Anti-MAG neuropathy: Role of IgM antibodies, the paranodal junction and juxtaparanodal potassium channels

Abstract Objective To improve understanding of disease pathophysiology in anti-myelin-associated glycoprotein (anti-MAG) neuropathy to guide further treatment approaches. Methods Anti-MAG neuropathy patients underwent clinical assessments, nerve conduction and excitability studies, and ultrasound assessment. Results Patients demonstrated a distinctive axonal excitability profile characterised by a reduction in superexcitability [MAG: −14.2 ± 1.6% vs healthy controls (HC): −21.8 ± 1.2%; p  2 vs HC: 9.1 ± 2.3 mm 2 ; p  Conclusions The imaging and neurophysiological results support the pathogenicity of anti-MAG IgM. Widening between adjacent loops of paranodal myelin due to antibodies would expand the pathway from the node to the juxtaparanode, increasing activation of juxtaparanodal fast potassium channels, thereby impairing saltatory conduction. Significance Potassium channel blockers may prove beneficial in restoring conduction closer to its normal state and improving nerve function in anti-MAG neuropathy.