Experimental meningitis in the rabbit. I. Arterial blood pressure and acid-base balance during halothane anesthesia and in situ freezing of the brain

Effects of halothane/N2O anesthesia and in situ freezing of the brain on mean arterial blood pressure (MABP), pH, pCO2 and pO2 were evaluated in rabbits with either Streptococcus pneumoniae or Escherichia coli meningitis. Prior to anesthesia infected rabbits had, compared to controls, significantly lower values for MABP and pCO2, either with a compensated (S. pneumoniae group) or decompensated (E. coli group) metabolic acidosis. In most animals a slight additional decrease in MABP was observed during anesthesia. With maintained pre-anesthetic hypocapnia no further disturbance in acid-base balance occurred during anesthesia. After one minute of freezing MABP increased towards preanesthetic levels. We conclude that the technique for in situ freezing of the brain under halothane/N2O anesthesia may be applied for studies of cerebral metabolism in rabbit with experimental meningitis.     

Utility of cerebrospinal fluid cortisol level in acute bacterial meningitis

Background:

Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known.

Objective:

To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis.

Materials and Methods:

Thirty patients with acute bacterial meningitis with no prior treatment were evaluated. Cortisol levels were compared with 20 patients with aseptic (viral) meningitis and 25 control subjects.

Results:

Mean CSF cortisol level was 13.85, 3.47, and 1.05 in bacterial meningitis, aseptic meningitis, and controls, respectively. Mean CSF cortisol level in bacterial meningitis was significantly higher as compared to controls (P < 0.001). There was significant difference in CSFcortisol levels in bacterial and aseptic meningitis (P < 0.001).

Conclusions:

Cortisol levels in CSF are highly elevated in patients with acute bacterial meningitis. This suggests that intrathecalcortisol may serve as a valuable, rapid, relatively inexpensive diagnostic marker in discriminatingbetween bacterial and aseptic meningitis. This helps in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality.     

Cerebrospinal fluid lactate in post-neurosurgical bacterial meningitis diagnosis

Background

Differential diagnosis between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. Inflammatory and biochemical cerebrospinal fluid (CSF) changes mimic those classically observed after CNS surgery. CSF lactate assay has therefore been proposed as a useful PNBM marker.

Objective

To evaluate the diagnostic accuracy of CSF lactate as a PNBM marker in patients hospitalized after a neurosurgical procedure.

Methods

Between July 2005 and June 2009, a prospective clinical study, in which all patients with clinical suspicion of PNBM were enrolled, was conducted at our neurosurgical Intensive Care Unit. PNBM diagnosis was categorized as proven, probable or negative before the analysis.

Results

Seventy-nine patients, 51 males with a mean age of 50 years (range 32–68 years) were included. Surgery was elective in 76% patients, mostly for brain tumors (57%); thirty PNBM episodes were identified. CSF parameters were significantly different in glucose concentration (27 mg% vs. 73 mg%, p < 0.001), lactate (8 mmol/L vs. 2.8 mmol/L, p < 0.001), CSF neutrophil pleocytosis (850 mm^–3 vs. 10 mm^–3, p < 0.001), and protein levels (449 mg% vs. 98 mg%) between the PNBM and non-PNBM groups. The ROC curve that best fits PNBM diagnosis is lactate.

Conclusion

Increased CSF lactate is a useful PNBM marker, with better predictive value than CSF hypoglycorrhachia or pleocytosis. Lactate levels ≥4 mmol/L showed 97% sensitivity and 78% specificity, with a 97% negative predictive value.     

脑脊液检测对隐球菌性脑膜炎的临床意义

目的探讨脑脊液(CSF)检测对隐球菌性脑膜炎(CM)的临床诊断、治疗及预后的意义。方法分析36例CM患者的CSF动态变化、疗效及转归。结果 CM患者在治疗前32例(88.9%)CSF压力升高、34例(94.4%)墨汁染色阳性、26例(72.2%)白细胞总数升高、33例(91.7%)蛋白质含量升高、27例(75.0%)氯化物含量降低,治疗后6例(33.3%)脑脊液压力升高、4例(22.2%)墨汁染色阳性、8例(44.4%)白细胞总数升高、10例(55.6%)蛋白质含量升高、4例(22.2%)氯化物含量降低,且上述指标均呈动态变化。36例患者中治愈17例(47.2%),好转10例(27.8%),死亡9例(死于脑疝)(25%)。结论脑脊液检查是CM临床诊断最重要的手段,在治疗过程中可作为动态观察CM疗效的指标。     

Comparative analysis of cerebrospinal fluid adenosine deaminase in tuberculous and non-tuberculous meningitis

Objective

To calculate cut-off point for the adenosine deaminase (ADA) activity in the CSF of patients with tuberculous meningitis (TBM).

Patients and methods

The ADA assay was based on the automatic indirect method in which ADA catalyzes adenosine to inosine. ADA activity in the CSF was calculated based on ammonia liberated from adenosine and quantified spectrophotometrically. Arithmetic mean values and standard deviation of each variable were measured. Mann–Whitney U and Fisher exact tests were applied to compare continuous and dichotomous variables between tuberculous and non-tuberculous groups. A receiver operating characteristic curve was plotted to identify various cut-off points to determine the best level for ADA activity.

Results

Totally 42 patients were enrolled into the study. The median of ADA activity in the TBM group was 22 and in the non-TBM group was 8.0. The mean CSF-ADA activity was found to be significantly higher in TBM group (23.05 ± 13.1 IU/L) than in the CSF from non-TBM patients (9.39 ± 5.18 IU/L). The highest accuracy is at the cut-off value of 10.5 IU/L. The sensitivity and specificity of the test at this cut-off to differentiate TBM from non-tuberculous meningitis is 81% and 86% respectively.

Conclusion

Considering that a high positive value of ADA activity cannot confirm TBM, however, in suspected patients it may lead the physician to treat patient earlier before the confirmatory diagnostic reports will be received. The suggested cut-off value in this pilot study is 10.5 IU/L with high sensitivity and specificity.     

Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis

Matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by gelatin zymography and an enzyme-linked immunosorbent assay (ELISA) in a cerebrospinal fluid (CSF) from patients with tuberculous meningitis (n=24), acute aseptic meningitis (n=23) and the control (n=10). The MMP-2 and MMP-9 levels were significantly higher in the samples from the tuberculous meningitis patients than those from either the aseptic meningitis patients or the controls. In tuberculous meningitis, the patients with late neurologic complications had higher MMP-2 and MMP-9 levels than those without. The persistent increase in the MMP-2 and MMP-9 levels was associated with the development of complications following tuberculous meningitis. Inhibiting the MMPs may be an effective strategy for preventing or reducing the complications in tuberculous meningitis.     

Polymorphonuclear pleocytosis in the cerebrospinal fluid during chemotherapy for tuberculous meningitis

Summary Five patients on chemotherapy for tuberculous meningitis developed sudden and unexpected cerebrospinal fluid pleocytosis consisting predominantly of polymorphonuclear leucocytes. The cellular changes, which developed 4–108 days after starting treatment, were not accompanied by an alteration in the clinical state and disappeared within a week whether or not an additional antibiotic was prescribed. Though the cause is uncertain, possible mechanisms are discussed. We are prompted to report these cases because the cytological changes are not well recognised and may cause difficulties in management.     

Immunoglobulin abnormalities in the cerebrospinal fluid during bacterial meningitis

11 patients with bacterial meningitis, examined during the course of the disease for immunoglobulin (Ig) abnormalities in the cerebrospinal fluid (CSF), all had an increased CSF IgM index equal to (CSF/serum IgM):(CSF/serum albumin), indicating intrathecal IgM production. Seven patients had a slightly increased CSF IgG index, and 7 a slightly increased IgA index. Six of the 11 patients had an increased IgM index in the presence of normal indices for IgG and IgA. Follow-up revealed the return of these values to normal. Four patients had identical oligoclonal IgG bands in the CSF and serum, probably representing a systemic immune response, but in only one case were oligoclonal bands suggestive of intrathecal IgG production found. No oligoclonal IgA response was demonstrable in the 4 patients examined. Antigen-immunofixation or antigen-absorption studies revealed evidence of a specific, intrathecal IgG antibody response in only 2 patients, while a search for IgG antibodies against aetiologically unrelated bacterial and viral antigens was negative. With the exception of IgM production, therefore, a humoral intrathecal immune response is less common in bacterial than in aseptic meningitis.     

Mollaret脑膜炎的临床和脑脊液特点(附1例报告)

目的探讨Mollaret脑膜炎(MM)的临床与脑脊液(CSF)特点。方法回顾性分析1例MM患者的临床资料。结果本例男,26岁,急性起病,以头痛、发热、恶心、呕吐及脑膜刺激征为主要表现,先后复发4次。每次复发时的症状及体征基本相似,间歇期完全正常。腰穿CSF检查:白细胞81×106/L,以淋巴细胞为主(0.89),蛋白含量0.71 g/L,氯化物116 mmol/L,IgG 79.5 mg/L。经对症治疗3周基本痊愈。结论MM以头痛、发热、恶心、呕吐及脑膜刺激征为主要临床表现,可反复发作,但预后良好。CSF有细胞数和蛋白增高,以淋巴细胞、单核细胞为主,疾病初期可找到特征性Mollaret细胞。     

脑脊液淋巴样细胞检出对结核性脑膜炎早期诊断价值

目的：为了使脑脊液细胞学检查能对结核性脑膜炎提供早期诊断依据。方法：用侯氏法收集脑脊液细胞,对７８例结核性脑膜炎与８５例其它中枢神经系统感染患者脑脊液细胞学结果经分析。结果：结核性脑膜炎脊液中淋巴样细胞和浆检出阳性率分别为９５％和６２％,而毒性脑膜炎则为７３％和４９％、隐球菌性脑膜炎为５０％和３３％、寄生虫性脑膜炎为５６％和３１％、化脓性脑膜炎为２５％和１３％,均明显低于结核性脑膜炎、结论：脑脊液     

儿童结核性脑膜炎脑脊液蛋白质组学初步研究

目的 结核性脑膜炎是致残、致死率较高的儿童时期常见中枢神经系统感染性疾病。本实验拟通过建立正常中国儿童及结核性脑膜炎患儿脑脊液蛋白质双向凝胶电泳图谱,筛选结核性脑膜炎特异性蛋白,为结核性脑膜炎的早期诊断提供线索,同时也为进一步探讨结核性脑膜炎的发病机制提供新思路。方法 收集结核性脑膜炎患儿和同年龄正常儿童脑脊液各4 ml,固相PH梯度二维聚丙烯酰胺凝胶电泳（2-DE）技术分离蛋白质,考马斯亮蓝染色,Imagescanner扫描仪以及LabScan扫描软件对凝胶进行扫描获取图像,利用图像分析软件PDQuest 7.0进行强度校正、点检测、背景消减、均一化和匹配等分析,以正常儿童脑脊液的2-DE凝胶为参考胶,将结核性脑膜炎患儿脑脊液的凝胶与之进行比较分析,寻找两组患儿脑脊液蛋白质谱的差异表达斑点。结果 正常儿童脑脊液分离获得蛋白质斑点546个,结核性脑膜炎患儿脑脊液分离获得蛋白质斑点533个,发现有64个蛋白质点存在质或量的差别,其中有14个蛋白质点仅在正常儿童CSF表达,有27个点仅在结脑患儿CSF中表达,与正常儿童CSF蛋白质点表达量比较发现,结脑患儿CSF有15个蛋白质点表达量有2倍以上上调,8个蛋白质点表达量有2倍以上下调。共选出20个差异蛋白质点进行MALDI-TOF-MS分析,获得了20张肽质量指纹图谱。进入数据库进行搜索后有15个差异蛋白质已经通过MALDI-TOF-MS鉴定。结论 本实验成功建立了正常儿童和结核性脑膜炎患儿脑脊液蛋白质2-DE图谱,通过凝胶图像分析和计算机信息处理,发现了一些与结核性脑膜炎相关的蛋白质差异位点。经质谱分析及生物信息学技术初步鉴定了部分差异蛋白质,发现载脂蛋白A-I、抗肿瘤坏死因子α抗体、HLA-II 类抗原DRB1-4、MRP14蛋白可能与结核性脑膜炎的发生发展密切相关,这些蛋白能否成为结核性脑膜炎诊断的标记物,值得进一步的研究。     

New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF)

Five new markers (tumor necrosis factor TNF-alpha, interleukin IL-1 beta, IL-6, IL-8, lipopolysaccharide binding protein (LBP)) and 11 old classical markers were evaluated in 180 cerebrospinal fluid (CSF) and serum pairs to discriminate acute bacterial meningitis (BM) on admission from aseptic (viral) meningitis (AM), bacterial meningitis treated with antibiotics (TM) from AM, and AM from multiple sclerosis (MS). Statistical tests were computed which classified correctly > or =90% of the patients with BM, TM, AM at a sum minimum of false positive plus false negative results, and which reached additionally > or =90% sensitivity and specificity. To discriminate BM from AM, CSF IL-6 test > or =500 ng/l and CSF IL-1 beta test > or =8 ng/l besides CSF lactate test > or =3.5mM/l and CSF granulocyte test > or =150 M/l were revealed. CSF lactate test > or =3.2 mmol/l discriminated TM from AM. CSF leukocyte test > or =35 M/l discriminated AM from MS. Tests with the new markers were more laborious, expensive, and time consuming compared to CSF lactate test. Test candidates, detecting > or =80% of patients with > or =80% sensitivity and specificity, were evaluated with CSF TNF-alpha, IL-8 and LBP, serum IL-6, CSF leukocytes, lymphocytes and monocytes, Qglucose, CSF total protein, albumin, and Qalbumin. All tests should be reviewed in context of clinical findings to diagnose BM reliably.     

结核性与化脓性脑膜炎的脑脊液生化指标鉴别诊断

目的研究脑脊液生化指标在结核性脑膜炎和化脓性脑膜炎鉴别诊断中的应用价值。方法选择我院收治的102例结核性脑膜炎患者(结脑组)及89例化脓性脑膜炎患者(化脑组)为研究对象。对全部患者血浆及脑脊液中的蛋白、糖、氯化物和腺苷脱氨酶(ADA)进行检测。同时,对脑脊液与血浆中的蛋白、糖、氯化物和ADA比值进行计算并比较。结果结脑组脑脊液检测中,氯化物水平显著低于化脑组(P0.01),ADA水平显著高于化脑组(P0.01);结脑组血浆检测中,蛋白及氯化物水平显著低于化脑组(P0.01),ADA水平显著高于化脑组(P0.01);结脑组脑脊液与血浆生化指标比值中,蛋白及ADA的比值显著高于化脑组(P0.05),氯化物的比值显著低于化脑组(P0.01)。结论脑脊液中氯化物和ADA水平及脑脊液和血浆中蛋白、ADA及氯化物的比值对结核性脑膜炎和化脓性脑膜炎的早期鉴别诊断具有一定的价值。     

脑脊液与血浆的蛋白、糖、氯化物不同比值鉴别诊断结核性脑膜炎与病毒性脑膜炎的意义

目的 研究脑脊液(CSF)与血浆的蛋白、糖、氯化物含量不同比值鉴别诊断结核性脑膜炎(结脑)与病毒性脑膜炎(病脑)的意义.方法 检测102例结脑和107例病脑患者CSF和血浆的蛋白、糖、氯化物含量,计算CSF与血浆的蛋白、糖、氯化物含量3种不同比值(CSF/血浆蛋白≥0.2、糖≤0.5、氯≤0.7,CSF/血浆蛋白≥0.1、糖≤0.6、氯≤1.1,CSF/血浆蛋白≥0.3、糖≤0.4、氯≤0.6)诊断结脑的敏感性和特异性.结果 结脑组CSF与血浆的蛋白、糖、氯化物含量3种比值的阳性率均显著高于病脑组(P<0.05～0.01);以CSF/血浆的蛋白≥0.2、糖≤0.5、氯≤0.7诊断结脑的敏感性(96.1%,97.1%,99.0%)和特异性(97.2%,98.1%,99.1%)均较高,而CSF/血浆的蛋白>10.1、糖≤0.6、氯≤1.1的特异性(66.4%,69.2%,75.7%)较低,CSF/血浆的蛋白≥0.3、糖≤0.4、氯≤0.6的敏感性(48.0%,44.1%,42.2%)较低.结论 CSF与血浆的蛋白、糖、氯化物含量比值≥0.2、≤0.5及≤0.7对鉴别诊断结脑与病脑具有重要意义.     

Appearance of antibodies to two viruses in cerebrospinal fluid of patients with aseptic meningitis

Two cases of aseptic meningitis with simultaneous presence of antibodies to lymphocytic choriomeningitis (LCM) and mumps viruses were observed. In the 1st patient antibodies to both viruses appeared in sera and cerebrospinal fluid (CSF). The 2nd patient displayed rising serum antibodies to both viruses and CSF antibodies to mumps virus. Immunological findings and clinical features of the patients are discussed.     

结核性脑膜炎脑脊液细胞学的特征性表现

目的探讨脑脊液细胞学检查对结核性脑膜炎早期临床诊断的价值。方法采用玻片离心沉淀法制片收集脑脊液细胞,瑞-姬姆萨染色(MGG),光学显微镜分类计数。结果37例临床诊断为结核性脑膜炎患者的脑脊液细胞学呈以下改变:细胞学形态以斑片状聚集分布的激活型单核细胞、单核吞细胞和巨噬细胞,周围伴中性粒细胞和淋巴细胞,中性粒细胞比例为35.57±22.95%,类似于无反应性肉芽肿样改变。结论形似无反应性肉芽肿样的脑脊液细胞学改变以及中性粒细胞特征性的比率,可能是结核性脑膜炎早期诊断的特征性改变。     

Cortisol kinetics in cerebrospinal fluid during bacterial meningitis

Bacterial meningitis (BM) remains an infectious disease with a significant morbidity and mortality. The aim of this study was to describe the kinetics of cerebrospinal fluid (CSF) cortisol levels during BM and to assess its relationship to disease severity and etiology. A total of 55 patients with BM were enrolled in the study. Elevated CSF cortisol upon admission and its rapid decrease after starting therapy were associated with increased BM severity as assessed by the Acute Physiology and Chronic Health Evaluation II score, the Sequential Organ Failure Assessment score, Glasgow Coma Scale score and the Glasgow Outcome Scale score. The comparison of CSF cortisol according to BM etiology revealed a trend toward higher concentrations in meningitis caused by Streptococcus pneumoniae compared to Neisseria meningitidis. Our results demonstrate that the initially elevated CSF cortisol concentrations decrease rapidly after administration of BM therapy (i.e. antibiotics and dexamethasone). Moreover, this rapid reduction of CSF cortisol was found in patients with high severity scores.     

结核性脑膜炎和疱疹病毒脑膜脑炎脑脊液细胞学检查的特点分析

目的观察分析结核性脑膜炎(TBM)和疱疹病毒脑膜脑炎(HVME)的脑脊液细胞学特点。方法对经下一代基因测序技术确诊的28例TBM和27例HVME患者进行脑脊液细胞学检查及动态观察。结果 TBM组脑脊液嗜中性粒细胞比例显著高于HVME组(P 0. 01),而小淋巴细胞比例低于HVME组(P 0. 01)。HVME组有6例(22. 22%)患者查见红细胞和/或含铁血黄素吞噬细胞,有2例查见细胞内包涵体,而TBM组则均未查见。脑脊液细胞学动态观察发现,TBM组白细胞计数和嗜中性粒细胞比例下降的速度、小淋巴细胞比例上升的速度均较HVME组缓慢,且呈波动性。结论TBM和HVME的脑脊液细胞反应类型不同,TBM表现为混合型细胞反应,HVME则以淋巴细胞反应为主。HVME并发出血的机率显著高于TBM,而且常见细胞内包涵体。动态观察结果表明脑脊液细胞学检查可做为病情观察、疗效判定和预后评估的客观指标,具有十分重要的临床意义。