What is the treatment modality for peripheral neuropathy associated with Lyme disease?

Peripheral Neuropathy in Lyme Disease: Clinical Features and Treatment

Clinical Presentation of Lyme-Associated Peripheral Neuropathy

Peripheral neuropathy occurs in approximately 36% of patients with late Lyme disease and presents most commonly with intermittent limb paresthesias, often without significant deficits on clinical examination. 1

• The neuropathy is predominantly axonal in nature and typically manifests as sensory symptoms affecting the extremities 2, 1
• Approximately two-thirds of patients with acrodermatitis chronica atrophicans (a late skin manifestation of Lyme disease) develop associated peripheral neuropathy, primarily involving the affected extremity with local sensory loss 3
• Cranial neuropathies are common in early neurologic Lyme disease, with facial nerve palsy (seventh cranial nerve) being the most frequent, occurring in approximately 90% of patients with Lyme meningitis 3
• Less common presentations include isolated mononeuropathies (such as femoral neuropathy), polyradiculopathies, and plexopathies 4
• Neurophysiologic testing provides a useful diagnostic tool and important measure of treatment response 1

Treatment Algorithm for Lyme-Associated Peripheral Neuropathy

For Cranial Neuropathy WITHOUT Meningitis (e.g., Isolated Facial Palsy):

Oral doxycycline 100 mg twice daily for 14-21 days is the recommended first-line treatment. 3, 5, 6

• Alternative oral options include amoxicillin 500 mg three times daily or cefuroxime axetil 500 mg twice daily for 14-21 days 5, 6
• For children ≥8 years: doxycycline 4-8 mg/kg per day in 2 divided doses (maximum 200-400 mg/day) 3
• For children <8 years: amoxicillin is preferred 5, 6
• 90% of patients recover without sequelae within 6 months with oral doxycycline therapy 7

For Peripheral Neuropathy WITH Meningitis or Moderate-to-Severe Neurological Manifestations:

Intravenous ceftriaxone 2 g once daily for 14-28 days is the preferred treatment. 5, 8, 6

• Alternative parenteral options include cefotaxime 2 g IV every 8 hours or penicillin G 18-24 million units per day IV divided every 4 hours 5, 8
• The decision between oral and parenteral therapy for cranial neuropathies other than facial palsy should be based on presence of meningitis 3
• Parenteral therapy is mandatory when both clinical and laboratory evidence of coexistent meningitis exists 3

For Persistent Neurological Symptoms After Initial Oral Therapy:

Switch to intravenous ceftriaxone 2 g once daily for 14-28 days if moderate neurological manifestations persist after completing 30 days of oral doxycycline. 8

• In the United States, treatment with intravenous ceftriaxone usually results in improvement of Lyme disease-associated peripheral neuropathy 3
• Response to treatment for late neurologic manifestations is typically slow and may be incomplete 5, 8
• Rapid improvement is documented in 11 of 12 patients following appropriate antibiotic treatment 1

Recent High-Quality Evidence on Treatment Equivalence

A 2021 multicenter randomized equivalence trial demonstrated that oral doxycycline 100 mg twice daily for 4 weeks is equally effective as intravenous ceftriaxone 2 g daily for 3 weeks in treating Lyme neuroborreliosis 9. This suggests that for patients who can tolerate oral therapy and do not have severe manifestations requiring hospitalization, oral doxycycline may be a reasonable alternative to parenteral therapy.

Critical Pitfalls to Avoid

The following treatments are explicitly NOT recommended and should be avoided: 3, 5, 6

• Long-term antibiotic therapy beyond recommended durations
• Multiple repeated courses of antimicrobials for the same episode
• Combination antimicrobial therapy
• Pulsed-dosing regimens
• First-generation cephalosporins, fluoroquinolones, carbapenems, vancomycin, metronidazole, tinidazole, or trimethoprim-sulfamethoxazole (all ineffective against B. burgdorferi)

Consider co-infections with Babesia microti or Anaplasma phagocytophilum in patients with persistent symptoms despite appropriate therapy, especially with fever or characteristic laboratory abnormalities 5, 8

Do not use serologic testing to monitor treatment response - antibody levels remain positive for months to years after successful treatment and do not correlate with clinical response 5