eMedicine Specialties > Neurology > Neuro-oncology

Paraneoplastic Cerebellar Degeneration: Differential Diagnoses & Workup

Author: Abbas Mehdi, MD, Director, MDA Center of Central California; Consulting Staff, Department of Neurology, California Neurological Center, Inc
Coauthor(s): David Y Ko, MD, Associate Professor, Department of Neurology, University of Southern California Keck School of Medicine
Contributor Information and Disclosures

Updated: Jul 13, 2009

Differential Diagnoses

Acute Disseminated Encephalomyelitis
Intracranial Hemorrhage
Ataxia with Identified Genetic and Biochemical Defects
Lacunar Syndromes
Brainstem Gliomas
Leptomeningeal Carcinomatosis
Cardioembolic Stroke
Meningioma
Cavernous Sinus Syndromes
Multiple Sclerosis
Cerebellar Hemorrhage
Neurosarcoidosis
Cerebral Aneurysms
Olivopontocerebellar Atrophy
Cerebral Venous Thrombosis
Posterior Cerebral Artery Stroke
CNS Melanoma
Primary CNS Lymphoma
Dissection Syndromes
Prion-Related Diseases
Glioblastoma Multiforme

Other Problems to Be Considered

Viral cerebellitis
Vascular disease
Tumor in the brain stem and/or cerebellum
Meningeal carcinomatosis
Acute disseminated encephalomyelitis
Prion disease

Workup

Laboratory Studies

  • Consider a diagnosis of paraneoplastic cerebellar degeneration in patients who present with acute or subacute cerebellar degeneration and no risk factors for cerebellar disorders (eg, stroke, alcoholism, primary or metastatic neoplasms in the cerebellum, treatment with chemotherapeutic agents).
  • Once a diagnosis of paraneoplastic cerebellar degeneration is made, a thorough search for an underlying malignancy is warranted. Analysis of samples of serum and CSF for autoantibodies helps to determine the underlying primary malignancy.
  • Diagnosis and treatment of paraneoplastic cerebellar degeneration is important because the disability caused by the paraneoplastic cerebellar degeneration is severe; correct diagnosis can lead to early discovery of an occult tumor with chances of being cured.

Imaging Studies

  • Magnetic resonance imaging (MRI) findings are normal early in the course of paraneoplastic cerebellar degeneration but can show cerebellar atrophy in advanced cases.
  • MRI of the brain with contrast is recommended to exclude any structural, demyelinating, vascular, or infectious causes. See Media file 2.

    MRI of a 29-year-old female with ARCA1. Sagittal ...

    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.

    [ CLOSE WINDOW ]
    MRI of a 29-year-old female with ARCA1. Sagittal ...

    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.

  • In paraneoplastic cerebellar degeneration with anti-Yo antibodies, perform radiography of the chest, mammography, and CT of the abdomen or chest to identify the primary malignancy.
  • In paraneoplastic cerebellar degeneration with anti-Hu antibodies, perform radiography and CT of the chest to identify a likely small-cell lung cancer. Also investigate other organs where small-cell cancers present, such as the cervix, esophagus, and prostate.

Other Tests

  • In addition to the imaging studies listed above, a thorough gynecologic examination should be performed in patients with paraneoplastic cerebellar degeneration with anti-Yo antibodies to identify the primary malignancy. 
  • CSF samples demonstrate mononuclear pleocytosis, elevated protein levels (immunoglobulin G), and oligoclonal bands. These findings may normalize late in the course of the illness. Evaluate CSF for antineuronal autoantibodies. Anti-Yo and Anti-Tr antibodies have the highest specificity for cerebellar dysfunction.
  • Whole body fluorodeoxyglucose positron emission tomography (FDG-PET) is useful in demonstrating occult neoplasms or small metastatic lesions.


See Media file 1 for an illustration of the workup of paraneoplastic cerebellar degeneration.

Procedures

  • If the initial workup of a patient who has paraneoplastic cerebellar degeneration with anti-Yo antibodies is nonrevealing, the usual next step is a total abdominal hysterectomy and a bilateral salpingo-oophorectomy in postmenopausal women. If histologic examination reveals no malignancy and/or the patients are men or premenopausal women, periodic surveillance is necessary. At times, the primary malignancy is discovered up to 2 years after the initial onset of paraneoplastic cerebellar degeneration.
  • Perform tumor resection.

Histologic Findings

The hallmark of paraneoplastic cerebellar degeneration is severe loss of Purkinje cells diffusely throughout the cerebellar cortex. These cells are completely absent on specimens. Other cell loss is observed but is rare. Occasionally, Purkinje cell loss is patchy. Inflammatory changes are also  observed with lymphocytic infiltration. Atrophy of the granular and molecular layers is demonstrated, with microglial proliferation and astrocytosis but relative sparing of basket cells. The deep cerebellar nuclei and the cerebellar connections to the brain stem are normal. Patients with APCA-1/anti-Yo antibody tend to demonstrate more inflammatory changes and characteristic immunofluorescence patterns with coarse granular staining of Purkinje cell cytoplasm as well as proximal axons and dendrites; nuclei and systemic tissues are not stained. In paraneoplastic cerebellar degeneration associated with anti-Hu, the cortical and cerebellar neuronal nuclei are stained.

More on Paraneoplastic Cerebellar Degeneration

Overview: Paraneoplastic Cerebellar Degeneration
Differential Diagnoses & Workup: Paraneoplastic Cerebellar Degeneration
Treatment & Medication: Paraneoplastic Cerebellar Degeneration
Follow-up: Paraneoplastic Cerebellar Degeneration
Multimedia: Paraneoplastic Cerebellar Degeneration
References
[ CLOSE WINDOW ]

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

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

  7. 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].

  8. 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].

  9. 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].

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

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

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

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

  18. 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].

  19. 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].

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

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

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

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

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

  25. 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].

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

  27. 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].

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

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

  30. 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].

  31. 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].

  32. 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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

paraneoplastic neurologic syndrome, PCD, breast cancer, ovarian cancer, uterine cancer, lung cancer, occult gynecologic cancers, malignancy, paraneoplastic cerebellar degeneration

[ CLOSE WINDOW ]

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, Department of Neurology, University of Southern California Keck School of Medicine
David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Medical Association, and California Medical Association
Disclosure: Pfizer Honoraria Speaking and teaching; UCB Grant/research funds clinical trials; Johnson and Johnson Grant/research funds clinical trials

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
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: Nothing to disclose.

Chief Editor

Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Stephen A Berman, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

RELATED EMEDICINE ARTICLES
 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.