What is Guillain-Barré Syndrome?
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that causes rapidly progressive bilateral limb weakness, typically triggered by preceding infections, and represents the most common cause of acute flaccid paralysis worldwide. 1
Core Definition and Epidemiology
GBS is an inflammatory disease of the peripheral nervous system with an annual global incidence of approximately 1-2 per 100,000 people 1. The syndrome affects males more frequently than females, and incidence increases with age, though all age groups can be affected 1.
Pathophysiology
GBS results from an aberrant immune response to infections that causes damage to peripheral nerves through molecular mimicry 1. The immune system generates antibodies against pathogen antigens that cross-react with gangliosides on peripheral nerves, leading to:
- Complement activation
- Macrophage infiltration
- Nerve and nerve root edema
- Either demyelination or axonal damage depending on the subtype 1
Clinical Presentation
Classic Features
The hallmark presentation is rapidly progressive bilateral weakness starting in the legs and ascending to the arms and cranial muscles 1. Key clinical features include:
- Distal paresthesias or sensory loss preceding or accompanying weakness
- Decreased or absent reflexes at presentation, nearly universal at disease nadir
- Progression to maximum disability within 2 weeks in most patients 1
- Monophasic course (though treatment-related fluctuations occur in a minority)
Associated Features
Dysautonomia is common and potentially life-threatening, manifesting as 1:
- Blood pressure instability
- Heart rate abnormalities
- Pupillary dysfunction
- Bowel/bladder dysfunction
Pain is frequently reported (muscular, radicular, or neuropathic) and can be severe 1.
Critical Timing
If maximum disability occurs within 24 hours or after 4 weeks from onset, consider alternative diagnoses 1. This timing criterion is essential for accurate diagnosis.
Clinical Variants
Beyond the classic sensorimotor form, several distinct variants exist 1:
- Pure motor variant: Weakness without sensory signs
- Miller Fisher syndrome (MFS): Ophthalmoplegia, areflexia, and ataxia
- Pharyngeal-cervical-brachial weakness: Upper limb and cranial nerve predominance
- Paraparetic variant: Lower limb-limited weakness
- Bilateral facial palsy with paresthesias
Atypical Presentations
Young children (<6 years) often present atypically, which can delay diagnosis 1:
- Poorly localized pain
- Refusal to bear weight
- Irritability
- Meningism
- Unsteady gait
In pure motor variants with AMAN subtype, reflexes may be normal or even exaggerated, contrary to the classic presentation 1.
Triggering Infections
Approximately two-thirds of patients report infection symptoms in the 6 weeks preceding GBS onset 1. Six pathogens have established temporal associations 1:
- Campylobacter jejuni
- Cytomegalovirus
- Hepatitis E virus
- Mycoplasma pneumoniae
- Epstein-Barr virus
- Zika virus
Disease Course and Prognosis
Acute Phase
- 20% of patients develop respiratory failure requiring mechanical ventilation 1
- Mortality is 3-10% even with optimal care, primarily from cardiovascular and respiratory complications 1
Recovery Phase
- 60-80% of patients walk independently at 6 months 1
- Recovery can continue for >3-5 years after onset 1
- Recurrence is rare (2-5%), but higher than the general population lifetime risk 1
Long-term Sequelae
- 60-80% experience persistent fatigue 1
- One-third have severe pain at 1 year, which can persist >10 years 1
- Incomplete motor/sensory recovery
- Psychological distress 1
Treatment
Two equally effective treatments exist 1:
- Intravenous immunoglobulin (IVIg): 0.4 g/kg daily for 5 days
- Plasma exchange: 200-250 mL/kg over 5 sessions
No other treatments have proven effective, including corticosteroids 1.
Diagnostic Approach
Diagnosis relies on 1:
- Clinical history and examination
- Electrophysiological studies (distinguish AIDP, AMAN, AMSAN subtypes)
- CSF examination (elevated protein with normal cell count is classic)
- Exclusion of alternative diagnoses
Important caveat: Early in disease course, both electrophysiology and CSF can be normal 1.
Chronic Evolution
In ~5% of patients, repeated relapses (≥3 treatment-related fluctuations or deterioration ≥8 weeks after onset) indicate acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) rather than GBS 1.