Significance of CSF-LDH in various types of meningitis

The cerebrospinal fluid concentration of Lactate dehydrogenase (LDH) was studied in patients with pyogenic and tubercular meningitis. Significant increase in LDH level (P<0.001) were observed in the test group when compared to the control group. LDH may useful in differentiating viral from other meningitis. It may act as corroborative evidence of meningitis.


Introduction
Meningitis refers to an inflammatory process of the leptomeninges and CSF within the subarachnoid space. Infectious meningitis is broadly classified into acute pyogenic (usually bacterial meningitis) aseptic (usually acute viral meningitis) and chronic usually (tuberculous, spirochetal or cryptococcal) [1].
Pyogenic meningitis is a major pediatric problem all over the world, especially in developing countries like India [2]. Antibiotics have reduced the mortality from almost 100% to 8-30%. Early and reliable diagnosis is the key to successful out come 2 .
As presenting signs and symptoms may be inconclusive laboratory tests are essential in establishing a definite diagnosis. So, the rapid diagnosis of bacterial meningitis is an important function of most laboratories and usually based on CSF examination [3].
Many test for rapid diagnoses of bacterial meningitis have been introduced including the nitroblue tetrazolium test, litmus test, counter immnoelecrophoresis and gram stain. Even though the above tests, favors rapid diagnosis, they have their own drawbacks. Counter immunoelectrophoresis is utilized in the diagnosis of meningitis due to haemophilus, pneumococci and meningococci but the method requires specific high tittered antisera and overall false negative rate is about 10%. The litmus lysate test for endotoxin is rapid and accurate in diagnosing gram negative meningitis but is of no value in cases of gram positive etiology further more if the gram negative bacterial count in the CSF is below 3000 to 400 microorganisms per cubic centimeter, a false negative litmus lysate test may result [4].
The information yielded by examination of Cerebrospinal fluid (CSF) is often of crucial importance in the diagnosis of neurological disease [5]. Various biochemical markers in CSF including lactate dehydrogenase (LDH) have been studied in diverse neurological conditions like leptomeningeal carcinomatosis, stroke and different types of meningitis [6]- [8].
The gram stain may be negative in as many as 30% of cultured proved bacterial meningitis prior antibiotic treatment may also alter bacteria, so as to IJBAR (2015) 6 (03) www.ssjournals.com obscure their morphological and staining characteristic [4].
Enzymatic study (CSF-LDH) is a better sensitive parameter in diagnosis of various types of meningitis when all the above rapid diagnostic method fail [4].

Aims and Objectives
 The purpose of this study was to establish early diagnosis and therapeutic value of CSF-LDH in bacterial and non bacterial meningitis.  To evaluate the importance of CSF-LDH estimation as compared to other investigation in diagnosis of bacterial meningitis in adults as well as in children.  To find out whether it is specific, superior and faster than other parameters in differential diagnosis of meningitis.  To find out its usefulness in differential diagnosis of meningitis.

Material and Methods
The present study carried out at Department of Pathology, Shree M.P. Shah Medical College and Guru Govind Singh Hospital, Jamnagar during the period from July 2004 to July 2006.
Total 140 CSF samples were examined. Out of them 100 patients of all age groups and either sex of clinically suspected cases of meningitis were taken as test group. The physical, Biochemical and microscopic examination of CSF were done in all cases of pyogenic, tuberculous and viral meningitis. 40 control subjects of all age and either sex were taken as control group.
In all cases, detailed history including age, sex, duration of symptoms, presenting symptoms, history of treatment prior to hospitalization.
Routine hematological investigation, X-ray, USG and CT scan finding were noted.CSF was obtain by lumber puncture and examined in detail including physical appearance, turbidity, presence of xanthochromia, cobweb, clot etc.
CSF microscopic examination including total cell count and differential count were done. Biochemistry analysis like (Sugar, Protein, Chloride, ADA and LDH) was also done.

Result
The present study consisted of 100 cases of suspected meningitis to differentiate them in to pyogenic of non pyogenic including tubersulous and view group by the help of CSF examination including physical color, appearance, xanthochromia etc. chemical (Sugar, Protein) microscopic examination with estimation of CSF LDH as mention in material and method.
The results were recorded, studied and tabulated as follow in 100 cases of meningitis and 40 cases of control group. Table no.01 shows that majority of cases (72.5%) occurred below 3 year of age in cases of pyogenic meningitis. The vast majority of cases (60%) were below one year. The cause of increase incidence during the first 3 year of life is possibly due to increase meningeal permeability.
In case of tuberculous meningitis, majority of cases below 5 year of age (72.5%) with the maximum incidence being in the age group of 1-2 years (25%) fallowed by 0-12 month (20%) and 3-5 years (20%).      In cases of pyogenic meningitis detection of 'p' value is <0.001 is highly significant.
So, this shows that test is highly significant for diagnosis of bacterial meningitis to other meningitis group.

Discussion
Meningitis is a significant cause of morbidity and mortality in children worldwide. Neurological outcome and survival depend largely on damage to central nervous system prior to effective treatment. Quick diagnosis in acute bacterial meningitis is due to large spectrum of signs and symptoms. However, it is usual practice to start antibiotics before the complete laboratory results are available. Such blind prescriptions are usually in non menigitis doses. Majority of children who reported to hospital, therefore, have already been treated with inadequate dose of antibiotics and present atypical features in CSF.
The activity of LDH varies from person to person and also from laboratory due to variation in the standardization of apparatus and reagents used.   [16]. In the present study the highest incidence of disease i.e. 65% occurred in children under 5 years of age.
The incidence decrease after 5 years of age i.e. 10% between 6-7 years of age and 5% above 7 years of age Udani et al [15] and Benakappa et al [16] has reported similar decrease in incidence. CSF-LDH activity is markedly increased in pyogenic meningitis group in the present study and it is correlated well with study of P.V. Nelson and study of Knight.

Conclusion
Bacterial meningitis is more common than non bacterial meningitis. Pyogenic meningitis is more prevalent under 1 year of age group while tuberculous meningitis is seen most frequently betweens 3 to 5 year of age. Estimation of CSF-LDH activity shows more sensitive (82.5%) and specificity (87.5%) to differentiate pyogenic meningitis from non bacterial meningitis. CSF-LDH level has inverse relationship with meningitis and direct relationship with leucocytosis.
So, overall conclusion of study is that estimation of CSF-LDH activity is not only supplementary aid but diagnostic and differentiating aid for meningitis.