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• Letter from Rome: Celiac disease and brain
  Ludovico Abenavoli
  Published on: 14 June 2024
• Neurologic complications of celiac disease
  Chiara Briani
  Published on: 14 April 2016

• Published on: 14 June 2024

  Letter from Rome: Celiac disease and brain

  • Ludovico Abenavoli, medicine doctor University Magna Graecia of Catanzaro

  Dear Editor

   

  The history of celiac disease (CD) is very long. The cultivation of grains, developed in the Neolithic period after the last ice age, particularly in the “Fertile Crescent” of the Near East including the Tigris, the Euphrates and the Upper Nile. With the development of cooking, agriculture came into its own and wheat became a main support of the vast growth in population in succe...

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  Dear Editor

   

  The history of celiac disease (CD) is very long. The cultivation of grains, developed in the Neolithic period after the last ice age, particularly in the “Fertile Crescent” of the Near East including the Tigris, the Euphrates and the Upper Nile. With the development of cooking, agriculture came into its own and wheat became a main support of the vast growth in population in successive millennia. Thus arose the possibility of development of syndromes, including CD, reflecting intolerance of wheat. In this context is interesting that the generally accepted earliest description of CD, is attributed to “Aretaeus the Cappadocian” (I-II century A.D.), and Cappadocia is a region in the eastern part of Turkey near to the ‘Fertile Crescent’. Further descriptions, which may have been of CD followed, by the Dutch physician Vincent Ketelaer, William Hillary of Yorkshire, England, and others.

  The origin of the modern history of CD is ascribed to Samuel Gee in a lecture in 1887 followed by his written account in the Saint Bartholomew’s Hospital Reports in 1888. He termed the condition ‘the Celiac Affection’ after the translation by Francis Adams, in 1856, of the description by Aretaeus. In a notably description, Gee refers to the appearance of the stools, the onset of the condition, the muscular weakness, the abdominal distension and the chronic course of the disease.

  Subsequent to the suggestion by Samuel Gee there were various attempts at dietary management which bore some relation to the eventual recognition of cereal grains as being responsible.

  Herter in 1908 suggested that fats were better tolerated than carbohydrates, Still in 1918 drew attention to the poor tolerance of bread, Howland in 1921 recognised intolerance to carbohydrates and Haas in 1924 suggested a banana diet which, even though it contains carbohydrates, excludes the damaging cereals.

  The great breakthrough was by Wim Dicke of The Juliana Children's Hospital in The Hague. In his doctoral thesis of 1950 to the University of Utrecht he showed that exclusion of wheat, rye and oats from the diet led to dramatic improvement in the general condition of the child and marked reduction in the fatty diarrhoea. Wheat starch did not have the same damaging effect. There are descriptions of how Dicke came across this association. During wartime the gruel supplied to children in hospital might, at different times, have contained wheat or other plant products, depending on what was available, which would have provided the clue. Confirmation came with Dicke's laboratory colleagues Weijers and Van de Kamer. With the chemical measurement of stool fat, it became possible to diagnose less severe cases showing that excluding wheat, rye, barley and oats led to reduction in the fat content of the stool and improvement in the clinical condition of the patient. French, showed that similar changes occurred in adults with otherwise unexplained steatorrhoea. Faecal fat is rarely estimated now because of the requirements for accurate diet and prolonged collection of stools, and the associated expense.

  Since wheat starch did not produce the effect, attention was drawn to the protein components of the relevant cereals, referred to as gluten since the work of Jacopo Bartolomeo Beccari in Bologna in 1745. At present the etiology and pathogenesis of these disorders is uncertain.

  In the recent years, same relevant studies concerning CD, are performed by Professor Giovanni Gasbarrini, Director to the Institute of Internal Medicine, Catholic University of Rome, and my chief. The research Group to Professor Gasbarrini, have been described pathophysiology mechanisms and clinical manifestations of CD and published more than 140 articles, on this topic, available in pub-med. In the May issue, Dr Grossman highlighted the relationship between CD and neurological disorders (1). Our group reported, a case of brain perfusion abnormalities, assessed by single photon emission computed tomography (SPECT) examination, in a 33-year-old CD patient with schizophrenia; regression of both cerebral hypoperfusion and schizophrenic symptoms was observed after 6 months of a gluten free diet (GFD) (2). On the basis of this case we performed a SPECT study evaluating regional cerebral perfusion in untreated CD adult patients (age: 37±9 years), comparing them with CD patients on GFD, and with healthy controls (3). The study showed the presence of regional cerebral hypoperfusion in 73% of the untreated CD patients, compared with only 7% of CD patients on GFD and none of the controls. An overall multivariate test showed a significant difference in cerebral perfusion among the three groups of subjects (p=0.01).

  Considering each single region, a significant lower cerebral perfusion was found in untreated celiac patients compared to controls in seven of the 26 cerebral regions evaluated. Perfusion defects were predominant in the superior and anterior areas of the frontal cortex with the involvement of the adjacent anterior cingulated cortex. We have been reported similar cerebral blood flow changes, in patients suffering from different neurological and psychiatric disorders (4,5). In according to the author, I suggest to early investigate the presence of CD in patients with neurological abnormalities.

  To conclude I want to give my gratitude to Professor Giovanni Gasbarrini, for his scientific commitment and to be a guide for us young researchers.

  References:

  1. Grossman G. Neurological complications of coeliac disease: what is the evidence? Pract Neurol. 2008; 8:77-89.
  2. De Santis A, Addolorato G, Romito A, et al. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med 1997; 242: 421-23.
  3. Addolorato G, Di Giuda D, De Rossi G, et al. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med 2004; 116: 312-17.
  4. Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and celiac disease. Am J Gastroenterol 2003; 98: 625-29
  5. Addolorato G, Leggio L, D'Angelo C, et al. Affective and psychiatric disorders in celiac disease. Dig Dis. 2008; 26: 140-48.

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  Conflict of Interest:
  None declared.

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• Published on: 14 April 2016

  Neurologic complications of celiac disease

  • Chiara Briani, MD
  • Other Contributors:
    • Armin Alaedini

  Dear Editor,

  We read with great interest the review by Grossman on neurologic complications of celiac disease in a recent issue of Pract Neurol.(1)
  

  Using an evidence-based approach, the author has carefully and critically analyzed articles published in the last decade on the most common neurologic manifestations associated with celiac disease, namely ataxia, epilepsy, and peripheral neur...

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  Dear Editor,

  We read with great interest the review by Grossman on neurologic complications of celiac disease in a recent issue of Pract Neurol.(1)
  

  Using an evidence-based approach, the author has carefully and critically analyzed articles published in the last decade on the most common neurologic manifestations associated with celiac disease, namely ataxia, epilepsy, and peripheral neuropathy. Grossman has rigorously dissected the evidence for, and against, the possible association of celiac disease with neurological manifestations.
  

  The association, the review concludes, does not seem to hold up when referral bias is considered or when strict criteria are applied.
  

  While still leaving open the possibility of an association between celiac disease and certain neurologic disorders, the author calls for well- controlled and prospective studies to help clarify the issue.
  

  We would like to call attention to a 2-year prospective study, which was recently published.(2)
  

  After a retrospective study of a cohort of celiac children, where we did not find a correlation between neurologic manifestations and improvement on gluten-free diet (3), we undertook a prospective study in an adult celiac population in order to evaluate the incidence of neurologic symptoms and examine the response to gluten-free diet. Our prospective study enrolled 71 patients with histologically proven celiac disease, who were prospectively followed for up to 28 months.
  

  Of the 71 patients, 69 were consecutively referred to our centre from the university’s gastroenterology department, whereas 2 directly sought treatment at our clinic for neuropathic symptoms. Forty-two patients were on gluten-free diet at recruitment. Adherence to the diet was assessed by testing for anti-transglutaminase antibodies. All patients underwent neurological and electrophysiological evaluation at recruitment and at every follow-up visit.
  

  The results of the prospective study showed that 3 patients were affected by sensory-motor polyneuropathy. However, 2 of the 3 patients with polyneuropathy had sought treatment at our clinic for neuropathic symptoms. Considering this referral bias, only one of the 69 celiac patients referred for evaluation was affected by neuropathy. Several other manifestations affecting the nervous system were detected in our celiac population (4 with headache, 4 with depression, 4 with entrapment syndromes, 1 with facial hemispasm, and one of the 3 patients with neuropathy was also affected by epilepsy). However, the relatively common occurrence in the general population of headache, depression, and entrapment neuropathies makes it difficult to conclude a likely association with celiac disease.
  

  Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients, but there was no clear correlation between anti-neural reactivity and active neurologic dysfunction.

  Follow-up of 62 patients during gluten-free diet did not reveal significant changes in electrophysiology. However, in 2 patients with neuropathy, improvement in symptoms did correlate with the diet.
  

  In conclusion, the results of our prospective study do not seem to support a causal relationship between biopsy-proven celiac disease and neurologic disease in the studied group of patients. We agree with Grossman that further well-controlled studies are warranted in order to clarify the relationship, as well as the effect of diet.
  

  The use of proper outcome measures should be considered when evaluating therapeutic efficacy of any intervention (e.g. diet) in such a heterogeneous disease.(4)
  

  While further research may end up refuting an association between celiac disease and neurologic dysfunction, gluten sensitivity, as defined only on the basis of presence of anti-gluten antibodies, might prove to have a connection with certain neurologic and psychiatric deficits.(5)
  

  The potential relevance and significance of elevated levels of these antibodies in the absence of celiac disease deserve proper attention as well and should not be overlooked.

  References

  1. Grossman G.
  Neurological complications of coeliac disease: what is the evidence?
  Pract Neurol. 2008;8:77-89.

  2. Briani C, Zara G, Alaedini A, Grassivaro F, Ruggero S, Toffanin E, Albergoni MP, Luca M, Giometto B, Ermani M, De Lazzari F, D’Odorico A, Battistin L.
  Neurological complications of celiac disease and autoimmune mechanisms: a prospective study.
  J Neurommunol. 2008;195(1-2):171-5.

  3. Briani C, Ruggero S, Zara G, Toffanin E, Ermani M, Betterle C, Guariso G.
  Anti-ganglioside antibodies in children with celiac disease: correlation with gluten-free diet and neurological complications.
  Alimentary Pharmacology and Therapeutics, 2004;20:231-235.

  4. Hobart JC, Cano SJ, Zajicek JP, Thompson AJ.
  Rating scales as outcome measures for clinical trials in neurology: problems, solutions, and recommendations.
  Lancet Neurol. 2007;6:1094-105.

  5. Briani C, Samario D, Alaedini A.
  Celiac disease: from gluten to autoimmunity.
  Autoimmun Rev. 2008;7(8):644-50.

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  Conflict of Interest:
  None declared.

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