Coeliac disease is a chronic, immune-mediated, inflammatory disorder triggered by the ingestion of grains containing gluten by genetically susceptible individuals expressing the HLA class II molecules DQ2 or DQ8.1 The clinical manifestations of the disease vary greatly, and range from typical gastrointestinal manifestations to absent, minimal, or unusual intestinal complaints with extraintestinal manifestations or disorders.1
The overall prevalence of coeliac disease varies between 0.7% and 2% in the general population, and between 0.4% and 1.3% in the childhood population.2 In adults, among the numerous extraintestinal manifestations and/or disorders of coeliac disease, the wide spectrum of neurological and psychiatric conditions reported includes peripheral neuropathy, cerebellar ataxia, myelopathy, myopathy, brainstem encephalitis, epilepsy, headache, and autism.3 The prevalence of neurological complications in adults with the disease has been estimated to be as high as 26%.3 Further data suggest that antibodies associated with the disease occur in 16 to 57% of individuals with neurological dysfunction.3
The pathogenesis of neurological manifestations in coeliac disease is multifactorial. The disease is characterized by malabsorption, and some neurological complications may, therefore, be secondary to vitamin B12 deficiency (e.g. myelopathy and neuropathy), vitamin D malabsorption (e.g. myopathy), or vitamin E deficiency (e.g. cerebellar ataxia and myopathy).3 However, neurological complications are also frequently reported in individuals without malabsorption, leading to the hypothesis that other factors may play a role in the pathogenesis of neurological defects. Emerging evidence suggests possible humoral mechanisms for both neuropathy and ataxia. Immunoglobulin (Ig) G antibody reactivity to peripheral nerve antigens has been recorded in individuals with coeliac disease and peripheral neuropathy.4 A humoral mechanism has also been postulated for gluten ataxia. Hadjivassiliou et al.5 detected antibodies against Purkinje cells in sera from individuals with coeliac ataxia as well as cross-reactivity between anti-gliadin antibodies and epitopes on Purkinje cells. However, other authors did not confirm these findings.6 Whether these antibodies are pathogenic or only a non-specific marker is still unclear. Few evidence-based data (mostly anecdotal) are available for these issues in children, the incidence varying according to the selection criteria and the individual’s characteristics. In this article we provide a meta-analysis and systematic review of the existing paediatric literature on the neurology of coeliac disease, and we try to answer the question of whether there is evidence of a causal relationship between the disease and neurological conditions.