What is the role of cerebrospinal fluid (CSF) analysis in diagnosing Guillain-Barré Syndrome (GBS)?

Role of Cerebrospinal Fluid Analysis in Diagnosing Guillain-Barré Syndrome

CSF examination is primarily used to rule out other causes of weakness rather than confirm GBS, and should be performed during initial evaluation, with albumino-cytological dissociation (elevated protein with normal cell count) being the classic finding, though normal protein levels do not rule out GBS. 1

CSF Findings in GBS

Classic Finding: Albumino-cytological Dissociation

• Characterized by elevated CSF protein levels with normal cell count (<10 cells/μl)
• Considered a supportive diagnostic feature for GBS 1, 2

Timing Considerations

• Protein levels are normal in:
  • 30-50% of patients in the first week after disease onset
  • 10-30% of patients in the second week 1
• Strong correlation between rising CSF protein and time from symptom onset to lumbar puncture 3
• Sensitivity of CSF protein is significantly lower (45%) in the first week and even lower (32%) in the first 3 days 3

Cell Count Interpretation

• Normal cell count: <10 cells/μl
• Mild pleocytosis (10-50 cells/μl): Compatible with GBS but should prompt consideration of alternative diagnoses like infectious polyradiculitis
• Marked pleocytosis (>50 cells/μl): Suggests other pathologies such as:
  • Leptomeningeal malignancy
  • Infectious diseases of spinal cord/nerve roots
  • Inflammatory diseases of spinal cord/nerve roots 1

Diagnostic Value and Limitations

Diagnostic Value

• Included as a supportive feature in diagnostic criteria for GBS 1
• Helps exclude alternative diagnoses that can mimic GBS
• Most valuable when the diagnosis is uncertain 4

Limitations

• Normal CSF protein does not rule out GBS diagnosis 1, 4
• Low sensitivity in early disease (first week) 3
• Age-adjusted reference limits further reduce sensitivity in early disease 3

Timing of Lumbar Puncture

• Should be performed during initial evaluation of suspected GBS 1
• Main role in first week may be to exclude other inflammatory or neoplastic causes of acute neuropathy 3
• After the first week, sensitivity increases significantly regardless of reference limits used 3

Emerging CSF Biomarkers

• Axonal protein biomarkers in CSF may improve prognostic accuracy:
  • High neurofilament (NfH) levels (>0.73 ng/ml) predict poor outcome with odds ratio of 7.3
  • NfH and tau levels correlate with functional outcome scores 5

Clinical Algorithm for CSF Analysis in GBS

1. Perform lumbar puncture during initial evaluation of suspected GBS

2. Interpret CSF findings:

   • Elevated protein with normal cell count: Supports GBS diagnosis
   • Normal protein with normal cell count: Does not rule out GBS, especially in first week
   • Mild pleocytosis (10-50 cells/μl): Compatible with GBS but consider alternative diagnoses
   • Marked pleocytosis (>50 cells/μl): Consider alternative diagnoses

3. If initial CSF is normal and clinical suspicion remains high:

   • Proceed with treatment if clinical presentation is typical
   • Consider repeat lumbar puncture after 1-2 weeks if diagnosis remains uncertain
   • Utilize electrodiagnostic studies to support diagnosis 1, 4

Important Caveats

• CSF examination alone is insufficient for GBS diagnosis
• Clinical features remain the cornerstone of diagnosis
• Normal CSF findings in early disease should not delay treatment when clinical suspicion is high 1, 4
• The European Academy of Neurology/Peripheral Nerve Society guidelines emphasize that CSF examination is particularly valuable when the diagnosis is less certain 4