Skip to main content

Advertisement

SpringerLink
Log in

Paraneoplastic diseases of the nervous system

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Several neurologic paraneoplastic disorders are believed to be caused by an autoimmune reaction against an antigen or antigens coexpressed by tumor cells and neurons. Of the paraneoplastic syndromes, the Lambert-Eaton myasthenic syndrome (LEMS)—in which autoantibodies downregulate voltage-gated calcium channels at the presynaptic nerve terminal—is associated with the strongest evidence of an autoimmune cause. For the other syndromes, including cerebellar degeneration, multifocal encephalomyelitis, sensory neuronopathy, limbic encephalitis, opsoclonus-myoclonus, and retinal degeneration, an autoimmune cause is indicated by the presence of specific antineuronal antibodies. These antibodies serve as a useful diagnostic tool, but their actual role in causing neuronal injury and clinical disease remains unclear. A small percentage of patients with paraneoplastic disorders shows major neurologic improvement after successful treatment of the associated tumor. Of patients who require further therapy for the neurologic disorder, those with LEMS have the best outcome. The response to immunosuppression among patients with paraneoplastic central nervous system (CNS) dysfunction is much less favorable. Although exceptions clearly exist, most patients with CNS paraneoplastic disorders do not improve despite tumor treatment and immunosuppressive therapy. It is likely that many patients already have irreversibl neuronal injury at the time of diagnosis. The decision to attempt immunosuppressive treatment must be made on an individual basis.

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

Access this article

Log in via an institution

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 and Recommended Reading

  1. Dropcho EJ: Neurologic paraneoplastic syndromes. J Neurol Sci 1998, 153:264278. This is a recent detailed update on clinical syndromes and their autoimmune aspects.

    Article  Google Scholar 

  2. Moll JW, Antoine JC, Brashear HR, et al.: Guidelines on the detection of paraneoplastic anti-neuronal-specific antibodies. Neurology 1995, 45:19371941.

    Google Scholar 

  3. Chalk CH, Murray NM, Newsom-Davis J, et al.: Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small cell lung carcinoma. Neurology 1990, 40:15521556.

    Google Scholar 

  4. Tim RW, Massey JM, Sanders DB: Lambert-Eaton myasthenic syndrome: clinical and electrodiagnostic features and response to therapy in 59 patients. Ann N Y Acad Sci 1998, 841:823826. Summary of response to pyridostigmine, diaminopyridine, and a variety of immunomodulatory treatments.

    Article  Google Scholar 

  5. Graus F, Bonaventura I, Uchuya M, et al.: Indolent anti-Hu-associated paraneoplastic sensory neuropathy. Neurology 1994, 44:22582261.

    Google Scholar 

  6. Dalmau J, Graus F, Rosenblum MK, et al.: Anti-Hu-associated paraneoplastic encephalomyelitis/ sensory neuronopathy: a clinical study of 71 patients. Medicine (Baltimore) 1992, 71:5972. Neurologic symptoms preceded discovery of tumor in 83% of patients. Only patients with a prominent component of limbic encephalopathy showed response to immunosuppressive treatment.

    Google Scholar 

  7. Peterson K, Rosenblum MK, Kotanides H, et al.: Paraneoplastic cerebellar degeneration: a clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 1992, 42:19311937. As in other smaller published series, all patients with antiPurkinje cell antibodies were women, most had cerebrospinal fluid abnormalities, and fewer than one third were ambulatory. Tumor or immunosuppressive treatments did not induce major neurologic improvement.

    Google Scholar 

  8. Uchuya M, Graus F, Vega F, et al.: Intravenous immunoglobulin treatment in paraneoplastic neurological syndromes with antineuronal antibodies. J Neurol Neurosurg Psychiatry 1996, 60:388392. Of four patients with paraneoplastic cerebellar degeneratio and 18 patients with paraneoplastic encephalomyelitis who were treated with intravenous immunoglobulin (IVIg), only one patient (with predominant sensory neuronopathy) showed significant neurologic improvement. Several patients stabilized during IVIg treatment; the effect of treatment on the disease course is debatable.

    Google Scholar 

  9. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncologic profiles of patients seropositive for type I antineuronal nuclear autoantibodies. Neurology 1998, 50:652657. Of 49 patients with varying clinical manifestations of paraneoplastic encephalomyelitis, none showed improvement with corticosteroids, plasmapheresis, intravenous immunoglobulin, or cyclophosphamide.

    Google Scholar 

  10. Goldstein JM, Waxman SG, Vollmer TL, et al.: Subacute cerebellar degeneration and Lambert-Eaton myasthenic syndrome associated with antibodies to voltage-gated calcium channels: differential effect of immunosuppressive therapy on central and peripheral defects. J Neurol Neurosurg Psychiatry 1994, 57:11381139.

    Google Scholar 

  11. Alamowitch S, Graus F, Uchuya M, et al.: Limbic encephalitis and small cell lung cancer: clinical and immunological features. Brain 1997, 120:923928.

    Article  Google Scholar 

  12. Antoine JC, Honnorat J, Anterion CT, et al.: Limbic encephalitis and immunological perturbations in two patients with thymoma. J Neurol Neurosurg Psychiatry 1995, 58:706710.

    Article  Google Scholar 

  13. Deodhare S, O’Connor P, Ghazarian D, et al.: Paraneoplastic limbic encephalitis in Hodgkin disease. Can J Neurol Sci 1996, 23:138140.

    Google Scholar 

  14. Anderson NE, Budde-Steffen C, Rosenblum MK, et al.: Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic syndrome. Medicine (Baltimore) 1988, 67:100109.

    Google Scholar 

  15. McEvoy KM, Windebank AJ, Daube JR, et al.: 3,4-diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med 1989, 321:15671571.

    Article  Google Scholar 

  16. Lundh H, Nilsson O, Rosen I, et al.: Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome. Acta Neurol Scand 1993, 88:136140.

    Google Scholar 

  17. Sanders DB: 3,4-diaminopyridine (DAP) in the treatment of Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci 1998, 841:811816. This paper gives a detailed description of a single institution’s experience with 45 patients.

    Article  Google Scholar 

  18. Oh SJ, Kim DS, Head TC, et al.: Low-dose guanidin and pyridostigmine: relatively safe and effective longterm symptomatic therapy in Lambert-Eaton myasthenic syndrome. Muscle Nerve 1997, 20:11461152.

    Google Scholar 

  19. Graus F, Vega F, Delattre JY, et al.: Plasmapheresis and antineoplastic treatment in CNS paraneoplastic syndromes with antineuronal autoantibodies. Neurology 1992, 42:536540.

    Google Scholar 

  20. Oh SJ, Dropcho EJ, Claussen GC: Anti-Hu-associated paraneoplastic sensory neuronopathy responding to early aggressive immunotherapy: report of tw cases and review of the literature. Muscle Nerve 1997, 20:15761582.

    Google Scholar 

  21. Luque A, Furneaux HM, Ferziger R, et al.: Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991, 29:241251.

    Article  Google Scholar 

  22. TelanderRL, Smithson WA, Groover RV: Clinical outcome in children with acute cerebellar encephalopathy and neuroblastoma. J Pediatr Surg 1989, 24:1114. Of 10 children in whom opsoclonus-myoclonus was the presenting feature of neuroblastoma, eight had ganglioneuroblastoma. All the children responded to adrenocorticotropic hormone, but nine had steroidresponsive exacerbations associated with febrile illnesses and all had persistent neurologic sequelae.

    Article  Google Scholar 

  23. Mitchell WG, Snodgrass SR: Opsoclonus-ataxia due to childhood neural crest tumors: a chronic neurologic syndrome. J Child Neurol 1990, 5:153158.

    Google Scholar 

  24. Koh PS, Raffensperger JG, Berry S, et al.: Long-term outcome in children with opsoclonus-myoclonus and ataxia and coincident neuroblastoma. J Pediatr 1994, 125:712716. Each of 10 children had a favorable tumor outcome, but nine children had a relapsing steroid-responsive course and nine had chronic neurologic sequelae.

    Google Scholar 

  25. Newsom-Davis J, Murray NM: Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome. Neurology 1984, 34:480485.

    Google Scholar 

  26. Kissel JT, Levy RJ, Mendell JR, et al.: Azathioprine toxicity in neuromuscular disease. Neurology 1986, 36:3539.

    Google Scholar 

  27. Stark E, Wurster U, Patzold U, et al.: Immunological and clinical response to immunosuppressive treatment in paraneoplastic cerebellar degeneration. Arch Neurol 1995, 52:814818. Two patients with antiPurkinje cell antibodies improved with intermittent intravenous cyclophosphamide.

    Google Scholar 

  28. Dropcho EJ, Kline LB, Riser J: Antineuronal (anti-Ri) antibodies in a patient with steroid-responsive opsoclonus-myoclonus. Neurology 1993, 43:207211.

    Google Scholar 

  29. BainPG, 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, 47:678683. This double-blind, placebo-controlled crossover trial of intravenous immunoglobulin in 10 patients showed temporary clinical improvement and decline in antiP/Q-type voltage-gated calcium channel antibody titers.

    Google Scholar 

  30. Rich MM, Teener JW, Bird SJ: Treatment of Lambert-Eaton syndrome with intravenous immunoglobulin. Muscle Nerve 1997, 20:614615.

    Google Scholar 

  31. Ben David Y, Warner E, Levitan M, et al.: Autoimmune paraneoplastic cerebellar degeneration in ovarian carcinoma patients treated with plasmapheresis and immunoglobulin. Cancer 1996, 78:21532156.

    Google Scholar 

  32. Counsell CE, McLeod M, Grant R: Reversal of subacute paraneoplastic cerebellar syndrome with intravenous immunoglobulin. Neurology 1994, 44:11841185.

    Google Scholar 

  33. Moll JW, Henzen-Logmans SC, Van derMecheFG, et al.: Early diagnosis and intravenous immune globulin therapy in paraneoplastic cerebellar degeneration [letter]. J Neurol Neurosurg Psychiatry 1993, 56:112115.

    Google Scholar 

  34. Brannaga TH, Nagle KJ, Lange DJ, et al.: Complications of intravenous immunoglobulin treatment in neurologic disease. Neurology 1996, 47:674677.

    Google Scholar 

  35. Dalakas MC: Mechanism of action of intravenous immunoglobulin and therapeutic considerations in the treatment of autoimmune neurologic diseases. Neurology 1998, 51(suppl 5):S2S8.

    Google Scholar 

  36. Cocconi G, Ceci G, Juvarra G, et al.: Successful treatment of subacute cerebellar degeneration in ovarian carcinoma with plasmapheresis. Cancer 1985, 56:23182320.

    Article  Google Scholar 

  37. Cher LM, Hochberg FH, Teruya J, et al.: Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption. Cancer 1995, 75:16781683.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, CL 365, Indiana University Medical Center, 46202, Indianapolis, IN, USA

    Edward J. Dropcho MD

Authors
  1. Edward J. Dropcho MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dropcho, E.J. Paraneoplastic diseases of the nervous system. Curr Treat Options Neurol 1, 417–427 (1999). https://doi.org/10.1007/s11940-996-0005-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-996-0005-y

Keywords

Search

Navigation