Clinical and Electrophysiologic Characteristics of Paraproteinemic Neuropathy

So Young Pyun; Byung-Jo Kim

doi:10.14253/KJCN.2015.17.2.45

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Pyun and Kim: Clinical and Electrophysiologic Characteristics of Paraproteinemic Neuropathy

Original Article

Korean J Community Nutr 2015;17(2):45-52.

Published online: 18 December 2015

DOI: https://doi.org/10.14253/KJCN.2015.17.2.45

Clinical and Electrophysiologic Characteristics of Paraproteinemic Neuropathy

So Young Pyun¹, Byung-Jo Kim²

¹Department of Neurology, National Police Hospital, Seoul, Korea

²Department of Neurology, Korea University College of Medicine, Seoul, Korea

Address for correspondence; Byung-Jo Kim Department of Neurology, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea Tel: +82-2-920-6619 Fax: +82-2-925-2472 E-mail: nukbj@korea.ac.kr

Received 24 October 2015 Revised 22 November 2015 Accepted 26 November 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The paraproteinemia is a disorder in which a single clone of plasma cells (monoclonal gammopathy) is responsible for the proliferation of monoclonal proteins (M-proteins). Approximately 10% of patients with idiopathic peripheral neuropathy have monoclonal gammopathy. Some M-proteins have the properties of an antibody to the components of peripheral nerve myelin, but the pathophysiological relationship between the neuropathy and the M-protein is often obscure. The relationship between peripheral neuropathy and monoclonal gammopathy requires the appropriate neurological and hematological investigations for precise diagnosis and treatment. In this review, we provide an update on the causal associations between peripheral neuropathy and monoclonal gammopathy as well as characteristics of clinical and electrophysiologic features. (Korean J Clin Neurophysiol 2015;17:45-52)

Keywords: Paraproteinemic neuropathy, Monoclonal gammopathy, Polyneuropathy, Diagnosis, Treatment

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Table 1.

Recommended survey for the patients with paraproteinemia

Neurological
Full clinical functional neuromuscular assessment at baseline, to be repeated at regular intervals
Detailed electrophysiologic studies including sensory and motor nerve conduction studies, which may be repeated, performed bilaterally, or use proximal stimulation for motor nerves with determination of DML/MNCV/SNCV/TLI, assessment for CB/TD
Cerebrospinal fluid study: cellularity/malignant cells/protein level
Serum anti MAG antibody
In selected cases: MR imaging of nerve roots/brachial plexus/lumbosacral plexus
In selected cases: nerve histology^a
Hematological
Full examination for other systemic diseases: hepatomegaly/splenomegaly/lymphadenopathy/macroglossia/signs of POEMS syndrome
Full blood count/renal function/liver function test/calcium/C-reactive protein/ESR/beta 2-microglobulin/lactate dehydrogenase/ rheumatoid factor/cryoglobulin
Serum immnofixation electrophoresis: total heavy chains (IgG, IgA, and IgM concentrations)/free light chains
Bence-Jones proteinuria and if positive 24-hr collection
Radiographic X-ray skeletal^b
Serum VEGF levels if POEMS syndrome suspected
Bone marrow examination^c
DML; distal motor latency, MNCV; motor nerve conduction velocity, SNCV; sensory nerve conduction velocity, TLI; terminal latency index, CB; conduction block, TD; temporal dispersion, MAG; myelin-associated glycoprotein, ESR; erythrocyte sedimentation rate, VEGF; vascular endothelial growth factor. ^aThe following conditions are being considered: 1) IgM paraproteinemic demyelinating neuropathy negative anti-MAG antibodies, or IgG or IgA paraproteinemic demyelinating neuropathy with a chronic progressive course, where the discovery of widely spaced myelin on electron microscopy or deposits of Ig and/or complement bound to myelin; 2) amyloidosis; 3) malignant lymphoproliferative infiltration of nerves are being considered. ^bConventional X-rays to evaluate for lytic or sclerotic lesions must include a posterior-anterior view of the chest and films of the cervical, thoracic, and lumbar spines, humeri and femurs, skull, and pelvis. Part or all of this may be replaced by CT, which is more sensitive but involves greater radiation exposure except where low-dose whole body CT is available. If the index of suspicion is high, CT and/or MRI of the spine, pelvis, or whole body, and perhaps whole body FDG-PET/CT, may be considered. ^cIn patients with an M- protein level of >15 g/L and abnormal free light chain ratio.

Table 2.

Summary of pathomechanism-based clinical trials for ALS

Diagnosis	Clinical	Laboratory (most common monoclonal protein type)	EDx	Nerve biopsy
IgM MGUS	Slowly progressive, distally predominant, and sensory more than motor	M protein 30 g/L IgM kappa	Demyelinating Marked prolonged distal motor latencies Reduced TLI Attenuated or absent sensory response	IgM and complement deposits on myelin lamellae
IgG and IgA MGUS	Distally predominant sensorimotor or proximal weakness as in CIDP Predominantly small fiber neuropathy	M protein 30 g/L Increased Ig G or A levels	Axonal or demyelinating (as in CIDP)	Endoneurial Ig deposits Widening of myelin lamellae Endoneurial inclusions in IgA
Multiple myeloma	Fatigue, weakness, bone pain, weight loss, and infections Symmetric, distal sensory or sensorimotor neuropathy	M protein >30 g/L IgG more often than IgA Bence-Jones proteinuria > 10% plasma cells in bone marrow Anemia, hypercalcemia	Almost always axonal (length dependent) but very rarely demyelinating	Axonal degeneration May show amyloid deposits
POEMS syndrome	Ascending sensorimotor symptoms Weakness eventually predominating	Ig G or IgA lambda M protein Elevated VEGF Sclerotic bone lesions	Mixed axonal, demyelinating (more predominantly in the intermediate than distal segment) No conduction block or dispersion Higher TLI than CIDP More severe attenuation of CMAP in lower than upper limbs	Axonal degeneration Loss of myelinated fibers Inflammation and uncompacted myelin lamellae
WM	Fatigue, weakness and hyperviscosity syndrome Neuropathy slowly progressive, distal, and sensory > motor	M protein (IgM kappa) 10% plasma cells in bone marrow Anti MAG antibodies sometimes	Similar to IgM MGUS	Similar to IgM MGUS
Amyloid	Varies with organ involved Neuropathy painful and distal sensorimotor Dysautonomia	Lambda	Axonal sensory > motor neuropathy Carpal tunnel syndrome	Amyloid on Congo-red staining Light chains on immunochemistry

EDx; electrodiagnosis, MGUS; monoclonal gammopathy of undetermined significance, TLI; terminal latency index, CIDP; chronic inflammatory demyelinating polyneuropathy, VEGF; vascular endothelial growth factor, CMAP; compound muscle action potential.

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