Published: 2017-02-22

Adenosine deaminase activity in cerebrospinal fluid: diagnostic investigation in central nervous system disorders in children

Sk Rafikul Rahaman, Anshuman Panda, Pradyut K. Mandal, Kripasindhu Chatterjee, R. V. Borgaonkar


Background: Tubercular meningitis (TBM) is an endemic disease in developing countries. Adenosine deaminase activity (ADA) has been of great importance for many years in TBM diagnosis. The objective of this study was to determine the CSF-ADA levels in different CNS disorders, to compare the CSF-ADA activity in different types of meningitis, to find out the sensitivity and specificity of CSF-ADA in the diagnosis of TBM and to establish the prognostic value of CSF-ADA in TBM in comparison to Control group.

Methods: For control group CSF was collected from the patients of simple febrile convulsions and idiopathic epilepsy.

Results: The present study was carried out in the 112 cases of different CNS disorders, age ranging from 4 months to 12 years with a mean age of 4.12 years and 38 cases (27+11) of control group (simple febrile convulsion and idiopathic epilepsy). In the present study CSF-ADA level was statistically significantly increased in all types of meningitis (p<0.05). In case of TBM, the mean CSF-ADA level increased statistically significantly with increase in CSF protein level (p<0.05). In case of TBM, there was no significant difference in the mean ADA value according to CSF sugar level (p<0.10). In case of TBM, the mean CSF-ADA level increased significantly with increase in CSF cell count (p< 0.01) mainly lymphocytes.

Conclusions: Thus it can be concluded from our study that CSF-ADA estimation is relatively simple and inexpensive procedure in the early diagnosis of tuberculous meningitis with high sensitivity (100%) and specificity (97.5%) at a cut-off level of 5IU/L and can be used in differentiating TBM from other types of meningitis. Along with diagnostic utility of CSF-ADA, it has also prognostic value in the follow-up case of tuberculous meningitis.


Adenosine deaminase, CNS, Children, Tuberculous meningitis

Full Text:



Van der Weyden MB, Kelley WN. Human adenosine deaminase. Distribution and properties. J Biol Chem. 1976;251(18):5448-56.

Sullivan JL, Osborne WR, Wedgwood RJ. Adenosine deaminase activity in lymphocytes. Br J Haematol. 1977;122:216-20.

Martinez-Vazquez JM, Ribera E, Ocaña I, Segura RM, Serrat R, Sagrista J. Adenosine deaminase activity in tuberculous pericarditis. Thorax. 1986;41(11):888-9.

Ribera E, Martinez-Vazquez JM, Ocaña I, Segura RM, Pascual C. Activity of adenosine deaminase in cerebrospinal fluid for the diagnosis and follow-up of tuberculous meningitis in adults. J Infect Dis. 1987;155(4):603-7.

Segura RM, Pascual C, Ocaña I, Martínez-Vázquez JM, Ribera E, Ruiz I, et al. Adenosine deaminase in body fluids: a useful diagnostic tool in tuberculosis. Clin Biochem. 1989;22(2):141-8.

Selvakumar N, Vanajakumar, Duraipandian M, Thillothammal N, Prabhakar R. Cerebrospinal fluid adenosine deaminase and lysozyme levels in the diagnosis of tuberculous meningitis. Ind J Tub. 1991;38:217-20.

Global Tuberculosis Report: 2016, WHO Library Cataloguing-in-Publication Data, World Health Organization 2016, WHO/HTM/TB/2016. Available at Accessed on 19 Novembe 2016.

Prasad R, Kumar A, Khanna BK. Adenosine deaminase activity in cerebrospinal fluid for diagnosis of tuberculous meningitis. Indian J Tub 1991;38:99-102.

Hass EJ, Madhavan T, Quinn EL. Tuberculous meningitis in an urban general hospital. Arch Intern Med. 1977;137:1518-21.

Molavi A, LeFrock JL. Tuberculous meningitis. Med Clin North Am. 1985;69(2):315-31.

Hankiewicz J, Lesniak M. Adenosine deaminase in cerebrospinal fluid. Enzymologia. 1972;43(6):385-95.

Piras MA, Gakis C. Cerebrospinal fluid adenosine deaminase activity in tuberculous meningitis. Enzyme. 1973;14:311-7.

Malan C, Donald PR, Golden M, Taljaard JF. Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis. J Trop Med Hyg. 1984;87:33-40.

Hirschhorn R, Paageorgiou PS, Kesarwala HH, Taft LT. Amerioration of neurologic abnormalities after enzyme replacement in adenosine deaminase deficiency. N Engl J Med. 1980;303(7):377-80.

Kluge H, Winkler G, Wieczorek V, Vollhardt A. Adenosine desaminase in the cerebrospinal fluid in neurologic and psychiatric patients. Klin Wochenschr. 1969;47(23):1268-9.

Viallon A, Botelho-Nevers E, Zeni F. Clinical decision rules for acute bacterial meningitis: current insights. Open Access Emergency Med OAEM. 2016;8:7-16.

Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23(3):467-92.

Bahr NC, Boulware DR. Methods of rapid diagnosis for the etiology of meningitis in adults. Biomarkers Med. 2014;8(9):1085-103.

Venkatesan A, Geocadin RG. Diagnosis and management of acute encephalitis: A practical approach. Neurology. Clin Pract. 2014;4(3):206-15.

Steiner I, Budka H, Chaudhuri A. Viral encephalitis: a review of diagnostic methods and guidelines for management. Eur J Neurol. 2005;12:331-43.

Gómez-Río M, Caballero MM, Górriz Sáez JM, Mínguez-Castellanos A. Diagnosis of neurodegenerative diseases: the clinical approach. Curr Alzheimer Res. 2016;13(5):469-74.

Leung DT, Bogetz J, Itoh M. Factors associated with encephalopathy in patients with salmonella enterica serotype typhi bacteremia presenting to a diarrheal hospital in Dhaka, Bangladesh. Am J Trop Med Hyg. 2012;86(4):698-702.

Sinha A, Sazawal S, Kumar R, Sood S, Reddaiah VP, Singh B, et al. Typhoid fever in children aged less than 5 years. Lancet. 1999;354:734-7.

Desai J, Mitchell WG. Acute cerebellar ataxia, acute cerebellitis, and opsoclonus-myoclonus syndrome. J Child Neurol. 2012;27(11):1482-8.

Misra UK, Kalita J, Prabhakar S, Chakravarty A, Kochar D, Nair PP. Cerebral malaria and bacterial meningitis. Ann Ind Aca Neurol. 2011;14(Suppl1):S35-39.

O’Shea TM. Diagnosis, treatment, and prevention of cerebral palsy in near-term/term infants. Clin Obstetr Gynecol. 2008;51(4):816-28.

Van der Meché FG, Van Doorn PA, Meulstee J, Jennekens FG. GBS-consensus group of the dutch neuromuscular research support centre. Diagnostic and classification criteria for the Guillain-Barré syndrome. Eur Neurol. 2001;45(3):133-9.

Mohammadi M. Febrile seizures: four steps algorithmic clinical approach. Iranian J Pediatr. 2010;20(1):5-15.

Engel J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE task force on classification and terminology. Epilepsia. 2001;42:796-803.

Giusti G. Adenosine deaminase. In: Bergmeyer HU, ed. Methods of Enzymatic Analysis. 2nd ed. New York: Academic Press; 1974:1092-9.

Malan C, Donald PR, Golden M, Taljaard JJ. Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis. J Trop Med Hyg. 1984;87(1):33-40.

Udani PM, Parekh UC, Dastur DK. Tuberculosis of the central nervous system: newer clinical types. in: Paper presented at the 12th International Congress of Pediatrics, Mexico. Vol. 2. Memoirs, Impresiones Modernas, Mexico; 1968:130.

Alarcón F, Escalante L, Pérez Y, Banda H, Chacón G, Dueñas G. Tuberculous meningitis. Short course of chemotherapy. Arch Neurol. 1990;47(12):1313-7.

Udani, PM. Incidence of tuberculosis in children. Indian J Child Hlth. 1961;10:515-25.

Lincoln EM, Sordillo VR, Davies PA. Tuberculous meningitis in children. A review of 167 untreated and 74 treated patients with special reference to early diagnosis. J Pediatr. 1960;57:807-23.

Udani PM. Evaluation of tuberculin test in pediatric practice. Indian Pediatr. 1982;19(6):469-86.

Zaarbi M, Sane S, Girdany BR. The chest roentgenorarnin the early diagnosis of tuberculous meningitis in the children. Am J Dis Child 1971; 121:389-392.

Udani PM, Bhat US, Dastur DK. Tuberculosis of central nervous system. Indian Pediatr. 1973;10(11):647-56.