What are the characteristic cerebrospinal fluid findings in Guillain‑Barré syndrome?

Cerebrospinal Fluid Findings in Guillain-Barré Syndrome

The characteristic CSF finding in Guillain-Barré syndrome is albuminocytologic dissociation—elevated protein (>0.45 g/L) with a normal white cell count (<50 cells/μL)—but this pattern is present in only 50-70% of patients during the first week and should never be used to exclude the diagnosis. 1, 2, 3

Timing of CSF Protein Elevation

The diagnostic yield of CSF analysis is highly time-dependent and represents a critical pitfall in early GBS diagnosis:

• During the first 4 days of symptom onset, CSF protein remains normal in 43-50% of patients, meaning albuminocytologic dissociation is absent in nearly half of early cases 4, 3
• After day 4, the frequency of elevated protein increases to 84%, demonstrating that CSF findings evolve as the disease progresses 3
• By the second week, 70-90% of patients will demonstrate elevated protein, but 10-30% still have normal levels 4
• A longer duration from clinical onset to lumbar puncture is independently associated with higher diagnostic yield for detecting blood-nerve barrier dysfunction 5

Protein Levels and Clinical Correlations

CSF protein elevation correlates with specific clinical and electrophysiological features:

• High CSF protein levels are associated with demyelinating subtypes (AIDP), proximal or global muscle weakness, and more severe early disease course 3
• Patients with high protein levels have reduced likelihood of being able to run at week 2 (OR 0.42) and week 4 (OR 0.44), indicating worse short-term functional outcomes 3
• Miller Fisher syndrome, distal predominant weakness, and normal/equivocal nerve conduction studies are more likely to have lower CSF protein levels 3

Cell Count Findings

The white cell count in GBS CSF has important diagnostic boundaries:

• 83% of patients have <5 cells/μL, representing the classic "acellular" pattern 3
• 16% have mild pleocytosis (5-49 cells/μL), which is compatible with GBS after excluding infectious causes 2, 3
• Only 1% have ≥50 cells/μL, and marked pleocytosis should prompt reconsideration of the diagnosis and investigation for alternative pathologies such as leptomeningeal malignancy, HIV-associated polyradiculitis, or Lyme disease 2, 3

Practical Diagnostic Approach

Do not delay treatment or dismiss GBS based on normal CSF protein in the first week—this is the single most important clinical caveat 1, 2, 4:

• Perform lumbar puncture during initial evaluation primarily to rule out alternative diagnoses (infections, malignancy) rather than to confirm GBS 2, 4
• Base the diagnosis on clinical features (progressive bilateral ascending weakness, diminished reflexes, preceding infection) rather than waiting for CSF confirmation 2, 4
• If clinical suspicion remains high but CSF protein is normal in the first week, consider repeat lumbar puncture after 1-2 weeks if the diagnosis remains uncertain 4
• Initiate immunotherapy based on clinical suspicion without waiting for CSF protein elevation to develop 2, 4

Additional CSF Markers

Beyond the classic albuminocytologic dissociation, other CSF findings have been investigated but lack clinical utility:

• Cytokines, chemokines, antibodies, complement components, and axonal damage markers have been examined, but none serve as reliable diagnostic biomarkers 6
• Albuminocytologic dissociation remains the only consistent CSF biomarker supporting the diagnosis of GBS 6
• The CSF/serum albumin quotient (Qalb) strongly correlates with CSF total protein (r=0.95) and has similar diagnostic yield, but offers no advantage over standard protein measurement 5