Annals of Clinical Neurophysiology

The Korean Society of Clinical Neurophysiology (대한임상신경생리학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical and Electrophysiologic Characteristics of Paraproteinemic Neuropathy

파라단백혈증신경병의 임상 및 전기생리학적 특징

  • Pyun, So Young (Department of Neurology, National Police Hospital) ;
  • Kim, Byung-Jo (Department of Neurology, Korea University College of Medicine)
  • Received : 2015.10.24
  • Accepted : 2015.11.26
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

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.

Keywords

References

  1. Kyle RA. Monoclonal gammopathy of undetermined significance. Blood Rev 1994;8:135-141. https://doi.org/10.1016/0268-960X(94)90073-Q
  2. Vladutiu AO. Prevalence of M-proteins in serum of hospitalized patients. Physicians' response to finding M-proteins in serum protein electrophoresis. Ann Clin Lab Sci 1987;17:157-161.
  3. Rajkumar SV. MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management. Hematology Am Soc Hematol Educ Program 2005:340-345.
  4. Kelly JJ Jr, Kyle RA, O'Brien PC, Dyck PJ. Prevalence of monoclonal protein in peripheral neuropathy. Neurology 1981;31:1480-1483. https://doi.org/10.1212/WNL.31.11.1480
  5. Raheja D, Specht C, Simmons Z. Paraproteinemic neuropathies. Muscle Nerve 2015;51:1-13. https://doi.org/10.1002/mus.24471
  6. Sobol U, Stiff P. Neurologic aspects of plasma cell disorders. Handb Clin Neurol 2014;120:1083-1099. https://doi.org/10.1016/B978-0-7020-4087-0.00073-5
  7. Mauermann ML. Paraproteinemic neuropathies. Continuum (Minneap Minn) 2014;20:1307-1322.
  8. Ramchandren S, Lewis RA. An update on monoclonal gammopathy and neuropathy. Curr Neurol Neurosci Rep 2012;12:102-110. https://doi.org/10.1007/s11910-011-0237-4
  9. El-Difrawy MM, Zaki NE, Marouf HM, Ayad MW, Farag AM. Clinical, electrophysiological and immunological study of peripheral nerves in Egyptian patients with monoclonal gammopathies. Int J Hematol 2012;95:71-76. https://doi.org/10.1007/s12185-011-0983-8
  10. Nobile-Orazio E. Update on neuropathies associated with monoclonal gammopathy of undetermined significance (2008-2010). J Peripher Nerv Syst 2010;15:302-306. https://doi.org/10.1111/j.1529-8027.2010.00283.x
  11. Ramchandren S, Lewis RA. Monoclonal gammopathy and neuropathy. Curr Opin Neurol 2009;22:480-485. https://doi.org/10.1097/WCO.0b013e32832fd563
  12. Kissel JT, Mendell JR. Neuropathies associated with monoclonal gammopathies. Neuromuscul Disord 1996;6:3-18. https://doi.org/10.1016/0960-8966(95)00021-6
  13. Braun PE, Frail DE, Latov N. Myelin-associated glycoprotein is the antigen for a monoclonal IgM in polyneuropathy. J Neurochem 1982;39:1261-1265. https://doi.org/10.1111/j.1471-4159.1982.tb12563.x
  14. Landgren O. Monoclonal gammopathy of undetermined significance and smoldering myeloma: new insights into pathophysiology and epidemiology. Hematology Am Soc Hematol Educ Program 2010:295-302.
  15. Kyle RA. 'Benign' monoclonal gammopathy. A misnomer? JAMA 1984;251:1849-1854. https://doi.org/10.1001/jama.1984.03340380031018
  16. Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005;106:812-817. https://doi.org/10.1182/blood-2005-03-1038
  17. Eurelings M, Notermans NC, Van de Donk NW, Lokhorst HM. Risk factors for hematological malignancy in polyneuropathy associated with monoclonal gammopathy. Muscle Nerve 2001;24:1295-1302. https://doi.org/10.1002/mus.1147
  18. Forssman O, Bjorkman G, Hollender A, Englund NE. IgM-producing lymphocytes in peripheral nerve in a patient with benign monoclonal gammopathy. Scand J Haematol 1973;11:332-335.
  19. Nobile-Orazio E, Barbieri S, Baldini L, Marmiroli P, Carpo M, Premoselli S, et al. Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies. Acta Neurol Scand 1992;85:383-390.
  20. Gosselin S, Kyle RA, Dyck PJ. Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol 1991;30:54-61. https://doi.org/10.1002/ana.410300111
  21. Yeung KB, Thomas PK, King RH, Waddy H, Will RG, Hughes RA, et al. The clinical spectrum of peripheral neuropathies associated with benign monoclonal IgM, IgG and IgA paraproteinaemia. Comparative clinical, immunological and nerve biopsy findings. J Neurol 1991;238:383-391. https://doi.org/10.1007/BF00319857
  22. Gorson KC, Allam G, Ropper AH. Chronic inflammatory demyelinating polyneuropathy: clinical features and response to treatment in 67 consecutive patients with and without a monoclonal gammopathy. Neurology 1997;48:321-328. https://doi.org/10.1212/WNL.48.2.321
  23. Gorson KC, Ropper AH. Axonal neuropathy associated with monoclonal gammopathy of undetermined significance. J Neurol Neurosurg Psychiatry 1997;63:163-168. https://doi.org/10.1136/jnnp.63.2.163
  24. Nobile-Orazio E, Manfredini E, Carpo M, Meucci N, Monaco S, Ferrari S, et al. Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 1994;36:416-424. https://doi.org/10.1002/ana.410360313
  25. Steck AJ, Murray N, Meier C, Page N, Perruisseau G. Demyelinating neuropathy and monoclonal IgM antibody to myelin-associated glycoprotein. Neurology 1983;33:19-23. https://doi.org/10.1212/WNL.33.1.19
  26. Niermeijer JM, Fischer K, Eurelings M, Franssen H, Wokke JH, Notermans NC. Prognosis of polyneuropathy due to IgM monoclonal gammopathy: a prospective cohort study. Neurology 2010;74:406-412. https://doi.org/10.1212/WNL.0b013e3181ccc6b9
  27. Nobile-Orazio E, Meucci N, Baldini L, Di Troia A, Scarlato G. Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain 2000;123:710-717. https://doi.org/10.1093/brain/123.4.710
  28. Chassande B, Leger JM, Younes-Chennoufi AB, Bengoufa D, Maisonobe T, Bouche P, et al. Peripheral neuropathy associated with IgM monoclonal gammopathy: correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases. Muscle Nerve 1998;21:55-62. https://doi.org/10.1002/(SICI)1097-4598(199801)21:1<55::AID-MUS8>3.0.CO;2-F
  29. Simmons Z, Albers JW, Bromberg MB, Feldman EL. Long-term follow-up of patients with chronic inflammatory demyelinating polyradiculoneuropathy, without and with monoclonal gammopathy. Brain 1995;118:359-368. https://doi.org/10.1093/brain/118.2.359
  30. Fazio R, Nemni R, Quattrini A, Lorenzetti I, Canal N. IgG monoclonal proteins from patients with axonal peripheral neuropathies bind to different epitopes of the 68 kDa neurofilament protein. J Neuroimmunol 1992;36:97-104. https://doi.org/10.1016/0165-5728(92)90041-I
  31. Stubbs EB, Jr., Lawlor MW, Richards MP, Siddiqui K, Fisher MA, Bhoopalam N, et al. Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block. Acta Neuropathol 2003;105:109-116.
  32. Bleasel AF, Hawke SH, Pollard JD, McLeod JG. IgG monoclonal paraproteinaemia and peripheral neuropathy. J Neurol Neurosurg Psychiatry 1993;56:52-57. https://doi.org/10.1136/jnnp.56.1.52
  33. Di Troia A, Carpo M, Meucci N, Pellegrino C, Allaria S, Gemignani F, et al. Clinical features and anti-neural reactivity in neuropathy associated with IgG monoclonal gammopathy of undetermined significance. J Neurol Sci 1999;164:64-71. https://doi.org/10.1016/S0022-510X(99)00049-0
  34. Nemni R, Mamoli A, Fazio R, Camerlingo M, Quattrini A, Lorenzetti I, et al. Polyneuropathy associated with IgA monoclonal gammopathy: a hypothesis of its pathogenesis. Acta Neuropathol 1991;81:371-376. https://doi.org/10.1007/BF00293456
  35. Magy L, Chassande B, Maisonobe T, Bouche P, Vallat JM, Leger JM. Polyneuropathy associated with IgG/IgA monoclonal gammopathy: a clinical and electrophysiological study of 15 cases. Eur J Neurol 2003;10:677-685. https://doi.org/10.1046/j.1468-1331.2003.00687.x
  36. Notermans NC, Wokke JH, Lokhorst HM, Franssen H, van der Graaf Y, Jennekens FG. Polyneuropathy associated with monoclonal gammopathy of undetermined significance. A prospective study of the prognostic value of clinical and laboratory abnormalities. Brain 1994;117:1385-1393. https://doi.org/10.1093/brain/117.6.1385
  37. Gorson KC. Clinical features, evaluation, and treatment of patients with polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). J Clin Apher 1999;14:149-153. https://doi.org/10.1002/(SICI)1098-1101(1999)14:3<149::AID-JCA8>3.0.CO;2-9
  38. Notermans NC, Wokke JH, van den Berg LH, van der Graaf Y, Franssen H, Teunissen LL, et al. Chronic idiopathic axonal polyneuropathy. Comparison of patients with and without monoclonal gammopathy. Brain 1996;119:421-427. https://doi.org/10.1093/brain/119.2.421
  39. Plasmati R, Pastorelli F, Cavo M, Petracci E, Zamagni E, Tosi P, et al. Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology 2007;69:573-581. https://doi.org/10.1212/01.wnl.0000267271.18475.fe
  40. Chaudhry V, Cornblath DR, Polydefkis M, Ferguson A, Borrello I. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 2008;13:275-282. https://doi.org/10.1111/j.1529-8027.2008.00193.x
  41. Kosturakis AK, He Z, Li Y, Boyette-Davis JA, Shah N, Thomas SK, et al. Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density. J Clin Oncol 2014;32:3156-3162. https://doi.org/10.1200/JCO.2013.54.5418
  42. Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, et al. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia 2012;26:595-608. https://doi.org/10.1038/leu.2011.346
  43. Walsh JC. The neuropathy of multiple myeloma. An electrophysiological and histological study. Arch Neurol 1971;25:404-414. https://doi.org/10.1001/archneur.1971.00490050038003
  44. Kelly JJ Jr. The electrodiagnostic findings in peripheral neuropathy associated with monoclonal gammopathy. Muscle Nerve 1983;6:504-509. https://doi.org/10.1002/mus.880060706
  45. Ohi T, Kyle RA, Dyck PJ. Axonal attenuation and secondary segmental demyelination in myeloma neuropathies. Ann Neurol 1985;17:255-261. https://doi.org/10.1002/ana.410170306
  46. Dispenzieri A. POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011;86:591-601. https://doi.org/10.1002/ajh.22050
  47. Dispenzieri A. POEMS syndrome: Update on diagnosis, risk-stratification, and management. Am J Hematol 2015;90:951-962. https://doi.org/10.1002/ajh.24171
  48. Sung JY, Kuwabara S, Ogawara K, Kanai K, Hattori T. Patterns of nerve conduction abnormalities in POEMS syndrome. Muscle Nerve 2002;26:189-193. https://doi.org/10.1002/mus.10182
  49. Min JH, Hong YH, Lee KW. Electrophysiological features of patients with POEMS syndrome. Clin Neurophysiol 2005;116:965-968. https://doi.org/10.1016/j.clinph.2004.11.011
  50. Nasu S, Misawa S, Sekiguchi Y, Shibuya K, Kanai K, Fujimaki Y, et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry 2012;83:476-479. https://doi.org/10.1136/jnnp-2011-301706
  51. Mauermann ML, Sorenson EJ, Dispenzieri A, Mandrekar J, Suarez GA, Dyck PJ, et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry 2012;83:480-486. https://doi.org/10.1136/jnnp-2011-301472
  52. Guo X, Qin X, Zhang Y, Huang C, Yu G. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Clin Neurosci 2014;21:587-590. https://doi.org/10.1016/j.jocn.2013.05.023
  53. Scarlato M, Previtali SC, Carpo M, Pareyson D, Briani C, Del Bo R, et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 2005;128:1911-1920. https://doi.org/10.1093/brain/awh519
  54. Arimura K. Increased vascular endothelial growth factor (VEGF) is causative in Crow-Fukase syndrome. Rinsho Shinkeigaku 1999;39:84-85.
  55. Klein CJ, Moon JS, Mauermann ML, Zeldenrust SR, Wu Y, Dispenzieri A, et al. The neuropathies of Waldenstrom's macroglobulinemia (WM) and IgM-MGUS. Can J Neurol Sci 2011;38:289-295. https://doi.org/10.1017/S0317167100011483
  56. Gertz MA. Waldenstrom macroglobulinemia: 2013 update on diagnosis, risk stratification, and management. Am J Hematol 2013;88:703-711. https://doi.org/10.1002/ajh.23472
  57. Gertz MA. Immunoglobulin light chain amyloidosis: 2013 update on diagnosis, prognosis, and treatment. Am J Hematol 2013;88:416-425. https://doi.org/10.1002/ajh.23400
  58. Wang AK, Fealey RD, Gehrking TL, Low PA. Patterns of neuropathy and autonomic failure in patients with amyloidosis. Mayo Clin Proc 2008;83:1226-1230. https://doi.org/10.4065/83.11.1226
  59. Kelly JJ Jr, Kyle RA, O'Brien PC, Dyck PJ. The natural history of peripheral neuropathy in primary systemic amyloidosis. Ann Neurology 1979;6:1-7. https://doi.org/10.1002/ana.410060102
  60. Rajkumar SV, Gertz MA, Kyle RA. Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am J Med 1998;104:232-237. https://doi.org/10.1016/S0002-9343(98)00037-0
  61. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995;32:45-59.