Gluten ataxia is a rare neurological condition that presents with difficulties in balance, coordination, gait, and overall muscle movement in response to the ingestion of gluten proteins found in food products. Researchers believe the disease is caused by an immune response to gluten molecules which affects a part of the brain known as the cerebellum. Gluten ataxia is often underdiagnosed and if the symptoms are not addressed through gluten cessation quickly permanent damage to the cerebellum can occur. 

Introduction

Gluten ataxia (GA) is one of several gluten-related disorders (GRDs) characterised by movement and gait difficulties which are triggered by the ingestion of gluten, a mixture of proteins found in wheat, barley, rye and derivatives.¹ Ataxia is a neurological sign that presents with abnormalities in muscle coordination, often resulting in impairments in gait, eye movement and speech. Ataxia affects up to 26 people per 100,000, with about one third of cases due to known hereditary syndromes. More commonly, ataxia is acquired due to exposure to toxins, brain lesions or for no apparent cause (sporadic ataxia).² Studies estimate that 1 in 5 people with non-hereditary ataxia suffer from gluten ataxia, making it a common, and often underdiagnosed cause.¹ 

The pathophysiology of gluten ataxia is believed to be similar to coeliac disease (CD), whereby the immune system produces antibodies against the gliadin protein found in gluten. However, instead of damaging the intestinal lining, these antibodies result in neuroinflammation, and potentially irreversible damage in the cerebellum - the part of the brain that helps coordinate balance and movement.^3,4  Gluten ataxia usually results in poor coordination and tremors particularly the upper limbs, as well as a form of gaze-evoked eye-ball tremors known as nystagmus.⁵

Diagnosis of gluten ataxia is often through a mixture of assessing clinical signs and onset as well as some laboratory tests, particularly testing for the presence of antigliadin antibodies. Brain imaging to identify cerebellar damage and gluten cessation tests are also used.⁶ 

Patients are typically recommended to completely cease consumption of dietary gluten, which normally results in symptom improvement. However, if diagnosis is delayed, damage to cerebellar neurons can sometimes be irreversible.² As such, raising awareness about the presentations and management of GA is fundamental to promote accurate diagnosis and prevent long-term impairment.

Pathophysiology and risk factors of GA

Gluten is a mixture of proteins that is found in commonly used cultivated cereals, often used to make bread, biscuits, cakes and other food products. It appears that the immune system responds to certain antigens in gluten and in the enzymes that break it down. Most typically, this results in CD, characterised by intestinal inflammation upon ingestion of these proteins. However, other symptoms related to gluten sensitivity can also occur in people with, and without digestive issues.¹

When the immune system produces antibodies and an inflammatory response to gluten proteins in the bloodstream, this can cause neuroinflammation involving the Punkje neurons of the cerebellum. Research shows that in an initial phase, the presence of anti-gliadin antibodies (AGA) can increase the excitability of these cells, which is then followed by a longer-lasting hypoactivity associated with neurodegenerative damage and ataxic symptoms.⁴

Typically, the average age of onset of GA is 53 years. Other risk factors include:^1,7

• CD: up to 6% of patients experience CD, however only a minority of people with GA have intestinal symptoms
• Having genetic markers commonly associated with CD, such as HLA-DQ2 and HLA-DQ8 haplotypes
• Non-coeliac gluten sensitivity (NCGS)
• Family history of GA, CD or NCGS
• Being diagnosed with another autoimmune disorder 

Symptoms of GA

The most common feature of GA is a general lack of motor coordination, characterised by:²

• Difficulty walking
• Clumsiness and difficulties in fine motor skills, such as writing
• Tremors
• Muscle weakness
• Eye movement disturbances, resulting in nystagmus or difficulty tracking objects with one's gaze
• Speech difficulties, particularly slurred or slow speech

Many patients also experience additional psychiatric, neurological and digestive symptoms similar to those seen in CD. These include:^2,8,9

• Cognitive impairment, including impairments in memory, attention, and decision-making
• Mood Changes such as depression and anxiety 
• Digestive issues since gluten ataxia is related to gluten sensitivity, about 20-30% of people may also experience symptoms typical of CD, such as bloating, diarrhoea, or abdominal pain
• Peripheral neuropathy, including numbness, tingling, or pain in the extremities and is reported by up to half of patients  

Diagnosis

Diagnosing GA can be challenging due to the overlap of its symptoms with other neurological conditions. A comprehensive approach is essential for an accurate diagnosis. Health professionals usually take several steps to determine the cause of symptoms and whether a diagnosis of GA is appropriate, based on different factors, such as:⁶

• Medical history - the doctor will take a detailed medical history, focusing on symptoms, their progression, and any family history of gluten sensitivity, CD, or ataxia
• Neurological examination -  a thorough neurological exam will be conducted to assess balance, coordination, muscle strength, reflexes, and eye movements
• Serological tests to identify the presence of antibodies such as AGA and anti-tissue transglutaminase (ATGT) antibodies
• Neuroimaging - Magnetic resonance imaging (MRI) scan of the brain can reveal atrophy (shrinkage) of the cerebellum, which is often present in GA patients. This imaging helps rule out other causes of ataxia
• Gluten-free diet - a significant improvement in symptoms after following a strict gluten-free diet for several months strongly supports the diagnosis of GA

Management and prognosis

The primary treatment for GA is a strict gluten-free diet, but management may also involve additional therapies and support:^10-12

• Dietary counselling - working with a dietitian specialised in gluten-related disorders can help ensure proper nutrition and adherence to the diet
• Immunosuppressants - in cases where a gluten-free diet alone does not fully control symptoms, medications that suppress the immune system may be considered, such as steroids or azathioprine
• Symptomatic treatment - medications to manage specific symptoms like tremors, muscle spasms, or neuropathic pain may also be prescribed
• Physical, occupational and speech therapy to improve motor and communication skills and provide assistance with daily activities
• Counseling and support groups - dealing with a chronic condition can be challenging. In addition, GA is particularly associated with a higher risk of depression, anxiety and other mood disorders. Counseling, cognitive behavioural therapy (CBT) or support groups can provide emotional support and coping strategies

GA typically responds well to gluten cessation within a few months, however, studies show some patients have permanent damage to the cerebellum that requires rehabilitation to improve functionality and quality of life.²

Summary

Ataxia is a neurological sign associated with damage to the cerebellum, which is characterised by severe movement and muscle coordination problems, affecting functions such as gait, speech, gaze and fine motor skills. Importantly, up to 20% of cases of non-hereditary ataxia are believed to be precipitated by gluten consumption.  GA is an autoimmune disease in which the immune system produces antibodies against the gluten proteins in the blood, which results in neuroinflammation affecting the cerebellum. In addition, some patients also experience other potentially debilitating symptoms such as cognitive impairment, peripheral neuropathy and mental health disturbances.

Prompt diagnosis through a combination of clinical examinations, laboratory tests, brain scans and trials with a gluten-free diet is fundamental to prevent irreversible damage. Unfortunately GA remains underdiagnosed. Up to 6% of people with CD also experience ataxia. Other risk factors include family history, middle age and suffering from non-coeliac gluten sensitivity. The most important aspect in the treatment of GA is complete gluten avoidance. Other therapies, such as immunosuppressant medications, dietary counseling and psychosocial interventions are often used too. Typically, symptoms improve within months of quitting gluten, however, in some cases they may persist and require rehabilitation.

Overall, anyone with new-onset ataxia should undergo the appropriate investigations to rule out common causes, one of which is autoimmune GA. Only a healthcare professional can diagnose GA in which case damage to the cerebellum can be avoided by adopting a gluten-free diet, as such it is important to discuss new onset coordination and movement difficulties with a doctor to determine the correct diagnosis and treatment.