Pathogenesis of acute and chronic inflammatory neuropathies

Abstract

Guillain-Barre syndrome (GBS) is classified into axonal and demyelinating categories. Acute motor axonal neuropathy (AMAN), an axonal subtype, was widely recognized in the 1990's. Whereas in Europe and North America, classical demyelinating GBS is the major subtype, AMAN is found for 30–80% of GBS cases in Asia. Over the past 25 years, major advances have been made in understanding the immunopathogenesis of AMAN; animal model studies have shown that there is good evidence to support an anti-GM1 antibody-mediated immune process, triggered by molecular mimicry between gangliosides of motor axons and the microorganism. Complement-mediated attack leads to disruption of nodal sodium channel clusters, and paranodal myelin detachment that is responsible for axonal dysfunction/degeneration in AMAN. CIDP is currently classified into “typical CIDP” and other variants such as “multifocal CIDP (mononeuropathy multiplex type)” and distal CIDP. Typical CIDP is a classic form, characterized by symmetric proximal and distal muscle weakness and motor-dominant manifestation. In typical CIDP, demyelination predominantly affects the distal nerve terminals and nerve roots, presumably because of the lack of the blood-nerve barrier in these regions, and this could be responsible for the “non-nerve length-dependent” distribution of muscle weakness. These findings suggest an importance of humoral immunity in typical CIDP. In contrast, multifocal CIDP is characterized by multifocal demyelination in the intermediate nerve trunks, suggesting that cellular immunity may be predominantly involved in breakdown of the blood-nerve barrier at the site of conduction block. The understanding of the pathophysiology of each CIDP subtype is important for appropriate immune-treatments.