From the Guidelines
Guillain-Barré syndrome (GBS) is an acute autoimmune disorder that primarily affects the peripheral nervous system, involving an immune response triggered by a preceding infection or other immune stimulus, which causes demyelination and/or axonal damage of peripheral nerves, disrupting nerve signal transmission. The pathophysiology of GBS is complex and not fully understood, but it is thought to involve molecular mimicry between pathogen antigens and nerve components, leading to an autoimmune response [ 1 ]. This immune attack causes damage to the myelin sheaths or axons of peripheral nerves, resulting in rapid-onset muscle weakness and sensory disturbances [ 1 ]. The process usually begins in the distal limbs and ascends proximally, often symmetrically, and can affect respiratory muscles and autonomic functions in severe cases.
Key Factors in GBS Pathophysiology
- Preceding infections, such as Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and SARS-CoV-2, can trigger the autoimmune response [ 1 ]
- Molecular mimicry between pathogen antigens and nerve components is thought to play a role in the development of GBS [ 1 ]
- Genetic and nutritional factors, such as polymorphisms in the TNF gene and MBL2 gene, and poor nutritional status, may influence the patient's susceptibility to producing cross-reactive antibodies [ 1 ]
- The severity and duration of symptoms can vary widely among patients, reflecting the degree of nerve damage and the body's ability to repair and regenerate affected nerve fibers [ 1 ]
Clinical Presentation and Diagnosis
The clinical presentation of GBS is heterogeneous, and diagnosis is based on patient history, neurological, electrophysiological, and cerebrospinal fluid (CSF) examinations [ 1 ]. Electrophysiological studies can distinguish between the subtypes of GBS, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN) [ 1 ]. Early recognition and diagnosis of GBS are crucial to initiate prompt treatment and improve outcomes.
From the Research
Pathophysiology of Guillain-Barré Syndrome (GBS)
The pathophysiology of GBS is complex and involves an immune-mediated attack on the peripheral nervous system. Key aspects include:
- Immune-mediated attack of peripheral nervous system myelin, axons, or both, presumed to be triggered by molecular mimicry, with both cell- and humoral-dependent mechanisms implicated in disease pathogenesis 2
- Autoimmune attack on the Schwann cell membrane wrapping the myelinated nerve fibers in acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 3
- Antibody-mediated attack on the axolemma at the nodes of Ranvier in acute motor or motor and sensory axonal neuropathy (AMAN and AMSAN) 3
- Production of symptoms and the course of the disease are influenced by the immune response and the resulting damage to the peripheral nerves 4
Immunopathogenesis
The immunopathogenesis of GBS involves:
- Autoimmune responses leading to neural damage and dysfunction, triggered by infectious and noninfectious factors 5
- Association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines, as well as flaviviruses, although a robust conclusion has yet to be reached 5
- Variable efficacy of immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), depending on GBS subtype and severity at initial presentation 2, 5
Disease Mechanisms
The disease mechanisms of GBS are not fully understood, but research suggests that:
- Molecular mimicry plays a role in GBS pathogenesis, especially in its axonal forms 2
- The immune response and resulting damage to the peripheral nerves influence the production of symptoms and the course of the disease 4
- Novel potential therapies, including leukocyte trafficking inhibitors, are being explored, but none have yet modified clinical practice 6, 2