Indications for CSF Analysis in Syphilis
CSF examination should be performed in patients with latent syphilis who have neurologic or ophthalmic symptoms, evidence of tertiary syphilis, serologic treatment failure, or in all infants and children with syphilis. 1
Clinical Indications Requiring Prompt CSF Examination
Symptomatic Disease
- Neurologic manifestations including auditory disease, cranial nerve dysfunction, acute or chronic meningitis, stroke, altered mental status, or loss of vibration sense 1
- Ophthalmic involvement such as iritis or uveitis 1
- Evidence of active tertiary syphilis including aortitis or gumma 1
Serologic Treatment Failure
- Fourfold increase in nontreponemal titers after initial treatment 1, 2
- Failure of initially high titers (≥1:32) to decline fourfold within 12-24 months of therapy 1
- Persistent or recurrent signs/symptoms attributable to syphilis after treatment 1
Special Populations
HIV-Infected Patients
- CSF examination is recommended for all HIV-infected persons with late-latent syphilis or syphilis of unknown duration 1
- Some specialists recommend CSF examination for all HIV-infected persons with syphilis regardless of stage, particularly if serum RPR is ≥1:32 or CD4+ count is <350 cells/µL 1
- The CDC guidelines note that CSF abnormalities are common in HIV-infected persons, making interpretation more challenging 1
Pediatric Patients
- All infants and children aged ≥1 month with diagnosed syphilis should have CSF examination to exclude neurosyphilis 1
- Birth and maternal medical records must be reviewed to distinguish congenital from acquired syphilis 1
When CSF Analysis is NOT Routinely Indicated
Primary and Secondary Syphilis
- CSF analysis is not recommended for routine evaluation of patients with primary or secondary syphilis unless neurologic or ophthalmic symptoms are present 1
- While CSF invasion by T. pallidum with abnormalities is common in early syphilis, neurosyphilis develops in only a limited number after standard penicillin treatment 1
Important Clinical Pitfalls
Interpretation Challenges
- CSF-VDRL is highly specific (100%) but poorly sensitive (27%) for active neurosyphilis, meaning a negative test does not exclude the diagnosis 3
- CSF abnormalities alone without positive treponemal tests do not confirm syphilitic CNS inflammation 4
- In HIV-infected patients, mild CSF pleocytosis (5-15 cells/µL) may be due to HIV itself rather than neurosyphilis, particularly with CD4+ counts >500 cells/µL 1
Treatment Failure Recognition
- A fourfold increase in titers (e.g., from 1:64 to 1:132) exceeds the threshold defining treatment failure and mandates CSF examination 2
- Even patients with appropriate initial serologic response (fourfold decline within 6 months) may still develop neurosyphilis, requiring CSF examination if titers remain serofast at 24 months 5