What is the recommended treatment for Neuroborreliosis?

Treatment of Neuroborreliosis

Primary Recommendation

For acute neuroborreliosis affecting the peripheral nervous system (meningitis, cranial neuropathy, radiculoneuropathy), treat with intravenous ceftriaxone 2g once daily for 14 days, or alternatively use oral doxycycline 200mg daily for 14 days, which has equivalent efficacy. 1, 2

Treatment Algorithm by Clinical Presentation

Early Neuroborreliosis (Peripheral Nervous System Involvement)

Isolated Facial Nerve Palsy (Cranial Neuropathy VII):

• First-line: Oral doxycycline 100mg twice daily for 14 days 1, 3
• Alternative: Oral amoxicillin or cefuroxime axetil for 14 days 1
• IV therapy is not required for isolated cranial neuropathy without meningitis 1

Meningitis, Radiculoneuropathy, or Multiple Cranial Neuropathies:

• First-line: IV ceftriaxone 2g once daily for 14 days 1, 2
• Equally effective alternative: Oral doxycycline 200mg daily for 14 days 2, 3
• Other IV alternatives: IV cefotaxime or IV penicillin G 1, 4

Late/Chronic Neuroborreliosis (CNS Involvement)

Encephalomyelitis, Spinal Cord Involvement, or Brain Parenchymal Disease:

• Mandatory treatment: IV ceftriaxone 2g once daily for 14-21 days (up to 4 weeks for severe cases) 1
• Alternative: IV cefotaxime or IV penicillin G 1
• Oral antibiotics are insufficient for CNS parenchymal involvement 1
• Treatment duration of 3 weeks is recommended for chronic forms 4

Key Evidence Supporting Oral vs. IV Therapy

The 2018 German S3 guideline demonstrated that oral doxycycline has equivalent efficacy to IV beta-lactam antibiotics for early neuroborreliosis (RR: 0.98,95% CI: 0.68-1.42, P=0.93) 2. This represents the highest quality recent evidence and supports oral therapy as first-line for peripheral nervous system manifestations without CNS parenchymal involvement.

However, the 2020 IDSA/AAN/ACR guidelines emphasize that IV therapy remains preferred for CNS involvement because oral antibiotics may have inadequate CNS penetration, particularly when probenecid is used with amoxicillin, which can impair beta-lactam penetration into brain parenchyma 1.

Treatment Duration: Critical Considerations

• 14 days suffices for early neuroborreliosis 2, 3
• 14-21 days for late/chronic neuroborreliosis 1, 2
• Do not extend beyond 21 days unless objective evidence of treatment failure exists 1, 2
• The duration of treatment is "very important for successful treatment"—at least 2 weeks for acute forms and 3 weeks for chronic forms 4

Pediatric Dosing

Children ≥8 years old:

• Doxycycline 4mg/kg/day divided twice daily (maximum 200mg/day) 5
• Alternative: Amoxicillin or cefuroxime axetil 1

Children <8 years old:

• Amoxicillin or cefuroxime axetil (avoid doxycycline due to dental staining risk) 1
• IV ceftriaxone for CNS involvement 1

Critical Pitfalls to Avoid

Do not use first-generation cephalosporins (cephalexin), fluoroquinolones, carbapenems, or vancomycin—these are ineffective against Borrelia burgdorferi 5

Do not combine amoxicillin with probenecid for neuroborreliosis, as probenecid impairs beta-lactam penetration into the CNS 1

Do not treat persistent subjective symptoms after standard therapy with prolonged or repeated antibiotics—multiple controlled trials show no benefit and significant risk of serious adverse events including IV catheter sepsis 1, 5, 2

Do not use corticosteroids routinely—they are recommended only for severe pain unresponsive to antibiotics and analgesics 4

Recognize subtle neurologic symptoms early: Patients with Lyme arthritis who develop subtle distal paresthesias or memory impairment require IV beta-lactam antibiotics, not oral therapy alone 1

When to Consider Treatment Failure

Re-treatment is indicated only when objective clinical manifestations persist or worsen, not for subjective symptoms alone 1, 5. If re-treatment is needed:

• Use a different antibiotic class 1
• Consider IV ceftriaxone 2g daily for 2-4 weeks if oral therapy was initially used 1
• Obtain CSF PCR and culture to document active infection before re-treating 1

Prognosis and Post-Treatment Symptoms

Neuroborreliosis has a favorable prognosis if treated early 2. However, 25-50% of patients report remaining symptoms 5 years after treatment 6. These persistent symptoms do not indicate ongoing infection and do not respond to additional antibiotics 1, 2. Response to treatment is usually slow and may be incomplete, particularly in late disease 1.

Current Practice Patterns in Scandinavia

A 2022 survey of 290 specialists revealed that 78% prefer oral doxycycline for early neuroborreliosis, with 85% treating for 10-14 days 3. In Sweden, 100% of respondents use oral doxycycline for 10-14 days, while 5% in Norway and 19% in Denmark still use IV antibiotics for the entire treatment course 3. This demonstrates a strong shift toward oral therapy based on recent evidence.