Myelin uncompaction and axo‐glial detachment in chronic ataxic neuropathy with monospecific IgM antibody to ganglioside GD1b. Issue 1 (19th December 2019)

• Record Type: Journal Article
• Authors: Tagliapietra, Matteo; Zanusso, Gianluigi; Ferrari, Sergio; Orlandi, Riccardo; Bertolasi, Laura; Cavallaro, Tiziana; Monaco, Salvatore
• Is Part Of: Journal of the peripheral nervous system. Volume 25:Issue 1(2020)
• Page Start: 54
• Page End: 59
• Publication Date: 2019-12-19
• Subjects: anti‐disialosyl ganglioside antibodies -- anti‐GD1b IgM -- chronic lymphocytic leukemia -- lipid rafts -- myelin vacuolation -- sensory ataxic neuropathy; Nervous system -- Periodicals; Nerves, Peripheral -- Diseases -- Periodicals; Peripheral Nervous System Diseases -- Periodicals; Peripheral Nervous System -- Periodicals; 612.81
• DOI: 10.1111/jns.12359
• Languages: English
• ISSNs: 1085-9489

Abstract

Abstract: To describe clinical features, disease course, treatment response, and sural nerve biopsy findings in a patient with chronic sensory ataxic neuropathy, Binet stage A chronic lymphocytic leukemia, and monoclonal IgMλ paraprotein against ganglioside GD1b. During 9 months of hospitalization at two neurologic centers, the patient underwent serial neurologic examinations, neurophysiologic studies, imaging investigations, extensive laboratory work‐up, bone marrow, and sural nerve biopsies. The patient had a severe progressive sensory neuropathy accompanied by motor involvement, dysautonomia, and marked bulbar weakness with preserved ocular movements. Conduction studies were characterized by prolonged F‐wave minimal latencies, prolonged distal latencies, reduction of compound motor action potentials, and absence of sensory nerve action potentials. Sural nerve biopsy showed endoneurial edema, axonal degeneration, and regeneration, in the absence of cellular inflammation, macrophagic activation, and B‐lymphocyte infiltration; no IgM or complement deposition was detected. Myelinated fibers showed redundant/abnormally thickened myelin, myelin vacuolation, and frank intramyelinic edema with condensed axoplasm. Ultrastructural features included axo‐glial detachment, disruption of membrane integrity, and myelin uncompaction. This study shows that monospecific anti‐GD1b IgM paraprotein is associated with non‐inflammatory nerve damage. We suggest that the loss of myelin and axonal integrity reflects antibody‐induced disruption of membrane lipid rafts.