Paraproteinemic Neuropathy: A Practical Review

Richard A. Rison; Said R. Beydoun


BMC Neurol. 2016;16(13) 

In This Article

Testing Strategy

A general and detailed neurological exam should be performed to characterize the neuropathic phenotype. Tests should include a hematology panel as well as serum and urine protein electrophoresis with immunofixation. Table 1 describes diagnostic tests, including urinalysis, imaging studies, electrodiagnostic tests, and biopsies.

For patients who are found to have a paraproteinemia, diagnostic testing leans towards investigations of possible hematologic neoplasms. If none are discovered, then other diseases should be considered, including primary (AL) amyloidosis and cryoglobulinemia.[22,24] Monoclonal proteins should be characterized by protein electrophoresis and immunofixation of the serum and the urine. Detailed electrophysiology includes determination of DML (distal motor latency)/MNCV (motor nerve conduction velocity)/TLI (terminal latency index), assessment for CB (conduction block)/ATD (abnormal temporal dispersion). If results of the CBC and/or peripheral smear examination are abnormal, a bone marrow biopsy is recommended, in consult with a hematologist. Even if the results of the CBC and/or peripheral smear examination are normal, then a bone marrow biopsy is still considered and usually recommended based on consultation with a hematologist before the diagnosis of MGUS is made. A skeletal X-ray survey can detect the presence of lytic lesions.

Cerebrospinal fluid (CSF) analysis including cytology and neuroimaging studies (MR neurography) may exclude leptomeningeal infiltration, especially in the presence of lymphoma. Nerve and muscle biopsy are occasionally performed to exclude infiltrative neoplasms, paraproteinemic vasculitis, or AL. If vasculitis is suspected, biopsy of the sural nerve is indicated. Alternatively, biopsy of the superficial peroneal nerve and peroneus brevis muscle obtains both nerve and muscle with a single incision and may increase the yield of identifying vasculitic pathology by up to 10 %. In the work-up of possible AL, abdominal fat aspiration biopsy is preferred over nerve biopsy due to the more favorable safety profile of the former procedure, despite lower sensitivity. If small fiber neuropathy is suspected, epidermal nerve twig analysis via skin biopsy may be performed.

VEGF Testing for POEMS

In patients with M-protein, endocrine and skin changes, and demyelinating polyneuropathy, testing for elevated vascular endothelial growth factor (VEGF) may help diagnose POEMS. A retrospective study found that VEGF levels in patients with POEMS syndrome were markedly elevated compared with patients with other plasma cell dyscrasias (P < .001), peripheral neuropathy (P < .001), and connective tissue disease/vasculitis (P < .009). The best VEGF cut-off for POEMS diagnosis was 146 pg/mL; however, a cut-off of 200 pg/mL had a specificity of 95 % with a sensitivity of 68 % in support of a POEMS diagnosis (level of evidence: 3).[37]