The term gluten-related disorders (GRD) refers to a spectrum of diverse clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals. They include both intestinal and extraintestinal manifestations. Gluten ataxia (GA) is one of the commonest neurological manifestations of GRD. It was originally defined as otherwise idiopathic sporadic ataxia in the presence of circulating antigliadin antibodies of IgA and/or IgG type. Newer more specific serological markers have been identified but are not as yet readily available. GA has a prevalence of 15% amongst all ataxias and 40% of all idiopathic sporadic ataxias. It usually presents with gait and lower limb ataxia. It is of insidious onset with a mean age at onset of 53 years. Up to 40% of patients have evidence of enteropathy on duodenal biopsy. Gastrointestinal symptoms are seldom prominent and are not a reliable indicator for the presence of enteropathy. Furthermore, the presence of enteropathy does not influence the response to a gluten-free diet. Most patients will stabilise or improve with strict adherence to gluten-free diet depending on the duration of the ataxia prior to the treatment. Up to 60% of patients with GA have evidence of cerebellar atrophy on MR imaging, but all patients have spectroscopic abnormalities primarily affecting the vermis. Recent evidence suggests that patients with newly diagnosed coeliac disease presenting to the gastroenterologists have abnormal MR spectroscopy at presentation associated with clinical evidence of subtle cerebellar dysfunction. The advantage of early diagnosis and treatment (mean age 42 years in patients presenting with gastrointestinal symptoms vs. 53 years in patients presenting with ataxia) may protect the first group from the development and/or progression of neurological dysfunction.

Keywords:
Gluten ataxia, Cerebellar ataxia, Myoclonic ataxia, TG6 antibodies
1.
Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PHR, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A: Spectrum of gluten-related disorders: consensus on nomenclature and classification. BMC Med 2012;10:13.
2.
Marks J, Shuster S, Watson AJ: Small bowel changes in dermatitis herpetiformis. Lancet 1966;ii:1280-1282.
3.
Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, Davies-Jones GAB, Gibson A, Jarratt JA, Kandler RH, Lobo A, Powell T, Smith CML: Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia. Lancet 1998;352:1582-1585.
4.
Hadjivassiliou M, Gibson A, Davies-Jones GAB, Lobo A, Stephenson TJ, Milford-Ward A: Does cryptic gluten sensitivity play a part in neurological illness? Lancet 1996;347:369-371.
5.
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;66:32-35.
6.
Luostarinen LK, Collin PO, Paraaho MJ, Maki MJ, Pirttila TA: Coeliac disease in patients with cerebellar ataxia of unknown origin. Ann Med 2001;33:445-449.
7.
Bürk K, Bösch S, Müller CA, Melms A, Zuhlke C, Stern M, Bessenthal L, Skalej M, Ruck P, Ferber S, Klockgether T, Dichgans J: Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 2001;124:1013-1019.
8.
Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M: Gluten sensitivity in sporadic and hereditary ataxia. Ann Neurol 2001;49:540-543.
9.
Abele M, Bürk K, Schöls L, Schwartz S, Bessenthal I, Dichgans J, Zuhlke C, Riess O, Klockgether T: The aetiology of sporadic adult-onset ataxia. Brain 2002;125:961-968.
10.
Hadjivassiliou M, Grünewald RA, Sharrack B, Sanders DS, Lobo A, Wood N, Williamson C, Woodroofe N, Davies-Jones GAB: Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 2003;126:685-691.
11.
Ihara M, Makino F, Sawada H, Mezaki T, Mizutani K, Nakase H: Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia. Intern Med 2006;45:135-140.
12.
Anheim M, Degos B, Echaniz-Laguna A, Fleury M, Grucker M, Tranchant C: Ataxia associated with gluten sensitivity, myth or reality? Rev Neurol 2006;162:214-221.
13.
Hadjivassiliou M, Aeschlimann P, Sanders DS, Maki M, Kaukinen K, Grunewlad RA, Bandmann O, Woodroofe N, Haddock G, Aeschlimann DP: Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 2013;80:1-6.
14.
Sarrigiannis PG, Hoggard N, Aeschlimann DP, Sanders DS, Grunewald RA, Unwin ZC, Hadjivassiliou M: Myoclonus ataxia and refractory coeliac disease. Cerebellum Ataxias 2014;1:11.
15.
Kheder A, Currie S, Romanowski C, Hadjivassiliou M: Progressive ataxia with palatal tremor due to gluten sensitivity. Mov Disord 2012;27:62-63.
16.
Deconinck N, Scaillon M, Segers V, Groswasser JJ, Dan B: Opsoclonus-myoclonus associated with celiac disease. Pediatr Neurol 2006;34:312-314.
17.
Wilkinson ID, Hadjivassiliou M, Dickson JM, Wallis L, Grunewald RA, Coley SC, Widjaja E, Griffiths PD: Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia. J Neurol Neurosurg Psychiatry 2005;76:1011-1013.
18.
Currie S, Hoggard N, Sanders DS, Wilkinson I, Griffiths PD, Hadjivassiliou M: Coeliac disease and neurological dysfunction: a case-control study. Lancet 2014;383:S39.
19.
Beversdorf D, Moses P, Reeves A, Dunn J: A man with weight loss, ataxia, and confusion for 3 months. Lancet 1996;347:448.
20.
Hahn JS, Sum JM, Bass D, Crowley RC, Horoupian DS: Celiac disease presenting as gait disturbance and ataxia in infancy. J Child Neurol 1998;13:351-353.
21.
Pellecchia MT, Scala R, Perretti A: Cerebellar ataxia associated with subclinical celiac disease responding to gluten-free diet. Neurology 1999;53:1606-1607.
22.
Sander HW, Magda P, Chin RL, Wu A, Brannagan TH, Green PH: Cerebellar ataxia and celiac disease. Lancet 2003;362:1548.
23.
Bürk K, Melms A, Schulz JB, Dichgans J: Effectiveness of intravenous immunoglobulin therapy in cerebellar ataxia associated with gluten sensitivity. Ann Neurol 2001;50:827-828.
24.
Hadjivassiliou M, Davies-Jones GAB, Sanders DS, Grünewald RAG: Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry 2003;74:1221-1224.
25.
Cooke WT, Smith WT: Neurological disorders associated with adult coeliac disease. Brain 1966;89:683-722.
26.
Hadjivassiliou M, Sanders DS, Grunewald RA, Woodroofe N, Boscolo S, Aeschlimann DP: Gluten sensitivity: from gut to brain. Lancet Neurol 2010;3:318-330.
27.
Hadjivassiliou M, Boscolo S, Davies Jones GA, Grunewald RA, Not T, Sanders DS, Simpson J, Tongiorgi E, Williamson C, Woodroofe N: The humoral response in the pathogenesis of gluten ataxia. Neurology 2002;58:1221-1226.
28.
Boscolo S, Lorenzon A, Sblattero D, Florian F, Stebel M, Marzari R, Not T, Aeschlimann D, Venture A, Hadjivassiliou M, Tongiorgi E: Anti-transglutaminase antibodies cause ataxia in mice. PLoS One 2008;3:e1580.
29.
Molberg O, McAdam SN, Sollid LM: Role of tissue transglutaminase in celiac disease. J Paediatr Gastroenterol Nutr 2000;30:232-240.
30.
Korponay-Szabo IR, Vecsei Z, kiraly R, Danlbom I, Chirdo F, Nemes E, Fesus L, Maki M: Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize. J Paediatr Gastroenterol Nutr 2008;46:253-261.
31.
Sardy M, Karpati S, Merkl B, Paulsson M, Smyth N: Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 2002;195:747-757.
32.
Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann DP: Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 2008;64:332-343.
33.
Hadjivassiliou M, Maki M, Sanders DS, Williamson CA, Grunewald RA, Woodroofe N, Korponay-Szabo I: Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. Neurology 2006;66:373-377.
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2015
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