CSF Findings in Neurosyphilis
Neurosyphilis typically presents with mild mononuclear pleocytosis (10-200 cells/µL), normal or mildly elevated protein concentration, and a reactive CSF-VDRL, though the absence of these findings does not exclude the diagnosis. 1
Cell Count and Differential
- White blood cell count is typically elevated at 10-200 cells/µL with a predominantly mononuclear (lymphocytic-plasmocytic) cell reaction 1, 2
- A CSF WBC >10 cells/µL combined with reactive CSF-VDRL strongly supports the diagnosis of neurosyphilis 1
- The WBC count is a sensitive indicator of inflammatory activity in the CNS and serves as a useful marker for treatment effectiveness 2
- Important caveat: HIV infection itself can cause mild mononuclear CSF pleocytosis (5-15 cells/µL), particularly in patients with CD4+ counts >500 cells/µL, which can complicate interpretation 1
Protein
- Protein levels are typically normal or mildly elevated in neurosyphilis 1
- Elevated protein alone, without other CSF abnormalities (reactive VDRL or elevated WBC), should not be used as the sole basis for diagnosis 1
- Protein serves as an indicator of inflammatory activity and can be used to monitor treatment response, though the response may be slower in late forms like paresis and tabes 2
- IgG index is often strongly positive with oligoclonal bands present 2
Glucose
- Glucose levels are generally normal in neurosyphilis 3
- Glucose concentration is the most unreliable parameter for diagnosing neurosyphilis (AUC=0.445, P=0.395) and should not be relied upon for diagnostic purposes 3
Lactate
- No specific lactate findings are described in the guideline literature for neurosyphilis diagnosis
- The available guidelines do not include lactate as a standard diagnostic parameter for neurosyphilis 1, 4, 5, 6
Diagnostic Algorithm
The diagnosis requires a combination of findings rather than any single test:
- Reactive CSF-VDRL (highly specific but only 49-87% sensitive) plus CSF WBC >10 cells/µL provides the strongest diagnostic support 1, 5
- A nonreactive CSF-VDRL does NOT exclude neurosyphilis due to limited sensitivity 1, 5
- CSF treponemal tests (FTA-ABS) are sensitive but not specific; a nonreactive test excludes neurosyphilis, but a reactive test does not confirm it 1, 6
- The combination of CSF-TRUST (or VDRL), nucleated cell count, and total protein has the highest diagnostic accuracy (AUC=0.989) for distinguishing neurosyphilis from latent CNS syphilis infection 3
Critical Pitfalls
- Never base the diagnosis solely on elevated CSF protein without reactive VDRL or elevated WBC 1
- Blood contamination during lumbar puncture can affect CSF-VDRL results and must be considered 5
- In HIV-infected patients, the diagnostic threshold of >10 WBC/µL may need adjustment given baseline HIV-related pleocytosis 1
- False-negative serologic tests can occur; if clinical suspicion is high despite negative serology, pursue alternative diagnostic procedures 6