T36. Motor axonal abnormalities in anti-MAG neuropathy

Abstract

Anti-MAG antibody was known to be associated with polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance, as we call anti-MAG neuropathy. Anti-MAG neuropathy is pathologically characterized by the presence of widely spaced myelin (WSM), which affects the structure of nodes of Ranvier. To help understand the physiological actions of anti-MAG antibody and WSM, we examined the effects on the excitability properties of peripheral motor axons. Four patients with anti-MAG neuropathy were studied. Multiple excitability measurements were made in the median nerve at the wrist, using computerized threshold-tracking (QTRACS with TRONDNF excitability protocol), and compared with normal control data. Subsequently we performed mathematical modeling of the excitability data, using the Bostock model of the human motor axon to simulate axonal excitability measurements (QTRACP with MEMFIT). Nerve excitability studies showed significantly smaller supernormality in recovery cycle and greater changes in excitability with depolarizing currents in threshold electrotonus. Mathematical modeling suggested that the results could be partially explained by abnormal fast K+ current and/or Na+ current at nodes of Ranvier. This study showed that patients with anti-MAG neuropathy exhibit abnormalities in their motor axons attributable to ion channel dysfunction at nodes. This suggests that anti-MAG antibody causes physiological dysfunction of nodes via changes caused by WSM in peripheral nerve.