ANALYSIS OF DIAGNOSTIC SCORINGS OF THWAITES AND

MARAIS IN TWO GROUPS OF DEFINITE AND PROBABLE

TUBERCULOUS MENINGITIS CASES
KADRIYE KART YASAR, MD, FILIZ PEHLIVANOGLU, MD, GONUL SENGOZ, PhD, MD
Department of Infectious Diseases and Clinical Microbiology,
Haseki Training and Research Hospital, ISTANBUL, TURKEY
INTRODUCTION
Tuberculosis is generally known as a pulmonary disease but tuberculous Table 3. Marais’ Case Definition Criteria*
meningitis (TBM) is the most dangerous form of it. TBM is not only a Diagnostic score
Clinical criteria Max score: 6
devastating form but also a challenge for clinicians in diagnosis and Symptom duration of more than 5 days 4
management of the disease. Because, the clinical features of TBM are non- Systemic symptoms suggestive of TB (one or more of the following): weight loss (or poor weight gain in children), night
2
specific; definitive diagnostic methods like showing or isolation of the agent are sweats, or persistent cough for more than 2 weeks
History of recent (within past year) close contact with an individual with pulmonary TB or a positive TST or IGRA (only in
time-consuming processes; neuroradiological signs may not be helpful in all children <10 years of age)
2

patients. There are still many question marks in most of clinicians’ minds and Focal neurological defi cit (excluding cranial nerve palsies) 1

we should review some challenges in diagnosis, treatment and prognosis of Cranial nerve palsy 1
Altered consciousness 1
TBM. CSF criteria Max score: 4
Laboratory-based diagnostic methods for rapid diagnosis of tuberculous Clear appearance 1

meningitis (TBM) are insufficient. The studies for the diagnostic guidelines Cells: 10–500 per μl 1
Lymphocytic predominance (>50%) 1
based on clinical and laboratory findings are currently progressing. In this study, Protein concentration greater than 1 g/L 1
the diagnostic criteria of Thwaites (TDS) and the case definition criteria of CSF to plasma glucose ratio of less than 50% or an absolute CSF glucose concentration less than 2·2mmol/L 1

Marais were applied to definite and probable TBM cases to investigate the Cerebral imaging criteria Max score=6
Hydrocephalus 1
presence of statistically difference and importance with respect to the data Basal meningeal enhancement 2
obtained in our country. Tuberculoma 2
Infarct 1
METHODS Pre-contrast basal hyperdensity 2
Evidence of TB elsewhere Max score=4
The 59 TBM cases with culture positivity and 89 probable TBM cases that Chest radiograph suggestive of active TB (signs of TB: 2; miliary TB: 4 2/4

clinically diagnosed have been included into this study. The TDS as a scoring CT/ MRI/ ultrasound evidence for TB outside the CNS 2

system and the “case definition criteria” of Marais were applied to the both
groups and the differences between the results were compared statistically.
Patient population and setting
Istanbul is the largest city of Turkey and has high rates of TB. The most of
AFB identified or MTB cultured from another source (sputum, lymph node, gastric washing, urine, blood culture) 4
Positive commercial MTB NAAT from extra-neural specimen 4
Exclusion of alternative diagnoses
An alternative diagnosis must be confi rmed microbiologically (by stain, culture, or NAAT when appropriate), serologically
(eg, syphilis), or histopathologically (eg, lymphoma). The list of alternative diagnoses that should be considered, dependent
upon age, immune status, and geographical region, include: pyogenic bacterial meningitis, cryptococcal meningitis, syphilitic

patients with extra pulmonary TB especially TBM receive care at Haseki
Training and Research Hospital (HTRH), a 550-bed tertiary referral center
hospital. 148 patients aged >14 years who were diagnosed as TBM in HTRH
between January 1998, and March 2009 were included in this study. Data were
meningitis, viral meningo-encephalitis, cerebral malaria, parasitic or eosinophilic meningitis (Angiostrongylus cantonesis,
Gnathostoma spinigerum, toxocariasis, systicercosis), cerebral toxoplasmosis and bacterial brain abscess (space-occupying
lesion on cerebral imaging)and malignancy (eg, lymphoma)
The individual points for each criterion (one, two, or four points) were determined by consensus and by considering

obtained from patients’ hospital files, discharge summaries and out-patient their quantified diagnostic value as defined in studies.

TB: tuberculosis, TST=tuberculin skin test, IGRA=interferon-gamma release assay, NAAT: nucleic acid amplification test, AFB: acid-fast bacilli, MTB:
records retrospectively. M.tuberculosis, *Marais S et al. (Lancet 2010)
Definitions
The diagnosis of TBM was performed with clinical, laboratory and
radiological criteria according to Table 1. RESULTS
Definite TBM: Microbiological identification of M. tuberculosis from CSF.
All of 59 definite and 89 clinically diagnosed TBM cases had scores lower
Clinically diagnosed TBM: Clinical, laboratory and radiological evidence for
than critical TDS scoring for TBM and there was no statistically difference
TBM or response to antituberculous therapy.
between two groups (Table 2).

Table 1. The diagnostic criteria for TBM Table 2. TDS scoring comparison of definite and clinically diagnosed TBM
cases.
MTB isolated from CSF or
59 Definite TBM n (%) 89 Clinically diagnosed
Lymphocytic meningitis: TBM n (%)
Yes No Yes No p
Negative Gram and India ink stains, and sterile cultures for bacteria and fungi, and ≥ 1 of the following: Age > 36 13 (22) 46 (78) 27 (30) 62 (70) 0,114
WBC > 15.000/mm3 6 (10) 53 (90) 5 (6) 84 (94) 0,226
Neuroradiological findings consistent with TBM such as tuberculoma, basal meningitis, etc.
History > 7 days 57 (97) 2 (3) 81 (91) 8 (9) 0,491
Accompanying chest radiographic findings for active pulmonary TB CSF WCC > 900/mm3 1 (2) 58 (98) 3 (3) 86 (97) 0,478
PNL > 75% 2 (3) 57 (97) 5 (6) 84 (94) 0,166
A positive culture or positive microscopy for AFB or PCR of other body fluids or tissues for MTB

Close contact with a person with active pulmonary TB

No statistical difference was found with respect to features of TDS between two
groups (p= 0,139).
Clinical response to antituberculous therapy

≤ 4 score for Thwaites* diagnostic index

Graph 1. Probable and possible Graph 2. Probable and possible
AFB: acid-fast bacilli, MTB: M.tuberculosis, *Thwaites GE et al. (Lancet 2002)) cases according to case definition cases according to case definition
criteria of Marais in 59 culture criteria of Marais in 89 clinically
Table 2. Thwaites’ Diagnostic Scoring*: positive TBM cases. diagnosed TBM cases.
Diagnostic index

≥ 36 2
Age
< 36 0
≥ 15000/mm3 4
Blood WCC
< 15000/mm3 0
< 6 day 0
History of illness
≥ 6 day -5
≥ 900/mm3 3
CSF total WCC
< 900/mm3 0
The rates of probable and possible TBM cases in definite and clinically
≥ 75 4 diagnosed groups of TBM were similar. No statistical difference was found
CSF % neutrophils
< 75 0 between two groups with respect to the compliance for each criterium of Marais
WCC: white cell count, CSF: cerebrospinal fluid, *Thwaites GE et al. (Lancet 2002) (p= 0,543).
Marais’ Case Definition Criteria*: CONCLUSION
Probable TBM: When imaging is available, a diagnostic score of 12 or above is
required, and when imaging is not available, a diagnostic score of 10 or above According to these results obtained in our definite and clinically diagnosed
is required. TBM cases, the TDS and the case definition criteria of Marais are seem to be
Possible TBM: When imaging is available, a diagnostic score of 6-11 is useful methods for early diagnosis. We conclude that both methods may be
required, and when imaging is not available, a diagnostic score of 6-9 is considered among routine investigations that can be applied safely in clinically
required. diagnosed TBM cases without culture positivity for tuberculosis.