How do you confirm Central Nervous System (CNS) involvement with Lyme disease?

Confirming CNS Involvement in Lyme Disease

For patients with suspected CNS involvement in Lyme disease, serum antibody testing is strongly recommended as the primary diagnostic approach rather than PCR or culture of cerebrospinal fluid (CSF) or serum. 1

Diagnostic Algorithm for CNS Lyme Disease

Step 1: Identify Clinical Presentations Warranting Testing

Testing for Lyme neuroborreliosis is recommended in patients with:

• Meningitis
• Painful radiculoneuritis
• Mononeuropathy multiplex
• Acute cranial neuropathies (especially facial nerve palsy)
• Evidence of spinal cord or brain inflammation
• Appropriate epidemiological exposure history to ticks infected with B. burgdorferi 1

Step 2: Initial Diagnostic Testing

1. Serum antibody testing (two-tier approach):

   • First tier: Enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA)
   • Second tier: Western blot confirmation if first tier is positive or borderline 1

2. Lumbar puncture for CSF analysis when CNS involvement is suspected:

   • Look for lymphocytic pleocytosis
   • Elevated total protein
   • Normal glucose levels 2

Step 3: Confirmatory Testing for CNS Involvement

When CSF is obtained, compare CSF to serum antibodies to demonstrate:

• Intrathecal antibody production - the strongest evidence of CNS infection 3
• Calculate the CSF/serum antibody index to correct for peripheral blood immunoreactivity that crosses the blood-brain barrier 3

Step 4: Additional Testing When Indicated

• Neuroimaging (MRI) is not routinely recommended for initial diagnosis but should be performed when:

  • Presentation is atypical for Bell's palsy
  • Symptoms suggest parenchymal involvement
  • Paralysis fails to recover in the expected timeframe
  • Symptoms worsen 1

• Electrodiagnostic studies may help confirm peripheral nervous system involvement 2

Clinical Manifestations of CNS Lyme Disease

CNS manifestations of Lyme disease include:

• Lymphocytic meningitis (occurs in approximately 1% of cases) 4
• Cranial neuropathies (especially facial nerve palsy)
• Radiculoneuritis (seen in 3-5% of acute neuroborreliosis) 4
• Encephalomyelitis (rare)
• Encephalopathy (more common, but often reflects systemic rather than CNS infection) 3

Treatment Considerations

For confirmed CNS Lyme disease with parenchymal involvement of brain or spinal cord:

• Intravenous antibiotics are strongly recommended over oral antibiotics 1
• Preferred regimen: IV ceftriaxone (2g daily for adults, 50-75 mg/kg daily for children) for 14-28 days 1, 5
• Alternatives: IV cefotaxime or IV penicillin G 1

Important Caveats

• Facial nerve palsy alone (without other CNS symptoms) can often be treated with oral antibiotics 1
• Encephalopathy in Lyme disease is often not specific to CNS infection but reflects systemic inflammation 5
• Longer antibiotic treatment beyond 2-4 weeks adds no therapeutic benefit but increases risk 5
• Avoid routine laboratory testing in patients with isolated Bell's palsy unless in Lyme-endemic areas 1
• Bilateral facial nerve paralysis is atypical of Bell's palsy and warrants more extensive testing 1

The diagnosis of CNS Lyme disease requires both appropriate clinical manifestations and laboratory confirmation, with demonstration of intrathecal antibody production being the gold standard for confirming CNS involvement.