Thiamin encephalopathy

Beri-beri or clinically manifest thiamin deficiency exists in several subforms infantile beri-beri and adult beri-beri. Infantile beri-beri occurs in exclusively breastfed infants of thiamin-deficient mothers. Adults can develop different forms of the disease, depending on their constitution, environmental conditions, the relative contribution of other nutrients to the diet as well as the duration and severity of deficiency. First of all, there is a so called dry or atrophic (paralytic or nervous) form, including peripheral degenerative polyneuropathy, muscle weakness and paralysis. Second, a wet or exudative (cardiac) form exists. In this form, typical symptoms are lung and peripheral oedema as well as ascites. Finally, there is a cerebral form, that can occur as Wernicke encephalopathy or Korsakoff psychosis. Tli is latter form mostly affects chronic alcoholics with severe thiamin deficiency. 

Thiamin has a very low toxicity (oral LD5o of thiaminchloride hydrochloride in mice 3-15 g/kg body weight). The vitamin is used therapeutically to cure polyneuropathy, beri-beii (clinically manifest thiamin deficiency), and Wernicke-Korsakoff Syndrome ( Wernicke encephalopathy and Korsakoff psychosis). In mild polyneuropathy, 10-20 mg/d water-soluble or 5-10 mg/d lipid-soluble thiamin are given orally. In more severe cases, 20-50 mg/d water-soluble or 10-20 mg/d lipid-soluble thiamin are administered orally. Patients suffering from beri-beri or from early stages of Wernicke-Korsakoff Syndrome receive 50-100 mg of thiamin two times a day for several days subcutaneously or intravenously until symptoms are alleviated. Afterwards, the vitamin is administered orally for several weeks. 

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart ilure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke s encephalopathy with KorsakofPs psychosis, which is associated especially with alcohol and dmg abuse. The central role of thiamin diphosphate in... 

Hepatic encephalopathy Hyperbilirubinemia Hypocalcemia Hypercalcemia Hyperparathyroidism Hypoparathyroidism Thiamine deficiency (Wernicke s) encephalopathy Diabetic ketoacidosis Nonketotic hyperosmolar coma Phosphate depletion Hypoglycemia Hypoxemia Hypercapnia... 

Thiamine deficiency results in early decreases in activity of the mitochondrial enzyme a-ketoglutarate dehydrogenase in brain. Wernicke s encephalopathy, also known as the Wernicke-Korsakoff syndrome is a neuropsychiatric disorder characterized by ophthalmoplegia, ataxia and memory loss. Wernicke s encephalopathy is encountered in chronic alcoholism, in patients with HIV-AIDS and in other disorders associated with grossly impaired nutritional status. The condition results from thiamine deficiency. 

Neuropathologic studies in animals with experimental thiamine deficiency consistently show early damage to glial cells rather than neurons. Studies in human patients with Wernicke s encephalopathy likewise show changes in astroglia, together with microglial proliferation, which is... 

Pannunzio, P., Hazell, A. S., Pannunzio, M., Rama Rao, K. V. and Butterworth, R. F. Thiamine deficiency results in metabolic acidosis and energy failure in cerebellar granule cells an in vitro model for the study of cell death mechanisms in Wernicke s encephalopathy. /. Neurosci. Res. 62 286-292, 2000. 

Inadequate nutrition and conditions which are complicated by malabsorption may lead to thiamine deficiency. Beriberi, a diet-deficiency disease, is especially prevalent in those parts of the East where the diet consists mainly of polished rice. The disease is characterized by neuritis but may also lead to serious heart failure. Recovery is prompt when adequate amounts of vitamin B1 are restored to the diet. Severe deficiency as can occur in alcoholics may lead to Wernicke s encephalopathy, often accompanied by Korsakoff s syndrome. Care should be taken with intravenous substitution with thiamine in these cases to prevent serious complications like vascular collapse with hypotension, respiratory distress or an-gioedema. 

Where patients are at risk of Wernicke s encephalopathy - for example, because of chronic alcohol abuse, hyperemesis gravidarum, or malnutrition - they should be given thiamine. In many countries no intravenous preparation of thiamine alone is available, and the compound preparations that are available are prone to cause anaphylactoid reactions, so they should be given by slow infusion, and with adequate facilities for resuscitation. A high potency preparation (Pabrinex ) that contains thiamine 250 mg in 10 ml with ascorbic acid, nicotinamide, pyridoxine and riboflavin, can be given by intravenous infusion over 10 min. 

The spectrum of cognitive deficits associated with chronic alcohol use extends to the extreme of Wernicke s encephalopathy and Korsakoff s psychosis. Wernicke s encephalopathy is an acute neurologic syndrome caused by thiamine deficiency. Symptoms include mental confusion, ophthalmoplegia, and ataxia. Many of these symptoms reverse with administration of thiamine however about 50% of patients are left with some degree of ataxia. Left untreated, Wernicke s encephalopathy can progress to stupor, coma, and death. Approximately 80% to 90% of alcoholics treated for Wernicke s encephalopathy are left with Korsakoff s psychosis, a syndrome of impaired learning and recent memory produced by lesions of the medial dorsal nuclei of the thalamus. 

It is indicated in wet beriberi, dry beriberi, Wernicke s encephalopathy, prophylaxis of thiamine deficiency, hyperemesis gravidarum, Korsakoff s syndrome, chronic alcoholics, multiple neuritis, toxic and confusional states, delirium tremens and anorexia nervosa. 

The Wernicke-Korsakofi syndrome consists of both an acute (i.e., Wernicke s encephalopathy) and a chronic phase (i.e., Korsakoff s psychosis). The acute encephalopathy may be precipitated or worsened by carbohydrates (including intravenous glucose) unless thiamine is also replenished before or during administration. Wernicke s encephalopathy may first be manifested by the following ... 

Thiamine is given for alcohol-induced liver toxicity (to prevent Wernicke s encephalopathy). 

HerouxM and Butterworth RF (1995) Regional alterations of thiamine phosphate esters and of thiamine diphosphate-dependent enzymes in relation to function in experimental Wernicke s encephalopathy. Neurochemistry Research 20,87-93. 

Homewood J and Bond NW (1999) Thiamin deficiency and Korsakoff s syndrome failure to find memory impairments following nonalcoholic Wernicke s encephalopathy. Alcohol 19, 75-84. 

Beriberi (infantile and adult) and Wernicke s encephalopathy (WE) are clinical manifestations attributed to thiamine deficiency. Beriberi is characterized by peripheral neuropathy including sensory, motor, and reflex functions affecting the distal segments of limbs more severely than proximal ones (TanPhaichitr, 1985). WE is a metabolic disease due to thiamine deficiency and is characterized by lesions in the thalamus, hypothalamus (including mammillary nuclei), and cerebellum (Victor et al., 1971 Harper and Butterworth, 1997). 

Aikawa H, Watanabe IS, Furuse T, Iwasaki Y, Satoyoshi E, Sumi T, Moroji T (1984) Low energy levels in thiamine-deficient encephalopathy. J Neuropathol Exp Neurol 43(3) 276-287... 

Butterworth RF (2006) Metabolic Encephalopathies. In Siegel GJ, Albers RW, Brady ST, Price DL (eds) Basic neurochemistry, 7th edn. Elsevier, London, pp 593-602 Butterworth RF, Besnard AM (1990) Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer s disease. Metab Brain Dis 5(4) 179-184 Butterworth RF, GaudreauC, Vincelette J, Bouigault AM, LamotheF, Nutini AM (1991) Thiamine deficiency and Wernicke s encephalopathy in AIDS. Metab Brain Dis 6(4) 207-212 Butterworth RF, Heroux M (1989) Effect of pyrithiamine treatment and subsequent thiamine rehabilitation on regional cerebral amino acids and thiamine-dependent enzymes. J Neurochem 52(4) 1079-1084... 

Harata N, Iwasaki Y (1995) Evidence for early blood-brain btirrier breakdown in experimental thiamine deficiency in the mouse. Metab Brain Dis 10(2) 159-174 Harper CG (1983) The incidence of Wernicke s encephalopathy in Australia A neuropathological study of 131 cases. J Neurol Neurosurg Psychiatry 46 593-598 Harper CG, Butterworth RF (1997) Nutritional and metabolic disorders. In Graham DI, Lantos PL (eds) Greenfield s neuropathology. Arnold, London, pp 601-655 Hayton SM, Kriss T, Wase A, Muller DP (2006) Effects on neural function of repleting vitamin E-deflcient rats with alpha-tocopherol. J Neurophysiol 95(4) 2553-2559 Hayton SM, MuUer DP (2004) Vitamin E in neural and visual function. Ann N Y Acad Sd 1031 263-270... 

TanPhaichitr V (1985) Epidemiology and clinical assessment of vitamin deficiencies in Thai children. In Eeckels RE, Ransome-Kuti O, Kroonenberg CC (eds) Child health in the tropics. Martinus Nijhoff Publishers, Dordrecht, pp 157-166 TanPhaichitr V (1999) Thiamin. In Shils ME, Olsen JA, Shike M et al (eds) Modem nutrition in health and disease, 9th edn. Lippincott Willitims Wilkins, Baltimore, MD Todd KG, Butterworth RE (1999) Early microglitil response in experimental thiamine deficiency tm immunohistochemical analysis. Glia 25(2) 190-198 Torvik A (1985) Two types of brain lesions in Wernicke s encephalopathy. Neuropathol Appl Neutobiol 11(3) 179-190... 

Giguere, J.-F., and Butten orth, R. R (1987). Activities of thiamine-dependent enzymes in tw o experimental models of thiamine deficiency encephalopathy. Neurachem. Res. 12, 3i)5-310. 

Buesa JM, Garcia-Teijido P, Losa R, Fra J. Treatment of ifosfamide encephalopathy with intravenous thiamin. Chn Cancer Res 2003 9(12) 4636-7. 

A 74-year-old man developed Wernicke s encephalopathy, which required treatment with intravenous thiamine after discontinuation of the glyceryl trinitrate infusion. 

Cases of Wernicke s encephalopathy caused by thiamine deficiency during parenteral nutrition are reported (21). 

A young man developed marked deterioration in his vision and oscillating vision, despite normal optic fundi, during parenteral nutrition he went on to develop a characteristic Wernicke s encephalopathy, confirmed by characteristic findings on MRI brain scan (42). The serum vitamin Bi concentration was 110 pg/ml (reference range 200-500). He responded fuUy to thiamine 300 mg/day in addition to betamethasone for 4 weeks. 

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