Abstract
Paraneoplastic neurological disorders can affect any part of the central or peripheral nervous system. Many of these syndromes have an immunopathogenesis, and are mediated by immunological responses triggered by the presence of a cancer. In this chapter, we focus on paraneoplastic disorders of the central and peripheral nervous system associated with leukemia or lymphoma. We also review paraneoplastic syndromes related to plasma cell malignancies (myeloma, Waldenström’s macroglobulinemia), which in contrast to leukemia and lymphoma, frequently cause paraneoplastic neuropathies.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Dalmau JO, Posner JB (1997) Paraneoplastic syndromes affecting the nervous system. Semin Oncol 24:318–328
Graus F, Delattre JY, Antoine JC et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1140
Dalmau J, Graus F, Villarejo A et al (2004) Clinical analysis of anti-Ma2-associated encephalitis. Brain 127:1831–1844
Samii A, Dahlen DD, Spence AM et al (2003) Paraneoplastic movement disorder in a patient with non-Hodgkin’s lymphoma and CRMP-5 autoantibody. Mov Disord 18:1556–1558
Bernal F, Shams’ili S, Rojas I et al (2003) Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 60:230–234
Baehring JM, Damek D, Martin EC et al (2003) Neurolymphomatosis. Neurooncol 5:104–115
Gherardi R, Gaulard P, Prost C et al (1986) T-cell lymphoma revealed by a peripheral neuropathy. A report of two cases with an immunohistologic study on lymph node and nerve biopsies. Cancer 58:2710–2716
Odabasi Z, Parrott JH, Reddy VV et al (2001) Neurolymphomatosis associated with muscle and cerebral involvement caused by natural killer cell lymphoma: a case report and review of literature. J Peripher Nerv Syst 6:197–203
Markert A, May A, Weber J et al (2009) Bilateral renal lymphoma after paraneoplastic limbic encephalitis. J Clin Oncol 27:1142–1144
Rajappa S, Digumarti R, Immaneni SR et al (2007) Primary renal lymphoma presenting with paraneoplastic limbic encephalitis. J Clin Oncol 25:3783–3785
Rosenfeld MR, Pruitt A (2006) Neurologic complications of bone marrow, stem cell, and organ transplantation in patients with cancer. Semin Oncol 33:352–361
Seeley WW, Marty FM, Holmes TM et al (2007) Post-transplant acute limbic encephalitis: clinical features and relationship to HHV6. Neurology 69:156–165
Wainwright MS, Martin PL, Morse RP et al (2001) Human herpesvirus 6 limbic encephalitis after stem cell transplantation. Ann Neurol 50:612–619
Graus F, Dalmau J, Valldeoriola F et al (1997) Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin’s disease. J Neuroimmunol 74:55–61
Graus F, Gultekin SH, Ferrer I et al (1998) Localization of the neuronal antigen recognized by anti-Tr antibodies from patients with paraneoplastic cerebellar degeneration and Hodgkin’s disease in the rat nervous system. Acta Neuropathol (Berl) 96:1–7
Hammack J, Kotanides H, Rosenblum MK et al (1992) Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin’s disease. Neurology 42:1938–1943
Sillevis SP, Kinoshita A, De Leeuw B et al (2000) Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. N Engl J Med 342:21–27
Carr I (1982) The Ophelia syndrome: memory loss in Hodgkin’s disease. Lancet 1:844–845
de Bot ST, Dorresteijn LD, Haaxma CA et al (2008) From psychiatric symptoms to paraneoplastic syndrome. Tijdschr Psychiatry 50:603–609
Deodhare S, O‘Connor P, Ghazarian D et al (1996) Paraneoplastic limbic encephalitis in Hodgkin’s disease. Can J Neurol Sci 23:138–140
Kung S, Mueller PS, Geda YE et al (2002) Delirium resulting from paraneoplastic limbic encephalitis caused by Hodgkin’s disease. Psychosomatics 43:498–501
Rosenbaum T, Gartner J, Korholz D et al (1998) Paraneoplastic limbic encephalitis in two teenage girls. Neuropediatrics 29:159–162
Shinohara T, Kojima H, Nakamura N et al (2005) Pathology of pure hippocampal sclerosis in a patient with dementia and Hodgkin’s disease: the Ophelia syndrome. Neuropathology 25:353–360
Werbrouck B, Meire V, De Bleecker JL (2005) Multiple neurological syndromes during Hodgkin lymphoma remission. Acta Neurol Belg 105:48–50
Dogel D, Beuing O, Koenigsmann M et al (2008) Paraneoplastic limbic encephalitis resulting from non-Hodgkin lymphoma: two case reports. Fortschr Neurol Psychiatry 76:41–46
Mihara M, Sugase S, Konaka K et al (2005) The “pulvinar sign” in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin’s lymphoma. J Neurol Neurosurg Psychiatry 76:882–884
Thuerl C, Muller K, Laubenberger J et al (2003) MR imaging of autopsy-proved paraneoplastic limbic encephalitis in non-Hodgkin lymphoma. Am J Neuroradiol 24:507–511
Gultekin SH, Rosenfeld MR, Voltz R et al (2000) Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123:1481–1494
Tüzun E, Dalmau J (2007) Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist 13:261–271
Dalmau J, Bataller L (2006) Clinical and immunological diversity of limbic encephalitis: a model for paraneoplastic neurologic disorders. Hematol Oncol Clin North Am 20:1319–1335
Epaulard O, Courby S, Pavese P et al (2004) Paraneoplastic acute diffuse encephalitis revealing Hodgkin’s disease. Leuk Lymphoma 45:2509–2512
Bernard P, Vinzio S, Talarmin F et al (2003) Hodgkin’s disease manifesting as paraneoplastic limbic encephalitis. Rev Med Interne 24:257–260
Gutmann B, Crivellaro C, Mitterer M et al (2006) Paraneoplastic stiff-person syndrome, heterotopic soft tissue ossification and gonarthritis in a HLA B27-positive woman preceding the diagnosis of Hodgkin’s lymphoma. Haematologica 91:ECR59
Anderson DW, Borsaru A (2008) Case report: lymphoma-related resolving paraneoplastic myelopathy with MRI correlation. Br J Radiol 81:e103–e105
Lee MT, Lee TI, Won JG et al (2004) Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome. Am J Med Sci 328:124–128
Lester EP, Feld E, Kinzie JJ et al (1979) Necrotizing myelopathy complicating Hodgkin’s disease. Arch Neurol 36:583–585
Dansey RD, Hammond-Tooke GD, Lai K et al (1988) Subacute myelopathy: an unusual paraneoplastic complication of Hodgkin’s disease. Med Pediatr Oncol 16:284–286
Hughes M, Ahern V, Kefford R et al (1992) Paraneoplastic myelopathy at diagnosis in a patient with pathologic stage 1A Hodgkin disease. Cancer 70:1598–1600
Schold SC, Cho ES, Somasundaram M et al (1979) Subacute motor neuronopathy: a remote effect of lymphoma. Ann Neurol 5:271–287
Younger DS, Rowland LP, Latov N et al (1990) Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. Neurology 40:595–599
Adamus G, Aptsiauri N, Guy J et al (1996) The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy. Clin Immunol Immunopathol 78:120–129
To KW, Thirkill CE, Jakobiec FA et al (2002) Lymphoma-associated retinopathy. Ophthalmology 109:2149–2153
Matus G, Dicato M, Focan C (2007) Cancer associated retinopathy (CAR). Two clinical cases and review of the literature. Rev Med Liege 62:166–169
Vigliani MC, Magistrello M, Polo P et al (2004) Risk of cancer in patients with Guillain-Barre syndrome (GBS). A population-based study. J Neurol 251:321–326
Wada S, Kimura T, Ikegame K et al (2008) Chronic inflammatory demyelinating polyradiculoneuropathy and hyponatremia in a patient with chronic graft versus host disease. Rinsho Shinkeigaku 48:426–429
Wanschitz J, Dichtl W, Budka H et al (2006) Acute motor and sensory axonal neuropathy in Burkitt-like lymphoma. Muscle Nerve 34:494–498
Wen PY, Alyea EP, Simon D et al (1997) Guillain-Barré syndrome following allogeneic bone marrow transplantation. Neurology 49:1711–1714
Rodriguez V, Kuehnle I, Heslop HE et al (2002) Guillain-Barré syndrome after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 29:515–517
Fujisaki G, Kami M, Murashige N et al (2006) Guillain-Barré syndrome associated with rapid immune reconstitution following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 37:617–619
Lachance DH, O‘Neill BP, Harper CM Jr et al (1991) Paraneoplastic brachial plexopathy in a patient with Hodgkin’s disease. Mayo Clin Proc 66:97–101
Symonds RP, Hogg RB, Bone I (1994) Paraneoplastic neurological syndromes associated with lymphomas. Leuk Lymphoma 15:487–490
Oh SJ (1997) Paraneoplastic vasculitis of the peripheral nervous system. Neurol Clin 15:849–863
Turner MR, Warren JD, Jacobs JM et al (2003) Microvasculitic paraproteinaemic polyneuropathy and B-cell lymphoma. J Peripher Nerv Syst 8:100–107
Yadav BS, Sharma SC, Kapoor RK (2006) Paraneoplastic leukocytoclastic vasculitis in chronic lymphoid leukemia. J Cancer Res Ther 2:206–208
Lahrmann H, Albrecht G, Drlicek M et al (2001) Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin’s disease. Muscle Nerve 24:834–838
Caress JB, Abend WK, Preston DC et al (1997) A case of Hodgkin’s lymphoma producing neuromyotonia. Neurology 49:258–259
Argov Z, Shapira Y, Averbuch-Heller L et al (1995) Lambert-Eaton myasthenic syndrome (LEMS) in association with lymphoproliferative disorders. Muscle Nerve 18:715–719
Tyagi A, Connolly S, Hutchinson M (2001) Lambert-Eaton myaesthenic syndrome: a possible association with Hodgkin’s lymphoma. Ir Med J 94:18–19
Abrey LE (1995) Association of myasthenia gravis with extrathymic Hodgkin’s lymphoma: complete resolution of myasthenic symptoms following antineoplastic therapy. Neurology 45:1019
Ambrosone L, Migliaresi S, Rambaldi A et al (1995) Adult polymyositis/dermatomyositis associated with acute myeloid leukemia. A case report. Clin Rheumatol 14:217–219
Langan SM, O‘Briain S, Barnes L (2003) Dermatomyositis associated with angiotropic lymphoma. Clin Exp Dermatol 28:597–599
Lima M, Coutinho J, Bernardo L et al (2002) Philadelphia-positive T-cell acute lymphoblastic leukemia with polymyositis, migratory polyarthritis and hypercalcemia following a chronic myeloid leukemia. Ann Hematol 81:174–177
Salvatore JR, Sarid R, Harrington J et al (2003) Primary non-Hodgkin’s lymphoma of the transverse colon presenting as dermatomyositis: case presentation and literature review. Med Oncol 20:413–424
Shen JK, Ding YM, Zhou WJ et al (2008) Polymyositis/dermatomyositis associated with acute myelocytic leukemia. Rheumatol Int 28:1265–1267
Morris P, Herrera-Guerra A, Parham D (2009) Lymphoma arising from a calcinotic lesion in a patient with juvenile dermatomyositis. Pediatr Dermatol 26:159–161
Sherry DD, Haas JE, Milstein JM (1993) Childhood polymyositis as a paraneoplastic phenomenon. Pediatr Neurol 9:155–156
Steck AJ, Erne B, Gabriel JM et al (1999) Paraproteinaemic neuropathies. Brain Pathol 9:361–368
Ropper AH, Gorson KC (1998) Neuropathies associated with paraproteinemia. N Engl J Med 338:1601–1607
Dispenzieri A, Kyle RA, Lacy MQ et al (2003) POEMS syndrome: definitions and long-term outcome. Blood 101:2496–2506
Rotta FT, Bradley WG (1997) Marked improvement of severe polyneuropathy associated with multifocal osteosclerotic myeloma following surgery, radiation, and chemotherapy. Muscle Nerve 20:1035–1037
Dispenzieri A, Moreno-Aspitia A, Suarez GA et al (2004) Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood 104:3400–3407
Silberstein LE, Duggan D, Berkman EM (1985) Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the POEMS syndrome. J Clin Apher 2:253–257
Henze T, Krieger G (1995) Combined high-dose 7S-IgG and dexamethasone is effective in severe polyneuropathy of the POEMS syndrome. J Neurol 242:482–483
Vingerhoets F, Kuntzer T, Delacretaz F et al (1995) Chronic relapsing neuropathy associated with Castleman’s disease (angiofollicular lymph node hyperplasia). Eur Neurol 35:336–340
Ku A, Lachmann E, Tunkel R et al (1995) Severe polyneuropathy: initial manifestation of Castleman’s disease associated with POEMS syndrome. Arch Phys Med Rehabil 76:692–694
Dispenzieri A, Gertz MA (2005) Treatment of Castleman’s disease. Curr Treat Options Oncol 6:255–266
Dimopoulos MA, Panayiotidis P, Moulopoulos LA et al (2000) Waldenstrom’s macroglobulinemia: clinical features, complications, and management. J Clin Oncol 18:214–226
Rudnicki SA, Harik SI, Dhodapkar M et al (1998) Nervous system dysfunction in Waldenstrom’s macroglobulinemia: response to treatment. Neurology 51:1210–1213
Weide R, Heymanns J, Koppler H (2000) The polyneuropathy associated with Waldenstrom’s macroglobulinaemia can be treated effectively with chemotherapy and the anti-CD20 monoclonal antibody rituximab. Br J Haematol 109:838–841
Wilson HC, Lunn MP, Schey S et al (1999) Successful treatment of IgM paraproteinaemic neuropathy with fludarabine. J Neurol Neurosurg Psychiatry 66:575–580
Latov N (2000) Prognosis of neuropathy with monoclonal gammopathy. Muscle Nerve 23:150–152
Kyle RA, Rajkumar SV, Therneau TM et al (2005) Prognostic factors and predictors of outcome of immunoglobulin M monoclonal gammopathy of undetermined significance. Clin Lymphoma 5:257–260
Montoto S, Rozman M, Rosinol L et al (2003) Malignant transformation in IgM monoclonal gammopathy of undetermined significance. Semin Oncol 30:178–181
Dyck PJ, Low PA, Windebank AJ et al (1991) Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance. N Engl J Med 325:1482–1486
Lee YC, Came N, Schwarer A et al (2002) Autologous peripheral blood stem cell transplantation for peripheral neuropathy secondary to monoclonal gammopathy of unknown significance. Bone Marrow Transplant 30:53–56
Katz JS, Saperstein DS, Gronseth G et al (2000) Distal acquired demyelinating symmetric neuropathy. Neurology 54:615–620
Vital A, Lagueny A, Julien J et al (2000) Chronic inflammatory demyelinating polyneuropathy associated with dysglobulinemia: a peripheral nerve biopsy study in 18 cases. Acta Neuropathol 100:63–68
Ilyas AA, Quarles RH, Dalakas MC et al (1985) Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosyl groups. Ann Neurol 18:655–659
Latov N, Hays AP, Donofrio PD et al (1988) Monoclonal IgM with unique specificity to gangliosides GM1 and GD1b and to lacto-N-tetraose associated with human motor neuron disease. Neurology 38:763–768
Nardelli E, Steck AJ, Barkas T et al (1988) Motor neuron syndrome and monoclonal IgM with antibody activity against gangliosides GM1 and GD1b. Ann Neurol 23:524–528
Dalakas MC, Quarles RH (1996) Autoimmune ataxic neuropathies (sensory ganglionopathies): are glycolipids the responsible autoantigens? Ann Neurol 39:419–422
Goldfarb AR, Weimer LH, Brannagan TH III (2005) Rituximab treatment of an IgM monoclonal autonomic and sensory neuropathy. Muscle Nerve 31:510–515
Niermeijer JM, Eurelings M, Lokhorst HL et al (2009) Rituximab for polyneuropathy with IgM monoclonal gammopathy. J Neurol Neurosurg Psychiatry 80:1036–1039
Rojas-Garcia R, Gallardo E, de Andrés I et al (2003) Chronic neuropathy with IgM anti-ganglioside antibodies: lack of long term response to rituximab. Neurology 61:1814–1816
Broglio L, Lauria G (2005) Worsening after rituximab treatment in anti-MAG neuropathy. Muscle Nerve 32:378–379
Comi G, Roveri L, Swan A et al (2002) A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol 249:1370–1377
Mariette X, Chastang C, Clavelou P et al (1997) A randomised clinical trial comparing interferon-alpha and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM. The IgM-associated Polyneuropathy Study Group. J Neurol Neurosurg Psychiatry 63:28–34
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Rosenfeld, M.R., Dalmau, J. (2012). Paraneoplastic Neurological Disorders in Leukemia and Lymphoma. In: Batchelor, T., DeAngelis, L. (eds) Lymphoma and Leukemia of the Nervous System. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7668-0_20
Download citation
DOI: https://doi.org/10.1007/978-1-4419-7668-0_20
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-7667-3
Online ISBN: 978-1-4419-7668-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)