Intravenous immunoglobulin treatment in multifocal motor neuropathy

Abstract

Introduction: Multifocal motor neuropathy (MMN) is characterized by asymmetric weakness of limbs and the electrophysiological finding of conduction block in motor nerves. Conduction block is the inability of nerves to propagate action potentials and is probably caused by immune-mediated dysfunction of the axon at the nodes of Ranvier or the myelin sheath. MMN immune pathogenesis has not been elucidated.

Results: In approximately 50% of all patients, IgM antibodies that bind to the glycolipid GM1, which is abundantly expressed in peripheral motor nerves, can be detected. A recent study showed an association with HLA-DRB1*15, and virtually all patients respond to treatment with intravenous immunoglobulin (IVIG) in at least the early stages of the disease.

Conclusion: This review aims at providing a concise overview of what is known about MMN pathogenesis, and how the beneficial effect of IVIG might be explained.

Fig. 1

Schematic depiction of assumed key players in MMN pathogenesis. Anti-GM1 IgM and possibly other antibodies are produced by B cells that may be specifically activated by antigen presenting cells (APC), or through “bystander” effects. There are no indications that T cells are involved. These IgM antibodies may bind to GM1 in nerves if the blood-nerve barrier is leaky, and may locally activate complement. The deposition of complement disrupts the architectural integrity of the nodes of Ranvier and paranodal regions, causing local disruption of Na⁺ channel clusters. This may ultimately contribute to axonal depolarization or hyperpolarization and conduction block. IVIG might interfere with B-cell antibody production through binding to the B-cell receptor or inducing inhibitory receptors, with anti-GM1 antibodies through anti-idiotypic effects, or it might attenuate complement deposition