|Year : 2019 | Volume
| Issue : 4 | Page : 344-348
Cerebrospinal lactate dehydrogenase and serum procalcitonin in the diagnosis of meningitis
Sayed M Farouk1, Taha S Hussein1, Mahmoud I Basstawy2, Nagla R Abdel Moniem3
1 Department of Tropical Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Pathology, Al-Azhar University, Cairo, Egypt
3 Departments of Medical Microbiology and Immunology, Faculty of Medicine, Beni-Suef, Egypt
|Date of Submission||02-Apr-2019|
|Date of Decision||25-Jul-2019|
|Date of Acceptance||14-Oct-2019|
|Date of Web Publication||14-Feb-2020|
Sayed M Farouk
Assistant Professor of Tropical Medicine Al-Azhar University, Cairo; Department of Tropical Medicine, Al-Azhar University, 11651, Cairo
Source of Support: None, Conflict of Interest: None
Background Meningitis is inflammation of the membranes that cover the brain, spinal cord, and the intervening cerebrospinal fluid..
Aim The aim of this paper was to assess the diagnostic role of cerebrospinal lactate dehydrogenase (LDH) and serum procalcitonin (PCT) in meningitis and to differentiate septic from aseptic meningitis.
Patients and methods The cases were divided into septic meningitis (group I), aseptic meningitis (group II), and meningism (group III) and 100 control cases of complaints other than central nervous system (CNS) infection. All patients were evaluated by full clinical examination, laboratory investigation (complete blood count, erythrocyte sedimentation rate, C-reactive protein, and random blood sugar, liver and renal function tests, and blood culture), lumbar puncture for cerebrospinal fluid examination, cerebrospinal LDH by spectrophotometer, serum PCT in selected patients, computed tomography, and MRI in complicated cases.
Results Cerebrospinal LDH 100% of 139 cases in septic meningitis and 98% of 104 cases in aseptic meningitis were elevated above normal range. All cases of meningism show normal range. Furthermore, serum PCT testing was positive in all patients with septic meningitis, while serum PCT testing is positive in 35 (34%) patients with aseptic meningitis and negative in 69 (66%) patients and serum PCT-Q testing was negative in all patients with meningism. Controls were assessed for normal serum PCT level.
Conclusion Cerebrospinal LDH can be used only as a preliminary screening test, whereas PCT-Q was a good diagnostic marker for distinguishing septic from aseptic meningitis.
Keywords: lactate dehydrogenase, procalcitonin, tropical
|How to cite this article:|
Farouk SM, Hussein TS, Basstawy MI, Abdel Moniem NR. Cerebrospinal lactate dehydrogenase and serum procalcitonin in the diagnosis of meningitis. Al-Azhar Assiut Med J 2019;17:344-8
|How to cite this URL:|
Farouk SM, Hussein TS, Basstawy MI, Abdel Moniem NR. Cerebrospinal lactate dehydrogenase and serum procalcitonin in the diagnosis of meningitis. Al-Azhar Assiut Med J [serial online] 2019 [cited 2020 Sep 29];17:344-8. Available from: http://www.azmj.eg.net/text.asp?2019/17/4/344/278397
| Introduction|| |
The triad of fever, boring headache, and projectile vomiting is suggestive of the disease . The most common organism of septic meningitis is pyogenic bacteria, while viruses are the main cause of aseptic meningitis . Septic meningitis is considered as one of vital causes of death worldwide , so it is considered an endemic disease in Egypt. Diagnosed septic meningitis was investigated by microscopy of a Gram-stained smear, positive cerebrospinal fluid (CSF) culture, and by results of lumbar puncture .
| Aim|| |
The primary objective of this study was to assess the diagnostic role of cerebrospinal lactate dehydrogenase (LDH) serum procalcitonin (PCT) in meningitis in Beni-Suef Governorate and for differentiating septic from aseptic meningitis.
| Patients and methods|| |
This study was conducted at Beni-Suef Fever Hospital for 2 years during the period between March 1, 2014 to March 30, 2017. A standardized form for collecting information on demographic and clinical characteristics of enrolled patients was designed and completed for all patients with inclusion criteria as fever, boring headache, and projectile vomiting is suggestive of the disease and exclusion criteria as viral infections such as HIV, autoimmune, neoplasm, cyst, sepsis, hypertension, diabetes mellitus, dyslipidemia, chronic liver disease, chronic kidney disease, chronic obstructive pulmonary disease, hematological myeloprolifertive disease, and trauma of surgical intervention. This study was conducted on 260 patients with symptoms and signs of clinically acute meningitis and 100 persons as controls after an written consent for each patients. The patients were selected from meningitis wards in Beni-Suef Fever Hospital, Beni-Suef Governorate, Egypt, while the controls were selected from inpatients at other words. The enrolled 100 controls and 260 patients were divided into four groups: septic meningitis (group I: 139 patients), aseptic meningitis (104 patients; group II), and meningism (group III; 17 patients) and 100 controls who were attending fever hospital for complains other than central nervous system (CNS) infection from where blood samples were taken to test serum protein, serum LDH, and PCT.
Data were collected and statistically analyzed using SPSS Version 11 Statistical Package (SPSS; IBM Inc., Chicago, Illinois, USA). Comparison of qualitative data was performed with χ2-test. The validity of screening tests was measured and expressed as sensitivity and specificity (in comparison to diagnostic tests). The level of significance was considered at 5%. The highly significant level was at less than 0.01. Spearman’s correlation coefficient test was used for correlation between nonparametric quantitative data. Also, Mann–Whitney test was used for comparison between nonparametric quantitative data between two groups.
| Results|| |
A total of 260 cases with clinical suspicion of meningitis within 1–5 days of onset of their illness presented to outpatient clinics and emergency room department were admitted to Beni-Suef Fever Hospital for whom a lumbar puncture and laboratory studies were performed at the same time to establish the diagnosis. It was reported that the most number of cases appeared in the summer months (June, July, and August), while the least number was seen in the winter months (January, February, and March) which means that there are linear seasonal variations in all the three groups with highly significant (P<0.0001) ([Table 1]).
The mean±SD values for protein level (serum protein and CSF protein levels) in meningitis were shown to have a significant difference between studied groups as regards the mean protein level. So the cutoff values confirm that CSF contains exudate indicated infections ([Table 2] and [Table 3], [Figure 1]).
|Table 3 Diagnostic performance of serum protein and cerebrospinal fluid protein regarding cutoff value of cerebrospinal fluid protein greater than 50 mg/dl in the studied groups|
Click here to view
|Figure 1 ROC curve of cut off value of CSF protein >50 mg/dl studied groups.|
Click here to view
This table shows a comparison of the results of serum LDH testing in the studied groups. It was found that all 139 (100%) cases were above the normal range of elevated serum LDH in septic meningitis while of the 104 cases, 102 (98%) were shown to have above normal range elevated serum LDH, while two (2%) of the 104 cases were below the normal range, in the aseptic meningitis group all cases of meningism show normal range, only two controls have shown serum LDH above normal and they complained of chest infection (pneumonia) ([Table 4]).
|Table 4 Comparison between the studied groups regarding serum lactate dehydrogenase level|
Click here to view
The mean±SD for LDH level (serum LDH and CSF LDH levels) in septic and aseptic meningitis are shown in [Table 5] and [Table 6] ([Figure 2]).
|Table 5 Comparison between studied groups regarding mean lactate dehydrogenase level|
Click here to view
|Table 6 Diagnostic performance of cerebrospinal fluid lactate dehydrogenase regarding cutoff- value of cerebrospinal fluid lactate dehydrogenase >0.6 Ul/l of serum lactate dehydrogenase level|
Click here to view
|Figure 2 ROC curve of cut off value of CSF LDH >0.6 U/L of Serum LDH level.|
Click here to view
This table shows a comparison of results of serum PCT-Q testing in the studied groups. It was found that serum PCT testing was positive in all patients with septic meningitis while serum PCT testing is positive in 35 (34%) patients with aseptic meningitis and negative in 69 (66%) patients. And serum PCT-Q testing was negative in all patients with meningism. Also all control cases were assessed as normal serum PCT level ([Table 7] and [Tbale 8], [Figure 3]).
|Table 7 Comparison between the studied groups regarding serum procalcitonin level|
Click here to view
|Table 8 Diagnostic performance of serum procalcitonin regarding cutoff value of serum procalcitonin greater than 2.5 ng/dl|
Click here to view
| Discussion|| |
All patients who were admitted to Beni-Suef Fever Hospital with clinical suspicion of meningitis and who had undergone a lumbar puncture and laboratory studies at the same time were enrolled in this study. According to the discharge diagnosis, the patients were classified into three diagnostic groups: septic, aseptic meningitis, and meningism. Septic meningitis is a bacterial inflammation of the meninges and is identified by an abnormal number of white blood cells in CSF . The second group, that is, aseptic meningitis, is defined as meningitis in which no bacterial pathogen can be isolated by routine cultures, and a clear CSF with a leukocyte count of less than or equal to 100 cell/mm3 and is caused by either infectious causes (viral, bacterial, and fungal infection) or noninfectious causes such as autoimmune diseases and is identified by an abnormal number of lymphocytic CSF pleocytosis. Neurologic examination in this disease is normal except for meningism . This stratification of meningitis patients was based on the WHO case definition of septic meningitis  and many other investigators .These references documented septic meningitis by the detection in the CSF of greater than 100 white blood cells per ml in cases of negative bacterial cultures, latex film ,. Meningism is usually applied to those conditions who present with meningeal symptoms but CSF examination is normal and the subsequent investigation and evolution of the disease reveal the true diagnosis, for example, pneumonia, or subarachnoid hemorrhage . A significant difference between studied groups was found as regards mean LDH. So the cutoff values confirm that the increased LDH values indicated exudate and infections. This study revealed that septic and aseptic meningitis cases were found to peak during the summer months. Several studies that agree with the current study  found that aseptic meningitis cases increased during the summer months. In contrast Tawfik , demonstrated that winter and early spring were the seasonal peak of infection, whereas Youssef et al.  conducted that meningitis peaked in late autumn and winter months, especially for patients with culture-confirmed disease. This result could be attributed to increased susceptibility to meningitis which occurred by dry and dusty winds from the Sahara desert that affect the back of the nose and throat lining. This study results also revealed that (0.6 Ul/l) CSF LDH level cutoff and (2.5 µg/dl) serum PCT level cutoff differentiate septic from aseptic meningitis. A serum CSF LDH of greater than 0.6 Ul/l referred to septic meningitis and serum CSF LDH below this level indicated aseptic meningitis with a sensitivity of 98% and a specificity of 98%. Several studies in accordance with the current study results have shown that (0.6 Ul/l) CSF LDH level cutoff was a good predictor for differentiating between septic and aseptic meningitis. The study by Tunkel and colleagues ,, found that elevation of LDH level in the CSF is one of the best predictors of septic meningitis. In bacterial meningitis the count was >6 µl/l) and in aseptic meningitis it was <2 µl/l. However, the Qateae et al.  findings were inconsistent with the findings of the current study that CSF LDH has no role in the differentiation of septic from aseptic meningitis. The other significant predictor for differentiating bacterial from aseptic meningitis was (2.5 µg/dl) serum PCT level cutoff. However patients with septic meningitis had a serum PCT level of more than 2.5 µg/dl and aseptic meningitis had a serum PCT level below this level with a sensitivity of 100% and a specificity of 100%. In accordance with this study results. Prasad et al.  identify a serum PCT level cutoff of greater than 5 µg/dl with a sensitivity of 98.3% and a specificity of 93.5%. Dubos et al.  conducted that serum PCT level cutoff was greater than 5 µg/dl with a sensitivity of 94% and specificity of 100%. In contrast Viallon et al.  obtained a serum PCT level cutoff greater than 0.2 µg/dl with a sensitivity and specificity up to 100% in the diagnosis of septic meningitis. Also Dubos et al.  found that a PCT used alone at a 0.5 µg/dl threshold offered the best sensitivity (99%) and specificity (83%). Similarly Dubos et al.  identified a PCT of up to 0.5 µg/dl and a CSF protein of up to 0.5 g/l and were the best biologic tests with 89 and 86% sensitivity rates, 89 and 78% specificity rates. Also Prasad et al.  demonstrated a cutoff level of 0.28 µg/dl with a sensitivity and specificity of up to 100%, whereas Youssef et al.  reported that there was no significance of PCT level sensitivity and specificity, especially in adult populations agglutination test or direct examination of a Gram-stained CSF. Regarding the inconsistency of results about PCT cutoff, it could be explained by the samples size variation, in addition to the influence of open sample age in this study, compared with studies with a restricted age. Furthermore some studies reported in languages other than English .
| Conclusion|| |
Cerebrospinal LDH cannot be used only as a preliminary screening test, whereas PCT-Q was a good diagnostic marker for distinguishing septic from aseptic meningitis with high sensitivity and specificity. These data should be confirmed in further studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Saif El-Din S, Abdel-Wahab MF. In: Saif El-Din. A Guide Book of Tropical Medicine and Infectious Diseases. 2nd ed. Cairo: National Library of Tropical Medicine Department, Ain-Shams University; 1995. 244–246.
Tunkel AR. Bacterial meningitis. In: Schlossberg D (editors) Current Therapy of Infectious Disease. D2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001. 260–265.
Afifi S, Karsany MS, Wasfy M, Pimentel G, Marfin A, Hajjeh R. Laboratory-based surveillance for patients with acute meningitis in Sudan. Eur J Clin Microbiol Infect Dis 2009; 28:429–435.
Bannister BA, Gillespie SH, Jones J. Infection: Microbiology and Management. 3rd ed. Malden: Blackwell Science; 2006. 245–285.
Tunkel R, Scheld WM. Acute meningitis (Chapter 80). In: Mandell GL, Bennett JE, Dolin R, (editors) Principles and Practice of Infectious Disease. 6th ed. Philadelphia: Elsevier, Churchill Livingstone; 2005. 1083–1119.
Campagne G, Schuchat A, Djibo S, Ousséini A, Cissé L, Chippaux JP. Epidemiology of bacterial meningitis in Niamey, Niger. Bull World Health Organization 1999; 77:499–508.
Youssef FG, El-Sakka H, Azab A, Eloun S, Chapman GD, Ismail T et al.
Etiology, antimicrobial susceptibility profiles, and mortality associated with bacterial meningitis among children in Egypt. Ann Epidemiol 2004; 14:44–48.
Takeshima S, Neshige S, Himeno T, Hara N, Yoshimoto T, Takamatsu K et al.
Clinical, epidemiological, and etiological studies of aseptic meningitis in adults. Rinsho Shinkeigaku Clin Neurol 2014; 54:791–797.
Tawfik MM. 1988 Acute bacterial meningitis admitted to Embaba Fever Hospital, a reappraisal. MD Thesis (Trop. Med.), Faculty of Medicine, Cairo University: Cairo.
Tunkel AR, Michael SWGL, Dollin RG, Bennett JE. Acute meningitis. In: Mandell GL (editor) Principles and Practice of Infectious Disease. Philadelphia: Elsevier, Churchill Livingstone; 2010. 1083–1119.
Huy NT, Thao NT, Diep DT, Kikuchi M, Zamora J, Hirayama K. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis. Crit Care 2010; 14:R240.
Kepa L, Oczko-Grzesik B, Błedowski D. Evaluation of cerebrospinal fluid and plasma lactate dehydrogenase activity in patients with purulent, bacterial meningoencephalitis. Przegl Epidemiol 2006; 60:291–298.
Qateae SO, Mushrif MM, Jasim AM. The role of lactate dehydrogenase in differentiating between bacterial and non-bacterial meningitis in children under five years in Ramadi Maternity and Children Hospital. Journal of University of Anbar for Pure science, 2009; 3:1–5.
Prasad R, Kapoor R, Mishra OP, Srivastava R, Kant Singh U. Serum procalcitonin in septic meningitis. Indian J Pediatr 2013; 80:365–370.
Dubos F, Korczowski B, Aygun DA, Martinot A, Prat C, Galetto-Lacour A et al.
Serum procalcitonin level and other biological markers to distinguish between bacterial and aseptic meningitis in children: a European multicenter case cohort study. Arch Pediatr Adolesc Med 2008; 162:1157–1163.
Viallon A, Zeni F, Lambert C, Pozzetto B, Tardy B, Venet C, Bertrand JC. High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis. Clin Infect Dis 1999; 28:1313–1316.
Dubos F, Moulin F, Gajdos V, De Suremain N, Biscardi S, Lebon P et al.
Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis. J Pediatr 2006;80:1083–1119.
Velissaris D, Pintea M, Pantzaris N, Spatha E, Karamouzos V, Pierrakos C, Karanikolas M. The role of procalcitonin in the diagnosis of meningitis: a literature review. J Clin Med 2018; 7:148.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]