What tests and assessments should be ordered for the initial evaluation of a patient with suspected neurosyphilis?

Initial Assessment for Suspected Neurosyphilis

Perform a lumbar puncture with CSF analysis including CSF-VDRL, cell count with differential, and protein, along with serum nontreponemal (RPR or VDRL) and treponemal testing. 1, 2

Serum Testing

Required Serologic Tests

• Obtain both nontreponemal (RPR or VDRL) and treponemal tests (FTA-ABS, TP-PA, or TPPA) on serum, as using only one type is insufficient for accurate diagnosis 1, 2
• Report nontreponemal test results quantitatively (with titers) as they correlate with disease activity 1, 2
• Serum RPR titers ≥1:32 significantly increase the likelihood of neurosyphilis (10.85-fold in HIV-uninfected, 5.98-fold in HIV-infected patients) 3

HIV Testing

• All patients with suspected neurosyphilis must be tested for HIV 1
• If HIV-positive, obtain CD4+ T cell count, as CD4 ≤350 cells/mm³ increases neurosyphilis odds 3.10-fold 3

Cerebrospinal Fluid Analysis

Indications for Lumbar Puncture

Perform lumbar puncture in patients with: 1

• Neurologic symptoms (altered mental status, cranial nerve palsies, meningismus, stroke, acute or chronic altered mental status)
• Ocular symptoms (uveitis, optic neuritis, vision changes)
• Auditory symptoms (hearing loss)
• Late latent syphilis (≥1 year duration or unknown duration)
• Serologic treatment failure (fourfold increase in nontreponemal titer or failure to decline fourfold within 6-12 months)

Additional indications in HIV-infected patients: 1

• Serum RPR titer >1:32 regardless of syphilis stage
• CD4+ count <350 cells/mm³ regardless of syphilis stage
• Some experts recommend CSF examination for all HIV-infected patients with syphilis at any stage

Essential CSF Tests

Order the following CSF studies: 1

1. CSF-VDRL (not RPR): This is the standard and most specific test for neurosyphilis 1, 2

   • Sensitivity: 49-87.5% (varies by study and symptom status) 1
   • Specificity: 74-100% 1
   • A reactive CSF-VDRL is diagnostic of neurosyphilis in the absence of blood contamination 1
   • Critical pitfall: CSF-VDRL can be nonreactive even when neurosyphilis is present 1

2. CSF white blood cell count with differential 1

   • CSF WBC >5 cells/mm³ suggests neurosyphilis 1
   • CSF WBC >10 cells/mm³ strongly supports neurosyphilis diagnosis 1
   • Most sensitive measure of treatment effectiveness 1
   • Important caveat: HIV infection alone can cause mild CSF pleocytosis (5-15 cells/µL), particularly with CD4 >500 cells/µL 1

3. CSF protein 1

   • Elevated protein (>45 mg/dL) supports neurosyphilis but is less specific 1
   • Changes occur more slowly than cell counts during treatment 1

4. Optional: CSF treponemal test (FTA-ABS) 1

   • Highly sensitive but less specific than CSF-VDRL 1
   • A negative CSF FTA-ABS may help exclude neurosyphilis 1
   • A positive result does not confirm neurosyphilis 1

Critical Testing Pitfalls to Avoid

Do not use CSF-RPR instead of CSF-VDRL: 4

• CSF-RPR has significantly lower sensitivity (51.5-56.4%) compared to CSF-VDRL (66.7-71.8%) for neurosyphilis diagnosis
• CSF-RPR has high false-negative rates and cannot replace CSF-VDRL

Assess for traumatic tap: 1

• Blood contamination during lumbar puncture can cause false-positive CSF-VDRL, especially in patients with high serum titers
• Document whether tap was traumatic and correlate with RBC count

Do not rely solely on CSF protein elevation: 1

• Most specialists would not diagnose neurosyphilis based on elevated CSF protein alone without CSF pleocytosis or reactive CSF-VDRL

Clinical Evaluation

Neurologic Examination

Assess specifically for: 1

• Cranial nerve abnormalities (especially II, VII, VIII)
• Meningeal signs
• Focal neurologic deficits
• Cognitive impairment
• Gait abnormalities
• Pupillary abnormalities (Argyll Robertson pupils)

Ophthalmologic and Audiologic Assessment

• Formal ophthalmologic examination if any visual symptoms or signs 1
• Audiologic evaluation if hearing loss or auditory symptoms 1

Diagnostic Interpretation

Neurosyphilis is diagnosed when: 1

• Reactive CSF-VDRL (highly specific, diagnostic) OR
• CSF WBC >10 cells/mm³ plus reactive serum treponemal test OR
• CSF WBC >5 cells/mm³ plus reactive CSF-VDRL

If CSF-VDRL is nonreactive but clinical suspicion remains high: 1

• Consider CSF FTA-ABS to help exclude neurosyphilis
• If neurosyphilis cannot be excluded and patient has neurologic symptoms, treat empirically for neurosyphilis