Coeliac Disease and Neurologic Manifestations

The effects of coeliac disease on the nervous system are often overlooked in overviews and guides, and without a background in medicine, it can seem daunting to try to understand. 

Coeliac disease not only affects the stomach but can also cause problems with the nerves in the body. These problems can range from tingling or weakness in the hands and feet to seizures, headaches, and trouble with thinking and memory. Some new studies are also suggesting a connection between coeliac disease and neurodegenerative disorders, like multiple sclerosis (MS) and Parkinson's disease.

Interested in learning more about coeliac disease and its impact on neurological health? Keep reading to uncover more insights and understand why avoiding bread might be good for your nerves as well as your gut!

Introduction - what is coeliac disease?

Coeliac disease is an autoimmune disease where the immune system wrongly attacks the lining of the gut (specifically the small intestines) like it's infected. It’s set off by eating gluten because the immune cells mistakenly identify parts of gluten as dangerous and cause damage to healthy tissues in the process of dealing with the “threat” of gluten. In the gut, it results in villous atrophy. Normally, the villi of the small intestine are small lumps or finger-like projections that exist to increase the surface area of the intestines to maximise nutrient absorption. However, in coeliac disease, they atrophy and become flattened or blunted and sometimes disappear. This leads to a range of gut problems (gastrointestinal symptoms), including diarrhoea, indigestion and bloating. The damaged intestine struggles to do its job and take in nutrients. In combination with gut problems, this malnutrition leads to general fatigue, involuntary weight loss and other health concerns like anaemia. 

In the UK, 1 in 100 people have coeliac disease, but experts believe that 70% of coeliacs are not clinically diagnosed.¹ In recent years, we have gained a better understanding of the non-gastrointestinal symptoms, and the neurological implications of celiac disease are beginning to be recognised. 

Understanding coeliac disease - who is affected?

Although the cause of celiac disease has not been determined yet, it has been linked with certain genes. There is no guarantee that someone with these genetic predispositions will develop celiac disease, but it does increase the risk. 

The genes involved belong to the family of human leukocyte antigen (HLA) class II genes. People with coeliac disease are likely to have one of the following: HLA DQ 2.5 (the most common), HLA DQ8 (less common), or HLA DQ2.2 (the least common).² These genes contribute to identifying cells as a threat to the immune system, thus it is easy to understand their link to coeliac disease. HLA genes alone do not cause the disease, because up to 40% of the population carries them. However, it is rare for someone to have coeliac disease and not the HLA-DQsconsidering them a risk indicator. 

Most people carrying HLA-DQs don’t develop coeliac disease but other genes outside of the HLA system have been linked to celiac disease and are believed to play a significant role in those who eventually develop the condition. They could have a direct or indirect impact on even more genes, though their exact relevance remains unclear.³ By a process called familial clustering, both direct and indirect factors are more likely to be present within first-degree family as they are hereditary. This means that you are recommended to get tested if someone in your family develops coeliac disease at any point in their gluten-consuming life.

Indirect factors are suspected to influence the development of coeliac disease, and there are a few environmental factors that might play a role.⁴ The evidence is varying but these factors  include:

• Exposure to toxic chemicals found in pesticides, nonstick cookware, and flame retardants
• Childhood gastrointestinal infections
• The timing and quantity of gluten ingestion around the time of weaning
• Whether or not the child is breastfed
• The type and duration of wheat dough fermentation

Currently, there are definite rules about coeliac disease development but a few other conditions seem to have an increased risk. This includes type 1 diabetes, Down's syndrome, Turner syndrome, and autoimmune thyroid disease. Overall, if you suspect you have some kind of intolerance to gluten speak to your doctor or healthcare provider and they can direct you to the next steps if required.

Coeliac disease and the nervous system

The neurological manifestations of coeliac disease are varied. 

Peripheral neuropathy

The most common neurological manifestation is peripheral neuropathy, where nerves in the peripheral nervous system (any nerves other than the brain and spinal cord) are damaged. This can have a range of impacts including sensory neuropathy (the sensation of tingling in hands and feet), motor neuropathy (weakened movement of extremities like hands and feet), and autonomic neuropathy (affecting involuntary bodily functions). The damage is caused when, triggered by the ingestion of gluten, the already mistaken immune cells attack nerve tissue instead of the lining of the gut.

Epilepsy and seizure disorders

Other manifestations of coeliac disease are epilepsy and seizure disorders. In fact, a coeliac (a person with celiac disease) is 1.8 times more likely to have epilepsy than people without celiac disease.⁵ While the exact mechanism is not yet understood, it is believed that the skewed immune response to gluten is also the cause. The potential damage to neuronal tissue by immune response could easily lead to inflammation and damage in the brain. This might disrupt regular brain activity and lead to seizures. 

The risk of seizure disorders is also increased by malnutrition (consequence of a damaged small intestine) in untreated coeliac disease because of deficiencies in vitamins and minerals essential for normal brain function. Because of this, clinicians have recognised the importance of testing people with epilepsy or even unexplained seizures for celiac disease, because if cutting out gluten from their diet can lower the chance of triggering a seizure, that helps increase their quality of life immensely, as well as improving any gut discomfort and other symptoms.

Migraines and headaches

 Coeliacs are more prone to experiencing chronic headaches or migraines than the general population. The exact mechanisms are not fully understood but it’s likely to be linked to the accidental jumpstarting of inflammatory processes in the brain, or nutrient deficiencies that are vital for a healthy brain like magnesium, B vitamins, and iron.

Other neurological disorders

Many people with coeliac disease have reported cognitive difficulties such as struggling with memory, attention, and problem-solving. The inability to think clearly is often referred to colloquially as “brain fog” and it is perceived as confusion, forgetfulness, and a general feeling of mental fatigue, making it challenging to perform daily tasks. This is likely linked to neuronal damage caused by the immune response to gluten. Inflammation might also disrupt the connectivity of the brain by impeding neurotransmitter function), further contributing to cognitive defects. Additionally, nutrient deficiencies like vitamin B12 can cause memory loss and concentration difficulties.

Neuropsychiatric disorders like mood disorders, anxiety, and depression are more common in coeliacs. This is not just because of the impact of inflammation on the brain's chemistry and function but also because of the stress and social challenges of living with a chronic illness and maintaining a strict gluten-free diet.⁶ One theory is that once gluten is partially broken down, some of its smaller components cross the barrier that separates the brain from blood to protect it. In this way, gluten can influence the biochemistry of the brain, which offers an alternative method of changing mood or cognition.⁷

Future links to neurodegenerative disorders

Research is also focused on the possible link between coeliac disease and some neurodegenerative disorders. 

• MS: As  coeliac disease and MS are autoimmune disorders, MS might be potentially associated with gluten sensitivity.⁸ 
• Parkinson’s disease: The role of gut inflammation in the development of Parkinson’s disease is currently being explored. Although both diseases share some symptoms like peripheral neuropathy, researchers have not yet found a link between Parkinson’s and coeliac disease.⁹ 
• Autoimmune encephalopathies: They have similar neurological clinical presentation and autoimmune status, although nothing has come of it as of yet.¹⁰

If you or someone you love would like more information about celiac disease, please visit the Celiac UK charity homepage www.coeliac.org.uk/home/ to find out more.

Summary

Coeliac disease is usually hereditary and can develop at any age, where eating gluten can cause your immune system to attack itself in retaliation. The impact of the early diagnosis of celiac disease cannot be overstated, because the less damage caused by gluten consumption the better. The only current treatment of avoiding gluten can help prevent not just the gastrointestinal symptoms but also the neurological manifestations discussed in this article, improving their quality of life. Genetic studies are focused on identifying other genetic causes, and some clinical trials are investigating potential therapies. Considering celiac disease in the differential diagnosis of neurological symptoms is being discussed to help with earlier diagnosis of celiac disease.