Polyneuropathy associated with IgG/IgA monoclonal gammopathy: a clinical and electrophysiological study of 15 cases

Abstract

Peripheral neuropathy has been widely reported in patients with monoclonal gammopathy (MG), more frequently immunoglobulin M (IgM) or IgG than IgA. Nevertheless, it remains unclear whether this association has clinical or pathogenic relevance. In order to clarify the possible role of IgG/IgA MG in neuropathy, we studied the clinical and electrophysiological features of 15 consecutive patients with polyneuropathy and IgG/IgA-MG, and compared them to those of 40 patients with polyneuropathy associated with IgM-MG, previously reported. Nine middle-aged patients (60%) had a chronic progressive or relapsing demyelinating polyneuropathy (DP) that was clinically and electrophysiologically indistinguishable from classic chronic inflammatory demyelinating polyneuropathy (CIDP) and frequently responded to immunosuppressive treatments, both characteristics supporting a dysimmune process. Six older patients (40%) had a chronic axonal distal polyneuropathy similar to the so-called chronic cryptogenic sensory polyneuropathy: there was no clear relationship with the MG in these patients and the response to immunosuppressive treatments was poor. Several features allowed us to distinguish between polyneuropathies associated with IgG/IgA-MG (IgG/IgA-PN) considered together and polyneuropathies associated with IgM-MG (IgM-PN). In the first group, the proportion of patients with a predominantly sensory clinical picture (27%) was less than that in the second group (75%), and there were fewer changes in nerve conduction studies. In addition, we found that the nine patients with DP associated with IgG/IgA-MG (IgG/IgA-DP) differed from the 31 with DP associated with IgM-MG (IgM-DP): clinical and electrophysiological studies clearly showed that the demyelinating pattern was more heterogeneous in IgG/IgA-DP than in IgM-DP. The spectrum of polyneuropathies associated with IgG/IgA-MG is heterogeneous, including DP, which is similar to classic CIDP, and axonal polyneuropathy, in which the pathogenic role of the MG remains elusive. In addition, IgG/IgA-DP differ from IgM-DP on clinical and electrophysiological grounds, suggesting probable different physiopathological mechanisms.

Paraproteinemic neuropathy

“…Another pattern is a chronic slowly progressive distal-predominant sensory axonopathy occurring in older patients. 41 The symptoms are usually mild, but the response to immunosuppressants is poor. These findings are consistent with those reported previously for other series.…”

“…45 Direct deposition of IgG or IgA has rarely been detected in peripheral nerves. 41,43,46 Occurrence in the elderly, which is the most common age group for the development of peripheral neuropathy, and the high prevalence of IgG paraproteins of up to 3% after the age of 70 years may support a coincidental association between neuropathy and IgG paraproteinemia. 43 However, the more frequent occurrences of antineural neurofilament, glycoprotein, or glycolipid antibodies, including tubulin, SGPG, and MAG, and antibodies to GM1, sulfatide, or chondroitin sulfate C have been observed in only a minority of patients with axonal neuropathy associated with MGUS, in contrast to those without MGUS.…”

“…49,50 Other observations and open trials involving plasma exchange, cyclophosphamide combined with steroid, IVIg, and corticosteroid monotherapy did not produce any significant evidence of treatment efficacy. 41,43,50 Neuropathy associated with MM MM secreting a monoclonal protein is a plasma-cell neoplasm of the bone marrow that mostly presents with bone pain (e.g., in the spine, ribs, or hip), tiredness, and repeated infections. 19,51 In nervous-system involvement, compressive radicular pain due to lytic bone lesions, pathologic fractures, and plasmacytoma in the spine are the most common symptoms.…”

Current treatments of chronic immune‐mediated demyelinating polyneuropathies

“…198 Patients with CIDP and IgG or IgA monoclonal gammopathies respond to the same treatments as do those without monoclonal gammopathies. 56,80,122 Maintenance Treatment. Less than a third of patients with CIDP remain in remission without therapy.…”

Treatment of dysimmune neuropathies

“…There have been few reports on neuropathy associated with IgA MGUS so that the clinical features [59,80] and the pathogenetic role of the paraprotein in this neuropathy remain unclear. The presence of deposits of the IgA M-protein in the sural nerve biopsy specimens of two patients with chronic demyelinating neuropathy associated with IgA MGUS [67,103] supports the hypothesis that, at least in some patients, this association may not be coincidental.…”