隐球菌性脑膜炎患者抗原及抗体检测的临床评价

目的:评价隐脑患者血液、脑脊液中抗原抗体检测的临床意义。方法:应用乳胶凝集试验和试管凝集法检测28例隐脑患者脑脊液和血液中的抗体和抗原并对部分患者的抗原抗体进行动态监测。结果:应用乳胶凝集试验检测,28例隐脑患者脑脊液和血液中的抗原全部阳性,15位患者血液中抗体12例阳性,3例阴性。结论:应用乳胶凝集法检测脑脊液和血液中的抗原对隐脑的早期诊断有重要临床诊断意义。动态监测抗原可对隐脑的治疗效果进行评价     

隐球菌性脑膜炎78例脑脊液细胞学改变

目的总结隐球菌性脑膜炎(CNM)的脑脊液标本细胞学检测资料,提高对隐球菌性脑膜炎的诊断。方法总结近6年(2003年1月至2008年7月)我院CNM的临床资料、脑脊液诊断情况。结果共78例患者,常规涂片墨汁染色首检阳性者48例(61.5%),26例(33.3%)重复送检时发现隐球菌,余4例(5.1%)墨汁染色始终呈阴性,靠隐球菌培养确诊。55例(70.5%)行细胞学检查的患者首次送检即直接找到隐球菌。结论脑脊液细胞学较常规涂片墨汁染色首检隐球菌阳性率更高。CNM的诊断有赖于脑脊液墨汁染色、细胞学检查、隐球菌培养等多种手段相结合以提高其阳性率。     

结核性脑膜炎的早期诊断

报道46例临床诊断为结核性脑膜炎、11例化脓性脑膜炎、11例病毒性脑膜炎和3例隐球菌性脑膜炎病人脑脊液中抗结核抗体分泌细胞和结核抗体阳性率的比较。结果提示:抗结核抗体分泌细胞阳性率89.1％,抗体阳性率为76.1％。抗体分泌细胞阳性率随病程延长而降低,抗体效价随病程延长而增高,提示抗结核抗体分泌细胞检测具有早期诊断结核性脑膜炎的特殊价值。     

新型隐球菌性脑膜炎与结核性脑膜炎的临床特点比较

目的对比和分析综合性医院新型隐球菌性脑膜炎(CNM)与结核性脑膜炎(TBM)的临床特点。方法分析62例CNM及219例TBM患者的一般资料、临床症状、脑脊液细胞学(CSFC)、头颅影像学的特点。结果两种脑膜炎均呈亚急性或慢性起病相对于TBM,CNM延误诊断时间更长、临床症状中癫痫出现比率(24.2%)、头颅影像学中脑膜强化出现比率(17.7%)较高,腰穿脑脊液(CSF)压力(268.7±67.6mmH_2O)、CSF单核细胞占比(21.0±17.5%)高,CSF白细胞计数(84.8±88.1×10~6/L)、CSF糖(1.9±1.4mmol·L~(-1))较低。结论两种脑膜炎临床表现不典型,两者之间不易鉴别,容易误诊漏诊。临床上需综合判断,CSF瑞氏吉姆萨染色和改良抗酸染色有助于两者病原学确诊。     

新型隐球菌颅内感染的临床表现及其抗原检测的临床应用

目的 探讨新型隐球菌性颅内感染的临床特点、脑脊液的相关检查和隐球菌抗原胶乳凝集系统检测的临床应用。方法应用临床病例分析统计方法，对本院78例确诊的新型隐球菌脑膜炎或脑炎患者的发病规律、临床特点和脑脊液检查进行归纳、分析，并进行脑脊液隐球菌抗原胶乳凝集系统的检测。结果78例患者中有69例（88．5％）为亚急性或慢性起病，9例（11．5％）为急性起病，64．1％以上的患者有头痛、发热；第1次腰穿隐球菌抗原胶乳凝集检查阳性者为97．4％。结论新型隐球菌颅内感染起病形式各异，临床表现、脑脊液常规、生化检查及头颅影像学检查均缺乏特异性；隐球菌抗原胶乳凝集对早期诊断新型隐球菌颅内感染有重要价值。     

隐球菌性脑膜炎23例脑脊液细胞学分析

目的分析隐球菌性脑膜炎脑脊液细胞学特点,比较脑脊液细胞学染色、墨汁染色、乳胶凝集实验检出隐球菌的敏感度及特异度,以提高对隐球菌性脑膜炎的认识。方法总结2008年1月至2013年2月确诊的23例隐球菌脑膜炎患者与同期住院的23例非隐球菌脑膜炎患者临床资料及脑脊液细胞学资料并予以分析。结果脑脊液细胞瑞氏吉姆萨染色检测灵敏度91.3%,明显高于墨汁染色灵敏度43.4%,差异有统计学意义(P0.05);脑脊液细胞学瑞氏吉姆萨染色检测特异度100%,明显高于乳胶凝集实验法特异度56.5%,差异有统计学意义(P0.05)。结论脑脊液细胞学检查比传统的墨汁染色法及乳胶凝集实验有更高的灵敏度及特异度,且更直接,是一种先进快捷便利的检测方法。     

60例中枢神经系统新型隐球菌感染脑脊液检测与临床分析

目的：分析中枢神经系统（ｃｅｎｔｒａｌ ｎｅｒｖｏｕｓ　ｓｙｓｔｅｍ,ＣＮＳ）新型隐球菌感染临床特征。方法：对 ６０例患者进行临床分析。结果：患者脑脊液呈无色浑浊、白细胞升高、其中以淋巴细胞和单核细胞为主。蛋白质升高、葡葡糖和氯化物减低,墨汁染色及苏木素－伊红染色均可发现新型隐球菌。几乎所有的患者有头痛、９０％有发热、７３％有呕吐、６５％有不同程度的意识障碍和偏瘫、约半数还有听力减退、双目失明和抽搐。结论：脑脊液墨汁或苏木素－伊红染色检查有助于鉴别。     

Monitoring of the cryptococcus count in the cerebrospinal fluid with negative cultures in two cases of serious cryptococcal meningitis]

We monitored the cryptococcus count in the cerebrospinal fluid(CSF) using the filter technique in two cases of serious cryptococcal meningitis during the course of treatment with antifungal agents. Lumbar puncture was performed once a week, and 1 ml of CSF was filtered through a Millipore filter(5.0-micron pore for cells), followed by staining of the filters with Alcian blue. All of the cryptococci on the filter were counted under a light microscope at a magnification of x 100. More than 500/ml and 2,000/ml of cryptococci were still observed in the CFS in Cases 1 and 2, respectively, in whom CFS cultures for Cryptococcus neoformans became negative after 4 weeks of treatment. Even though the treatment with antifungal agents were continued in these cases, cryptococci could still be observed for 5 weeks and 60 weeks on the filter preparations of Cases 1 and 2, respectively, after the CSF cultures became negative. The cryptococcal antigen could also be detected in the CSF during the positive filter preparations in these cases. At autopsy in Case 2, patchy lepromeningeal inflammatory lesions with the characteristic capsules of cryptococci were observed in the subarachnoid space. These observations suggest that cryptococci, which persisted in the CSF despite the negative cultures, were responsible for the lesions in the subarachnoid space and protracted clinical course in the two cases of cryptococcal meningitis.     

A case of Mycobacterium fortuitum meningitis following surgery for meningioma]

A 57-year-old woman had undergone surgery for meningioma. After the surgery, she suffered from repeated fever and headache. One year after surgery, she was admitted to our hospital for further examination. Cerebro-spinal fluid (CSF) findings indicated bacterial meningitis infection. Germ culture, acid-fast bacterium culture, PCR for mycobacteriosis and cryptococcus antigens as well as cytological examination of CSF were checked repeatedly. However, all examinations were negative and etiology was unknown. We treated with many anti-bacterial, anti-fungal and anti-tubercular drugs, but CSF findings were not improved. We repeated CSF examination and finally Mycobacterium fortuitum (M. fortuitum) was isolated. Clarithromycin (CAM) was started for M. fortuitum meningitis. After drug sensitivity testing, levofloxacin (LVFX), which was effective against M. fortuitum, was added to CAM, after which clinical and CSF findings improved dramatically. M. fortuitum rarely causes CNS infection. Several English literatures on M. fortuitum meningitis after traumatic injury and surgery have been published. Its CSF findings distinctly resemble those of bacterial meningitis, but are resistant to the usual antituberculosis drugs. We reported a case of M. fortuitum meningitis associated with surgery for meningioma.     

CSF in 85 patients with AIDS and CNS cryptococcosis.

In an eight years time period (July 1984-June 1992) CSF samples of 40718 patients were studied, and 610 were from patients with AIDS clinically diagnosed and immunologically confirmed through HIV antibodies detection. Among opportunistic infections detected in them 85 were CNS cryptococcosis. For the purpose of this study the CSF of these 85 patients are the AIDS group of CNS cryptococcosis. For comparison, CSF data from 50 patients with CNS cryptococcosis but without AIDS were taken (non-AIDS group); in this group, 22 patients were immunosuppressed after renal transplant. In AIDS group, the more frequent CSF findings were: yeast presence at direct exam (Fuchs-Rosenthal cell counting chamber), growing of the yeast in cultures, and gamma globulins increase. In non-AIDS group were more frequent: hypercytosis, neutrophil cells presence, and total protein increase. Differences between the two groups are discussed taking into account CNS/CSF immune changes induced by HIV infection. It is concluded that in CNS cryptococcosis of patients with AIDS the CSF evidenced more extensive signs of the fungal opportunistic infection than signs of inflammatory response to the infection. The latter were more prominent among patients of the non-AIDS group of CNS cryptococcosis.     

Cerebrospinal fluid in infection of the central nervous system by yeasts of the genus Candida: analysis of 11 cases

This study is based on the analysis of 44 cerebrospinal fluid (CSF) samples from 11 patients with central nervous system (CNS) Candida infection. Risk factors for CNS fungal infection were present in all patients. Five had a chronic meningitis syndrome; two had acquired immunodeficiency syndrome (AIDS); two had cranial trauma followed by chronic meningities; one had intravascular disseminated coagulation syndrome and sepsis; and one had systemic candidiasis after kidney transplant. Etiological diagnosis was made in all by the CSF examination. Nine cases had positive CSF culture for Candida. Two patients presented the yeast in the direct examination, and one of them had reagent complement fixation test for Candida in three successive samples of CSF. Changes found in the CSF composition are discussed in order to evaluate the inflammatory response to CNS infection by Candida.     

Candida parapsilosis meningitis associated with shunt infection in an adult male

Candida parapsilosis is a very rare cause of meningitis. Though several cases have now been reported in neonates and children, only one has been described in an adult. We report on a 55-year-old male that was admitted due to altered mental status. He had recent sinus drainage and polypectomy, craniotomy with drainage of brain abscess, and ventriculo-peritoneal shunt placement. On admission, imaging studies showed no evidence of shunt dysfunction but did reveal extensive white matter decreased attenuation. Microscopic examination of the first 10 daily cerebrospinal fluid (CSF) cultures revealed yeast. Flucytosine and liposomal amphotericin B were started and externalization of shunt was performed on day 3. On day 8, CSF culture from admission grew C. parapsilosis; fluconazole was added. On day 10, daily CSF still showed yeast and cultures consistently grew C. parapsilosis. Shunt was removed and bilateral ventriculostomy drains were inserted. CSF after procedure as well as at follow-up examinations throughout his 3-month hospitalization were negative for yeast. Extended treatment with flucytosine and fluconazole was initiated. At 8-month follow-up, successful treatment of C. parapsilosis infection without recurrence was confirmed. This case underscores the need for suspicion of C. parapsilosis as a cause of meningitis after invasive surgeries in adults.     

Chronic relapsing experimental allergic encephalomyelitis: cerebrospinal fluid cytology and a comparison with meningeal and spinal cord pathology

Cerebrospinal fluid (CSF) was taken from strain 13 guinea pigs in various stages of chronic relapsing experimental allergic encephalomyelitis, the spinal cords removed for histological examination and meningeal stretch preparations made. CSF cells were counted and characterized by morphological studies, anti-IgG and alpha-naphthyl acetate esterase (ANAE) staining. Approximately 65% of normal CSF lymphocytes were ANAE positive and 10% stained with anti-IgG. No polymorphonuclear leucocytes were seen. Five out of eight relapsing animals had raised cell counts (up to 152/μl) as did three animals in remission. There was no change in the proportion of various types of CSF cells where increased numbers were recorded. Infiltrating cells in spinal cord sections and meningeal preparations were similarly characterized and the results compared with CSF cell findings. Animals in relapse which had, in addition, macroscopically visible cord plaques showed the most severe infiltrative changes in spinal cord tissue and in the meninges. There were differences between the proportion of various types of CSF cells and meningeal infiltrate cells on ANAE staining reaction. In general there were far more lymphocyte-type cells in the CSF but more monocyte-type cells in meningeal infiltrates.     

Accumulation of class switched IgD-IgM- memory B cells in the cerebrospinal fluid during neuroinflammation

Inflammatory diseases of the central nervous system (CNS) are characterized by cerebrospinal fluid (CSF) pleocytosis often involving the recruitment of B cells. Little is still known about B cells that are found in the CSF during neuroinflammation. To address the phenotype of these B cells, we studied the distribution of the major B cell subsets in peripheral blood (PB) and CSF of 25 patients with inflammatory diseases of the nervous system by flow cytometry. Six different B cell subsets were identified in PB and CSF according to the surface expression of IgM, IgD, CD27 and CD19. In all patients analysed, memory B cells outnumbered naïve B cells in the CSF, whereas naïve B cells were more prevalent in PB. The accumulation of memory B cells in the CSF was largely due to the recruitment of IgM−IgD− class switched memory B cells. The distribution of IgM+IgD+, IgM−IgD+, IgM+IgD− memory cells and immature cells did not differ significantly between CSF and PB. These findings demonstrate a selective recruitment of IgM−IgD− memory B cells to the CSF suggesting a specific role of these cells during neuroinflammation.     

Biased expression of T cell receptor genes characterizes activated T cells in multiple sclerosis cerebrospinal fluid

To better characterize the inflammatory response that occurs in the nervous system in multiple sclerosis (MS), T-cell receptor (TCR) gene expression was quantified from cerebrospinal fluid (CSF) cells of 21 patients with active disease. Unstimulated CSF cells expressed each of 22 different TCR beta chain variable region (Vβ) gene families in proportion to their expression in simultaneously sampled peripheral blood. When CSF cells from individuals with MS were expanded by in vitro culture in T-cell growth factor/interleukin 2 and 4-containing medium (TCGF/IL2/IL4), restricted numbers of Vβ genes were expressed. In many subjects, expanded CSF cells expressed predominantly Vβ2. In contrast to CSF, expansion of corresponding peripheral blood mononuclear cells (PBMC) in TCGF/IL2/IL4 resulted in persistent expression of an Vβ gene families. Within individuals, different Vβ genes were overexpressed by PBMC compared with CSF cells. No effect of the HLA haplotype of the individual on CSF Vβ gene expression was observed. Expanded CSF cells retained their capacity to respond to mitogen stimulation, but the proliferative response to myelin basic protein (MBP) was not enhanced. Finally, freshly obtained CSF cells stimulated directly with MBP also expressed a limited number of Vβ genes, although these were generally different from patterns observed following stimulation with TCGF/IL2/IL4. Thus, restricted populations of T cells capable of responding to TCGF/IL2/IL4, presumably reflecting in vivo activated cells, are compartmentalized in the nervous system in MS. © 1996 Wiley-Liss, Inc.     

Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration

Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from oxidized CSF lipoproteins in culture. Since inheritance of different alleles of the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to neurons. To test this hypothesis, we adapted a method previously used with isolated plasma lipoproteins to specifically label lipid particles in situ in native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma cells. CSF lipoproteins were delivered to neuronal cells largely through apoE-dependent processes. Importantly, CSF lipoproteins from AD patients were delivered more efficiently than CSF lipoproteins from age-matched controls; this effect was not associated with apoE genotype or degree of CSF lipoprotein oxidation but was associated with apoE monomer concentration that tended to be lower in AD patients. The inverse relationship between apoE monomer concentration and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human astrocytoma cells, using artificial lipid particles and purified human apoE. These results suggest that lipoproteins in CSF from AD patients are delivered more efficiently to neurons than are CSF lipoproteins from controls, and that this abnormality may be explained largely by variations in CSF apoE concentration.     

Asymptomatic oligoclonal CSF IgG and progressive increase of intrathecal IgG synthesis in a patient with myasthenia gravis treated with thymectomy--a 4-years follow-up

A young woman is described who had myasthenia gravis which was favourably influenced by thymectomy. Although there was no evidence for another neurological disease over 7.5 years of clinical observation and computed tomography as well as visual evoked response were normal, CSF studies over 0.5 years prior to and 3.5 years after thymectomy revealed persistent mononuclear pleocytosis, high CSF IgG index, oligoclonal IgG bands in CSF, and increasing IgG synthesis rate within the CNS, reflecting a continuous local humoral immune response. CSF/serum ratios of antibodies to acetylcholine receptors (AChR) were continuously lower than CSF/serum IgG ratios, contradicting intrathecal AChR antibody production. Proportion of total T cells was slightly higher in CSF than peripheral blood, while active T cells were lower in CSF. CSF lymphocytes did not proliferate on PHA stimulation but responded in allogeneic mixed lymphocyte culture. B cells were 4% in CSF and 4.5% in peripheral blood, but 227 IgG, 0 IgA and 0 IgM producing cells were detected among 20 X 10(3) CSF lymphocytes, compared to 5, 4 and 0 in 20 X 10(3) peripheral blood lymphocytes. This patient represents an in vivo 'experiment' regarding influence of thymectomy on CSF compartment constituents. The present study also shows that an individual can be clinically healthy despite continuous and pronounced intrathecal immune response.     

脑脊液细胞学在中枢神经系统白血病诊治中的应用

目的探讨脑脊液细胞学在中枢神经系统白血病(CNSL)的诊断、病情进展及指导治疗中的作用。方法采用粟氏FMU-5型细胞玻片离心沉淀仪收集脑脊液细胞,迈-格-姬(MGG)染色,显微镜下进行细胞分类,计数白血病细胞所占的百分比。分析2000～2008年我院住院的58例CNSL患者的脑脊液细胞学检查结果。结果 58例患者包括19例儿童和39例成人病例。其脑脊液细胞学均发现白血病细胞,占脑脊液细胞的5～96%。其中5例首次检测诊断为CNSL后失访,其余病例均于治疗过程中重复进行脑脊液细胞学检查。白血病细胞所占比例多数呈不同程度的降低,直至完全消失;11例比值出现反复,最终逐渐降低;8例未见明显降低。结论脑脊液细胞学检查对CNSL的诊断、治疗及预后评估具有重要的临床意义。     

Supplementary cytodiagnostic analyses of mononuclear cells of the cerebrospinal fluid using cytological markers

Summary Various methods of CSF cell differentiation are discussed. These methods provide additional information regarding the origin and, therefore, the types of pathological alterations occurring in the leptomeninges. They include the application of immunological and cytochemical markers to differentiate and identify B and T lymphocytes as well as cells from the monocyte-macrophage series and precursor cells of polymorphnuclear leukocytes. Application of these methods to CSF cells and the differentiation of CSF cells from 16 patients with inflammatory or neoplastic alterations were discussed. B cell or T cell type lymphocytes predominate with multiple sclerosis, T lymphocytes with tubercular meningitis. Varying quantities of B and T lymphocytes are found with viral meningitis. In one case the tumor cells of a reticulum cell sarcoma were identified in the CSF as T cells; in one case of plasmacytoma, tumor cells in the CSF were identified as B lymphocytes. In selected cases of leukemic or carcinomatous infiltration of the meninges and of medulloblastoma, CSF cells did not react to treatment with immunological markers.This study was supported by the Deutsche Forschungsgemeinschaft     

CSF cells in multiple sclerosis: monoclonal antibody analysis and relationship to peripheral blood T-cell subsets

Mononuclear cells were analyzed in CSF and blood of 102 patients with MS. In CSF, the majority (78%) of cells were T lymphocytes (T3+), and the ratio of inducer (T4+) to suppressor/cytotoxic (T8+) cells was 2:1. No characteristic alterations in CSF phenotypes could be related to changes in circulating T8 cells or to disease activity. In a group of 75 patients, CSF cell count was higher in patients with low numbers of circulating T8 cells than in those with normal T8 cells. Thus, decreases in suppressor cells in the blood of MS patients are associated with CSF pleocytosis but not with fluctuations in the ratio of different subsets in CSF. Furthermore, large numbers of T8 cells are not sequestered in CSF when these cells are decreased in peripheral blood.