Polyneuropathy, thiamin deficiency

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. 

As might be predicted from these similarities between PNS and CNS, many disease entities can affect both these tissues. It should be noted, however, that the clinical expression of such diseases is variable and is sometimes restricted to the PNS. For example, patients with thiamine deficiency may display symmetrical distal sensorimotor polyneuropathy without accompanying CNS degeneration. Untreated infection with human immunodeficiency virus (HIV) may cause early polyneuropathy, with dementia appearing months or years later. Similarly, patients with sulfatidase deficiency or adrenoleukodystrophy may present initially with polyneuropathy, while their CNS dysfunction remains clinically undetectable. 

Thiamin deficiency in alcoholics may be caused by decreased intake, reduced absorption, and impaired ability to use ihe absorbed vitamin. The ataxia and ocular symptoms associated with the deficiency in alcoholics are known as Wernicke s disease. Vitamin therapy can provide relief from nystagmus within a few hours of treatment and from ataxia within several weeks. The treatment of alcoholics also involves the supply of other nutrients lacking in the diet, such as folate, vitamin B12, and protein. Left imtreated, patients suffering from Wernicke s disease continue to develop Korsakoff s psychosis, which involves amnesia and confusion. Only about 25% of patients with Korsakoff s psychosis can be completely cured by thiamin treatment, which must be continued for a few weeks or months. The two conditions just described constitute the Wemicke-Korsakoff syndrome. The S5mdrome was named after two researchers. Karl Wernicke, a German, noted impaired or paralyzed eye movements and imstable walking and disorientation in his patients, most of whom were alcoholics. Polyneuropathy, a weakness of the hands, calves, and feet, was also noted. Sergei Korsakoff, a Russian, observed amnesia and confusion and an inability to learn new names or tasks in alcoholic patients. 

Beriberi occurs whenever thiamine intake is less than 0.4 mg/d for an extended period of time. It occurs where polished rice is a dietary staple, and, in Western society, in poor and elderly populations and alcoholics. Beriberi has wet, dry, and cardiac types, and an individual may have more than one type. Wet refers to pleural and peritoneal effusions and edema dry refers to polyneuropathy without effusions. Cardiomyopathy is the principal feature of the cardiac type. An infantile form occurs in breast-fed infants, usually 2-5 months of age, nursing from thiamine-deficient mothers. The symptoms of beriberi remit completely upon thiamine supplementation. A subclinical deficiency of thiamine occurs in hospital patients and the elderly. Deficiency of thiamine and other vitamins may contribute to a generally reduced state of health in these populations. 

In its more severe forms thiamine deficiency can present as (1) wet beri-beri with generalized oedema 2md tendency to heart failure, (2) dry beri-beri, a chronic polyneuropathy with degenerative changes in the peripheral nerves, (3) infantile beri-beri, a chronic marasmic state also frequently associated with sudden heart failure, and (4) Wernicke s encephalopathy, which may be seen in chronic alcoholics and may be regarded as a cerebral beri-beri . Less severe states of thiamine deficiency usually manifest themselves as a chronic polyneuropathy. Problems of differential diagnosis from other forms of peripheral neuritis therefore arise, and it is in this connection that studies of pyruvate metabolism may be of help. 

Nutritional deficiencies—A number of alcohol-related neurological disorders are due to nutritional deficiencies— primarily the B vitamins, including thiamin. These deficiencies result from decreased taste for food, decreased appetite (alcohol is high in calories and suppresses the appetite), and malabsorption of nutrients due to the irritated lining of the stomach and small intestine. A common nutritional deficiency disorder, peripheral polyneuropathy, is characterized by weakness, numbness, partial paralysis of extremities, pain in the legs, and impaired sensory reaction and motor reflexes. This condition is reversible with adequate diet and supplemental thiamin and other B vitamins. 

The biochemical changes that are present in the polyneuropathy which can result from a deficiency of thiamine in the diet have been well worked out in the years that have elapsed since 1885 when the Japanese naval surgeon, Takaki, first claimed that beri-beri is a nutritional disease resulting from the ingestion of excessive quantities of polished rice [2]. Eijkmann in 1897 [3] carried out a classical nutritional experiment when he showed for the first time that fowls fed on a diet of polished rice developed weakness of the legs and opisthotonus. As a result of his observations he was able to... 

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