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. 2006 Apr 5;9(2):261–273. doi: 10.1111/j.1750-3639.1999.tb00225.x

Autoimmunity in Paraneoplastic Neurological Syndromes

B Giometto 1,✉, B Taraloto 1, F Graus 2
PMCID: PMC8098596  PMID: 10219744

Abstract

In patients with Paraneoplastic Neurological Disorders, the researcher detected several autoanti‐bodies reacting with neuronal antigens and tumors; their characteristics supported the hypothesis that autoimmunity plays a part in these diseases and gave impetus to the study of these neurological disorders.

The relationship between detection of anti‐neuronal antibodies, clinical syndromes, and certain types of tumors suggested the utility of these antibodies as a new tool for clinical diagnosis, although their function in the pathogenesis of the various syndromes is still unclear.

This paper intends to review the characteristics of the anti‐neuronal antibodies so far identified, their correlation with clinical syndromes, and the function of antigens. In addition, the paper will offer some insights on the immunological mechanisms of neuronal damage and on treatment options.

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References

  • 1. Altermatt HJ, Rodriguez M, Scheithauer BW, Lennon VA (1991) Paraneoplastic anti‐Purkinje and type I anti‐neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells. Lab Invest 65: 412–420. [PubMed] [Google Scholar]
  • 2. Anderson NE, Rosenblum, MK , Posner, JB (1988) Paraneoplastic cerebellar degeneration: clinical‐immunological correlation. Ann Neurol 24: 559–567. [DOI] [PubMed] [Google Scholar]
  • 3. Antoine JC, Honnorat J, Thomas Anterion C, Aguera M, Absi L, Fournel P, Michel D (1995). Limbic encephalitis and immunologial perturbations in two patients with thymoma. J Neurol Neurosurg Psychiatr 58: 706–710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Bain PG, Motomura M, Newson‐Davies J, Misbah SA, Chapel HM, Lee ML, Vincent A, Lang B (1996) Effects of intravenous immunoglobulin on muscle weakness and calcium‐channel autoantibodies in the Labert‐Eaton myastenic syndrome. Neurology 47: 678–683. [DOI] [PubMed] [Google Scholar]
  • 5. Baker, ME , Kirbs, DR , Korobkia, M , Bowie, JD , Filston, HC. (1985) The association of neuroblastoma and myoclonic encephalopathy: an imaging approach. Pediatr Radiol 15: 185–189. [DOI] [PubMed] [Google Scholar]
  • 6. Brashear HR, Greenlee JE, Jaeckle KA, Rose JW (1989) Anticerebellar antibodies in neurologically normal patients with ovarian neoplasms. Neurology 39: 1605–1609. [DOI] [PubMed] [Google Scholar]
  • 7. Byrne T, Mason WP, Posner JB, Dalamau J (1997) Spontaneous neurological improvement in anti‐Hu encephalomyelitis. J Neurol Neurosurg Psychiatr 62: 276–278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Buckanovich RJ, Posner JB, Darnell RB (1993) Nova, the paraneoplastic Ri antigen, is homologous to an RNA‐binding protein and is specifically expressed in the developing motor system. Neuron 11: 657–672. [DOI] [PubMed] [Google Scholar]
  • 9. Buckanovich RJ, Yang YYZ, Darnell RB (1996) The onconeural antigen Nova‐1 is a neuron‐specific RNA binding protein, the activity of which is inhibited by paraneoplastic antibodies. J Neuroscience 16:1114–1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Chalk CH, Murray NM, Newson‐Davies J, OiNeill JH, Spiro SG. (1990) Response of Lambert‐Eaton myastenic syndrome to treatment od associated small cell lung carcinoma. Neurology 40:1552–1556. [DOI] [PubMed] [Google Scholar]
  • 11. Chen YT, Rettig WJ, Yenamandra AK, Kozac A, Chaganti RSK, Posner JB, Old LJ. (1990) Cerebellar degeneration related antigen: a highly conserved neuroectodermal marker mapped to chromosome X in human and mouse. Proc Natl Acad Sci USA 87: 3077–3081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Cher LM., Hochberg FH., Teruya J, Nitschke M, Valenzuela RF, Schmahmann J.D, Herbert M, Rosas HD, Stowel C (1995) Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption. Cancer 75:1678–1683. [DOI] [PubMed] [Google Scholar]
  • 13. Consuell CE, McLeod M, Grant R (1994) Reversal of sub‐acute paraneoplastic cerebellar syndrome with intravenous immunoglobulin. Neurology 44: 1184–1185. [DOI] [PubMed] [Google Scholar]
  • 14. Corradi JP, Yang C, Darnell JC, Dalmau J, Darnell RB. (1997) A post‐transcriptional regulatory mechanism restricts expression of the paraneoplastic cerebellar degeneration antigen cdr2 to immune privileged tissues. J Neurosci 17 (4): 1406–1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Cuuningham J, Graus F, Anderson N, Posner JB (1986) Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneraton. Neurology 36: 1163–1168. [DOI] [PubMed] [Google Scholar]
  • 16. Dalmau J, Furneaux HM., Gralla R.J., Kris MG., Posner JB (1990) Detection of the anti‐Hu antibody in the serum of patients with small cell lung cancer ‐ a quantitative Western blot analysis. Ann Neurol 27: 544–552. [DOI] [PubMed] [Google Scholar]
  • 17. Dalmau J, Graus F, Rosenblum MK, Posner JB (1991). Detection of the anti‐Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuropathy. Neurology 41: 1757–1764. [DOI] [PubMed] [Google Scholar]
  • 18. Dalmau J, Graus F, Rosenblum MK, Posner JB (1992) Anti‐Hu‐associated paraneoplastic encephalomyelitis/sensory neuronopathy A Clinical Study of 71 patients. Medicine 71:59–72. [DOI] [PubMed] [Google Scholar]
  • 19. Dalmau J, Furneaux HM, Cordon‐Cardo C, Posner JB (1992) The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in normal and tumor tissues. Am J Pathol 141: 881–886. [PMC free article] [PubMed] [Google Scholar]
  • 20. Dalmau J, Posner JWB (1994) Neurologic paraneoplastic antibodies (anti‐Yo; anti‐Hu; anti‐Ri): the case for a nomenclature based on antibody and antigen specificity. Neurology 44:2241–2246. [DOI] [PubMed] [Google Scholar]
  • 21. Dalmau J, Graus F, Cheung NK, Rosenblum MK, Ho A, Canete A, Delattre JY, Thompson SJ, Posner JB (1995) Major histocompatibilility proteins, anti‐Hu antibodies and paraneoplastic encephalolomyelitis in neuroblastoma and small cell lung cancer. Cancer 75: 99–109. [DOI] [PubMed] [Google Scholar]
  • 22. Dalmau J. (1998) Paraneoplastic neurological disorders. Clinical immunological correlation. J Neurol 245:339–340. [Google Scholar]
  • 23. Dalmau, JO , Posner, JB (1996) Purkinje cell autoantibodies, type 1 (Yo). In: Autoantibodies. Peter, J.B. & Shoenfeld, Y eds. Elsevier Science B.V. Amsterdam . 655–659. [Google Scholar]
  • 24. Darnell RB, De Angelis LM. (1993) Regression of small cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet 341: 21–22. [DOI] [PubMed] [Google Scholar]
  • 25. De Camilli P, Thomas A, Cofiell R, Folli F, Lichte B, Piccolo G, Menick HM, Austoni M, Fassetta G, Bottazzo GF, Solimena M (1993) The synaptic vesicle‐associated protein amphiphysin is the 128 kD autoantigen of stiff‐man syndrome with breast cancer. J Exp Med 178:2219–2223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Denny‐Brown (1948) Primary sensory neuropathy with muscular changes associated with carcinoma. J Neurol Neurosurg Psychiatr 11: 73–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Dropcho EJ, King PH. (1994) Autoantibodies against the Hel‐N1 RNA‐binding protein among patients with lung carcinoma: an association with type I anti‐neuronal nuclear antibodies. Ann Neurol 36:200–205. [DOI] [PubMed] [Google Scholar]
  • 28. Dropcho EJ. (1995) Autoimmune central nervous system paraneoplastic disorders: mechanism, diagnosis, and therapeutic options. Ann Neurol 37(S1): S102–S113. [DOI] [PubMed] [Google Scholar]
  • 29. Dropcho EJ (1996) Antiamphiphysin antibodies with small‐cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol 39: 659–667. [DOI] [PubMed] [Google Scholar]
  • 30. Fatallah‐Shaykh H, Wolf S, Wong E, Posner JB, Furneaux HM (1991). Cloning of a leucine‐zipper protein recognized by the sera of patients with antibody‐associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci USA 88: 3451–3545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Felician O, Renard JL, Vega F, Creange A, Chen QM, Bequet D, Delattre JY (1995) Paraneoplastic cerebellar degeneration with anti‐Yo antibody in a man. Neurology 45: 1226–1227. [DOI] [PubMed] [Google Scholar]
  • 32. Folli F, Solimena M, Cofiell R, Austoni M, Tallini G, Fassetta G, Bates D, Carlidge N, Bottazzo GF, Piccolo G, De Camilli P. (1993). Autoantibodies to a 128‐kd synaptic protein in three women with the stiff‐man syndrome and breast cancer. N Engl J Med 328: 546–551. [DOI] [PubMed] [Google Scholar]
  • 33. Furneaux HM, Rosenblum MK, Dalmau J, Wong E, Woodruff P, Graus F, Posner JB. (1990) Selective expression of Purkinje‐cell antigens in tumor tissue from patients with paraneoplastic cerebellar degeneration. N Eng J Med 227: 1844–1851. [DOI] [PubMed] [Google Scholar]
  • 34. Furneaux HM, Reich L, Posner JB. (1990) Autoantibodies synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 40: 1985–1991. [DOI] [PubMed] [Google Scholar]
  • 35. Gennaula CP, Eidelman BH (1995) Anti‐Ri paraneoplastic syndrome in association with primary lung carcinoma. Neurology 45: 1417. [Google Scholar]
  • 36. Giometto B, Marchiori GC, Nicolao P, Scaravilli T, Lion A, Bardin PG, Tavolato B (1997) Subacute cerebellar degeneration with anti‐Yo autoantibodies: immunohistochemical analysis of the immune reaction in the central nervous system. Neuropathol Appl Neurobiol 23: 468–474. [DOI] [PubMed] [Google Scholar]
  • 37. Graus F, Cordon‐Cardo C, Posner JB. (1985) Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology 35: 538–543. [DOI] [PubMed] [Google Scholar]
  • 38. Graus F, Elkon KB, Cordon‐Cardo C, and Posner JB. (1986) Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor. Am J Med 80: 45–52. [DOI] [PubMed] [Google Scholar]
  • 39. Graus F, IIIa I, Agusti M, Ribalta T, Cruz‐Sanchez F, Juarez C (1991) Effect of intraventricular injection of an anti‐Purkinje cell antibody (anti‐Yo) in a guinea pig model. J Neurol Sci 106: 82–87. [DOI] [PubMed] [Google Scholar]
  • 40. Graus F, Vega F, Delattre J‐Y, Bonaventura I, Rene R, Arbaiza D, Tolosa E. (1992) Effect of plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology 42: 536–540. [DOI] [PubMed] [Google Scholar]
  • 41. Graus F, Delattre JY (1993) Immune modulation of paraneoplastic neurological disorders. Clin Neurol Neurosurg 97:112–116. [DOI] [PubMed] [Google Scholar]
  • 42. Graus F, Dalmau J, Rene R, Tora M, Malats N, Verschuuren JJ, Cardenal F, Vinolas J, Garcia del Muro, Vadell C, Mason WP, Rosell R, Posner JB, Real FX (1997) Anti‐Hu antibodies in patients with small‐cell lung cancer†: association with complete response to therapy and improved survival. J Clin Oncol 51: 2866–2872. [DOI] [PubMed] [Google Scholar]
  • 43. Graus F, Dalamau J, Valldeoriola F, Ferrer I, Rene R, Marin C, Vecht CJ., Arbizu T, Targa C, Moll JW. (1997). Immunological characterization of a neuronal antibody (anti‐Tr) associated with paraneoplastic cerebellar degeneration and Hodgkinis disease. J Neuroimmunol 74: 55–61. [DOI] [PubMed] [Google Scholar]
  • 44. Greenlee JE, Brashear HR. (1983) Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 1983;14: 609–613. [DOI] [PubMed] [Google Scholar]
  • 45. Greenlee JE, Brashear HR, Herndon RM. (1988) Immunoperoxidase labelling of rat brain section with sera from patients with paraneoplastic cerebellar degeneration and systemic neoplasia. J Neuropathol Exp Neurol 47: 561–571. [DOI] [PubMed] [Google Scholar]
  • 46. Greenlee JE, Burns JB, Rose JW, Jaeckle KA, Clawson S. (1995) Uptake of systemically administered human cerebellar antibody by rat Purkinje cells following blood‐brain barrier disruption. Acta Neuropathol 1995; 89: 341–345. [DOI] [PubMed] [Google Scholar]
  • 47. Greenlee JE, Parks TN, Jaeckle KA. (1993) Type la (“anti‐Hu”) antineuronal antibodies produce destruction of rat cerebellar granule neurons in vitro. Neurology 1993; 43: 2049–2054. [DOI] [PubMed] [Google Scholar]
  • 48. Gress T, Baldini A, Rocchi M, Furneaux H, Posner JB, Siniscalco M (1992) In situ mapping of the gene coding for a leucine‐zipper DNA binding protein (CDR62) to 16p12–16p13.1. Genomics 13: 1340–1342. [DOI] [PubMed] [Google Scholar]
  • 49. Gultekin SH, Dalmau J, Graus F, Posner JB, Rosenblum MK (1998) Anti‐Hu immunolabeling as an index of neuronal differentiation in human brain tumors: a study of 112 central neuroepithelial neoplasms. Am J Surg Pathol 22: 195–200. [DOI] [PubMed] [Google Scholar]
  • 50. Hammack, JE , Kimmel, DW , OiNeil, BP , Lennon, VA. (1991) Paraneoplastic cerebellar degeneration: a clinical comparison of patients with and without Purkinje cell cytoplasmatic antibodies. Mayo Clin Proc 1991; 65: 1423–1431. [DOI] [PubMed] [Google Scholar]
  • 51. Hammack J, Kotanides H, Rosenblum MK, Posner JB. (1992) Paraneoplastic cerebellar degeneration. II. Clinical and immunologic finding in 21 patients with Hodgkinis disease. Neurology 42: 1938–1943. [DOI] [PubMed] [Google Scholar]
  • 52. Henson RA, Russell DS and Wilkinson M (1954) Carcinomatous neuropathy and myopathy A clinical and pathological study. Brain 77:82–121. [DOI] [PubMed] [Google Scholar]
  • 53. Henson RA, Urich H. (1982) Encephalomyelitis with carcinoma. In: Cancer and Nervous System. Henson, RA and Urich, H. eds. pp 314–345. Oxford Blackwell Scientific Pubblication. Oxford . [Google Scholar]
  • 54. Henson RA, Urich H. (1982) Cortical Cerebellar Degeneration In: Cancer and Nervous System. Henson R.A. and Urich H. eds., pp. 346–367 Oxford Blackwell Scientific Publications. Oxford . [Google Scholar]
  • 55. Honnorat J, Antoine JC, Derrington E, Aguera M, Belin MF. (1996) Antibodies to a subpopulation of glial cells and a 66 kDa developmental protein in patients with paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatr 61:270–278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Honnorat J, Aguera M, Zalc B, Goujet C, Quach T, Antoine JC, Belin MF (1998) POP66, a paraneoplastic encephalomyelitis‐related antigen, is a marker of adult oligodendrocytes. J Neuropathol Exp Neurol 57:311–322. [DOI] [PubMed] [Google Scholar]
  • 57. Hormigo A, Lieberman F. (1994) Nuclear localization of anti‐Hu antibody is not associated with in vitro cytotoxicity. J Neuroimmunol 55: 205–212. [DOI] [PubMed] [Google Scholar]
  • 58. Hormigo A, Dalmau J, Rosenblum MK, River ME, Posner JB (1994) Immunological and Pathological Study of anti‐Ri‐associated Encephalopathy. Ann Neurol 36:896–902. [DOI] [PubMed] [Google Scholar]
  • 59. Jaeckle KA, Graus F, Houghton A, Cordon‐Cardo C, Nielsen SL, Posner JB. (1985) Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen. Ann Neurol 18: 592–600. [DOI] [PubMed] [Google Scholar]
  • 60. King, PH (1994) Hel‐N2: a novel isoform of Hel‐N1 which is conserved in rat neural tissue and produced in early embryogenesis. Gene 151: 261–265. [DOI] [PubMed] [Google Scholar]
  • 61. King PH, Levine TD, Fremeau RT Jr, Keene JD. (1994) Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3 UTR of mRNA encoding the Id transcriptional repressor. J Neuroscience 14: 1943–1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62. King PH, Dropcho EJ (1996) Expression of Hel‐N1 and Hel‐N2 in small‐cell lung carcinoma. Ann Neurol 39: 679–681. [DOI] [PubMed] [Google Scholar]
  • 63. Lang B, Vincent A (1996) Autoimmunity to ion‐channel and other proteins in paraneoplastic disorders. Cur Op Immunol 8:865–871. [DOI] [PubMed] [Google Scholar]
  • 64. Lennon VA (1994) Paraneoplastic autoantibodies†: the case for a descriptive generic nomenclature. Neurology 44: 2236–2240. [DOI] [PubMed] [Google Scholar]
  • 65. Lennon VA, Kryzer TJ, Griesmann GE, OiSulleabhain PE, Windebank AJ, Woppmann A, Miljanich GP, Lambert EH (1995) Calcium channel antibodies in the Lambert‐Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 332: 1467–1474. [DOI] [PubMed] [Google Scholar]
  • 66. Lennon VA (1996) Calcium channel and related paraneoplastic disease autoantibodies. In: Autoantibodies. Peter J.B. & Shoenfeld Y. eds. Pp 139–147 Elsevier Science B.V. Amsterdam . [Google Scholar]
  • 67. Lennon VA, Kryzer TJ (1998) Neuronal calcium channel antibodies coexisting with type 1 Purkinje cell cytoplasmic autoantibodies (PCA‐1 or anti‐Yo). Neurology 51: L327–328. [DOI] [PubMed] [Google Scholar]
  • 68. Leys K, Lang B, Johnston I, Newsom‐Davies J. (1991) Calcium Channel Autoantibodies in the Lambert‐Eaton Myastenic Syndrome. Ann Neurol 29:307–314. [DOI] [PubMed] [Google Scholar]
  • 69. Liu J, Dalmau J, Szabo A, Rosenfeld M, Huber J, Furneaux H (1995) Paraneoplastic encephalomyelitis antigens bind to the AU‐rich elements of mRNA. Neurology 45: 544–550. [DOI] [PubMed] [Google Scholar]
  • 70. Lucchinetti CF, Kimmel DW, Lennon VA. (1998) Paraneoplastic and oncologic profile of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology 50:652–657. [DOI] [PubMed] [Google Scholar]
  • 71. Luque FA, Furneaux HM, Ferziger R, Rosenblum M Wray SH, Clifford Schold S, Glantz MJ, Jaeckle KA, Biran H, Lesser M, Paulsen WA, River ME, Posner JB. (1991) Anti‐Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 29: 241–251. [DOI] [PubMed] [Google Scholar]
  • 72. Manley GT, Smitt PS, Dalmau J, Posner JB. (1996) Hu antigens: reactivity with Hu antibodies, tumor expression, and major immunogenic sites. Ann Neurol 38: 102–110. [DOI] [PubMed] [Google Scholar]
  • 73. Marusich MF, Weston JA (1992) Identification of early neurogenic cells in the normal crest lineage. Develop Biol 149: 295–306. [DOI] [PubMed] [Google Scholar]
  • 74. Mason WP, Graus F, Lang B, Honnorat J, Delattre AJ, Valldeoriola F, Antoine JC, Rosemblum MK, Rosenfeld MR, Newson‐Davies J, Posner JB, Dalmau J (1997) Small‐cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert‐Eaton myastenic syndrome. Brain 120: 1279–1300. [DOI] [PubMed] [Google Scholar]
  • 75. Moll JWB, Henzen‐Logmans SC, van der Meche FGA, Vecht C.J. (1993). Early diagnosis and intravenous immune globulin therapy in paraneoplastic cerebellar degeneration. J Neurol Neurosurg Psychiatr 56: 112–115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Moll JWB, Antoine JC, Brashear HR, Delattre J, Drlicek M, Dropcho EJ, Giometto B, Graus F, Greenlee J, Honnorat J, Jaeckle KA, Tanaka K, Vech CJ. (1995) Guidelines on the detection of paraneoplastic anti‐neuronal‐specific antibodies: report from the Workshop to the Fourth Meeting of the International Society of Neuroimmunology on paraneoplastic neurological diseases, held October 22–23, 1994, in Rotterdam, The Netherlands. Neurology 45: 1937–1941. [DOI] [PubMed] [Google Scholar]
  • 77. Molinuevo J, Rene R, IIIa I, Guerrero A, Graus F (1998) Utility of anti‐Hu antibodies (Hu‐Ab) in the diagnosis of paraneoplastic sensory neuropathy (PNS) Ann Neurol: 44: 476–80. [DOI] [PubMed] [Google Scholar]
  • 78. Motomura M, Lang B, Johnston I, Palace J, Vincent A, Newson‐Davies J. (1997) Incidence of serum anti‐P/Q type and N‐type calcium channel autoantibodies in the Lambert‐Eaton myastenic syndrome. J Neurol Sci 147: 35–42. [DOI] [PubMed] [Google Scholar]
  • 79. Muresu R, Baldini A, Gress T, Posner JB, Furneaux HM, Siniscalco M. (1994) Mapping of the gene coding for a paraneoplastic encephalomyelitis antigen (HuD) to human chromosome site 1p34. Cytogenet. Cell Genet 65: 177–178. [DOI] [PubMed] [Google Scholar]
  • 80. Oh SJ, Dropcho EJ (1990) Steroid‐responsive Paraneoplastic Encephaloneuropathy Neurology 40: 246. [Google Scholar]
  • 81. Peterson K, Rosenblum MK, Kotanides H, Posner JB (1992) Paraneoplastic cerebellar degeneration. A clinical analysis of 55 anti‐Yo antibody‐positive patients. Neurology 42: 1931–1937. [DOI] [PubMed] [Google Scholar]
  • 82. Posner JB (1989) Paraneoplastic syndromes involving the nervous system. In: Aminoff MJ. eds. Neurology and General Medicine. Churchill Livingstone. 341–364. [Google Scholar]
  • 83. Posner JB (1992) Pathogenesis of central nervous system paraneoplastic syndromes. Rev Neurol 148: 502–513. [PubMed] [Google Scholar]
  • 84. Posner JB. (1995) Paraneoplastic Syndromes. In: Neurologic Complication of Cancer. Posner J.B. eds. Contemporary Neurology series 45. pp 353–383 F.A. Davis Company; Philadelphia . [Google Scholar]
  • 85. RenÉ R, Ferrer I, Graus F (1996) Clinical and immunohistochemical comparison of in vivo injected anti‐Hu and control IgG in the nervous system of the mouse. Eur J Neurol 3: 319–323. [Google Scholar]
  • 86. Rodriguez M, Truh LI, OíNeill BP, Lennon VA (1988) Autoimmune paraneoplastic cerebellar degeneration: ultrastructural localization of antibody binding sites in Purkinje cells. Neurology 38: 1380–1386. [DOI] [PubMed] [Google Scholar]
  • 87. Rosenblum, M.K. (1993) Paraneoplasia and autoimmunologic injury of the nervous system: the anti‐Hu syndrome. Brain Pathol. 3: 199–212. [DOI] [PubMed] [Google Scholar]
  • 88. Russel Brain W, Daniel PM, Greenfield JG. (1951) Subacute cortical cerebellar degeneration and its relation to carcinoma. J Neurol Neurosurg Psychiatr 14: 59–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89. Saiz A, Dalmau J, Butler M, Chen Q, Delattre JY, De Camilli P, Graus F (1999) Anti‐Amphiphysin antibodies in patients with paraneoplastic neurologic disorders (PND) and small‐cell lung cancer (SCLC). J Neurol Neurosurg Psychiatr, in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90. Sakai K, Negami T, Yoshioka A, Hirose G. (1992) The expression of a cerebellar degeneration‐associated neural antigen in human tumor line cells. Neurology 42:361–366. [DOI] [PubMed] [Google Scholar]
  • 91. Sakai K, Gofuku M, Kitagawa Y, Ogasawara T, Hirose G, Yamazaki M, Koh CS, Yanagisawa N, Steinman L (1994) A hippocampal protein associated with paraneoplastic neurologic syndrome and small cell lung carcinoma. Bioch Biophys Res Commun 199: 1200–1208. [DOI] [PubMed] [Google Scholar]
  • 92. Sekido Y, Bader SA, Carbone DP, Johnson BE, Minna JD (1994) Molecular analysis of the HuD gene encoding a paraneoplastic encephalomyelitis antigen in human lung cancer cell lines. Cancer Res 54: 4988–4992. [PubMed] [Google Scholar]
  • 93. Sillevis‐Smitt PAE, Manley GT, Posner JB. (1994) High titer antibodies but no disease in mice immunized with the paraneoplastic antigen HuD. Neurology 43: 2049–2054. [DOI] [PubMed] [Google Scholar]
  • 94. Sillevis‐Smith P, Manley G, Moll JWB, Dalmau J, Posner JB. (1996) Pitfalls in the diagnosis of autoantibodies associated with paraneoplastic neurologic disease. Neurology 46: 1739–1741. [DOI] [PubMed] [Google Scholar]
  • 95. Stark E, Wurster U, Patzold U, Sailer M, Haas J. (1995) Immunological and clinical response to immunosuppressive treatment in paraneoplastic cerebellar degeneration. Arch Neurol 52: 814–818. [DOI] [PubMed] [Google Scholar]
  • 96. Szabo A, Dalmau J, Manley G, Rosenfeld M, Wong E, Henson J, Posner JB, Furneaux HM (1991) HuD a paraneoplastic encephalomyelitis antigen, contain RNA‐binding domains and is homologous to Elav and Sex‐lethal. Cell 67: 325–333. [DOI] [PubMed] [Google Scholar]
  • 97. Tanaka M, Tanaka K, Onodera O, Tsuji S (1995) Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti‐Yo antibody. Mouse strains ‐bearing different MHC molecules produce antibodies on immunization with recombinant Yo protein, but do not cause Purkinje cell loss. Clin Neurol Neurosurg 97: 95–100. [DOI] [PubMed] [Google Scholar]
  • 98. Tanaka K, Tanaka K, Igarashi S, Onodera O, Miyatake T, Tsuji S (1995) Trial to establish an animal model of paraneoplastic cerebellar degeneration with anti‐Yo antibody. Passive transfer of murine mononuclear cells activated with recombinant Yo protein to paraneoplastic cerebellar degeneration lymphocytes in severe combined immunodeficiency mice. Clin Neurol Neurosurg 97:101–105. [DOI] [PubMed] [Google Scholar]
  • 99. Tanaka K, Tanaka M, Tsukamoto T, Uehara T, Tsuji S. (1996) Anti‐Yo antibody binding to 62‐, 52‐, or 58‐kD protein recognizes a single molecule. Neurology 46: 1777–1778. [DOI] [PubMed] [Google Scholar]
  • 100. Trotter JL, Hendin BA, Osterland CK. (1976) Cerebellar degeneration with Hodgkinís disease. Arch Neurol 33:660–661. [DOI] [PubMed] [Google Scholar]
  • 101. Tsukamoto T, Yamamoto H, Iwasaki Y, Yoshie O, Terunuma H, Suzuki H (1989) Antineuronal autoantibodies in patients with paraneoplastic cerebellar degeneration. Arch Neurol 46: 1225–1229. [DOI] [PubMed] [Google Scholar]
  • 102. Uchuya M, Graus F, Vega F, Rene R, Delattre J‐Y. (1996) Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal autoantibodies. J Neurol Neurosurg Psychiatr 60: 388–392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 103. Verschuuren JJ, Chuang L, Rosenblum MK, Lieberman F, Pryor A, Posner JB, Dalmau J. (1996) Inflammatory infiltrates and complete absence of Purkinje cells in anti‐Yo‐associated paraneoplastic cerebellar degeneration. Acta Neuropathol (Berl.) 91: 519–525. [DOI] [PubMed] [Google Scholar]
  • 104. Verschuuren JJ, Dalmau J, Hoard R, Posner JB (1997) Paraneoplastic anti‐Hu serum: studies on human tumor cell lines. J Neuroimmunol 79: 202–205. [DOI] [PubMed] [Google Scholar]
  • 105. Voltz RD, Carpenter AF, Rosenfeld MR, Posner JB, Dalmau J (1998) Anti‐P/Q type VGCC antibodies with paraneoplastic disorders of the central nervous system. Neurology 50 (suppl 4):A422. [Google Scholar]
  • 106. Wilkinson PC, Zeromski J. (1965). Immunofluorescent detection of antibodies against neurons in sensory carcinomatous neuropathy. Brain, 88: 529–538. [DOI] [PubMed] [Google Scholar]
  • 107. Wolpow, ER , Richardson, ed. (1988) Case records of the Massachusettes General Hospital. Case 9–1988. A 57‐year‐old woman with worsening opsoclonus. N Eng J Med 318:563–570. [DOI] [PubMed] [Google Scholar]

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