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Celiac.com 10/23/2021 - A compelling new idea has dawned on the medical/scientific horizon. Dr. Rodney Ford, a pediatric gastroenterologist in New Zealand who calls himself "doctorgluten" on the Internet, has come up with a startling hypothesis that synthesizes and makes sense out of a wide range of otherwise confounding findings in the celiac and gluten sensitivity literature. For instance, why have Dr. Marios Hadjivassiliou and his group found that some people with neurological disease with anti-gliadin antibodies but without celiac disease, recover on a gluten-free diet? And why do other neurology patients sometimes recover from their neurological problems after treatment of their coexisting celiac disease? (Sadly, as Dr. Ford points out, by the time neurological disease develops the prognosis is often very poor.) Further, why do so many celiac patients present with such a wide range of symptoms, most of which are not obviously or usually associated with gut disease? And why are so many individuals who suffer from psychiatric, autoimmune, and even some infectious diseases, helped by a gluten-free diet? The answer to all these questions, according to Dr. Ford's hypothesis, is that the gluten-driven disease is primarily an affliction of the brain. Gluten proteins and/or derivative peptides reach the brain and cause neurological damage along with hormonal and neurotransmitter abnormalities. The nerves in the gut, about as voluminous as the brain, are also damaged by these proteins and peptides. The net result is a cacophony of signs, symptoms, and manifestations across a broad range of organs and body systems. From epilepsy to abdominal distress to schizophrenia, gluten induced damage to the brain and connected nerve fibers can and does disrupt virtually any and every part of the body. Dr. Ford marshals a large body of evidence in his new book, Full of it!, to support this radical departure from conventional wisdom in the celiac/gluten-sensitivity research field. Step by step he explains very simply how the enormous complex of nerves in the brain, spine, and abdomen interact to control all our body systems. He avoids technical terminology as much as possible by using terms such as "tummy brain" which are both clear and instructive even to those who are unfamiliar with medical terminology. The implications of this hypothesis are startling and extensive. If, as Dr. Ford suggests, gluten actually damages the brain in most of us who are gluten sensitive, then celiac disease is just one result of that damage. Instead of occupying the center of the research stage it should be viewed as just one of many gluten mediated illnesses, and that is exactly what Dr. Ford articulates. His hypothesis highlights the need to test for anti-gliadin antibodies frequently and recommend a gluten-free diet whenever these positive test results are found, whether or not celiac disease is present. Dr. Ford credits a number of research heroes of gluten-related medical research, including Dr. Curtis Dohan, Dr. Marios Hadjivassiliou, Dr. Michael N. Marsh, Dr. Alessio Fasano, Dr. W.T. Cooke, Dr. A De Sanctis, Dr. Kenneth Fine, Dr. G.K.T. Holmes, Dr. A-M Knivsberg, Dr. Kalle Reichelt, and a host of others too numerous to list. Without doubt, Dr. Ford has ‘seen further because he was standing on the shoulders of these giants,' (to paraphrase Sir Isacc Newton's famous statement). Nonetheless, Dr. Ford's novel view of this mass of research findings has led to his well supported hypothesis - one that threatens to overturn the current conception of gluten mediated disease. The symmetry and beauty of Ford's insight comes, in part, from its simplicity. It explains why there are so many and such varied manifestations of gluten sensitivity while making a minimal number of assumptions. And that, according to the long-standing principle of science called Occam's Razor, is the best possible explanation for a particular phenomenon.

Celiac.com 11/06/2023 - Celiac disease is a condition where the body cannot properly process gluten. It is primarily known as a gastrointestinal disorder, but it can also lead to various neurological and psychiatric issues. Often, children receive diagnoses of neurological symptoms, such as epilepsy, attention-deficit hyperactivity disorder (ADHD), restless leg syndrome (RLS), and peripheral neuropathy, without identifying the root cause. Recent research delved into the neurological manifestations of gluten-related disorders and the influence of a gluten-free diet on these conditions, with a particular focus on pediatric patients. A team of researchers recently set out to review the pathological manifestations of gluten-related neuro-psychiatric disorders, and the impact of gluten-free diet in children. The research team included Prajwala Nagarajappa, Sree Mahathi Chavali, and Maneeth Mylavarapu. They are variously affiliated with the Department of Public Health, Adelphi University in Garden City, New Jersey, USA; the Department of Pediatrics, Graduate from GSL Medical College, Charlotte, USA; and the Mysore Medical College and Research Institute in Mysore, India. Many of these pediatric patients experience neuropsychiatric symptoms with no apparent cause. However, these symptoms might be linked to celiac disease, as studies show that antibody levels could be indicators. What's striking is that these neurological manifestations can often be managed, or even eliminated, with a gluten-free diet. Comprehensive Literature Review on Neuropathological Manifestations and the Impact of a Gluten-Free Diet To explore these issues, researchers conducted a comprehensive literature review, sourcing studies from major databases like PubMed and Google Scholar. They sought studies providing individual-level data on neuropathological manifestations and the impact of a gluten-free diet on extra-intestinal celiac disease symptoms. Their research protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The inclusion criteria covered prospective studies, observational studies, and case reports on pediatric patients with biopsy-confirmed celiac disease, serologically positive celiac disease, celiac disease with neuropsychiatric symptoms, and research reporting the effects of a gluten-free diet. After a stringent quality assessment to ensure minimal bias, 20 studies were included for discussion. In six studies, patients with neuropsychiatric symptoms had positive serological findings and more severe biopsy results. Seven studies explored the positive influence of a gluten-free diet, and five of these reported statistically significant results. The findings of this study underscore the role of gluten in the severity of neuropsychiatric symptoms in celiac disease. The research strongly indicates that a gluten-free diet can significantly impact the prognosis of this disease. Furthermore, neuropsychiatric symptoms without accompanying gastrointestinal manifestations are more frequently observed in pediatric patients. The study provides clear evidence of a substantial association between gluten and various neurological conditions, including neuropathy, ADHD, epilepsy, and RLS. These conditions can potentially benefit from a gluten-free diet. Given these insights, the study suggests that guidelines should incorporate a combination of serological, biopsy, and imaging techniques for early detection and the initiation of a gluten-free diet. Moreover, the research supports introducing gluten-free diet as a primary preventive measure in the pediatric population. By addressing the significance of gluten in pediatric neurological conditions, this study aims to raise awareness about this frequently misdiagnosed, but manageable disease. Read more in DOI: 10.7759/cureus.47062

Celiac.com 03/27/2023 - Celiac disease, a chronic inflammatory disorder of the intestines, affects about 1% of the world's population. Celiac disease causes diarrhea, abdominal discomfort, bloating, flatulence, and, in rare cases, constipation in the digestive tract. Since the identification of gluten as the disease-causing antigen, celiac patients have been treated with a gluten-free diet, which usually eliminates symptoms and restores gut health, but which also has limitations for some patients. Celiac disease is also associated with numerous neurological and psychological manifestations. A recent article details findings from the most recent study, but here we try to provide more comprehensive information. Neurological Manifestations of Celiac Disease The neurological manifestations of celiac disease are varied and can include psychiatric and neurological symptoms such as ataxia, peripheral neuropathy, seizures, headaches, cognitive impairment, and myoclonus. The specific mechanisms of celiac disease's neurological effects are still being researched, but they may involve gluten-mediated pathogenesis that can lead to antibody cross-reactions, immune-complex deposition, direct neurotoxicity, or extreme vitamin or food deficiencies. A gluten-free diet can alleviate most celiac disease symptoms, except for cortical myoclonus and dementia, which may require immunosuppressive therapy. However, there is currently no consensus on whether serological or neurophysiological data can accurately predict or monitor celiac disease-related neurological involvement. Treatment for gluten-related neurological symptoms typically involves embarking on a strict gluten-free diet as soon as possible, which can have a positive therapeutic effect for most cases. Symptomatic management may also be required. Immunosuppression is only used in cases where a gluten-free diet alone has not been beneficial or for patients with refractory celiac disease. Peripheral Neuropathy and Gluten Ataxia Peripheral neuropathy and gluten ataxia are common in celiac patients, with up to 39% of patients experiencing gluten neuropathy. Gluten-free diets have been shown to improve neuropathy and ataxia. Gluten ataxia is an uncommon immune-mediated neurological disease that can be difficult to identify. The early signs of ataxia may be subtle, but worsen if left untreated. Patients with gluten ataxia may experience structural alterations in different parts of the brain, including the cerebellum and thalamus, and have larger lateral ventricles. Higher Epilepsy Risk Celiac disease increases the risk of epilepsy, especially in children and adolescents. The presence of villus atrophy on follow-up biopsies may reduce the risk of epilepsy but does not affect hospitalizations for epilepsy emergencies. Unexplained epilepsy should prompt celiac disease screening since early identification and therapy may increase the effectiveness of anti-epileptic drugs. Celiac patients also have a higher prevalence of migraines and tension headaches. The underlying relationship between celiac disease and headache involvement is still unknown, but adherence to a gluten-free diet can alleviate neurological symptoms. Celiac disease can also cause cognitive impairment, including memory loss, clouded thinking, personality shifts, and an inability to calculate. Nutrient deficiencies, systemic inflammation, and low brain serotonin levels have been suggested as possible reasons for this. Celiac disease has also been associated with Alzheimer's and vascular and fronto-temporal dementias. Neuropsychological assessments should be conducted in celiac disease patients to assess cognitive function. Psychiatric Manifestations of Celiac Disease Celiac disease is associated with depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. The relationship between celiac disease and these psychiatric disorders is not well-known or established. Particular biological aspects as well as the effect of a gluten-free diet require additional research. Depression and Anxiety Celiac disease has been associated with various psychiatric disorders such as depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. However, the relationship between these disorders and celiac disease remains unclear and requires further research. Research suggests that gastrointestinal disorders have a link with depression and anxiety due to prolonged pain and inflammation, affecting specific brain targets like the anterior cingulate cortex. Gastrointestinal disorder patients have reduced cognitive and mood status, leading to anxio-depressive phenotypes, even in the absence of clear evidence of threats. Children with celiac disease may experience anxiety and depressive symptoms, and pediatric patients with celiac disease should be frequently assessed for mental health issues, especially anxiety and sadness. Adults with celiac disease have reported experiencing anxiety and depression as well, particularly due to clinical illnesses and symptoms. Following a gluten-free diet may worsen symptoms like anxiety and fatigue, leading to a diminished quality of life. Therefore, clinicians must recognize the importance of promoting both dietary adherence and social and emotional well-being in celiac disease patients. Studies have shown that individuals with celiac disease experience low quality of life, anxiety, and depressive symptoms, and nutrition plays a crucial role in reducing these effects. However, the role of motivation in the quality of life and adherence remains unclear and requires further research. Eating Disorders Eating disorders may be a comorbidity with celiac disease (celiac disease) and the need for further investigation. celiac disease patients may experience disordered eating due to the disease itself or other factors such as food neophobia. It is crucial for gastroenterology clinicians to be aware of potential risks for eating disorders in celiac disease patients. The article notes that while numerous examples of eating disorders have been described in celiac disease patients, few epidemiological studies have investigated this potential link. One study found that patients with celiac disease had higher Eating Attitude Test scores than controls when testing individuals aged 13 and up, but no clear differences were seen between patients with celiac disease and controls when using other screening measures for ED. The article suggests that further investigations with larger samples and prospective designs are needed to corroborate these results. The article also discusses how celiac disease may cause food neophobia, which is linked to sensory aversions or fears of the negative effects of eating particular foods. This fear may be more severe in celiac disease patients than in non-celiac disease patients who choose to follow a gluten-free diet and can be linked to the possibility of having an unfavorable reaction to gluten-contaminated food products. The article emphasizes the importance of gastroenterology clinicians being aware of potential risks for eating disorders in celiac disease patients. It notes that eating disorders are defined by thoughts and actions linked to physical and/or psychological problems and that it is crucial to identify past, current, and potential risks for eating disorders in celiac disease patients. Autism Disorder Autism spectrum disorder is caused by a complex interplay of genetic and environmental factors, affecting individuals in diverse ways. Recent studies suggest that immune system dysfunction could contribute to the development of autism spectrum disorder in some people [55]. While some research suggests a connection between celiac disease, an autoimmune disorder triggered by gluten consumption that mainly affects the small intestine, and autism spectrum disorder, other studies have not found a significant association between the two conditions. Attention Deficit Hyperactivity Disorder (ADHD) Research has suggested a potential link between celiac disease and ADHD, with studies showing that celiac disease is overrepresented in ADHD patients, and a gluten-free diet improved ADHD symptoms in celiac disease patients. However, routine screening for ADHD in people with celiac disease or vice versa is not recommended. Cognitive problems similar to those seen in children with ADHD, such as a lack of focus or trouble paying attention, were linked to gluten-free diet noncompliance in childhood celiac disease, as were psychosomatic symptoms and antisocial behavior. Individuals with untreated celiac disease may be at risk for engaging in ADHD-like behavior, specifically inattention. Out of 23 studies, 13 found a favorable correlation between ADHD and celiac disease. Bipolar Disorder Bipolar Disorders refer to a group of serious and long-term mental health conditions that are characterized by manic and depressive episodes. Research has shown that people with bipolar disorder have higher levels of immunoglobulin G (IgG) antibodies against gliadin than those without a history of psychiatric illness. However, there is still a need for further investigation into the specific antibody response to gluten antigens in bipolar disorder. Close associations have also been observed between celiac disease and major depressive disorder, panic disorder, and bipolar disorder, leading to reduced quality of life. Therefore, early reporting of symptoms and screening for celiac disease is recommended, especially for those with a family history of the disease or essential symptoms. Schizophrenia Schizophrenia is a severe mental illness that increases the risk of premature death 2-4 times compared to the general population. Genetic and environmental factors, including drug abuse, especially involving cannabis, are associated with an increased risk of developing schizophrenia. Research suggests an association between schizophrenia and celiac disease, although a causal link has yet to be established. Although having elevated antibodies against gliadin is a common immunological abnormality between schizophrenia and celiac disease, most patients with schizophrenia who had elevated anti-gliadin antibodies (AGA) did not have celiac disease. However, there is evidence that a gluten-restricted diet may benefit schizophrenia patients with immunological gluten sensitivity. One treatment-resistant schizophrenia patient with immunological gluten sensitivity benefited from a gluten-restricted diet improvement in both mental and physical symptoms, as well as a reduction in the plasma quantitative level of AGA-IgG. Chronic inflammation, which is thought to increase due to gluten intolerance, may worsen the symptoms of schizophrenia and make it harder for patients to respond to treatment and absorb medications. Schizophrenia patients also have a higher rate of digestive and liver problems. While removing gluten from the diet may alleviate some symptoms, it is not recommended for all patients. Gluten intolerance is believed to increase chronic inflammation, exacerbating symptoms and reducing medication absorption. However, the available data on the link between celiac disease, gluten allergies, and schizophrenia are inconsistent, and a gluten-free diet is not recommended for people with psychosis and mood disorders without further research. Other Psychiatric Disorders Previous research has shown that people with celiac disease are more likely to suffer from neuropsychiatric disorders than the general population. So far, more than 60 non-human leukocyte antigen (HLA) genes have been linked to celiac disease by genome-wide association studies; of these, it is believed that 15% have a role in neurological health. Many common neuropsychiatric disorders include celiac disease as a primary predisposing factor. It's possible that the co-occurrence of diseases is in large part due to shared molecular networks and biological processes. To determine what causes these disorders, we need to look at the underlying molecular mechanisms. Celiac disease was associated with an increased risk of psychiatric problems in children, raising their lifetime risk by 1.4 times that of the general population. Celiac disease in children has been linked to an increased likelihood of developing psychosocial difficulties later in life, including depression, anxiety, eating disorders, antisocial behavior, attention deficit hyperactivity disorder, autism spectrum disorder, and intellectual disability. It was also more common to have been diagnosed with a mood, eating, or behavioral condition prior to the celiac disease diagnosis. In contrast, no elevated risk was found for any of the psychological diseases studied in the siblings of people with celiac disease. A cohort study included nearly 20,000 children with biopsy-verified celiac disease, pairing each patient with 5 reference child controls. Approximately 16.5% of celiac children were diagnosed with a psychological condition during a median follow-up of 12.3 years, compared to 14.1% of controls. Celiac disease in childhood increased the risk of psychiatric illness by 19% and this risk increases during maturity, in particular, mood, anxiety, eating, ADHD, and autism spectrum problems. There was no statistically significant increase in psychotic disorders, psychoactive substance use, behavioral disorders, personality disorders, suicide attempts, or suicides. Celiac disease increases the use of psychiatric medication. Psychological issues associated with celiac disease were also more prevalent. As a result, the attending physician should conduct routine surveillance of potential psychiatric symptoms in patients of all ages who have gluten-related diseases, including both children and adults. Conclusions In conclusion, celiac disease has been linked to numerous neurological and psychiatric conditions, including depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. Clinicians should assess mental health factors when making a celiac disease diagnosis. Overall, the relationship between celiac disease and these neurological and psychiatric disorders is not well-known or established. More research is needed to understand the pathophysiology of celiac disease's neurological and psychiatric manifestations. Particular biological aspects as well as the effect of a gluten-free diet require additional research. Read more at Cureus.com

Celiac.com 10/08/2022 - Celiac disease is now recognized as a spectrum of gluten-sensitive illness in which the gut is no longer seen as the sole target. For example, dermatitis herpetiformis is a skin manifestation of gluten sensitivity. Celiac disease is no longer considered just in individuals with classic intestinal damage but in individuals with other signs of immune activation and/or degrees of gut involvement, triggered by the ingestion of gluten. Substantial evidence demonstrates that the nervous system also can be a target organ with or without the presence of gut involvement(1). Neurological Complications in Celiac Disease Approximately ten percent of celiac disease patients develop neurological complications(2) . Based on case studies, the most common neurological disorders associated with celiac disease are cerebellar dysfunction, epilepsy and peripheral neuropathy. From 1964 to 2000, data compiled from case reports of 83 celiac patients with neurological complications revealed that 70% of them were diagnosed with either ataxia or peripheral neuropathy(3) . A retrospective data survey of 620 patients attending the Derby Coeliac Clinic found the following neurological and psychiatric complications: Depression (12%), epilepsy (4%), migraine (3%), carpal tunnel syndrome (2%), stroke (2%), anxiety (2%), self poisoning (2%), myopathy (1%), learning difficulty (1%), sciatica (1%), meningitis (1%), Parkinson’s disease (1%), tension headache (1%), multiple sclerosis (1%) and peripheral neuropathy (1%)2 . However, further study needs to clarify the relationship between celiac disease and these complications. A recent study found 13 (8%) among 160 celiac patients had neurological disorders(4) . Ten of the thirteen patients had central nervous system disorders such as epilepsy, attention/memory impairment, and cerebellar ataxia. The remaining patients had peripheral nervous system disorders. In eleven out of thirteen cases, the celiac disease diagnosis came after the onset of the neurological disorder. Seven celiac patients were diagnosed and treated within six months of the neurological onset. All seven had either substantial or complete resolution of their neurological symptoms. In contrast, four out of five patients who were diagnosed with celiac disease from 10 to 264 months after the appearance of their neurological disorder showed no improvement in their neurological symptoms on the gluten-free diet. This study demonstrated that the crucial timing of treatment with a gluten-free diet in celiac patients who have neurological disorders might affect whether the neurological symptoms are reversible. While the incidence of neurological complications in celiac disease is estimated to be ten percent, the incidence of celiac disease in neurological patients is still unknown. Celiac disease can escape detection in blood antibody screenings(5). Not all gluten-sensitive individuals demonstrate classic biopsy evidence of celiac disease, but exhibit milder intestinal features. Also, not all celiac patients present with gastrointestinal symptoms. Therefore, neurological patients with gluten-sensitivity may be missed if they are evaluated for neurological symptoms alone. To identify gluten-sensitivity in neurological patients, antigliadin antibodies were determined in two groups of neurological patients. In a group with idiopathic neurological illness versus another group with identifiable neurological illness, a marked difference of 57% versus 5%, respectively, were antigliadin antibody positive(2) . Twenty-six (86%) of those in the idiopathic group consented to small bowel biopsy and nine (34%) of them had intestinal features characteristic of celiac disease. However, 12% of the healthy blood donors were also antigliadin antibody positive and no explanation was given. Therefore, it was unclear whether the rate of gluten-sensitive neurological illness could be overstated by 12 percent or that 12 percent of the normal population could have gluten-sensitivity. Gluten Ataxia Gluten ataxia is the most common form of neurological dysfunction to be attributed to gluten sensitivity1 . Up to 41% of sporadic idiopathic ataxia is caused by gluten ataxia, as evidenced by the presence of antigliadin antibodies. Patients with gluten ataxia have difficulty controlling their upper and/or lower limb movements. Hadjivassiliou et al found 79% (54 of 68) of gluten ataxia patients had damage to the part of the brain called the cerebellum which is involved in coordination and steadiness. Not all gluten-sensitive, neurological patients will also have classic intestinal biopsy evidence of celiac disease. Of 51 gluten ataxia patients who underwent duodenal biopsy, 24% of them had biopsy proof of celiac disease and only 13% had gastrointestinal symptoms1 . Yet, treatment with a gluten-free diet can be helpful, irrespective of gut involvement. For example, 26 patients with gluten ataxia were offered a gluten-free diet and were confirmed to be adhering to the gluten-free diet by evidence of negative serology within six months to one year of treatment(6). When compared to the control group of patients with gluten ataxia who did not receive treatment of a gluten-free diet, all 26 patients in the treatment group improved significantly in their ataxia based on a battery of tests. The response observed in the treatment group was irrespective of gut involvement or the duration of the ataxia (mean duration of nine years). These results contrasted with the expectation that the ataxia would remain despite evidence of the loss of cerebellar Purkinje cells which are the target cells in gluten ataxia(3, 6). Malabsorption or Autoimmunity? Two potential mechanisms to explain the neurological dysfunctions of celiac disease are nutrient deficiencies due to malabsorption, and autoimmune disease. Currently, it is unknown which of these, or both, is the underlying cause of neurological disorder in celiac disease. A reference to these potential mechanisms came in 1966 when Cooke and Smith reported a landmark study of 16 adult celiac patients with neurological complications3 . For most of them, symptoms of classic celiac disease pre-existed their neurological symptoms. All 16 were found with extreme weight loss and vitamin deficiencies along with anemia due to severe malabsorption. Subsequently, over half of them died, despite gluten restriction, due to the progression of their neurological complications involving sensory ataxia and/or other features. Post-mortem findings in four patients revealed cerebellar Purkinje cell loss and T-cells (type of white blood cell) infiltrating parts of the brain, brainstem, and spinal cord(7). Deficiencies of folic acid, vitamin B-12, and vitamin E have been implicated as a potential cause of neurological complications(4). However, vitamin deficiencies alone do not explain the absence of neurological deficits in some patients(2). In addition, vitamin deficiencies are rarely found or can be attributed to neurological dysfunction in association with gluten ataxia patients of which the majority don’t have histological evidence of celiac disease(3). Furthermore, in a current study of 13 neurological celiac patients, only 2 had been diagnosed with malabsorption(4). In support of the hypothesis of an autoimmune mechanism of celiac disease neurological complications, Hadjivassiliou et al found that gluten ataxia patients with inflammation located in the white matter of the cerebellum part of the brain was marked by the loss of Purkinje cells. The inflammation in celiac disease, which is thought to be mediated by T-cells, is not confined to the small bowel as gliadin-specific T cells and antigliadin antibodies are found in the blood(8). Antigliadin antibodies also have been found in the cerebrospinal fluid(3) . In gluten ataxia patients, antigliadin antibodies were found to bind to Purkinje cells in the cerebellum that might result in damage to this part of the brain(9). This finding suggests that common binding sites are shared between cerebellar Purkinje cells and gliadin proteins. Patients with gluten ataxia also have anti-Purkinje cell antibodies. How antigliadin antibodies gain access to the cerebellum might be due to possible alterations of the blood-brain barrier. In further support of an autoimmune basis of celiac disease neurological complications, 8 of 13 celiac patients with neurological dysfunction had anti-neuronal antibodies to the central nervous system(4). This was significantly higher when compared with only 1 in 20 celiac patients who had anti-neuronal antibodies but no neurological involvement. Furthermore, 30 non-celiac control patients, who had other autoimmune gastrointestinal diseases or had donated blood, had no detectable anti-neuronal antibodies. After one year of treatment on a gluten-free diet, anti-neuronal antibodies disappeared in 6 of the 8 celiac patients with neurological dysfunction. In 5 of these 6 patients, the neurological symptoms partially or completely resolved. However, anti-neuronal antibodies are not specific for neurological disorders associated with celiac disease since they are also found in other patients with nervous system disorders. Identification of neurological patients with gluten-sensitivity with or without histological evidence of celiac disease is necessary in order to provide them the opportunity for treatment with a gluten-free diet. Identification should be further aided when the exact mechanisms of neurological complications in gluten-sensitive patients are understood. Finally, immediate treatment with a gluten-free diet early in the progression of the disease may be crucial in the prognosis of whether the neurological disorder is reversible. Glossary of Terms: ataxia: impaired muscle coordination Central Nervous System (CNS): the portion of the nervous system involving the brain and spinal cord cerebellum: portion of the brain involved in equilibrium and coordination; cerebellar (adj.) dementia: impaired intellectual function epilepsy: neurologic disease resulting in convulsions or loss of consciousness idiopathic: the disease has an unknown cause neurological: having to do with the nervous system neuron: nerve cell neuropathy: any disease of the nervous system paroxysm: convulsion Peripheral Nervous System (PNS): the portion of the nervous system outside of the brain and spinal cord; peripheral (adj.) Purkinje cell: a type of neuron that is highly branched, mostly found in the cerebellum References: Hadjivassiliou M et al 2003. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 126: 685-91. Tengah D et al 2002. Neurological complications of coeliac disease. Postgrad Med J 78: 393-98. Hadjivassiliou, et al. 2002. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 72: 560-3 Volta U, et al. 2002. Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders. Scand J Gastroenterol 37: 1276-81. Tursi A et al 2001. Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease. Am J Gastroenterol 96: 1507-1510. Hadjivassiliou M, et al. 2003. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry 74: 1221-24. Will AJ. 2000. The neurology and neuropathy of coeliac disease. Neuropathy and Applied Neurobio 226: 493-96. Cross A, and Golumbek, P. 2003. Neurologic manifestations of celiac disease. Neurology 60: 1566-1568. Hadjivassiliou M, et al. 2002. The humoral response in the pathogenesis of gluten ataxia. Neurology 58: 1221-26.

Celiac.com 01/25/2021 - What's the connection between celiac disease, and cognitive impairment? Does the connection change over time? Does following a gluten-free diet help reduce cognitive impairment? There really hasn't been much good study data on this so far. One of the main problems, according to researchers, previous reports of cognitive deficit in celiac disease often study widely variable groups of patients at multiple stages of the disease, and/or lack control data. To better understand the connection between cognitive impairment and celiac disease duration and gluten-free diet adherence, a team of researchers recently set out to examine groups of newly diagnosed and long-standing celiac disease patients. The research team included Iain D Croall, Claire Tooth, Annalena Venneri, Charlotte Poyser, David S Sanders, Nigel Hoggard and Marios Hadjivassiliou. They are variously affiliated with the Department of Neuroscience, the Department of Infection, Immunity & Cardiovascular Disease, and the Institute for Silico Medicine, at the University of Sheffield in Sheffield, UK; the Department of Psychological Services, Royal Hallamshire Hospital, STH, Sheffield, UK; the South West Yorkshire Partnership NHS Foundation Trust in Wakefield, UK; the Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK; and the Department of Neurology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals National Health Service Foundation Trust in Sheffield, UK. The team recruited 21 healthy control subjects, along with 19 newly diagnosed celiac patients (NCD) and 35 established celiac patients (ECD). Each participant took cognitive tests that established seven baseline domain scores. Patients also responded to SF-36 quality of life (QoL) questionnaires. The team then controlled for age, and compared data in between-group ANCOVAs with Tukey’s post-hoc test. The team then compared significant outcomes in the ECD group between fully gluten-free patients patients who not fully gluten-free diet, as defined by Biagi scores and blood tests. In visual, verbal, and memory tasks, the NCD and ECD groups underperformed relative to controls, by comparable measures. The ECD group only underperformed in visual-constructive tasks. In terms of QoL measures, the NCD patients reported lower vitality, while the ECD patients reported more bodily pain. Comparisons based on dietary adherence were non-significant. The team's findings confirm cognitive deficit in celiac patients, which seems to exist at the time of diagnosis, after which it seems to level off. While it seems that a gluten-free diet may be that cause of the leveling off, more research is needed to establish the degree to which this is true, and to what extent any further decline might result from ongoing gluten exposure. Read the team's paper entitled, Brain fog and non-coeliac gluten sensitivity: Proof of concept brain MRI pilot study, in Nutrients 2020, 12(7), 2028

Celiac.com 04/30/2019 - Doctors recognize that patients with gluten sensitivity, whether or not they have enteropathy, or even gastrointestinal symptoms, can suffer from a range of debilitating neurological manifestations. Researchers Panagiotis Zis and Marios Hadjivassiliou of the Academic Department of Neurosciences, Sheffield Teaching hospitals NHS Trust and University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK, recently published an overview of current literature in an effort to assess the available treatment options for the neurological manifestations of gluten-related disorders, specifically, serologically confirmed gluten sensitivity and celiac disease. For patients with gluten sensitivity, ataxia is the most common neurological manifestation, followed by peripheral neuropathy. Other conditions linked to gluten sensitivity and celiac disease and discussed in the review include: epilepsy headache encephalopathy movement disorders cognitive impairment muscle disorders The team found that a strict gluten-free diet is effective in treating neurological manifestations of gluten-related disorders. Rarely, patients need additional immunosuppressive treatment, usually mycophenolate. There have been cases where gluten ingestion triggered schizophrenic episodes in an undiagnosed patient. Meanwhile, a number of studies have shown that a gluten-free diet seems to help improve symptoms of psychological, neurological and inflammatory conditions, including schizophrenia, neuropathy, and diabetes. Stay tuned for more news about gluten and related health issues. Read more in Current Treatment Options in Neurology

Celiac.com 12/06/2016 - Neurological problems are a very common effect of gluten intolerance. Whether you have celiac disease or gluten sensitivity, there is research showing that gluten can cause nervous system problems in affected individuals. What kind of problems? When it comes to the nervous system, symptoms run the gamut from depression to schizophrenia, from migraines to brain fog, and from seizures to numbness and pain. I want to share more information with you about a particular type of nervous system ailment called peripheral neuropathy. The name basically means damage to the nerves of the extremities (arms and legs) that typically manifests in numbness and pins and needles-type pain that all of us have experienced at one time or another if we sat on our feet too long or fell asleep in a weird position and had a hand ‘go to sleep'. While these latter type incidents are normal, having such symptoms occur when no pressure is being put on the nerve is abnormal. Not only is it uncomfortable to have such sensations, but when truly numb, accidents from tripping or burning oneself can occur due to not having adequate sensation. I think it is interesting to note that the most common occurrence of peripheral neuropathy is seen in type I diabetes, an autoimmune disease. Celiac is also an autoimmune disease and according to the University of Chicago's Center for Peripheral Neuropathy, 10% of those diagnosed with celiac disease have a neurological problem, and peripheral neuropathy is quite common. Taking it a step further, we know that gluten creates a leaky gut and we know that a leaky gut is associated with autoimmune disease, through several wonderful studies brought to us by Dr. Alessio Fasano and his team. Therefore, seeing a connection between gluten and peripheral neuropathy is not unexpected based on research. Further, despite a dearth, or scarcity, of research on gluten sensitivity, doctors currently engaged in such research cite peripheral neuropathy as one of the most common symptoms associated with gluten sensitivity. In fact neurological symptoms are frequently associated with gluten sensitivity before any digestive symptoms ever develop. And in some cases, the nervous system disorders are present with no digestive disturbances. A lack of any digestive symptoms is perhaps one of many reasons why these individuals' gluten sensitivity is missed by their doctors. When it comes to comparing gluten sensitivity to celiac disease, according to Dr Fasano, 30% of the patients he diagnoses with gluten sensitivity suffer a neurological ailment, a much higher percentage than that associated with celiac disease. How Do You Know if You Have Peripheral Neuropathy? The symptoms of peripheral neuropathy are numbness, a feeling of hot/cold or a pins and needles feeling that tends to start at the ends of your body's long nerves, meaning your feet and hands, before moving upwards. The symptoms can be in legs and/or arms, right side and/or left. Certainly, considering that type 1 diabetes is the most common cause of peripheral neuropathy, with an estimated 50% suffering some type of nerve damage, that would be the first thing to rule out. What Should You Do? If you have these symptoms and your doctor has ruled out diabetes and any other obvious sources of the problem (including any drugs you may be taking that create neuropathy as side effects), you may fit into the category of "idiopathic neuropathy". This means that you have the problem but the reason is unknown. Or is it? Let's look at the result of a study where researchers worked with more than 200 individuals with neuropathy, 140 of whom fell within the ‘idiopathic' category. These smart doctors tested those 140 people for antibodies to gluten, specifically utilizing the anti-gliadin antibody test – AGA-IgA and AGA-IgG. This blood test is a general blood test that is not specific to celiac disease or gluten sensitivity, but shows that the body's immune system is reacting negatively to these proteins in gluten called gliadin. Of those tested, 34% were positive to one or both tests, compared to 12% of the general population. Interestingly, a full 9% of those tested in the ‘idiopathic' group actually had celiac disease, compared to 1% of the general population. And perhaps even more interesting, 80% of that same idiopathic group had the genes for celiac disease, either HLA-DQ2 or HLA-DQ8. 80%!! In the normal population that number is about 40%. Our takeaway message is that peripheral neuropathy has a rather high correlation to immune reaction to gluten – be it celiac disease or gluten sensitivity. Therefore anyone you know who suffers with such symptoms absolutely should be checked for gluten intolerance. Regaining one's strength and correcting nervous system abnormalities is well worth the change in diet when gluten is the cause. Such cases have been described in the literature where the only treatment that led to success was a gluten-free diet. So many diseases and symptoms can be prevented and reversed by discovering their true underlying root cause and for many of those ailments it is gluten that is the culprit. Don't continue suffering nor let you friends and family members suffer. Find out why the symptom is there rather than just masking it with a drug. If you need assistance, consider calling us for a free health analysis – call 408-733-0400. Our destination clinic treats patients from across the country and internationally. You don't need to live local to us to receive assistance. We are here to help! To your good health, References: Hadjivassiliou M. et al. Neuropathy associated with gluten sensitivity. Journal of Neurology, Neurosurgery, and Psychiatry. 2006 Nov;77(11):1262-6. Rigamonti A. et al. Celiac disease presenting with motor neuropathy: effect of gluten-free diet. Muscle & Nerve. 2007 May;35(5):675-7. University of Chicago Center for Peripheral Neuropathy. Types of Peripheral Neuropathy - Inflammatory - Celiac Disease.

Celiac.com 11/25/2017 - We have long known that gluten intolerance, both celiac disease and gluten sensitivity, are highly associated with neurological symptoms. Migraines, ataxia (unstable gait), seizures, schizophrenia – the list is long. But a recent research study just published last month sheds some new light on exactly what the mechanism may be. Understanding why these debilitating symptoms occur as a result of a gluten intolerance will, hopefully, go a long way toward increased awareness among the lay public and clinicians alike. It is certainly true that too many millions of Americans suffer the effects of a gluten intolerance unknowingly. They only know that they feel unhealthy but have no idea that gluten is the culprit. The digestive tract is sometimes called the second brain. Some say that is because it is second in importance to the brain. After all, if the food that is consumed doesn't turn into fuel that can effectively feed the 10 trillion cells in the body, those cells will be unable to perform their job and keep the body healthy. In fact, poor digestion is absolutely linked to poor health and increased onset of degenerative disease. This article in Current Pain and Headache Reports looks at another possibility for naming the digestive tract the second brain, and it simply stems from anatomy. The digestive tract actually has a ‘mind of its own'; more correctly, it has a nervous system of its own, called the enteric nervous system. ‘Enteric' simply means having to do with the intestine. This nervous system, according to research, is very similar to the brain housed in the head in that it is bathed in similar chemicals (called neurotransmitters – which, interestingly enough, are mostly produced in the gut!). It sends and receives impulses and records experiences and is influenced by emotions. Some proof of the latter: Have you ever been nervous and had diarrhea? This particular study stated that experiencing ‘adverse events' created a state of hypervigilance (a state of being overly responsive - not a good thing) in the nervous system which was associated with migraines and IBS. Such ‘hypervigilance' was previously only associated with the central nervous system – the one attached to the brain in the head. This group of researchers suggests that the initiation of hypervigilance may very likely lie in the enteric nervous system also. What this means is that if the small intestine is genetically sensitive to gluten and gluten is ingested, it could set off a nervous system response that could create disabling diseases, such as migraines and IBS, but likely others as well. The take-away message is that it is truly critical to diagnose gluten intolerance as soon as possible. Once that hurdle is surmounted it then needs to be followed with a program of nutrition, lifestyle and diet that will ensure healing of the small intestine and a ‘calming' of the hypervigilant nervous system. You may sometimes hear this referred to as healing a leaky gut. Here at HealthNOW we often see this clinically in patients who seem intolerant to many different foods and can't seem to enjoy stable improvement of their symptoms, even after they eliminate gluten from their diet. The reason for this insufficient improvement is that a comprehensive follow-up program is missing – a program that addresses what we call the Secondary Effects of Gluten. This entails evaluating for any other food sensitivities, cross reactive foods, a tendency towards autoimmune disease, the presence of any infectious organisms, healing the leaky gut, balancing the probiotic population, and more. While increasing awareness of the presence of gluten intolerance is absolutely critical, neglecting the secondary effects, as mentioned above, can result in long-term ill health that is truly preventable. Have you experienced such symptoms? Have you removed gluten but are only partially healthier? I'd love to hear from you. To your good health.

Celiac.com 06/12/2017 - Previously, Transcranial Magnetic Stimulation in de novo celiac disease patients has signaled an imbalance in the excitability of cortical facilitatory and inhibitory circuits. Researchers have reported that, after about of 16 months on a gluten-free diet, patients experience a global increase of cortical excitability, which suggests some kind of compensation for disease progression, likely mediated by glutamate. To better assess these finding, a team of researchers recently conducted cross-sectional evaluation of the changes in cortical excitability to TMS after a much longer gluten-free diet. The research team included M. Pennisi, G. Lanza, M. Cantone, R. Ricceri, R. Ferri, C.C. D’Agate, G. Pennisi, V. Di Lazzaro, and R. Bella. They are variously affiliated with the Spinal Unit, Emergency Hospital "Cannizzaro", Catania, Italy, the Department of Neurology IC, I.R.C.C.S. "Oasi Maria SS.", Troina, Enna, Italy, the Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy, the Gastroenterology and Endoscopy Unit, University of Catania, Catania, Italy, the Department "Specialità Medico-Chirurgiche,” University of Catania, Catania, Italy, and the Institute of Neurology, Campus Bio-Medico University, Rome, Italy. For their study, the team enrolled twenty patients who had followed an adequate gluten-free diet for about 8.35 years, on average. They then compared the results with twenty de novo patients, and twenty more healthy controls. The team measured Transcranial Magnetic Stimulation, recorded from the first dorsal interosseous muscle of the dominant hand, as follows: resting motor threshold, cortical silent period, motor evoked potentials, central motor conduction time, mean short-latency intracortical inhibition and intracortical facilitation. De novo patients showed a shorter cortical silent period, while responses for gluten-free diet participants were similar to controls. Regardless of diet, all celiac patients showed a significantly smaller amplitude of motor response than did control subjects, Again, without regard to diet, all celiac patients showed a statistically significant decrease of mean short-latency intracortical inhibition and enhancement of intracortical facilitation with respect to controls. The team also observed that gluten-free celiac patients showed more intracortical facilitation compared to non-gluten-free patients. Neurological examination and celiac disease-related antibodies were both negative. This study showed that a gluten-free diet helps to mitigate the electrocortical changes associated with celiac disease. Even so, in many patients, an intracortical synaptic dysfunction, mostly involving excitatory and inhibitory interneurons within the motor cortex, may persist. The calls for further investigation into the clinical significance of subtle neurophysiological changes in celiac disease. Source: PLoS One. 2017 May 10;12(5):e0177560. doi: 10.1371/journal.pone.0177560. eCollection 2017.

Celiac.com 09/17/2012 - Many aspects of celiac disease simply have not been well studied, so they remain poorly understood. For example, researchers have not done enough study on people with celiac disease to understand if they show any readily available serological markers of neurological disease. To better understand this issue, a research team recently assessed the amount of brain abnormality in patients with celiac disease, along with looking into MR imaging sequences as biomarkers for neurological dysfunction. The study team included S. Currie, M. Hadjivassiliou, M.J. Clark, D.S. Sanders, I.D. Wilkinson, P.D. Griffiths, and N. Hoggard, of the Academic Unit of Radiology at University of Sheffield, Royal Hallamshire Hospital, in Sheffield, UK. For their study, they conducted a retrospective examination of a consecutive group of 33 patients with biopsy proven celiac disease, who had been referred for neurological opinion. The group ranged in age from 19 to 64 years old, with an average of 44±13 years. Researchers divided the group into subgroups based on their main neurological complaints of balance disturbance, headache and sensory loss. They used 3T MR to evaluate variations in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between celiac patients and control subjects. The results showed that the celiac patients had a significantly lower cerebellar volume than did control subjects. Celiac patients had 6.9±0.7% of total intracranial volume, compared with 7.4±0.9% for control subjects (p<0.05). Celiac patients also showed significantly less grey matter density in multiple brain regions, both above and below the tentorium cerebelli, compared with the control subjects (p<0.05). The data showed that 12 (36%) patients demonstrated WMAs unexpected for the patient's age, with the highest incidence occurring in the headache subgroup. This group of patients averaged nearly double the number of WMAs per MR imaging session than the subgroup with balance disturbance, and six times more than the subgroup with sensory loss. The MR images of celiac patients who have neurological symptoms show significant brain abnormality on MR imaging, which means that MR imaging may serve as valuable biomarkers of disease in celiac patients. Source: J Neurol Neurosurg Psychiatry. 2012 Aug 20.

Celiac.com 11/01/2012 - Although most instances of gluten sensitivity manifest as a chronic, autoimmune disorder of the small intestine (celiac disease), around 10% of gluten sensitive patients suffer neurological symptoms. Usually these neurological symptoms accompany the more common intestinal issues, but some patients exhibit neurological symptoms exclusively. For this reason, it is thought that gluten-related symptoms in different parts of the body could be the result of autoimmune reactions to different members of the transglutaminase gene family. A recent lab study suggests that neurological gluten-related symptoms could be the result of an immune reaction to a particular neuronal enzyme known as TG6, and that this reaction occurs separate from other autoimmune reactions to gluten. Sera were collected from 6 groups: 20 newly diagnosed celiac disease patients (pre gluten-free diet) with no neurological symptoms, 34 gluten ataxia patients who tested positive for anti-gliadin antibodies, 17 peripheral idiopathic neuropathy patients, also positive for anti-gliadin antibodies, a control group of 18 genetic (non-gluten related) ataxia patients or individuals with clear family history of ataxia, a second control group of 14 patients with various immune-mediated but gluten-unrelated diseases and a third control group of 19 healthy individuals. Sera were tested through a series of protein analyses and enzyme-linked immunosorbent assays. In the celiac disease group, 18 of 20 patients tested positive for the TG2 autoantibody, with the remaining two testing postive for the TG3 or TG6 autoantibodies. 55% of celiac disease patients had multiple transglutaminase autoantibodies: 45% of all celiac disease patients had antibodies for both TG2 and TG3, 45% had antibodies for both TG2 and TG6, and 35% had antibodies for TG2, TG3 and TG6. Gluten ataxia patients were separated into two groups: those with intestinal symptoms (group GAE), and those without (group GAo). TG2 autoantibodies correlated well with intestinal symptoms: 12 of 15 in the GAE group tested positive for TG2 autoantibodies, while only 1 of 19 in the GAo group tested positive for them. TG3 autoantibody results were similar: group GAE results were comparable to the celiac disease group, while group GAo was no different from the control groups. In contrast, both gluten ataxia groups had similar results for TG6 autoantibodies. Overall prevalence of TG6 autoantibodies in the gluten ataxia group was 62%, compared to 45% in the celiac disease group. Inhibition studies showed that in group GAE (gluten ataxia with intestinal symptoms), autoantibodies reacted separately from one another, with TG2 and TG6 autoantibodies reacting independently of one another to their respective TG isozymes. This, along with the fact that some patients tested positive exclusively for TG6 would suggest that intestinal and neurological gluten-related symptoms are caused by separate immune reactions to different TG isozymes (TG2 and TG6, respectively). This is further supported by postmorten analysis of a gluten ataxia patient without intestinal symptoms, where TG6 deposits were found in the brain (TG6 could not be detected in a normal cerebellum). The findings of this study suggest that with more research, doctors may have another diagnostic tool in the form of TG6 autoantibody tests. This would help determine which patients with gluten sensitivity might be most at risk for developing neurological symptoms. Source: http://www.ncbi.nlm.nih.gov/pubmed/18825674