CSF Findings in Tuberculous Meningitis
Tuberculous meningitis presents with characteristic CSF findings including lymphocytic pleocytosis (typically 5-500 cells/μL), markedly elevated protein (>1 g/L), very low glucose (<2.2 mmol/L), and very low CSF/plasma glucose ratio (<0.5), with raised opening pressure and clear or cloudy appearance. 1, 2
Key CSF Parameters
Cell Count and Differential
- White cell count is typically elevated in the range of 5-500 cells/μL, which is lower than the typical bacterial meningitis range of >100 cells/μL 1, 2
- Lymphocytes predominate in the cell differential, distinguishing TB meningitis from acute bacterial meningitis 1, 2
- Important caveat: Neutrophils may predominate early in the disease course, potentially causing diagnostic confusion with bacterial meningitis 1, 2
- In approximately 5% of cases, CSF white cell count may be normal, particularly in immunocompromised patients 1
Biochemical Parameters
- CSF protein is markedly raised, typically >1 g/L, with sensitivity of 78% and specificity of 94% for diagnosing TB meningitis 2, 3
- CSF glucose is very low, typically <2.2 mmol/L, with sensitivity of 68% and specificity of 96% 2, 3
- CSF/plasma glucose ratio is very low (<0.5), with sensitivity of 90%, making this the most sensitive single parameter 2, 3
- The CSF/plasma glucose ratio is more informative than absolute CSF glucose values alone 3
Physical Characteristics
- Opening pressure is typically raised 1, 2
- Appearance is usually clear or cloudy, unlike the turbid or purulent appearance of acute bacterial meningitis 1, 2
Diagnostic Approach
Microbiological Testing
- CSF acid-fast smear and culture have relatively low sensitivity but remain the gold standard for definitive diagnosis 4
- Yield is increased with multiple, large volume CSF samples 4
- PCR/nucleic acid amplification is highly specific but has suboptimal sensitivity, so a negative test cannot rule out TB meningitis 4, 5
- CSF adenosine deaminase (ADA) >6 U/L strongly supports TB meningitis diagnosis with specificity of 95% and positive likelihood ratio of 10.7, though sensitivity is only 55% 6
Clinical Pearls
- No single CSF parameter provides absolute diagnostic certainty; all results must be interpreted in clinical context including TB contact history, Mantoux skin test, chest radiograph, and CT/MRI findings 1, 5
- The combination of CSF glucose <2.2 mmol/L and protein >1 g/L differentiates TB meningitis from non-bacterial meningitis with good specificity (94-96%), though sensitivity remains suboptimal (68-78%) 3
- Treatment should be initiated as soon as clinical suspicion is supported by initial CSF studies, even before microbiological confirmation, given the high morbidity and mortality of delayed treatment 4
Differential Diagnosis Comparison
TB meningitis shares some CSF features with fungal meningitis (both show lymphocytic pleocytosis and raised protein), but TB meningitis typically has more markedly elevated protein and lower glucose levels than fungal meningitis 1, 2
Unlike viral meningitis, which shows normal or slightly low glucose, TB meningitis demonstrates very low glucose levels comparable to bacterial meningitis 1, 2
The subacute presentation with symptoms persisting for weeks before diagnosis, combined with the characteristic CSF profile, helps distinguish TB meningitis from acute bacterial meningitis 4, 5