Guillain-Barré Syndrome: Definition, Diagnosis, and Treatment
What is Guillain-Barré Syndrome?
Guillain-Barré syndrome is an acute immune-mediated inflammatory disease of the peripheral nervous system that causes rapidly progressive, ascending bilateral weakness, typically reaching maximum disability within 2 weeks, and is the most common cause of acute flaccid paralysis worldwide. 1
Key Epidemiologic and Clinical Features
GBS has a global incidence of approximately 1-2 per 100,000 person-years, affecting males more frequently than females, with incidence increasing with age 1
The disease is typically triggered by a preceding infection (occurring in about two-thirds of patients within 6 weeks before symptom onset), with Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, hepatitis E virus, and Zika virus being the most commonly implicated pathogens 2, 3
The pathophysiology involves molecular mimicry where immune responses against infectious agents cross-react with peripheral nerve components, particularly gangliosides on the axolemma or myelin components 1, 3
Disease Course and Prognosis
GBS follows a triphasic pattern: a progressive phase (days to 2 weeks), plateau phase (days to weeks/months), and recovery phase 4
Approximately 20% of patients develop respiratory failure requiring mechanical ventilation, which can occur rapidly without preceding dyspnea symptoms 1, 4
Mortality remains 3-10% even with optimal medical care, largely due to autonomic nervous system involvement causing cardiac arrhythmias and blood pressure instability 1
Recovery prognosis is generally favorable: 60-80% of patients can walk independently at 6 months, with clinical improvement continuing for more than 3 years in some cases 1, 4
Treatment-related fluctuations occur in a minority of patients, and true relapses occur in only 2-5% of cases 1, 2
Diagnosis of Guillain-Barré Syndrome
Diagnosis is based on clinical presentation of rapidly progressive bilateral ascending weakness with areflexia, supported by cerebrospinal fluid examination showing albumino-cytological dissociation and electrophysiological studies demonstrating peripheral nerve dysfunction. 1
Clinical Diagnostic Criteria
Bilateral ascending weakness starting in the legs and progressing to the arms and cranial muscles over days to 4 weeks (typically less than 2 weeks) 1, 2
Decreased or absent deep tendon reflexes in affected limbs at presentation, with almost all patients showing areflexia at nadir 2, 5
Distal paresthesias or sensory loss that precede or accompany weakness 2, 5
Pain (muscular, radicular, or neuropathic) is frequently an early symptom, affecting approximately two-thirds of patients 2, 5
Cranial nerve involvement, particularly bilateral facial palsy, occurs commonly due to the facial nerve's extensive myelin coverage and long intracranial course 5
Dysautonomia including blood pressure/heart rate instability, pupillary dysfunction, and bowel/bladder dysfunction 2, 5
Critical Red Flags
If nadir is reached in less than 24 hours, this should cast doubt on the diagnosis of GBS 4
Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis (>50 cells/μL) should prompt reconsideration of the diagnosis 5, 6
If progression continues beyond 8 weeks from onset, consider acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP), which occurs in approximately 5% of patients initially diagnosed with GBS 6, 7
Laboratory and Electrophysiological Studies
Cerebrospinal Fluid Analysis:
Classic finding is albumino-cytological dissociation: elevated protein (>0.45 g/L) with normal cell count (<10 cells/μL) 1, 5
Do not dismiss GBS based on normal CSF protein in the first week, as protein elevation may not be present early in the disease course 1, 5
CSF examination is essential to rule out alternative diagnoses such as infectious meningitis or malignant meningitis 5, 6
Electrophysiological Studies:
Nerve conduction studies and EMG should be performed to support diagnosis and classify the neuropathy subtype 5, 6
Look for sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 5, 6
The "sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses) is typical for GBS 5
Electrophysiological studies can distinguish between subtypes: acute inflammatory demyelinating polyradiculoneuropathy (AIDP, most common in Europe/North America), acute motor axonal neuropathy (AMAN, more common in Asia), and acute motor sensory axonal neuropathy (AMSAN) 1, 3
Additional Laboratory Tests:
Initial workup should include complete blood count, glucose, electrolytes, kidney function, and liver enzymes to exclude metabolic or electrolyte causes of weakness 5
Serum creatine kinase may be elevated but is nonspecific 5
Anti-ganglioside antibody testing has limited clinical value in typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected 6
Do not wait for antibody test results before starting treatment if GBS is suspected 5
Clinical Variants
Classic sensorimotor GBS (70% in Europe/Americas, 30-40% in Asia): rapidly progressive symmetrical weakness with sensory signs and areflexia 5
Pure motor variant (5-70% of cases): motor weakness without sensory signs 5
Miller Fisher syndrome (5-25% of cases): characterized by the triad of ophthalmoplegia, ataxia, and areflexia 5, 6
Treatment of Guillain-Barré Syndrome
Intravenous immunoglobulin (IVIg) 0.4 g/kg daily for 5 days or plasma exchange are equally effective treatments and should be initiated within 2-4 weeks of symptom onset in patients unable to walk unaided. 1, 6
Specific Immunomodulating Treatment
Intravenous Immunoglobulin (IVIg):
Recommended dose: 0.4 g/kg/day for 5 consecutive days in patients unable to walk unaided within 2-4 weeks of symptom onset 4, 6
IVIg is typically preferred over plasma exchange for practical reasons (easier administration, better availability) 6, 7
Mechanisms of action include complement inactivation, neutralization of idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on macrophages 3
Plasma Exchange (PE):
Recommended regimen: 200-250 mL/kg total volume divided into 4-5 exchanges (12-15 L total) over 1-2 weeks in patients unable to walk unaided within 4 weeks of symptom onset 5, 6
PE and IVIg are equally effective; choice depends on local availability and patient factors 1, 6
What NOT to Do:
Do not use oral or intravenous corticosteroids alone, as they are ineffective in GBS 3, 6
Do not perform PE followed immediately by IVIg, as this combination is not more effective than either treatment alone 6
Do not routinely give a second course of IVIg to patients with poor prognosis, as evidence for efficacy is uncertain 1, 6
Critical Care Management
Respiratory Monitoring (Essential for All Patients):
Immediately assess respiratory function at presentation and monitor serially, as respiratory failure can occur without symptoms of dyspnea 1, 5
Measure vital capacity, negative inspiratory force (NIF), and maximum inspiratory/expiratory pressures 5
Apply the "20/30/40 rule": patient is at risk of respiratory failure if vital capacity <20 mL/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O 5
Single breath count ≤19 predicts need for mechanical ventilation 5
Approximately 20% of patients require mechanical ventilation, which may be needed for days to months 1, 7
Autonomic Monitoring:
Perform electrocardiography and continuously monitor heart rate and blood pressure for arrhythmias and blood pressure instability 5
Autonomic dysfunction contributes significantly to mortality risk 1
Functional Assessment:
Grade muscle strength using Medical Research Council scale in neck, arms, and legs 5
Assess functional disability using GBS disability scale 5
Test swallowing and coughing ability to identify aspiration risk 5
Check corneal reflex in patients with facial palsy to prevent corneal ulceration 5
Symptomatic Treatment
Pain Management:
Gabapentinoids, tricyclic antidepressants, or carbamazepine are weakly recommended for neuropathic pain treatment 6
Pain is a frequent and often early symptom that can be muscular, radicular, or neuropathic in nature 2, 5
Fatigue:
- No specific treatment is recommended for fatigue, though it is a common residual complaint 6
Prognostic Assessment
Use the modified Erasmus GBS Outcome Score (mEGOS) to assess outcome probability 6, 7
Use the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess risk of requiring artificial ventilation 6, 7
These prognostic models can aid in selecting patients with poor prognosis for more individualized intensive care 8, 7
Psychological Support
Recognize that patients with GBS, even those with complete paralysis, usually have intact consciousness, vision, and hearing 5
Screen for anxiety, depression, and hallucinations, which are frequent complications 5
Be mindful of bedside conversations and explain all procedures to reduce anxiety 5
Common Pitfalls to Avoid
Do not delay treatment waiting for CSF protein elevation or antibody results in clinically suspected GBS 1, 5
Do not dismiss bilateral simultaneous facial weakness as Bell's palsy—this is extremely rare in Bell's palsy and should immediately raise suspicion for GBS 5
Do not overlook respiratory monitoring in patients without dyspnea symptoms, as respiratory failure can occur rapidly without warning 1, 4
Do not confuse treatment-related fluctuations (occurring within 8 weeks) with true relapses or A-CIDP 6, 7
Do not assume normal electrophysiological studies or CSF early in the disease course exclude GBS 1, 5