By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: Nerve conduction and electromyography can help differentiate the neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) from polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS).
SOURCE: Kim H, Lim YM, Jin JY, et al. Electrophysiological features of POEMS syndrome compared to MGUS-related neuropathy. Muscle Nerve 2017; May 4. doi: 10.1002/mus.25684 [Epub ahead of print].
Paraproteinemia, found in approximately 1% of the population, often is associated with demyelinating neuropathy. Most commonly seen with monoclonal gammopathy of undetermined significance (MGUS), paraproteinemic neuropathies also are seen with hematologic malignant and nonmalignant conditions, including lymphoma, multiple myeloma, amyloidosis, and cryoglobulinemia. POEMS, an acronym coined in 1980, represents a constellation of findings, including Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes, in association with osteosclerotic myeloma, Castleman's disease, increased levels of serum vascular endothelial growth factor, edema, or papilledema. Can MGUS neuropathy be differentiated electrodiagnostically from that seen in POEMS?
In this retrospective study, performed between March 1996 and June 2016 at Asan Medical Center and Ulsan University Hospital, South Korea, records of 37 MGUS and 24 POEMS neuropathy patients were reviewed. MGUS neuropathy was diagnosed based on the presence of a monoclonal protein on immunoelectrophoresis, in the absence of any plasma cell disorder or other cause of polyneuropathy, including diabetes, vitamin deficiency, and metabolic or autoimmune disease. POEMS diagnosis satisfied Dispenzieri criteria.1 Nerve conduction studies were performed using standard technique, and included the bilateral peroneal, tibial, median, and ulnar motor nerves, and median ulnar and sural sensory nerves. Motor nerve conduction block was diagnosed in the presence of a ≥ 50% proximal:distal drop in amplitude, with the stipulation that distal motor amplitude had to be ≥ 1 mV. Terminal latency index (TLI) was calculated for each motor study, using the formula: TLI = terminal distance (mm)/(distal latency (ms) x MCV (m/s). Statistical analysis encompassed, as appropriate, the Student’s t test or Mann-Whitney U test, analysis of variance (ANOVA) or Kruskal-Wallis test, and Chi-square or Fisher’s exact test. P values < 0.05 were considered statistically significant.
Most patients in both groups were male, but those in the MGUS neuropathy group were older (mean age 69.7 years), with longer disease duration (mean 1.83 years) and higher monoclonal peak compared to the POEMS neuropathy group. POEMS patients had significantly lower evoked motor amplitudes in the arms and legs, with motor responses more frequently absent in the leg, and motor conduction velocities slower in the median and ulnar nerves compared to MGUS patients. Sensory amplitudes were comparably reduced in both groups. F-wave latencies were more prolonged in the upper extremities of POEMS patients compared to MGUS, but conduction block was present equally in both, 6.7% and 7.2%, respectively. TLIs were significantly greater in the POEMS compared to MGUS neuropathy group. Receiver operating curve analysis of nerve conduction parameters revealed a sensitivity and specificity of 67% and 88%, respectively, in discriminating POEMS from MGUS-related neuropathy in the median nerve, and of 73% and 84%, respectively, in the ulnar nerve. Reduced motor amplitudes, slow motor conduction velocities, and high TLIs are indicative of POEMS rather than MGUS neuropathy.
POEMS may be difficult to distinguish clinically from chronic inflammatory demyelinating polyradiculopathy (CIDP), as both may present with a demyelinating polyneuropathy. POEMS should be considered in CIDP patients who do not respond to standard treatment. Vascular endothelial growth factor levels almost always are elevated in patients with active POEMS, with serum levels 10-50 times higher than plasma levels. M-protein is usually low, rarely > 3.0 g/dL, and usually is IgG or IgA, almost always lambda type. Cerebrospinal fluid protein levels always are elevated and, hence, do not aid differentiating CIDP from POEMS. Osteosclerotic lesions occur in 95% but may be confused with aneurysmal bone cysts, fibrous dysplasia, and benign bone islands.
- Dispenzieri A. POEMS syndrome: Update on diagnosis, risk-stratification, and management. Am J Hematol 2015;90:951-962.