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Show EDITORIAL Wernicke Encephalopathy in Infants Arthur L. Prensky, MD Our knowledge of cellular biochemistry has increased enormously in recent decades, but the effects of profound reduction of single dietary constituents on function and stability of nerve cells in selected areas of the brain remain puzzling. In this issue of the Journal of Neuro- Ophthalmology, Kesler et al. ( 1) report the clinical features of three of twenty patients who developed Wernicke encephalopathy after being fed a soy- based thiamine- deficient diet during the first months of life. Apathy, vomiting, and abnormal eye movements brought them to medical attention and helped make the diagnosis. Although isolated cases have been reported previously in infants fed thiamine- deficient formulas by oral or parenteral routes ( 2,3,4), this is the first epidemic of thiamine deficiency in human infants resulting from the ingestion of a commercial formula. Phosphorylated esters of thiamine are stored in tissue and act as coenzymes in the function of major oxidative enzymes such as pyruvate, alpha- ketoglutarate dehydrogenase, and transketolase. A severe deficiency of thiamine in an otherwise satisfactory diet initially produces restricted damage in the nervous system. The signs of Wernicke encephalopathy predominate in the neonate. On the other hand, where infants suffer from thiamine deficiency associated with severe protein- calorie malnutrition, as in the Karen in southeast Asia, infantile beri- beri is a major cause of death ( 5). At least two factors could be responsible for this difference in clinical presentations. The diet of Karen dwellers contains foods that have considerable thiaminase, which is not found in formulas. Commercial formulas, on the other hand, contain much higher amounts of glucose, which is known to worsen the CNS effects of thiamine deficiency in the rat ( 6). This epidemic raises again two interesting questions in regard to thiamine deficiency. First, why does a thiamine- deficient diet preferentially affect neurons in particular areas of the nervous system such as the putamen, parts of the thalamus, and the periaqueductal gray matter? In neonates, these structures have high rates of oxidative metabolism which could make them more vulnerable? Thiamine turnover is also higher in these areas ( 7). Second, why did these children have no neurologic signs for up to six months on this thiamine- deficient diet, after which there was rapid progression and, in one case, lack of recovery with treatment? Thiamine is preferentially concentrated in the fetus by the placenta ( 8). Stores in the neonate should be adequate at birth. We can presume that a gradual decrease in tissue stores of thiamine and its esters after birth in infants placed on a low thiamine diet could result in a decrease in oxidative metabolism and mitochondrial function which progressively interferes with the normal activity of neurons and endothelial cells. As these cells begin to die, there is an influx of microglia and eventually macrophages and a rapid accumulation of toxic substances such as glutamate and elements capable of creating rapid oxidative damage to the cell that would accelerate cell death. Once cell death is extensive enough, there may be no recovery after treatment with thiamine ( 9). Kesler et al. ( 1) note that only 20 of 3,500 babies fed this diet became ill. They suggest that these may have been infants whose mothers had low stores of thiamine during From the Departments of Pediatrics and Neurology, Washington University School of Medicine. Address correspondence to Arthur L. Prensky, Departments of Pediatrics and Neurology, Washington University School of Medicine, 1 Childrens Place, St. Louis, MO 63110- 1002, E- mail: prenskya@ neuro. wustl. edu J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 167 J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 Editorial pregnancy or that there may have been a genetic predisposition in this group of symptomatic children. The reason for the selective vulnerability of this group of infants, like so many other aspects of isolated dietary deficiencies during development, is still not resolved. These cases of thiamine deficiency are reminiscent of a prior nutritional epidemic of the late 1970s when another soy- based formula was manufactured that was deficient in chloride ( 10). Acutely, children were lethargic with gastrointestinal symptoms and growth failure. The more severely involved children had a chloride- induced metabolic alkalosis. Some patients in this group have had deficits in language development that are still unexplained. These mini-epidemics suggest that when infants fed a commercial diet develop unexplained symptoms, an isolated dietary deficiency should be considered presumptively and treated before permanent damage is done. REFERENCES 1. Kesler A, Stolovitch C, Hoffmann C, et al. Acute ophthalmoplegia and nystagmus in infants fed a thiamine- deficient formula: an epidemic of Wernicke encephalopathy. J Neuro- Ophthalmol 2005; 25: 171- 174. 2. Davis RA, Wolf A. Infantile beriberi associated with Wernicke's encephalopathy. Pediatrics 1958; 21: 409- 20. 3. Wyatt DT, Noetzel MJ, Hillman RE. Infantile beriberi presenting as subacute necrotizing encephalomyelopathy. The JPediatr 1987; 110: 888- 92. 4. Meyers CC, Schochet SS, Jr, McCormick WE Wernicke's encephalopathy in infancy. Development during parenteral nutrition. Acta Neuropathol 1978; 43: 267- 9. 5. Luxemburger C, White NJ, ter Kuile F, Singh HM, et al. Beri- beri: the major cause of infant mortality in karen refugees. Trans R Soc Trop Med Hyg 2003; 97: 251- 5. 6. Zimitat C, Nixon PE Glucose induced IEG expression in the thiamin-deficient rat brain. Brain Res 2001; 892: 218- 27. 7. Todd K, Butterworth RE Mechanisms of selective neuronal cell death due to thiamine deficiency. Ann NY Acad Sci 1999; 893: 404- 11. 8. Dancis J, Wilson DJ, Hoskins IA, Levitz M. Placental transfer of thiamine in the human subject: in vitro perfusion studies and maternal-cord plasma concentrations. Am J Obstet Gynecol 1988; 159: 1435- 9. 9. Ke ZJ, Gibson GE. Selective response of various brain cell types during neurodegeneration induced by mild impairment of oxidative metabolism. Neurochem Intern 2004; 45: 361- 9. 10. Malloy MH, Graubard B, Moss H, et al. Hypochloremic metabolic alkalosis from ingestion of a chloride- deficient infant formula: outcome 9 and 10 years later. Pediatrics 1991; 87: 811- 22. 168 © 2005 Lippincott Williams & Wilkins |
