What is Guillain-Barré Syndrome (GBS), its cause, symptoms, clinical examination, features, and management?

Guillain-Barré Syndrome (GBS): Comprehensive Overview

What is GBS?

GBS is an acute immune-mediated inflammatory disease of the peripheral nervous system causing rapidly progressive bilateral weakness, typically ascending from legs to arms, and is the most common cause of acute flaccid paralysis—a potentially fatal condition with 3-10% mortality even with optimal care. 1

• GBS has an annual global incidence of approximately 1-2 per 100,000 person-years, occurring more frequently in males and with increasing age 1
• The disease is monophasic, with most patients reaching maximum disability within 2 weeks of symptom onset 2
• Approximately 20% of patients develop respiratory failure requiring mechanical ventilation 3, 4

Cause and Pathophysiology

GBS is triggered by an aberrant immune response to preceding infections that results in damage to peripheral nerves through molecular mimicry. 2

Preceding Infections

• About two-thirds of patients report symptoms of infection in the 6 weeks preceding GBS onset 2
• Common antecedent pathogens include:
  • Campylobacter jejuni (most common bacterial trigger) 5
  • Cytomegalovirus 5
  • Epstein-Barr virus 5
  • Mycoplasma pneumoniae 5
  • Zika virus (linked to epidemic increases in French Polynesia 2013 and Latin America 2015-2016) 2

Immune Mechanism

• Infecting organisms share homologous epitopes with peripheral nerve components (molecular mimicry) 5
• Immune responses cross-react with nerves, causing either axonal degeneration or demyelination 5
• Complement activation, macrophage infiltration, and edema characterize affected peripheral nerves and nerve roots 2
• In AMAN (acute motor axonal neuropathy), target molecules are gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a on motor axolemma 5

Clinical Symptoms and Presentation

Classic Presentation

Rapidly progressive bilateral weakness starting in the legs and ascending to arms and cranial muscles, accompanied by distal paresthesias or sensory loss, with decreased or absent reflexes. 2, 1

• Motor symptoms:

  • Weakness begins distally in legs, progresses to arms and cranial muscles 2
  • Bilateral but can be asymmetrical 2
  • Patients typically reach maximum disability within 2 weeks 2
  • Progression within 24 hours or after 4 weeks should prompt consideration of alternative diagnoses 2

• Sensory symptoms:

  • Distal paresthesias or sensory loss 1
  • Can accompany or precede weakness 2

• Reflex changes:

  • Decreased or absent reflexes in most patients at presentation 2
  • Almost all patients areflexic at nadir 2
  • Pitfall: Pure motor variant with AMAN subtype may show normal or even exaggerated reflexes 2

Autonomic Dysfunction (Dysautonomia)

Autonomic involvement is common and creates life-threatening cardiovascular instability. 3

• Blood pressure instability (severe hypertension to hypotension) 2, 3
• Heart rate instability and cardiac arrhythmias 2, 3
• Pupillary dysfunction 2
• Bowel or bladder dysfunction 2

Pain

• Frequently reported and can be muscular, radicular, or neuropathic 2
• Severe diffuse pain can precede onset of weakness 2
• Can be confusing in diagnosis, especially when preceding weakness 6

Respiratory Involvement

• Respiratory muscle weakness develops in 20-30% of patients 3
• Critical danger: Can occur rapidly without obvious dyspnea 3, 4

Atypical Presentations in Children

Young children (<6 years) can present with nonspecific features that delay diagnosis. 2

• Poorly localized pain 2
• Refusal to bear weight 2
• Irritability 2
• Meningism 2
• Unsteady gait 2

Clinical Variants

Major Variants

GBS has distinct clinical variants that do not progress to the classic sensorimotor pattern. 2

• Pure motor variant: Weakness without sensory signs 2, 1
• Miller Fisher syndrome (MFS): Ophthalmoplegia, areflexia, and ataxia 2, 1
• Regional variants: 2, 1
  • Bilateral facial palsy with paresthesias
  • Pharyngeal-cervical-brachial weakness
  • Paraparetic variant (weakness limited to lower limbs)

Electrophysiological Subtypes

GBS is classified into three main electrophysiological subtypes based on nerve conduction studies. 1, 7

• AIDP (Acute Inflammatory Demyelinating Polyneuropathy): Most common in Europe and North America, characterized by demyelinating features 1, 5
• AMAN (Acute Motor Axonal Neuropathy): More frequent in East Asia, with motor axonal damage 1, 5
• AMSAN (Acute Motor and Sensory Axonal Neuropathy): Both motor and sensory axonal damage 1
• Important: Approximately one-third of patients cannot be classified initially and are labeled "equivocal" or "inexcitable" 1

Clinical Examination

Neurological Examination Findings

The diagnosis is primarily clinical, based on patient history and neurological examination. 2, 1

• Motor examination:

  • Bilateral weakness, typically ascending pattern 1
  • Weakness can be asymmetrical or predominantly proximal/distal 2
  • Test strength in all limbs and cranial nerves 2

• Reflex examination:

  • Areflexia or hyporeflexia in affected limbs strongly suggests GBS 1
  • Pitfall: Normal or preserved reflexes suggest alternative diagnoses (botulism, myasthenia gravis) unless pure motor AMAN variant 2, 1

• Sensory examination:

  • Distal sensory loss or paresthesias 2
  • Can be absent in pure motor variant 2

• Cranial nerve examination:

  • Facial weakness (bilateral facial palsy) 2
  • Ophthalmoplegia in Miller Fisher syndrome 2
  • Bulbar weakness 2

Respiratory Assessment

Respiratory function must be monitored in all patients as failure can occur without dyspnea symptoms. 2

• Vital capacity: Risk when <20 ml/kg 3
• Maximum inspiratory pressure: Risk when <30 cmH₂O 3
• Maximum expiratory pressure: Risk when <40 cmH₂O 3
• Single breath count: ≤19 predicts need for mechanical ventilation 3

Cardiovascular Monitoring

Continuous cardiac monitoring is critical due to unpredictable autonomic complications. 3, 1

• Monitor for cardiac arrhythmias 3
• Blood pressure instability 3

Diagnostic Features and Investigations

Cerebrospinal Fluid (CSF) Analysis

CSF typically shows albumino-cytological dissociation (elevated protein with normal cell count). 1, 7

• CSF examination is valuable, particularly when diagnosis is less certain 7
• Pitfall: Not all patients demonstrate albumino-cytological dissociation, especially early in disease course 2, 8

Electrophysiological Studies

Nerve conduction studies provide evidence of peripheral nervous system dysfunction and distinguish between GBS subtypes. 2, 1

• Electrodiagnostic testing is advised to support diagnosis 7
• Shows demyelinating features in AIDP 1
• Repeating studies 3-8 weeks after onset may help classify initially unclassifiable cases 1

Antibody Testing

Anti-ganglioside antibody testing has limited clinical value in typical motor-sensory GBS. 7

• Anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected 7
• Nodal-paranodal antibodies should be tested when autoimmune nodopathy is suspected 7

Imaging

MRI or ultrasound imaging should be considered in atypical cases to rule out alternative diagnoses. 7

Differential Diagnosis Considerations

Key distinguishing features from other causes of acute flaccid paralysis: 1

• GBS: Ascending bilateral symmetric weakness (legs → arms → cranial nerves) with areflexia 1
• Botulism: Descending flaccid paralysis (cranial nerves → trunk → extremities) with normal/preserved reflexes 1
• Myasthenia gravis: Normal/preserved reflexes with fluctuating weakness 1

Diagnostic Criteria

Multiple criteria exist to assist diagnosis: 8

• National Institute of Neurological Disorders and Stroke criteria 8
• Brighton criteria 8

Management: Step-by-Step Approach

Step 1: Initial Assessment and Stabilization

First priority is assessment of hemodynamic and respiratory status, which may require emergent intervention. 8

• Assess airway, breathing, circulation 8
• Evaluate respiratory function (vital capacity, negative inspiratory force) 1
• Establish continuous cardiac monitoring 3, 1
• Obtain intravenous access 8

Step 2: Respiratory Management

Monitor respiratory function closely as 20% develop respiratory failure requiring mechanical ventilation. 3, 4

• Indications for intubation and mechanical ventilation: 3

  • Vital capacity <20 ml/kg
  • Maximum inspiratory pressure <30 cmH₂O
  • Maximum expiratory pressure <40 cmH₂O
  • Single breath count ≤19
  • Clinical signs of respiratory distress

• Pitfall: Respiratory failure can occur rapidly without obvious dyspnea 3, 4

Step 3: Cardiovascular and Autonomic Management

Manage autonomic dysfunction with continuous monitoring and supportive care. 3

• Continuous cardiac monitoring for arrhythmias 3, 1
• Blood pressure management (avoid aggressive treatment of transient hypertension) 3
• Avoid medications that worsen neuromuscular function: 3
  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides

Step 4: Definitive Immunotherapy

Early treatment with immunotherapy (within first 2 weeks) is associated with better outcomes. 4, 7

First-Line Treatment Options (Equally Effective)

Intravenous immunoglobulin (IVIg) or plasma exchange are first-line treatments for patients unable to walk unaided. 2, 4, 7

• IVIg regimen: 2, 4, 7

  • 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg)
  • Recommended within 2 weeks of weakness onset if unable to walk unaided
  • Good practice point: Consider within 2-4 weeks 7

• Plasma exchange regimen: 2, 7

  • 200-250 ml/kg total volume over 5 sessions
  • 12-15 L in 4-5 exchanges over 1-2 weeks
  • Recommended within 4 weeks of weakness onset if unable to walk unaided

• Treatment selection: IVIg usually preferred for practical reasons 6

What NOT to Do

Do not use corticosteroids alone or in combination with IVIg. 7, 5

• Oral corticosteroids: Recommended against 7
• IV corticosteroids: Weakly recommended against 7
• Corticosteroids alone do not alter GBS outcome 5
• Do not use plasma exchange followed immediately by IVIg 7

Step 5: Management of Treatment-Related Fluctuations

Treatment-related fluctuations (TRFs) occur in 6-10% of patients within 2 months of initial improvement. 4, 6

• TRFs require repeated IVIg treatment 6
• However: Second IVIg course is not recommended in GBS patients with poor prognosis based on current evidence 7
• Pitfall: Efficacy of repeat treatment in patients with insufficient clinical response is uncertain, though commonly practiced 2

Step 6: Distinguish from Acute-Onset CIDP

Consider changing diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) if progression continues after 8 weeks from onset. 7

• Occurs in approximately 5% of patients initially diagnosed with GBS 7, 6
• These patients may require different long-term treatment 7

Step 7: Pain Management

Pain is frequently reported and requires specific treatment. 2, 7

• Weakly recommended medications: 7
  • Gabapentinoids (gabapentin, pregabalin)
  • Tricyclic antidepressants
  • Carbamazepine

Step 8: Fatigue Management

No specific treatment is recommended for fatigue based on current evidence. 7

Step 9: Prognostic Assessment

Use validated scoring systems to predict outcome and need for intensive care. 2, 7

• Modified Erasmus GBS Outcome Score (mEGOS): Calculate on admission to assess outcome 2, 7
• Modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS): Assess risk of requiring artificial ventilation 7

Step 10: Long-Term Recovery and Follow-Up

Recovery is typically most extensive in the first year but can continue for >5 years. 2

• 60-80% of patients walk independently at 6 months 2, 4, 6
• Clinical improvement can continue >3 years after onset 2
• Recurrence is rare (2-5%) 2
• Many patients have residual pain, fatigue, or other complaints persisting for months or years 6

Critical Pitfalls to Avoid

Diagnostic Pitfalls

• Delayed diagnosis due to atypical presentations: Especially in young children presenting with nonspecific symptoms 2, 3
• Normal reflexes: Pure motor AMAN variant can have normal or exaggerated reflexes 2
• Normal CSF early in disease: Albumino-cytological dissociation may not be present initially 2, 8
• Pain preceding weakness: Can confuse diagnosis and delay recognition 2, 6

Management Pitfalls

• Underestimating respiratory risk: Failure can occur rapidly without dyspnea 3, 4
• Using contraindicated medications: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides worsen neuromuscular function 3
• Delayed immunotherapy: Treatment window is narrow (within first 2 weeks for optimal outcomes) 4, 7
• Using corticosteroids: Ineffective alone and not recommended in combination 7, 5

Resource Limitations

In low- and middle-income countries, limited ICU beds, ventilators, and access to immunotherapy lead to higher mortality rates. 3