What are the diagnostic criteria for neurobrucellosis?

Diagnostic Criteria for Neurobrucellosis

The diagnosis of neurobrucellosis requires meeting any one of the following criteria: (1) symptoms and signs consistent with neurobrucellosis; (2) isolation of Brucella species from cerebrospinal fluid (CSF) and/or presence of anti-Brucella antibodies in CSF; (3) the presence of lymphocytosis, increased protein, and decreased glucose levels in CSF; or (4) diagnostic findings in cranial magnetic resonance imaging or CT. 1

Clinical Presentation

Neurobrucellosis can present with various neurological manifestations:

• Common neurological findings 1:

  • Agitation (25%)
  • Behavioral disorders (25%)
  • Muscle weakness (23%)
  • Disorientation (21%)
  • Neck rigidity (17%)
  • Cranial nerve involvement (19%)

• Clinical categories 2:

  • Meningoencephalitis (most common form)
  • Cerebral demyelination
  • Myelitis
  • Neuropsychiatric disorders

• Other presentations 3, 4:

  • Neuropsychiatric symptoms (aphasia, diplopia, hemiparesis)
  • Facial paralysis
  • Tremor, ataxia
  • Depression, personality disorder, hallucinations
  • Chronic low-grade relapsing fever

Diagnostic Workup

Laboratory Testing

1. CSF Analysis:

   • Lymphocytosis
   • Increased protein levels
   • Decreased glucose levels
   • Mean adenosine deaminase level of 12.15 u/L 2

2. Serological Testing:

   • CSF tube agglutination (TA) test with Coombs (sensitivity 94%, specificity 96%) 1
   • A cutoff of ≥1:8 for CSF TA is diagnostic 1
   • Blood standard agglutination test (SAT) ≥1:320 2

3. Microbiological Culture:

   • Isolation of Brucella species from CSF (gold standard but low yield - only 15-17.6% positive) 1, 3
   • Blood cultures (positive in approximately 35% of cases) 3

Imaging Studies

• MRI is recommended as the primary imaging modality for suspected neurobrucellosis 5
• When MRI cannot be obtained (e.g., implantable cardiac devices, cochlear implants, claustrophobia), alternative options include:
  • Combination spine gallium/Tc99 bone scan
  • CT scan
  • Positron emission tomography scan 5

Diagnostic Pitfalls and Caveats

1. False negatives in serological tests:

   • Serum SAT can be negative in up to 23.5% of cases 3
   • CSF SAT can be negative in up to 23.5% of cases 3
   • Always perform Coombs' test in both CSF and serum to prevent missed diagnoses 3

2. Low culture yield:

   • Brucella isolation from CSF is challenging (15-17.6% positive) 1, 3
   • Growth is slow and time-consuming 3

3. Nonspecific imaging findings:

   • Imaging techniques may not provide specific findings for Brucella infection 6

4. Endemic considerations:

   • In endemic regions, neurobrucellosis should be considered in the differential diagnosis of neurological and psychiatric cases 3
   • For patients with subacute NVO residing in endemic areas for brucellosis, blood cultures and serologic tests for Brucella species are strongly recommended 5

Diagnostic Algorithm

1. Initial assessment:

   • Evaluate for neurological symptoms in patients with known or suspected brucellosis
   • Perform neurological examination focusing on cranial nerves, motor/sensory function, and meningeal signs

2. Laboratory testing:

   • Obtain blood cultures (2 sets) 5
   • Perform serological tests for Brucella (SAT and Coombs)
   • Conduct lumbar puncture for CSF analysis:
     • Cell count and differential
     • Protein and glucose levels
     • Brucella culture
     • Brucella antibody testing (SAT and Coombs)

3. Imaging:

   • MRI of the brain and/or spine (depending on symptoms)
   • Alternative imaging if MRI contraindicated

4. Definitive diagnosis if any of the following criteria are met 1:

   • Clinical symptoms and signs consistent with neurobrucellosis
   • Positive CSF culture for Brucella species or positive CSF antibodies
   • CSF showing lymphocytosis, increased protein, decreased glucose
   • Diagnostic findings on neuroimaging

Conclusion

Early diagnosis of neurobrucellosis is crucial to prevent sequelae and mortality. The tube agglutination test with Coombs in CSF is highly sensitive and specific using a cutoff of ≥1:8. While culture remains the gold standard, its low yield necessitates reliance on serological testing in both serum and CSF. In endemic regions, neurobrucellosis should be considered in patients presenting with neurological or psychiatric symptoms, particularly those with severe and persistent headache.