The cerebrospinal fluid (CSF) is a clear, colourless, plasma-like fluid that circulates in the brain ventricles and the cranial and spinal subarachnoid spaces. The mean CSF volume is around 150 ml and it is renewed about four times every 24 hours. Reduction of the CSF turnover rate during ageing leads to the accumulation of catabolites in the brain and CSF that are also observed in certain neurodegenerative diseases [1,2]. The CSF space is a dynamic pressure system. CSF pressure determines intracranial pressure with physiological values ranging between 3 to 4 mmHg before the age of one year, and between 10 and 15 mmHg in adults. Apart from its function of hydromechanical protection of the central nervous system, CSF also plays a prominent role in brain development and regulation of brain interstitial fluid homeostasis, which influences neuronal functioning [3]. Meningitis is an inflammation of the meninges (the membranes surrounding the brain and spinal cord) and the cerebrospinal fluid (CSF) in the arachnoid space. It is most often caused by a tubercular, bacterial or viral infection. Bacterial meningitis remains a serious threat to global health accounting for an estimated annual 1,70,000 deaths worldwide. Three species, H. influenza, Streptococcus pneumoniae and N. meningitides, are responsible for most cases of bacterial meningitis [2-5]. C- reactive protein (CRP) is the prototype acute phase protein since its discovery approximately 80 years ago. It is a normal serum constituent present in healthy individuals in very low concentrations (<5 mg/L). Invasive bacterial infection and extensive tissue damage cause an increase in CRP levels. CRP is the fastest rising acute phase reactant and normalizes rapidly following successful therapy or removal of the stimulus [5]. Measurement of CRP concentration provides valuable information for the diagnosis of bacterial meningitis, septicemia and pneumonia. CRP levels are sometimes used as a rapid test for presumptive diagnosis of a bacterial infection versus viral infection. CRP is often used by a rheumatologist to monitor the progression or remission of autoimmune disease [6,7].

Due to overlap in clinical features and CSF findings in various types of meningitis, sometimes it becomes difficult to differentiate bacterial meningitis from other meningitis in resource-limited settings. In such circumstances the estimation of CSF CRP concentration provides a new dimension to the specific diagnosis of meningitis.

CRP level was estimated by liquid phase immune precipitation assay with nephelometric endpoint detection. Fresh undiluted CSF was used. Turbid samples were centrifuged before assay. The normal value was taken below 6 mg/L. The study was approved by Institutional Ethical Committee and written informed consent was obtained from each patient/guardian and controls. Statistical analysis was done by SPSS version 12.0 for Window. Observations were tested statistically by the Chi-square and the Student t-test was used for sensitivity, specificity and positive predictive value of CSF CRP in different types of meningitis. For the significance of the test Pearson chi-square test was done. A p-value of < 0.05 was considered statistically significant.

The present study was conducted on 80 patients with meningitis admitted in the Medicine ward of Hind Institute of Medical Sciences, Safedabad. Twenty age and sex-matched individuals in which clinical diagnosis was other than meningitis were taken as the control group. 64 subjects were present in Study Group A (Viral Meningitis). The maximum number of subjects were in the age group 18-30 yrs with 32 patients (50%) being males and 32(50%) were females. The mean age of patients in Group A was 26.38 yrs. Group B (Pyogenic Meningitis) included 16 subjects. The mean age of this study group was 22.38 yrs, 12(75%) were males and 4(25%) were females. A maximum number of the subjects were in the age group 18-30 yrs. Among the 20 subjects in the control group, 11(55%) were male and 9(45%) were female. The mean age was 28.95 years. (Table 1).

Table 1: Sex Distribution of Study Group

It was observed that out of these 80 cases, males 44(55%) outnumbered the females 36(45%) as shown in table 1

The table shows estimates of CRP in CSF for pyogenic meningitis with 100% sensitivity, specificity and positive predictive value. The absence of CRP rather than its presence is more important for the diagnosis of viral meningitis.

Meningitis is a major health problem all over the world, especially in developing countries like India. Early and reliable etiological diagnosis is the key to a successful outcome. The etiological diagnosis of meningitis in developing countries remains a problem in clinical practice as CSF biochemical analysis and cellular response often overlap. This becomes even more difficult in a population like India where tuberculous meningitis is more prevalent. The rapid diagnostic tests including counter immunoelectrophoresis and enzyme-linked immune sorbent assay (ELISA) help establish the diagnosis but these tests are costly, difficult to perform and not easily available. In such circumstances, the estimation of CRP concentration in the CSF provides a new dimension to the specific diagnosis of meningitis. Peltola, H.O (1982) and Debeer, F.C., Kirsten et al (1984) used serum CRP levels to monitor the infections of the central nervous system and also to differentiate between pyogenic and viral meningitis, since the CRP levels are significantly lower in cases of viral meningitis.

The mechanism by which CRP gains access to CSF is still not known, however, passive diffusion across the highly inflamed meninges would be a reasonable explanation [8]. S, Tiamkao S et al (2005) measured the serum and CRP levels in patients who were diagnosed clinically as bacterial and aseptic meningitis. The mean and serum CRP level in bacterial meningitis and aseptic meningitis group was 209.25±105.23 and 67.05±40.81 respectively (p value<0.001) [9]. In a study conducted by Vaishnavi C et al (1992) CRP in CSF was significantly higher in patients with pyogenic meningitis compared to TBM. The authors concluded that the estimation of CRP in patients with suspected meningitis might be made to give a preliminary diagnosis of pyogenic meningitis [10]. The study by Hemavani V et al (2001) concluded that CSF CRP determination can be of value to differentiate pyogenic versus other microbial meningitis etiology.

Twenty-six cases were proved either by direct or indirect evidence as tuberculous meningitis. In all these cases, CSF-CRP was positive. The remaining 4 cases were bacteriologically sterile. In these 4 cases, CSF cell count was 100-200 cells, the polymorph-lymphocyte ratio was overlapping, the protein was marginally increased and sugar was normal. All these cases were clinically diagnosed as viral meningitis. CSF-CRP was negative. Three cases were followed up, and repeat CSF showed a decrease in cell number and CRP was again negative [15]. Sutinen J, Sombrero L et al (1998/1999): Among 103 patients with CNS infection, etiology was identified in 60 (58%) cases. Bacteria were found in 19 (including 7 Streptococcus pneumoniae, 5 Haemophilus influenzae, 3 Neisseria meningitidis), tuberculosis in 4, viruses in 38 (including 20 coxsackievirus, 8 measles, 4 adenovirus, and 4 poliovirus infections), and brain abscess in 3 patients. C-reactive protein was elevated on admission in all 18 cases of bacterial meningitis tested, exceeding 50 mg/L in 17 (94%), and was not affected by prior antibacterial treatment. The mean CRP was significantly higher in the bacterial group than in the viral group (207 +/- 111 mg/L vs. 39 +/- 34 mg/L; P < 0.001). In the viral group one third had CRP above 50 mg/L. In patients with tuberculous meningitis, brain abscess, or cryptococcal meningitis, CRP was moderate to highly elevated [16].

Meningitis because of its acute morbidity and long term risk of brain damage, learning disabilities, mental retardation, hearing loss or death, differentiation between pyogenic meningitis and viral meningitis is extremely important because of their therapeutic and prognostic significance. To date there are various tests available that help establish the etiological diagnosis but every test has some drawbacks. The rapid diagnostic tests including counter immunoelectrophoresis and enzyme-linked immunosorbent assay (ELISA), help establish an etiologic diagnosis, but these tests are costly, difficult to perform and not easily available. If the patient has received inadequate antibiotics and ATT, the CSF often becomes sterile. Biochemistry may be altered and pleocytosis persists though the nature of the cells changes. It poses a difficult problem in the differential diagnosis from bacterial and viral meningitis. In such circumstances the estimation of CSF CRP concentration provides a new dimension to the specific diagnosis of meningitis.