When should neurosyphilis be considered in a patient?

When to Consider Neurosyphilis

Neurosyphilis should be considered in any patient with clinical evidence of neurologic involvement with syphilis, including cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and signs or symptoms of meningitis. 1

Clinical Scenarios Requiring CSF Examination

A cerebrospinal fluid (CSF) examination should be performed in patients with:

• Neurologic signs or symptoms (cognitive dysfunction, motor/sensory deficits, meningitis symptoms) 1
• Ophthalmic manifestations (uveitis, neuroretinitis, optic neuritis) 1
• Auditory symptoms (hearing loss, tinnitus) 1
• Cranial nerve palsies 1
• Evidence of tertiary syphilis (aortitis, gumma, iritis) 1
• Treatment failure of prior syphilis therapy 1
• HIV infection 1
• Serum nontreponemal titer ≥1:32 (unless duration of infection is known to be <1 year) 1
• When non-penicillin therapy is planned (unless duration of infection is known to be <1 year) 1

Special Considerations for HIV-Infected Patients

In HIV-infected patients, neurosyphilis should be considered in the differential diagnosis of neurologic disease even with atypical presentations 1. Additional considerations include:

• CSF abnormalities consistent with neurosyphilis are more likely in HIV-infected persons with CD4 count ≤350 cells/mL and/or RPR titer ≥1:32 1
• HIV-infected patients with early syphilis may be at increased risk for neurologic complications 1
• Unusual serologic responses may occur in HIV-infected patients, including higher than expected titers, false-negative results, or delayed seroreactivity 1

Clinical Presentations of Neurosyphilis

Neurosyphilis can present in various forms depending on the stage:

• Early neurosyphilis (weeks to years after infection):

  • Syphilitic meningitis (often with cranial neuropathies) 2
  • Meningovascular syphilis (with ischemic stroke) 2
  • Asymptomatic neurosyphilis 2

• Late neurosyphilis (years to decades after exposure):

  • Cerebral or spinal gummatous disease 2
  • General paresis (syphilitic encephalitis) 2
  • Tabes dorsalis (affecting spinal cord and nerve roots) 2

Atypical Presentations Requiring High Index of Suspicion

• Progressive cognitive decline or dementia-like symptoms 3, 4
• Psychiatric manifestations (psychosis, mania, paranoia) 4
• Seizures or epileptic activity 4, 5
• Encephalitis-like presentation, especially involving temporal lobes 4, 5
• Behavioral changes or personality alterations 3, 4

Diagnostic Approach

When neurosyphilis is suspected:

• Perform both treponemal and non-treponemal serologic tests 1, 6
• CSF examination is essential, looking for:
  • Pleocytosis (predominantly lymphocytic) 3
  • Elevated protein 3
  • Positive CSF-VDRL (gold standard for diagnosis, though not invariably positive) 6
• Consider MRI imaging, which may show temporal lobe abnormalities in some cases 5
• Test all patients with syphilis for HIV 1

Treatment Considerations

Once neurosyphilis is diagnosed, treatment should be initiated promptly:

• Aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days 1, 7
• For patients with penicillin allergy, ceftriaxone 2g daily either IM or IV for 10-14 days can be considered, though cross-reactivity is possible 1, 8
• Follow-up CSF examination should be performed every 6 months until the cell count normalizes 1

Common Pitfalls to Avoid

• Failing to consider neurosyphilis in patients with unexplained neurologic deficits, especially when presenting with encephalitis-like symptoms 4, 5
• Not performing CSF examination in patients with ocular syphilis, which is frequently associated with neurosyphilis 1
• Overlooking the possibility of neurosyphilis in patients with psychiatric symptoms or cognitive decline 3, 4
• Inadequate follow-up after treatment (CSF examination should be repeated every 6 months until cell count normalizes) 1
• Not testing for HIV in all patients with syphilis 1