I’m not suffering from Celiac Disease, but I know a bunch of our readers are living with this affliction. Have you had any brain problems?
WHEN Andre H. Lagrange, a neurologist at Vanderbilt University in Nashville, saw the ominous white spots on the patient’s brain scan, he considered infection or lymphoma, a type of cancer. But tests ruled out both. Meanwhile, anti-epilepsy drugs failed to halt the man’s seizures. Stumped, Dr. Lagrange turned to something the mother of the 30-year-old man kept repeating. The fits coincided, she insisted, with spells of constipation and diarrhea.
That, along with an odd rash, prompted Dr. Lagrange to think beyond the brain. Antibody tests, followed by an intestinal biopsy, indicated celiac disease, an autoimmune disorder of the gut triggered by the gluten proteins in wheat and other grains. Once on a gluten-free diet, the man’s seizures stopped; those brain lesions gradually disappeared. He made a “nearly complete recovery,” Dr. Lagrange told me.
I began encountering case descriptions like this some years ago as I researched autoimmune disease. The first few seemed like random noise in an already nebulous field. But as I amassed more — describing seizures, hallucinations, psychotic breaks and even, in one published case, what looked like regressive autism, all ultimately associated with celiac disease — they began to seem less like anomalies, and more like a frontier in celiac research.
They tended to follow a similar plot. What looked like neurological or psychiatric symptoms appeared suddenly. The physician ran through a diagnostic checklist without success. Drugs directed at the brain failed. Some clue suggestive of celiac disease was observed. The diagnosis was made. And the patient recovered on a gluten-free diet.
The cases highlighted, in an unusually concrete fashion, the so-called gut-brain axis. The supposed link between the intestinal tract and the central nervous system is much discussed in science journals, often in the context of the microbial community inhabiting the gut. But it’s unclear how, really, we can leverage the link to improve health.
Here, though, was a rather spectacular example: Treating an autoimmune disease of the gut (by avoiding gluten) resolved what looked like a debilitating disorder of the brain. The broader takeaway was that, in some subset of patients, apparent neurological symptoms could signal undiagnosed celiac disease.
These are individual cases, but Celiac disease has long been associated with symptoms beyond the gut, including blistering rashes, burning nerve pain, and a loss of muscle control called ataxia. Historically, scientists often attributed these problems to nutrient deficiencies, which undoubtedly occur in some cases. Gut inflammation can hinder the absorption of critical nutrients, such as copper or B vitamins, prompting neurological dysfunction.
But as antibodies specific to tissues beyond the gut have come to light, some now suspect that the autoimmune firestorm ignited in the gut may descend on other organs, including the brain. This idea, which remains hypothetical, has gained traction during a time of progress in understanding autoimmune diseases of the central nervous system.
Celiac disease differs from most other autoimmune diseases in one critical respect: The trigger, gluten, is known. And in most cases, removing gluten will turn off the autoimmune destruction in the gut. Around 10 percent of people with celiac disease, and possibly more, are thought to suffer neurological symptoms, ranging from headache and nerve pain, to ataxia and to epilepsy.
When I called Alessio Fasano, director of the Center for Celiac Research at Massachusetts General Hospital in Boston, he spoke of his own celiac-related miracle stories. In one, a boy with autism-like symptoms actually had undiagnosed celiac disease, and recovered on a gluten-free diet. Dr. Fasano told me he had seen a few similar cases in his native Italy.
In another, a former professor diagnosed with dementia and institutionalized, recovered on a gluten-free diet. Her doctors knew she had celiac disease, but thought it irrelevant to her degenerative brain disorder.
Some researchers have proposed autoimmune mechanisms to explain these phenomena. The presence of antibodies that bind to an enzyme called transglutaminase 2 is used to help diagnose celiac disease. Among other functions, transglutaminases help seal barriers in the body. Scientists at the Royal Hallamshire Hospital in Sheffield, Britain, have identified an antibody that binds to a version of transglutaminase, called TG6, which occurs primarily in the brain.
Not everyone buys the idea, however. In a recent study, the neuroimmunologist Andrew McKeon at the Mayo Clinic mostly found copper deficiencies in his celiac patients with neurological problems; others had autoimmune diseases of the central nervous system. A relative minority — six of 33 — saw neurological improvements on a gluten-free diet.
Rather than celiac disease driving autoimmune brain problems, he thinks, distinct autoimmune diseases are likely to cluster in the same individual. Avoiding gluten won’t entirely mend these patients.
By one recent estimate, meanwhile, one in three Americans dabbles in a gluten-free diet. That vastly outnumbers those thought to have celiac disease — about 1 percent — or the (still unmeasurable) percentage of people with gluten sensitivity, estimated at slightly higher. And yet, the prevalence of celiac disease is indeed rising. Symptoms are increasingly understood to manifest beyond the gut, including occasionally in the brain. Gluten sensitivity may yet prove to be real and measurable.