Abstract: 
The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with peripheral neuropathy. Our role, as physicians, is to determine whether the neuropathy is directly related to the gammopathy or whether the co-occurrence of these two disorders is purely coincidental. The evaluating physician needs to be familiar with
the different types of neuropathies associated with monoclonal gammopathies, their clinical and electrodiagnostic characteristics, and their appropriate diagnostic evaluation and management. Testing for monoclonal protein disorders includes serum protein electrophoresis (SPEP) and immunofixation of blood, and in some cases of urine, as well as measurement of free light chains and quantitative immunoglobulins. Specific antibody testing is directed by paraprotein type and neuropathy phenotype. Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis. When a lambda monoclonal protein is identified together with a clinical phenotype of chronic inflammatory demyelinating neuropathy (CIDP), a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome should be considered. Patients with IgM paraprotein associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti myelin associated glycoprotein (MAG) antibody or CANOMAD syndrome. In many cases, a monoclonal gammopathy of uncertain significance (MGUS) is incidental and unrelated to the neuropathy. Collaboration with oncology is critical in evaluating patients with monoclonal proteins to assess for underlying plasma cell neoplasms or B cell lymphomas.

Chafic Karam has received honoraria for consulting from Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Alpine Pharmaceuticals,
Argenx, AstraZeneca, Corino Therapeutics, CSL Behring, Genetech, Ionis Pharmaceuticals, Neuroderm Ltd., Novo Nordisk, Pfizer, Sanofi,
Takeda Pharmaceutical Company, UCB, and Zai Lab Ltd. He has received research funding from Argenx, AstraZeneca, Genzyme, and Ionis Pharmaceuticals. Rebecca Traub has received research funding from Alnylam Pharmaceuticals, Argenx, Ionis Pharmaceuticals, and Pharnext and has received honoraria for consulting from Takeda Pharmaceuticals and UCB. Adam Cohen has received honoraria for consulting from Janssen, Genentech/Roche, Bristol Meyers Squibb, GlaxoSmithKline, Arcellx, Legend, Abbvie, Pfizer, Ichnos, and Iteos. He has received research funding from GlaxoSmithKline, Genentech and Novartis. Taha Qarni has no relevant disclosures. Conflicts have been resolved according to ACCME guidelines.