From the Guidelines
The diagnosis of neurosyphilis should be based on a combination of clinical evaluation, serologic testing, and cerebrospinal fluid (CSF) analysis, with CSF VDRL being the standard serologic test for CSF, as it is highly specific but not very sensitive for neurosyphilis 1. The diagnostic protocol for neurosyphilis involves several steps:
- Serologic testing with both a treponemal test (such as FTA-ABS or TP-PA) and a non-treponemal test (RPR or VDRL) should be performed on all patients with suspected neurosyphilis.
- If these tests are positive, a lumbar puncture should be performed to obtain CSF for analysis.
- The CSF should be tested for VDRL, which has a sensitivity ranging from 49–87.5% and a specificity ranging from 74–100% for diagnosing neurosyphilis 1.
- Additional CSF parameters that support the diagnosis include elevated protein (>45 mg/dL), pleocytosis (>5 white blood cells/μL), and sometimes a decreased glucose level.
- The diagnosis is confirmed if the CSF-VDRL is positive, but a negative CSF-VDRL does not rule out neurosyphilis, especially if clinical symptoms are present and other CSF abnormalities exist.
- In cases with negative CSF-VDRL but high clinical suspicion, additional tests like CSF-FTA-ABS or PCR for T. pallidum may be helpful, though these are not routinely available 1. The diagnosis ultimately relies on a combination of clinical presentation, serologic evidence of syphilis, and CSF abnormalities, with treatment often initiated empirically in highly suspicious cases even without definitive CSF confirmation. Some key points to consider:
- The sensitivity of CSF RPR ranges from 51.5–81.8% and the specificity ranges from 81.8–100% 1.
- Limited data suggest that the sensitivity of CSF RPR may be lower than that of CSF VDRL 1.
- False-positive CSF VDRL results can occur in the setting of central nervous system malignancy or bloody contamination of the CSF during a traumatic tap 1.
From the Research
Diagnostic Protocol for Neurosyphilis
The diagnostic protocol for neurosyphilis involves a combination of clinical and cerebrospinal fluid (CSF) analysis findings, as there is no existing standardized testing 2. The diagnosis can be made based on the presence of ocular or hearing manifestations with positive serum treponemal and non-treponemal tests, regardless of the presence or absence of CSF abnormalities 2.
Key Diagnostic Findings
- Elevated cell count with lymphocytic-plasmocytic cell reaction in CSF 3
- Increased protein content in CSF 3
- Strongly positive IgG index in CSF 3
- Numerous positive IgG oligoclonal bands in CSF 3
- Positive blood and CSF serology 3
- Pleocytosis and protein are indicators of inflammatory activity in the central nervous system 3
Laboratory Tests for Neurosyphilis
- CSF-TPPA (Treponema pallidum particle agglutination assay) 4, 5
- CSF-VDRL (Venereal Disease Research Laboratory) 4, 5
- CSF-TPHA (Treponema pallidum hemagglutination assay) 3, 6
- Albumin quotient for estimation of the blood-brain barrier function 6
- IgG index, which is a measure of intrathecal immunoglobulin production 6