Cerebrospinal Fluid Adenosine Deaminase Levels and Adverse Neurological Outcome in Pediatric Tuberculous Meningitis

Government of India, New Dilli, NCT, India
Infection (Impact Factor: 2.62). 09/2005; 33(4):264-6. DOI: 10.1007/s15010-005-5005-4
Source: PubMed


There is a lack of data on the prognostic significance of changes in cerebrospinal fluid (CSF) parameters in tuberculous meningitis. Our objective was to determine whether changes in CSF parameters are associated with poor neurological outcome in tuberculous meningitis.
We conducted a prospective cohort study on children admitted with a diagnosis of tuberculous meningitis to Government General Hospital in Kakinada, India. On admission, CSF parameters including cell count with fraction of lymphocytes and neutrophil leukocytes, glucose, protein, lactic dehydrogenase (LDH), and adenosine deaminase (ADA) levels were measured. We compared levels in children with and without adverse neurological outcome.
A total of 26 children was enrolled over a 2-year period. Ten had an adverse neurological outcome. Six had permanent neurological deficits (four hemiplegia and two cranial nerve palsies), two a hydrocephalus and two died. There was no significant (p>0.05) difference in age, gender and in CSF parameters, including cell count, lymphocyte and neutrophil leukocyte fraction, glucose, protein, and LDH levels between patients with and without adverse neurological outcome. Patients with adverse outcome had with a mean (SD) of 17.1 (3.2) IU/l a significantly higher ADA level than patients without, who had a mean (SD) level of 11.3 (2.7) IU/l (p<0.001, t-test).
Adverse neurological outcome in childhood tuberculous meningitis is associated with increased cerebrospinal fluid adenosine deaminase levels.

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    • "However, this study used only 12 cases of TBM patients, and pyogenic and viral meningitis were not distinguished from the group with other central nervous system diseases. Similarly increased CSF ADA levels have been reported in childhood TBM with adverse neurological outcome [27]. However, Gambhir et al reported a low sensitivity of 44% and specificity of 75% for ADA test with a cut off value 8 IU/L/min, which showed overlap between TBM and non-TBM patients, especially for infectious neurological disorders like pyogenic meningitis [28]. "
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    ABSTRACT: Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of TBM and non-TBM patients. ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 +/- 3.87 (2.99-26.94), mean +/- SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 +/- 2.14 (4.99-13.96) and from the non-infectious neurological disorders group, 2.71 +/- 1.96 (0.00-7.68), P < 0.0001 for both comparisons. A cut-off value of 11.39 U/L/min for the TBM patients was calculated from the mean + SD of the non-TBM patients. The ADA test gave a sensitivity of 82% and a specificity of 83% for infectious TBM when this cut-off value was used. This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.
    Cerebrospinal Fluid Research 03/2006; 3:5. DOI:10.1186/1743-8454-3-5 · 1.81 Impact Factor
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    • "CSF was obtained by lumbar puncture as soon as possible after admission if there were no contraindications, and after informed consent by the parents. CSF cell count, glucose, protein and CSF and serum LDH levels were determined by standard methods as in a previous study published by this group [9]. ADA levels were determined using the Berthelot reaction, through the ammonia released when adenosine is broken down to inosine. "
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    ABSTRACT: In developing countries where Plasmodium falciparum malaria is endemic, viral encephalitis and cerebral malaria are found in the same population, and parasitemia with Plasmodium falciparum is common in asymptomatic children. The objective of this study was to investigate the cerebrospinal fluid (CSF) biochemistry in children with cerebral malaria compared to those with presumed viral encephalitis. We studied the following CSF parameters: cell count, glucose, protein, lactic dehydrogenase (LDH) and adenosine deaminase (ADA) levels, in children with cerebral malaria, with presumed viral encephalitis, and in control subjects who had a lumbar puncture after a febrile convulsion with postictal coma. We recruited 12 children with cerebral malaria, 14 children with presumed viral encephalitis and 20 controls prospectively, over 2 years in the Government General Hospital in Kakinada, India. Patients with cerebral malaria had significantly lower CSF glucose, and higher protein, LDH, CSF/blood LDH ratio and CSF ADA levels but a lower CSF/serum ADA ratio compared to controls (p < 0.01). Patients with cerebral malaria had lower CSF white cell count, glucose, protein, LDH levels and CSF/serum ADA ratio compared to patients with presumed viral encephalitis. CSF/serum ADA ratio was lower in patients with cerebral malaria due to the fact that serum ADA levels were significantly higher in patients with cerebral malaria compared to the other two groups. A CSF/serum ADA ratio of <0.38 and a CSF glucose level of <3.4 mmol/l were selected as the cut-off values with the highest sensitivities and specificities for comparing the two conditions. CSF/serum ADA ratio and CSF glucose levels were the best discriminators of cerebral malaria from presumed viral encephalitis in our study. Further studies are needed to explore their usefulness in epidemiological studies.
    Cerebrospinal Fluid Research 02/2006; 3:8. DOI:10.1186/1743-8454-3-8 · 1.81 Impact Factor

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