How is neurosyphilis diagnosed in an adult with possible neurologic symptoms?

Diagnosis of Neurosyphilis

Neurosyphilis is diagnosed by cerebrospinal fluid (CSF) examination showing a reactive CSF-VDRL combined with CSF white blood cell count >10 cells/µL, which together strongly support the diagnosis. 1, 2

When to Perform Lumbar Puncture

CSF examination should be performed in the following clinical scenarios:

• Neurologic or ocular symptoms or signs in any patient with syphilis 3, 1
• Active tertiary syphilis (cardiovascular or gummatous disease) 3
• Treatment failure of non-neurologic syphilis 3
• HIV-infected patients with late-latent syphilis or syphilis of unknown duration 3, 1
• HIV-infected patients with serum RPR ≥1:32 or CD4+ count <350 cells/µL, regardless of stage 3, 1

Some specialists recommend CSF examination for all HIV-infected persons with syphilis regardless of stage, though this remains controversial. 3

Diagnostic CSF Findings

The Gold Standard Combination

A reactive CSF-VDRL plus CSF WBC >10 cells/µL provides the strongest diagnostic support for neurosyphilis. 3, 1, 2

Individual CSF Parameters

CSF-VDRL:

• Highly specific but not sensitive - a reactive test establishes the diagnosis, but a nonreactive test does NOT exclude neurosyphilis 3, 1, 2
• This is the most specific test available for neurosyphilis 3

CSF White Blood Cell Count:

• Typically shows mild mononuclear pleocytosis of 10-200 cells/µL 3, 1, 2
• A count >10 cells/µL combined with reactive CSF-VDRL strongly supports the diagnosis 3, 1, 2

CSF Protein:

• Usually normal or mildly elevated 3, 1, 2
• The majority of specialists would NOT base the diagnosis solely on elevated CSF protein in the absence of reactive VDRL or elevated WBC 3, 2

CSF Treponemal Tests (e.g., CSF FTA-ABS)

• Sensitive but NOT specific - a nonreactive test excludes neurosyphilis, but a reactive test does NOT establish the diagnosis 3, 1, 2
• Useful primarily for ruling out neurosyphilis when negative 3, 1

Special Considerations in HIV-Infected Patients

HIV infection complicates the diagnosis because HIV itself can cause mild mononuclear CSF pleocytosis (5-15 cells/µL), particularly in patients with CD4+ counts >500 cells/µL. 3, 2

Critical decision point: If neurosyphilis cannot be excluded by a nonreactive CSF treponemal test in an HIV-infected patient, treat for neurosyphilis despite diagnostic uncertainty. 3, 1

The diagnostic threshold of >10 WBC/µL may need adjustment given baseline HIV-related pleocytosis. 2

Diagnostic Algorithm

1. Establish indication for lumbar puncture based on clinical presentation and HIV status 1

2. Obtain CSF for:

   • VDRL (most specific test) 3, 1
   • White blood cell count with differential 1, 2
   • Protein level 1, 2
   • Consider treponemal test if diagnosis uncertain 3, 1

3. Interpret results:

   • Reactive CSF-VDRL + WBC >10 cells/µL = Neurosyphilis confirmed 3, 1, 2
   • Nonreactive CSF-VDRL does NOT exclude neurosyphilis - consider clinical context and other CSF abnormalities 3, 1, 2
   • Nonreactive CSF treponemal test = Neurosyphilis excluded 3, 1

Critical Pitfalls to Avoid

• Never diagnose neurosyphilis based solely on elevated CSF protein without reactive VDRL or elevated WBC 3, 2
• Do not exclude neurosyphilis based on a nonreactive CSF-VDRL alone - the test has limited sensitivity 3, 1, 2
• Blood contamination during lumbar puncture can cause false-positive CSF-VDRL results and must be considered 2
• PCR-based diagnostic methods are NOT currently recommended for neurosyphilis diagnosis 3
• Calculated indices (e.g., TPHA-index) are of limited value in establishing the diagnosis 3

Serum Testing Before CSF Examination

All patients should have positive serum syphilis serology (nontreponemal tests like VDRL or RPR confirmed by treponemal tests) before pursuing neurosyphilis diagnosis. 4

HIV-infected persons may have atypical responses to nontreponemal serologic tests (higher, lower, or delayed), but treponemal tests perform similarly in HIV-infected and uninfected patients. 3