Cerebrospinal fluid C-reactive protein measurement--a bedside test in the rapid diagnosis of bacterial meningitis

C-reactive protein (C-RP) determinations were performed by the Latex agglutination method on the cerebrospinal fluid (CSF) samples of 212 patients with clinical features suggestive of meningitis. Patients were grouped as follows Group I: bacterial meningitis and partially treated bacterial meningitis (n = 22). Group II: viral encephalitis (n = 11). Group III: tuberculous meningitis (n = 18). Group IV: (i) febrile convulsions (n = 87); (ii) epileptic seizures (n = 70); (iii) intracranial haemorrhage (n = 4). C-RP was a better indicator of bacterial meningitis (sensitivity 91 per cent) than the Gram's stain (sensitivity 46 per cent). C-RP was positive in 91 per cent of patients in Group I, none in Groups II and III and 0.6 per cent in Group IV. C-RP determination in CSF proved to be a useful indicator of bacterial meningitis and served to distinguish it from viral encephalitis, tuberculous meningitis, febrile convulsions and other central nervous system disorders.     

Cerebrospinal fluid C-reactive protein in the diagnosis of meningitis in children

The mortality rate of bacterial meningitis in infants and children is still high (40-50%). Such a mortality rate can be reduced by establishing a prompt and accurate diagnosis. Until now the diagnosis of meningitis is still an important clinical problem. The examination of cerebrospinal fluid C-reactive protein had been done in 44 clinical meningitis patients in the Paediatrics Department, Dr. Sardjito General Hospital qualitatively by means of latex agglutination slide test. Cerebrospinal fluid C-reactive protein was positive in 90% (18/20) of bacterial meningitis patients compared to 8.3% (2/24) of non bacterial meningitis patients. The sensitivity and specificity of cerebrospinal fluid C-reactive protein were 90% and 91.7% respectively and these values were more sensitive and specific than those of white cell count, absolute polymorphonuclear, glucose and protein levels and the cerebrospinal fluid smear (50-80% and 80-91% respectively) which had been performed in the diagnosis of meningitis. It can be concluded that the examination of cerebrospinal fluid C-reactive protein can be used as a diagnostic tool of bacterial meningitis.     

Cerebrospinal fluid C-reactive protein in meningitis: diagnostic value and pathophysiology

We examined the diagnostic value of C-reactive protein (CRP) in cerebrospinal fluid (CSF) on initial lumbar puncture in a prospective study including 126 patients (30 neonates, 96 infants and children) suspected of having meningitis. Twenty patients were considered to have bacterial and 25 were considered to have viral meningitis. In infants and children, a retrospectively chosen cut-off CRP titre of 4 (i.e. 0.4 mg/l CRP) had a sensitivity of 100% and a specificity of 94% for differentiating bacterial meningitis from both viral meningitis and normal. It was a more sensitive and selective test for differentiating bacterial from viral meningitis on initial CSF examination than was the CSF leucocyte count, glucose concentration or protein concentration. In neonates, no such cut-off CRP titre could be found, presumably due to the immaturity of the blood-CSF-barrier (Bl-CSF-B) during the first weeks of life. In a parallel study including a non-selected group of 13 infants and children (4 without, 9 with bacterial meningitis), the serum/CSF CRP concentration ratios were determined and inserted in the individual Bl-CSF-B diagrams according to Felgenhauer. The results were fully consistent with the hypothesis that the CRP concentration in CSF reflects the normal permeability characteristics of the Bl-CSF-B, or the degree of its impairment. Based on our results, we recommend the CSF CRP estimation in the routine evaluation of infants and children suspected of having meningitis.Abbreviations CRP C-reactive protein - CSF cerebrospinal fluid - Bl-CSF-B blood-cerebrospinal fluid-barrier - Qp Concentration ratio in serum/CSF of a given protein P - IgG immunoglobulin G - R (Å) hydrodynamic radius in ångström     

C-reactive protein and bacterial meningitis

We have studied prospectively the C-reactive protein values in the cerebrospinal fluid of 54 patients with bacterial meningitis, tuberculous meningitis, and severe malarial infection and convulsions without infections of the central nervous system. CSF CRP above 1 mg/l was observed in 23 out of 28 patients with bacterial meningitis (sensitivity of 82%). The specificity was 73% at the 1 mg/l level. Five out of 19 patients with severe malarial infection had CSF CRP levels above 1 mg/l. Two patients with TB meningitis were also studied. Both of them had CSF CRP above 1 mg/l. Five patients with febrile convulsions or sepsis without meningitis had CSF CRP below 1 mg/l. It is concluded that CSF CRP would not be used as a useful discriminatory test in areas where malaria and TB meningitis are common.     

Cerebrospinal fluid lactic acidosis in bacterial meningitis.

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.     

Cerebrospinal fluid enrichment broth cultures rarely contribute to the diagnosis of bacterial meningitis

This study included children undergoing lumbar puncture in the emergency department. Bacteria were isolated from 34 (1.7%) of 1898 cerebrospinal fluid (CSF) enrichment broth cultures; 30 were contaminants. The primary CSF Gram stain was negative in all specimens with a positive enrichment broth culture. Enrichment broth cultures rarely contributed to the diagnosis of bacterial meningitis, and positive CSF enrichment broth cultures contributed to diagnostic uncertainty.     

Acute bacterial meningitis. Cerebrospinal fluid differential count

A retrospective analysis of 112 cases of pediatric bacterial meningitis over a 3-year period was performed to determine the rate of cerebrospinal fluid (CSF) lymphocytosis at initial evaluation. Of 14 neonates and 98 children older than 1 month of age not receiving preadmission antibiotic therapy, only one instance of CSF lymphocytosis occurred. This patient's CSF exhibited pleocytosis, hypoglycorrhachia, abnormally elevated protein content, and organisms visualized on gram stain smear. In children with bacterial meningitis not receiving antibiotic therapy at the time of evaluation, CSF differential cell count with relative lymphocytosis is rare.     

Cerebrospinal fluid concentrations of alpha-melanocyte-stimulating hormone in bacterial and aseptic meningitis

-Melanocyte-stimulating hormone (-MSH) has potent anti-inflammatory effects in several experimental models of inflammation. It inhibits both the actions and production of proinflammatory cytokines and neutrophil migration. We investigated whether -MSH in cerebrospinal fluid (CSF) increases during the acute stage in patients with bacterial and aseptic meningitis by measuring -MSH in CSF via radioimmunoassay. The -MSH concentrations in CSF from the children with bacterial meningitis who survived (n = 8), those with aseptic meningitis (n = 16), and the control subjects (n = 23) were all below the detection limit. However, CSF -MSH was elevated in four of the five children with bacterial meningitis who had neurological sequelae. We speculate that elevated -MSH levels in CSF during acute bacterial meningitis reflect negative feedback in response to severe inflammation associated with neurological sequelae induced by proinflammatory cytokines. Conclusion: CSF -MSH is elevated in children with severe bacterial meningitis who had neurological sequelae.     

Cerebrospinal fluid N-acetyl neuraminic acid estimation for early diagnosis and differentiation of bacterial meningitis.

Cerebrospinal fluid (CSF) analysis for free, bound and total N-Acetyl Neuraminic Acid (NANA) as well as serum NANA was done in 68 patients of bacterial meningitis, of which 37 cases were of pyrogenic meningitis and 31 of tuberculous meningitis. Ten patients were included in the control group. The free NANA levels were increased in only pyogenic meningitis, independent of protein levels but the bound form increased with the increase in CSF proteins. The increase of free NANA in CSF of pyogenic meningitis patients was not related to the cell count or sugar content in CSF or to the duration or severity of illness. This finding can be of great help in differentiating cases of pyogenic meningitis, particularly partially treated patients, who may have ambiguous pictures of CSF analysis, from the cases of tuberculous meningitis.     

Evaluation of cerebrospinal fluid (CSF) C-reactive protein in the diagnosis of suspected meningitis

Cerebrospinal fluid C-reactive protein (CSF-CRP) was studied in 183 consecutive infants and children with suspected meningitis, using a nephelometric technique. Cerebrospinal fluid C-reactive protein was above an empirically chosen level of 1 mg/1 in seven of 19 children with culture-proven bacterial meningitis, in only one of 15 children with viral meningitis, and three of 139 children with no meningitis. All 10 children with partially treated meningitis had CSF-CRP levels below 1 mg/1. There was good correlation between CSF-CRP and total protein levels in children with bacterial meningitis (R value 0.4999 P less than 0.05). The test was not sensitive enough for early differentiation between bacterial and viral meningitis. The test also did not add extra information regarding aetiology in partially treated meningitis.     

Cerebrospinal fluid and serum lysozyme activity in bacterial and viral meningitis

Cerebrospinal fluid (CSF) and serum lysozyme concentrations were determined in infants and children with and without acute infectious disease of the central nervous system. Serum lysozyme values from patients with bacterial and viral meningitis were found within the normal range. Lysozyme activity was absent or very low (below 0.5 microgram/ml) in normal CSF. High levels (4-12 microgram/ml) in patients with viral meningitis. A decrease of the lysozyme activity coincided with the clinical improvement of the bacterial meningitis. The lysozyme activity in CSF should be of significant value in detecting an inflammatory disease of the central nervous system.     

Cerebrospinal fluid lysozyme level for the diagnosis of tuberculous meningitis in children

Lysozyme activity was assayed in the cerebrospinal fluid (CSF) of 32 tuberculous meningitis (TBM), 17 bacterial meningitis, 10 partially treated bacterial meningitis, 18 encephalitis and 18 control subjects. The mean CSF lysozyme activity was significantly raised (p < 0.001) in TBM patients compared with other study groups. A cut-off CSF lysozyme level of > or = 26 U/l had a sensitivity and specificity of 93.7 and 84.1 per cent, respectively for the diagnosis of TBM. Overall, it was found to be a better test than any other single test and thus can be used for rapid and early diagnosis of TBM in children.     

Serum C-reactive protein in the differential diagnosis of childhood meningitis

BACKGROUND: Although determination of serum C-reactive protein (CRP) is considered one of the most useful tests for differentiating between bacterial and aseptic meningitis, its diagnostic accuracy in comparison with other laboratory parameters is yet to be further evaluated. METHODS: A total of 192 pediatric cases, aged between 2 months and 14 years, comprising patients with bacterial meningitis (n = 66) and aseptic meningitis (n = 126), were retrospectively analyzed on the basis of data from the initial examination. The area under the best fit binormal curve of the receiver operating characteristics (Az) for CRP was determined and compared with that for several other analytic parameters, including white blood cell count and erythrocyte sedimentation rate of peripheral blood, standard cerebrospinal fluid analysis variables and the combination test (probability of acute bacterial meningitis (pABM)) derived from Hoen's model. RESULTS: Compared with each of the other variables, the Az for serum CRP (0.97 +/- 0.02) was found to be significantly greater (P < 0.01) for all except pABM (0.99 +/- 0.01; P > 0.05). False-negative cases among the CRP test results were found to have been examined too early. CONCLUSIONS: The diagnostic accuracy of a single CRP determination was found to be equivalent to that of the most effective combination test. Patients with meningitis in whom serum CRP values are determined at least 12 h after the onset of fever and are < 2 mg/dL are far less likely to have bacterial meningitis.     

Cerebrospinal fluid lysozyme in meningitis in children. Value in establishing the etiologic diagnosis

Cerebrospinal fluid lysozyme (CSF-LZM) concentrations were determined in 62 controls, 28 viral meningitis and 22 bacterial meningitis, as compared to CSF lactic acid routinely used. CSF-LZM measurement was performed by a rapid turbidimetric assay which required 50 microliters CSF only. The mean CSF-LZM concentration of the control group was 0.23 mg/l, the highest value being 0.65 mg/l. The mean LZM levels in viral meningitis were 1.10 mg/l, never exceeding 3 mg/l. The range of pretreatment LZM levels in bacterial meningitis was 7.2 to 65 mg/l and above 3 mg/l in all cases 48 h after treatment. On the 6th day after admission, 12 of 16 samples showed abnormal values. The CSF-LZM assay seems to be of more value than that of lactic acid. Thus, before treatment, LZM concentrations were 10 to 100 fold higher than that of the normal values, with persistent high levels on the 2nd and even on the 6th day of treatment (whereas lactic acid values were all normal on day 6).