Oman Medical Journal (2013) Vol. 28, No.

DOI 10. 5001/omj.2013.47

Original Articles
Tuberculous Meningitis: A Comparison of Scoring Systems for Diagnosis
Roshan Kurien, Thambu David Sudarsanam, Samantha S, and Kurien Thomas

Received: 11 Feb 2013 / Accepted: 19 Apr 2013
© OMSB, 2013

Abstract Introduction

Objectives: Tuberculous meningitis (TBM) is a major clinical and
public health problem, both for diagnosis and management. We
compare two established scoring systems, Thwaites and the Lancet
C entral nervous system (CNS) tuberculosis is one of the more
serious manifestation of extra pulmonary TB constituting 6% of
consensus scoring system for the diagnosis of TB and compare the all TB cases.1 Among CNS tuberculosis, tuberculous meningitis
clinical outcome in a tertiary care setting. (TBM) remains the most common presentation. In spite of
Methods: We analyzed 306 patients with central nervous system advances in diagnostic technology and effective therapeutic options,
(CNS) infection over a 5-year period and classified them based on the it continues to pose significant management challenges. Despite
unit’s diagnosis, the Thwaites classification as well as the newer Lancet anti-TB chemotherapy, 20-50% of the affected people die and many
consensus scoring system. Patients with discordant results-reasons who survive have significant neurological deficits. The case fatality
for discordance as well as differences in outcome were also analyzed. is noted to be associated significantly with delay in diagnosis,
Results: Among the 306 patients, the final diagnosis of the treating treatment and HIV infection. The poor sensitivity of cerebrospinal
physician was TBM in 84.6% (260/306), acute CNS infections in fluid (CSF) culture in diagnosis of pyogenic,2 and TBM is one of
9.5% (29/306), pyogenic meningitis in 4.2% (13/306) and aseptic the major challenges in the diagnostic workup, hence many patients
meningitis in 1.3% (4/306). Among these 306 patients, 284 (92.8%) are treated empirically with antibiotics by care givers even before
were classified as "TBM" by the Thwaites" score and the rest as coming to a hospital leading to confusion with the entity "partially
"Pyogenic". The Lancet score on these patients classified 29 cases treated pyogenic meningitis".
(9.5%) as 'Definite-TBM', 43 cases (14.1%) as "Probable-TBM", 186 Two commonly used methods -Thwaites' system,3 and more
cases (60.8%) as "Possible-TBM" and the rest as "Non TBM". There recently, the Lancet consensus scoring system have been developed
was moderate agreement between the unit diagnosis and Thwaites to improve the diagnostic accuracy.4 The scoring systems include
classification (Kappa statistic = 0.53), as well as the Lancet scoring clinical features, CSF findings, as well as neurological imaging in
systems. There is only moderate agreement between the Thwaites making a diagnosis. Our medical unit diagnosis of TBM is made on
classification as well as the Lancet scoring systems. It was noted a combination of clinical features and CSF findings (largely based
that 32/ 284 (11%) of patients who were classified as TBM by the on the Thwaites criteria), though finally decided by the treating
Thwaites system were classified as "Non TBM" by the Lancet score consultant. CT and MRI tests were used only when there was
and 6/258 (2%) of those who were diagnosed as possible, probable suspected neurological defecit. We did not use any algorithm.
or definite TB were classified as Non TB by the Thwaites score. The present study evaluates the profile of patients with a
However, patients who had discordant results between these scores diagnosis of CNS infections attending a tertiary care centre in
were not different from those who had concordant results when India with a focus on TBM and compares the diagnosis made by
treatment was initiated based on expert clinical evaluation in the the treating team with that of the Thwaites and the Lancet scoring
tertiary care setting. systems.
Conclusion: There was only moderate agreement between the
Thwaites' score and the Lancet consensus scoring systems. There Methods
is need to prospectively evaluate the cost effectiveness of simple but
more effective rapid diagnostic alogrithm in the diagnosis of TB, Patients admitted under one medical unit of a tertiary level university
particularly in a setting without CT and MRI facilities. teaching hospital with approximately 40,000 outpatients (OP)
and 2000 inpatients (IP) per year were eligible for inclusion. The
Keywords: Tuberculosis; Meningitis; Scoring systems; Thwaites hospital has excellent medical records, and all information is stored
score; Lancet Consensus score; Agreement. electronically and coded according to International Classification of
Diseases (ICD) 9 system of coding. The study data was collected for
a period of 5 years (2006-2010) from IP charts of the medical unit.
Roshan Kurien, Thambu David Sudarsanam , Samantha S, Kurien All patients who had readmission and did not have a diagnosis of
Thomas CNS infection were included.
Medicine Unit 2, Christian Medical College, Vellore, TN India
E-mail: The search terms included pyogenic meningitis, tubercular

Oman Medical Specialty Board

6 TBM" by the Lancet score. all *TBM-TB Meningitis. the CSF cell count "TBM" by the Thwaites’ score and the rest as "Pyogenic".3%) diagnosis of TBM is made if there is evidence of Acid Fast Bacilli cases classified as "TBM" by Thwaites’ score were not diagnosed as (AFB) in CSF smear. probable.8%) as "Possible-TBM" tubercular meningitis and a score of more than 4 is suggestive of and 48 cases (15. The possible TB category.11 was used for entry and The results of the cranial nerve palsy and abnormal CT scan all statistical analysis was done using Statistical Package for Social results contribute towards the difference between the scores. 3:163-166 meningitis. acute CNS infections in entered into epidata version 3. The extracted data 9.3 (SD: 16. Epidata 3. Namely only 17 /186 (9%) cases outcomes at discharge from the hospital were evaluated based on diagnosed as "Non TBM" by the unit were classified as "Possible the Modified Rankin Score (MRS). If a patient has a total score of 4 or less. Based on the total scores assigned. 32 were either readmissions or were not CNS infections and were excluded based on inclusion/exclusion criteria.8% (36/306) died and All patients diagnosed as TBM were also scored using the medical 33. The comparison of the two scoring systems is given in Table using frequencies and percentages. A probable diagnosis is made if the total score is >10 pts if the Unit were not classified as TBM by the Thwaites score. classification of the same patients by the Thwaites’ score. only 29 of 234 (11%) cases for Total 284 22 306 which mycobacterial cultures were sent grew had M.4. It was noted that 32/284 (11. A definite classification (kappa 0. We evaluated whether there was any difference were diagnosed as possible. There were 192 (62.5 discharge as evidenced by an MRS of 3-6. There which are devided in 4 categories (clinical. Of these. For all patients. CSF.5% (29/306). 338 IP records were Unit Diagnosis Total identified using the search strategy as having CNS infections. with a maximum score of the Lancet classified 29 cases (9. 43 cases 13. Association between categorical 3.3 The clinical methods in diagnosing TBM. aseptic Meningitis and acute CNS infection. Inc. Table 1: Comparison of the Medical unit’s diagnosis vs. While and the percentage of CSF neutrophilia. patients have no imaging. probable or definite TB were classified in outcomes based on the three scoring methods (i. No.1%) as "Probable-TBM". UK score. The age varied from 15 to 83 years system and the Lancet scoring system for TBM.11 for analysis. TBM Pyogenic Among these. 186 cases (60. Oman Medical Specialty Board . TBM* 252 8 260 leaving 306 cases with a diagnosis of CNS infection.7%) as "Non TBM". which indicates that there is reasonably good agreement between variables was assessed using Chi-square test and comparison of the scores. which were Non. Oman Medical Journal (2013) Vol. tuberculosis. the Thwaites score and the Lancet score). Some Sciences (SPSS) software (version 16. variables such as the presence of TB elsewhere appear more in those USA).3% (4/306). the Results Thwaites score classification. It was also noted that 32/ 284 (11%) patients who means was done using independent two sample t-test.3% (102/306) had significant residual neurological problems at research council (MRC). 284 (92. with concordant results. pyogenic meningitis in 4. differences in the discordant results between systems were analyzed Table 4 highlights the reasons for the difference in classification.7%) males adequate data was available from records to calculate both scores.2). with a mean of 37. the diagnosis of Table 2. culture or on histopathology of brain or spinal "TBM" by the unit and 8/260 (3%) patients diagnosed as TBM by cord. SPSS.. IL. study No: IRB (EC) . the Among these 306 patients. As expected. The Thwaites' Score has 5 parameters including age.53).e. total white blood cell count.2 Table 1 compares the unit’s clinical diagnosis with the The Lancet consensus scoring system has 20 parameters. CNS imaging and was moderate agreement between the unit diagnosis and Thwaites evidence of TB elsewhere) with a maximum score of 20. or >12 pts if imaging was used. 11. The data Among the 306 patients.ER-4-24-08-2011. the final diagnosis of the treating from the records was extracted into a clinical research form and physician was TBM in 84.4. Chicago. Patients with were classified as TBM by the Thwaites' system were classified as an MRS between 0-2 were catigorized as good outcomes and the 3-6 "Non TBM" by the Lancet score and 6/258 (2%) of those who as poor outcomes.8%) were classified as duration of illness.3%) females. 28. using chi-square statistics. All of the six patients were under units’ diagnosis. the medical as Non TB by Thwaites' score.TB 32 14 46 included in the analysis. possible or no TBM. but do not pose any statistical significance.2% (13/306) and aseptic was used to score all patients according to the Thwaites' scoring meningitis in 1. he/she is classified as (14. The study was approved by the institution of research board. bacterial meningitis.5%) as "Definite-TBM". Only a moderate agreement was observed between the two TBM is either definite. and 18/260 (7%) cases diagnosed as Data analysis of continuous variables was described using means "TBM" by the unit were classified as "Non TBM" by the Lancet with standard deviations and categorical variables were summarized score. 9892 patients were Diagnosis based on Thwaites Score admitted under the medical unit. and 114 (37.527 of whom were diagnosed as TB by all 3 methods. A possible A comparison of the unit’s clinical diagnosis with the diagnosis is made with scores between 6-9 without imaging or 6-11 classification of the same patients by the Lancet score is seen in with imaging.6% (260/306). During the 5 year study period (2006-2010). Kappa statistic = 0. Of these.

84% were TBM. This study describes a large cohort of patients with CNS infections Lancet Scoring classification M2 Primary in a tertiary care centre in South India.03 7 Motor deficit 50/250 2/31 0.17 8 Abnormal CT Brain findings 120/188 5/22 0. diagnosis was however.Oman Medical Journal (2013) Vol. based largely on the clinical features and Thwaites Scoring CSF findings used in the Thwaites' score. The units’ classification for the patients. 2 months of daily intensive therapy with INH. 28.23 5 Presence of Papilloedema 31/248 3 0. Concurrent extra CNS TB 13 0 0. In the medical unit all patients with suspected or Non.4) 0. over a 5 year period. The TB Pyogenic Lancet score with CNS imaging criteria in addition to clinical Lancet Definite TBM 29 0 29 criteria of cranial nerve palsies seemed to rule out many cases that Score would have been treated as TBM based on the Thwaites' score Probable TBM 43 0 43 alone. other cases) Pyrazinamide and Ethambutol.0001 9. with intravenous *TBM: TB Meningitis dexamethasone for the first 1-2 weeks. Rifampicin.9 *TBM: TB Meningitis Table 4: Comparison of the patients’ characteristics in those with concordance and discordance of the Thwaites and Lancet consensus scores.mean (SD deviation) 34. the Lancet score medical unit’s diagnosis and the two scoring systems.8 The clinical outcome measure as described by the modified Rankin score was no different for the patients No TBM 32 16 48 who had concordance between the scores and those who did not.4) 37. followed by a continuation phase Total 29 43 186 48 306 of INH and Rifampicin. Among the cohort.94 6 Presence of Cranial nerve palsy 58/247 2 0. No.49 2 Presence of Diabetes Mellitus 27 5 0. Steroids were given.41 3 HIV Positive 35 4 0. S. Total 284 22 306 Another study from India has found age greater than 40 and a high CSF protein concentration to predict mortality in TBM patients. The overall outcomes were classified as "Poor" in more than a 29 43 170 18 260 of TBM* third of patients.97(16. Modified Rankin’s outcome Normal 118 18 0. These Diagnosis Definite Probable Possible Not constitute approximately 3% of all inpatient admissions in a Total TBM TBM TBM TBM medical ward.414 Mild deficit at discharge 30 2 Moderate deficit at discharge 27 2 Deficit with mild disruption of daily life 22 2 Deficit with moderate disruption to daily life 14 0 Severe disruption and patient becomes bedridden 21 3 Death 19 5 Oman Medical Specialty Board .94(15. No Variable Concordance (N= 252) Non-concordance (N= 38) p value 1 Age . Cranial nerve palsies in these patients had also been reported Possible TBM 180 6 186 to have a poor outcome.TB cases confirmed TBM were treated for 9 months to 1 year with anti TB (includes all 0 0 16 30 46 therapy. 3:163-166 Table 2: Comparison of the Medical unit’s diagnosis vs.7 It was noted that there was a moderate agreement between the Table 3: Comparison of the Thwaites score vs.82 4 Seizures during illness 41 8 0.46 5. the Lancet Discussion score classification. mostly young Unit diagnosis men. followed by a tapering schedule of prednisolone. and when there was System Lancet Diagnosis Total neurological defecity the CT scan results were used as well.

7. Chau TT. Nguyen TB. Oman Medical Specialty Board .15(4):262-267. Chandy S.19(5):604-607. Schouten HJ. et al. Chuong LV.10(11):803-812. No. Koudstaal PJ.60(1):18-22. Prasad S. It is evident that Available from. Tran TH. and without CNS imaging in the tertiary care setting. Sinh DX. However. Neurol India 2012 Jan-Feb. MR angiography in from those who had concordant results when treatment was tuberculous meningitis. Török ME. Ahmed R. et al. make the diagnosis and initiate prompt treatment. pyogenic meningitis or viral infections. al.23(1):32-33. Visser MC. CDC. Pehlivanoglu F. Also. van Swieten JC.360(9342):1287-1292. Prasad K. Atlanta. Interobserver agreement for the assessment of handicap in stroke patients. Hoang TQ. We also found that outcomes for patients who Predictors of mortality in patients with meningeal tuberculosis. The lack 268. of CSF serology and virology data on all studied patients limited 6. et The following limitations of the study need to be highlighted. US Department of Health and Human Services. No conflicts of interest to disclose difference in the clinical outcome based on categorization with and no funding was received for this work. Lancet Infect Dis 2010 Nov. September 2005. clinicians will have to continue to use their References clinical judgment based on clinical examination. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory The scores were done on patients who had a final diagnosis of CNS features. Schoeman JF. prospective evaluation of cost-effectiveness of simple but more effective and rapid diagnostic tests are needed in the primary care setting where imaging facilities are lacking. initiated based on expert clinical evaluation in a tertiary care setting.10 bacterial meningitis. Qasim S. et al. data was not available which would have been invaluable to compare 5. Maurya PK. Misra UK. if done on patients with suspected CNS disease. Thomas V. Fallon RJ. Acta Radiol 2012 Apr. In developing countries like India. Stepniewska K.241(3):264- the validity of different scoring systems more optimally. reported tuberculosis in the United States. CDC.53(3):324-329. had discordant results between these scores were not different 10. 8. 3. Stroke 1988 our ability to assess how many could have been partially treated as May. Kumar S. van Gijn J. Tuberculous meningitis. and CSF examinations. 28.pdf the diagnosis of TBM. Thwaites GE. compares well with the more detailed and resource intensive Lancet 9. Kennedy DH. Cherian A. Oman Med J 2008 Jan. GA. Kumar A. Oman Medical Journal (2013) Vol. Iype T.6(12):e27821. follow-up Tuberculous meningitis: a uniform case definition for use in clinical research. Cerebro spinal fluid analysis in childhood TBM had MRI Brain findings suggestive of vascular involvement. Thwaites diagnostic criteria are still imperfect and better tools are needed for TBSurvFULLReport. Yasar KK. Sengoz G. department of the Christian Medical College for their diligent work It is however. infections and so their sensitivity and specificity may be higher than 4. Thwaites G. Misra UK. Kalita J. Balakrishnan A. scoring systems. Medical records without CNS imaging facilities due to poor access or availability. 3:163-166 While it is evident that neuro-imaging has significantly Acknowledgements contributed to understanding the pathology and improved outcome in complicated CNS conditions. George EL. heartening to note that there was no significant that makes such studies possible. consensus score. Prognostic factors of neurological sequel in adult patients with tuberculous meningitis. Phu NH. http://www. JAMA 1979 Jan. A study showed that half the patients with 2. Török ME. Lancet 2002 Oct. Nguyen DB. Given the lack of a gold standard. as well as imaging studies where available to 1. Marais S. We acknowledge the microbiology department for their untiring TBM will continue to be managed in the near future in canters work and 24 hour service for the diagnosis of TBM. Neurosciences (Riyadh) 2010 This study demonstrates that the widely used Thwaites' score Oct. 2004. Dexamethasone and long-term outcome of tuberculous meningitis in Conclusion Vietnamese adults and adolescents. PLoS One 2011.cdc.