Peripheral neuropathy associated with monoclonal gammopathy

Peripheral neuropathy associated with monoclonal gammopathy is a group of neurological conditions in which damage to the peripheral nerves occurs in the context of an abnormal proliferation of a single clone of plasma cells or B-lymphocytes that produces a monoclonal immunoglobulin (M-protein) detectable in the blood. This condition is also referred to as paraproteinemic neuropathy or dysimmune neuropathy associated with monoclonal gammopathy. The monoclonal protein may be of IgM, IgG, or IgA class, and the underlying hematological condition can range from monoclonal gammopathy of undetermined significance (MGUS) to more serious disorders such as Waldenström macroglobulinemia, multiple myeloma, or amyloidosis. The peripheral nervous system is the primary system affected, though systemic involvement may occur depending on the underlying cause. Patients typically present in adulthood with slowly progressive sensory symptoms including numbness, tingling, and painful sensations in the feet and hands, often in a length-dependent (stocking-glove) pattern. Motor weakness may develop over time, leading to difficulty with balance, walking, and fine motor tasks. In IgM-associated neuropathy, the monoclonal antibody frequently targets myelin-associated glycoprotein (MAG), resulting in a predominantly demyelinating sensory neuropathy with tremor and gait ataxia. IgG and IgA paraproteinemic neuropathies may present similarly to chronic inflammatory demyelinating polyneuropathy (CIDP) and can be axonal or demyelinating in nature. Treatment depends on the type of monoclonal gammopathy and the severity of neuropathy. For IgM anti-MAG neuropathy, rituximab (an anti-CD20 monoclonal antibody) is commonly used, though responses are variable. Neuropathies resembling CIDP associated with IgG or IgA monoclonal gammopathy may respond to intravenous immunoglobulin (IVIg), plasma exchange, or corticosteroids. When an underlying malignancy such as myeloma or Waldenström macroglobulinemia is identified, treatment of the hematological condition is essential. Symptomatic management of neuropathic pain and rehabilitation are important supportive measures. Early diagnosis and identification of the monoclonal protein type are critical for guiding appropriate therapy.

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