The Cerebellum

, 7:494 | Cite as

Gluten ataxia

  • Marios Hadjivassiliou
  • David S. Sanders
  • Nicola Woodroofe
  • Claire Williamson
  • Richard A. Grünewald
Invited Review

Abstract

Gluten ataxia is an immune-mediated disease triggered by the ingestion of gluten in genetically susceptible individuals. It should be considered in the differential diagnosis of all patients with idiopathic sporadic ataxia. Early diagnosis and treatment with a gluten free diet can improve ataxia and prevent its progression. Readily available and sensitive markers of gluten ataxia include antigliadin antibodies. IgA deposits against TG2 in the small bowel and at extraintestinal sites are proving to be additional reliable and perhaps more specific markers of the whole spectrum of gluten sensitivity. They may also hold the key to its pathogenesis.

Key words

Gluten ataxia cerebellum 

References

  1. 1.
    Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, Davies-Jones GAB, Gibson A, Jarratt JA, et al. Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia. Lancet. 1998;352:1582–85.PubMedCrossRefGoogle Scholar
  2. 2.
    Hadjivassiliou M, Grünewald RA, Sharrack B, Sanders D, Lobo A, Wood N, et al. Gluten ataxia in perspective: Epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003;126:685–91.PubMedCrossRefGoogle Scholar
  3. 3.
    Abele M, Schols L, Schwartz S, Klockgether T. Prevalence of antigliadin antibodies in ataxia patients. Neurology. 2003;60:1674–5.PubMedGoogle Scholar
  4. 4.
    Bushara KO, Nance M, Gomez C. Antigliadin antibodies in Huntington’s disease. Neurology. 2004;62:132–3.PubMedGoogle Scholar
  5. 5.
    Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M. Gluten sensitivity in sporadic and hereditary ataxia. Ann Neurol. 2001;49:540–43.PubMedCrossRefGoogle Scholar
  6. 6.
    Sanders DS, Patel D, Stephenson TJ, Milford-Ward A, McCloskey EV, Hadjivassilou M, et al. A primary care crosssectional study of undiagnosed adult coeliac disease. Eur J Gastro Hep. 2003;15:407–13.CrossRefGoogle Scholar
  7. 7.
    Pereira AC, Edwards MJ, Buttery PC, Hawkes CH, Quinn NP, Giovannoni G, et al. Choreic syndrome and coeliac disease: A hitherto unrecognised association. Mov Disord. 2004;19:478–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Deconinck N, Scaillon M, Segers V, Groswasser JJ, Dan B. Opsoclonus-myoclonus associated with celiac disease. Pediatr Neurol. 2006;34:312–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Hadjivassiliou M, Grünewald RAG, Lawden M, Davies-Jones GAB, Powell T, Smith CML. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology. 2001;56:385–8.PubMedGoogle Scholar
  10. 10.
    Wilkinson ID, Hadjivassiliou M, Dickson JM, Wallis L, Grunewald RA, Coley SC, et al. Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia. J Neurol Neurosurg Psychiatry. 2005;76:1011–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Cooke WT, Thomas-Smith W. Neurological disorders associated with adult coeliac disease. Brain. 1966;89:683–722.PubMedCrossRefGoogle Scholar
  12. 12.
    Hadjivassiliou M, Boscolo S, Davies-Jones A, Grunewald R, Not T, Sanders D, et al. The humoral response in the pathogenesis of gluten ataxia. Neurology. 2002;58:1221–6.PubMedGoogle Scholar
  13. 13.
    Hadjivassiliou M, Williamson CA, Woodroofe N. The immunology of gluten sensitivity: Beyond the gut. Trends Immunol. 2004;25:278–82.CrossRefGoogle Scholar
  14. 14.
    Ward ME, Murphy JT, Greenberg GR. Coeliac disease and spinocerebellar degeneration with normal vitamin E status. Neurology. 1985;35:1199–1201.PubMedGoogle Scholar
  15. 15.
    Kaplan JG, Pack D, Horoupian D, DeSouza T, Brin M, Schaumburg H. Distal axonopathy associated with chronic gluten enteropathy: A treatable disorder. Neurology. 1988;38:642–5.PubMedGoogle Scholar
  16. 16.
    Bhatia KP, Brown P, Gregory R, Lennox GG, Manji H, Thompson PD, et al. Progressive myoclonic ataxia associated with coeliac disease: The myoclonus is of cortical origin, but the pathology is in the cerebellum. Brain. 1995;118:1087–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Pellecchia MT, Scala R, Perretti A, De Michelle G, Santoro L, Filla A, et al. Cerebellar ataxia associated with subclinical celiac disease responding to gluten-free diet. Neurology. 1999;53:1606–07.PubMedGoogle Scholar
  18. 18.
    Bürk K, Melms A, Schulz JB, Dichgans J. Effectiveness of intravenous immunoglobulin therapy in cerebellar ataxia associated with gluten sensitivity. Ann Neurol. 2001;50:827–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Hadjivassiliou M, Davies-Jones GAB, Sanders DS, Grünewald RAG. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry. 2003;74:1221–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 1997;7:797–801.CrossRefGoogle Scholar
  21. 21.
    Korponay-Szabo IR, Halttunen T, Szalai Z, Laurila K, Kiraly R, Kovacs JB, et al. In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies. Gut. 2004;53:641–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Hadjivassiliou M, Maki M, Sanders DS, Williamson C, Grunewald RA, Woodroofe N, et al. Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. Neurology. 2006;66:373–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Sardy M, Karpati S, Merkl B, Paulsson M, Smyth N. Epidermal transglutaminase (Tgase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med. 2002;195:747–57.PubMedCrossRefGoogle Scholar
  24. 24.
    Pellecchia MT, Scala R, Filla A, De Michele G, Ciacci C, Barone P. Idiopathic cerebellar ataxia associated with celiac disease: Lack of distinctive neurological features. J Neurol Neurosurg Psychiatry. 1999;66:32–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Bürk K, Bösch S, Müller CA, Melms A, Zuhlke C, Stern M, et al. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain. 2001;124:1013–19.PubMedCrossRefGoogle Scholar
  26. 26.
    Abele M, Bürk K, Schöls L, Schwartz S, Bessenthal I, Bessenthal I, Dichgans, et al. The aetiology of sporadic adultonset ataxia. Brain. 2002;125:961–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Luostarinen LK, Collin PO, Paraaho MJ, Maki MJ, Pirttila TA. Coeliac disease in patients with cerebellar ataxia of unknown origin. Ann Med. 2001;33:445–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Ihara M, Makino F, Sawada H, Mezaki T, Mizutami K, Nakase H, et al. Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia. Intern Med. 2006;45:135–40.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Marios Hadjivassiliou
    • 1
    • 4
  • David S. Sanders
    • 2
  • Nicola Woodroofe
    • 3
  • Claire Williamson
    • 3
  • Richard A. Grünewald
    • 1
  1. 1.Department of NeurologyThe Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS TrustSheffieldUK
  2. 2.Department of GastroenterologyThe Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS TrustSheffieldUK
  3. 3.Department of Biomedical ScienceSheffield Hallam UniversitySheffieldUK
  4. 4.Department of NeurologyThe Royal Hallamshire HospitalSheffieldUK

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