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Guillain-Barré Syndrome (GBS)

From Harrison's Principles of Internal Medicine, 22nd Edition (2025)

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1. DEFINITION

• Acute onset
• Rapidly progressive, relatively symmetric limb weakness
• Areflexia
• Cytoalbuminologic dissociation in CSF

• Harrison's 22E, p. 3657; Adams & Victor, p. 1299

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2. EPIDEMIOLOGY

• Annual incidence: 1-2 per 100,000 (range 0.4-1.7/100,000; median 1.1)
• Affects all ages, both sexes, all seasons, worldwide
• Generally non-seasonal and non-epidemic
• Slight female preponderance
• Attack rates highest in persons 50-74 years of age
• Outbreaks reported in rural China linked to C. jejuni exposure in children
• Harrison's 22E, p. 3657; Adams & Victor, p. 1299

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3. ANTECEDENT EVENTS / PRECIPITATING FACTORS

• Harrison's 22E, p. 3657; Adams & Victor, p. 1299

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4. PATHOLOGY AND PATHOGENESIS

Gross/Microscopic Pathology

• Essential lesion: perivascular mononuclear (lymphocytic) inflammatory infiltration of nerve roots and peripheral nerves (established by Asbury et al., 1969)
• Edema of nerve roots is an important early change
• In AIDP: segmental demyelination with sparing of axons initially
• In AMAN/AMSAN: macrophage invasion from nodes of Ranvier into periaxonal space, scavenging injured axons

Immunopathogenesis

1. T-cell mediated immunity: Sensitized T-cells attack peripheral nerve myelin. Experimental allergic neuritis (EAN) in animals after immunization with peripheral nerve homogenates is the experimental model.
2. Humoral (antibody-mediated) immunity: Antimyelin antibodies (particularly IgG) initiate myelin destruction. The earliest change is complement deposition on the inner layer of myelin.
3. Key steps in AIDP (demyelinating form):
   • Lymphocytes attach to endoneurial vessel walls and migrate through
   • Mononuclear exudate mediates breakdown of myelin (segmental demyelination), axon initially spared
   • More intense lesions: polymorphonuclear cells join; axonal interruption occurs in addition to myelin damage
   • Distal axonal injury: nerve cell body survives, regeneration and recovery likely
   • Proximal axonal injury at root level: nerve cell body may die, no regeneration
4. Specific autoantibodies and gangliosides (key exam point):

1. In AMAN: IgG anti-GM1 or anti-GD1a autoantibodies bind to nodal axolemma → MAC (membrane attack complex) formation → disappearance of Nav channel clusters + detachment of paranodal myelin → nerve-conduction failure and muscle weakness → subsequent axonal degeneration → macrophages invade periaxonal space.

• Harrison's 22E, p. 3658-3664; Adams & Victor, p. 1302-1303

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5. SUBTYPES OF GBS

• Harrison's 22E, p. 3660; Adams & Victor, p. 1308

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6. CLINICAL FEATURES

Onset and Progression

• Begins with paresthesias and/or weakness in the lower limbs
• Weakness ascends symmetrically over days to weeks
• Reaches nadir within 2-4 weeks in most patients (maximum between 12 hours and 28 days)
• Followed by a plateau phase, then gradual recovery

Motor Features

• Ascending, symmetric, flaccid weakness - hallmark
• Begins distally, ascends proximally
• Proximal muscles also involved (cannot raise arms, difficulty with climbing)
• Respiratory muscle weakness in ~30% - may require mechanical ventilation
• Bilateral facial weakness/diplopia in ~50%
• Oropharyngeal weakness - dysphagia, dysarthria

Sensory Features

• Paresthesias (tingling, "pins and needles") in feet and hands - often the first symptom
• Sensory loss in glove-and-stocking pattern
• Deep aching pain in weakened muscles (likened to post-exercise pain)
• Dysesthetic pain in extremities from sensory nerve fiber involvement
• Pain is self-limited and responds to standard analgesics

Reflexes

• Areflexia - characteristic and early finding
• Loss of deep tendon reflexes in all affected limbs
• Even mildly affected limbs may lose reflexes

Autonomic Features (important for ICU/exam)

• Sinus tachycardia - most common
• Sinus bradycardia
• Hypertension or hypotension (labile BP)
• Orthostatic hypotension
• Cardiac arrhythmias (may be fatal)
• Loss of sweating or excessive sweating
• Urinary retention (early, transient - causes diagnostic confusion with cord lesion)
• Ileus

Cranial Nerve Involvement

• Facial diplegia (most common cranial nerve palsy)
• Ophthalmoplegia (especially in MFS and severe GBS)
• Dysphagia
• Dysarthria
• Rarely: hypoglossal, hypoglossal involvement

Pain

• Deep aching in back and limbs
• Radicular/nerve root pain early in some cases
• Often underappreciated
• Harrison's 22E, p. 3658-3661; Adams & Victor, p. 1300

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7. INVESTIGATIONS

CSF (Cerebrospinal Fluid) - KEY EXAM FEATURE

• Cytoalbuminologic (albuminocytologic) dissociation:
  • Elevated CSF protein (above normal)
  • WBC count < 10 cells/μL (normal cell count)
• Protein elevation may not appear until 1 week after onset - may be normal in first week
• Opening pressure: normal
• CSF WBC > 50 cells/μL should prompt consideration of HIV, CMV, or Lyme-related GBS

Electrodiagnostic Studies (EDx) - KEY EXAM FEATURE

• Reduced conduction velocity (< 60% normal)
• Prolonged distal latencies
• Prolonged or absent F-waves (earliest abnormality - reflects proximal nerve/root involvement)
• Conduction block
• Temporal dispersion
• Normal or slightly reduced compound muscle action potential (CMAP) amplitudes early

• Reduced CMAP amplitudes (early and prominent)
• Normal or near-normal conduction velocities
• Absent SNAPs in AMSAN

Antibody Testing

• Anti-GQ1b: if MFS suspected
• Anti-GM1, anti-GD1a: if AMAN suspected (post-C. jejuni)
• Anti-GT1a: pharyngeal-cervical-brachial variant

Other

• HIV serology: if risk factors present or if CSF pleocytosis
• Complete blood count, electrolytes, LFTs, renal function
• MRI spine: to exclude cord compression (may show gadolinium enhancement of nerve roots in GBS)
• Nerve biopsy: rarely needed
• Harrison's 22E, p. 3661-3664

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8. DIAGNOSTIC CRITERIA

Brighton Collaboration / Sejvar et al. Criteria (as cited in Harrison's 22E)

• Bilateral AND flaccid limb weakness
• Decreased or absent DTRs in weak limbs
• Monophasic illness; onset to nadir 12 hours to 28 days, then plateau
• Electrodiagnostic findings consistent with GBS
• Cytoalbuminologic dissociation (elevated CSF protein + WBC < 50 cells/μL)
• No alternative diagnosis

• Above motor/reflex criteria + monophasic pattern
• CSF WBC < 50 cells/μL (protein may or may not be elevated)
• OR if CSF unavailable: EDx consistent with GBS
• No alternative diagnosis

• Bilateral flaccid limb weakness + decreased/absent DTRs + monophasic pattern
• No alternative diagnosis (CSF and EDx results not required)

Classic Asbury Criteria (still commonly cited in exams):

1. Progressive weakness of more than one limb
2. Areflexia (at least of ankles)

1. Progression over days to 4 weeks
2. Relative symmetry
3. Mild sensory symptoms/signs
4. Cranial nerve involvement (facial diplegia)
5. Recovery beginning 2-4 weeks after progression stops
6. Autonomic dysfunction
7. Pain (often)
8. CSF protein elevated with < 10 cells/mm³
9. EDx evidence of polyneuropathy

• Harrison's 22E, p. 3662-3665

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9. DIFFERENTIAL DIAGNOSIS

• Harrison's 22E, p. 3663; Adams & Victor, p. 1304

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10. TREATMENT

Specific / Immunotherapy

• Dose: 2 g/kg body weight given as 5 daily infusions (0.4 g/kg/day × 5 days)
• Mechanism: Anti-idiotypic antibodies in IVIg neutralize GBS autoantibodies
• Preferred due to ease of administration and excellent safety profile

• Dose: 40-50 mL/kg per exchange, 4-6 times over 7-12 days
• Meta-analysis of RCTs shows:
  • Reduces need for mechanical ventilation by nearly half (27% → 14%)
  • Increases likelihood of full recovery at 1 year (55% → 68%)

• IVIg and PLEX are equally effective for typical GBS
• Combination of both is NOT significantly better than either alone
• Treat as soon as possible after diagnosis; each day counts
• After 2 weeks from first motor symptoms, uncertain if immunotherapy is still effective
• If patient has reached plateau - treatment may not be indicated (unless severe weakness and active immunologic attack cannot be excluded)
• If no noticeable improvement after one therapy, do NOT switch to the other
• Occasional relapse within 1 month after early treatment - brief re-treatment with original therapy is usually effective
• Glucocorticoids (steroids) are NOT effective in GBS - do not use

Supportive Care (equally important for exams)

• Harrison's 22E, p. 3664-3665; Adams & Victor, p. 1308

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11. PROGNOSIS

• 85% of patients achieve full functional recovery within 6-12 months
• 5-10% have severe permanent disability
• 3-5% mortality (from respiratory failure, autonomic instability, pulmonary embolism, sepsis)
• Recovery begins weeks to months after progression stops
• Recovery depends on degree of axonal damage - demyelinating (AIDP) recovers faster than axonal forms (AMAN/AMSAN)
• AMAN: variable - some recover rapidly (reversible conduction failure), others have prolonged course
• About 3% relapse after initial recovery (treatment-related fluctuation or overlap with CIDP)
• Poor prognostic factors: advanced age, rapid progression, need for ventilation, preceding C. jejuni infection, AMAN/AMSAN subtype, very low CMAP amplitudes
• Harrison's 22E, p. 3665; Adams & Victor, p. 1308

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12. MILLER FISHER SYNDROME - Detailed Criteria (from Harrison's 22E)

• Bilateral ophthalmoparesis + bilateral reduced/absent tendon reflexes + ataxia
• Absence of limb weakness
• Monophasic, onset to nadir 12h-28 days, then plateau
• Cytoalbuminologic dissociation in CSF
• Nerve conduction: normal OR only sensory involvement
• No altered consciousness or corticospinal tract signs
• No alternative diagnosis

• Harrison's 22E, p. 3665

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13. HIGH-YIELD EXAM SUMMARY POINTS

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