PEDIATRICS Vol. 114 No. 6 December 2004, pp. 1734 (doi:10.1542/peds.2004-1248)
Neurologic Disorders in Patients With Celiac Disease: Are They Mediated by Brain Perfusion Changes?
Ludovico Abenavoli, MDLorenzo Leggio, MD
Daniela Di Giuda, MD
Giovanni Gasbarrini, MD
Giovanni Addolorato, MD
Institute of Internal Medicine
Catholic University of Rome
00168 Rome, Italy
To the Editor.—
We read with great interest the recent study reported by Zelnik et al1 on the relationship between celiac disease (CD) and neurologic disorders. The authors screened patients with CD and showed a strong association not only between CD and specific neurologic disorders such as cerebral ataxia, chronic neuropathies, myoclonic ataxia, progressive leukoencephalopathy, and dementia but also between CD and milder and more common neurologic conditions such as headache, learning disabilities and attention-deficit/hyperactivity disorder, development delay, and hypotonia.
In the discussion section the authors suggest that chronic immune-mediated inflammation, lymphocytic infiltration, or vasculitis of the central nervous system might cause irreversible neuronal, glial, or axonal damage, with little clinical improvement even after the start of a gluten-free diet (GFD) and cessation of the various autoantibodies in the peripheral blood or cerebrospinal fluid.
However, at present, the etiology and pathogenesis of these disorders are uncertain. In a recent study our group evaluated regional cerebral perfusion assessed by single-photon-emission computed tomography (SPECT) in untreated CD patients, comparing them with CD patients on a GFD and with healthy controls. The study showed the presence of regional cerebral hypoperfusion in 73% of the untreated CD patients, compared with only 7% of CD patients on a GFD and none of the controls.2 An overall multivariate test showed a significant difference in cerebral perfusion among the 3 groups of subjects (P = .01). Considering each single region, a significant lower cerebral perfusion was found in untreated patients with CD compared with controls in 7 of the 26 cerebral regions evaluated. There were no significant differences in cerebral perfusion between untreated patients and those on a GFD or between patients on a GFD and healthy controls, reflecting a beneficial effect of a GFD on these alterations.2 Perfusion defects were predominant in the superior and anterior areas of the frontal cortex with the involvement of the adjacent anterior cingulated cortex. Similar cerebral blood flow changes have been reported in patients suffering from different neurologic and psychiatric disorders. Our previous article reported a case of brain perfusion abnormalities, assessed by SPECT examination, in a CD patient with schizophrenia; regression of both cerebral hypoperfusion and schizophrenic symptoms was observed after 6 months of a GFD.3
In conclusion, we think that the presence of regional cerebral blood flow alteration in CD patients could play a pathogenetic role in psychiatric and neurologic manifestations, including the more common problems such as migraine headache and learning disabilities. In this connection, in the longitudinal study correctly quoted by the authors, our group showed that migraine patients with CD had regional cerebral blood flow alteration evaluated by SPECT; 6 months of GFD improved both SPECT abnormalities and the frequency, duration, and intensity of migraine.4 Finally, because the hemodynamic changes in CD seem to be linked to disease activity and resolved after GFD,3–5 a GFD should be started as soon as possible and also in patients who do not show the classic form of CD.
REFERENCES
- Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease.
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[Abstract/Free Full Text] - Addolorato G, Di Giuda D, De Rossi G, et al. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med. 2004;116 :312 –317[Medline]
- 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 –423[CrossRef][Medline]
- Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol. 2003;98 :625 –629[CrossRef][Web of Science][Medline]
- Arienti V, Califano C, Brusco G, et al. Doppler ultrasonographic evaluation of splanchnic blood flow in coeliac disease.
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[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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- Neurologic Disorders in Patients With Celiac Disease: Are They Mediated by Brain Perfusion Changes?: In Reply
- Nathanel Zelnik
Pediatrics 2004 114: 1734.[Extract] [Full Text]
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