Diagnosis of Paraproteinemic Neuropathy Commonly Missed

Motor Neurons (Multipolar) with many Processes (mostly Dendrites), Spinal Cord–50X. Shows: 4 multipolar neurons, processes (mostly dendrites), cell bodies, nuclei and neuroglial cells. These motor neurons are located in the anterior (ventral) horn of the spinal cord (gray matter).
The correct diagnosis of paraproteinemic neuropathy was missed in almost 1 in 5 patients in this study cohort.

About 1 in 5 patients who present to an academic neuromuscular clinic for neuropathy with a monoclonal protein do not receive an appropriate diagnosis of paraproteinemic neuropathy, according to a study in the Journal of the Neurological Sciences.

The study was an analysis of medical charts for 410 patients with neuropathy who attended a tertiary academic neuromuscular clinic between 2017 and 2019. A total of 54 (13%) of patients with neuropathy also had a monoclonal protein and were included in the study (median age, 65.6 years). Of these, 30 patients (55%) had immunoglobulin (Ig) G monoclonal protein, 14 (26%) had IgM, 4 (7%) had IgA, 3 (5%) had light chain, and 3 patients (5%) had mixed IgM and IgG. Neuropathy was related to the monoclonal protein in 24 (44%) patients. The investigators obtained patient-specific characteristics and assessed diagnoses and outcomes.

Prior to their referral, approximately one-quarter (25%) of patients did not have serum protein electrophoresis or immunofixation checked. In addition, none of the patients had serum free light chain checked before referral. Up to 19% (n=10) of patients were misdiagnosed because of a lack of screening for monoclonal protein or because their monoclonal protein was considered a monoclonal protein of unknown significance.

The most frequently missed diagnoses in this cohort included light chain amyloidosis and POEMS (polyneuropathy, organomegaly, monoclonal plasmaproliferative disorder, skin changes; also referred to as osteosclerotic myeloma) syndrome.

Limitations of this study were the small sample size as well as the inclusion of patients from a single academic medical center.

The researchers from the academic center wrote that they hope their “experience may help neurologists revisit the vast spectrum of neuropathies that can be associated with monoclonal proteins and that a systematic testing approach can allow prompt and accurate diagnosis and initiation of appropriate therapy.”


Karam C, Moshe-Lilie O, Chahin N, et al. Diagnosis of paraproteinemic neuropathy: Room for improvement [published online May 18, 2020]. J Neurol Sci. doi: 10.1016/j.jns.2020.116902