Chapter 41 - Gluten-related neurologic dysfunction
Section snippets
Historical perspective
Celiac disease (CD) was first described by the Greek doctor Aretaeus the Cappadocian, in ad 100, only to be forgotten and then rediscovered by Samuel Gee in 1888 (Gee, 1888). In a lecture on “the coeliac affection,” Gee described the classic pediatric presentation of the disease. Whilst clinicians began to recognize this disease entity, the etiologic agent remained obscure until the observations of Willem Dicke, a Dutch pediatrician, in 1953 of “the presence in wheat, of a factor having a
Epidemiology of neurologic manifestations
The prevalence of CD in the healthy population has been shown to be at least 1% in both European and North American studies (Sanders et al., 2003). There are no accurate figures of the prevalence of the neurologic manifestations of gluten sensitivity in the general population. Figures of between 10% and 22.5% have been reported amongst patients with established CD attending gastrointestinal clinics (Holmes, 1997, Briani et al., 2008). These are unlikely to be accurate because such figures are
The diagnosis of gluten-related diseases
CD is characterized by the presence of an enteropathy, a reliable gold standard. It is now accepted, however, that an enteropathy is not a prerequisite for the diagnosis of GRD with predominantly neurologic or other extraintestinal manifestations. Furthermore, the small bowel mucosal changes in the context of GRD represent a spectrum, from histologically normal mucosa to full-blown enteropathy to a pre-lymphomatous state also referred to as the Marsh classification (Marsh, 1992). Most pathology
Gluten ataxia
Gluten ataxia (GA) was originally defined as otherwise idiopathic sporadic ataxia with positive AGA (Hadjivassiliou et al., 2003a). This original definition was based on the serologic tests available at the time. In a series of 853 patients with progressive ataxia evaluated over a period of 15 years in Sheffield, UK, there were 152 patients out of 681 with sporadic ataxia who had serologic evidence of GRD. Therefore gluten ataxia had a prevalence of 22% amongst sporadic ataxias but as high as
Pathogenesis
Current evidence suggests that neurologic manifestations are immune mediated. Postmortem examination from patients with gluten ataxia demonstrate patchy loss of Purkinje cells throughout the cerebellar cortex, a nonspecific finding in many cerebellar disorders. However, additional findings supporting an immune-mediated pathogenesis include diffuse infiltration mainly of T lymphocytes within the cerebellar white matter as well as marked perivascular cuffing with inflammatory cells (
Conclusions
GRD include immune-mediated diseases triggered by ingestion of gluten proteins. While celiac disease has been the most comprehensively studied of all GRD, dermatitis herpetiformis and neurologic manifestations are the commonest extraintestinal manifestations. To fully understand the immunologic insults resulting from gluten ingestion, the emphasis should perhaps shift toward the study of extraintestinal manifestations. In addition there is a need for the early identification of those patients
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2022, International Review of Research in Developmental DisabilitiesCitation Excerpt :Because these symptoms are very common in DS, and because the evaluation of behavior changes among individuals with ID may be challenging, diagnostic overshadowing can lead to missed diagnoses of celiac disease. Late identification or missed diagnosis of CD can have important health and neurodevelopmental implications, such as failure to thrive, anemia, osteoporosis, lymphoma, and neurologic symptoms (Hadjivassiliou, Duker, & Sanders, 2014; Jericho & Guandalini, 2018). It is important to assess for symptoms of celiac disease regularly in individuals with DS, and, if present, to proceed with further lab-based screening evaluation typically with tissue transglutaminase immunoglobulin A (tTG-IgA) and total IgA (Bull et al., 2022).
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