Paraproteinemic Neuropathy: A Practical Review

Richard A. Rison; Said R. Beydoun


BMC Neurol. 2016;16(13) 

In This Article

Abstract and Introduction


The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients.


Peripheral neuropathy is defined as a disease or degenerative state of the peripheral nerves in which motor, sensory, or vasomotor nerve fibers are affected. The condition appears clinically as muscle weakness and atrophy, pain, and numbness.[1] Several monoclonal antibody-producing conditions are associated with peripheral neuropathy, and in these circumstances, the constellation of neurological symptoms are often referred to as paraproteinemic neuropathy (PPN).[2,3] As neuropathy is relatively common with M-protein and vice-versa, PPN may therefore be defined further as a heterogeneous group of neuropathies, which share the common feature of a homogeneous immunoglobulin in the serum.[4] Typically manifested neurologically as a length-dependent axonal loss sensorimotor polyneuropathy, PPN affects some or all sensory modalities causing allodynia, hyperpathia, cramps, or mild distal weakness (rarely it can be associated with more profound motor symptoms). Sometimes there is multiorgan involvement. Peripheral neuropathy symptoms may precede by years other clinical symptoms or diagnosis of the antibody-producing condition, whether it be hematologic malignancy or monoclonal gammopathy of undetermined significance.[5] Therapies depend on the particular PPN subtype and the pathophysiology involved, and range from intravenous immunoglobulin (IVIG), plasma exchange, and corticosteroids to rituximab and various chemotherapies.