Journal of Infection (I994) 29, 41-44

Adenos ine deaminase concentrat ion in cerebrospinal fluid during bruce l la mening i t i s

Mohammad S. Abduljabbar

Division of Neurology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

Accepted for publication 22 March I994

Summary

Adenosine deaminase (ADA) activity was measured in the CSF of five patients with confirmed brucella meningitis. The mean enzyme value was 20.00 U/1 in the presence of high lymphocyte counts in the CSF. We conclude from this preliminary result that the quick and simple estimation of ADA in CSF could be of great value in the diagnosis of brucella meningitis as the enzyme concentration was high in all five patients. This finding is however not specific and similar results have been reported in other meningitides such as tuberculous meningitis.

I n t r o d u c t i o n

Adenosine deaminase (EC 3 .5 .4 .4 ) is an enzyme of purine catabolism which catalyses the pathway from adenosine to inosine. 1 It is widely distributed in the human organism, but its physiological role is especially important in lymphoid tissues. 2 In certain infectious diseases an increased concentration of ADA has been observed to be associated with an active participation of cell- mediated immune response. 3,~

There have been several publications concerning the diagnostic value in tuberculosis of ADA measurement in various body fluids, including the CSF.5.6 To the best of our knowledge such studies have not investigated ADA values in brucellosis.

Brucella meningitis is a very important cause of chronic meningitis in Saudi Arabia. Its specific diagnosis requires positive CSF culture of brucella and/or an increase in brucella antibody titre. The lengthy time required to confirm the results may lead to delay in treatment. We report our observations regarding the value of ADA analysis in patients with brucella meningitis.

Patients and results

Five patients were seen in the neurology clinic or emergency room with subacute onset of headache, malaise, low grade fever and blurred vision. Ali gave a history of contact with animals.

On physical examination all patients were febrile and had the classical features of meningeal irritation: neck stiffness and positive Kernig's and Brudezinski signs. Patients I and 2 had bilateral papilloedcma. Clinical examination was otherwise normal and there was no focal neurological deficit.

Address correspondence to: Dr. Mohammad Abduljabbar, Associate Professor of Neurology, King Khalid University Hospital, P.O. Box 78o5 (38), Riyadh 11472 , Saudi Arabia.

oi63-4453/94/29oo4I +04 $o8.00/0 © I994 The British Society for the Study of Infection

42 M.S . A B D U L J A B B A R

Table I CSF findings and brucella serology in five patients

Blood CSF

Patient brucella titres Cells (% Lymph) Protein (g/l) Sugar (mmol) Serology

r IO24 o 92 (98 %) 0'93 I- 5 Positive 2 2560 I35 (92 %) I'36 2-0 Positive 3 2560 85 ° (IO0 %) 0"72 2' 3 Positive 4 256o I7O (97 %) 4"4 2'I Positive 5 r28o 15o (98 %) 1"5 2'0 Positive

Table II Adenosine deaminase values in CSF of patients with brucella meningitis

A D A value in CSF (U/l) After Patient before treatment treatment

I 23 '03 8"4 2 I9"50 0 3 I4"75 0 4 22"3 0 5 20 '5 0

The results of routine laboratory investigations, which included complete blood count, liver function tests, renal profile and electrolytes estimation, were unremarkable.

The CSF findings and brucella serology results are shown in Table I. T h e y clearly indicate the involvement of the meninges by brucella. The CSF changes were mainly of an increase in WBC count with predominance of lymphocytes ( 9 2 % - I o o % ) , an increase in protein and reduced sugar concentration (below 2 mmols with blood sugar value of 6 mmols). Table II shows the changes in ADA concentration in the five patients. These ranged between I4"75 and 23"o3 U/1 (upper limit of normal values for our laboratory is 2"I U/l) . Patient number I had a second estimation of ADA concentration in CSF after 8 weeks therapy, when it was found to have dropped from 23"03 to 8"4 U/1.

Discuss ion

Chronic meningitis remains a diagnostic challenge to clinicians because bacteriological support for diagnosis is usually lacking or delayed. T u - berculosis and brucellosis remain the two commonest causes of chronic meningitis in Saudi Arabia. 7

Dur ing the past decade, various biochemical tests on CSF, such as lactate concentration,8.9 lactate dehydrogenase activity 1°' 11 and the bromide partit ion test, 12,13 have been reported to help in early diagnosis particularly of tuberculous meningitis. The estimation of ADA in CSF has also been studied

C S F adenosine deaminase in brucellosis 43

in tuberculous and pyogenic meningitis. 13 All available data indicate that A D A analysis is of great benefit in differentiating between these two types of meningitis . Recently, however, Chawla 14 suggested that ADA concentrat ion in C S F may not be of such diagnostic significance as previously reported.

Meningi t is due to brucella species is rare but may be the only manifestat ion of the disease. 15 Recognit ion of such a presentat ion is important , particularly in endemic areas. 16 T h e prognosis in brucella meningit is is closely linked to the stage at which t rea tment is started, and the diagnosis and decision to start t rea tment will often rest upon indirect evidence such as the history and typical C S F findings, as well as positive serology and /o r culture.

T h e finding of high A D A concentrations in our patients appears helpful in early diagnosis of brucella meningitis . I t can also be used as a simple test to differentiate brucella f rom acute pyogenic meningitis as the A D A value in C S F of the latter is reported to be low. 1~ Unfor tuna te ly however the estimation may be unhelpful in dist inguishing quickly between tuberculous and brucella meningit is as a high concentrat ion of ADA may be observed in both. However , P C R has been shown to be diagnostic in tuberculous meningitis. ~7 In addition, an abnormal chest X-ray and a positive tubercul in test may also be helpful. T h e high concentrat ion of ADA is considered to be the result of lymphocytosis in the CSF. ~ T h e decrease of A D A after t reatment in patient number I points to the usefulness of this test in moni tor ing the course of the disease.

In conclusion, this prel iminary report of A D A estimation in C S F in brucella meningit is is no tewor thy and could prove useful in diagnosis. I t is not a specific test for brucella meningit is as other meningit ides may have the same abnormali ty. A well designed prospective s tudy of a large number of patients is needed to confirm the observation.

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44 M. S. ABDULJABBAR

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