The role of cerebrospinal fluid shunting in tuberculous meningitis

Twenty-three patients with severe tuberculous meningitis who underwent cerebrospinal fluid shunting within the first month of illness were reviewed nine months later. The criteria for and results of the use of cerebrospinal fluid shunts in tuberculous meningitis are reviewed.     

Temporal evolution of cerebrospinal fluid following initiation of treatment for tuberculous meningitis

OBJECTIVE: Clinicians often perform follow-up lumbar punctures (LPs) on patients with tuberculous meningitis (TBM) to document changes occurring in the cerebrospinal fluid (CSF). Normalisation of the CSF then serves as indirect confirmation of the diagnosis. However, changes occurring in CSF following the initiation of anti-tuberculosis (TB) treatment are not well described. We undertook a retrospective study to determine the temporal evolution of CSF in patients with TBM on anti-TB treatment in an attempt to provide a more rational basis for the interpretation of repeat LPs. METHODS: Patients diagnosed with TBM at King George V Hospital in Durban from 1994 to 2003 were identified. Demographic, clinical, laboratory and radiological data were recorded. We examined the change in CSF lymphocyte cell count, polymorphonuclear (PMN) cell count, glucose concentration and protein concentration. Initially, scatter plots of the data modelled over time were produced and random effects models were then used to model the predicted changes in CSF over time. RESULTS: Ninety-nine patients were identified, and a total of 327 LPs were done. The average number of LPs per patient was 3 (range 3 - 9). Statistically significant changes in all four variables (lymphocytes, PMN cells, glucose and protein) were demonstrated, with a p value < 0.001. The predicted models showed that lymphocyte count and protein concentration change slowly over time. PMN cells and glucose concentration changed rapidly in an exponential manner. CONCLUSIONS: Our results demonstrate the tendency for CSF to normalise over time. The slow change in lymphocyte count and protein concentration limits clinical use. The rapid change in PMN cells and glucose concentration allows us to make reasonable clinical decisions. If a repeat LP does not show definite improvement in these two parameters, it should be considered atypical for TBM.     

Role of cerebrospinal fluid shunting for human immunodeficiency virus-positive patients with tuberculous meningitis and hydrocephalus

OBJECTIVE: Tuberculous meningitis (TBM) and its complications continue to have devastating neurological consequences for patients. Budgetary constraints, especially in developing countries, have made it necessary to select patients for shunting who are likely to experience good recoveries. To date, the value of cerebrospinal fluid shunting for human immunodeficiency virus (HIV)-positive patients with TBM has not been clearly established. METHODS: Thirty patients with TBM and hydrocephalus were prospectively evaluated. Coincidentally, one-half of the patients were HIV-positive. All patients underwent uniform treatment, including ventriculoperitoneal shunt placement and antituberculosis treatment. CD4 counts were measured for all patients. Outcomes were assessed at 1 month. RESULTS: No complications related to shunt insertion were noted. The HIV-positive group fared poorly (death, 66.7%; poor outcome, 64.7%), compared with the HIV-negative group (death, 26.7%; poor outcome, 30.8%). Despite cerebrospinal fluid shunting, no patient in the HIV-positive group experienced a good recovery (Glasgow Outcome Scale score of 5). This is in contrast to the six patients (40%) in the HIV-negative group who, with the same treatment, experienced good recoveries (Glasgow Outcome Scale scores of 5) at discharge (P<0.14). No patient (either HIV-positive or HIV-negative) who presented in TBM Grade 4 survived, whereas no HIV-positive patient who presented in TBM Grade 3 survived. A significant relationship was noted between CD4 counts and patient outcomes (P<0.031). CONCLUSION: In the absence of obvious clinical benefit, HIV-positive patients with TBM should undergo a trial of ventricular or lumbar cerebrospinal fluid drainage, and only those who exhibit significant neurological improvement should proceed to shunt surgery.     

Enzyme-linked immunosorbent assay for serum renal tubular antigen in kidney transplant patients

A mouse monoclonal antibody, specific for binding with the epithelial surface antigen in human renal proximal tubules, was produced by hybridoma culture. Using this antibody, an enzyme-linked immunosorbent assay was developed to measure the human renal tubular epithelial antigen (HRTE) concentrations in serum samples from 25 normal subjects and 66 consecutive renal allograft recipients. In 46 patients treated with azathioprine and prednisone, serum HRTE was elevated more than two-fold in 56 of 62 rejection episodes 2-5 days before the clinical diagnosis was made. Of the 56 rejection episodes, the antigen level fell to baseline after treatment in 44 steroid-responsive episodes, but it remained elevated in 8 steroid-resistant rejections, and it became undetectable 3-4 days after the initial elevation in 4 episodes in which allografts were lost to rejection. In 20 patients treated with cyclosporine and prednisone, all 25 rejection episodes demonstrated a greater than two-fold increase of serum HRTE 1-6 days prior to the diagnosis of rejection. The antigen level fell to baseline in 23 reversible rejection episodes, however serum HRTE remained elevated in 2 steroid-resistant patients whose grafts were lost to rejection. Cyclosporine nephrotoxicity without rejection was confirmed in 6 episodes, each of which demonstrated a more than two-fold increase in HRTE 2-4 days before toxicity was diagnosed. When the cyclosporine dose was reduced, the antigen level decreased as the serum creatinine declined. Serial determinations of serum HRTE in renal transplant recipients can provide valuable information for the early diagnosis and management of allograft rejection and cyclosporine nephrotoxicity.     

脑脊髓液中腺苷脱氨酶活性对结核性脑膜炎诊断价值的临床研究

目的 探讨脑脊髓液中腺苷脱氨酶（CSF-ADA）活性对结核性脑膜炎的诊断价值及在病程中的动态变化.方法 选择160例患者纳入本研究,76例结核性脑膜炎为病例组;84例非结核性脑膜炎为对照组,其中细菌性脑膜炎36例,病毒性脑膜炎30例,隐球菌性脑膜炎18例.每例患者均于治疗前抽取CSF,采用酶耦联Trinder法测定CSF-ADA活性,结果以（-x）±s表示,组间差异使用Mann-Whitney U检验.47例结核性脑膜炎患者于抗结核治疗后2周和6周时再次检测CSF-ADA,治疗前后差异使用配对t检验.结果 结核性脑膜炎组CSF-ADA活性为（12.9±6.4）U/L,非结核性脑膜炎组为（6.0±4.1）U/L,两组比较差异有统计学意义（U=7.860,P＜0.05）.取CSF-ADA≥9 U/L作为临界值时鉴别结核性脑膜炎与非结核性脑膜炎价值最高,灵敏度为84.21%,特异度为83.33%.随着患者病情好转,CSF-ADA活性逐渐降低.结论 CSF-ADA活性≥9 U/L可作为诊断结核性脑膜炎的一项辅助诊断指标,抗结核治疗后CSF-ADA活性可作为疗效判断的参考指标.     

An enzyme-linked immunosorbent assay using adsorbed mycobacterial sonicates for the serodiagnosis of tuberculosis

Sera from 123 patients with confirmed tuberculosis and 576 patients with other non-mycobacterial diseases were tested for antibodies to an adsorbed mycobacterial sonicate antigen employing an enzyme-linked immunosorbent assay. The results show significant differences in IgG levels between sera from tuberculosis patients and controls. The results of delayed hypersensitivity skin-test reactions to purified protein derivative in both the patient and control groups were unrelated to antibody levels. The assay was able to detect antibodies for at least 4 months after diagnosis and treatment. Patients diagnosed as having tuberculosis 7 months or more before being tested did not demonstrate increased antibody levels. The assay could be useful not only as a screening technique for diagnosing tuberculosis in an immunised population but also as a means of monitoring antituberculosis treatment.     

Detection of bacterial antigens in cerebrospinal fluid by a latex agglutination test in 'septic unknown' meningitis and serogroup B meningococcal meningitis

The latex agglutination test (Wellcogen) was evaluated specifically in cases of 'septic unknown' meningitis, with CSF findings characteristic of bacterial meningitis but with no bacterial organisms grown on CSF culture or seen on microscopy after Gram staining. In only 4 (12%) of 33 cases of 'septic unknown' meningitis were antigens identified in the CSF. This kit contains for the first time reagents for the detection of serogroup B Neisseria meningitidis antigens and was also evaluated for this bacteria. Only 6 (27%) of 22 serogroup B N. meningitidis cases were identified.     

The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis

The simultaneous determination of cerebrospinal fluid (CSF) and plasma adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in tuberculous meningitis (TBM). CSF and plasma ADA activity were determined in four groups of patients: (i) a 'no meningitis' group of 174 children investigated for possible meningitis, but found to be uninfected; (ii) an aseptic meningitis group of 40 children; (iii) a bacterial meningitis group of 31 children; and (iv) a TBM group of 27 patients (24 children and 3 adults). CSF ADA alone was determined in a further 23 children with aseptic meningitis, 19 with bacterial meningitis and 13 children and 7 adults with TBM. Both the CSF/plasma ADA ratio and the absolute CSF ADA activity were raised in TBM (mean values 0,24 and 12,61 U/I respectively) and bacterial meningitis (mean values 0,59 and 15,43 U/I respectively), but not in the aseptic meningitis group (mean values 0,06 and 2,00 U/I) or the 'no meningitis' group (mean values 0,04 and 1,51 U/I). Both values will distinguish TBM from aseptic meningitis, but do not appear to hold any marked advantages over conventional CSF criteria in the diagnosis of TBM.     

Enzyme-linked immunosorbent assay for human leukocyte antigen antibody detection and urine protein test recommended for follow-up monitoring after renal transplantation

BACKGROUND: Although the usefulness of posttransplant human leukocyte antigen (HLA) antibody monitoring has been demonstrated, detailed recommendations have not been worked out in its frequency, the type of patients and methods to be used. Enzyme-linked immunosorbent assay is a simple and cost-efficient assay. The urine protein test that reflects renal dysfunction is performed everywhere. We assessed the clinical value of HLA antibody and urine protein monitoring after renal transplantation. METHODS: Serum samples were consecutively collected from outpatients (n=323) in 2004 and in 2006. Because 18 had graft failure and 8 died with functioning graft for 2 years, 297 paired sera were tested for HLA antibody using enzyme-linked immunosorbent assay. Urine protein was determined to be positive when the dipstick protein reaction was+/-or over (20 mg/dL). RESULTS: Total 297 patients were divided according to the change of HLA antibody status. Only patients with all of (i) de novo HLA antibody production, (ii) continuous detection from peripheral blood, and (iii) positive urine protein test had a significantly higher serum creatinine than the others and demonstrated rapid deterioration of Cr (DeltaCr 1.26 mg/dL during 2 years). Negative change of HLA antibody stopped the increase of serum creatinine. CONCLUSION: The status of HLA antibody and urine protein provides useful information on graft prognosis. Although the tempo of graft injury is relatively slow, a yearly routine HLA antibody test for all patients and the attempt to reduce HLA antibody to negative levels is recommended, when HLA antibody is newly detected and urine protein test is positive.     

Enzyme-linked immunosorbent assay (ELISA) and a passive haemagglutination test (PHT) for the detection of pseudomonas antibodies in burned patients

Pseudomonas antibodies were measured in serial plasma samples from patients with burns using an enzyme-linked immunosorbent assay (ELISA), passive haemagglutination test (PHT) and a passive protection test (PPT). ELISA and PHT showed that from 7 days after burning, 15 patients immunized with a 16-part polyvalent vaccine had higher titres of antibody to the 16 antigens in the vaccine than 15 unvaccinated patients. There was evidence that ELISA and PHT detected different pseudomonas antibodies in the plasma samples. When a single antigen (type 6) from the polyvalent vaccine was used in ELISA it failed to monitor antibodies in the plasma from vaccinated and unvaccinated burned patients shown by a PPT to protect mice against Pseudomonas aeruginosa serotype 6. PHT gave a closer correlation of protective antibodies against type 6 antigen than ELISA.     

Haemophilus influenzae meningitis in the presence of a cerebrospinal fluid shunt

Haemophilus influenzae meningitis in the presence of a cerebrospinal fluid shunt has been reported uncommonly. Staphylococcus aureus and Staphylococcus epidermidis, the most common etiological agents, are usually acquired by contiguous spread from an intraoperative or perioperative source. These infections usually occur within 2 months of shunt insertion and are rarely associated with bacteremia. Review of the literature shows that infection with H. influenzae typically occurs later than with the more common pathogens, is commonly associated with bacteremia, and frequently can be treated with antibiotics alone.     

Usefulness of beta 2-transferrin assay in the detection of cerebrospinal fluid leaks following head injury.

The clinical value of analyzing various fluids and exudates for beta 2-transferrin (beta 2-Tfn) to detect cerebrospinal fluid (CSF) leakage following head trauma was reviewed in a series of 11 cases. Qualitative detection of beta 2-Tfn was performed by agarose gel electrophoresis of tears, ear and nose exudates, cerebral cyst fluid, and wound discharge fluid in different cases. In each instance the presence of beta 2-Tfn in the analyzed fluid supported the diagnosis of a CSF leak. Equally, the demonstration of the absence of beta 2-Tfn in the fluid excluded the diagnosis of such a leak. Neither false-positive nor false-negative results were found, as indicated by separate radiological investigations and/or subsequent clinical assessment of patients. The detection of beta 2-Tfn in suspect fluids thus provides a highly sensitive and selective, rapid, and noninvasive test for the detection of CSF leakage in cases of head trauma.     

鞘内置管脑脊液置换与反复腰穿放脑脊液分别鞘内注药治疗结核性脑膜炎的疗效比较

目的探讨鞘内置管脑脊液置换与反复腰穿放脑脊液分别鞘内注药治疗结核性脑膜炎的疗效。方法在常规综合治疗的基础上,对照组采用反复腰穿放脑脊液并鞘内注药,观察组采用鞘内置管脑脊液置换加鞘内注药。结果观察组总有效率（93.1%）明显高于对照组（73.0%）（P〈0.01）;观察组脑脊液压力恢复正常和住院时间均明显短于对照组（P〈0.01）;对照组不良反应（5例）明显多于观察组（0例）（P〈0.05）。结论相比反复腰穿放脑脊液,鞘内置管脑脊液置换疗效高,疗程短,不良反应少,值得临床推广应用。     

脑脊液半胱氨酸蛋白酶抑制剂C在隐球菌性脑膜炎中临床价值的探讨

目的 探讨脑脊液半胱氨酸蛋白酶抑制剂C(cystatin C)在隐球菌性脑膜炎(CM)中的临床应用价值.方法 前瞻性观察和对比分析本院2007年1月~2011年5月所收治的隐球菌性脑膜炎(n = 14)、单纯结核性脑膜炎(n = 61)和结核性脑膜脑炎患者(n = 37)脑脊液cystatin C水平及相关生物化学指标的差异.结果 隐球菌性脑膜炎患者脑脊液cystatin C水平(3.18 ± 1.14 mg/L)显著低于单纯结核性脑膜炎的患者(4.62 ± 1.42 mg/L)(P< 0.01),而与结核性脑膜脑炎患者脑脊液cystatin C水平(3.68 ± 1.42 mg/L)相比,差异无统计学意义(P> 0.05);CM组的其他脑脊液生化标志物,如糖(Glu)、氯化物(Cl-)、总蛋白(TP)、腺苷脱氨酶(ADA)、乳酸(LAC)、C-反应蛋白(CRP)和微量蛋白(mALB)等,与其他两组比较均无统计学意义(P> 0.05).HIV(+)的隐球菌性脑膜炎患者(6例)cystatin C水平为(3.48 ± 1.16 mg/L),与HIV(-)隐球菌性脑膜炎组(8例)(2.96 ± 1.15 mg/L)相比,差异无统计学意义(P> 0.05).结论 脑脊液cystatin C可作为脑膜疾病鉴别诊断的一种新的标记物,有利于隐球菌性脑膜炎与结核性脑膜炎的鉴别,但其与结核性脑膜脑炎的鉴别诊断应慎重考虑.     

Cerebrospinal fluid lactate and lactate dehydrogenase levels as diagnostic aids in tuberculous meningitis

The value of cerebrospinal fluid (CSF) lactate and lactate dehydrogenase (LD) values as aids in differentiating tuberculous meningitis (TBM) from aseptic meningitis has been investigated. Using an upper limit of normal for CSF lactate levels of 2,75 mmol/l resulted in detection of 24 out of 26 cases of TBM (a sensitivity of 92%). If, however, a level of 3,85 mmol/l was taken as the upper limit of normal, then 18 out of 26 cases were detected (a sensitivity of 69%). Using 40 U/l as the upper limit of normal for LD levels detected 21 out of 38 cases of TBM (a sensitivity of 55%). Both tests may give normal values in the presence of TBM, but this should not cause specific antituberculosis therapy to be withheld. Neither test appears to hold marked advantages over conventional chemical analysis of CSF in differentiating TBM from aseptic meningitis.