Causes of Guillain-Barré Syndrome
Guillain-Barré Syndrome (GBS) is primarily caused by an aberrant immune response to preceding infections that damages peripheral nerves, with Campylobacter jejuni being the most frequently identified infectious trigger worldwide. 1, 2
Infectious Triggers
GBS typically develops following an infection, with approximately two-thirds of patients reporting symptoms of infection in the 6 weeks preceding onset. The main infectious agents associated with GBS include:
- Campylobacter jejuni - Most common trigger globally
- Cytomegalovirus
- Epstein-Barr virus
- Mycoplasma pneumoniae
- Hepatitis E virus
- Zika virus 1, 2
These infections are believed to trigger an autoimmune response through a mechanism called molecular mimicry, particularly in the acute motor axonal neuropathy (AMAN) form of GBS. In this process, the infecting organisms share homologous epitopes with components of peripheral nerves, causing immune responses to cross-react with the nerves and resulting in damage 3.
Pathophysiological Mechanisms
The pathophysiology varies by GBS subtype:
In AMAN: The immune system targets gangliosides (GM1, GM1b, GD1a, and GalNAc-GD1a) expressed on motor axolemma, leading to axonal degeneration 3
In Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Immune reactions target Schwann cells or myelin, causing demyelination, though the exact target molecules remain unidentified 1, 3
Complement activation, macrophage infiltration, and edema are typical characteristics of affected peripheral nerves and nerve roots 1
Non-Infectious Triggers
While infections are the primary triggers, other potential causes include:
Vaccines: Rarely associated with GBS. The 1976 swine flu vaccine showed a 7.3-fold increased risk, but subsequent influenza vaccines have shown only approximately one additional GBS case per million vaccinations 1, 2
Immunobiologicals: Tumor necrosis factor antagonists, immune checkpoint inhibitors, and type I interferons have been reported as potential triggers 1
Surgery: Temporal relationships have been reported, though causal links are not well established 1, 4
Geographic Variations
The predominant GBS subtypes vary by region:
- AIDP: Most common form in Europe and North America
- AMAN and AMSAN: More frequent in East Asia (China and Japan)
- Miller Fisher syndrome: Higher prevalence (20-26%) in Eastern Asia compared to 5-10% elsewhere 2, 3
Important Clinical Considerations
- GBS can occur in all age groups, though incidence increases with age 2
- The absence of an identifiable preceding illness does not exclude GBS diagnosis, as infections may be subclinical 1
- The disease is monophasic, though treatment-related fluctuations and rare relapses (2-5% of patients) can occur 1, 2
Understanding these causes is essential for proper diagnosis and management, as early recognition and treatment significantly impact outcomes, with mortality rates of 3-10% even with optimal care 1, 2.