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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 15  |  Issue : 3  |  Page : 444-447

Estimation of biochemical markers in differential diagnosis of meningitis in a tertiary care hospital


Department of Biochemistry, Veer Surendra Sai Institute of Medical Science and Research, Burla, Odisha, India

Date of Submission03-Sep-2020
Date of Decision15-Sep-2020
Date of Acceptance24-Sep-2020
Date of Web Publication1-Feb-2021

Correspondence Address:
Dr. Madhusmita Acharya
Department of Biochemistry, Veer Surendra Sai Institute of Medical Science and Research, Burla - 768 017, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdmimsu.jdmimsu_347_20

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  Abstract 


Background: The clinical syndrome of meningitis is caused by inflammation of the meninges. Infections due to viruses, bacteria, mycobacterium, fungi, and other organisms are the most frequent causes of meningitis. It may contribute to extreme long-term neurological sequelae such as deafness, epilepsy, hydrocephalus, and cognitive deficits, if not recognized earlier. Our aim was to evaluate the cerebrospinal fluid (CSF)-adenosine deaminase (ADA), lactate dehydrogenase (LDH), glucose, and protein in differential diagnosis of meningitis. Materials and Methods: A total of 60 meningitis patients, of which 26 tubercular, 18 bacterial, and 16 viral meningitis, were analyzed based on the data from the initial clinical examinations. Results: Increased level CSF-ADA was found in tubercular meningitis as compared to bacterial and viral meningitis. Increased levels of CSF-LDH and protein were found in bacterial meningitis as compared to tubercular and viral meningitis, whereas the decreased level of CSF-glucose in bacterial meningitis as compared to tubercular meningitis, while normal level in viral meningitis. Conclusion: CSF-ADA, LDH, glucose, and protein may be sensitive biochemical markers for diagnosing and differentiating meningitis. CSF-ADA was higher in patients with tubercular meningitis as compared to bacterial and viral meningitis, and LDH activity was higher in patients with bacterial meningitis as compared to tubercular and viral meningitis. CSF-glucose was very low and CSF-Protein was very high in both bacterial and tubercular meningitis as compared to viral meningitis.

Keywords: Cerebrospinal fluid-adenosine deaminase, glucose, lactate dehydrogenase, protein and meningitis


How to cite this article:
Vaishya P, Acharya M, Yadav MK, Mishra PK. Estimation of biochemical markers in differential diagnosis of meningitis in a tertiary care hospital. J Datta Meghe Inst Med Sci Univ 2020;15:444-7

How to cite this URL:
Vaishya P, Acharya M, Yadav MK, Mishra PK. Estimation of biochemical markers in differential diagnosis of meningitis in a tertiary care hospital. J Datta Meghe Inst Med Sci Univ [serial online] 2020 [cited 2021 Feb 28];15:444-7. Available from: http://www.journaldmims.com/text.asp?2020/15/3/444/308566




  Introduction Top


Meningitis is an inflammation of meninges. Meninges are the three membranes that cover the brain and spinal cord. The inflammation of meninges leads to several clinical patterns. Microorganism comes to the meninges by the circulatory system or once in a while by spreading from nearby sites, for example, the middle ear or nasal sinuses. The diseases might be brought about by contamination with microorganisms such as bacteria, virus, mycobacterium tuberculi, or other pathogens and less ordinarily by specific medications. Among all these, acute bacterial meningitis is the most well-known type of suppurative central nervous system contamination that happens all through the world.[1],[2] Approximately 4–6 persons per 100,000 population are infected every year worldwide.[3] The adenosine deaminase (ADA) is a purine salvage pathway enzyme that catalyzes the deamination of adenosine to inosine and ammonia by hydrolysis. There are two isoenzymes of ADA, i.e., ADA1 and ADA2. ADA2 constitutes about 73% of the total ADA activity in serum of healthy individuals. ADA is a lot more prominent proclivity for adenosine and discovers distinctly in lymphocytes, macrophages, and monocytes which discharge it when stimulated by the microorganism.[4] Lactate dehydrogenase (LDH) is a zinc containing most significant intracellular enzyme, which plays a crucial role in intermediary glucose metabolism. It is distributed ubiquitously in animal cells which are found especially in the heart, liver, muscle, brain, and blood cells. LDH in cerebrospinal fluid (CSF) is usually employed in the diagnosis of various meningitis. Bacterial meningitis continues to be a substantial region for mortality and morbidity, especially in children.[5],[6],[7] If a diagnostic assay such as ADA and LDH in CSF gives added information regarding early diagnosis together with other traditional tests, it's going to be easier to begin treatment of this deadly disease and forestall morbidity and mortality. In the present study, we measure CSF-ADA, LDH, glucose, and protein in the differential diagnosis of meningitis to find out their diagnostic significance of different meningitis.


  Materials and Methods Top


This cross-sectional study was conducted in the Department of Biochemistry, VIMSAR, Burla, with the collaboration of the medicine department during the period from June 2019 to July 2020. A total of sixty meningitis patients, of which 26 tubercular, 18 bacterial, and 16 viral meningitis patients were analyzed on the basis of initial clinical examinations.

Inclusion criteria

  • Both male and female patients within the age group of 5–65 years with clinically suspected sign, symptoms, and clinical features suggestive of meningitis.


Exclusion criteria

  • Patients whose lumbar puncture is contraindicated
  • Patients are on treatment of meningitis
  • Patients with antilipidemic drug, steroids, and oral contraceptives
  • Patients who are critically ill.


Biochemical parameters

The CSF was obtained by lumber puncture under aseptic precaution, and all biochemical parameters were done on autoanalyzer. The CSF-ADA was measured by Quantiamate (Tulip) and CSF-LDH, glucose, and protein were measured by Cobas C311 (Roche) intergra.

Statistical analysis

Test results have been compiled and analyzed statistically. The? SPSS for the window 22.0 (IBM Corp., Armonk, NY) has been used in the evaluation of the data. The quantitative data of the groups have been compared using ANOVA test for comparison. The result is considered statistically significant if it comes P < 0.05.

Ethical clearance

The Institutional Ethics Committee of Veer Surendra Sai Institute of Medical Science and Research, Burla, Odisha, India has approved the Research work proposed to be carried out at Veer Surendra Sai Institute of Medical Science and Research, Burla, Odisha, India Date: 7th Jan 2019 with Reference no VSSI/EC/2019/18.


  Observation and results Top


This present study includes sixty meningitis patients, out of which 26 (43.4%) tubercular meningitis, 18 (30%) bacterial meningitis, and 16 (26.6) viral meningitis. [Table 1] and [Figure 1] shows the maximum number of cases belongs to the age group of 30–45 years (28.3%), 25% in < 15 years, 20% in 15–30 years, 18.3% in 45–60 years, and minimum 8.4% >60 age group. The age group range was 5–65 years with a mean and standard deviation of 32.88 ± 17.81, and out of 60 meningitis patients, 39 (65%) were male and 21 (35%) were female in [Figure 2].
Table 1: Age distribution

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Figure 1: The age group distribution in different meningitis

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Figure 2: The sex distribution in different meningitis

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The mean values for CSF-ADA, LDH, glucose, and protein levels in various meningitis are shown in [Table 2].
Table 2: Level of cerebrospinal fluid-adenosine deaminase, lactate dehydrogenase, glucose, and protein in different meningitis

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The mean value of CSF-ADA is 10.36 ± 3.17 U/L in tubercular meningitis, 4.43 ± 1.14 U/L in bacterial meningitis, and 2.4 ± 0.93 U/L in viral meningitis. These difference values between all CSF-ADA are statistically significant in all groups.

The mean values of CSF-LDH are 251.93 ± 20.34 IU/L in bacterial meningitis, 151.96 ± 15.93 IU/L in tubercular meningitis, and 52.7 ± 8.2 IU/L in viral meningitis. These difference values between all CSF-LDH are statistically significant in all groups.

CSF-Glucose, mean levels in bacterial meningitis, tubercular meningitis, and viral meningitis were 22.7 ± 5.5 mg/dl, 37.1 ± 6.3 mg/dl, and 67.3 ± 7.6 mg/dl, respectively. Statistically significant lower values were observed in bacterial meningitis compared to tubercular meningitis (P < 0.001) while in viral meningitis shows a normal level. The difference between CSF-glucose is statistically significant between all groups (P < 0.001).

The mean values of CSF-protein were 212.9 ± 41.7 mg/dl in bacterial meningitis, 152.7 ± 35.4 mg/dl in tubercular meningitis, and in viral meningitis value was 52.4 ± 13.1 mg/dl. Statistically significant higher values were observed with bacterial meningitis compared to tubercular and viral meningitis (P < 0.001). The difference between CSF-protein is statistically significant between all groups (P < 0.001).


  Discussion Top


Meningitis is a significant cause of morbidity and mortality. Hence, to differentiate different types of meningitis, several studies have been shown the effectiveness of rapid and definite tests using CSF variable and markers of peripheral blood for common and uncommon laboratory measurements. The mean values of CSF-LDH were 251.4 ± 20.34 IU/L in bacterial meningitis, 151.96 ± 15.93 IU/L in tubercular, and in viral meningitis value was 52.7 ± 8.2 IU/L. These difference values between all CSF-LDH are statistically significant in all groups. The observation of this study matches the observation documented by Sharma and Nand.[8] Moshe Nussinovitch et al.[9] also observed raised LDH levels within the CSF of patients of bacterial meningitis. Few researchers have recommended and aggravation in the blood–brain barrier, which empowers plasma LDH to arrive at the CSF or formation of LDH by neoplastic tissue or by WBCs and exogenous bacterial sources.[10],[11],[12] CSF-LDH estimation may separate viral meningitis from that of bacterial and tubercular meningitis and so of diagnostic significance. Hence, CSF-LDH assessment is of the significant diagnostic and prognostic tools as far because the dreaded disease of various kinds of meningitis is concerned.

The mean ADA level was 10.36 ± 3.17 U/L in tubercular meningitis, 4.43 ± 1.14 U/L in bacterial meningitis, and 2.40 ± 0.93U/L in viral meningitis. The difference in the level of ADA in different meningitis was found to be significant (P < 0.05) compared to bacterial and viral meningitis; CSF-ADA levels in tubercular meningitis were considerably higher. The findings were maximum similarity with the other studies.[13],[14],[15],[16] Choi et al. examined ADA activity in CSF of 182 patients with meningitis. Mean ADA was 12.7 ± 7.5 U/L in the tubercular group and was significantly higher than the other groups 3.10 ± 2.9 U/L; (P < 0.001). Hence, we concluded that the level of CSF-ADA will assist in the differentiating bacterial and viral meningitis from tubercular meningitis. In addition to that, the clinical symptoms of patients' physical, biochemical, and microscopic features of CSF should be investigated for improved diagnosis.

The mean levels for CSF-glucose in bacterial meningitis, tubercular, and viral meningitis were in the range of 22.7 ± 5.5 mg/dl, 37.1 ± 6.8 mg/dl, and 67.3 ± 7.6 mg/dl. A highly significant decrease in CSF glucose was observed in bacterial and tubercular meningitis while in viral meningitis within in normal range.

The decrease level of CSF glucose in patients with bacterial meningitis observed in this study is in following the result reported by various researchers such as Reddy et al.,[17] Prasad et al.,[18]? Bhat,[19] Gupta,[20] and Sigurdardottir et al.[21]

The decrease level of CSF glucose in patients with tubercular meningitis observed in this study are in agreement with the result reported by various researchers such as Kennedy and Fallon,[22] Klein et al.,[23] and Berenguer and Sinha.[24] We observed significantly decreased values of CSF glucose in bacterial and tubercular and almost normal level in viral meningitis. This suggests that estimation of CSF glucose is not only valuable for diagnosing meningitis but also helps to differentiate bacterial and tubercular from viral meningitis.

The mean levels for CSF-protein in bacterial meningitis, tubercular meningitis, and viral meningitis were in the range of 212.9 ± 41.7 mg/dl, 152.7 ± 35.4 mg/dl, and 52.4 ± 13.1 mg/dl. A highly significant increase in CSF protein was observed in bacterial meningitis as compared to tubercular meningitis and viral meningitis.

The increase level of CSF protein in patients with bacterial meningitis, tubercular meningitis, and viral meningitis was observed in this study are following the result reported by various researchers such as? Reddy,[17] Prasad,[18] Bhat,[19] Gupta,[20] Kennedy,[22] and Klein.[23]


  Conclusion Top


These findings suggest that the CSF-ADA, LDH, glucose, and protein may be the sensitive biochemical markers for diagnosing and differentiating meningitis. CSF-ADA was higher in patients with compared to bacterial and viral meningitis in patients with tubercular meningitis and LDH activity was higher compared to tubercular and viral meningitis in patients' with bacterial meningitis. In contrast to viral meningitis, CSF-glucose was very low and CSF-protein was very high in both bacterial and tubercular meningitis as compared to viral meningitis. Hence, it can be used to utilized as simple rapid and inexpensive test for differentiating tubercular, bacterial, and viral meningitis. However, further studies in larger groups are needed to explain the diagnostic role of biochemical markers for different meningitis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Groer MW, Shekleton ME. Basic Pathophysiology-Holistic Approach. 3rd ed. Philadelphia, PA: Mosby Inc.; 1989. p. 367.  Back to cited text no. 1
    
2.
Aggarwal AP, Kumar M, Avasthi G, Soni RK. Diagnostic and prognostic significance of lactate dehydrogenase in cerebrospinal fluid in patients of meningitis. J Indian Med Assoc 1994;92:288-90.  Back to cited text no. 2
    
3.
The Association of Physicians of India. Pyogenic infections of the central nervous system. In: API Textbook of Medicine. 8th ed., Ch. 15. Mumbai: The Association of Physicians of India; 2009.  Back to cited text no. 3
    
4.
Ungerer JP, Osthuizen HM, Retief JH. Significance of Adenosine deaminase activity and its isoenzymes in tubercular effusions. Chest 1994;106:33-7.  Back to cited text no. 4
    
5.
Tunkel AR, Michael SW. Acute meningitis. In: Mandell GL, Dollin RG, Bennett JE, editors. Principle and Practice of Infectious Disease. 8th ed. Philadelphia, USA: Churchill Livingstone/Elsevier; 2010. p. 1083-119.  Back to cited text no. 5
    
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Roos KL, Tyler KL. Meningitis. In: Kasper DL, Braunwald LE, Fauci AS, Hauser SL, Longo DL, editors. Harrison Principle of Internal Medicine. New York, USA: McGraw-Hill; 2008. p. 2471-90.  Back to cited text no. 6
    
7.
Feigin RD, Pearlman E. Bacterial meningitis beyond the neonatal period. In: Feigin RD, Demmler GJ, Cherry JD, Kaplan SL, editors. Text Book of Pediatric Infectious Disease. Philadelphia, USA: Saunders; 2004. p. 443-74.  Back to cited text no. 7
    
8.
Sharma M, Nand N. Evaluation of enzymes in pyogenic and tuberculous meningitis. J Assoc Physicians India 2006;54:118-21.  Back to cited text no. 8
    
9.
Nussinovitch M, Finkelstein Y, Elishkevitz KP, Volovitz B, Harel D, et al. Cerebrospinal fluid lactate dehydrogenase isoenzyme in children with bacterial and aseptic meningitis. Transl Res 1964;154:214-8.  Back to cited text no. 9
    
10.
Lending M, Slobody LB, Mestern J. Cerebrospinal fluid glutamic oxalacetic transaminase and lactic dehydrogenase activities in children with neurologic disorders. J Pediatr 1964;65:415-21.  Back to cited text no. 10
    
11.
Wroblewski, F, Decker B, Wroblewski R. The clinical implications of spinal fluid LDH activity. N Engl J Med 1958;258:635-9.  Back to cited text no. 11
    
12.
Aicardi J. Disease of the nervous system in childhood. Clin Dev Med 1992;1115:1132-5.  Back to cited text no. 12
    
13.
Prasa R, Kumar A, Khanna BK, Mukherji PK, Agarwal SK, Kumar A, et al. Adenosine deaminase in cerebrospinal fluid for diagnosis of tubercular meningitis. Ind J Tuberc 1991;38:99-102.  Back to cited text no. 13
    
14.
Kashyap RS, Kainthla RP, Mudaliar AV, Purohit GJ, Taori GM, Daginawala HF. Cerebrospinal fluid adenosine deaminase activity: A complimentary tool on the early diagnosis of tubercular meningitis. Cerebrospinal Fluid Res 2006;3:5.  Back to cited text no. 14
    
15.
Gautam N, Aryal M, Bhatta N, Bhattacharya SK, Basal N, Lamsal M. Comparative study of cerebrospinal fluid adenosine deaminase activity in patients with meningitis. Nepal Med Coll J 2007;9:104-6.  Back to cited text no. 15
    
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Rohani MY, Cheong YM, Rani JM. The use of adenosine deaminase activity as a biochemical marker for the diagnosis of tubercular meningitis. Malays J Pathol 1995;17:67-71.  Back to cited text no. 16
    
17.
Reddi YR, Rao VS, Subhash R, Reddy C, Ramchander N. Pyogenic meningitis in infants and children. A clinical and bacteriologic study.Indian Pediatrics. 1973;10:413-18.  Back to cited text no. 17
    
18.
Prasad R, Kalra K, Mathur PP, Singh M, Kalra A, Dayal R, et al Study on outbreak of meningococcal meningitis. Indian Pediatr. 1985;22:307-12.   Back to cited text no. 18
    
19.
Bhat BV, Verma IC, Puri RK, Srinivasan S, Nalini P. A profile of pyogenic meningitis in children. JIMA 1991;89:224-7.  Back to cited text no. 19
    
20.
Gupta V. Hearing evaluation in children with bacterial meningitis. Indian Paediatr 1993;30:1175-9.  Back to cited text no. 20
    
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Sigurdardottir B, Björnsson OM, Jónsdóttir KE, Erlendsdóttir H, Gudmundsson S. Acute bacterial meningitis in adults. Arch Intern Med 1997;157:425-30.  Back to cited text no. 21
    
22.
Kennedy DH, Fallon RJ. Tubercular meningitis. JAMA 1979;241:264-68.  Back to cited text no. 22
    
23.
Klein NC, Damsker B, Hirschman SZ. Mycobacterial meningitis. Am J Med 1985;79:29-34.  Back to cited text no. 23
    
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Berenguer J, Sinha MK. Tuberculous meningitis in patients infected with the human immunodeficiency virus. N Engl J Med 1992;326:668-72.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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