The astonishing link between your brain, neurological disorders and gluten.
In 2008, Julie Hahn, then 51, dropped and broke every one of her coffee mugs in a matter of weeks. The Colorado Springs resident had not only become suddenly and inexplicably clumsy, she was also having trouble with her balance.
“It started as weakness on the right side of my body,” she says. “I was dragging my right leg and arm as I walked.”
Before long, Hahn was using walls and furniture to catch herself and the once-avid runner was forced to use a cane. She met with a series of neurologists who ran batteries of tests, including multiple MRIs of her head and an EEG, which detects abnormal electrical activity in the brain. But no definitive diagnosis was made.
Meanwhile Hahn developed crushing fatigue. She’d sleep 14 hours a day and still feel exhausted. When her co-workers had to help her home one afternoon—the fatigue was so profound, she couldn’t get up from her desk—Hahn resigned from her job as an administrative assistant.
“After that point, I was spending 24 hours a day in bed,” she says. Friends and family later told Hahn they feared she was dying.
Then 18 months after the frightening symptoms first appeared, Hahn got some surprising news. A rheumatologist she’d been seeing for joint pain had run a test for celiac disease.
“She told me I needed to see a gastroenterologist. I was confused because I’d never had any stomach problems,” Hahn says. “Celiac disease? That didn’t sound like me.”
It wasn’t long before Hahn’s gastroenterologist, Scot Lewey, DO, clinical professor of medicine at Kansas City University of Medicine and Bioscience, confirmed the celiac diagnosis. Hahn had celiac antibodies and her intestinal villi were flattened. Lewey also diagnosed gluten ataxia, a gluten-related autoimmune disorder that causes damage to the cerebellum, the balance and coordination center of the brain.
“What I thought was probably multiple sclerosis or a devastating brain disease was actually a problem with gluten,” Hahn says. “It came as a total shock.”
The Brain on Gluten
Hahn isn’t alone. Five to 10 percent of people with celiac disease present with neurological—not gastrointestinal—symptoms, according to Kourosh Rezania, MD, assistant professor of neurology at the University of Chicago. And that rate may be even higher, he says.
Rezania points to a recent survey out of Columbia University in New York that showed when celiac patients were asked about symptoms related to neuropathy—a disease of the peripheral nerves that causes numbness, pain and sometimes weakness—40 percent reported having such symptoms.
“According to that paper, a large proportion of celiac patients have neuropathic symptoms,” says Rezania.
Neurologist and ataxia expert Marios Hadjivassiliou, MD, agrees. Research conducted at the Royal Hallamshire Hospital in Sheffield, England, where Hadjivassiliou is based, has shown that for every seven patients diagnosed with celiac disease due to gastrointestinal symptoms, two patients were diagnosed with celiac due to neurological ones.
More recently, Hadjivassiliou has reported that roughly 50 percent of newly diagnosed adult celiacs have signs or symptoms of neurological problems. These neurological issues are often present but overlooked.
“From our work, which is ongoing but not yet published, we’ve shown that if you look at the presence of neurological symptoms in newly diagnosed celiacs, it’s extremely high. But it gets ignored because these patients go to the gastroenterologist and don’t expect to talk about balance or sensory problems (like numbness, tingling or unpleasant sensations in their feet or hands),” says Hadjivassiliou.
Neuropathy and ataxia are the two most common neurological manifestations of celiac disease; they were first described as such in 1966. However, another important neurological manifestation is gluten encephalopathy, a type of severe episodic headache. Gluten encephalopathy may mimic migraine but it tends to respond (the headaches improve) with treatment on the gluten-free diet. Those with gluten encephalopathy often have brain abnormalities that aren’t present in a typical migraine sufferer, says Hadjivassiliou. In fact, in a study he led in 2012, Hadjivassiliou found that MRI-detected brain abnormalities were common in celiacs with neurological symptoms. In particular, cerebellar volume was significantly less among these celiacs than in a comparison group.
There are a number of less common neurological disorders linked with celiac disease, including a muscular disease known as myopathy and a spinal cord problem called myelopathy. Certain forms of epilepsy are also associated with celiac disease.
The key to understanding how celiac disease can cause neurological effects is to strip away its association with the gut.
“Celiac disease is not just a gastrointestinal condition as we believed before,” says celiac expert Alessio Fasano, MD, director of the Center for Celiac Research at MassGeneral Hospital for Children. “It can affect any organ. Inflammation that starts in the intestine can spread to the joints causing arthritis or to the liver causing hepatitis. In dermatitis herpetiformis, it affects the skin. It’s not too much of a stretch that this inflammation can also affect the nerves and cause neuropathy or travel to the part of the brain that affects balance and gait.”
Neurological manifestations may be on the rise, adds Fasano.
“I don’t have an explanation for it but the presentation of celiac disease has changed over time,” he says. “Back in the 1970s, people with celiac disease only had gastrointestinal symptoms. In the 1990s to 2000, it became clear that the most frequent presentation was fatigue and anemia. Now neurological symptoms are more prominent. I suspect they were less frequent a few decades ago than they are today.”
Gluten Tests Needed
Julie Hahn was walking with a cane when she first met gastroenterologist Scot Lewey in 2009.
“Stroke, brain tumor and multiple sclerosis had been ruled out, making gluten ataxia seem very likely,” recalls Lewey, who became familiar with the link between gluten and neurological disorders after a close family member with celiac disease began experiencing neurological symptoms. It was Hahn’s slow but steady improvement on the gluten-free diet that convinced Lewey and others of the diagnosis. Over the next year, Hahn went from using a cane—and sometimes a wheelchair—to getting back on the treadmill and walking an hour a day. Her energy level rebounded, too.
“Usually cerebellar ataxia is associated with progressive deterioration,” says Lewey. “So when you see this kind of improvement on the gluten-free diet, the diagnosis becomes quite compelling. Julie Hahn’s experience changed the beliefs and practice patterns of a number of local neurologists.”
Uncovering Gluten Ataxia
Marios Hadjivassiliou, MD, began describing the condition he later coined “gluten ataxia” in the 1990s. After seeing a series of patients with unexplained ataxia, Hadjivassiliou began systematically screening them for anti-gliadin antibodies (AGA), which point to an immune response to gluten but not necessarily celiac disease. To his surprise, nearly a quarter of these patients appeared to be reacting to gluten, yet only a fraction had evidence of celiac disease when biopsied. (Today, Hadjivassiliou estimates that a third of his patients with gluten ataxia also have celiac disease.)
In 2011, gluten ataxia was officially recognized as distinct from celiac by a panel of 15 international celiac experts who convened in London to describe and define the growing set of gluten-related disorders, especially non-celiac gluten sensitivity.
Although the underlying mechanisms of gluten ataxia haven’t been fully mapped out, the London group noted evidence of antibody cross-reactivity between gluten proteins and Purkinje cells in the cerebellum, which are key to balance and coordination. (Prolonged gluten exposure is thought to result in the loss of these Purkinje cells.) The group called for prompt screening for AGA and celiac antibodies in those with unexplained ataxia.
A new screening tool for gluten ataxia may soon be available. Recently, Hadjivassiliou found that approximately 70 percent of individuals with gluten ataxia have an antibody, TG6, which is related to the main antibody detected in untreated celiac disease, TG2. But unlike TG2, which is expressed in the gut, TG6 is primarily expressed in the brain.
“We think TG6, along with other antibodies, probably plays a role in the disease process of gluten ataxia and possibly other gluten-related neurological diseases, as well,” says Hadjivassiliou.
In his research, just 5 percent of a healthy population tested positive for TG6. However, approximately 30 percent of individuals with unexplained ataxia and no other markers of gluten sensitivity (like AGA or celiac antibodies) were TG6 positive, suggesting that TG6 may be the only marker of sensitivity to gluten in some people. This group of patients benefits from a gluten-free diet, says Hadjivassiliou.
“It looks as if TG6 might be a good marker even when other markers of gluten sensitivity and celiac are negative,” he says.
TG6 may also be useful in other gluten-related neurologic disorders, like headache and neuropathy, although more work is needed to confirm this, says Hadjivassiliou. He expects a TG6 test will be available to doctors sometime this year.
Jess Madden, MD, a neonatologist and mother of four small children, was diagnosed with celiac disease in 2009. Three years later, Madden, a resident of Green Bay, Wisconsin, was visiting family in Boston when she suddenly developed numbness and tingling in her feet, hands, tongue and upper lip. She tried to ignore the strange sensations and enjoy the vacation but as the feelings persisted, she grew increasingly anxious.
“I thought it might be MS,” she says. “I had no idea neuropathy could be linked with celiac disease. Apparently, neither did my gastroenterologist.”
When Madden returned from her vacation, she had a quick “curbside consultation” with her gastroenterologist, who told her the neuropathy had nothing to do with celiac disease. However, her neurologist had a hunch it could be caused by gluten—perhaps an accidental exposure while Madden was traveling—or a lingering vitamin deficiency like B12. Madden underwent an MRI of her brain and a panel of tests to rule out other possible causes for her neuropathy, including tests of her thyroid levels since she also has Hashimoto’s thyroiditis.
As her neurologist predicted, the numbness and tingling stopped three weeks later. In the meantime, however, Madden was having difficulty concentrating at work and her short-term memory seemed nonexistent. Could it be chalked up to stress or was this somehow related to the neuropathy?
Julie Hahn experienced severe cognitive troubles that hit her at the same time as the ataxia and fatigue.
“It was like I had Alzheimer’s,” she says. “One night, my husband brought me a plate of plain white rice but I didn’t even recognize it! ‘What is this?’ I finally asked him. It was like my brain couldn’t function enough to identify something as familiar as white rice.”
Doctors documented these cognitive lapses. As part of her extensive neurologic testing, Hahn underwent a series of neuropsychiatric exams that measure cognitive performance.
“I tested in the bottom 10th percentile for my age, IQ and educational background,” she says. “But nine months after I went gluten-free, the difference was profound—I’d jumped to the 60th percentile.”
Hahn still searches for words and needs to set reminders to take medications, remember birthdays and even drink water but she’s continued to notice a huge improvement. If she’s accidentally exposed to gluten, however, her symptoms all come rushing back. (Indeed, a third neuropsychiatric exam revealed a dramatic plunge in her cognitive performance after a major glutening incident.)
“I feel a tremendous amount of pressure and weight in my head—what some people call brain fog—and cognitively, I’m lost. I can’t remember how to crack an egg or open a can,” she says. “I’d like to see more people with gluten ataxia get neuropsychiatric exams to see how much gluten is impacting their cognitive abilities.”
In fact, a small 2006 study from the Mayo Clinic suggested a possible link between celiac disease and cognitive impairment. The researchers looked at 13 adults, ranging from 45 to 79 years old, who developed cognitive deficits a year or two before being diagnosed with celiac disease. Interestingly, ten of them had ataxia and four had neuropathy. Several—but not all—experienced improvement in their cognitive function after treatment with the gluten-free diet.
Cognitive symptoms can be due to many things, stresses Alessio Fasano, MD.
“It would be wrong to leave the impression that everyone with these symptoms should be on a gluten-free diet,” he says. “There’s no question that gluten can cause symptoms like brain fog in people with these conditions. I see large numbers of people in clinic who think they need to be on a gluten-free diet. Unfortunately for many of them, however, nothing changes by withdrawing gluten.”
Behavioral disorders, like depression and anxiety are very common in both celiac disease and gluten sensitivity, Fasano adds.
The Gluten Free Diet Matters
Those with severe or established neurological problems typically have an uphill battle. For them, the goal is to stabilize but not always reverse their neurological symptoms. Those with milder symptoms tend to have a good outlook, as long as they’re vigilant with the gluten-free diet, says Hadjivassiliou.
He makes the case that all newly diagnosed adults with celiac disease should be screened for neurological problems.
“Just like we ask patients about diarrhea or weight loss, celiac patients should be asked about headache, balance and sensory problems,” Hadjivassiliou says. “There are patients who think cheating once in a while on the gluten-free diet is okay. But for those with neurological symptoms, it might be very detrimental. The bowel eventually heals from a dietary mishap—but brain cells that are lost don’t come back.”
Julie Hahn needed little convincing to commit to a strict gluten-free diet. But it still took six months for her to see any improvement.
The neurologic system is slow to heal, says Lewey. As an example, he cites one patient with gluten-related neuropathy who didn’t notice much improvement until she’d been gluten-free for a year. Now five years later, her neuropathy is 70 to 80 percent better.
“Complete resolution is unlikely because she had neuropathy for over 20 years. But her dedication to the diet has led to a really good outcome,” says Lewey. (This patient was tested for celiac disease after her adult daughter was diagnosed with celiac. Although her test results were negative, her AGA levels were high and she decided to go gluten-free, he says.)
“It can be hard to be consistent with the diet if you’re not getting positive feedback,” says Lewey. “Patients with neurological symptoms need to be prepared to feel frustrated by the slow pace of recovery. It can be reinforcing to check antibody levels at six-month intervals to ensure they’re moving in the right direction.”
Before starting a gluten-free diet, it’s important to be tested for celiac, stresses Lewey.
“Some physicians, nutritionists, alternative healthcare providers and others still encourage a trial of the gluten-free diet without doing any diagnostic testing,” he says. “It’s a problem because people will try it and if they have a dramatic response, they want to know if they have celiac disease. At that point, tests are often normal and we’re left with, ‘I don’t know.’ It’s very frustrating. I tell my patients, you can go gluten-free as soon as you leave the lab. You don’t even need to wait for the results.”
Neonatologist Jess Madden attributes her neuropathy to gluten cross-contamination.
“For three years, I was the only one in my household who was gluten-free,” she says. “With four little children, there were a lot of peanut butter and jelly sandwiches—and even more crumbs.”
After her neuropathy diagnosis, Madden and her husband purged their household of gluten and focused on eating whole, unprocessed foods, a move Madden believes has kept her neuropathy—and her cognitive symptoms—at bay.
Although Madden has since developed neuropathy twice while traveling, the symptoms were much milder than her first bout and lasted just a few hours. And since she started toting along her own foods when she leaves town—she stocks up on her favorite gluten-free protein bars and buys fresh bananas and sweet potatoes on the road—she’s been fine.
Hadjivassiliou says the most likely explanation for neurological problems that begin after a celiac diagnosis—or continue to get worse—is ongoing exposure to gluten. This can be confirmed by checking antibody levels.
Some people with gluten-related neurological disorders report heightened sensitivity to gluten.
“I’ve heard from patients that they’re particularly sensitive but this is hard to verify with tests,” says Koroush Rezania, MD. Interestingly, persons with dermatitis herpetiformis have also reported exquisite sensitivity to even trace amounts of gluten.
Like Madden, Julie Hahn eats naturally gluten-free foods and avoids any processed products that have a long list of ingredients.
“It’s just not worth getting sick,” she says.
When Hahn is accidentally exposed to gluten, she’s bed-bound for weeks at a time. The threat of this has kept her from returning to full-time work. Instead, she has found fulfilling volunteer opportunities and she travels with her husband on his business trips.
“We bring a portable kitchen—a good knife, cutting board and hot plate. It’s not the way we used to travel—but life is about adapting to new challenges,” she says. “I think we’re doing pretty well.”
Senior medical correspondent Christine Boyd lives in Baltimore, Maryland.