A Case of CANOMAD with Review of the Literature

Abstract

Introduction: CANOMAD (an acronym for its full manifestation of chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies) is an uncommon paraproteinaemic neuropathy. Methods and Results:We present the case of a man of 58 years at presentation, with chronic ataxic neuropathy, ophthalmoplegia, and an IgM paraprotein who was found to have antibodies active against disialosylgangliosides. Despite treatment trials with a range of immunosuppressive therapies, intravenous immunoglobulin proved the only effective treatment strategy in his case. Conclusions: CANOMAD has been described in a growing number of individual reports and small series for which we have methodically searched the literature. In the absence of randomised trials of treatment for this disabling condition, we bring together these published clinical experiences, describing the degree of heterogeneity in the presentation/laboratory findings and demonstrating that intravenous immunoglobulin is the therapy found most frequently to be successful.

CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell–targeted therapies

“…Different therapeutic options have included intravenous immunoglobulins (IVIg), plasma exchange, corticosteroids, and immunosuppressive drugs. 7 More recently, small case series have reported encouraging results with rituximab. [21][22][23][24] Finally, although virtually all cases of CANOMAD/CANDA syndrome are associated with the presence of a monoclonal IgM, the spectrum of underlying hematologic malignancies and the efficacy of B-cell-targeting therapies have not been thoroughly investigated.…”

“…Hautepierre, Strasbourg, France; 7 Service de Neurologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France; 8 Department of Neurology, Amyotrophic Lateral Sclerosis (ALS) Reference Center, CHU Tours (Bretonneau Hospital), Tours, France; 9 EA 4391, Excitabilité Nerveuse et Thérapeutique, Université Paris-Est-Créteil, Créteil, France; 10 Service de Neurologie, Hôpital Henri Mondor, Assistance Publique -Hôpitaux de Paris, Créteil, France; 11 Department of Neurology, Nancy University Hospital, Nancy, France; 12 Department of Neurology, La Casamance Hospital, Aubagne, France; 13 Department of Neurology, AP-HP, CHU de Bicêtre, Le Kremlin Bicêtre, France; 14 French National Reference Center for Rare Neuropathies, Le Kremlin Bicêtre, France; 15 INSERM U1195, Paris-Saclay University, Le Kremlin Bicêtre, France; 16 Department of Neurology, University Hospital of Saint-Etienne, Saint-Etienne, France; 17 Saint-Louis University Hospital AP-HP, Paris, France; 18 Peripheral Nervous System and Muscle Department, Université Côte d'Azur, CHU Nice, Nice, France; and 19 Referral Centre for Neuromuscular Diseases and ALS, La Timone Hospital, Marseille, France…”

“…This latter activity can be responsible for a neurologic syndrome termed CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies), which is characterized by chronic neuropathy with sensory ataxia and motor weakness involving oculomotor and bulbar muscles, occurring in the presence of monoclonal IgM directed against disialosyl ganglioside epitopes. As some of the symptoms defining CANOMAD are not observed in all patients, 6,7 this acronym may be restrictive, and the term CANDA (chronic ataxic neuropathy with disialosyl antibodies) has also been proposed. 8 The first case of neuropathy associated with monoclonal IgM with anti-ganglioside auto-activity was described in 1985, 9 and the largest series to date, published in 2001, comprised 18 patients.…”

CANOMAD: A Multi-Faceted Disease

“…Respiratory muscle weakness is rarely observed. Symptoms persistence is widely variable about its duration in years, from 4 years up to 4 decades, but often extended over decades [4,13]. It is reasonable to mention CANOMAD syndrome's course can be wavering over its chronicity [14].…”

“…duced by long-lived CD20 negative plasma cells, which explains the poor response to rituximab treatment [17,18]. Though, owing to the disease's site, rituximab might not be able to reach B Limphocytes in the nervous system due to the large size of the molecule incapable to cross the brain blood barrier [13,16].…”