The Anti-Hu Syndrome: A Model Paraneoplastic Disorder

  • J. B. Posner
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 135)

Abstract

In 1948 Derek Denny-Brown, one of the major figures in twentieth century neurology, published a paper describing two patients with a rapidly developing sensory neuropathy [1]. The pathological abnormalities included an inflammatory degeneration of neurons in the dorsal root ganglia and small cell lung cancer that had not metastasized to the nervous system. Although paraneoplastic syndromes affecting the nervous system had been described in occasional case reports as far back as the last century [2,3], and although a subacutely developing sensory neuropathy associated with occult cancer had also been described previously [4], Denny-Brown’s careful clinical and pathological description was a major contribution, generating interest in these rare but physiologically interesting nervous system disorders. (This despite an almost certainly incorrect hypothesis that the tumor and the nervous system were competing for an essential substrate; he believed it to be pantothenic acid.)

Keywords

Corticosteroid Neuropathy Sarcoma Neurol Cyclophosphamide 

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References

  1. 1.
    Denny-Brown D (1948) Primary sensory neuropathy with muscular changes associated with carcinoma. J Neurol Neurosurg Psychiatr 11: 73–81PubMedCrossRefGoogle Scholar
  2. 2.
    Oppenheim H (1888) Uber hirnsymptome bein carcinomatose ohne nachweisbare veranderungen im gehim. Charite-Ann 13: 335–344Google Scholar
  3. 3.
    Oppenheim H (1899) Weiterer beitrag zur lehre von der acuten, nichteitrigen encephalitis and der poliencephalomyelitis. Z Nervenheilkd 15: 1–27CrossRefGoogle Scholar
  4. 4.
    Wyburn-Mason R (1948) Bronchial carcinoma presenting as polyneuritis. Lancet i: 203–206Google Scholar
  5. 5.
    Brain L, Norris F (eds) (1965) The remote effects of cancer on the nervous system. Contemporary Neurology Symposia, vol 1. Grune and Stratton, New YorkGoogle Scholar
  6. 6.
    Guichard A, Vignon G (1949) La polyradiculonevrite cancereuse metastatique. J Med Lyon 5 (March): 197–207Google Scholar
  7. 7.
    Guichard MMA, Cabanne F, Tommasi M, Fayolle J (1956) Polynevrites chez les cancereux et polynevrites paraneoplasiques. Lyon Med 41: 309–329Google Scholar
  8. 8.
    Posner JB (1992) Pathogenesis of central nervous system paraneoplastic syndromes. Rev Neurol 148: 505–512Google Scholar
  9. 9.
    Posner JB (1991) Paraneoplastic syndromes. Neurol Clin 9: 919–936PubMedGoogle Scholar
  10. 10.
    Hawley RJ, Cohen MH, Saini N, et al. (1980) The carcinomatous neuromyopathy of oat cell lung cancer. Ann Neurol 7: 65–72PubMedCrossRefGoogle Scholar
  11. 11.
    Croft PB, Wilkinson M (1965) The incidence of carcinomatous neuromyopathy in patients with various types of carcinoma. Brain 88: 427–434PubMedCrossRefGoogle Scholar
  12. 12.
    Erlington GM, Murray NMF, Spiro SG, Newsom-Davis J (1991) Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective survey of 150 patients. J Neurol Neurosurg Psychiat 54: 764–767CrossRefGoogle Scholar
  13. 13.
    Peterson K, Rosenblum MK, Kotanides H, Posner JB (1992) Paraneoplastic cerebellar degeneration: I. A clinical analysis of 55 anti-Yo antibody positive patients. Neurology 42: 1938–1943Google Scholar
  14. 14.
    Dalmau J, Graus F, Rosenblum MK, Posner JB (1992) Anti-Hu associated paraneoplastic encephalomyelitis/sensory neuronopathy: A clinical study of 71 patients. Medicine 71: 59–72PubMedCrossRefGoogle Scholar
  15. 15.
    Henson RA, Russell DS, Wilkinson M (1954) Carcinomatous neuropathy and myopathy. A clinical and pathological study. Brain 77: 82–121Google Scholar
  16. 16.
    Henson RA, Hoffman HL, Urich H (1965) Encephalomyelitis with carcinoma. Brain 88: 449–464PubMedCrossRefGoogle Scholar
  17. 17.
    Brierley JB, Corsellis JAN, Hierons R, Nevin S (1960) Subacute encephalitis of later adult life. Mainly affecting the limbic areas. Brain 83: 357–368Google Scholar
  18. 18.
    Corsellis JAN, Goldberg GJ, Norton AR (1968) “Limbic encephalitis” and its association with carcinoma. Brain 91:481–496Google Scholar
  19. 19.
    Russell DS (1961) In: van Bogaert L, Radermecker J, Hozay J, Lowenthal A (eds) Encephalitides. Elsevier, Amsterdam, pp 131–135Google Scholar
  20. 20.
    Wilkinson PC, Zeromski J (1965) Immunofluorescent detection of antibodies against neurons in sensory carcinomatous neuropathy. Brain 88: 529–538PubMedCrossRefGoogle Scholar
  21. 21.
    Henson RA, Urich H (1982) Cancer and the nervous system. Blackwell Scientific, LondonGoogle Scholar
  22. 22.
    Graus F, Cordon-Cardo, Posner JB (1985) Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology 35: 538–543PubMedGoogle Scholar
  23. 23.
    Graus F, Elkon KB, Cordon-Cardo C, Posner JB (1986) Sensory neuronopathy and small cell lung cancer: An antineuronal antibody that also reacts with the tumor. Am J Med 80: 45–52Google Scholar
  24. 24.
    Dalmau J, Furneaux HM, Cordon-Cardo C, Posner JB (1992) The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol 141: 881–886PubMedGoogle Scholar
  25. 25.
    Dalmau J, Furneaux HM, Gralla RJ, 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: 544–552PubMedCrossRefGoogle Scholar
  26. 26.
    Altman AJ, Bachner RL (1976) Favorable prognosis for survival in children with coincident opso-myoclonus and neuroblastoma. Cancer 37: 846–852PubMedCrossRefGoogle Scholar
  27. 27.
    Luque FA, Furneaux HM, Ferziger R, Rosenblum MK, Wray SH, Schold SC, Glantz MJ, Jaeckle KA, Biran H, Lesser M, Paulsen WA, River ME, Posner JB (1991) Anti-Ri: an antibody 29 associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 29: 241–251PubMedCrossRefGoogle Scholar
  28. 28.
    Fumeaux HM, Reich L, Posner JB (1990) Autoantibody synthesis in the central nervous system of patients with paraneoplastic syndromes. Neurology 40: 1085–1091Google Scholar
  29. 29.
    Anderson NE, Budde-Steffen C, Wiley RG, Thurman L, Nadeau SE, Posner JB (1988) A variant of the anti-Purkinje cell antibody in a patient with paraneoplastic cerebellar degeneration. Neurology 38: 1018–1026PubMedGoogle Scholar
  30. 30.
    Din LY, Elster AD, Donofrio PD, Smith M (1990) Evolution of brain MRI abnormalities in limbic encephalitis. Neurology 40: 1304–1306Google Scholar
  31. 31.
    Graus F, Vega F, Delattre JY, Bonaventura I, Rene R, Arbaiza D, Tolosa E (1992) Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology 42: 536–540PubMedGoogle Scholar
  32. 32.
    Dalmau J, Furneaux HM, Rosenblum MK, Graus F, Posner JB (1991) Detection of the anti-Hu antibody in specific regions of the nervous system and tumor from patients with paraneoplastic encephalomyelitis/sensory neuronopathy. Neurology 41: 1757–1764PubMedGoogle Scholar
  33. 33.
    Hetzel DJ, Stanhope R, O’Neil BP, Lennon VA (1990) Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. Mayo Clin Proc 65: 1558–1563PubMedGoogle Scholar
  34. 34.
    Szabo A, Dalmau J, Manley G, Rosenfeld M, Wong E, Henson J, Posner JB, Furneaux HM (1991) HuD a paraneoplastic encephalomyelitis antigen contains RNA binding domains and is homologous to elav and sex-lethal. Cell 67: 325–333PubMedCrossRefGoogle Scholar
  35. 35.
    Graus F, Ribalta T, Campo E, Monforte R, Urbano A, Rozman C (1990) Immunohistochemical analysis of the immune reaction in the nervous system in paraneoplastic encephalomyelitis. Neurology 40: 219–222PubMedGoogle Scholar
  36. 36.
    Liu HM, Atack JR, Rapoport SI (1989) Immunohistochemical localization of intracellular plasma proteins in the human central nervous system. Acta Neuropathol 78: 16–21PubMedCrossRefGoogle Scholar
  37. 37.
    Engelhardt JI, Appel SH (1990) IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. Arch Neurol 47: 1210–121PubMedCrossRefGoogle Scholar
  38. 38.
    Fabian RH, Petroff G (1987) Intraneuronal IgG in the central nervous system: Uptake by retrograde axonal transport. Neurology 37: 1780–1784PubMedGoogle Scholar
  39. 39.
    Graus F, Illa 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: 82–87PubMedCrossRefGoogle Scholar
  40. 40.
    Muresu R, Baldini A, Gress T, Posner JP, Furneaux HM, Siniscalco M HuD (1994) Mapping of the gene coding for a paraneoplastic encephalomyelitis antigen (HuD) to human chromosome site 1p34. Genet 65: 171–178Google Scholar
  41. 41.
    Marusich MF, Weston JA (1992) Identification of early neurogenic cells in the neural crest lineage. Dev Biol 149: 295–306PubMedCrossRefGoogle Scholar
  42. 42.
    Graus F, Ferrer I (1990) Analysis of a neuronal antigen ( Hu) expression in the developing rat brain detected by autoantibodies from patients with paraneoplastic encephalomyelitis. Neurosci Letters 112: 14–18CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • J. B. Posner
    • 1
  1. 1.Memorial Sloan-Kettering Cancer CenterNew YorkUSA

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