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Celiac Disease Symptoms: Gluten Encephalopathy with Psychiatric Onset

Celiac Disease Symptoms: Gluten Encephalopathy with Psychiatric Onset

Patients who are gluten sensitive often exhibit celiac disease symptoms. Celiac disease or gluten-sensitive enteropathy is an immune reaction in the small intestine caused by the digestion of foods with gluten. The diagnosis of this autoimmune disease can be moderately simple, but psychiatric symptoms can greatly hinder it. Find out more about their relationship in this case study.

Celiac Disease Symptoms: A Case Study of Gluten Encephalopathy with Psychiatric Onset!

In This Article:

Article Source!

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited: Nicola Poloni, Simone Vender, Emilio Bolla, Paola Bortolaso, Chiara Costantini and Camilla Callegari, Department of Clinical Medicine-Psychiatry, University of Insubria, Via O. Rossi 9, 21100 Varese, Italy Clinical Practice and Epidemiology in Mental Health 2009, 5:16doi:10.1186/1745-0179-5-16. This medical article was received on July 7, 2008, and accepted and published on June 26, 2009, while licensed under BioMed Central Ltd.


Abstract | Celiac Disease Symptoms: Gluten Encephalopathy With Psychiatric Onset | Gastrointestinal Disorder

The Autoimmune Disease!

Many cases of celiac disease, an autoimmune and gastrointestinal disorder caused by sensitivity to gluten, can remain in a subclinical stage or undiagnosed. In a significant proportion of cases (10-15%), gluten intolerance can be associated with the central or peripheral nervous system and psychiatric disorders.

The Patient!

A 38-year-old man, an inpatient, was admitted to our department for worsening anxiety symptoms and behavioral alterations. After the addition of second-generation antipsychotic to the therapeutic regimen, the patient presented neuromotor impairment with high fever, sopor, leukocytosis, raised rhabdomyolysis-related indicators. The neuroleptic malignant syndrome was strongly suspected.

The Case!

After worsening of his neuropsychiatric conditions, with the onset of a frontal cognitive deficit, bradykinesia, and difficulty walking, dysphagia, anorexia, and hyperaemic anemia, SPET revealed a reduction of cerebral perfusion, and ENeG results were compatible with a mainly motor polyneuropathy. Extensive laboratory investigations gave positive results for Anti-Gliadin antibodies, and an appropriate diet led to a progressive remission of the encephalopathy.


Celiac Disease Definition!

Celiac disease is an inflammatory disease of the upper small intestine resulting from gluten ingestion [1]. The diagnosis is based on: A clinical picture suggesting malabsorption of nutrients, serology for anti-gliadin, anti-endomysial, and anti-transglutaminase antibodies, sometimes a biopsy of the intestinal mucosa, and resolution of the lesions following the institution of a gluten-free diet [1]. Many cases of celiac disease long remain in a subclinical stage [2], Or undiagnosed because of poor awareness of the condition among primary care physicians [1]. In a significant proportion of cases (10-15%) gluten intolerance can be associated with central or peripheral nervous system disorders, such as cerebellar ataxia, myoclonus, epilepsy, ophthalmoplegia, dementia, multifocal leukoencephalopathy, peripheral neuropathies, and myopathies [3], and with psychiatric disorders such as anxiety, depression, psychotic symptoms, and personality disorders [4]. These manifestations are sometimes the presenting symptoms of the disease [4-6]. The physiopathological mechanisms underlying these associations are still not known, even though genetic causes [6] and autoimmune factors [7,8] have been hypothesized.

Article Summary!

The literature describes cases of cerebral perfusion abnormalities in patients with untreated and undiagnosed celiac disease [9,10]. There is also a report of a case of regression of frontal hypo perfusion following the institution of a diet of gluten-free foods [9].

Case Report!

Case Report | Celiac Disease Symptoms: Gluten Encephalopathy With Psychiatric Onset | Gastrointestinal Disorder


In May 2001, a 38-year-old man with anxious-depressive symptoms was referred to us for psychiatric assessment. These symptoms, occurring sporadically for around two years, had worsened following a protracted absence from work (due to a disabling right wrist fracture). The patient had a history of surgical operations to correct kyphoscoliosis.

Treatment Pre-Admission!

He was diagnosed with reactive depressive disorder in the context of personality disorder NOS (not otherwise specified) and put on paroxetine 10 mg with benzodiazepines. Following the appearance of bizarre behaviors and heteroaggressiveness towards family members, antipsychotic therapy (Haloperidol Decanoate 50 mg every four weeks) was added.

Upon Admission into the Department!

In May 2002, worsening anxiety symptoms and behavioral alterations that could not be managed at home culminated in the patient's hospitalization in our department for re-assessment and review of therapy. Two days after the addition of risperidone 2 mg to the existing therapeutic regimen (Citalopram 20 mg and BDZ), the patient presented muscle rigidity, cramp-like muscle pain, and increased osteotendinous reflexes leading to bradykinesia and difficulty walking.

Withdrawal of the antipsychotic drug did not improve the picture significantly. Laboratory investigations revealed raised CK (536 U/l) and a brain CT-Scan showed an area of hypodensity of possible ischaemic origin in the posterior fossa, as well as moderate deepening of the cortical sulci in the frontal-temporal region bilaterally. The EEG showed mild, non-specific, non-focal abnormalities.

Worsening and Additional Symptoms!

The severe anxiety symptoms and behavioral alterations persisted and a week later, antipsychotic treatment was reintroduced. The clinical picture, already characterized by neuromotor impairment, worsened abruptly and unexpectedly, with the onset of high fever (39C), sopor, acute respiratory insufficiency with peripheral cyanosis, leukocytosis (WBC Count 16680/mm3), and raised rhabdomyolysis-related indicators (CK 1216 U/l and LDH 718 U/l). The patient was transferred to the infectious diseases department.

Since neuroleptic malignant syndrome was strongly suspected, the antipsychotic was withdrawn and dantrolene 50 mg/day and cardio-respiratory support were started, substantially resolving the acute symptomatology. The patient developed an Enterococcus faecalis infection of the urinary tract and deep-vein thrombosis (DVT), which were treated with antibiotic therapy and subcutaneous heparin.

Lack of Medical Connections!

Although the patient's general conditions improved, the neurological picture of diffuse muscle rigidity, psychomotor slowing, and dysarthria persisted and despite further investigations (MRI, evaluation of autoantibodies, and circulating immunocomplexes), continued to lack a plausible explanation.

Readmission for Malnutrition and Worsening Neuropsychiatric Conditions!

In mid-June, a further worsening of his neuropsychiatric conditions prompted his readmission to our department. During this second stay, he displayed the progressive onset of a frontal cognitive deficit together with affective lability, behavioral and affective regression, and verbal and motor stereotypes. Furthermore, the appearance of dysphagia and anorexia led to significant weight loss (20 kg in two months), which necessitated parenteral nutrition.

Referral to C. Besta Neurological Institute!

The patient was then sent to the neuropathology unit at the C. Besta Neurological Institute in Milan, where single-photon emission computed tomography (SPECT) revealed a reduction of perfusion and thus of neuronal activity and density in the right superior and middle frontal gyri, The left superior frontal gyrus, and the left medial temporal and occipital gyri; electroneurography (ENeG) results were compatible with a mainly motor polyneuropathy. Subsequently, mild hypoferraemic anemia was found.

Silent Celiac Disease!

Gluten sensitivity tests (part of further and more extensive laboratory investigations) gave positive results for anti-gliadin (IgG 32 UI/ml), anti-endomysial, and anti-transglutaminase antibodies. An appropriate diet was instituted and led to a progressive remission of the encephalopathy and an improvement in the psychiatric symptoms and the lesions detected on SPECT and ENeG, which at follow-up, were no longer present. After a period of rehabilitation, This patient is still followed by our psychiatric service for mild anxiety symptoms. He takes olanzapine 2.5 mg and derives benefit from the treatment.


Conclusion | Celiac Disease Symptoms: Gluten Encephalopathy With Psychiatric Onset | Gastrointestinal Disorder

Diagnosis of Celiac Disease!

The diagnostic process in this patient proved particularly complicated. This is, in fact, a case of the clinical onset of celiac disease in adulthood, without signs of malabsorption and with exclusively psychiatric involvement (non-specific anxious-depressive symptoms associated with effective and behavioral personality disorders). In our view, this clinical picture could be attributed to the SPET-Documented frontal hypoperfusion. This would indeed explain the lack of benefit of the initial psychopharmacological treatment and the progressive worsening of the symptoms that, together with the onset of behavioral disinhibition, necessitated the patient's hospitalization.

Complications with the Diagnosis!

During hospitalization, the administration of antipsychotic drugs triggered the onset of neuroleptic malignant syndrome, which, initially atypical (without fever and leukocytosis) and then full-blown, slowed down the diagnostic process and delayed the recognition of the true nature (Organic) of the etiology. We cannot rule out the possibility that this celiac patient presented a particular susceptibility to this rare complication associated with the use of second-generation antipsychotic drugs [11], given the cerebral involvement documented on brain CT scan and subsequently on SPECT. The picture was complicated further by the onset of DVT and a urinary tract infection, probably due to the patient's prolonged confinement to bed.

Psycho-Organic Syndrome!

After the resolution of the acute picture, there remained a progressively worsening psycho-organic syndrome. This is secondary to the abovementioned cerebral involvement and neuromotor deficits due to the polyneuropathy detected on ENeG. The case we describe recalls literature reports of an Adult-Onset progressive frontal, subcortical-type cognitive deficit, characterized by confusion, personality disturbances, and associated neurological (ataxia-and peripheral neuropathy-type) pictures, coinciding with the exacerbation of a malabsorption syndrome [12].

Blood Test for Autoimmune Antibodies!

The appearance of the first signs pointing to malabsorption, i.e., the weight loss and hypoferraemic anemia finally prompted us to investigate a possible autoimmune etiology, and to test for anti-gliadin antibodies, for which the patient was positive.

The diagnostic hypothesis of gluten encephalopathy was confirmed by the remission of the symptoms and of the lesions observed on SPECT following the institution of an appropriate diet.

Patients with Celiac Disease and Psychiatric Symptoms!

In addition to the objective diagnostic difficulties presented by this case, we wish to add a further, ideological consideration relating to an unwitting tendency of colleagues from other specialist disciplines to stigmatize patients classified as psychiatric. Indeed, both the possible organic etiology of the clinical picture and the concomitant medical disorders presented by psychiatric patients are often underestimated, slowing down the diagnostic process and the taking of the necessary therapeutic measures.


Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal.

Closing Remarks:

Competing Interests!

The authors declare that they have no competing interests.

Authors Contributions!

NP has made substantial contributions to the acquisition of clinical data; VS has given the final approval of the version to be published; BE has made substantial contributions to the acquisition of clinical data; PB participated in the analysis and interpretation of clinical data; CC was involved in drafting the manuscript; CC was involved in revising the manuscript critically.

All authors read and approved the final manuscript.

To know more about how gluten affects one’s mental health, watch this video from the Gluten-Free Works channel:

May this case study of Gluten Encephalopathy with Psychiatric Onset help you in your medical studies. The electronic version of this article is the complete one and can be found online at http://www.cpementalhealth.com/content/5/1/16.

What are your insights in the case study on gluten encephalopathy? Tell us in the comments section below!

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These statements have not been evaluated by the Food and Drug Administration. None of the nutritional products mentioned are intended to Diagnose, Treat, Cure, or Prevent any Disease.
Editor’s Note: This article was originally published in 2014, and has been updated for quality and relevancy.



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