What is the recommended workup for chronic meningitis in cerebrospinal fluid (CSF)?

Chronic Meningitis Workup in CSF

The recommended workup for chronic meningitis in cerebrospinal fluid (CSF) should include CSF pressure measurement, cell count with differential, glucose and protein levels, Gram stain, culture, and targeted testing for specific pathogens based on clinical presentation and epidemiology. 1, 2

Definition and General Approach

• Chronic meningitis is defined as inflammatory CSF profile with pleocytosis that persists for at least 4 weeks without spontaneous resolution 3, 4, 5
• The differential diagnosis falls into four main categories: infectious, autoimmune, neoplastic, and idiopathic causes 4, 5

Initial CSF Studies

• Opening pressure measurement (typically raised in tuberculous and fungal meningitis) 1, 2
• Cell count with differential:
  • Lymphocytic predominance suggests viral, tuberculous, or fungal etiology 1, 2
  • Neutrophilic predominance suggests bacterial etiology, though early tuberculous meningitis may present with neutrophils 1
• Glucose level and CSF:plasma glucose ratio:
  • Very low in bacterial and tuberculous meningitis (ratio <0.36 has high sensitivity and specificity) 1
  • Normal or slightly low in viral meningitis 1, 2
• Protein level:
  • Markedly elevated in tuberculous meningitis 1, 6
  • Moderately elevated in bacterial and fungal meningitis 1
  • Mildly elevated in viral meningitis 1, 2

Microbiological Studies

• Gram stain (sensitivity 60-90% for bacterial meningitis) 1
• CSF culture (gold standard for bacterial diagnosis) 1
• Acid-fast bacilli (AFB) stain for tuberculosis 7
• India ink preparation for fungal pathogens 7
• Cryptococcal antigen testing 7

Advanced Diagnostic Testing

• Polymerase Chain Reaction (PCR):
  • For bacterial pathogens (especially if antibiotics were given prior to lumbar puncture) 1, 8
  • For viral pathogens (HSV, VZV, enteroviruses) 2
  • For tuberculosis 2
• Antigen detection tests:
  • Latex agglutination for bacterial antigens (though sensitivity varies and routine use is not recommended) 1
  • Cryptococcal antigen testing has high sensitivity and specificity 7
• CSF cytology for suspected neoplastic meningitis 4, 5

Special Considerations

• Large volume CSF collection (40-50mL) may be necessary for tuberculous or fungal meningitis diagnosis 7
• If CT scan is required before lumbar puncture (due to contraindications), blood cultures should be obtained and empiric antimicrobial therapy started immediately 9, 8
• Contraindications to immediate lumbar puncture include:
  • Immunocompromised state
  • History of CNS disease
  • New onset seizure
  • Papilledema
  • Abnormal level of consciousness
  • Focal neurologic deficit 1

Timing Considerations

• CSF culture yield decreases significantly after antibiotic administration:
  • 73% positive if LP performed within 4 hours of antibiotics
  • 11% positive if LP performed after 4 hours
  • 0% positive if LP performed after 8 hours 8
• Repeat lumbar puncture may be necessary if initial results are inconclusive but clinical suspicion remains high 2

Pitfalls and Caveats

• A traumatic lumbar puncture can falsely elevate white cell count 1
• Prior antibiotic administration reduces yield of CSF cultures and Gram stain but other CSF parameters (cell count, glucose, protein) remain useful 2
• Empiric therapy should not be delayed for neuroimaging if bacterial meningitis is suspected 8, 7
• Potential infectious and neoplastic conditions should be excluded before starting steroids or immunosuppressive medications for suspected autoimmune causes 4