Guillain-Barré Syndrome (GBS) is a rare but serious autoimmune disorder where the body’s immune system mistakenly attacks its own peripheral nerves. This condition can lead to muscle weakness, numbness, and in some cases, paralysis. Understanding these mechanisms is important for comprehending GBS progression and effects.
The Autoimmune Trigger
GBS often develops after an infection, with symptoms appearing one to three weeks following a bacterial or viral illness. This connection points to molecular mimicry, where the immune system, while fighting a pathogen, encounters structures resembling components of its own peripheral nerves. Due to this similarity, the immune response inadvertently extends to self-tissues.
A common infectious agent linked to GBS is Campylobacter jejuni, a bacterium often responsible for gastrointestinal infections. The lipooligosaccharide (LOS) on C. jejuni shares a structural resemblance with gangliosides, which are complex lipids abundant in human peripheral nerves. When the immune system generates antibodies to combat C. jejuni LOS, these antibodies may then cross-react with nerve gangliosides, initiating an autoimmune attack. Other pathogens associated with GBS include cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Zika virus, which can also trigger this mistaken immune response.
Damage to Peripheral Nerves
The immune system’s attack in GBS primarily targets the peripheral nervous system. This attack can manifest in two main forms of damage: demyelination and axonal damage. Demyelination involves the destruction of the myelin sheath, a fatty layer that insulates nerve fibers for rapid electrical signal transmission. When myelin is damaged, nerve signals slow or are disrupted entirely.
The immune response can also directly damage the axon, the core part of the nerve fiber responsible for transmitting signals. This axonal degeneration involves direct injury to the nerve itself. Immune cells, such as macrophages and T-cells, along with antibodies produced by B-cells, mediate this destruction. These immune components infiltrate the peripheral nerves, leading to inflammation and the breakdown of myelin or axons, impairing the normal flow of electrical impulses.
How Nerve Damage Leads to Symptoms
Damage to peripheral nerves, whether through demyelination or axonal degeneration, directly impairs electrical signal transmission from the brain and spinal cord to muscles, and from sensory receptors back to the brain. When nerve signals are slowed, weakened, or blocked, muscles receive inadequate instructions, leading to progressive strength loss. This often begins as muscle weakness, which can advance to paralysis in affected limbs.
Sensory disturbances also arise from this disrupted signal transmission. Patients may experience numbness, tingling, or an altered sense of touch because sensory nerves are unable to relay accurate information to the brain. The autonomic nervous system, which controls involuntary bodily functions like heart rate, blood pressure, and digestion, can also be affected. This can lead to fluctuations in blood pressure or abnormal heart rhythms. GBS symptoms often progress in an ascending pattern, starting in the legs and moving upwards to the arms and facial muscles.
Understanding GBS Variants
GBS is not a single disease but a spectrum of disorders, with several variants distinguished by the specific parts of the nerve targeted by the immune system and their clinical presentation. The most common variant in Western countries is Acute Inflammatory Demyelinating Polyneuropathy (AIDP), characterized by extensive damage to the myelin sheath. This demyelination impairs nerve conduction, leading to weakness and sensory changes.
Another variant is Acute Motor Axonal Neuropathy (AMAN), where the immune attack primarily targets motor nerve axons, leading to direct nerve fiber damage. AMAN is more prevalent in regions like Japan and China. A less common variant is Miller Fisher Syndrome (MFS), which presents with distinct symptoms such as eye muscle weakness, unsteadiness, and absent reflexes. The specific antibodies and nerve structures they target determine which GBS variant develops and its unique symptoms.