Neurobrucellosis

Neurobrucellosis is nervous system infection with Brucella species (B. melitensis, B. abortus, B. suis), occurring in about 3 to 5% of brucellosis. It results from unpasteurised dairy products or animal contact, and is common in the Middle East, Mediterranean, Africa, Central Asia and Latin America.

Pathophysiology. Brucella is a facultative intracellular organism. Direct invasion and an immune response cause meningitis, meningoencephalitis, vasculitis, demyelination and radiculomyelitis.

Fever, sweats and malaise are followed by chronic meningitis (headache, neck stiffness, cranial nerve palsies, especially VI and VIII), meningoencephalitis, myelitis, radiculitis, polyneuropathy, brain abscess, stroke from vasculitis and papilloedema from raised intracranial pressure. Sensorineural deafness is common. Spondylitis and sacroiliitis may coexist.

Red flags.

• Subacute meningitis in an endemic area or after exposure to animals or raw dairy.
• Cranial nerve palsy with lymphocytic CSF.
• Back pain with myelopathy.

Blood culture (prolonged incubation, alert the laboratory) and serology (tube agglutination titre at least 1 in 160, Coombs test). CSF shows lymphocytic pleocytosis, raised protein, low glucose and positive Brucella agglutination titre (at least 1 in 20 in CSF is supportive) or culture. PCR is available. MRI may show meningeal enhancement, white matter lesions, abscess or granuloma. Exclude tuberculosis.

Differential diagnosis.

• Tuberculous and fungal meningitis, neurosyphilis and Lyme neuroborreliosis.
• Sarcoidosis, lymphoma and multiple sclerosis.

Combination therapy for a prolonged period using antibiotics that penetrate the CNS.

• Doxycycline 100 mg orally twice daily.
• Rifampicin 600 to 900 mg orally daily.
• Ceftriaxone 2 g IV every 12 hours for the first 4 to 6 weeks (or co-trimoxazole 160/800 mg twice daily).

Duration. At least 3 months, often 6 to 9 months, until clinical and CSF resolution.

Adjuncts. Dexamethasone 0.15 mg/kg every 6 hours for 4 days in selected cases with severe inflammation or raised pressure. Neurosurgical drainage of abscess or hydrocephalus.

Monitoring. CSF cell count and protein at 3 months, liver tests on rifampicin, drug interactions (rifampicin induces many drugs), serology at 3, 6 and 12 months, and relapse in the 12 months after treatment.

Referral and escalation. Refer to infectious diseases and neurology.

Special groups. In pregnancy, avoid doxycycline and give rifampicin with co-trimoxazole or ceftriaxone with specialist input. In children under 8 years, use rifampicin with co-trimoxazole and an aminoglycoside as advised by paediatric infectious diseases.