How is Guillain-Barré Syndrome diagnosed?

Diagnosis of Guillain-Barré Syndrome

The diagnosis of Guillain-Barré Syndrome (GBS) is primarily based on clinical history and neurological examination, supported by cerebrospinal fluid analysis and electrophysiological studies. 1

Core Clinical Features

• Progressive bilateral weakness of arms and legs (may initially involve only legs) is the hallmark feature required for diagnosis 2
• Absent or decreased tendon reflexes in affected limbs (at some point during the clinical course) is another required diagnostic feature 2
• Progressive phase typically lasts from days to 4 weeks (usually less than 2 weeks) 2, 1
• Relative symmetry of symptoms and signs strongly supports the diagnosis 2
• Mild sensory symptoms and signs (absent in pure motor variant) 2
• Cranial nerve involvement, especially bilateral facial palsy, is common 1
• Autonomic dysfunction may be present 2
• Muscular or radicular back or limb pain is frequently reported 2

Laboratory Investigations

• Cerebrospinal fluid (CSF) analysis typically shows albumino-cytological dissociation: elevated protein with normal cell count 1
• Important caveat: Protein levels are normal in 30-50% of patients in the first week and 10-30% in the second week of illness, so normal protein does not rule out GBS 1
• CSF pleocytosis (>50 cells/μL) suggests alternative diagnoses 2, 1

Electrophysiological Studies

• Electrodiagnostic testing is recommended to support the diagnosis, especially in atypical presentations 1
• Typical findings include reduced conduction velocities, reduced sensory and motor evoked amplitudes, abnormal temporal dispersion, and/or partial motor conduction blocks 1
• "Sural sparing pattern" (normal sural SNAP with abnormal median/ulnar SNAPs) is characteristic, seen in 67% of patients under 60 years 3
• Electrodiagnostic studies can differentiate between subtypes: AIDP (acute inflammatory demyelinating polyneuropathy), AMAN (acute motor axonal neuropathy), and AMSAN (acute motor and sensory axonal neuropathy) 2, 3
• Normal electrophysiological findings early in the disease course do not rule out the diagnosis 2, 3
• Repeating studies 3-8 weeks after symptom onset may help classify initially unclassifiable cases 2, 3

Imaging Studies

• MRI is not part of routine diagnostic evaluation but can help exclude differential diagnoses 2
• Nerve root enhancement on gadolinium-enhanced MRI is a sensitive but nonspecific finding that can support the diagnosis 2
• Ultrasound imaging of peripheral nerves is an emerging diagnostic tool that may show enlarged cervical nerve roots early in the disease course 2, 1

Features That Cast Doubt on Diagnosis

• Increased numbers of mononuclear or polymorphonuclear cells in CSF (>50 × 10^6/l) 2
• Marked, persistent asymmetry of weakness 2
• Bladder or bowel dysfunction at onset or persistent during disease course 2
• Severe respiratory dysfunction with limited limb weakness at onset 2
• Sensory signs with limited weakness at onset 2
• Fever at onset 2
• Nadir <24 hours 2
• Sharp sensory level indicating spinal cord injury 2
• Hyper-reflexia or clonus 2
• Extensor plantar responses 2

Diagnostic Algorithm

1. Identify bilateral progressive weakness with reduced or absent reflexes 1
2. Evaluate supporting characteristics (progression <4 weeks, relative symmetry) 1
3. Perform lumbar puncture to look for albumin-cytological dissociation 1
4. Perform electrophysiological studies to confirm and classify the subtype 1
5. Consider clinical variants if the presentation is atypical (sensorimotor, pure motor, paraparetic, pharyngo-cervical-brachial, Miller Fisher syndrome) 1
6. Test for anti-GQ1b antibodies when Miller Fisher syndrome is suspected (positive in up to 90% of cases) 1
7. Consider nodal-paranodal antibodies when autoimmune nodopathy is suspected 1
8. Exclude alternative diagnoses using laboratory tests and imaging studies as needed 1
9. Consider changing diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) if progression continues after 8 weeks from onset 4

Common Pitfalls and Caveats

• Relying solely on CSF protein elevation for diagnosis - protein levels may be normal early in the disease course 1
• Dismissing the diagnosis based on normal initial electrophysiological studies - these can be normal early in the disease 2, 3
• Failing to consider clinical variants of GBS that may present atypically 1
• Not recognizing that continued progression beyond 8 weeks suggests A-CIDP rather than GBS 4
• Overlooking the broad differential diagnosis, including CNS disorders, muscle disorders, and other conditions that can mimic GBS 2