.采用分型引物经2次PCR检测通用引物扩增阳性的47例急性期的CSF标本共3l例(62.0%)阳性,其中4例脑炎和20例脑膜炎进行了序列测定.测序结果通过BLAST软件进行同源性对比分析,发现同-型别内序列同源性在97%～99%,不同型别之间同源性只有74%～76%,其中COX B3(9例)、ECHO 12(7例)、ECHO 30(3例)、COX A7(2例)、COX A9(1例)、COX B5(1例)、COX A11(1例).所有CSF进行病毒分离,11例(11/63,17.5%)阳性,阳性率明显低于VP1段分子分型的检测结果,除1例CSF标本病毒分离为ECHO7的患儿,通用引物扩增阳性而VP1分型引物扩增失败外,其余血清型别与VP1段分子分型研究结果完全-致.结论 EV是儿童无菌性脑膜炎和脑炎最重要的病原体;采用通用引物所建的RTPCR是快速检测EV中枢神经系统感染的有效方法;分型引物扩增VP1部分序列并测序,与GENBANK中的EV标准毒株进行对比,根据基因序列的同源性进行EV分型,为EV的分型研究提供了新的方法和思路.