What are the diagnostic tests for neurosyphilis (infection of the central nervous system caused by Treponema pallidum)?

From the Guidelines

Testing for neurosyphilis should involve a combination of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, and a reactive VDRL-CSF with or without clinical manifestations, as no single test can be used alone to diagnose neurosyphilis. The diagnosis of neurosyphilis is complex and requires a comprehensive approach. According to the most recent and highest quality study 1, the CSF-VDRL is specific but not sensitive, and a reactive test establishes the diagnosis of neurosyphilis, but a nonreactive test does not exclude the diagnosis.

Key Diagnostic Considerations

• The CSF leukocyte count is usually elevated (greater than 5 WBCs/mm3) in patients with neurosyphilis, and it is also a sensitive measure of the effectiveness of therapy 1.
• The VDRL-CSF is the standard serologic test for CSF, and when reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of neurosyphilis 1.
• Some specialists recommend performing an FTA-ABS test on CSF, which is less specific but highly sensitive, and a negative CSF FTA-ABS test excludes neurosyphilis 1.

Treatment and Follow-up

• Treatment for neurosyphilis consists of intravenous aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units every 4 hours for 10-14 days.
• For penicillin-allergic patients, desensitization is preferred, but alternatives include ceftriaxone 2g daily for 10-14 days.
• Follow-up CSF examinations are recommended at 6-month intervals until the cell count normalizes, as neurosyphilis can cause significant neurological damage if left untreated, and the organism (Treponema pallidum) can persist in the central nervous system despite adequate treatment of early syphilis.

From the Research

Diagnostic Challenges

• The diagnosis of neurosyphilis can be challenging due to its variable clinical presentations and the limitations of serologic testing 2, 3, 4.
• A sound understanding of the clinical manifestations and the strengths and limitations of diagnostic tests are essential tools for neurologists 2.
• The diagnosis of neurosyphilis requires a high index of suspicion and awareness of the variable clinical presentations of the disease 3.

Diagnostic Tests

• The CSF Venereal Disease Research Laboratory (VDRL) test remains a mainstay of diagnostic testing for neurosyphilis 3.
• Using a higher titer cutoff (greater than 1:320) for the Treponema pallidum particle agglutination assay (TPPA) from the CSF may improve the utility of the TPPA as a supporting criterion for the diagnosis of neurosyphilis 3.
• Neurologic symptoms such as photophobia, vision loss, gait incoordination, or hearing loss may be more common in individuals with neurosyphilis, but the diagnostic sensitivity of these symptoms is low 5.

Lumbar Puncture and CSF Analysis

• Current guidelines recommend lumbar puncture (LP) in patients with syphilis who have neurologic symptoms 5.
• The results of routine CSF analysis in patients with a possible diagnosis of neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF 6.
• Empirical neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis 6.

Treatment

• Penicillin G is the recommended treatment for neurosyphilis, but ceftriaxone may be an acceptable alternative 2, 3.
• Penicillin G is the treatment of choice for neurosyphilis, although ceftriaxone may be a reasonable alternative therapy 3.