Neurological Manifestations of Neuropathy and Ataxia in Celiac Disease: A Systematic Review

Abstract

Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed. MEDLINE, Embase, the Cochrane Library, and conference proceedings were systematically searched from January 2007 through September 2018. Included studies evaluated patients with CD with at least one neurological manifestation of interest and reported prevalence, and/or incidence, and/or clinical outcomes. Sixteen studies were included describing the risk of gluten neuropathy and/or gluten ataxia in patients with CD. Gluten neuropathy was a neurological manifestation in CD (up to 39%) in 13 studies. Nine studies reported a lower risk and/or prevalence of gluten ataxia with a range of 0%–6%. Adherence to a gluten-free diet appeared to improve symptoms of both neuropathy and ataxia. The prevalence of gluten neuropathy and gluten ataxia in patients with CD varied in reported studies, but the increased risk supports the need for physicians to consider CD in patients with ataxia and neurological manifestations of unknown etiology.

Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease

“…Although gluten neuropathy is common in adults with CD [4], in children with CD we show no evidence of corneal nerve loss. In a recent systematic review, age was the main driver of neuropathy in patients with CD [4]. Furthermore, we have observed a significant lower corneal nerve fibre tortuosity.…”

“…This indicates that children with CD do not show a reduction in corneal nerves comparable to children with T1DM [11,31,46]. Although gluten neuropathy is common in adults with CD [4], in children with CD we show no evidence of corneal nerve loss. In a recent systematic review, age was the main driver of neuropathy in patients with CD [4].…”

“…Neurological manifestations including cerebellar ataxia, gluten encephalopathy, sensorineural hearing loss, headache and cognitive decline occur in about 10% of adults with CD [3]. A recent systematic review established that up to 39% of adults with CD may have gluten neuropathy [4]. Luostarinen et al demonstrated a chronic axonal neuropathy using quantitative needle electromyography (EMG) in 23% of patients with CD [5].…”

Opportunities and challenges in the management of celiac disease in Asia

“…While traditionally believed that the hypersensitivity to gluten peptides is limited to the small intestine in patients with CeD, it is now known that CeD affects many other organs, including skin, liver, kidney, bone, and brain, and hence, CeD is now considered to be a systemic disorder altogether. [23][24][25][26] While symptoms of CeD were typically defined as those related to malabsorption, such as chronic diarrhea, steatorrhea, weight loss, failure-to-thrive in children, short stature, irritability, excessive flatulence, and recurrent aphthous ulcers (classical CeD), [27][28][29] it is increasingly being recognized that the patients can have extraintestinal manifestations in the absence of or minimal gastrointestinal symptoms such as short stature, ataxia, hypertransaminasemia, cirrhosis of liver, and osteomalacia (atypical CeD). 30 Education and increased awareness of medical communities across specialties, as well as during initial years of training, is thus needed to allow for a timely diagnosis of CeD and institution of early intervention, which will prevent organ damage.…”

Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus

“…Neuropathy occurs in patients with T1DM and CD and is more prevalent in those with both diseases [ 18 , 19 , 20 ]. Patients with T1DM and CD have a higher prevalence of retinopathy, nephropathy and neuropathy compared to patients with T1DM alone [ 18 ] and CD was found to be an independent risk factor for the development of retinopathy and nephropathy in a large cohort of patients with T1DM [ 21 ].…”