What is the diagnostic approach for neurosyphilis?

Diagnostic Approach for Neurosyphilis

Neurosyphilis diagnosis requires lumbar puncture with CSF analysis combining VDRL-CSF, white blood cell count, and protein levels—no single test can diagnose or exclude neurosyphilis. 1, 2

Essential CSF Testing Components

The diagnostic workup must include:

• VDRL-CSF (not RPR): This is the standard serologic test for CSF and is considered diagnostic when reactive in the absence of blood contamination 3, 1

  • Specificity: 99-100% 4
  • Sensitivity: Only 49-87%, meaning a negative result does NOT exclude neurosyphilis 1, 4
  • A reactive VDRL-CSF is highly specific and confirms the diagnosis 1, 2

• CSF white blood cell count: Typically elevated >5 WBC/mm³ (some guidelines use >10 WBC/mm³) when active neurosyphilis is present 3, 2

  • This is the most sensitive measure of disease activity and treatment effectiveness 3, 1
  • A WBC >10 cells/µL combined with reactive CSF-VDRL strongly supports the diagnosis 2

• CSF protein: Usually normal or mildly elevated 2

  • Elevated protein alone should NOT be used as the sole diagnostic criterion 2

Diagnostic Algorithm

Step 1: Obtain serum syphilis testing first

• Both nontreponemal (RPR or VDRL) and treponemal tests (FTA-ABS or TP-PA) are required 5
• These establish the presence of syphilis but cannot diagnose neurosyphilis specifically 1

Step 2: Perform lumbar puncture when neurosyphilis is suspected

• Obtain CSF for VDRL, cell count with differential, and protein 1, 2

Step 3: Interpret results in combination

• Confirmed neurosyphilis: Reactive CSF-VDRL + elevated CSF WBC (>10 cells/µL) 2
• Probable neurosyphilis: Elevated CSF WBC and/or protein with nonreactive CSF-VDRL but clinical suspicion remains high 1
• Neurosyphilis unlikely but not excluded: Normal CSF parameters with nonreactive VDRL-CSF 1

Optional Supplementary Testing

Some experts recommend CSF FTA-ABS as an adjunct test 3, 1:

• Highly sensitive but less specific than VDRL-CSF (more false positives) 3
• A negative CSF FTA-ABS may help exclude neurosyphilis, though this remains controversial 3, 1
• Should never be used alone for diagnosis 1

Critical Pitfalls to Avoid

• Never rely on serum RPR/VDRL titers alone to diagnose or exclude neurosyphilis—CSF examination is mandatory 1, 5
• Do not use RPR on CSF—only VDRL is validated for CSF testing 3
• Blood contamination during lumbar puncture can cause false-positive VDRL-CSF results 1, 2
• Never base diagnosis solely on elevated CSF protein without other abnormalities 2
• A nonreactive VDRL-CSF does NOT rule out neurosyphilis due to limited sensitivity—clinical judgment and other CSF parameters are essential 1, 2

Special Considerations in HIV-Infected Patients

• Standard serologic tests remain accurate for most HIV patients 3, 5
• HIV itself can cause mild CSF pleocytosis, complicating interpretation of elevated WBC counts 2
• The diagnostic threshold of >10 WBC/µL may need adjustment in HIV patients with baseline pleocytosis 2
• Some HIV patients may have atypical serologic patterns requiring additional testing 3