The Neurological Manifestations of Gluten

The Gluten File

  

Hadjivassiliou from:
Gluten sensitivity as a neurological illness, M Hadjivassiliou, et al.

"IgG anti-gliadin antibodies have been the best diagnostic marker in the neurological population we have studied. IgG anti-gliadin antibodies have a very high sensitivity for CD but they are said to lack specificity. In the context of a range of mucosal abnormalities and the concept of potential CD, they may be the only available immunological marker for the whole range of gluten sensitivity of which CD is only a part.  "

 

 

Hadjivassiliou and Grunewald From:

"While we wait for more definitive studies to be done, what should be the strategy of the practical neurologist? The everyday practise of  medicine requires weighing costs and benefits for each individual patient under conditions of uncertainty, with inadequate data. When  faced with these dilemmas, we often consider most the concept of harm. We are more willing to propose a therapy with lower degrees of
evidence of therapeutic efficacy when the severity of the neurological illness produces significant pain or disability, and the potential harm of the treatment is low.

Therefore, when faced with a patient who has progressive disability due to ataxia or neuropathy of unknown aetiology or uncontrolled seizures, it is reasonable to discuss with the patient the inadequacy of our knowledge, but offer evaluation for coeliac disease, including anti-tTG, anti-EMA and AGA, as well as a confirmatory intestinal biopsy if the antibodies are positive.

Dietary treatment can be offered to those with either classical coeliac disease (with positive intestinal biopsy) or those with positive serology alone, as long as the patient understands we have no definitive clinical trial data that a gluten-free diet will improve neurological function either in patients with classical coeliac disease or those with just positive serology."

 

  

Mark B. Skeen From: Neurologic Manifestations of Gastrointestinal Disease, Neurologic Clinics, Volume 20, Number 1, February 2002

"Neurologic disease associated with gluten sensitivity or celiac disease includes a wide range of manifestations:

Central nervous system (CNS) manifestations include dementia, cerebellar ataxia, myelopathy, encephalopathy, brain stem encephalitis, progressive multifocal leukoencephalopathy,chronic, progressive leukoencephalopathy, progressive myoclonic ataxia, seizures, isolated CNS vasculitis, and a syndrome of celiac disease with encephalopathy and bilateral occipital calcifications.”

“Several reports document the existence of peripheral neuropathy in association with celiac disease.”

 

 

Full text articles

Gluten sensitivity as a neurological illness, M Hadjivassiliou, et al.

 

Neuromuscular disorder as a presenting feature of celiac disease, M Hadjivassiliou, et al.

 

Gluten sensitivity: a many headed hydra, M Hadjivassiliou, et al.

Gluten sensitivity: time to move from gut to brain, M Hadjivassiliou

 

Celiac Disease and Peripheral Neuropathy, Norman Latov, MD, PHD 

Is the prevalence of celiac disease increased among epileptic patients? Pratesi, et al

Neurological manifestations of coeliac disease by Liisa Luostarinen 

Neurological complications of coeliac disease, D.S.N.A Pengiran Tengah, A.J. Wills, G.T.K. Holmes (2002)

 

Pub Med Abstracts

 

In a significant proportion of cases (10-15%) gluten intolerance can be associated with central or peripheral nervous system and psychiatric disorders. A 38-year-old man was admitted as to our department an inpatient for worsening anxiety symptoms and behavioural 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. Neuroleptic malignant syndrome was strongly suspected. After worsening of his neuropsychiatric conditions, with the onset of a frontal cognitive deficit, bradykinesia and difficulty walking, dysphagia, anorexia and hypoferraemic anaemia, 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.

Gluten encephalopathy with psychiatric onset: case report.
PMID: 19558661  June 2009

Celiac disease as a possible cause for low serum ferritin in patients with restless legs syndrome.
PMID: 19138881 Jan 2009

 

DISCUSSION: The mechanisms of vascular involvement in celiac disease are controversial. The most widely incriminated factor is autoimmune central nervous system vasculitis, in which tissue transglutaminase, the main auto-antigen contributing to maintaining the integrity of endothelium tissue, plays a major role. Other mechanisms are still debated, mainly vitamin deficiency. CONCLUSION: Being a potentially treatable cause of ischemic stroke, celiac disease must be considered as a potential etiology of stroke of unknown cause, particularly in young patients, and even without gastrointestinal manifestations.
Celiac disease and ischemic stroke
PMID: 19144365   Jan 2009

 

A case of stiff-person syndrome, type 1 diabetes, celiac disease and dermatitis herpetiformis.
PMID: 19150172 Jan 2009

 

A 42-year-old woman presented with inability to walk and marked loss of motor function. She had elevated liver enzymes with a cholestatic pattern. Antimitochondrial antibody M2 band, anti-endomysial antibody, antigliadin IgA and IgM were positive. Histopathologic findings of the liver revealed PBC and duodenal biopsy was consistent with CD. She was also found to have osteomalacia. She showed slow response to gluten-free diet, but accelerated full recovery with vitamin D replacement. CONCLUSION: In PBC patients with subclinical CD and myopathy, vitamin D status can provide a basis for treatment.

Osteomalacic myopathy associated with coexisting coeliac disease and primary biliary cirrhosis.

PMID: 18685287 Aug 2008

  

Celiac disease may initially present as a neurological disorder. Alternatively, celiac disease may be complicated by neurological changes. With impaired nutrient absorption, different deficiency syndromes may occur and these may be manifested clinically with neurological changes. However, in patients with deficiency syndromes, extensive involvement of the small intestine with celiac disease is often evident. There are a number of reports of celiac disease associated with neuropathy, ataxia, dementia and seizure disorder. In these reports, there is no clear relationship with nutrient deficiency and a precise mechanism for the neurological changes has not been defined. A small number of patients have been reported to have responded to vitamin E administration, but most do not. In some, gluten antibodies have also been described, especially in those with ataxia, but a consistent response to a gluten-free diet has not been defined. Screening for celiac disease should be considered in patients with unexplained neurological disorders, including ataxia and dementia. Further studies are needed, however, to determine if a gluten-free diet will lead to improvement in the associated neurological disorder.

Neurological disorders in adult celiac disease.
PMID: 19018335  Nov 2008

 

In the celiac disease the most common neurological manifestations are ataxia, peripheral neuropathy and myopathy. Up to 85% of patients with histologically proven coeliac disease have no gastrointestinal symptoms; consequently, measurement of antigliadin antibody titre is therefore vital in all cases of idiopathic ataxia. Complete resolution of neurological symptoms is the result of gluten-free diet.

[Neurological and psychiatric aspects of some gastrointestinal diseases.]

PMID: 18952527  Nov 2008

 

Celiac disease (CD) has long been known to be associated with neurological and psychiatric manifestations; its in association with myotonic dystrophy however has not yet been reported. We report the case of a 27-year old female patient who presented to us with diarrhoea, weight loss, easy fatigability, irritability and alopecia of 8 months duration and was diagnosed to have celiac disease and put on gluten free diet. 8 weeks later she developed neurological symptoms and was found to have myotoni dystrophy in addition. At six month follow up patient had gained 5 kg, but the neurological symptoms remained the same. Treatment of neurological symptoms associated with gluten hypersensitivity depends on the type of neurological syndrome associated. Only exceptionally do these symptoms improve with gluten restriction and, in some patients, the neurological manifestations even progress despite resolution of both pathologic findings and intestinal symptoms.

Myotonic dystrophy in a patient of celiac disease: a new association?

PMID: 18972777  June 2008

[Untreated casein sensitivity as well? Soy? jcc]

 

 A 42-year-old white man presented with recurrent attacks of muscle pain and swelling. Clinically, he looked like he had severe pyogenic infection. He failed to respond to multiple courses of wide-spectrum antibiotics. Repeated cultures from muscle lesions and from the blood were negative. Hospital course was very hectic and life threatening at times. Upon further questioning, the patient gave a history of frequent loose-bowel movements for many years. A duodenal biopsy with villous blunting and positive antiglidin antibodies confirmed the diagnosis of celiac disease. The patient had complete recovery and remained in remission on a gluten-free diet.
Neutrophilic myositis as a manifestation of celiac disease: a case report.
PMID: 18180977  Jan 2008

 

Neurological complications of coeliac disease: what is the evidence?
PMID: 18344378  April 2008

Neurological complications of celiac disease and autoimmune mechanisms: A prospective study.
PMID: 18343508  Mar 2008

A case of celiac disease mimicking amyotrophic lateral sclerosis. 

PMID: 17914346 Oct 2007   On Medscape:

Celiac disease is a rare cause of neuropathy that most commonly presents with symmetric distal sensory disturbances. We describe two patients with celiac disease in whom neuropathy presented unusually with progressive weakness of the limbs. In both patients a gluten-free diet induced a significant improvement of muscle strength and neurophysiological abnormalities, suggesting a direct pathogenetic role of sensitivity to gluten. Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent.

Celiac disease presenting with motor neuropathy: effect of gluten free-diet. 
PMID: 17226827  May 2007

Celiac disease is an immune-mediated disorder triggered by ingestion of wheat gliadin and related proteins in genetically susceptible individuals. In addition to the characteristic enteropathy, celiac disease is associated with various extraintestinal manifestations, including neurologic complications such as neuropathy, ataxia, seizures, and neurobehavioral changes. The cause of the neurologic manifestations is unknown, but autoimmunity resulting from molecular mimicry between gliadin and nervous system proteins has been proposed to play a role. In this study, we sought to investigate the immune reactivity of the anti-gliadin Ab response toward neural proteins. We characterized the binding of affinity-purified anti-gliadin Abs from immunized animals to brain proteins by one- and two-dimensional gel electrophoresis, immunoblotting, and peptide mass mapping. The major immunoreactive protein was identified as synapsin I. Anti-gliadin Abs from patients with celiac disease also bound to the protein. Such cross-reactivity may provide clues into the pathogenic mechanism of the neurologic deficits that are associated with gluten sensitivity.

Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I.  
PMID: 17475890  May 2007

Myopathy associated with gluten sensitivity.
PMID: 17143894  April 2007

Celiac disease has been associated with ataxia and other neurological signs but has not been associated with paroxysmal nonkinesigenic dyskinesias (PNKD) to date. We present a child with biopsy-proven celiac disease and a movement disorder resembling PNKD since the age of 6 months. She had complete resolution of her neurological symptoms with introduction of a gluten-free diet. Because a susceptibility locus for celiac disease has been reported on 2q33 and studies in PNKD show linkage to 2q, this report suggests further genetic investigations around this locus may be useful. 

Paroxysmal nonkinesigenic dystonia and celiac disease.
PMID: 17377923 March 2007

Celiac disease has been associated with a variety of neurological illnesses, most frequently cerebellar ataxia and peripheral neuropathy. We report presentation as Landry-Guillaine-Barriota syndrome in a 28-year-old woman with previously unsuspected celiac disease.

Landry-Guillaine-Barre syndrome as presentation of celiac disease.
PMID: 17401241 Feb 2007

CONCLUSION: Four of the nine patients with CP had increased levels of antigliadin antibodies AGA (IgA), a finding which calls for further studies concerning the possible connection between increased celiac markers and CP.

Is there a connection between severe cerebral palsy and increased gluten sensitivity? 
PMID: 17187621  Jan 2007

Celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathy.
PMID: 16967485  Jan 2007

 

We report the case of a woman with refractory celiac disease who developed abnormal spontaneous movements of the extremities and face consistent with myorhythmia. Investigation led to a diagnosis of encephalitis, confirmed by postmortem examination. The movements were likely caused by nonparaneoplastic encephalitis associated with refractory celiac disease. Etiologic and diagnostic considerations and treatment options are discussed.
Fatal encephalitis in a patient with refractory celiac disease presenting with myorhythmia and carpal spasm.
PMID: 17230474 Jan 2007

 

Celiac disease is a rare cause of neuropathy that most commonly presents with symmetric distal sensory disturbances. We describe two patients with celiac disease in whom neuropathy presented unusually with progressive weakness of the limbs. In both patients a gluten-free diet induced a significant improvement of muscle strength and neurophysiological abnormalities, suggesting a direct pathogenetic role of sensitivity to gluten. Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent.
Celiac disease presenting with motor neuropathy: Effect of gluten free-diet.
PMID: 17226827 Jan 2007

 

Symptomatic myoclonus.
PMID: 17336775  Dec 2006

Cognitive impairment and celiac disease.

PMID: 17030661 Oct 2006
 
Anti-ganglioside antibodies in coeliac disease with neurological disorders.  PMID: 16458087 Mar 2006

Encephalopathy due to carnitine deficiency in an adult patient with gluten enteropathy. PMID: 16325996 Nov 2005

Mechanisms underlying celiac disease and its neurologic manifestations. PMID: 15868404  Apr 2005 

Neurologic presentation of celiac disease.
PMID: 15825133 April  2005

 

Autonomic neuropathy and coeliac disease.

PMID: 15774451  April 2005

Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease. PMID: 15389648 Feb 2005

Neurological abnormalities associated with celiac disease.
PMID: 15592736 Nov 2004

Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. PMID: 15526989 June 2004 

 

Neurologic manifestations of gastrointestinal disease

PMID:  11754307  Feb 2002

 

Celiac disease can be associated with a wide spectrum of neurological and psychiatric symptoms (cerebellar ataxia, neuromuscular manifestations, epilepsy, dementia), even in the absence of malabsorption or gastrointestinal symptoms.

[Celiac disease can be associated with severe neurological symptoms. Analysis of gliadin antibodies should be considered in suspected cases]
PMID: 11571796   Aug 2001

 

It is well known that coeliac disease may be associated with various neurological manifestations. We have had a high index of suspicion of coeliac disease during recent years in our neurological clinic. As a result 10 (7%) out of 144 of our new coeliac patients were detected because of neurological symptoms. The most common neurological manifestations were neuropathy, memory impairment and cerebellar ataxia.

Coeliac disease presenting with neurological disorders.
PMID: 10529537   1999

 

Does cryptic gluten sensitivity play a part in neurological illness? 

 PMID: 8598704 Feb 1996

 

Celiac disease and childhood stroke. PMID: 15301836

Range of neurologic disorders in patients with celiac disease.
PMID: 15173490  June 2004  Full text

Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders
PMID: 12465725  Nov 2002

Neurological complications of inflammatory intestinal diseases
PMID: 12910446  Aug 2003

The neurological manifestations of celiac disease in children
PMID: 14702754  Dec 2003

Celiac disease can be associated with severe neurological symptoms
PMID: 11571796  Aug 2001

Atypical neurological involvement associated with celiac disease.
PMID: 11509083  Jan 2001

Sporadic cerebellar ataxia associated with gluten sensitivity.
PMID: 11335703   May 2001  Full Text
 

Choreic syndrome and coeliac disease: A hitherto unrecognised association. PMID: 15077250 Aug 2004

Gait and Balance Dysfunction in Adults. PMID: 12628066  Mar 2003

Cortical myoclonus and cerebellar pathology.
PMID: 10746609  March 200