The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies

Willison, Hugh J.; O’Leary, Colin; Veitch, J.; Blumhardt, L D; Busby, Mark; Donaghy, Michael; Fuhr, Peter; Ford, Henry C.; Hahn, Angelika F.; Renaud, Susanne; Katifi, Haider; Ponsford, S.; Reuber, Markus; Steck, Andreas; Sutton, Ian; Schady, W.; Thomas, P. K.; Thompson, Alan J.; Vallat, Jean‐Michel; Winer, John

doi:10.1093/brain/124.10.1968

Cited by 271 publications

(237 citation statements)

References 47 publications

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“…In contrast to the acute neuropathy associated with IgG autoantibodies against disialosyl epitopes, including GD1b and GQ1b, monoclonal IgM antidisialosyl ganglioside antibodies are typically associated with a chronic ataxic sensory neuropathy, sometimes presenting with CANOMAD. 114 In this syndrome, the IgMs react with the disialosyl epitope shared by gangliosides GD1b, GQ1b, GT1c, and GD3. This form of sensory ataxic neuropathy, occasionally with ophthalmoplegia or bulbar signs, affects large sensory fibers and is characterized by distal paresthesias, numbness, prominent ataxia, areflexia, and mild or no limb weakness.…”

Section: Differential Diagnosismentioning

confidence: 99%

Clinical features and pathophysiological basis of sensory neuronopathies (ganglionopathies)

Antoine²,

2004

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Sensory ganglionopathies have a frequent association with neoplastic disorders (paraneoplastic subacute sensory neuronopathy, or SSN) or dysimmune disorders (Sjögren's syndrome, SS; Miller Fisher syndrome; and Bickerstaff's brainstem encephalitis, BBE), with drugs, such as cisplatin or pyridoxine, and with inherited disorders with degeneration of dorsal root ganglion cells. Unsteady gait and pseudoathetoid movements of the hand are the distinctive signs encountered in these disorders. The chronic disorders are characterized by non-length-dependent abnormalities of sensory nerve action potentials (SNAPs) and differ from other sensory neuropathies in showing a global, rather than distal, decrease in SNAP amplitudes. This review focuses on recent advances in defining the mechanisms involved in sensory ganglionopathies. Specific topics include a summary of their clinical features, pathological findings, and immunopathology. In SSN, early diagnosis by the detection of anti-Hu antibodies and early treatment of the cancer gives the best chance of stabilizing the disorder. In SS sensory ganglionitis, response to treatment has been disappointing, but immunomodulating treatments are emerging. The immunological profile common to BBE and Fisher syndrome supports a common pathogenesis. In toxic sensory neuronopathy, no treatment is available. The differential diagnosis involves separating sensory ganglionopathies from other ataxic polyneuropathies, such as infectious neuropathies, sensory neuropathies with various autoantibodies, and the neuropathies seen in celiac disease.

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Section: Differential Diagnosismentioning

confidence: 99%

Clinical features and pathophysiological basis of sensory neuronopathies (ganglionopathies)

Antoine²,

2004

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“…Sensory ataxic neuropathy is the clinical hallmark in several patients with IgM paraprotein reacting with gangliosides containing disialosyl moieties (Ilyas et al, 1985;Dalakas and Quarles, 1996;Willison et al, 2001). Pathological examination of dorsal root ganglia of our SGPG-immunized cats revealed sensory ganglionitis with inflammatory infiltrates.…”

Section: Discussionmentioning

confidence: 73%

Induction of experimental ataxic sensory neuronopathy in cats by immunization with purified SGPG

Ilyas

Dalakas

et al. 2008

Journal of Neuroimmunology

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SummaryIgM paraproteins in about 50% of the patients with neuropathy associated with IgM gammopathy react with carbohydrate moieties in myelin associated glycoprotein (MAG) and in sulfated glucuronic glycolipids (SGGLs) in human peripheral nerves. However, the role of anti-MAG/SGGL antibodies in the pathogenesis of neuropathy remains unclear. In order to induce an animal model of neuropathy associated with anti-MAG/SGGL antibodies, cats were immunized with sulfoglucuronyl paragloboside (SGPG). All four cats immunized with SGPG developed clinical signs of sensory neuronopathy within 11 months after initial immunization, characterized by unsteadiness, falling, hind limb weakness and ataxia. In two cats the ataxia and hind limb paralysis were so severe that the animals had to be euthanized. Pathological examination revealed sensory ganglionitis with inflammatory infiltrates in the dorsal root ganglia. No overt signs of pathology were noted in the examined roots or nerves. High titer anti-SGPG/MAG antibodies were detected in all 4 cats immunized with SGPG but not in 3 control cats. Our data demonstrate that immunization of cats with SGPG induced anti-SGPG antibodies and sensory neuronopathy clinically resembling the sensory ataxia of patients with monoclonal IgM anti-MAG/SGPG antibodies. This study suggests that these anti-MAG/SGPG antibodies play a role in the pathogenesis of this neuropathy.

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“…However, several relevant autoantibodies in nonparaneoplastic inflammatory neuropathies are of the IgM isotype. This includes anti‐MAG antibodies associated to monoclonal gammopathy of unknown significance and plasma cell dyscrasias,30 anti‐GM1 antibodies in multifocal motor neuropathy31, and anti‐disialosyl antibodies in CANOMAD syndrome 32. Four out of 10 patients with sensory‐motor neuropathy stained Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Siles

Martínez‐Hernández

Araque

et al. 2018

Ann Clin Transl Neurol

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ObjectiveParaneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN).MethodsThirty‐four patients fulfilling diagnostic criteria of possible (n = 9; 26.5%) and definite (n = 25; 73.5%) PN without onconeural antibodies and 28 healthy controls were included in our study. Sera were tested for known antibodies against neural cell adhesion molecules and screened for novel IgG and IgM reactivities against nerve components: dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells. Patients showing autoantibodies against any of these cell types were used for immunoprecipitation (IP) studies.ResultsOverall, 9 (26.5%) patients showed significant reactivity against DRG neurons, motor neurons, or Schwann cells, whereas 5 (17.9%) healthy controls only showed moderate reactivity. Compared with control sera, serum samples from patients with paraneoplastic sensory‐motor neuropathies had a higher frequency of IgM antibodies against Schwann cells (0% vs. 40%; P = 0.0028). No novel antigens were identified from our IP experiments. Antibodies against the neural adhesion molecules CNTN1, NF155, NF140, NF186, NCAM1, L1CAM, and the CNTN1/CASPR1 complex were not detected in patients with PN. One (2.9%) patient with CIDP and thymoma had CASPR2 antibodies.InterpretationAlmost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm‐associated antigens remain to be discovered.

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The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies

Cited by 271 publications

References 47 publications

Clinical features and pathophysiological basis of sensory neuronopathies (ganglionopathies)

Clinical features and pathophysiological basis of sensory neuronopathies (ganglionopathies)

Induction of experimental ataxic sensory neuronopathy in cats by immunization with purified SGPG

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

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