What is the primary cause of Guillain-Barré Syndrome (GBS)?

Primary Causes of Guillain-Barré Syndrome (GBS)

Guillain-Barré Syndrome (GBS) is primarily caused by an autoimmune response triggered by a preceding infection, with Campylobacter jejuni being the most common infectious trigger worldwide. 1

Infectious Triggers of GBS

Bacterial Triggers

• Campylobacter jejuni: The predominant trigger, responsible for approximately one-third of all GBS cases globally 2

  • Regional variations exist:
    • Higher prevalence (60-70%) in Bangladesh, China, and Curaçao
    • Lower prevalence (30-32%) in other countries 1
  • C. jejuni typically causes the axonal subtype of GBS (AMAN) through molecular mimicry between bacterial lipo-oligosaccharides and human nerve gangliosides 1
  • GBS associated with C. jejuni is generally more severe than other causes 2

• Other bacterial triggers:

  • Mycoplasma pneumoniae 3, 2
  • Haemophilus influenzae 3

Viral Triggers

• Cytomegalovirus 3, 4
• Epstein-Barr virus 3, 4
• Zika virus (associated with significant outbreaks) 3, 5
• SARS-CoV-2 5
• Enterovirus 3

Pathophysiological Mechanisms

Molecular Mimicry

• The primary mechanism involves molecular mimicry, where the immune response against infectious agents cross-reacts with peripheral nerve components due to structural similarities 4, 2

• In AMAN (acute motor axonal neuropathy):

  • Target molecules are gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on motor axolemma 4
  • Immune reactions attack axonal membrane components 6

• In AIDP (acute inflammatory demyelinating polyneuropathy):

  • Immune reactions target epitopes in Schwann cell surface membrane or myelin 4, 6
  • Specific target molecules in AIDP remain less well-defined 4

Epidemiological Patterns

Regional Variations

• Subtype distribution varies geographically:

  • AIDP is most common in Europe and North America (85% of cases) 4, 6
  • AMAN is more frequent in East Asia (China and Japan) 4
  • MFS (Miller Fisher Syndrome) is more common in eastern Asia (20-26% in Taiwan, Singapore, Japan vs. 5-10% elsewhere) 3

• Antecedent illness patterns:

  • Respiratory infections predominate in Europe, North America, South America, and parts of Asia (22-53%) 3
  • Gastroenteritis is more common in India and Bangladesh (36-47%) 3

Risk Factors

• Despite strong associations with specific infections, the overall risk of developing GBS after infection is very small (only 1 in 1,000-5,000 patients with C. jejuni infection develop GBS) 3
• Genetic factors may play a role (polymorphisms in TNF and MBL2 genes) 3
• Nutritional status may influence susceptibility 3

Important Clinical Considerations

• GBS has a median annual incidence of 1.3 cases per 100,000 population, with men more frequently affected than women 4
• Despite favorable overall prognosis, GBS has approximately 10% mortality and 20% of patients are left with severe disability 4
• Early recognition and treatment are essential for improving outcomes
• Immunomodulation with intravenous immunoglobulin (IVIg) or plasma exchange can shorten the disease course 4, 6

Prevention Strategies

• Public health interventions targeting C. jejuni can reduce GBS incidence
  • New Zealand's initiative to reduce Campylobacter contamination in poultry led to a 13% reduction in GBS hospital admissions 1
• Preventive measures for C. jejuni infection include:
  • Proper food handling and thorough cooking of poultry 1
  • Water safety measures 1
  • Hand hygiene 1
  • Avoiding unpasteurized dairy products 1

Understanding the primary causes of GBS is crucial for early recognition, appropriate treatment, and potential prevention strategies to reduce morbidity and mortality associated with this condition.