Neurological manifestations in celiacs and vitamin E status

CORRESPONDÊNCIA

Neurological manifestations in celiacs and vitamin E status

To the Editor - I read with interest the article by Siqueira Neto et aI.¹ concerning neurological manifestations of celiac disease (CD). The authors had investigated serum vitamin E concentration in only one of the three presented patients, and it was reduced. Siqueira Neto et aI. discussed pathogenic mechanisms of neurological dysfunction in celiacs and concluded "the immune rather than the nutritional changes of CD are given more credit in the literature". In my opinion, although the nutritional concept of neurological manifestations is "outmoded"², we should keep in mind reports on possible associations between vitamin E deficiency in CD and neurological complications^3,4. Twelve of 32 (37.5%) patients, presented in English literature, with CD and neurological complications with examined tocopherol had reduced plasma or serum concentrations of this vitamin⁵. The nervous tissue is particulary vulnerable to free radical damage. Several experimental observations have emphasized the role of oxidative stress and vitamin E deficiency in pathogenesis of neurological abnormalities^6-9. Probably there is association between low alpha-tocopherol (the major vitamin E component) level in erythrocytes and multiple sclerosis in humans¹⁰.

Recently, several workers have suggested that the concentration of alpha-tocopherol in red blood cells is more useful as a measure of the vitamin status than its plasma/serum level^11-13. I examined alpha-tocopherollevel both in plasma and in erythrocytes of 18 untreated patients with CD⁵. All of them had alpha-tocopherol concentrations in erythrocytes below the norm, but only six had reduced plasma concentrations of the vitamin. Two of the three celiacs with neurological manifestations had normal plasma alpha-tocopherol levels.

The possibility should not be excluded that a least some neurological manifestations in celiacs may have their origin in a deficiency of tocopherol^3,14 and correction of the vitamin status may offer some benefit for patients. Further more detailed investigation is required into this subject.

REFERENCES

1. Siqueira JI Neto, Costa AC, Magalhaes FG, Silva GS. Neurological manifestations of celiac disease. Arq Neuropsiquiatr 2004;6:969-972.

2. Hadjivassiliou M, Grünewald RA, Davies-Jones GAB. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 2002;72:560-563.

3. Trabert W. Celiac disease and vitamin E deficiency. Neurology 1992; 42:1641-1642.

4. Battisti C, Dotti MT, Formichi P, et al. Disappearance of skin lipofuscin storage and marked clinical improvement in adult onset coeliac disease and severe vitamin E deficiency after chronic vitamin E megatherapy. J Submicrosc Cytol Pathol 1996;28:339-344.

5. Hozyasz KK, Chelchowska M, Laskowska-Klita T. Vitamin E levels in patients with coeliac disease (in Polish). Med Wieku Rozwoj 2003;7:593-604.

6. Muller DP, Goss-Sampson MA. Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency. Crit Rev Neurobiol 1990;5:239-263.

7. Enrione EV, Weeks OI, Kranz S, Shen J. A vitamin E-deficient diet affects nerve regeneration in rats. Nutrition 1999;15:140-144.

8. Frantseva MV, Perez Velazquez JL, Tsoraklidis G, et al. Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 2000;97:431-435.

9. Podratz JL, Rodriguez EH, Windebank AJ. Antioxidants are necessary for myelinationofdorsal root ganglion neurons, in vitro. Glia 2004;45:54-58.

10. Karg E, Klivenyi P, Bencsik K, Turi S, Vecsei L. Alpha-tocopherol and NADPH in the erythrocytes and plasma of multiple sclerosis patients: effect of interferon-beta-l b treatment. Eur Neurol 2003;50:215-219.

11. Solichova D, Korecka L, Svobodova I, et al. Development and validation of HPLC method for the determination of alpha-tocopherol in human erythrocytes for clinical applications. Anal Bioanal Chem 2003;376:444-447.

12. Simon E, Gariepy J, Cogny A, Moatti N, Simon A, Paul JL. Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima-media thickening in asymptomatic men at risk for cardiovascular disease. Atherosclerosis 2001;159:193200.

13. Ochoa JJ, Ramirez-Tortosa MC, Quiles JL, et aI, Oxidative stress in erythrocytes from premature and full-term infants during their first 72 h of life. Free Radic Res 2003;37:317-322.

14. Pengiran Tengah C, Wills A. Neurological associations of coeliac disease. Adv Clin Neurol Rehab 2002;2:7-9.

Kamil K. Hozyasz, MD

Pediatric Department, Institute of Mother and Child

ul. Kasprzaka 17a, 01-211 Warsaw, Poland

e-mail: [e-mail]

The Author's Response - We thank Dr. Kamil K. Hozyasz for his interest in our study¹. Dr Hozyasz suggests that some of the neurological manifestations in celiacs have their origin in deficiency of tocopherol and that correction of the vitamin status may offer some benefit for patients. We agree with him, and although not mentioned in our article all the patients had a slight reduction of serum vitamin E that was corrected after vitamin supplementation. Despite the normalization of tocopherol levels, improvement was not observed. We did not measure alpha-tocopherol in red blood cells and maybe this measurement could be of help in our cases². Although we think the nutritional concept of neurological manifestations in celiac disease (CD) can not be forgotten, we still believe that in our specific cases the immune changes are more important. The recommended daily allowance of tocopherol, based on the [alpha]-tocopherol form, is 22IU (14.7 mg) for adults and 28IU (18.7 mg) for lactating mothers³. Our patients are still receiving a 400 IU daily dose of tocopherol and neurologic status remains unaffected. We think that using this supplemental dose of tocopherol and with normalized serum tocopherol levels, it is not probable that our patients have low red blood cell levels of tocopherol, although it is still possible. We know that manifestations like dementia and ataxia have been described in patients with low tocopherol levels, but in CD neurological presentation can range from eplilepsy to polymyositis which are not conditions related to tocopherol deficiency^4-6. The neuropathologic findings in gluten ataxia include perivascular cuffing with inflammatory cells which also suggest an immune mediated event⁷. In conclusion, we think that vitamin supplementation should be administered to all patients with CD and neurological manifestations, although it is not possible to predict how many of this patients will recover because the immune origin of many of this symptoms will still be there.

REFERENCES

1. Siqueira Neto JI, Costa ACLV, Magalhães FG, Silva GS. Neurological manifestations of celiac disease. Arq. Neuro-Psiquiatr 2004;62: 969-972.

2. Hozyasz KK, Chelchowska M, Laskowska-Klita T. Vitamin E levels in patients with celiac disease. Med Wieku Rozwoj 2003;7:593-604.

3. US Department of Health and Human Services, National Institutes of Health. Vitamin E [online]. Available from URL: http://www.nih.gov/

4. Wills AJ, Unsworth DJ. The neurology of gluten sensitivity: separating the wheat from the chaff. Curr Opin Neurol 2002;15:519-523.

5. Chin RL, Sander HW, Brannagan TH, et al. Celiac neuropathy. Neurology 2003; 60:1581-1585

6. Hadjivassiliou M, Gibson A, Davis-Jones GAB, Lobo JA, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play part in neurological illness? Lancet 1996;347:369-371.

7. Hadjivassiliou M, Grunewald RA, Chattopadhyay AK, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet 1998;352:1582-1585.

Gisele Sampaio Silva, MD

UNIFESP-EPM - São Paulo, Brasil

Publication Dates

• Publication in this collection
  05 July 2005
• Date of issue
  June 2005