What is the likely diagnosis and treatment for a patient with hyperproteinorrachia, positive globulin, pleocytosis with polymorphonuclear predominance, and normal glucose in the cerebrospinal fluid (CSF)?

Likely Diagnosis: Tuberculous Meningitis with Empiric Treatment Required

Based on the CSF profile showing marked hyperproteinorrachia (672 mg/dL), polymorphonuclear predominance (59%), pleocytosis (36 cells), and normal-to-elevated glucose (134.79 mg/dL), tuberculous meningitis is the most likely diagnosis, though the polymorphonuclear predominance suggests early-stage disease or requires consideration of partially treated bacterial meningitis and atypical infections. 1

Critical Immediate Action Required

Start empiric four-drug anti-tuberculous therapy immediately (isoniazid, rifampin, pyrazinamide, and ethambutol) without waiting for microbiological confirmation, while simultaneously covering for bacterial meningitis and HSV encephalitis until definitively excluded. 1

• Administer IV acyclovir 500 mg/m² every 8 hours until HSV PCR results return negative 1
• Continue empiric antibiotics (ceftriaxone + vancomycin) until bacterial cultures are negative for 48-72 hours 2

Diagnostic Reasoning

Why Tuberculous Meningitis is Most Likely

• The markedly elevated protein (672 mg/dL = 6.72 g/L) is characteristic of TB meningitis, which typically shows protein >1 g/L, far exceeding the mild elevation seen in viral infections 1
• The normal-to-elevated glucose (134.79 mg/dL) requires calculation of CSF/plasma glucose ratio, as absolute values are misleading when serum glucose is abnormal 1
• If the CSF/plasma glucose ratio is <0.5, TB meningitis is highly likely; if <0.36, bacterial meningitis becomes more probable 1
• Lymphocytic predominance is characteristic of TB meningitis, though neutrophils may predominate early in the disease course 1

Critical Differential Diagnoses to Exclude

Partially treated bacterial meningitis must be urgently excluded because:

• It can present with lymphocytic pleocytosis and confusing CSF profiles after antibiotic exposure 1
• CSF lactate <2 mmol/L effectively rules out bacterial disease 1
• Bacterial meningitis typically shows protein >220 mg/dL (>2.2 g/L) and CSF glucose <60 mg/dL, though this patient's protein is markedly elevated 2, 3

Viral encephalitis is less likely because:

• Viral infections typically show only mildly elevated protein with normal glucose, not the marked hyperproteinorrachia seen here 2
• Polymorphonuclear predominance may occur early in viral encephalitis, but persistent neutrophilic pleocytosis is seen in West Nile virus encephalitis 2

Atypical infections to consider:

• Scrub typhus (Rickettsia tsutsugamushi) can present with polymorphonuclear pleocytosis and hypoglycorrhachia, though this patient has normal glucose 4
• Fungal meningitis (histoplasmosis, cryptococcosis) typically presents with lymphocytic pleocytosis, low glucose, and raised protein 1

Essential Immediate Workup

Obtain simultaneously:

• Plasma glucose measurement to calculate CSF/plasma glucose ratio (critical for differentiating TB from bacterial meningitis) 1
• CSF bacterial culture, Gram stain, and lactate level 1
• 6 mL CSF for AFB smear, TB culture, and TB PCR (Xpert MTB/RIF if available) 1
• CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses 1
• HIV testing (IV drug users and immunocompromised patients have higher TB meningitis risk) 1
• CSF cytology to exclude leptomeningeal metastases 1

Clinical history to obtain:

• Duration of symptoms >5 days is independently predictive of TB meningitis with 93% sensitivity 1
• Subacute course >3 weeks strongly favors TB meningitis 1
• History of TB exposure, immunocompromised state, or HIV infection 1
• Recent antibiotic use (suggests partially treated bacterial meningitis) 1

Treatment Protocol

Immediate empiric therapy (start all three simultaneously):

1. Anti-tuberculous therapy: Isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 10 months (total 12 months) 1

2. Empiric antibiotics: Continue until bacterial cultures negative for 48-72 hours and CSF lactate <2 mmol/L 2, 1

3. Acyclovir: Continue until HSV PCR negative 1

Critical Pitfalls to Avoid

• Do not rely on absolute CSF glucose values when serum glucose is abnormal—always calculate the CSF/plasma glucose ratio 1
• Do not wait for microbiological confirmation before starting anti-tuberculous therapy, as TB culture can take 6-8 weeks 1
• Do not assume viral etiology based solely on normal glucose—TB meningitis can present with normal glucose early in disease 1
• Do not dismiss bacterial meningitis based on polymorphonuclear count alone—after 48-72 hours of effective antibiotic therapy, differential cell count can convert from PMN predominance to relative lymphocytosis 5
• Polymorphonuclear predominance does not rule out Guillain-Barré syndrome, though this diagnosis is unlikely given the elevated glucose and clinical context 6

Monitoring Strategy

• Repeat lumbar puncture at 48-72 hours to assess treatment response 5
• After 48 hours of effective therapy, CSF pleocytosis and elevated protein usually persist, while hypoglycorrhachia typically resolves 5
• Monitor for complications: hydrocephalus, vasculitis, cranial nerve palsies 1