Acute and chronic ataxic neuropathies with disialosyl antibodies: A continuous clinical spectrum and a common pathophysiological mechanism

Abstract

Acute ataxic neuropathies with disialosyl antibodies include Fisher syndrome, ataxic Guillain-Barré syndrome (GBS), and acute sensory ataxic neuropathy. Fisher syndrome and ataxic GBS are more strongly associated with IgG anti-GQ1b and anti-GT1a than with anti-GD1b antibodies, whereas the association is reversed in the case of acute sensory ataxic neuropathy. Chronic ataxic neuropathy with disialosyl antibodies is associated with IgM paraprotein to GD1b and GQ1b, which occasionally reacts with GT1a. The clinical, electrophysiological, and pathological features, along with experimental findings, suggest that acute and chronic ataxic neuropathies with disialosyl antibodies form a continuous clinical and pathophysiological spectrum characterized by a complement-mediated disruption at the nodal region and are better classified in the new category of nodo-paranodopathies.

Diagnosis and management of sensory polyneuropathy

“…The remaining acute ataxic neuropathies, including both ASAN and ataxic GBS, have recently been classified as incomplete forms of MFS by some experts 110111. In the past, ASAN was not considered to be a GBS variant because affected patients do not meet the diagnostic criteria for sensory GBS and lack demyelinating features on electrodiagnostic studies.…”

“…Like the acute ataxic neuropathies and MFS, the chronic ataxic neuropathies are also associated with anti-disialosyl antibodies (such as GD1b and GQ1b.) These disialosyl antibody mediated neuropathies can be separately categorized as nodo-paranodopathies 107111116. When the full spectrum of clinical features is present in these disialosyl antibody mediated chronic ataxic neuropathies, the disorder goes by the acronym CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies).…”

“…When the full spectrum of clinical features is present in these disialosyl antibody mediated chronic ataxic neuropathies, the disorder goes by the acronym CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies). CANDA (chronic ataxic neuropathy with disialosyl antibodies) is a more general term and allows for the inclusion of patients without ophthalmoplegia and those in whom the cold agglutinins are IgM antibodies 111. CANDA can relapse, remit, and have cranial neuropathies that result in bulbar dysfunction 117.…”

Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies

“…Autoantibodies against gangliosides can be found in a subset of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), and some autoantibodies like GQ1b or diasilosyl antibodies are associated with distinct clinical syndromes 1 2. Nodes of Ranvier are suspected to be an important site of attack in immune-mediated neuropathies.…”

Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B-cell Lymphoma: A Case Report and Literature Review

“…Since the first case report of antibody-mediated neuropathy with disialylated gangliosides in 1985 (10), the clinical features of this type of neuropathy have been well documented in the literature (11,12). The clinical features of immune-mediated polyneuropathy with IgM antibodies against the disialosyl residues are typically marked sensory ataxia, areflexia, relatively preserved motor function (except for ophthalmoplegia), and a chronic or relapsing course.…”