Paraneoplastic syndromes involving the nervous system

New England Journal of Medicine

Volumn 349, Issue 16, 2003, Pages 1543-1554

  Darnell, Robert B ^a,b   Posner, Jerome B ^b  

^a ROCKEFELLER UNIVERSITY   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTEROID; CYCLOPHOSPHAMIDE; IMMUNOGLOBULIN; IMMUNOSUPPRESSIVE AGENT; METHYLPREDNISOLONE; TACROLIMUS; ANTIBODY;

CLINICAL FEATURE; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; PARANEOPLASTIC SYNDROME; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; REVIEW; TUMOR IMMUNITY; BLOOD; DISEASE MODEL; IMMUNOLOGY; PARANEOPLASTIC NEUROPATHY;

ANTIBODIES; DISEASE MODELS, ANIMAL; HUMANS; IMMUNOGLOBULINS, INTRAVENOUS; IMMUNOSUPPRESSIVE AGENTS; PARANEOPLASTIC SYNDROMES, NERVOUS SYSTEM; PROGNOSIS;

EID: 0142009530     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMra023009     Document Type: Review

References (95)

1. Inui A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin 2002;52:72-91.
2. Luh JY, Han ES, Simmons JR, Whitehead RP. Poorly differentiated colon carcinoma with neuroendocrine features presenting with hypercalcemia and cutaneous metastases: case report and review of the literature. Am J Clin Oncol 2002;25:160-3.
3. 111In-pentetreotide in a patient with paraneoplastic Cushing's syndrome due to a bronchial carcinoid. Eur J Endocrinol 1997;137:688-90.
4. Denko NC, Giaccia AJ. Tumor hypoxia, the physiological link between Trousseau's syndrome (carcinoma-induced coagulopathy) and metastasis. Cancer Res 2001;61: 795-8.
5. Siu LL, Chapman W, Moore MJ. Use of the somatostatin analogue octreotide acetate in the treatment of encephalopathy associated with carcinoid tumor: case report. Am J Clin Oncol 1997;20:558-61.
6. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123: 1481-94.
7. Barnett M, Prosser J, Sutton I, Halmagyi GM, Davies L, Harper C, et al. Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J Neurol Neurosurg Psychiatry 2001;70:222-5.
8. Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody positive patients. Neurology 1992; 42:1931-7.
9. Cao Y, Abbas J, Wu X, Dooley J, van Amburg AL. Anti-Yo positive paraneoplastic cerebellar degeneration associated with ovarian carcinoma: case report and review of the literature. Gynecol Oncol 1999;75:178-83.
10. Bataller L, Graus F, Saiz A, Vilchez JJ. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain 2001;124:437-43.
11. Goldstein SM, Syed NA, Milam AH, Maguire AM, Lawton TJ, Nichols CW. Cancer-associated retinopathy. Arch Ophthalmol 1999;117:1641-5.
12. Lieberman FS, Odel J, Hirsch J, Heinemann M, Michaeli J, Posner J. Bilateral optic neuropathy with IgGkappa multiple myeloma improved after myeloablative chemotherapy. Neurology 1999;52:414-6.
13. Croteau D, Owainati A, Dalmau J, Rogers LR. Response to cancer therapy in a patient with a paraneoplastic choreiform disorder. Neurology 2001;57:719-22.
14. Golbe LI, Miller DC, Duvoisin RC. Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism. Mov Dis 1989;4:147-52.
15. Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the spinal cord, nerve, and muscle. Muscle Nerve 2000;23:1800-18.
16. Babikian VL, Stefansson K, Dieperink ME, et al. Paraneoplastic myelopathy: antibodies against protein in normal spinal cord and underlying neoplasm. Lancet 1985;2: 49-50.
17. Case Records of the Massachusetts General Hospital (Case 14-1988). N Engl J Med 1988;318:903-15.
18. Younger DS. Motor neuron disease and malignancy. Muscle Nerve 2000;23:658-60.
19. Schold SC, Cho ES, Somasundaram M, Posner JB. Subacute motor neuronopathy: a remote effect of lymphoma. Ann Neurol 1979;5:271-87.
20. Brown P, Marsden CD. The stiff man and stiff man plus syndromes. J Neurol 1999;246:648-52.
21. Silverman IE. Paraneoplastic sfiff limb syndrome. J Neurol Neurosurg Psychiatry 1999;67:126-7.
22. Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001;124:1138-48.
23. Antoine JC, Mosnier JF, Absi L, Convers P, Honnorat J, Michel D. Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies. J Neurol Neurosurg Psychiatry 1999;67:7-14.
24. Lee HR, Lennon VA, Camilleri M, Prather CM. Paraneoplastic gastrointestinal motor dysfunction: clinical and laboratory characteristics. Am J Gastroenterol 2001;96:373-9.
25. Lisak RP, Mitchell M, Zweiman B, Orrechio E, Asbury AK. Guillain-Barre syndrome and Hodgkin's disease: three cases with immunological studies. Ann Neurol 1977;1: 72-8.
26. Lachance DH, O'Neill BP, Harper CM Jr, Banks PM, Cascino TL. Paraneoplastic brachial plexopathy in a patient with Hodgkin's disease. Mayo Clin Proc 1991;66:97-101.
27. Blumenthal D, Schochet S Jr, Gutmann L, Ellis B, Jaynes M, Dalmau J. Small-cell carcinoma of the lung presenting with paraneoplastic peripheral nerve microvasculitis and optic neuropathy. Muscle Nerve 1998;21: 1358-9.
28. Lahrmann H, Albrecht G, Drlicek M, et al. Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin's disease. Muscle Nerve 2001;24:834-8.
29. Vincent A. Understanding neuromyotonia. Muscle Nerve 2000;23:655-7.
30. Carpentier AF, Delattre JY. The Lambert-Eaton myasthenic syndrome. Clin Rev Allergy Immunol 2001;20:155-8.
31. Vemino S, Auger RG, Emslie-Smith AM, Harper CM, Lennon VA. Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability. Neurology 1999;53:1233-9.
32. Stockton D, Doherty VR, Brewster DH. Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study. Br J Cancer 2001;85:41-5.
33. Levin MI, Mozaffar T, Al-Lozi MT, Pestronk A. Paraneoplastic necrotizing myopathy: clinical and pathologic features. Neurology 1998;50:764-7.
34. Pascual J, Sanchez-Pernaute R, Berciano J, Calleja J. Paraneoplastic myotonia. Muscle Nerve 1994;17:694-5.
35. Sculier J-P, Feld R, Evans WK, et al. Neurologic disorders in patients with small cell lung cancer. Cancer 1987;60:2275-83.
36. Levy Y, Afek A, Sherer Y, et al. Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 1998;28: 73-9.
37. Latov N. Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neurol 1995;37:Suppl 1:S32-S42.
38. Erlington GM, Murray NM, Spiro SG, Newsom-Davis J. Neurological paraneoplastic syndromes in patients with small cell lung cancer: a prospective survey of 150 patients. J Neurol Neurosurg Psychiatry 1991; 54:764-7.
39. 18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Ann Neurol 2000;48:105-8.
40. Graus F, Dalmou J, Reñé R, et al. Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 1997;15:2866-72.
41. Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47:9-17.
42. Dalmau J, Posner JB. Neurologic paraneoplastic antibodies (anti-Yo, anti-Hu, anti-Ri): the case for a nomenclature based on antibody and antigen specificity. Neurology 1994;44:2241-6.
43. Lennon VA. The case for a descriptive generic nomenclature: clarification of immunostaining criteria for PCA-1, ANNA-1, and ANNA-2 autoantibodies. Neurology 1994; 44:2412-5.
44. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuropathy: a clinical study of 71 patients. Medicine (Baltimore) 1992;71:59-72.
45. Szabo A, Dalmau J, Manley G, et al. HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell 1991;67:325-33.
46. Levine TD, Gao F, King PH, Andrews LG, Keene JD. Hel-N1: an autoimmune RNA-binding protein with specificity for 3′ uridylate-rich untranslated regions ofgrowth factor mRNAs. Mol Cell Biol 1993;13:3494-504.
47. Sakai K, Gofuku M, Kitagawa Y, et al. A hippocampal protein associated with paraneoplastic neurologic syndrome and small cell lung carcinoma. Biochem Biophys Res Commun 1994;199:1200-8.
48. Fathallah-Shaykh H, Wolf S, Wong E, Posner JB, Furneaux HM. Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci U S A 1991;88:3451-4.
49. Darnell JC,Albert ML, Darnell RB. Cdr2, a target antigen of naturally occurring human tumor immunity, is widely expressed in gynecological tumors. Cancer Res 2000;60: 2136-9.
50. Jensen KB, Dredge BK, Stefani G, et al. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 2000;25:359-71.
51. Yang YY, Yin GL, Darnell RB. The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proc Natl Acad Sci U S A 1998;95:13254-9.
52. Luque FA, Furneaux HM, Ferziger R, et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991;29:241-51.
53. Buckanovich KI, Posner JB, Darnell RB. Nova, a paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron 1993;11:657-72.
54. Peltola J, Hietaharju A, Rantala I, Lehtinen T, Haapasalo H. A reversible neuronal antibody (anti-Tr) associated paraneoplastic cerebellar degeneration in Hodgkin's disease. Acta Neurol Scand 1998;98:360-3.
55. Maeda T, Maeda A, Maruyama I, et al. Mechanisms of photoreceptor cell death in cancer-associated retinopathy. Invest Ophthalmol Vis Sci 2001;42:705-12.
56. Polans AS, Buczylko J, Crabb J, Palczewski K. A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy. J Cell Biol 1991;112:981-9.
57. Thirkill CE, Tait RC, Tyler NK, Roth AM, Keltner JL. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci 1992;33:2768-72.
58. Saiz A, Dalmau J, Butler MH, et al. Anti-amphiphysin I antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma. J Neurol Neurosurg Psychiatry 1999;66:214-7.
59. De Camilli P, Thomas A, Cofiell R, et al. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med 1993;178:2219-23.
60. Folli F, Solimena M, Cofiell R, et al. Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med 1993;328: 546-51.
61. Yu ZY, Kryzer TJ, Griesmann GE, Kim KK, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker oflung cancer and thymoma-related autoimmunity. Ann Neurol 2001;49:146-54.
62. Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol 2001;50:339-48.
63. Chan KH, Vernino S, Lennon VA. ANNA-3 anti-neuronal nuclear antibody: marker oflung cancer-related autoimmunity. Ann Neurol 2001;50:301-11.
64. Smitt PS, Kinoshita A, De Leeuw B, et al. Paraneoplastic cerebellar ataxia due to auto-antibodies against a glutamate receptor. N Engl J Med 2000;342:21-7.
65. Vernino S, Lennon VA. Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability. Muscle Nerve 2002;26:702-7.
66. Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR, Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;125:1887-95.
67. Vital A. Paraproteinemic neuropathies. Brain Pathol 2001;11:399-407.
68. Carpentier AF, Voltz R, DesChamps T, Posner JB, Dalmau J, Rosenfeld MR, Absence of HuD gene mutations in paraneoplastic small cell lung cancer tissue. Neurology 1998;50:1919.
69. Byrne T, Mason WP, Posner JB, Dalmau J. Spontaneous neurological improvement in anti-Hu associated encephalomyelitis. J Neurol Neurosurg Psychiatry 1997;62:276-8.
70. Corradi JP, Yang CW, Darnell JC, Dalmau J, Darnell RB. A post-transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues. J Neurosci 1997;17:1406-15.
71. Sekido Y, Bader SA, Carbone DP, Johnson BE, Minna JD. Molecular analysis of the HuD gene encoding a paraneoplastic encephalomyelitis antigen in human lung cancer cell lines. Cancer Res 1994;54:4988-92.
72. Cooper R, Khakoo Y, Matthay KK, et al. Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: histopathologic features - a report from the Children's Cancer Group. Med Pediatr Oncol 2001;36:623-9.
73. Rosenblum MK. Paraneoplasia and autoimmunologic injury of the nervous system: the anti-Hu syndrome. Brain Pathol 1993;3:199-212.
74. Altman AJ, Baehner R.L. Favorable prognosis for survival in children with coincident opso-myoclonus and neuroblastoma. Cancer 1976;37:846-52.
75. Maddison P, Newsom-Davis J, Mills KR, Souhami RL. Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma. Lancet 1999;353:117-8.
76. Hiyama E, Yokoyama T, Ichikawa T, et al. Poor outcome in patients with advanced stage neuroblastoma and coincident opsomyoclonus syndrome. Cancer 1994;74: 1821-6.
77. Rojas I, Graus F, Keime-Guibert F, et al. Long-term clinical outcome ofparaneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 2000;55:713-5.
78. Dalmau J, Furneaux HM, Gralla RJ, Kris MG, Posner JB. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer - a quantitative Western blot analysis. Ann Neurol 1990;27:544-52.
79. Albert ML, Darnell JC, Bender A, Francisco LM, Bhardwaj N, Darnell RB. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nat Med 1998;4:1321-4.
80. Voltz R, Dalmau J, Posner JB, Rosenfeld MR, T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis. Neurology 1998;51:1146-50.
81. Okano HJ, Park WY, Corradi JP, Darnell RB. The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival. Genes Dev 1999;13:2087-97.
82. Furneaux HM, Reich L, Posner JB. Auto-antibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 1990;40:1085-91.
83. Dalmau J, Furneaux HM, Rosenblum MK, Graus F, Posner JB. Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. Neurology 1991;41:1757-64.
84. Alarcon-Segovia D, Ruiz-Arguelles A, Llorente L. Broken dogma: penetration of autoantibodies into living cells. Immunol Today 1996;17:163-4.
85. Musunuru K, Darnell RB. Paraneoplastic neurologic disease antigens: RNA-binding proteins and signaling proteins in neuronal degeneration. Annu Rev Neurosci 2001;24:239-62.
86. Carpentier AF, Rosenfeld MR, Delattre J-Y, Whalen RG, Posner JB, Dalmau J. DNA vaccination with HuD inhibits growth of a neuroblastoma in mice. Clin Cancer Res 1998;4:2819-24.
87. Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A 1996;93: 4529-36.
88. Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat Immunol 2001;2:1010-7.
89. Ridley A, Kennard C, Scholtz CL, Buttner-Ennever JA, Summers B, Turnbull A. Omnipause neurons in two cases of opsoclonus associated with oat cell carcinoma of the lung. Brain 1987;110:1699-709.
90. Fukunaga H, Engel AG, Osame M, Lambert EH. Paucity and disorganization of pre-synaptic membrane active zones in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 1982;5:686-97.
91. Corriveau RA, Huh GS, Shatz CJ. Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron 1998;21:505-20.
92. Vigliani MC, Palmucci L, Polo P, et al. Paraneoplastic opsoclonus-myoclonus associated with renal cell carcinoma and responsive to tumour ablation. J Neurol Neurosurg Psychiatry 2001;70:814-5.
93. Bain PG, Motomura M, Newsom-Davis J, et al. Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Neurology 1996;47: 678-83.
94. Schneider C, Gold R, Reiners K, Toyka KV. Mycophenolate mofetil in the therapy of severe myasthenia gravis. Eur Neurol 2001; 46:79-82.
95. Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry 2000;68:479-82.