Neuropathy and paraproteins: review of a complex association
- 21 March 2011
- journal article
- review article
- Published by Wiley in European Journal of Neurology
- Vol. 18 (11), 1291-1298
- https://doi.org/10.1111/j.1468-1331.2011.03380.x
Abstract
Coexistence of neuropathy and monoclonal gammopathy represents a common but complex problem in clinical practice. This association is here reviewed considering latest available literature. The association is not infrequent, and various possible syndromes need to be distinguished. However, coincidental co‐occurrence also needs to be recognized. The monoclonal gammopathy may be a ‘monoclonal gammopathy of uncertain significance’ (MGUS) or occur in a context of malignancy such as multiple myeloma or Waldenström’s macroglobulinaemia. IgM paraproteins can bind to myelin‐associated glycoprotein (MAG) in peripheral nerve. In this case, the paraprotein is directly linked to the neuropathy, causing a specific phenotype. One randomized controlled trial of this (‘Anti‐MAG’) neuropathy showed possible moderate effect of rituximab on disability. Results of another trial are awaited. IgM/G/A paraproteins can be associated with a polyneuropathy indistinguishable from chronic inflammatory demyelinating polyneuropathy. Axonal neuropathies may coexist with IgM/G/A MGUS. There is insufficient evidence about causality or effective treatment in such cases. Pain/dysautonomia with an axonal neuropathy and serum paraprotein raises the possibility of amyloidosis. Specific haematological treatment is required for malignant disorders, although caution is required with neurotoxic agents. Polyneuropathy, organomegaly, endocrinopathy, M‐protein, skin changes syndrome and chronic ataxic neuropathy with ophthalmoplegia, M‐protein, cold agglutinins and disialosyl antibodies represent rare separate entities for which evidence‐based treatment options are still lacking. The association of monoclonal gammopathy and neuropathy requires the appropriate neurological/haematological investigations for a precise diagnosis. Causality is only established in few cases. Adequate management ideally requires joint neurological/haematological input for diagnosis, monitoring and treatment.Keywords
This publication has 50 references indexed in Scilit:
- Prognosis of polyneuropathy due to IgM monoclonal gammopathyNeurology, 2010
- Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European studyJournal of Neurology, Neurosurgery & Psychiatry, 2009
- Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: Study of a UK populationMuscle & Nerve, 2009
- LONG-TERM EFFECT OF RITUXIMAB IN ANTI-MAG POLYNEUROPATHYNeurology, 2008
- Terminal latency index in neuropathy with antibodies against myelin‐associated glycoproteinsMuscle & Nerve, 2007
- Anti-myelin-associated glycoprotein neuropathyCurrent Opinion in Neurology, 2006
- Lymphoma and peripheral neuropathy: A clinical reviewMuscle & Nerve, 2004
- Rituximab in the treatment of polyneuropathy associated with anti‐MAG antibodiesMuscle & Nerve, 2003
- A randomised double blind trial versus placebo does not confirm the benefit of alpha -interferon in polyneuropathy associated with monoclonal IgMJournal of Neurology, Neurosurgery & Psychiatry, 2000
- A randomised clinical trial comparing interferon-alpha and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgMJournal of Neurology, Neurosurgery & Psychiatry, 1997