Lyme Neuroborreliosis

Lyme neuroborreliosis is infection of the nervous system by Borrelia burgdorferi sensu lato, acquired from Ixodes tick bites. Early disease causes lymphocytic meningitis, cranial neuritis (especially facial palsy) and painful radiculitis; late disease is rare and causes encephalomyelitis or neuropathy.

Lyme disease has an incidence of about 20 to 100 in every 100,000 people each year in endemic parts of Europe and the northeastern United States. Nervous system involvement occurs in about 10 to 15% of untreated infections, with peaks in children aged 5 to 9 years and adults aged 50 to 60 years, and men slightly more.

Syndromes. Bannwarth syndrome (painful meningoradiculitis, the commonest in Europe), facial nerve palsy (commonest in children and in North America, bilateral in up to 25%), lymphocytic meningitis, and rare encephalitis, myelitis, cerebral vasculitis and peripheral neuropathy.

Timing. Early neuroborreliosis appears 2 to 12 weeks after the tick bite, often after an erythema migrans rash that may have been unnoticed (absent in about half of patients with neurological disease).

Pathophysiology.

Spirochaetes disseminate from the skin through blood and along nerves to the meninges and nerve roots, where the host immune response, with B cell chemokine CXCL13 activation, causes inflammation.

Direct invasion is limited, and many features reflect immune mediated injury.

• Severe radicular pain, worse at night and unresponsive to usual analgesics, with segmental weakness or sensory loss.
• Unilateral or bilateral lower motor neuron facial palsy; other cranial neuropathies (abducens, vestibulocochlear) in some.
• Headache, neck stiffness, mild fever and fatigue (lymphocytic meningitis).
• Late disease: encephalomyelitis (spastic paraparesis, cognitive change), mononeuritis multiplex, distal polyneuropathy with acrodermatitis chronica atrophicans.
• Past erythema migrans, tick exposure in an endemic area, and arthritis or carditis (conduction block) in some.

Red flags.

• Atrioventricular block or syncope (Lyme carditis).
• Encephalitis, myelitis or stroke like syndrome.
• Pregnancy, immunosuppression, or signs of another infection.

• Clinical suspicion with an endemic exposure and a compatible syndrome.
• Lumbar puncture: lymphocytic pleocytosis, raised protein, and intrathecal Borrelia specific antibody production (antibody index); raised CXCL13 supports early disease.
• Serum two tier serology (screening immunoassay then immunoblot); serology may be negative in the first 2 to 4 weeks, and persistent antibodies do not prove active infection.
• MRI of brain and spine with contrast in encephalomyelitis, cranial nerve enhancement or atypical features; ECG for conduction block.
• Test for HIV and syphilis when relevant; consider tick borne co-infections.

Differential diagnosis. Idiopathic facial palsy (Bell palsy), viral meningitis, herpes zoster radiculitis, disc radiculopathy, neurosyphilis, Guillain-Barré syndrome, multiple sclerosis, sarcoidosis and tuberculous meningitis.

• Doxycycline, first line for early neuroborreliosis (meningitis, radiculitis, cranial neuritis) in adults: 100 mg orally twice daily for 14 days (21 days for meningitis or radiculitis). Maximum 200 mg daily. Take with fluids and upright; monitor liver function, photosensitivity and oesophagitis. Avoid in pregnancy, breastfeeding and children under 8 years; separate from antacids, iron and calcium by 2 hours; no renal adjustment; use caution in hepatic impairment.
• Ceftriaxone for severe disease (encephalitis, myelitis, vasculitis), for those who cannot take doxycycline, or pregnancy: 2 g intravenously once daily for 14 to 28 days (28 days for central nervous system parenchymal disease). Maximum 4 g daily. Monitor liver function, full blood count, biliary sludge and diarrhoea (Clostridioides difficile). Avoid in cephalosporin anaphylaxis; reduce dose in severe renal and hepatic impairment together.
• Children under 8 years: amoxicillin 25 to 50 mg/kg orally daily in 3 divided doses for 14 to 21 days. Maximum 500 mg for each dose in children under 12 years and 1 g for each dose in older children. Monitor rash and diarrhoea; avoid in penicillin allergy; reduce dose in renal impairment.
• Isolated facial palsy without meningitis: doxycycline 100 mg orally twice daily for 14 days (amoxicillin 500 mg orally three times daily for 14 days in pregnancy), with eye protection for incomplete closure.
• Radicular pain: paracetamol 1 g orally every 6 hours (maximum 4 g in 24 hours, or 3 g if under 50 kg, with alcohol excess or liver disease), and gabapentin 300 mg orally at night on day 1, 300 mg twice daily on day 2, then 300 mg three times daily on day 3, increased every 3 to 7 days to 900 to 2400 mg daily (maximum 3600 mg daily; adjust for creatinine clearance: 50 to 79 mL/min, 600 to 1800 mg daily; 30 to 49 mL/min, 300 to 900 mg daily; 15 to 29 mL/min, 150 to 600 mg daily; under 15 mL/min, 150 to 300 mg daily).
• Lyme carditis with high grade block: admission, cardiac monitoring and intravenous ceftriaxone.
• Post-treatment symptoms (fatigue, pain, cognitive complaints) do not need longer antibiotics; use symptomatic and rehabilitative care.

Monitoring. Review at 2 to 4 weeks and 3 months; repeat lumbar puncture only if symptoms persist or fail to improve; most patients improve within weeks, with facial palsy recovering in 1 to 3 months.

Referral and escalation. Infectious diseases and neurology for central nervous system disease, treatment failure or pregnancy; cardiology for conduction block.

Special groups. Pregnancy: ceftriaxone or amoxicillin; avoid doxycycline. Children: amoxicillin under 8 years.