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Overview of cerebellar ataxia in adults

Peter K Todd, MD, PhD
Section Editor
Howard I Hurtig, MD
Deputy Editor
John F Dashe, MD, PhD


Cerebellar ataxia is a common finding in patients seen in neurologic practice and has a wide variety of causes [1]. Although cerebellar degeneration may be chronic and slowly progressive, acute cerebellar swelling due to infarction, edema, or hemorrhage can have rapid and catastrophic effects and is a true neurological emergency. Here we set out to briefly describe the clinical/anatomic correlates of cerebellar disease, to provide a broad differential diagnosis for patients who present with cerebellar ataxia, and to provide a methodological approach to the evaluation of patients with cerebellar signs. A special emphasis is placed on causes of cerebellar ataxia, both acquired and genetic, that are reversible when timely therapy is initiated.


The anatomy of the cerebellum in the posterior fossa of the intracranial cavity is complex, but it can be separated into three major structures:

The midline cerebellum, which includes the cerebellar vermis, the fastigial and interposed (globus and emboliform) nuclei, the vestibulocerebellum (composed of the flocculus and nodulus), and the paravermis/intermediate zone

The two large cerebellar hemispheres, including the dentate nuclei

Cerebellar syndromes can be divided into symptoms arising from damage to the midline structures or hemispheric structures, although there is significant clinical overlap between these syndromes [2].


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Literature review current through: Sep 2016. | This topic last updated: May 6, 2016.
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  1. Timmann D, Diener HC. Coordination and ataxia. In: Textbook of Clinical Neurology, 3rd edition, Goetz C (Ed), Saunders 2007. p.307.
  2. Grimaldi G, Manto M. Topography of cerebellar deficits in humans. Cerebellum 2012; 11:336.
  3. Benini R, Ben Amor IM, Shevell MI. Clinical clues to differentiating inherited and noninherited etiologies of childhood ataxias. J Pediatr 2012; 160:152.
  4. Manto M. Mechanisms of human cerebellar dysmetria: experimental evidence and current conceptual bases. J Neuroeng Rehabil 2009; 6:10.
  5. Liu GT, Volpe NJ, Galetta SL. Eye movement disorders. Curr Opin Ophthalmol 1995; 6:27.
  6. Spencer KA, Slocomb DL. The neural basis of ataxic dysarthria. Cerebellum 2007; 6:58.
  7. Abele M, Bürk K, Schöls L, et al. The aetiology of sporadic adult-onset ataxia. Brain 2002; 125:961.
  8. Cho TA, Schmahmann JD, Cunnane ME. Case records of the Massachusetts General Hospital. Case 30-2013. A 19-year-old man with otalgia, slurred speech, and ataxia. N Engl J Med 2013; 369:1253.
  9. Ravi V, Rozen TD. Acute cerebellitis: MRI findings. Neurology 2000; 54:213.
  10. Sawaishi Y, Takada G. Acute cerebellitis. Cerebellum 2002; 1:223.
  11. Abele M, Weller M, Mescheriakov S, et al. Cerebellar ataxia with glutamic acid decarboxylase autoantibodies. Neurology 1999; 52:857.
  12. Honnorat J, Saiz A, Giometto B, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001; 58:225.
  13. Bayreuther C, Hieronimus S, Ferrari P, et al. Auto-immune cerebellar ataxia with anti-GAD antibodies accompanied by de novo late-onset type 1 diabetes mellitus. Diabetes Metab 2008; 34:386.
  14. Pedroso JL, Braga-Neto P, Dutra LA, Barsottini OG. Cerebellar ataxia associated to anti-glutamic acid decarboxylase autoantibody (anti-GAD): partial improvement with intravenous immunoglobulin therapy. Arq Neuropsiquiatr 2011; 69:993.
  15. Fernandes M, Munhoz RP, Carrilho PE, et al. Neurological disorders associated with glutamic acid decarboxylase antibodies: a Brazilian series. Arq Neuropsiquiatr 2012; 70:657.
  16. Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet 1998; 352:1582.
  17. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 2012; 10:13.
  18. Hadjivassiliou M, Aeschlimann P, Sanders DS, et al. Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 2013; 80:1740.
  19. Hadjivassiliou M, Mäki M, Sanders DS, et al. Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. Neurology 2006; 66:373.
  20. Baizabal-Carvallo JF, Jankovic J. Movement disorders in autoimmune diseases. Mov Disord 2012; 27:935.
  21. Hadjivassiliou M, Grünewald R, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 2003; 126:685.
  22. Hadjivassiliou M, Sanders DS, Grünewald RA, et al. Gluten sensitivity: from gut to brain. Lancet Neurol 2010; 9:318.
  23. Bushara KO, Goebel SU, Shill H, et al. Gluten sensitivity in sporadic and hereditary cerebellar ataxia. Ann Neurol 2001; 49:540.
  24. Hadjivassiliou M, Davies-Jones GA, Sanders DS, Grünewald RA. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry 2003; 74:1221.
  25. Zuliani L, Sabater L, Saiz A, et al. Homer 3 autoimmunity in subacute idiopathic cerebellar ataxia. Neurology 2007; 68:239.
  26. Höftberger R, Sabater L, Ortega A, et al. Patient with homer-3 antibodies and cerebellitis. JAMA Neurol 2013; 70:506.
  27. Becker EB, Zuliani L, Pettingill R, et al. Contactin-associated protein-2 antibodies in non-paraneoplastic cerebellar ataxia. J Neurol Neurosurg Psychiatry 2012; 83:437.
  28. Fritzler MJ, Kerfoot SM, Feasby TE, et al. Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1). J Investig Med 2000; 48:28.
  29. Zochodne DW, Auer R, Fritzler MJ. Longstanding ataxic demyelinating polyneuronopathy with a novel autoantibody. Neurology 2003; 60:127.
  30. Allen RK, Sellars RE, Sandstrom PA. A prospective study of 32 patients with neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20:118.
  31. Meissner W, Tison F. Acquired hepatocerebral degeneration. Handb Clin Neurol 2011; 100:193.
  32. Fernández-Rodriguez R, Contreras A, De Villoria JG, Grandas F. Acquired hepatocerebral degeneration: clinical characteristics and MRI findings. Eur J Neurol 2010; 17:1463.
  33. Ferrara J, Jankovic J. Acquired hepatocerebral degeneration. J Neurol 2009; 256:320.
  34. Winchester S, Singh PK, Mikati MA. Ataxia. Handb Clin Neurol 2013; 112:1213.
  35. Edvardsson B, Persson S. Subclinical hypothyroidism presenting with gait abnormality. Neurologist 2010; 16:115.
  36. Barnard RO, Campbell MJ, McDonald WI. Pathological findings in a case of hypothyroidism with ataxia. J Neurol Neurosurg Psychiatry 1971; 34:755.
  37. Le Ber I, Moreira MC, Rivaud-Péchoux S, et al. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain 2003; 126:2761.
  38. Le Ber I, Bouslam N, Rivaud-Péchoux S, et al. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain 2004; 127:759.
  39. Moreira MC, Klur S, Watanabe M, et al. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 2004; 36:225.
  40. Le Ber I, Dubourg O, Benoist JF, et al. Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1. Neurology 2007; 68:295.
  41. Roy CN, Andrews NC. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum Mol Genet 2001; 10:2181.
  42. Synofzik M, Soehn AS, Gburek-Augustat J, et al. Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum. Orphanet J Rare Dis 2013; 8:41.
  43. Stevens JC, Murphy SM, Davagnanam I, et al. The ARSACS phenotype can include supranuclear gaze palsy and skin lipofuscin deposits. J Neurol Neurosurg Psychiatry 2013; 84:114.
  44. de Bot ST, Willemsen MA, Vermeer S, et al. Reviewing the genetic causes of spastic-ataxias. Neurology 2012; 79:1507.
  45. Pilliod J, Moutton S, Lavie J, et al. New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. Ann Neurol 2015; 78:871.
  46. Gerwig M, Krüger S, Kreuz FR, et al. Characteristic MRI and funduscopic findings help diagnose ARSACS outside Quebec. Neurology 2010; 75:2133.
  47. Gazulla J, Benavente I, Vela AC, et al. New findings in the ataxia of Charlevoix-Saguenay. J Neurol 2012; 259:869.
  48. Prodi E, Grisoli M, Panzeri M, et al. Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series. Eur J Neurol 2013; 20:138.
  49. Dupré N, Gros-Louis F, Chrestian N, et al. Clinical and genetic study of autosomal recessive cerebellar ataxia type 1. Ann Neurol 2007; 62:93.
  50. Gros-Louis F, Dupré N, Dion P, et al. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat Genet 2007; 39:80.
  51. Synofzik M, Smets K, Mallaret M, et al. SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. Brain 2016; 139:1378.
  52. Dupré N, Gros-Louis F, Bouchard JP, et al. SYNE1-related autosomal recessive cerebellar ataxia. GeneReviews [internet]. www.ncbi.nlm.nih.gov/books/NBK1379/ (Accessed on July 26, 2013).
  53. Renaud M, Anheim M, Kamsteeg EJ, et al. Autosomal recessive cerebellar ataxia type 3 due to ANO10 mutations: delineation and genotype-phenotype correlation study. JAMA Neurol 2014; 71:1305.
  54. Vermeer S, Hoischen A, Meijer RP, et al. Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10 mutations in patients with autosomal-recessive cerebellar ataxia. Am J Hum Genet 2010; 87:813.
  55. Chamova T, Florez L, Guergueltcheva V, et al. ANO10 c.1150_1151del is a founder mutation causing autosomal recessive cerebellar ataxia in Roma/Gypsies. J Neurol 2012; 259:906.
  56. Migliaccio AA, Halmagyi GM, McGarvie LA, Cremer PD. Cerebellar ataxia with bilateral vestibulopathy: description of a syndrome and its characteristic clinical sign. Brain 2004; 127:280.
  57. Szmulewicz DJ, Waterston JA, Halmagyi GM, et al. Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome. Neurology 2011; 76:1903.
  58. Szmulewicz DJ, Waterston JA, MacDougall HG, et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis. Ann N Y Acad Sci 2011; 1233:139.
  59. Wu TY, Taylor JM, Kilfoyle DH, et al. Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome. Brain 2014; 137:2649.
  60. Szmulewicz DJ, Seiderer L, Halmagyi GM, et al. Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome. Muscle Nerve 2015; 51:600.
  61. Szmulewicz DJ, McLean CA, Rodriguez ML, et al. Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS. Neurology 2014; 82:1410.
  62. Zeviani M, Simonati A, Bindoff LA. Ataxia in mitochondrial disorders. Handb Clin Neurol 2012; 103:359.
  63. Finsterer J. Mitochondrial ataxias. Can J Neurol Sci 2009; 36:543.
  64. Chinnery PF. Mitochondrial disorders overview. GeneReviews [Internet]. www.ncbi.nlm.nih.gov/books/NBK1224/ (Accessed on August 01, 2013).
  65. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71:670.
  66. Németh AH, Kwasniewska AC, Lise S, et al. Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model. Brain 2013; 136:3106.
  67. Fogel BL, Lee H, Deignan JL, et al. Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. JAMA Neurol 2014; 71:1237.