What is the recommended treatment for Central Nervous System (CNS) Lyme disease?

Treatment for Central Nervous System (CNS) Lyme Disease

For patients with CNS Lyme disease involving parenchymal brain or spinal cord, intravenous (IV) antibiotics are strongly recommended over oral antibiotics. 1

First-line Treatment Options

• IV ceftriaxone (2g once daily for 14-21 days) is the preferred parenteral regimen for CNS Lyme disease due to its convenient once-daily dosing and excellent CNS penetration 1
• Alternative parenteral options include:
  • IV cefotaxime (2g every 8 hours or 150-200 mg/kg/day divided into 3-4 doses, maximum 6g/day) 1
  • IV penicillin G (18-24 million units per day divided every 4 hours) 1

Treatment Based on Neurological Manifestations

Lyme Meningitis, Radiculopathy, or Other PNS Manifestations

• For Lyme disease-associated meningitis, cranial neuropathy, or radiculoneuropathy without parenchymal involvement:
  • IV ceftriaxone, cefotaxime, penicillin G, or oral doxycycline are all recommended options 1
  • Treatment route may be changed from IV to oral during treatment 1
  • Treatment duration is 14-21 days 1

Parenchymal Brain or Spinal Cord Involvement

• For Lyme disease with parenchymal involvement of brain or spinal cord:
  • IV antibiotics are strongly recommended over oral antibiotics 1
  • Standard duration is 14-21 days 1

Isolated Facial Nerve Palsy

• For patients with isolated facial nerve palsy without other CNS symptoms:
  • Oral antibiotics (same as for erythema migrans) for 14-21 days 1
  • Patients with normal CSF examination or those for whom CSF examination is deemed unnecessary can be treated with oral regimens 1

Special Considerations

• Patients with increased intracranial pressure may require additional interventions such as serial lumbar punctures, corticosteroids, or acetazolamide 1
• In rare cases with severe increased intracranial pressure affecting vision, CSF shunting may be necessary 1
• The response to treatment for late neurologic manifestations is typically slow and may be incomplete 2

Important Pitfalls to Avoid

• Avoid using first-generation cephalosporins (e.g., cephalexin), fluoroquinolones, carbapenems, vancomycin, metronidazole, and tinidazole as they are ineffective against B. burgdorferi 2
• Avoid long-term antibiotic therapy, pulsed-dosing, or combination antimicrobials as these approaches lack supporting evidence and may cause harm 2
• Do not use macrolides (e.g., azithromycin, clarithromycin) as first-line agents as they are less effective than other antibiotics 2
• Avoid interpreting persistent positive serology after treatment as evidence of ongoing infection; antibodies may persist for years after successful treatment 2

Monitoring and Follow-up

• Clinical improvement is the most reliable indicator of treatment success, not laboratory testing 2
• Most patients respond promptly to appropriate antibiotic therapy, but approximately 10% may have persistent symptoms 3
• Consider co-infections with Babesia microti or Anaplasma phagocytophilum in patients with persistent symptoms despite appropriate therapy 2

Emerging Evidence

• Recent research suggests that oral doxycycline may be effective even for CNS symptoms of Lyme neuroborreliosis, showing similar decreases in CSF mononuclear cell counts compared to patients with PNS symptoms 4
• However, current guidelines still strongly recommend IV antibiotics for parenchymal CNS involvement 1

By following these evidence-based recommendations, clinicians can effectively treat CNS Lyme disease while minimizing potential complications and unnecessary treatments.