Tuberculous Meningitis
Most Likely Diagnosis
The clinical presentation is most consistent with tuberculous (TB) meningitis, based on the combination of subacute fever and headache, multifocal brain lesions (tuberculomas) with basal cisternal enhancement on CT, and CSF showing lymphocytic pleocytosis (87% monocytes/lymphocytes), elevated protein, and clear-to-slightly turbid appearance. 1, 2, 3
Key Diagnostic Features Supporting TB Meningitis
CSF profile is classic for TB meningitis: lymphocytic predominance (87%), WBC count of 451 cells/μL (within the typical 5-500 range), clear-to-slightly turbid appearance, and absence of RBCs 1, 2
The multifocal low-attenuation lesions represent intracranial tuberculomas, which develop when Rich foci rupture and are characteristic of CNS tuberculosis 3, 4
Basal cisternal enhancement on CT is highly specific for TB meningitis and distinguishes it from viral or bacterial etiologies 5, 1
The subacute presentation with fever and headache over days-to-weeks is typical; a clinical history >5 days has 93% sensitivity for TB meningitis 1
Critical Next Steps in Diagnosis
Immediate CSF Studies Required
Measure simultaneous plasma glucose NOW to calculate CSF/plasma glucose ratio—this is the single most important discriminator 1, 2:
- Ratio <0.5 = highly suggestive of TB meningitis
- Ratio <0.36 = bacterial meningitis more likely
- Ratio >0.36 = viral meningitis more likely
Send 6 mL of CSF for TB PCR (87-100% sensitivity, 98-100% specificity), AFB smear, and TB culture 1
Measure CSF protein level—expect >1 g/L in TB meningitis (78% sensitivity, 94% specificity); values >3 g/L strongly favor TB over viral causes 1, 2
Obtain CSF opening pressure—typically elevated in TB meningitis 1, 2
Send CSF for bacterial culture, Gram stain, and lactate to exclude partially treated bacterial meningitis; lactate <2 mmol/L rules out bacterial disease 1, 6
Send HSV PCR on CSF to exclude herpes simplex encephalitis, which can present with similar imaging findings 1
Additional Workup
Obtain chest X-ray to identify pulmonary TB as the primary source 3, 7
Perform HIV testing—HIV-positive patients have higher incidence and mortality from TB meningitis 1
MRI brain with contrast is superior to CT for demonstrating basal meningeal enhancement, tuberculomas, hydrocephalus, and vasculitic infarcts 1
Key Differential Diagnoses
Fungal Meningitis (Cryptococcus, Histoplasma)
CSF findings can be identical to TB meningitis: lymphocytic pleocytosis (5-500 cells/μL), low glucose, raised protein 1, 2
However, the imaging pattern of multiple tuberculomas with basal enhancement is more specific for TB 1
Send CSF for cryptococcal antigen, India ink stain, and fungal culture 1, 7
If confirmed, treat histoplasmosis meningitis with amphotericin B 0.7-1 mg/kg/day for 3-4 months, then fluconazole 800 mg daily for 9-12 months 1
Partially Treated Bacterial Meningitis
Can shift to lymphocytic profile after antibiotics; CSF may sterilize within 2 hours for meningococcus, 4 hours for pneumococcus 1
Against this diagnosis: typical bacterial meningitis shows neutrophil predominance (80-95%), WBC >1000 cells/μL, and turbid appearance—none of which are present here 1, 2, 6
CSF lactate >35 mg/dL indicates bacterial meningitis with 93% sensitivity and 96% specificity 1, 6
Viral Meningitis/Encephalitis
Against this diagnosis: viral meningitis produces only mildly elevated protein (typically <0.6 g/L), normal or slightly low glucose (ratio >0.36), and does not explain multifocal brain lesions with basal cisternal enhancement 1, 6
HSV encephalitis must still be excluded with CSF PCR, as 5-10% of cases have initially normal CSF 6
Immediate Management Protocol
Start Empiric Therapy NOW—Do Not Wait for Microbiologic Confirmation
Delaying treatment for microbiologic confirmation worsens outcomes in TB meningitis. 1, 3, 8
Four-Drug Anti-TB Regimen (Start Immediately)
- Isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for 2 months, followed by isoniazid and rifampin for 10 months (total 12 months) 1, 3, 8
Adjunctive Corticosteroids
Corticosteroids reduce mortality in TB meningitis without changing neurological morbidity 3, 8
Dexamethasone for 4-8 weeks is recommended 4
Concurrent Empiric Coverage Until Exclusion
Start IV acyclovir 500 mg/m² (or 10 mg/kg) every 8 hours until HSV PCR returns negative 1
Consider ceftriaxone 2 g IV q12h plus ampicillin 2 g IV q4h until bacterial cultures are negative at 48 hours and CSF lactate excludes bacterial meningitis 1
Critical Pitfalls to Avoid
AFB smear sensitivity is only 50-99% and is reduced after prior antibiotic exposure—a negative smear does NOT rule out TB meningitis 1
Never rely on absolute CSF glucose without the plasma glucose; the ratio must always be calculated to avoid misinterpretation 1, 2
If initial HSV PCR is negative but clinical suspicion persists, repeat lumbar puncture at 24-48 hours, as 5-10% of viral encephalitis cases have initially normal CSF 1, 6
Tuberculomas may paradoxically enlarge or develop during the first weeks-to-months of appropriate anti-TB therapy in up to 34 documented cases; this does NOT indicate treatment failure—continue therapy and add dexamethasone for 4-8 weeks 4
Hydrocephalus may develop and require urgent VP shunt or endoscopic third ventriculostomy; patients in Vellore grade IV have >80% mortality 9
Follow-Up Strategy
Continue anti-TB therapy for at least 12 months, and some experts recommend 18 months or until tuberculomas resolve on neuroimaging 4, 9
Adjust therapy based on culture sensitivities when available; drug-resistant TB requires second-line agents 8
Monitor for immune reconstitution inflammatory syndrome (IRIS) if HIV-positive and starting antiretroviral therapy 8
Serial neuroimaging to assess response and monitor for complications (hydrocephalus, new tuberculomas, infarcts) 4, 9