Guillain-Barré syndrome pathophysiology


 * Associate Editors-In-Chief: Priyamvada Singh, MBBS [mailto:psingh@perfuse.org]

Overview
Guillain-Barré syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy affecting the peripheral nervous system, usually triggered by an acute infectious process. It involves an auto-immune mechanism in which the antibodies formed against the lipopolysaccharides of bacteria or certain vaccines cross reacts with the gangliosides present in myelin of peripheral nerves. As a result of which, myelin degeneration occurs leading to conduction defects that manifests as flaccid paralysis.

Pathophysiology

 * GBS is often associated with an antecedent infection with agents such as Campylobacter jejuni or exposure to some vaccines (influenza vaccine).


 * These causative agents have certain lipopolysaccharides antigens in their capsules that are similar to gangliosides and  glycolipids, such as GM1 and GD1b found in myelin tissues of the peripheral nerve.


 * The immune responses directed against these bacterial capsular lipopolysaccharides also targets the similar GM1 ganglioside which are complex glycosphingolipids present in large quantities on human nerve tissues, especially in the nodes of Ranvier. An example is the GM1 ganglioside, which can be affected in as many as 20-50% of cases, especially in those preceded by Campylobacter jejuni infections. Another example is the GQ1b ganglioside, which is the target in the Miller Fisher syndrome variant.


 * Cellular and humoral immune mechanisms play an important role in the development of disease. Pathologic findings in GBS include lymphocytic infiltration of peripheral nerves, followed by macrophage-mediated, multifocal attack of myelin.


 * These type of immune response that are primarily for foreign antigens (such as infectious agents or vaccines) but are mis-targeted to host nerve tissues instead are called antigenic mimicry or molecular mimicry.


 * The end result of such autoimmune attack on the peripheral nerves is inflammation of myelin, defects in the propagation of electrical nerve impulses and conduction block, leading to a muscle paralysis that may be accompanied by sensory or autonomic disturbances.


 * However, in mild cases, axonal function remains intact and recovery can be rapid if remyelination occurs.


 * In severe cases, such as in the AMAN or AMSAN variants, axonal degeneration occurs, and recovery depends on axonal regeneration. Recovery becomes much slower, and there is a greater degree of residual damage.


 * Recent studies on the disease have demonstrated that approximately 80% of the patients have myelin loss, whereas, in the remaining 20%, the pathologic hallmark of the disease is indeed axon loss.