What is the recommended test for diagnosing neurosyphilis?

Recommended Tests for Diagnosing Neurosyphilis

The diagnosis of neurosyphilis requires cerebrospinal fluid (CSF) examination with VDRL-CSF as the standard serological test, which is considered diagnostic when reactive in the absence of blood contamination. 1, 2

Diagnostic Approach

• No single test can diagnose all cases of neurosyphilis; diagnosis relies on a combination of serological tests, CSF abnormalities, and clinical manifestations 3, 1
• CSF examination is the cornerstone of neurosyphilis diagnosis and should include:
  • VDRL-CSF (standard serological test) 3, 1, 2
  • CSF cell count (typically elevated >5 WBCs/mm³ in neurosyphilis) 3, 1
  • CSF protein levels (often elevated) 2, 4

VDRL-CSF Test Characteristics

• VDRL-CSF is highly specific (90.3-99.3%) for neurosyphilis when reactive 4
• A reactive VDRL-CSF in the absence of blood contamination is considered diagnostic 3, 1
• However, VDRL-CSF has limited sensitivity (49-87%), meaning a negative result does NOT exclude neurosyphilis 1, 4
• Sensitivity varies by neurosyphilis type: 85.7-100% in symptomatic cases vs. 62.5-69.6% in asymptomatic cases 4

Additional Recommended Tests

• FTA-ABS test on CSF is recommended by some experts 3, 1
  • Less specific than VDRL-CSF (more false positives) 3, 1
  • Highly sensitive - a negative CSF FTA-ABS test may exclude neurosyphilis 3, 1
• CSF leukocyte count is a sensitive measure of disease activity and treatment effectiveness 3, 2
  • Typically elevated >5 WBCs/mm³ in neurosyphilis 3, 1
  • A count >10 cells/μL plus reactive CSF-VDRL strongly supports the diagnosis 2

Important Considerations and Limitations

• False-positive VDRL-CSF results are rare but can occur with CNS tumors and meningeal carcinomatosis 4
• Blood contamination during lumbar puncture can affect results (≥3 lambda of syphilitic blood can produce false-positive VDRL-CSF) 4
• Sequential serologic tests (VDRL or RPR) should be performed using the same testing method, preferably by the same laboratory 3
• Recent research suggests RPR could be an alternative to VDRL for CSF testing, with comparable specificity (99.3% vs. 99%) and sensitivity (75% vs. 70.8%) 5
• PCR testing for Treponema pallidum in CSF has excellent specificity (97-100%) but limited sensitivity (27-42.5%) 6, 7

Special Populations

• In HIV-infected patients:
  • Serologic tests are generally accurate and reliable for diagnosis 3
  • However, interpretation should be careful as these patients may have abnormal serologic results (unusually high, low, or fluctuating titers) 3, 2
  • Consider additional tests (biopsy, direct microscopy) in HIV patients with clinical syndromes suggestive of early syphilis 3

Diagnostic Algorithm

1. Perform serological tests for syphilis (VDRL/RPR and treponemal tests) 4
2. If positive, proceed to lumbar puncture for CSF analysis 2, 4
3. Evaluate CSF for:
   • VDRL-CSF (primary diagnostic test) 3, 1, 2
   • CSF leukocyte count (typically >5 WBCs/mm³) 3, 2
   • CSF protein levels 2, 4
   • Consider CSF FTA-ABS (if VDRL-CSF is negative but suspicion remains high) 3, 1