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

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology
Nidhi GargMatthew C Kiernan

Abstract

To improve understanding of disease pathophysiology in anti-myelin-associated glycoprotein (anti-MAG) neuropathy to guide further treatment approaches. Anti-MAG neuropathy patients underwent clinical assessments, nerve conduction and excitability studies, and ultrasound assessment. 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 < 0.01] without alterations in most other excitability parameters. Mathematical modelling of nerve excitability recordings suggested that changes in axonal function could be explained by a 72.5% increase in juxtaparanodal fast potassium channel activation and an accompanying hyperpolarization of resting membrane potential (by 0.3 mV) resulting in a 94.2% reduction in discrepancy between anti-MAG data and the healthy control model. Superexcitability changes correlated strongly with clinical and neurophysiological parameters. Furthermore, structural assessments demonstrated a proximal pattern of nerve enlargement (C6 nerve root cross-sectional area: 15.9 ± 8.1 mm2 vs HC: 9.1 ± 2.3 mm2; p < 0.05). The imaging and neurophysiological results support the pathogenicity of anti-MAG IgM....Continue Reading

Citations

Jan 26, 2020·Journal of the Peripheral Nervous System : JPNS·Peter Y K Van den BerghDavid R Cornblath
Aug 4, 2020·World Journal of Radiology·Antonia S Carroll, Neil G Simon
Sep 1, 2019·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Matthew C KiernanDavid Burke
Mar 2, 2021·Journal of the Neurological Sciences·Sabrina MatàSandro Sorbi
Mar 9, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Tushar IssarArun V Krishnan
Aug 26, 2021·International Journal of General Medicine·Andrew HannafordNeil G Simon

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