Pathophysiology of Gluten Ataxia
Gluten ataxia is characterized by the “patchy loss of Purkinje cells throughout the cerebellar cortex” (Hadjivassiliou, Sanders, & Aeschlimann, 2015). This is a chronic, progressive condition caused by activation of transglutaminase 2 which crosslinks with gluten peptides causing deamination of the proteins and activation of an immune response. Additionally, transglutaminase 6 and immunoglobulin A have also been shown to be evident in patients with gluten ataxia. The immune response can cause perivascular changes in the cerebellum caused by inflammation which “may compromise blood brain barrier and allow the entry of gluten-related antibodies into the central nervous system” (Hadjivassiliou, Sanders, & Aeschlimann, 2015).
Signs & Symptoms
Pure cerebellar ataxia will lead to nystagmus and ocular signs in 80% of gluten ataxia patients.
Gait ataxia (100%)
Gastrointestinal symptoms related to celiac disease (< 10%)
Enteropathy (33%)
Cerebellar atrophy (60%)
Rare→ myoclonus, palatal tremor, or opsoclonus myoclonus along with cerebellar ataxia
(Sapone et al., 2012)
Diagnostic Criteria
Must present with ataxia and antibodies to gliadin for traditional diagnosis; IgG more likely to present than IgA. Promising evidence for antibody TG6 and association to gluten ataxia (Hadjivassiliou et al., 2015).
Prevalence
15% among all ataxias; 40% among all idiopathic sporadic ataxia (Hadjivassiliou et al., 2015).
Differential Diagnoses
Vitamin B12 and E, folic acid, and copper deficiency; congenital disorders; genetic disorders; mitochondrial disorders; toxic and metabolic disorders; drugs; vascular conditions; neoplastic processes; and autoimmune diseases (Hadjivassiliou et al., 2015; Todd & Shakkottai, 2018).
Treatment
Strict gluten-free diet can stabilize or improve ataxia. Purjinke cell damage is not reversible, but other cerebellum abnormalities caused by gluten ataxia are reversible. Serum immunoglobulin levels normalize after 6-12 months of gluten-free diet (Hadjivassiliou, Sanders, & Aeschlimann, 2015).
References
Hadjivassiliou, M., Sanders, D. D., & Aeschlimann, D. P. (2015). Gluten-Related Disorders:
Gluten Ataxia. Digestive Diseases,33(2), 264-268. doi:10.1159/000369509
Lieberman, S. (2007). The gluten connection. Emmaus, PA: New York.
Sapone et al. (2012). Spectrum of gluten-related disorders: consensus on new nomenclature
and classification. BMC Medicine, 10(13), 1741-7015.
Todd, P.K., & Shakkottai, V.G. (2018). Overview of cerebellar ataxia in adults. Up To Date.
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