Treatment‐responsive primary autoimmune cerebellar ataxia in a patient with IgG and IgM anticerebellar antibodies

• Published in: European journal of neurology Vol. 28; no. 5; pp. 1771 - 1773
• Main Authors: Jaffe, Stephen L., Carlson, Noel G., Peterson, Lisa K., Greenlee, John E.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2021
• Subjects: Antibodies; Antigens; Apheresis; Ataxia; Binding; Brain slice preparation; Cerebellar ataxia; cerebellar autoantibodies; Cerebellum; Exchanging; Glycoproteins; Granule cells; Health services; Immunoglobulin G; Immunoglobulin M; Intracellular; MGUS; monoclonal gammopathy of undetermined significance; Myelin; Myelin-associated glycoprotein; Pathogenesis; Patients; plasma exchange; primary autoimmune cerebellar ataxia; Purkinje cells; immunoglobulin G; primary autoimmune cerebellar ataxia; immunoglobulin M; monoclonal gammopathy of undetermined significance; cerebellar autoantibodies; MGUS; plasma exchange
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/ene.14659

Background and purpose Primary autoimmune cerebellar ataxia (PACA) in the absence of another triggering disease represents an emerging category of neurological illness. We report such a case whose ataxia was markedly responsive to plasma exchange. We analyzed patient serum for the presence of IgM or IgG anticerebellar neuronal antibodies. Methods Case presentation: rat cerebellar slice cultures incubated with patient sera were studied for IgG and IgM antibody uptake, intracellular binding, and neuronal death. Patient serum was evaluated for anti‐myelin associated glycoprotein (anti‐MAG) and associated anti‐glycolipid antibodies. Results Antibodies were taken up by viable cerebellar neurons and bound to intracellular antigens. Uptake and predominantly nuclear binding of IgG were seen in granule cells whereas cytoplasmic binding of IgM was observed predominantly in Purkinje cells. Intracellular antibody accumulation was not accompanied by neuronal death, consistent with the patient’s excellent clinical response to plasma exchange. Anti‐MAG or other associated anti‐glycolipid antibodies were not detected. Conclusions PACA may be associated with both IgG and IgM antibodies reactive with cerebellar neuronal antigens. Our patient’s response to plasma exchange supports a role for antineuronal antibodies in disease pathogenesis and emphasizes the need for rapid diagnosis and treatment. We report a case of plasma exchange‐responsive cerebellar ataxia in a patient with monoclonal gammopathy of undetermined significance. Incubation of the patient’s serum with organotypic (slice) cultures of rat cerebellum demonstrated uptake and intracellular binding of two different antineuronal autoantibodies: IgG antibodies reactive with cerebellar granule cell nuclei and IgM antibodies reactive with Purkinje cell cytoplasm. Neither antibody caused neuronal death, consistent with the patient’s excellent response to plasma exchange.