Anti‐disialosyl‐immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study

Abstract

Background and purpose In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti‐disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA). Results Fifty‐five patients with a polyneuropathy evolving for more than 2 months and with at least one anti‐disialosyl ganglioside IgM antibody, that is, anti‐GD1b, ‐GT1b, ‐GQ1b, ‐GT1a, ‐GD2 and ‐GD3, were identified. Seventy‐eight percent of patients were male, mean age at disease onset was 55 years (30–76) and disease onset was progressive (82%) or acute (18%). Patients presented with limb sensory symptoms (94% of cases), sensory ataxia (85%), oculomotor weakness (36%), limb motor symptoms (31%) and bulbar muscle weakness (18%). Sixty‐five percent of patients had a demyelinating polyradiculoneuropathy electrodiagnostic profile and 24% a sensory neuronopathy profile. Anti‐GD1b antibodies were found in 78% of cases, whilst other anti‐disialosyl antibodies were each observed in less than 51% of patients. Other features included nerve biopsy demyelination (100% of cases), increased cerebrospinal fluid protein content (75%), IgM paraprotein (50%) and malignant hemopathy (8%). Eighty‐six percent of CNDA patients were intravenous immunoglobulins‐responsive, and rituximab was successfully used as second‐line treatment in 50% of cases. Fifteen percent of patients had mild symptoms and were not treated. CNDA course was progressive (55%) or relapsing (45%), and 93% of patients still walked after a mean disease duration of 11 years. Conclusion Chronic neuropathies with anti‐disialosyl ganglioside IgM antibodies have a recognizable phenotype, are mostly intravenous immunoglobulins‐responsive and present with a good outcome in a majority of cases.

Advances in diagnosis and management of distal sensory polyneuropathies

“…Another recent study of 55 patients with chronic neuropathies with antidisialosyl ganglioside antibodies showed variability in the neurophysiological findings. Although a demyelinating polyradiculoneuropathy was seen in most participants (65%), a clinical and electrophysiological phenotype matching axonal sensory polyneuropathy was seen only in 16% 38…”

The autoimmune vulnerability of the node of Ranvier

“…73,74 IgM antidisialosyl gangliosides (anti-GD1b, anti-GT1b, anti-GD3, and anti-GQ1b occasionally reacting with GT1a) are associated with chronic ataxic neuropathies, such as CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies). 75,76 These antibodies have also been shown to target the NoR: in cocultures with stem cell-derived human sensory neurons, human and mouse antidisialosyl antibodies targeted the nodal axolemma and induced acute axonal degeneration in the presence of complement, while prolonged application of IgM from a CANOMAD patient induced complementindependent demyelination. 77,78…”

Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee

“…No double-blind, placebo-controlled studies were identified evaluating the use of IVIG in treating chronic autoimmune large fiber polyneuropathy. However, a number of case series and anecdotal reports have shown benefit in patients with polyneuropathy associated with Sjögren syndrome, [54][55][56] systemic lupus erythematosus, 57,58 sarcoidosis, 59 systemic sclerosis, 60 inflammatory bowel disease, 61 and CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, monoclonal protein, agglutination, and disialosyl antibodies) 62,63 with mixed results in paraneoplastic neuropathy. 64,65 There is also evidence suggesting that IVIG may be detrimental in patients with cryoglobulinemic neuropathy due to immune complex precipitation, organ failure, and other complications.…”