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The Neuropathies of Waldenström's Macroglobulinemia (WM) and IgM-MGUS

Published online by Cambridge University Press:  02 December 2014

Christopher J. Klein ,
Joon-Shik Moon ,
Michelle L. Mauermann ,
Steven R. Zeldenrust ,
Yanhong Wu ,
Angela Dispenzieri  and
Peter J. Dyck
Christopher J. Klein*
Affiliation:
Peripheral Nerve Research Laboratory, Mayo Clinic, Rochester, Minnesota, U.S.A
Joon-Shik Moon
Affiliation:
Peripheral Nerve Research Laboratory, Mayo Clinic, Rochester, Minnesota, U.S.A
Michelle L. Mauermann
Affiliation:
Peripheral Nerve Research Laboratory, Mayo Clinic, Rochester, Minnesota, U.S.A
Steven R. Zeldenrust
Affiliation:
Department of Hematology, Mayo Clinic, Rochester, Minnesota, U.S.A
Yanhong Wu
Affiliation:
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, U.S.A
Angela Dispenzieri
Affiliation:
Department of Hematology, Mayo Clinic, Rochester, Minnesota, U.S.A
Peter J. Dyck
Affiliation:
Peripheral Nerve Research Laboratory, Mayo Clinic, Rochester, Minnesota, U.S.A
*
Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, U.S.A.
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Abstract

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Background:

Neuropathy is common in Waldenström's macroglobulinemia (WM, an IgM-associated lymphoplasmacytic lymphoma) and in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS). Paraneoplastic or paraimmune mechanisms are thought to be involved in the pathogenesis of these neuropathies. Attempts at distinguishing WM and IgM-MGUS neuropathies are lacking especially among bone marrow (BM) confirmed patients.

Methods:

Retrospective analyses were performed on BM confirmed WM (N=30) and IgM-MGUS (N=73) neuropathy patients with neurologic assessments and hematologic features.

Results:

The presence of anemia and quantity of IgM monoclonal protein were significantly greater in WM. Based on multiple neurologic assessments differences were not found for: 1) length of time from neurologic symptom onset to evaluation; 2) chief complaint of painless loss of feeling in the feet, Romberg's sign and tremor; and 3) clinical motor, sensory and reflex abnormalities. Autonomic testing was normal in both diseases. Using nerve conduction (NCS) criteria for demyelination, 62% of IgM-MGUS and 27% of WM met this criteria (p=0.013). IgM MGUS patients had greater terminal conduction slowing by ulnar residual latency calculation (<0.01). The degree of axonal loss as measured by summated compound muscle action potentials and available nerve biopsy was not significantly different between diseases.

Conclusion:

Although WM and IgM-MGUS must be distinguished for hematologic prognosis and treatment, clinical neuropathy presentations of WM and IgM-MGUS are similar and likely related to comparable axonal loss in both conditions. Despite these similarities, evidence of demyelination was found by electrophysiologic studies much more commonly in IgM-MGUS. This difference may reflect varied immune mechanism(s) in the two disorders.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 38 , Issue 2 , March 2011 , pp. 289 - 295
Copyright
Copyright © The Canadian Journal of Neurological 2011

References

1Kyle, RA.Neuropathy associated with the monoclonal gammopathies. In: Noseworthy, JH, editor. Neurologic therapeautics: principles and practice. London, New York: Martin Dunitz; 2003. p. 2126–36.Google Scholar
2Lozeron, P, Adams, D.Monoclonal gammopathy and neuropathy. Curr Opin Neurol. 2007 Oct;20(5):536–41.CrossRefGoogle ScholarPubMed
3Katz, JS, Saperstein, DS, Gronseth, G, Amato, AA, Barohn, RJ.Distal acquired demyelinating symmetric neuropathy. Neurology. 2000;54:615–20.CrossRefGoogle ScholarPubMed
4Levine, T, Pestronk, A, Florence, J, et al.Peripheral neuropathies in Waldenstrom’s macroglobulinaemia. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):224–8.CrossRefGoogle ScholarPubMed
5Baldini, L, Nobile-Orazio, E, Guffanti, A, et al.Peripheral neuropathy in IgM monoclonal gammopathy and Waldenstrom’s macroglobulinemia: a frequent complication in elderly males with low MAG-reacitve serum monoclonal component. Am J Hematol. 1994;45:25–31.CrossRefGoogle ScholarPubMed
6Owen, RG, Treon, SP, Al-Katib, A, et al.Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin Oncol. 2003 Apr;30(2):110–5.CrossRefGoogle ScholarPubMed
7Gertz, MA.Waldenstrom macroglobulinemia: a review of therapy. Am J Hematol. 2005 Jun;79(2):147–57.CrossRefGoogle ScholarPubMed
8Kaku, DA, England, JD, Sumner, AJ.Distal accentuation of conduction slowing in polyneuropathy associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside. Brain. 1994 Oct;117(Pt 5):941–7.CrossRefGoogle ScholarPubMed
9Lupu, VD, Mora, CA, Dambrosia, J, Meer, J, Dalakas, M, Floeter, MK.Terminal latency index in neuropathy with antibodies against myelin-associated glycoproteins. Muscle Nerve. 2007 Feb;35(2):196–202.CrossRefGoogle ScholarPubMed
10Capasso, M, Torrieri, F, Di Muzio, A, De Angelis, MV, Lugaresi, A, Uncini, A.Can electrophysiology differentiate polyneuropathy with anti-MAG/SGPG antibodies from chronic inflammatory demyelinating polyneuropathy? Clin Neurophysiol. 2002 Mar;113(3):346–53.CrossRefGoogle ScholarPubMed
11Attarian, S, Azulay, JP, Boucraut, J, Escande, N, Pouget, J.Terminal latency index and modified F ratio in distinction of chronic demyelinating neuropathies. Clin Neurophysiol. 2001 Mar;112 (3):457–63.CrossRefGoogle ScholarPubMed
12Bain, PG, Britton, TC, Jenkins, IH, et al.Tremor associated with benign IgM paraproteinaemic neuropathy. Brain. 1996 Jun;119 (Pt 3):789–99.CrossRefGoogle ScholarPubMed
13Gabriel, JM, Erne, B, Miescher, GC, et al.Selective loss of myelin-associated glycoprotein from myelin correlates with anti-MAG antibody titre in demyelinating paraproteinaemic polyneuropathy. Brain. 1996;119:775–87.CrossRefGoogle ScholarPubMed
14Hays, AP, Latov, N, Takatsu, M, Sherman, WH.Experimental demyelination of nerve induced by serum of patients with neuropathy and an anti-MAG IgM M-protein. Neurology. 1987 Feb;37(2):242–56.CrossRefGoogle Scholar
15Tatum, AH.Experimental paraprotein neuropathy, demyelination by passive transfer of human IgM anti-myelin-associated glycoprotein. Ann Neurol. 1993 May;33(5):502–6.CrossRefGoogle ScholarPubMed
16Gosselin, S, Kyle, RA, Dyck, PJ.Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol. 1991;30:54–61.CrossRefGoogle ScholarPubMed
17Suarez, GA, Kelley, JJ.Polyneuropathy associated with monoclonal gammopathy of undetermined significance: Further evidence that IgM-MGUS neuropathies are different than IgG-MGUS. Neurology. 1993;43:1304–8.CrossRefGoogle ScholarPubMed
18Garces-Sanchez, M, Dyck, PJ, Kyle, RA, et al.Antibodies to myelin-associated glycoprotein (anti-Mag) in IgM amyloidosis may influence expression of neuropathy in rare patients. Muscle Nerve. 2008 Apr;37(4):490–5.CrossRefGoogle ScholarPubMed
19Kraft, GH, Halvorson, GA.Median nerve residual latency: normal value and use in diagnosis of carpal tunnel syndrome. Arch Phys Med Rehabil. 1983 May;64(5):221–6.Google ScholarPubMed
20Radziwill, AJ, Steck, AJ, Renaud, S, Fuhr, P.Distal motor latency and residual latency as sensitive markers of anti-MAG poly-neuropathy. J Neurol. 2003 Aug;250(8):962–6.CrossRefGoogle Scholar
21Shahani, B, Young, R, Potts, F, Maccabee, P.Terminal latency index (TLI) and late response studies in motor neuron disease (MND), peripheral neuropathies and entrapment syndromes (abstract). Acta Neurol Scand. 1979; Supp 73:118.Google Scholar
22Mauermann, ML, Burns, TM.Pearls and Oysters: evaluation of peripheral neuropathies. Neurology. 2009 Feb 10;72(6):e28–31.CrossRefGoogle ScholarPubMed
23Dyck, PJ, Dyck, PJB, Chalk, CH.The 10 P’s: a mnemonic helpful in characterization and differential diagnosis of peripheral neuropathy. Neurology. 1992;42:14–8.CrossRefGoogle Scholar
24Low, PA, Benarroch, EE.Clinical autonomic disorders: Philadelphia. Wolters Kluwer; 2008.Google Scholar
25Low, PA.Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748–52.CrossRefGoogle ScholarPubMed
26Dyck, PJ, Sherman, WR, Hallcher, LM, et al.Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry. Ann Neurol. 1980;8(6):590–6.CrossRefGoogle ScholarPubMed
27Daube, J.Clinical Neurophysiology. 1st ed. Philadelphia: Davis; 1996.Google Scholar
28Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Neurology. 1991 May;41(5):617–8.Google Scholar
29Dyck, PJ, O’Brien, PC, Litchy, WJ, Harper, CM, Daube, JR, Dyck, PJB.Use of percentiles and normal deviates to express nerve conduction and other test abnormalities. Muscle Nerve. 2001; 24:307–10.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
30Dyck, PJ, Litchy, WJ, Lehman, KA, Hokanson, JL, Low, PA, O’Brien, PC.Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects. Neurology. 1995 Jun;45(6):1115–21.CrossRefGoogle ScholarPubMed
31O’Brien, PC, Dyck, PJ.Procedures for setting normal values. Neurology. 1995 Jan;45(1):17–23.CrossRefGoogle ScholarPubMed
32Daube, JR.Clinical neurophysiology (CD disc monogram of EMG needle examination). New York: Oxford University Press; 2009.Google Scholar
33Dyck, PJ, Dyck, PJB, Giannini, C, Sahenk, Z, AJ, W, Engelstad, J.Peripheral nerves. In: Graham, DI, Lantos, PL, editors. Greenfields Neuropathology. London: Oxford University Press; 2002. p. 551–675.Google Scholar
34McMaster, ML, Kristinsson, SY, Turesson, I, Bjorkholm, M, Landgren, O.Novel aspects pertaining to the relationship of Waldenstrom’s macroglobulinemia, IgM monoclonal gammopathy of undetermined significance, polyclonal gammopathy, and hypoglobulinemia. Clin Lymphoma Myeloma. 2009 Mar;9 (1):19–22.CrossRefGoogle Scholar
35Facon, T, Brouillard, M, Duhamel, A, et al.Prognostic factors in Waldenstrom’s macroglobulinemia: a report of 167 cases. J Clin Oncol. 1993 Aug;11(8):1553–8.CrossRefGoogle ScholarPubMed