What are the diagnostic criteria and treatment options for Guillain-Barré syndrome?

Diagnosis of Guillain-Barré Syndrome

The diagnosis of Guillain-Barré syndrome is primarily clinical, requiring progressive bilateral limb weakness with absent or decreased reflexes, supported by cerebrospinal fluid analysis showing elevated protein with normal cell count (albuminocytologic dissociation) and electrodiagnostic studies demonstrating motor or sensorimotor neuropathy. 1, 2

Required Clinical Features for Diagnosis

The diagnosis fundamentally depends on two mandatory clinical findings 1:

• Progressive bilateral weakness of arms and legs (initially only legs may be involved) 1, 2
• Absent or decreased tendon reflexes in affected limbs at some point during the clinical course 1, 2

Strongly Supporting Clinical Features

Once the required features are present, look for these characteristics that substantially strengthen the diagnosis 1:

• Temporal pattern: Progressive phase lasting days to 4 weeks, usually less than 2 weeks 1, 2
• Symmetry: Relative symmetry of symptoms and signs 1, 2
• Sensory involvement: Relatively mild sensory symptoms and signs (absent in pure motor variant) 1, 2
• Cranial nerve involvement: Especially bilateral facial palsy 1, 2
• Autonomic dysfunction 1, 2
• Pain: Muscular or radicular back or limb pain 1, 2

Cerebrospinal Fluid Analysis

Perform lumbar puncture to identify albuminocytologic dissociation—the classic finding of elevated protein with normal cell count. 2, 3

Critical caveats about CSF findings 2:

• Protein levels are normal in 30-50% of patients in the first week and 10-30% in the second week, so normal protein does not exclude GBS 2
• Marked pleocytosis (>50 cells/μL) casts significant doubt on the diagnosis and suggests alternative diagnoses such as CNS infection or malignancy 1

Electrodiagnostic Studies

Electrodiagnostic testing is advised to support the diagnosis, particularly in atypical presentations, though not mandatory for typical cases. 2, 3

Key electrodiagnostic findings include 2:

• Reduced conduction velocities
• Reduced sensory and motor evoked amplitudes
• Abnormal temporal dispersion
• Partial motor conduction blocks

Important limitation: Normal electrophysiology in early stages does not rule out the diagnosis 1. Consider repeating studies 3-8 weeks after onset if initial results are equivocal or unclassifiable 1.

Features That Cast Doubt on the Diagnosis

Be alert to these red flags that suggest alternative diagnoses 1:

• Increased CSF mononuclear or polymorphonuclear cells (>50 × 10⁶/L) 1
• Marked, persistent asymmetry of weakness 1
• Bladder or bowel dysfunction at onset or persistent during disease course 1
• Fever at onset 1
• Nadir reached in less than 24 hours 1
• Sharp sensory level indicating spinal cord injury 1
• Hyperreflexia, clonus, or extensor plantar responses 1
• Continued progression for more than 4 weeks after symptom onset 1
• Alteration of consciousness (except in Bickerstaff brainstem encephalitis) 1

Additional Laboratory Testing

Obtain complete blood count, glucose, electrolytes, renal function, and liver enzymes to exclude other causes of acute flaccid paralysis such as hypokalemia, thyrotoxic periodic paralysis, or hypophosphatemia 2.

Anti-ganglioside antibody testing has limited diagnostic value in classical GBS 2, 3. However, anti-GQ1b antibodies should be tested when Miller Fisher syndrome is suspected, as they are found in up to 90% of these patients 2, 3.

Imaging Studies

MRI is not part of routine diagnostic evaluation but should be considered to exclude differential diagnoses 1, 2, 3:

• Brainstem infection, stroke, or inflammation
• Spinal cord inflammation or compression
• Leptomeningeal malignancy
• Acute flaccid myelitis (particularly important in young children) 1

Nerve root enhancement on gadolinium-enhanced MRI is a sensitive but nonspecific finding that can support the diagnosis, especially in young children where clinical and electrophysiological assessment is challenging 1, 2.

Diagnostic Algorithm

1. Identify the two required features: progressive bilateral weakness with reduced/absent reflexes 1, 2
2. Evaluate supporting characteristics: progression less than 4 weeks, relative symmetry, mild sensory symptoms, cranial nerve involvement 2
3. Perform lumbar puncture looking for albuminocytologic dissociation (remembering protein may be normal in first 1-2 weeks) 2
4. Obtain electrodiagnostic studies to confirm and classify the subtype 2
5. Exclude alternative diagnoses using laboratory tests and imaging if atypical features present 2
6. Consider A-CIDP if progression continues beyond 8 weeks from onset, which occurs in approximately 5% of patients initially diagnosed with GBS 3

Key Differential Diagnoses to Exclude

The differential diagnosis is broad and depends on individual clinical features 1:

CNS causes: Brainstem or spinal cord inflammation (sarcoidosis, Sjögren syndrome, neuromyelitis optica), transverse myelitis, leptomeningeal metastases, brainstem stroke, vitamin B1 or B12 deficiency 1

Muscle disorders: Hypokalemia, thyrotoxic periodic paralysis, hypomagnesemia, hypophosphatemia, inflammatory myositis, acute rhabdomyolysis, drug-induced toxic myopathy (colchicine, chloroquine, statins) 1

Other: Conversion or functional disorder 1