What labs should be ordered for a patient suspected of having a neuroinflammatory condition?

Laboratory Tests for Suspected Neuroinflammatory Conditions

For patients with suspected neuroinflammatory conditions, cerebrospinal fluid (CSF) analysis through lumbar puncture is the cornerstone of diagnosis, accompanied by specific blood tests including inflammatory markers, autoimmune panels, and infectious disease testing.

Initial Diagnostic Approach

Cerebrospinal Fluid Analysis (First Priority)

• Lumbar puncture should be performed as soon as possible unless contraindicated 1
• Basic CSF studies should include:
  • Cell count and differential (lymphocytic pleocytosis of 20-200 cells is common in autoimmune encephalitis) 1
  • Glucose and protein concentrations (elevated protein is common)
  • CSF/serum glucose ratio
  • Gram stain and bacterial cultures
  • Albumin quotient
  • IgG index and synthesis rate
  • Oligoclonal bands (unmatched in serum)

Contraindications to Immediate Lumbar Puncture 1

• Clinical signs of raised intracranial pressure causing brain shift
• Significant brain shift or tight basal cisterns on imaging
• Coagulopathy (requires correction before LP)
• Severe immunocompromise (may require imaging first)

Blood Tests (Tier 1)

1. Basic inflammatory markers:

   • C-reactive protein (CRP)
   • Erythrocyte sedimentation rate (ESR)
   • Complete blood count with differential

2. Metabolic assessment:

   • Complete metabolic panel with renal and hepatic function
   • Electrolytes, glucose, calcium, magnesium, phosphate
   • Thyroid-stimulating hormone (TSH)
   • Vitamin B12 level
   • Homocysteine level 1

3. Autoimmune markers:

   • Antinuclear antibodies (ANA)
   • Extractable nuclear antigen antibodies (ENA)
   • Double-stranded DNA antibodies (dsDNA)
   • Anti-neutrophil cytoplasmic antibodies (ANCA)
   • Complement levels (C3, C4)
   • Lupus anticoagulant
   • Cardiolipin antibodies
   • Thyroglobulin and thyroperoxidase antibodies 1

4. Infectious disease screening:

   • HIV testing
   • Viral hepatitis panel (B and C)
   • Tuberculosis testing (prior to immunosuppressive therapy) 1

Specialized Testing Based on Clinical Presentation

Autoimmune Encephalitis Evaluation

• Neural autoantibody panels in serum and CSF:
  • NMDA receptor antibodies
  • Voltage-gated potassium channel complex antibodies
  • Other relevant autoantibodies based on clinical presentation 1
• CSF viral studies:
  • HSV1/2 PCR
  • Varicella zoster virus PCR and IgG/IgM
  • Enterovirus PCR
  • Other viral PCRs based on epidemiology 1

Inflammatory Myopathy Evaluation

For patients with suspected inflammatory myopathy:

• Creatine kinase (CK)
• Transaminases (AST, ALT)
• Lactate dehydrogenase (LDH)
• Aldolase
• Troponin (to evaluate myocardial involvement)
• Consider paraneoplastic autoantibody testing 1

Multiple Sclerosis Evaluation

• Anti-MOG antibodies
• Aquaporin-4 antibodies
• Serum ACE (to rule out sarcoidosis)
• 25-OH Vitamin D level 1, 2

Imaging Studies

Brain and Spine Imaging

• MRI brain with and without contrast is preferred over CT 1
• MRI spine may be indicated based on clinical presentation
• Consider advanced neuroimaging techniques if diagnosis remains uncertain 1

Important Considerations

Timing of Testing

• Blood samples should be collected prior to treatment with intravenous immunoglobulins or plasmapheresis to avoid false results 1
• CSF should be obtained before antimicrobial therapy when possible

Limitations of Inflammatory Markers

• CRP and ESR have limited specificity for neuroinflammation 3, 4
• ESR has a longer half-life than CRP, making it better for monitoring chronic conditions 3
• CRP is more useful for acute inflammatory conditions and monitoring response to therapy 4
• Normal inflammatory markers do not exclude neuroinflammation 5

Diagnostic Pitfalls

• Routine CSF studies may be normal in some autoimmune encephalitis patients; neural autoantibody testing should still be performed if clinical suspicion is high 1
• Multiple conditions can cause false elevations in inflammatory markers 6
• Consider non-inflammatory neurological conditions in the differential diagnosis, particularly in elderly patients who may present atypically 7

By systematically applying this laboratory approach, clinicians can effectively evaluate patients with suspected neuroinflammatory conditions while avoiding unnecessary testing and diagnostic delays.