What serum tests are needed for neurosyphilis diagnosis and monitoring?

Serum Testing for Neurosyphilis Diagnosis and Monitoring

Initial Serum Testing Required

For neurosyphilis diagnosis, you must obtain both a nontreponemal test (RPR or VDRL) and a treponemal test (FTA-ABS or TP-PA) on serum, as using only one type of test is insufficient for diagnosis. 1, 2

Nontreponemal Tests (Serum)

• Order either RPR or VDRL quantitatively - these tests correlate with disease activity and must be reported with titers (e.g., 1:16,1:32) 1
• RPR appears more sensitive than VDRL across all stages of syphilis, though both are acceptable 1
• A serum RPR >1:32 indicates highest risk for neurosyphilis, particularly in HIV-infected patients 1
• Critical pitfall: RPR and VDRL titers cannot be directly compared or used interchangeably - RPR titers are often slightly higher than VDRL 1, 2

Treponemal Tests (Serum)

• Order FTA-ABS or TP-PA - these confirm treponemal infection but do not correlate with disease activity 1, 2
• These tests remain reactive for life in most patients regardless of treatment, so they cannot be used to monitor treatment response 1
• 15-25% of patients treated during primary stage may revert to nonreactive after 2-3 years 1

CSF Testing (Not Serum) - The Definitive Diagnostic Tests

Serum tests alone cannot diagnose neurosyphilis - CSF examination is mandatory when neurosyphilis is suspected. 1, 3

Required CSF Tests

• CSF VDRL (not RPR on CSF) - this is the standard and most specific test 1, 3

  • When reactive in absence of blood contamination, it is diagnostic of neurosyphilis 1, 3
  • Sensitivity ranges 49-87%, specificity 74-100% 1, 3
  • A nonreactive CSF VDRL does NOT exclude neurosyphilis due to limited sensitivity 1, 3

• CSF white blood cell count - typically elevated >5 cells/mm³ in active neurosyphilis 1, 3

  • This is the most sensitive measure of disease activity and treatment effectiveness 1, 3
  • In HIV patients, use >10 cells/µL as the threshold due to HIV-related baseline pleocytosis 4

• CSF protein - usually normal or mildly elevated 4

  • Elevated protein alone without other abnormalities should not be used as sole diagnostic criterion 4

Optional CSF Tests

• CSF FTA-ABS - some experts recommend this test 1, 3
  • Less specific than CSF VDRL (more false positives) but highly sensitive 1
  • A negative CSF FTA-ABS may help exclude neurosyphilis, though this is debated 1, 5

Monitoring Treatment Response

Use the same nontreponemal test (RPR or VDRL) performed by the same laboratory for all follow-up testing. 1, 2

• A fourfold change in titer (two dilutions, e.g., 1:32 to 1:8) indicates clinically significant treatment response 1, 2
• CSF WBC count is the most sensitive measure of treatment effectiveness for neurosyphilis 1, 3
• Never use treponemal tests to monitor treatment - they remain positive regardless of cure 1, 2

Special Considerations for HIV-Infected Patients

• Standard serologic tests remain accurate and reliable for most HIV-infected patients 1, 2
• Some HIV patients may have atypical results (unusually high, low, or fluctuating titers) - consider additional testing like biopsy if results are discordant with clinical picture 1
• HIV itself can cause mild CSF pleocytosis, complicating interpretation 4

Critical Pitfalls to Avoid

• Never diagnose neurosyphilis based on serum tests alone - CSF examination is mandatory 3, 6
• Never use RPR on CSF - only VDRL is validated for CSF testing 1
• Blood contamination during lumbar puncture can cause false-positive CSF VDRL, especially with high serum titers 1, 4
• Do not switch between RPR and VDRL when monitoring the same patient - this invalidates titer comparisons 1, 2
• A nonreactive CSF VDRL does not rule out neurosyphilis when clinical suspicion is high 1, 3, 5