What is the diagnosis and treatment for a patient with abnormal cerebrospinal fluid (CSF) analysis showing low glucose (hypoglycorrhachia) and elevated protein (hyperproteinorrachia) with lymphocytic predominance?

Diagnosis: Tuberculous Meningitis

Based on the CSF findings of glucose 62 mg/dL, protein 136 mg/dL, and lymphocytic predominance, tuberculous (TB) meningitis is the most likely diagnosis and empiric four-drug anti-tuberculous therapy should be initiated immediately without waiting for microbiological confirmation. 1, 2

Critical Diagnostic Features Supporting TB Meningitis

The CSF profile strongly suggests TB meningitis:

• Lymphocytic predominance is characteristic of TB meningitis, though neutrophils may predominate early in the disease course 1
• Markedly elevated protein (136 mg/dL) is typical of TB meningitis, which characteristically shows protein >100 mg/dL 3, 1
• Low CSF glucose (62 mg/dL) with CSF/plasma glucose ratio likely <0.5 is highly suggestive of TB meningitis 1
• The combination of lymphocytic pleocytosis, low glucose, and raised protein is the classic triad for TB meningitis 1

Essential Immediate Workup

Before finalizing the diagnosis, you must obtain:

• Simultaneous plasma glucose to calculate the CSF/plasma glucose ratio—this is critical as absolute CSF glucose can be misleading 3, 1
  • If ratio <0.5: TB meningitis highly likely 1
  • If ratio <0.36: bacterial meningitis becomes more likely 1
  • Normal ratio is >0.66 1
• HIV testing immediately, as HIV-positive patients have higher incidence and mortality from TB meningitis 1
• CSF opening pressure measurement 1
• Brain MRI with contrast looking for basilar meningeal enhancement (suggests TB or fungal meningitis) 2

Immediate Treatment Protocol

Start empiric four-drug anti-tuberculous therapy immediately based on clinical suspicion without waiting for microbiological confirmation 1, 2:

• Isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for 2 months 1
• Followed by two-drug continuation phase (isoniazid + rifampin) for 10 months (total 12 months) 1

Simultaneously start IV acyclovir 500 mg/m² every 8 hours along with empiric antibiotics (ceftriaxone and vancomycin) until bacterial meningitis and HSV encephalitis are definitively excluded 2:

• This is critical because lymphocytic pleocytosis with low glucose does NOT exclude bacterial meningitis or HSV encephalitis 2
• HSV encephalitis can present with normal or minimally abnormal CSF in 5-10% of cases 3, 2, 4
• Delays beyond 48 hours in treating HSV encephalitis significantly worsen outcomes (mortality 70% untreated vs 20-30% with treatment) 2

Critical Differential Diagnoses That Must Be Excluded

Never assume lymphocytic CSF means "just viral"—several life-threatening conditions present identically 2:

1. Partially treated bacterial meningitis: Can present with lymphocytic pleocytosis and low glucose 3, 2
2. Fungal meningitis (histoplasmosis, cryptococcosis): Identical CSF findings to TB meningitis 1
3. Listeriosis: Presents with lymphocytic pleocytosis and low glucose 2
4. HSV-2 chronic meningitis: Can cause lymphocytic pleocytosis, elevated protein, and hypoglycorrhachia 5
5. Neurosarcoidosis: Can mimic TB meningitis with similar CSF findings 6

Additional CSF Studies to Send Immediately

• CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses—these account for 90% of viral CNS infections 3, 2
• CSF bacterial culture and Gram stain 2
• CSF lactate: Levels <2 mmol/L effectively rule out bacterial disease 3, 2
• Mycobacterium tuberculosis testing (6 mL CSF for AFB smear, culture, and TB PCR) 3
• Fungal studies (India ink, cryptococcal antigen, fungal culture) 1
• CSF cytology to exclude leptomeningeal metastases 3

Follow-Up Strategy

• Repeat lumbar puncture in 24-48 hours if initial CSF HSV PCR is negative and clinical suspicion remains high, as HSV PCR can be negative early in disease course 3, 2
• Continue acyclovir for 14-21 days if HSV is confirmed 2
• Discontinue antibiotics once bacterial meningitis is excluded by culture and clinical course 2
• Continue anti-tuberculous therapy for full 12-month course even if cultures are negative, if clinical picture supports TB meningitis 1

Common Pitfalls to Avoid

• Never delay acyclovir waiting for HSV PCR results—start immediately in any patient with decreased level of consciousness and CSF abnormalities 2
• Never rely on absolute CSF glucose alone—always calculate the CSF/plasma glucose ratio 3, 1
• Never assume bacterial meningitis is excluded by lymphocytic predominance—10% of bacterial meningitis patients have fewer than 100 cells/mm³ 4
• Never wait for TB culture results before starting treatment—TB cultures can take 6-8 weeks, and delays worsen outcomes 1