What are the typical cerebrospinal fluid (CSF) findings in neurosyphilis?

Cerebrospinal Fluid Findings in Neurosyphilis

The diagnosis of neurosyphilis requires a combination of CSF abnormalities including elevated white blood cell count (>5 WBC/mm³), elevated protein (>45 mg/dL), and reactive CSF-VDRL test, along with clinical assessment and serum serologies. 1

Key CSF Findings

CSF Serological Tests

• CSF-VDRL:

  • Gold standard serological test for CSF
  • Sensitivity: 49-87.5%
  • Specificity: 74-100%
  • When reactive (in absence of blood contamination), considered diagnostic of neurosyphilis
  • May be nonreactive even when neurosyphilis is present 1

• CSF-RPR:

  • Sensitivity: 51-82%
  • Specificity: 82-100%
  • May be less sensitive than CSF-VDRL 1

• CSF-TRUST:

  • Sensitivity: 76.2%
  • Specificity: 93.1% 1

• CSF-FTA-ABS:

  • Less specific (more false positives) than CSF-VDRL
  • Highly sensitive
  • Some specialists believe a negative CSF-FTA-ABS excludes neurosyphilis 1
  • Sensitivity reported as high as 90% 2

CSF Cellular and Biochemical Abnormalities

• CSF WBC Count:

  • Usually elevated (>5 WBC/mm³) in active neurosyphilis
  • Sensitive measure of treatment effectiveness
  • Lymphocytic-plasmocytic cell reaction 1, 3
  • Present in 42% of patients with high serum VDRL titers (≥1:32) 4

• CSF Protein:

  • Typically elevated (>45 mg/dL)
  • Present in 39% of patients with high serum VDRL titers (≥1:32) 4

Diagnostic Challenges

1. No Single Definitive Test:

   • No test alone can diagnose neurosyphilis
   • Diagnosis relies on combinations of:
     • Reactive serologic tests
     • CSF abnormalities
     • Clinical manifestations 1

2. Sensitivity Issues:

   • CSF-VDRL is highly specific but insensitive
   • In ocular syphilis, CSF-VDRL sensitivity is <50%
   • In otic syphilis, CSF-VDRL sensitivity is poor (<10%) 1

3. False Positives/Negatives:

   • False positive CSF-VDRL can occur with:
     • CNS malignancy
     • Blood contamination during lumbar puncture 1
   • False negative results can occur despite active infection 5

4. HIV Considerations:

   • HIV infection itself may cause mild CSF pleocytosis (5-15 cells/μL)
   • Makes neurosyphilis diagnosis more challenging in HIV-infected patients 1

Advanced Diagnostic Indices

• TPHA Index:

  • Measures intrathecal production of treponemal antibodies
  • Specificity: 100%, Sensitivity: 98.3% 2

• CSF-CXCL13 Concentration:

  • Newer biomarker with higher sensitivity (78-83%)
  • Specificity: 76-81%
  • May help diagnose neurosyphilis when CSF-VDRL is nonreactive 6

Clinical Correlation

The interpretation of CSF findings must always be correlated with clinical presentation and serum serologies. Patients with high serum RPR/VDRL titers (>1:32) have higher risk of neurosyphilis, especially those with HIV 1, 4.

Pitfalls to Avoid

1. Relying on a single test: No single test has sufficient sensitivity and specificity to rule in or rule out neurosyphilis.

2. Ignoring clinical context: CSF findings must be interpreted in the context of clinical symptoms and serum serology.

3. Missing asymptomatic neurosyphilis: CSF examination should be considered in high-risk patients (high serum titers, HIV infection) even without neurological symptoms.

4. Traumatic lumbar puncture: Blood contamination can cause false-positive CSF-VDRL in patients with high serum titers.

5. Overlooking ocular/otic syphilis: These conditions may have normal CSF findings in up to 40% of cases despite active infection 1.