Celiac Disease and the Nervous System: A Comprehensive Overview of Neurological Manifestations and Underlying Mechanisms.

Abstract

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically susceptible individuals. While traditionally associated with gastrointestinal (GI) symptoms, CD is increasingly recognized as a systemic disorder with significant neurological involvement. A growing body of evidence links CD to a broad spectrum of neurological manifestations, including gluten ataxia (GA), peripheral neuropathy (PN), epilepsy, migraine, myoclonic disorders, and cognitive impairment. These symptoms may precede or occur independently of GI symptoms, complicating diagnosis and delaying treatment. The underlying mechanisms are multifactorial, involving autoantibody cross-reactivity, neuroinflammation, increased permeability of the intestinal and blood-brain barrier (BBB), gut dysbiosis, and micronutrient deficiencies. This review synthesizes current insights into the pathophysiological basis of CD-related neurological disorders. We also explore the therapeutic impact of a strict gluten-free diet (GFD) on CD-related neurological manifestations. Early recognition of neurological signs and their prompt management are essential to mitigate irreversible neural injury and improve long-term outcomes in these patients. Given the potential for symptom reversibility with dietary treatment, routine screening for CD should be considered in patients presenting with idiopathic neurological syndromes, even in the absence of GI symptoms.