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Neurological manifestations of Waldenström macroglobulinemia

Nature Clinical Practice Neurology volume 4, pages 547–556 (2008)Cite this article

Abstract

Waldenström macroglobulinemia, a condition that most commonly occurs in lymphoplasmacytic lymphoma, typically manifests with diffuse lymphadenopathies, cytopenias, and a markedly elevated erythrocyte sedimentation rate. Peripheral neuropathy occurs in nearly half of patients with this condition, and hyperviscosity-related nervous system disorders are encountered in up to a third. Other neurological complications, such as encephalopathy or myelopathy caused by direct tumor infiltration, paraprotein deposition or autoimmune phenomena, are rare. Diagnosis of Waldenström macroglobulinemia requires identification of monoclonal IgM protein in the serum, bone marrow biopsy, and appropriate neurological testing (e.g. imaging studies of affected areas of the central neuraxis, electrophysiological studies). Treatment options, which should address both the paraprotein burden and the lymphoplasmacytic clone, include plasmapheresis and chemotherapy with alkylating agents, nucleoside analogs, and rituximab. As the disease is incurable and its course indolent, these treatments are only provided to symptomatic patients.

Key Points

  • Waldenström macroglobulinemia (WM), a condition most commonly associated with lymphoplasmacytic lymphoma, typically manifests with diffuse lymphadenopathies, cytopenias, and a markedly elevated erythrocyte sedimentation rate

  • Nearly half of patients with WM develop symptomatic peripheral neuropathy; clinical manifestations of hyperviscosity, including encephalopathy, are seen in up to a third of WM cases

  • The effects of WM on the nervous system reflect the rheological properties of the IgM paraprotein, nonspecific IgM deposition, antibody-mediated damage to nerves or vessels, and direct infiltration of the neuraxis by the lymphoplasmacytoid clone or high-grade lymphoma after WM transformation

  • Diagnosis of WM requires identification of monoclonal IgM protein in the serum, bone marrow biopsy, and appropriate neurological testing (e.g. imaging studies of affected areas of the central neuraxis, electrophysiological studies, cerebrospinal fluid analysis)

  • Treatment is provided to symptomatic patients only, with options including plasmapheresis and chemotherapy with alkylating agents, nucleoside analogues, and rituximab

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Figure 1: Electron microscopy findings in IgM-related neuropathies.
Figure 2: T2-weighted brain MRI scans of a patient with CNS involvement by Waldenström macroglobulinemia.

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References

  1. Waldenström J (1944) Incipient myelomatosis or “essential” hyperglobulinemia with fibrinogenopenia—a new syndrome? Acta Med Scand 117: 216–247

    Google Scholar 

  2. Owen RG et al. (2003) Clinicopathological definition of Waldenström's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. Semin Oncol 30: 110–115

    PubMed  Google Scholar 

  3. Dimopoulos MA et al. (2000) Waldenström's macroglobulinemia: clinical features, complications, and management. J Clin Oncol 18: 214–226

    CAS  PubMed  Google Scholar 

  4. Groves FD et al. (1998) Waldenström's macroglobulinemia: incidence patterns in the United States, 1988–1994. Cancer 82: 1078–1081

    CAS  PubMed  Google Scholar 

  5. Nobile-Orazio E (2004) IgM paraproteinaemic neuropathies. Curr Opin Neurol 17: 599–605

    CAS  PubMed  Google Scholar 

  6. Kyle RA et al. (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346: 564–569

    PubMed  Google Scholar 

  7. Walsh SH et al. (2005) Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia derives from an extensively hypermutated B cell that lacks ongoing somatic hypermutation. Leuk Res 29: 729–734

    CAS  PubMed  Google Scholar 

  8. Chng WJ et al. (2006) Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood 108: 2755–2763

    CAS  PubMed  PubMed Central  Google Scholar 

  9. San Miguel JF et al. (2003) Immunophenotypic analysis of Waldenström's macroglobulinemia. Semin Oncol 30: 187–195

    CAS  PubMed  Google Scholar 

  10. Vijay A and Gertz MA (2007) Waldenström macroglobulinemia. Blood 109: 509–5103

    Google Scholar 

  11. Fonseca R and Hayman S (2007) Waldenström macroglobulinaemia. Br J Haematol 138: 700–720

    CAS  PubMed  Google Scholar 

  12. Jonsson V et al. (1999) Autoimmunity in Waldenström's macroglobulinaemia. Leuk Lymphoma 34: 373–379

    CAS  PubMed  Google Scholar 

  13. Logothetis J et al. (1960) Neurologic aspects of Waldenström's macroglobulinemia; report of a case. Arch Neurol 3: 564–573

    CAS  PubMed  Google Scholar 

  14. Levine T et al. (2006) Peripheral neuropathies in Waldenström's macroglobulinaemia. J Neurol Neurosurg Psychiatry 77: 224–228

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Ropper AH and Gorson KC (1998) Neuropathies associated with paraproteinemia. N Engl J Med 338: 1601–1607

    CAS  PubMed  Google Scholar 

  16. Garcia-Sanz R et al. (2001) Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol 115: 575–582

    CAS  PubMed  Google Scholar 

  17. Kyrtsonis MC et al. (2001) Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit. Ann Hematol 80: 722–727

    CAS  PubMed  Google Scholar 

  18. Menke MN et al. (2006) Hyperviscosity-related retinopathy in Waldenström macroglobulinemia. Arch Ophthalmol 124: 1601–1606

    PubMed  Google Scholar 

  19. Syms MJ et al. (2001) Waldenström's macroglobulinemia and sensorineural hearing loss. Am J Otolaryngol 22: 349–353

    CAS  PubMed  Google Scholar 

  20. Wells M et al. (1977) Otolaryngological disturbances in Waldenström's macroglobulinaemia. Clin Otolaryngol Allied Sci 2: 327–338

    CAS  PubMed  Google Scholar 

  21. Scheithauer BW et al. (1984) Leukoencephalopathy in Waldenström's macroglobulinemia. Immunohistochemical and electron microscopic observations. J Neuropathol Exp Neurol 43: 408–425

    CAS  PubMed  Google Scholar 

  22. Kanda T et al. (1988) Blood-nerve barrier in IgM paraproteinemic neuropathy: a clinicopathologic assessment. Acta Neuropathol 95: 184–192

    Google Scholar 

  23. Vital C et al. (1985) Waldenström's macroglobulinemia and peripheral neuropathy: deposition of M-component and kappa light chain in the endoneurium. Neurology 35: 603–606

    CAS  PubMed  Google Scholar 

  24. Vital A et al. (2001) Anti-myelin-associated glycoprotein antibodies and endoneurial cryoglobulin deposits responsible for a severe neuropathy. Acta Neuropathol 102: 409–412

    CAS  PubMed  Google Scholar 

  25. Vital A and Vital C (1993) Immunoelectron identification of endoneurial IgM deposits in four patients with Waldenström's macroglobulinemia: a specific ultrastructural pattern related to the presence of cryoglobulin in one case. Clin Neuropathol 12: 49–52

    CAS  PubMed  Google Scholar 

  26. Gertz MA and Kyle RA (2003) Amyloidosis with IgM monoclonal gammopathies. Semin Oncol 30: 325–328

    PubMed  Google Scholar 

  27. Stone MJ et al. (2003) Human monoclonal macroglobulins with antibody activity. Semin Oncol 30: 318–324

    CAS  PubMed  Google Scholar 

  28. Steck AJ et al. (2006) Anti-myelin-associated glycoprotein neuropathy. Curr Opin Neurol 19: 458–463

    CAS  PubMed  Google Scholar 

  29. Vital A et al. (1989) Polyneuropathy associated with IgM monoclonal gammopathy. Immunological and pathological study in 31 patients. Acta Neuropathol 79: 160–167

    CAS  PubMed  Google Scholar 

  30. Vital C et al. (1997) Myelin modifications in 8 cases of peripheral neuropathy with Waldenström's macroglobulinemia and anti-MAG activity. Ultrastruct Pathol 21: 509–516

    CAS  PubMed  Google Scholar 

  31. Julien J et al. (1978) Polyneuropathy in Waldenström's macroglobulinemia: deposition of M component on myelin sheaths. Arch Neurol 35: 423–425

    CAS  PubMed  Google Scholar 

  32. Dellagi K et al. (1983) Waldenström's macroglobulinemia and peripheral neuropathy: a clinical and immunologic study of 25 patients. Blood 62: 280–285

    CAS  PubMed  Google Scholar 

  33. Nobile-Orazio E et al. (1994) Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 36: 416–424

    CAS  PubMed  Google Scholar 

  34. Léger JM et al. (1992) Frequency of central lesions in polyneuropathy associated with IgM monoclonal gammopathy: an MRI, neurophysiological and immunochemical study. J Neurol Neurosurg Psychiatry 55: 112–115

    PubMed  PubMed Central  Google Scholar 

  35. Sen HN et al. (2004) Waldenström's macroglobulinemia-associated retinopathy. Ophthalmology 111: 535–539

    PubMed  Google Scholar 

  36. Liberato B et al. (2003) Myelopathy from Waldenström's macroglobulinemia: improvement after Rituximab therapy. J Neurooncol 63: 207–211

    PubMed  Google Scholar 

  37. Vital C et al. (1982) Peripheral nerve damage during multiple myeloma and Waldenström's macroglobulinemia: an ultrastructural and immunopathologic study. Cancer 50: 1491–1497

    CAS  PubMed  Google Scholar 

  38. Aarseth S et al. (1961) Macroglobulinaemia Waldenström: a case with haemolytic syndrome and involvement of the nervous system. Acta Med Scand 169: 691–699

    CAS  PubMed  Google Scholar 

  39. Rudnicki SA et al. (1998) Nervous system dysfunction in Waldenström's macroglobulinemia: response to treatment. Neurology 51: 1210–1213

    CAS  PubMed  Google Scholar 

  40. Tojo K et al. (2004) Multiple brain tumors of diffuse large B cell lymphoma in a patient with Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma: PCR and DNA sequence analysis show evidence of differences in clonality of the two B cell malignancies. Intern Med 43: 990–996

    PubMed  Google Scholar 

  41. Al Halabi H and Roberge D (2006) Waldenström's macroglobulinemia presenting with spinal cord compression: a case report. Am J Hematol 81: 955–958

    PubMed  Google Scholar 

  42. Richter MN (1928) Generalized reticular cell sarcoma of lymph nodes associated with lymphatic leukemia. Am J Pathol 4: 285–292

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Lin P et al. (2003) Diffuse large B-cell lymphoma occurring in patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia: clinicopathologic features of 12 cases. Am J Clin Pathol 120: 246–253

    PubMed  Google Scholar 

  44. Kihara Y et al. (2002) A case of POEMS syndrome associated with reactive amyloidosis and Waldenström's macroglobulinaemia. J Intern Med 252: 255–258

    CAS  PubMed  Google Scholar 

  45. Mauermann ML et al. (2007) Case of mononeuritis multiplex onset with rituximab therapy for Waldenström's macroglobulinemia. J Neurol Sci 260: 240–243

    PubMed  Google Scholar 

  46. Klokkevold PR et al. (1989) Mental nerve neuropathy: a symptom of Waldenström's macroglobulinemia. Oral Surg Oral Med Oral Pathol 67: 689–693

    CAS  PubMed  Google Scholar 

  47. Bartoloni C et al. (1981) Waldenström's macroglobulinemia and myasthenia gravis. J Clin Lab Immunol 6: 275–278

    CAS  PubMed  Google Scholar 

  48. Lin YT et al. (2001) Myasthenia gravis and Waldenström's macroglobulinemia: a case report and review of the literature. Acta Neurol Scand 104: 246–248

    CAS  PubMed  Google Scholar 

  49. Al Lozi MT et al. (1997) A skeletal muscle-specific form of decorin is a target antigen for a serum IgM M-protein in a patient with a proximal myopathy. Neurology 49: 1650–1654

    CAS  PubMed  Google Scholar 

  50. Gertz MA et al. (1993) Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenström's macroglobulinemia. J Clin Oncol 11: 914–920

    CAS  PubMed  Google Scholar 

  51. Wuhrmann F (1956) Coma paraproteinaemicum in myeloma and macroglobulinemia [German]. Schweiz Med Wochenschr 86: 623–625

    CAS  PubMed  Google Scholar 

  52. Wanner J and Siebenmann R (1957) Subacute osteolytic form of Waldenström's macroglobulinemia with plasma cell leukaemia [German]. Schweiz Med Wochenschr 87: 1243–1246

    CAS  PubMed  Google Scholar 

  53. Bing J and Neel A (1936) Two cases of hyperglobulinemia with affection of the central nervous system on a toxi-infection basis. Acta Med Scand 88: 492–506

    Google Scholar 

  54. Delgado J et al. (2002) Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing–Neel syndrome: case report and review of the literature. Am J Hematol 69: 127–131

    CAS  PubMed  Google Scholar 

  55. Civit T et al. (1997) Waldenström's macroglobulinemia and cerebral lymphoplasmocytic proliferation: Bing and Neel syndrome: apropos of a new case [French]. Neurochirurgie 43: 245–249

    CAS  PubMed  Google Scholar 

  56. Knox CM et al. (1998) Vitreitis and Waldenström's macroglobulinemia. Am J Ophthalmol 126: 314–315

    CAS  PubMed  Google Scholar 

  57. Shen DF et al. (2000) Rearrangement of immunoglobulin gene in metastatic Waldenström macroglobulinemia to the vitreous. Am J Ophthalmol 129: 395–396

    CAS  PubMed  Google Scholar 

  58. Bhatti MT et al. (2005) Bilateral sixth nerve paresis in the Bing–Neel syndrome. Neurology 64: 576–577

    CAS  PubMed  Google Scholar 

  59. Kumar S et al. (2005) Bilateral orbital tumor formation and isolated facial palsy in Waldenström's macroglobulinemia. Int Ophthalmol 26: 235–237

    PubMed  Google Scholar 

  60. Moulis H and Mamus SW (1989) Isolated trochlear nerve palsy in a patient with Waldenström's macroglobulinemia: complete recovery with combination therapy. Neurology 39: 1399

    CAS  PubMed  Google Scholar 

  61. Pinna A et al. (2003) Bilateral optic disc swelling as the presenting sign of Waldenström's macroglobulinaemia. Acta Ophthalmol Scand 81: 413–415

    PubMed  Google Scholar 

  62. Monteiro PL and Wildi E (1975) Waldenström's macroglobulinemia with lymphorproliferative changes in the central nervous system: 4 cases [French]. Schweiz Arch Neurol Neurochir Psychiatr 116: 59–82

    CAS  PubMed  Google Scholar 

  63. Arias M et al. (2004) Rapidly progressing dementia as the presenting symptom of Waldenström's macroglobulinemia: findings from magnetic resonance imaging of the brain in Bing Neel syndrome [Spanish]. Rev Neurol 38: 640–642

    CAS  PubMed  Google Scholar 

  64. Donix M et al. (2007) Nonfluent aphasia in a patient with Waldenström's macroglobulinemia. J Clin Neurosci 14: 601–603

    PubMed  Google Scholar 

  65. Welch D et al. (2002) Pathologic quiz case: a man with long-standing monoclonal gammopathy and new onset of confusion: central nervous system involvement by Waldenström macroglobulinemia-Bing–Neel syndrome. Arch Pathol Lab Med 126: 1243–1244

    PubMed  Google Scholar 

  66. Massengo S et al. (2003) Nervous system lymphoid infiltration in Waldenström's macroglobulinemia: a case report. J Neurooncol 62: 353–358

    CAS  PubMed  Google Scholar 

  67. Shimizu K et al. (1993) Importance of central nervous system involvement by neoplastic cells in a patient with Waldenström's macroglobulinemia developing neurologic abnormalities. Acta Haematol 90: 206–208

    CAS  PubMed  Google Scholar 

  68. Hug A et al. (2004) Leptomeningeal tumor cell infiltrations as a first manifestation of an immunocytoma (Waldenström's macroglobulinemia) [German]. Nervenarzt 75: 1012–1015

    CAS  PubMed  Google Scholar 

  69. Fraser DM et al. (1976) Mononeuritis multiplex in a patient with macroglobulinaemia. J Neurol Neurosurg Psychiatry 39: 711–715

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Kyle RA et al. (2003) Prognostic markers and criteria to initiate therapy in Waldenström's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. Semin Oncol 30: 116–120

    PubMed  Google Scholar 

  71. Mehta J and Singhal S (2003) Hyperviscosity syndrome in plasma cell dyscrasias. Semin Thromb Hemost 29: 467–471

    PubMed  Google Scholar 

  72. Dyck PJ et al. (1991) Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance. N Engl J Med 325: 1482–1486

    CAS  PubMed  Google Scholar 

  73. Lunn MP and Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database of Systematic Reviews 2006, Art. No.: CD002827. doi: 10.1002/14651858.CD002827.pub2

    Google Scholar 

  74. Treon SP et al. (2006) Update on treatment recommendations from the Third International Workshop on Waldenström's macroglobulinemia. Blood 107: 3442–3446

    CAS  PubMed  Google Scholar 

  75. Wilson HC et al. (1999) Successful treatment of IgM paraproteinaemic neuropathy with fludarabine. J Neurol Neurosurg Psychiatry 66: 575–580

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Ghosh A et al. (2002) Cladribine in the treatment of IgM paraproteinemic polyneuropathy. Neurology 59: 1290–1291

    PubMed  Google Scholar 

  77. Renaud S et al. (2003) Rituximab in the treatment of polyneuropathy associated with anti-MAG antibodies. Muscle Nerve 27: 611–615

    CAS  PubMed  Google Scholar 

  78. Renaud S et al. (2006) High-dose rituximab and anti-MAG-associated polyneuropathy. Neurology 66: 742–744

    CAS  PubMed  Google Scholar 

  79. Noronha V et al. (2006) Flare in neuropathy following rituximab therapy for Waldenström's macroglobulinemia. J Clin Oncol 24: e3

    PubMed  Google Scholar 

  80. Chen CI et al. (2007) Bortezomib is active in patients with untreated or relapsed Waldenström's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25: 1570–1575

    CAS  PubMed  Google Scholar 

  81. Langevin JP et al. (2008) Waldenström's macroglobulinemia and large B-cell central nervous system lymphoma: a case report. Surg Neurol 69: 407–410

    PubMed  Google Scholar 

  82. Ghobrial IM et al. (2003) Waldenström macroglobulinaemia. Lancet Oncol 4: 679–685

    PubMed  Google Scholar 

  83. Dhodapkar MV et al. (2001) Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood 98: 41–48

    CAS  PubMed  Google Scholar 

  84. Bing J et al. (1937) Reports of a third case of hyperglobulinemia with affection of the central nervous system on a toxi-infectious basis. Acta Medica Scand 91: 410–427

    Google Scholar 

  85. Imai F et al. (1995) Intracerebral infiltration by monoclonal plasmacytoid cells in Waldenström's macroglobulinemia—case report. Neurol Med Chir (Tokyo) 35: 575–579

    CAS  Google Scholar 

  86. Tommasi M et al. (1966) Waldenström's macroglobulinemia: lesions of the central nervous system [French]. Ann Anat Pathol (Paris) 11: 309–313

    CAS  Google Scholar 

  87. Zollinger HU (1958) Pathological anatomy of Waldenström's macroglobulinemia [German]. Helv Med Acta 25: 153–183

    CAS  PubMed  Google Scholar 

  88. Edgar R and Dutcher TF (1961) Histopathology of the Bing–Neel syndrome. Neurology 11: 239–245

    CAS  PubMed  Google Scholar 

  89. Garderet L et al. (2006) 'Indolent' Waldenström's macroglobulinemia and a cerebrospinal fluid protein level of 16 g/L. Eur J Haematol 77: 80–82

    PubMed  Google Scholar 

  90. Noel J et al. (2002) Primary central nervous system lymphoma with Waldenström's macroglobulinaemia. Eur Neurol 47: 184–185

    PubMed  Google Scholar 

  91. Prasad AS and Bloch HS (1960) Macroglobulinemia secondary to a lymphosarcoma of the brain. Arch Intern Med 105: 316–319

    CAS  PubMed  Google Scholar 

  92. Quilichini R et al. (1989) Waldenström's macroglobulinemia with cerebral lymphoproliferative involvement of tumor appearance (Bing and Neel syndrome): an anatomo-clinical case [French]. Ann Med Interne (Paris) 140: 25–29

    CAS  Google Scholar 

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Authors and Affiliations

  1. JM Baehring is a Neuro-oncologist at Yale University School of Medicine and the Director of the Yale Brain Tumor Center, New Haven, CT, USA.,

    Joachim M Baehring

  2. EP Hochberg is a Medical Oncologist and Director of Clinical Lymphoma Research, N Raje is a Hematologist and Oncologist, M Ulrickson is a Resident in Internal Medicine and FH Hochberg is an Attending Neurologist (Neuro-oncology) at the Massachusetts General Hospital, Boston, MA, USA.,

    Ephraim P Hochberg, Noopur Raje, Matthew Ulrickson & Fred H Hochberg

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Supplementary information

Supplementary Table 1

Cases of Waldenstom's macroglobulinemia with documented transformation to malignant lymphoma with nervous system involvement (DOC 51 kb)

Supplementary Table 2

Cases of CNS involvement by Waldenstrom's macroglobulinemia ('Bing–Neel syndrome') (DOC 110 kb)

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Baehring, J., Hochberg, E., Raje, N. et al. Neurological manifestations of Waldenström macroglobulinemia. Nat Rev Neurol 4, 547–556 (2008). https://doi.org/10.1038/ncpneuro0917

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