Skip to main content
Log in

Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody

  • Case Report
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laserscanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson NE, Rosenblum MK, Graus F, Wiley RG, Posner JB (1988) Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 38:1391–1398

    Google Scholar 

  2. Brashear HR, Caccamo DV, Heck A, Keeney PM (1991) Localization of antibody in the central nervous system of a patient with paraneoplastic encephalomyeloneuritis. Neurology 41:1583–1587

    Google Scholar 

  3. Corsellis JAN, Goldberg GJ, Norton AR (1968) “Limbic encephalitis” and its association with carcinoma. Brain 91:481–496

    Google Scholar 

  4. 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 27:544–552

    Google Scholar 

  5. Dalmau J, Graus F, Rosenblum MK, Posner JB (1992) Anti-Hu-associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 71:59–72

    Google Scholar 

  6. 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 141:881–886

    Google Scholar 

  7. Dorfman LJ, Forno LS (1972) Paraneoplastic encephalomyelitis. Acta Neurol Scand 48:556–567

    Google Scholar 

  8. Drlicek M, Grisold W, Liszka U (1993) Correlation of circulating antineuronal antibodies (CANA) with paraneoplastic syndromes in lung cancer. Lung Cancer 8:245–258

    Google Scholar 

  9. Graus F, Cordon-Cardo C, Posner JB (1985) Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology 35:538–543

    Google Scholar 

  10. Graus F, Elkon KB, Cordon-Cardo C, Posner JB (1986) Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor.Am J Med 80:45–52

    Google Scholar 

  11. Graus F, Elkon KB, Lloberes P, Ribalta T, Torres A, Ussetti P, Valls J, Obach J, Agusti-Vida A (1987) Neuronal antinuclear antibody (anti-Hu) in paraneoplastic encephalomyelitis simulating acute polyneuritis. Acta Neurol Scand 75:249–252

    Google Scholar 

  12. 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 40:219–222

    Google Scholar 

  13. Greenlee JE, Parks TN, Jaeckle KA (1993) Type IIa (‘anti-Hu’) antineuronal antibodies produce destruction of rat cerebellar granule neurons in vitro. Neurology 43:2049–2054

    Google Scholar 

  14. Grisold W, Drlicek M, Popp W, Jellinger K (1987) Antineuronal antibodies in small cell lung carcinoma: a significance for paraneoplastic syndromes? Acta Neuropathol (Berl) 75:199–202

    Google Scholar 

  15. Hammack JE, Kimmel DW, O'Neill BP, Lennon VA (1990) Paraneoplastic cerebellar degeneration: a clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies. Mayo Clin Proc 65:1423–1431

    Google Scholar 

  16. Henson RA, Urich H (1982) Cancer and the Nervous System. Blackwell, Oxford, pp 314–345

    Google Scholar 

  17. Kawaguchi K, Kishida S, Okeda R, Funata N, Koike M (1988) Encephalomyeloneuritis with mediastinal germ cell tumor. A paraneoplastic condition? Acta Pathol Jpn 38:351–359

    Google Scholar 

  18. Osamura Y, Komatsu N, Izumi S, Yoshimura S, Murakoshi M, Watanabe K (1981) Pre-embedding immunoelectron microscopy by peroxidase-labeled antibody method: applications to endocrinology. Acta Histochem Cytochem 14:383–390

    Google Scholar 

  19. Panegyres PK, Reding MC, Esiri MM (1993) The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study. J Neurol 240:93–97

    Google Scholar 

  20. Peterson K, Rosenblum MK, Kotanides H, Posner JB (1992) Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 42:1931–1937

    Google Scholar 

  21. Rodriguez M, Truh LI, O'Neill BP, Lennon VA (1988) Autoimmune paraneoplastic cerebellar degeneration: ultrastructural localization of antibody-binding sites in Purkinje cells. Neurology 38:1380–1386

    Google Scholar 

  22. Ropper AH (1993) Seronegative, non-neoplastic acute cerebellar degeneration. Neurology 43:1602–1605

    Google Scholar 

  23. 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 67:325–333

    Google Scholar 

  24. Tomimoto H, Brengman JM, Yanagihara T (1993) Paraneoplastic cerebellar degeneration with a circulating antibody against neurons and non-neuronal cells. Acta Neuropathol 86:206–211

    Google Scholar 

  25. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamada, M., Inaba, A., Yamawaki, M. et al. Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody. Acta Neuropathol 88, 85–92 (1994). https://doi.org/10.1007/BF00294364

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00294364

Key words

Navigation