Paraneoplastic Cerebellar Degeneration Treatment & Management

  • Author: Abbas Mehdi, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA   more...
 
Updated: Feb 3, 2012
 

Medical Care

Two approaches can be used to treat paraneoplastic neurologic syndrome. The first treatment is directed toward the underlying tumor, while the second approach is toward the autoimmune disease causing the cerebellar dysfunction.

Since neurologic paraneoplastic syndromes are immune-mediated, 2 distinct approaches to therapy have been reported: removal of the antigen source by treatment of the underlying tumors and suppression of the immune response. Immunosuppression can be beneficial for some conditions.[23]

  • Paraneoplastic syndromes are a therapeutic challenge for the neurologist, and treatment of paraneoplastic syndromes is generally unsatisfactory.
  • Early tumor detection and treatment should be the primary objective in these patients.
  • The response of the paraneoplastic neurologic syndromes to immunosuppressive agents or antitumor treatment is influenced greatly by the underlying neuropathology.
    • The effect of the combination of intravenous immunoglobulins (IVIG), cyclophosphamide, and methylprednisolone on the clinical course of patients with paraneoplastic neurologic syndrome or paraneoplastic cerebellar degeneration and antineuronal antibodies is unsatisfactory.
    • Some reports indicate partial or complete remission of cerebellar symptoms after treating the primary neoplasm. This has been observed only in small-cell carcinomas and is not reported in gynecologic malignancies.
    • In a minority of patients who are not disabled severely at the onset of treatment, a transient stabilization is possible and deserves further evaluation.
Next

Surgical Care

Surgical care is required for patients who undergo tumor resection.

Previous
Next

Consultations

A team approach is required in treating patients with paraneoplastic cerebellar degeneration.

  • Neurologic consultation is needed for basic workup and to exclude other possible causes of cerebellar dysfunction.
  • Oncology consultation is needed for tumor workup and treatment protocols.
  • Surgical consultation is needed in patients for whom tumor resection is recommended.
Previous
Next

Diet

The patient may require nutritional support in severe cases of nausea and vomiting.

Previous
Next

Activity

Bed rest is usual because patients with severe cerebellar dysfunction are at high risk of falls.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Abbas Mehdi, MD  Director, MDA Center of Central California; Consulting Staff, Department of Neurology, California Neurological Center, Inc

Abbas Mehdi, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

David Y Ko, MD  Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of Southern California

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Headache Society

Disclosure: GSK Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Lundbeck Consulting fee Consulting; Westward Consulting fee Consulting

Specialty Editor Board

Frederick M Vincent Sr, MD  Clinical Professor, Department of Neurology and Ophthalmology, Michigan State University Colleges of Human and Osteopathic Medicine

Frederick M Vincent Sr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American College of Forensic Examiners, American College of Legal Medicine, American College of Physicians, and Michigan State Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jorge C Kattah, MD  Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and New York Academy of Sciences

Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Stephen A Berman, MD, PhD, MBA  Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

References

  1. Lorusso L, Hart IK, Giometto B, et al. Immunological features of neurological paraneoplastic syndromes. Int J Immunopathol Pharmacol. May-Aug 2004;17(2):135-44. [Medline].

  2. BRAIN WR, DANIEL PM, GREENFIELD JG. Subacute cortical cerebellar degeneration and its relation to carcinoma. J Neurol Neurosurg Psychiatry. May 1951;14(2):59-75. [Medline].

  3. Posner JB. Paraneoplastic cerebellar degeneration. Can J Neurol Sci. May 1993;20 Suppl 3:S117-22. [Medline].

  4. Inuzuka T. Autoantibodies in paraneoplastic neurological syndrome. Am J Med Sci. Apr 2000;319(4):217-26. [Medline].

  5. Vernino S. Paraneoplastic cerebellar degeneration. Handb Clin Neurol. 2012;103:215-23. [Medline].

  6. Bolla L, Palmer RM. Paraneoplastic cerebellar degeneration. Case report and literature review. Arch Intern Med. Jun 9 1997;157(11):1258-62. [Medline].

  7. Nath U, Grant R. Neurological paraneoplastic syndromes. J Clin Pathol. Dec 1997;50(12):975-80. [Medline].

  8. 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. Jan 2000;47(1):9-17. [Medline].

  9. 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. Aug 15 1999;13(16):2087-97. [Medline].

  10. Rojas I, Graus F, Keime-Guibert F, et al. Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology. Sep 12 2000;55(5):713-5. [Medline].

  11. Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. Apr 1998;121 ( Pt 4):561-79. [Medline].

  12. Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology. Oct 1992;42(10):1931-7. [Medline].

  13. Finsterer J, Voigtländer T, Grisold W. Deterioration of anti-Yo-associated paraneoplastic cerebellar degeneration. J Neurol Sci. Sep 15 2011;308(1-2):139-41. [Medline].

  14. Tanaka M, Tanaka K, Shinozawa K, et al. Cytotoxic T cells react with recombinant Yo protein from a patient with paraneoplastic cerebellar degeneration and anti-Yo antibody. J Neurol Sci. Nov 26 1998;161(1):88-90. [Medline].

  15. Greenlee JE, Brashear HR. Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol. Dec 1983;14(6):609-13. [Medline].

  16. Jaeckle KA, Graus F, Houghton A. Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen. Ann Neurol. Nov 1985;18(5):592-600. [Medline].

  17. Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Valldeoriola F. Small-cell lung cancer, paraneoplastic cerebellar degeneration and the Lambert-Eaton myasthenic syndrome. Brain. Aug 1997;120 ( Pt 8):1279-300. [Medline].

  18. Wilkinson PC, Zeromski J. Immunofluorescent detection of antibodies against neurones in sensory carcinomatous neuropathy. Brain. Sep 1965;88(3):529-83. [Medline].

  19. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. Apr 1985;35(4):538-43. [Medline].

  20. Graus F, Elkon KB, Cordon-Cardo C, Posner JB. Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor. Am J Med. Jan 1986;80(1):45-52. [Medline].

  21. Mancuso M, Orsucci D, Bacci A, Caldarazzo Ienco E, Siciliano G. Anti-Ri-associated paraneoplastic cerebellar degeneration. Report of a case and revision of the literature. Arch Ital Biol. Sep 2011;149(3):318-22. [Medline].

  22. Dalmau J, Gonzalez RG, Lerwill MF. Case records of the Massachusetts General Hospital. Case 4-2007. A 56-year-old woman with rapidly progressive vertigo and ataxia. N Engl J Med. Feb 8 2007;356(6):612-20. [Medline].

  23. Rosenfeld MR, Dalmau J. Current Therapies for Paraneoplastic Neurologic Syndromes. Curr Treat Options Neurol. Jan 2003;5(1):69-77. [Medline].

  24. Bataller L, Dalmau J. Paraneoplastic neurologic syndromes: approaches to diagnosis and treatment. Semin Neurol. Jun 2003;23(2):215-24. [Medline].

  25. Dalmau JO, Posner JB. Paraneoplastic syndromes. Arch Neurol. Apr 1999;56(4):405-8. [Medline].

  26. Darnell RB. The importance of defining the paraneoplastic neurologic disorders. N Engl J Med. Jun 10 1999;340(23):1831-3. [Medline].

  27. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. Oct 16 2003;349(16):1543-54. [Medline].

  28. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. Aug 2004;75(8):1135-40. [Medline].

  29. Greenlee JE. Cytotoxic T cells in paraneoplastic cerebellar degeneration. Ann Neurol. Jan 2000;47(1):4-5. [Medline].

  30. Greenlee JE, Brashear HR, Jaeckle KA, et al. Pursuing an occult carcinoma in a patient with subacute cerebellar degeneration and anticerebellar antibodies. Need for vigorous follow-up. West J Med. Feb 1992;156(2):199-202. [Medline].

  31. Jaeckle KA. Paraneoplastic nervous system syndromes. Curr Opin Oncol. May 1996;8(3):204-8. [Medline].

  32. Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. Nov 2004;56(5):715-9. [Medline].

  33. Rousseau A, Benyahia B, Dalmau J, Connan F, Guillet JG, Delattre JY, et al. T cell response to Hu-D peptides in patients with anti-Hu syndrome. J Neurooncol. Feb 2005;71(3):231-6. [Medline].

  34. Sommer C, Weishaupt A, Brinkhoff J, Biko L, Wessig C, Gold R. Paraneoplastic stiff-person syndrome: passive transfer to rats by means of IgG antibodies to amphiphysin. Lancet. Apr 16-22 2005;365(9468):1406-11. [Medline].

  35. Voltz RD, Posner JB, Dalmau J, Graus F. Paraneoplastic encephalomyelitis: an update of the effects of the anti- Hu immune response on the nervous system and tumour. J Neurol Neurosurg Psychiatry. Aug 1997;63(2):133-6. [Medline].

 
Previous
Next
 
The workup of paraneoplastic cerebellar degeneration.
MRI of a 29-year-old female with ARCA1. Sagittal T1 shows marked diffuse cerebellar atrophy with no atrophy of the cerebral cortex, midbrain, pons, or medulla. Image from National Institutes of Health.
Table. Antibodies Associated With Paraneoplastic Cerebellar Degeneration* (Adapted from Dalmau et al[22] )
Antibodies Predominantly Associated With PCDPredominant SyndromeAssociated Cancer
Anti-Yo (PCA-1) antibodiesPCDOvarian



Breast cancers



Anti-Tr antibodiesPCDHodgkin's lymphoma
Anti-mGluR1 antibodies**PCDHodgkin's lymphoma
Anti-Zic4 antibodies†PCDSmall-cell lung cancer
Sometimes Associated With PCD
Anti-VGCC antibodiesEaton-Lambert syndrome, PCDSmall-cell lung cancer



Lymphoma



Anti-Hu (ANNA-1) antibodiesEncephalomyelitis, PCD, sensory neuronopathySmall-cell lung cancer



Other cancers



Anti-Ri (ANNA-2) antibodiesPCD, brain-stem encephalitis, paraneoplastic opsoclonus-myoclonusBreast cancer



Gynecologic cancer



Small-cell lung cancer



Anti-CV2/CRMPS antibodiesEncephalomyelitis, PCD, chorea, peripheral neuropathy, uveitisSmall-cell lung cancer



Thymoma



Other cancers



Anti-Ma protein antibodies‡Limbic, hypothalamic, brain-stem encephalitis (infrequently PCD)Testicular cancer



Lung cancer



Other cancers



Anti-amphiphysin antibodiesStiff-person syndrome, encephalomyelitis, PCDBreast cancer



Small-cell lung cancer



*There is no uniform nomenclature for some of these antibodies; variant names appear in parentheses. mGluR1: metabotropic glutamate receptor 1, Zic4: zing finger of the cerebellum 4, and VCGG: voltage-gated calcium channel.



**Anti-mGluR1 antibodies have been identified in only 2 patients.



† Anti-Zic4 antibodies are predominantly associated with PCD only when no other paraneoplastic antibodies are detectable.



‡Ma proteins include Ma1 and Ma2. Patients with brain-stem and cerebellar dysfunction usually have antibodies against both MA1 and Ma2.



Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.