From the Guidelines
Neurosyphilis is typically diagnosed through cerebrospinal fluid (CSF) analysis via lumbar puncture, which reveals characteristic findings including pleocytosis, elevated protein levels, and positive CSF-VDRL or CSF-FTA-ABS tests. The diagnosis of neurosyphilis can be made based on various combinations of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, or a reactive VDRL-CSF with or without clinical manifestations 1. According to the most recent and highest quality study, the sensitivity of the CSF VDRL ranged from 49–87.5% and the specificity ranged from 74–100% for diagnosing neurosyphilis 1.
Key Findings
- Pleocytosis (elevated white blood cell count, usually 10-400 cells/μL with lymphocyte predominance)
- Elevated protein levels (45-200 mg/dL)
- Normal or slightly decreased glucose
- Positive CSF-VDRL or CSF-FTA-ABS tests
- The CSF-VDRL is highly specific but less sensitive (30-70%), while the CSF-FTA-ABS is more sensitive but less specific
Diagnostic Considerations
The CSF leukocyte count usually is elevated (greater than 5 WBCs/mm3) when neurosyphilis is present, and it also is a sensitive measure of the effectiveness of therapy 1. A reactive CSF-VDRL confirms neurosyphilis, but a negative result doesn't exclude it. Some experts recommend performing an FTA-ABS test on CSF, which is believed to be highly sensitive, and some experts believe that a negative CSF FTA-ABS test excludes neurosyphilis 1.
Treatment and Follow-up
Treatment for neurosyphilis consists of intravenous aqueous crystalline penicillin G at 18-24 million units daily (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 cell count normalizes. These findings reflect the inflammatory response and direct invasion of the central nervous system by Treponema pallidum, the causative organism of syphilis.
From the Research
Lumbar Puncture Findings in Neurosyphilis
The diagnosis of neurosyphilis relies heavily on the analysis of cerebrospinal fluid (CSF) obtained through a lumbar puncture (LP). Key findings in neurosyphilis include:
- CSF white blood cell count >10/μL without or with neurological symptoms, including new vision or hearing loss 2
- Reactive Venereal Disease Research Laboratory (VDRL) test in CSF, although this test is diagnostically specific but not sensitive 2, 3
- Elevated CSF protein concentration (≥ 45 mg/dL) 3
- Presence of Treponema pallidum DNA in CSF, as detected by semi-nested PCR, even in asymptomatic patients with normal CSF findings 4
CSF Abnormalities
CSF abnormalities in neurosyphilis can include:
- Elevated CSF white blood cell count (≥ 5/ul) 3
- Elevated CSF protein concentration (≥ 45 mg/dL) 3
- Reactive CSF-VDRL 2, 3
- Presence of Treponema pallidum DNA in CSF 4
- Elevated chemokine (C-X-C motif) ligand 13 (CXCL13) concentration, which has been shown to have a diagnostic sensitivity of 78% to 83% and specificity of 76% to 81% 2
Diagnostic Tests
Various diagnostic tests can be used to diagnose neurosyphilis, including:
- CSF-VDRL test, which has a sensitivity of 54%-69% and specificity of 73%-75% 5
- Treponemal immunochromatographic strip tests (ICSTs), such as the Syphicheck-WB test, which has a diagnostic sensitivity of 62%-64% and specificity of 79%-81% 5
- Nontreponemal tests, such as the TRUST test, which has a pooled sensitivity of 0.83 and pooled specificity of 0.99 6
- Treponemal tests, such as the EIA test, which has a pooled sensitivity of 0.99 and pooled specificity of 0.98 6