What is neurobrucellosis?

Neurobrucellosis: A Serious Neurological Complication of Brucellosis

Neurobrucellosis is a rare but serious complication of brucellosis characterized by the invasion of Brucella bacteria into the central nervous system, presenting with diverse neurological manifestations including meningitis, encephalitis, myelitis, and cranial nerve involvement, requiring prompt diagnosis and prolonged antibiotic treatment to prevent long-term neurological sequelae. 1, 2

Definition and Epidemiology

• Neurobrucellosis occurs in approximately 1.7-10% of systemic brucellosis cases and represents one of the most serious complications of the disease 3
• The condition affects males more frequently than females, with studies reporting a male-to-female ratio of approximately 4.25:1 1
• Most commonly affects adults in their 30s-40s (median age 30-40 years), though it can occur at any age, including children 1, 2
• More prevalent in regions where brucellosis is endemic, particularly areas with unpasteurized dairy consumption and occupational exposure to livestock 4

Pathophysiology and Transmission

• Neurobrucellosis develops when Brucella bacteria, most commonly B. melitensis, cross the blood-brain barrier and invade the central nervous system 1
• Primary routes of Brucella transmission include:
  • Ingestion of unpasteurized dairy products (most common route) 4
  • Direct contact with infected animal tissues through cuts or abrasions (common among farmers, veterinarians, and abattoir workers) 4
  • Inhalation of aerosolized particles (risk for laboratory workers) 4

Clinical Manifestations

• Neurological presentations of neurobrucellosis are diverse and often nonspecific:

  • Meningitis and meningoencephalitis (most common presentations) 5
  • Spinal cord damage (66.7% of cases) 1
  • Cranial nerve involvement (61.9% of cases), with auditory nerve most commonly affected 1
  • Central demyelination (28.6% of cases) 1
  • Limb weakness (52.4% of cases) and sensory abnormalities (52.4% of cases) 1
  • Hearing loss (47.6% of cases) 1
  • Cerebral vein thrombosis (rare but serious complication) 6

• Systemic manifestations often accompany neurological symptoms:

  • Fever (66.7% of cases) 1
  • Fatigue (57.1% of cases) 1
  • Urination or defecation disturbances (42.9% of cases) 1

Diagnosis

• Diagnosis requires high clinical suspicion, especially in endemic areas or with history of animal contact 5

• Laboratory findings include:

  • Cerebrospinal fluid (CSF) abnormalities (present in virtually all cases) 1
  • Positive serum agglutination test (SAT) in 94.7% of cases 1
  • Blood culture positive for Brucella in 37.5% of cases 1
  • CSF culture positive for Brucella in 25% of cases 1
  • Positive IgM and/or IgG antibodies in serum and CSF 3

• Neuroimaging findings:

  • MRI should be performed when spinal involvement is suspected 4
  • White matter changes on neuroimaging are associated with poor prognosis 2
  • Hemorrhagic lesions and venous thrombosis may be seen in severe cases 6

Treatment

• Treatment principles include early initiation, combination therapy, and prolonged duration 1

• Standard regimen for neurobrucellosis typically includes:

  • Doxycycline (100 mg twice daily) for at least 6 weeks, combined with 7
  • Rifampicin (600-900 mg daily) for at least 6 weeks 7
  • Plus a third agent such as ceftriaxone, trimethoprim-sulfamethoxazole, or an aminoglycoside 1, 6

• Treatment duration is typically longer than for uncomplicated brucellosis:

  • Minimum of 6 weeks, often extended to 3-6 months depending on clinical response 7, 1
  • Treatment should continue until CSF normalizes and clinical improvement is observed 1

• Special considerations:

  • For brucellar spondylitis, aminoglycoside-containing regimens may be superior to rifampicin-containing ones 4
  • Immobilization of the spine is crucial when cervical involvement is present to prevent neurological complications 4
  • Surgical intervention may be necessary in cases with increased intracranial pressure or other complications 6

Prognosis and Outcomes

• With appropriate treatment, approximately 71% of patients show improvement 1
• Long-term morbidity affects approximately 23.5% of patients 2
• In-hospital mortality rate is approximately 4.7% 2
• Predictors of poor outcomes include:
  • Older age 2
  • Altered level of consciousness 2
  • Seizures 2
  • Elevated body temperature on admission 2
  • White matter changes on neuroimaging 2

Prevention and Public Health Considerations

• Prevention focuses on:

  • Avoiding consumption of unpasteurized dairy products 4
  • Using appropriate personal protective equipment when handling potentially infected animals 4
  • Following proper laboratory safety protocols when handling Brucella specimens 4

• Healthcare providers should maintain high suspicion for neurobrucellosis in patients with unexplained neurological symptoms, especially those from endemic areas or with history of animal contact 5, 3