Diagnosis of Neoplastic and Paraneoplastic Cerebellar Ataxia

Reference work entry

Abstract

Acquired cerebellar ataxia encompasses various diseases. Neoplastic causes have specific characteristics. First, because of the limited space in the posterior fossa, these tumors are considered as critical brain lesions. Clinically, patients with cerebellar tumors frequently present with signs of intracranial pressure, such as headache, vomiting, or decreased level of consciousness. Second, the incidence and the type of cerebellar tumors vary considerably with age. Pilocytic astrocytomas and medulloblastoma are common cerebellar neoplasms in children. Conversely, the most frequent cerebellar tumors in adults are metastases. However, in a context of a systemic cancer and in absence of brain metastase, paraneoplastic cerebellar ataxia (PCA) must be considered. In the past 20 years, several antibodies directed against neuronal and tumoral antigens have been described in association with PCA, leading to the description of different subtypes of PCA based on the associated antibodies, the clinical evolution, and the type of associated tumor. The purpose of this chapter is to present the main etiologies of neoplastic and paraneoplastic causes of acute cerebellar ataxia in children and adults.

Keywords

Apparent Diffusion Coefficient Cerebellar Ataxia Primary Central Nervous System Lymphoma Pilocytic Astrocytoma Paraneoplastic Neurological Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Akimoto J, Fukami S, Tsutsumi M, Hashimoto T, Miki T, Haraoka J, Kudo M (2009) Radiopathological characteristics of cerebellar malignant glioma in adults. Brain Tumor Pathol 26:59–68PubMedCrossRefGoogle Scholar
  2. Antoine JC, Honnorat J, Koenig F, Aguera M, Belin MF, Michel D (1993) Posterior uvéitis and paraneoplastic encephalomyelitis with auto-antibodies reacting against cytoplasmic proteins of brain and retina. J Neurol Sci 117:215–223PubMedCrossRefGoogle Scholar
  3. Antoine JC, Absi L, Honnorat J, Boulesteix JM, De Brouker Th, Vial C et al (1999) Anti-amphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumours. Arch Neurol 56:172–177PubMedCrossRefGoogle Scholar
  4. Arai K, Sato N, Aoki J, Yagi A, Taketomi-Takahashi A, Morita H, Koyama Y, Oba H, Ishiuchi S, Saito N, Endo K (2006) MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images: is it useful for differentiation from medulloblastoma? Neuroradiology 48:233–237PubMedCrossRefGoogle Scholar
  5. Balegno S, Ceroni M, Corato M, Franciotta D, Giometto B, Marinu-Aktipu K et al (2005) Antibodies to cerebellar nerve fibres in two patients with paraneoplastic cerebellar ataxia. Anticancer Res 25:3211–324PubMedGoogle Scholar
  6. Bataller L, Wade DF, Graus F, Stacey HD, Rosenfeld MR, Dalmau J (2004) Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer. Neurology 62:778–782PubMedCrossRefGoogle Scholar
  7. Bernal F, Shams’ili S, Rojas I, Sanchez-Valle R, Saiz A, Dalmau J et al (2003) Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin’s disease. Neurology 60:230–234PubMedCrossRefGoogle Scholar
  8. Bonneville F, Savatovsky J, Chiras J (2007a) Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions. Eur Radiol 17:2472–2482PubMedCrossRefGoogle Scholar
  9. Bonneville F, Savatovsky J, Chiras J (2007b) Imaging of cerebellopontine angle lesions: an update. Part 2: intra-axial lesions, skull base lesions that may invade the CPA region, and non-enhancing extra-axial lesions. Eur Radiol 17:2908–2920PubMedCrossRefGoogle Scholar
  10. Brain WR, Daniel PM, Greenfield JG (1951) Subacute cortical cerebellar degeneration and its relation to carcinoma. J Neurol Neurosurg Psychiatry 14:59–75PubMedCrossRefGoogle Scholar
  11. Brieva-Ruíz L, Diaz-Hurtado M, Matias-Guiu X, Márquez-Medina D, Tarragona J, Graus F (2008) Anti-Ri-associated paraneoplastic cerebellar degeneration and breast cancer: an autopsy case study. Clin Neurol Neurosurg 110:1044–1046PubMedCrossRefGoogle Scholar
  12. Brouwer B (1919) Beitrag zur kenntnis der chronischen diffusen kleinhirnerkranghkungen. Neurol Centralbl 38:674–682Google Scholar
  13. Chamberlain MC, Glantz M, Groves MD, Wilson WH (2009) Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk, and determining benefit of treatment. Semin Oncol 36:S35–45PubMedCrossRefGoogle Scholar
  14. Clouston PD, Saper CB, Arbizu T, Johnston I, Lang B, Newsom-Davis J et al (1992) Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome. Neurology 42:1944–1950PubMedCrossRefGoogle Scholar
  15. Crawford JR, MacDonald TJ, Packer RJ (2007) Medulloblastoma in childhood: new biological advances. Lancet Neurol 6:1073–1085PubMedCrossRefGoogle Scholar
  16. Dalmau J, Rosenfeld MR (2008) Paraneoplastic syndromes of the CNS. Lancet Neurol 7:327–340PubMedCrossRefGoogle Scholar
  17. Dalmau J, Graus F, Rosenblum MK, Posner JB (1992) Anti-Hu associated paraneoplastic encephalomyelitis/sensory neuropathy. Medicine 71:59–72PubMedCrossRefGoogle Scholar
  18. Dalmau JO, Gultekin SH, Voltz R, Hoard R, Deschamps T, Balmaceda C et al (1999) Ma1, a novel neuron-and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. Brain 122:27–39PubMedCrossRefGoogle Scholar
  19. Djalilian HR, Hall WA (1998) Malignant gliomas of the cerebellum: an analytic review. J Neurooncol 36:247–257PubMedCrossRefGoogle Scholar
  20. Eran A, Ozturk A, Aygun N, Izbudak I (2010) Medulloblastoma: atypical CT and MRI findings in children. Pediatr Radiol 40:1254–1262PubMedCrossRefGoogle Scholar
  21. Esposito M, Penza P, Orefice G, Pagano A, Parente E, Abbadessa A, Bonavita V (2008) Successful treatment of paraneoplastic cerebellar degeneration with Rituximab. J Neurooncol 86:363–364PubMedCrossRefGoogle Scholar
  22. Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell’Oro S, Zucca E, Cavalli F (2003) Prognostic scoring system for primary CNS lymphomas: the international extranodal lymphoma study group experience. J Clin Oncol 21:266–272PubMedCrossRefGoogle Scholar
  23. Giometto B, Grisold W, Vitaliani R, Graus F, Honnorat J, Bertolini G, PNS Euronetwork (2010) Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol 67:330–335PubMedCrossRefGoogle Scholar
  24. Graus F, Cordon-Cardo C, Posner JB (1985) Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology 35:538–543PubMedCrossRefGoogle Scholar
  25. Graus F, Dalmau J, Valldeoriola F, Ferrer I, René R, Marin C, Arbizu T, Targa C, Moll JWB (1997) Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin’s disease. J Neuroimmunol 74:55–61PubMedCrossRefGoogle Scholar
  26. Graus F, Lang B, Pozo-Rosich P, Saiz A, Casamitjana R, Vincent A (2002) P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 59:764–766PubMedCrossRefGoogle Scholar
  27. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W et al (2004) Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 75:1135–1140PubMedCrossRefGoogle Scholar
  28. Graus F, Saiz A, Dalmau J (2010) Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 257:509–517PubMedCrossRefGoogle Scholar
  29. Greenlee JE, Brashear HR (1983) Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma. Ann Neurol 14:609–613PubMedCrossRefGoogle Scholar
  30. Hammack J, Kotanides H, Rosenblum MK, Posner JB (1992) Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin’s disease. Neurology 42:1938–1943PubMedCrossRefGoogle Scholar
  31. Honnorat J, Antoine JC, Derrington E, Aguera M, Belin MF (1996) Antibodies to a subpopulation of glial cells and a 66 kD developmental protein in patients with paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry 61:270–278PubMedCrossRefGoogle Scholar
  32. Honnorat J, Guillon B, De Ferron E, Aguera M, Antoine JC, Dalmau J (1997) Association of anti-Neural autoantibodies in a patient with paraneoplastic cerebellar syndrome and small cell lung carcinoma. J Neurol Neurosurg Psychiatry 62:425–426PubMedCrossRefGoogle Scholar
  33. Honnorat J, Cartalat-Carel S, Ricard D et al (2009) Onco-neural antibodies and tumour type determine survival and neurological syndromes with Hu or CV2/CRMP5 antibodies. J Neurol Neurosug Psychiatry 80:412–416CrossRefGoogle Scholar
  34. Koeller KK, Rushing EJ (2003) From the archives of the AFIP: medulloblastoma: a comprehensive review with radiologic-pathologic correlation. Radiographics 23:1613–1637PubMedCrossRefGoogle Scholar
  35. Küker W, Nägele T, Korfel A, Heckl S, Thiel E, Bamberg M, Weller M, Herrlinger U (2005) Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. Neurooncol 72:169–177CrossRefGoogle Scholar
  36. Lennon VA, Kryzer TJ, Griesmann GE, O’Suilleabhain PE, Windebank AJ, Woppmann A et al (1995) Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 332:1467–1474PubMedCrossRefGoogle Scholar
  37. Luque FA, Furneaux HM, Ferziger R, Rosenblum MK, Wray SH, Schold SC et al (1991) Anti-Ri: an autoantibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 29:241–251PubMedCrossRefGoogle Scholar
  38. Malamud N (1957) Atlas of neuropathology. University of California Press, Berkeley, p 118Google Scholar
  39. Marignier R, Chenevier F, Rogemond V, Sillevis Smitt P, Renoux C, Cavillon G et al (2010) Metabotropic glutamate receptor type 1 autoantibody-associated cerebellitis: a primary autoimmune disease? Arch Neurol 67:627–630PubMedCrossRefGoogle Scholar
  40. Mason WP, Graus F, Lang B, Honnorat J, Delattre JY, Vallderiola F et al (1997) Paraneoplastic cerebellar degeneration and small cell lung cancer. Brain 120:1279–1300PubMedCrossRefGoogle Scholar
  41. Menon G, Krishnakumar K, Nair S (2008) Adult medulloblastoma: clinical profile and treatment results of 18 patients. J Clin Neurosci 15:122–126PubMedCrossRefGoogle Scholar
  42. Motomura M, Lang B, Johnston I, Palace J, Vincent A, Newsom-Davis J (1997) Incidence of serum anti-P/O-type and anti-N-type calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. J Neurol Sci 147:35–42PubMedCrossRefGoogle Scholar
  43. Omuro AM, Leite CC, Mokhtari K, Delattre JY (2006) Pitfalls in the diagnosis of brain tumours. Lancet Neurol 5:937–948PubMedCrossRefGoogle Scholar
  44. Peterson K, Rosenblum MK, Kotanides H, Posner JB (1992) Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology 42:1931–1937PubMedCrossRefGoogle Scholar
  45. Phuphanich S, Brock C (2007) Neurologic improvement after high-dose intravenous immunoglobulin therapy in patients with paraneoplastic cerebellar degeneration associated with anti-Purkinje cell antibody. J Neurooncol 81:67–69PubMedCrossRefGoogle Scholar
  46. Pompili A, Carapella CM, Cattani F, Fabi A, Giannarelli D, Giovannetti M, Mirri A, Occhipinti E, Telera S, Vidiri A, Pace A (2008) Metastases to the cerebellum. Results and prognostic factors in a consecutive series of 44 operated patients. J Neurooncol 88:331–337PubMedCrossRefGoogle Scholar
  47. Psimaras D, Carpentier AF, Rossi C (2010) PNS Euronetwork. Cerebrospinal fluid study in paraneoplastic syndromes. J Neurol Neurosurg Psychiatry 81:42–45PubMedCrossRefGoogle Scholar
  48. Qaddoumi I, Sultan I, Gajjar A (2009) Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the surveillance, epidemiology, and end results database. Cancer 115:5761–5770PubMedCrossRefGoogle Scholar
  49. Rogemond V, Honnorat J (2000) Anti-CV2 autoantibodies and paraneoplastic neurological syndromes. Clin Rev Allergy Immunol 19:48–57CrossRefGoogle Scholar
  50. Rojas I, Graus F, Keime-Guibert F, René R, Delattre JY, Ramon JM et al (2000) Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 55:713–715PubMedCrossRefGoogle Scholar
  51. Rumboldt Z, Camacho DL, Lake D, Welsh CT, Castillo M (2006) Apparent diffusion coefficients for differentiation of cerebellar tumors in children. AJNR Am J Neuroradiol 27:1362–1369PubMedGoogle Scholar
  52. Sabater L, Bataller L, Carpentier AF, Aguirre-Cruz ML, Saiz A, Benyahia B et al (2006) Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer. J Neurol Neurosurg Psychiatry 77:1359–1362PubMedCrossRefGoogle Scholar
  53. Sabater L, Bataller L, Suárez-Calvet M, Saiz A, Dalmau J, Graus F (2008) ZIC antibodies in paraneoplastic cerebellar degeneration and small cell lung cancer. J Neuroimmunol 201–202:163–165PubMedCrossRefGoogle Scholar
  54. Seok HY, Eun MY, Yoo JK, Jung KY (2011) Neoplastic meningitis presenting with acute cerebellar ataxia. J Clin Neurosci 18:441–442PubMedCrossRefGoogle Scholar
  55. Shams’ili S, Grefkens J, de Leeuw B, van den Bent M, Hooijkaas H, van der Holt B et al (2003) Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain 126:1409–1418PubMedCrossRefGoogle Scholar
  56. Sievert AJ, Fisher MJ (2009) Pediatric low-grade gliomas. J Child Neurol 24:1397–408PubMedCrossRefGoogle Scholar
  57. Sillevis-Smitt P, Kinoshita A, De Leeuw B, Moll W, Coesmans M, Jaarsma D et al (2000) Paraneoplastic cerebellar ataxia due to autoantibodies against a glutamate receptor. New Engl J Med 342:21–27PubMedCrossRefGoogle Scholar
  58. Slater A, Moore NR, Huson SM (2003) The natural history of cerebellar hemangioblastomas in von Hippel-Lindau disease. AJNR Am J Neuroradiol 24:1570–1574PubMedGoogle Scholar
  59. Stark AM, Maslehaty H, Hugo HH, Mahvash M, Mehdorn HM (2010) Glioblastoma of the cerebellum and brainstem. J Clin Neurosci 17:1248–1251PubMedCrossRefGoogle Scholar
  60. Thöne J, Hohaus A, Lamprecht S, Bickel A, Erbguth F (2008) Effective immunosuppressant therapy with cyclophosphamide and corticosteroids in paraneoplastic cerebellar degeneration. J Neurol Sci 272:171–173PubMedCrossRefGoogle Scholar
  61. Trasimeni G, Lenzi J, Di Biasi C, Anichini G, Salvati M, Raco A (2008) Midline medulloblastoma versus astrocytoma: the position of the superior medullary velum as a sign for diagnosis. Childs Nerv Syst 24:1037–1041PubMedCrossRefGoogle Scholar
  62. Villarejo F, de Diego JM, de la Riva AG (2008) Prognosis of cerebellar astrocytomas in children. Childs Nerv Syst 24:203–210PubMedCrossRefGoogle Scholar
  63. Voltz RD, Posner JB, Dalmau J, Graus F (1997) Paraneoplastic encephalomyelitis: an update of the effects of the anti-Hu immune response on the nervous system and tumour. J Neurol Neurosurg Psychiatry 63:133–136PubMedCrossRefGoogle Scholar
  64. Weber DC, Miller RC, Villà S, Hanssens P, Baumert BG, Castadot P, Varlet P, Abacioglu U, Igdem S, Szutowicz E, Nishioka H, Hofer S, Rutz HP, Ozsahin M, Taghian A, Mirimanoff RO (2006) Outcome and prognostic factors in cerebellar glioblastoma multiforme in adults: a retrospective study from the Rare Cancer Network. Int J Radiat Oncol Biol Phys 66(1):179–186PubMedCrossRefGoogle Scholar
  65. Yoshida S, Takahashi H (2009) Cerebellar metastases in patients with cancer. Surg Neurol 71:184–187PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Centre de Référence, de Diagnostic et de Traitement des Syndromes Neurologiques ParanéoplasiquesHospices Civils de LyonLyonFrance
  2. 2.Université Claude Bernard Lyon 1LyonFrance
  3. 3.Neuro–OncologieHôpital NeurologiqueBRON CedexFrance

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