Thiamin deficiency can result in three distinct syndromes:
● a chronic peripheral neuritis, beriberi, which may or may not be associated with heart failure and edema
● acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, with little evidence of peripheral neuritis
● Wernicke’s encephalopathy with Korsakoff’s psy-chosis, a thiamin-responsive condition associated especially with alcohol and narcotic abuse.
In general, a relatively acute deficiency is involved in the central nervous system lesions of the Wernicke– Korsakoff syndrome, and a high energy intake, as in alcoholics, is also a predisposing factor. Dry beriberi is associated with a more prolonged, and presumably less severe, deficiency, and a generally low food intake, whereas higher carbohydrate intake and physical activity predispose to wet beriberi.
Chronic deficiency of thiamin, especially associated with a high carbohydrate diet, results in beriberi, which is a symmetrical ascending peripheral neuritis. Initially, the patient complains of weakness, stiffness and cramps in the legs, and is unable to walk more than a short distance. There may be numbness of the dorsum of the feet and ankles, and vibration sense may be diminished. As the disease progresses, the ankle jerk reflex is lost, and the muscular weakness spreads upwards, involving first the extensor muscles of the foot, then the muscles of the calf, and finally the extensors and flexors of the thigh. At this stage there is pronounced toe and foot drop: the patient is unable to keep either the toe or the whole foot extended off the ground. When the arms are affected there is a similar inability to keep the hand extended: wrist drop.
The heart may also be affected in beriberi, with dilata-tion of arterioles, rapid blood flow, and increased pulse rate leading to right-sided heart failure and edema, so-called wet beriberi. The signs of chronic heart failure may be seen without peripheral neuritis. The arteriolar dilatation probably results from high circulating concentrations of lactate and pyruvate as a result of impaired activity of pyruvate dehydrogenase.
Heart failure without increased cardiac output, and no peripheral edema, may also occur acutely, associ-ated with severe lactic acidosis. This was a common presentation of deficiency in Japan, where it was called shoshin (meaning acute) beriberi; in the 1920s some 26 000 deaths a year were recorded.
With improved knowledge of the cause and improved nutritional status, the disease has become more or less unknown, although in the 1980s it reappeared among Japanese adolescents consuming a diet based largely on such high-carbohydrate, low-nutrient, foods as sweet carbonated drinks, “instant” noodles, and polished rice. It also occurs among alcoholics, when the lactic acidosis may be life-threatening, without clear signs of heart failure. Acute beriberi has also been reported when previously starved subjects are given intravenous glucose.
Whereas peripheral neuritis, acute cardiac beriberi and lactic acidosis occur in thiamin deficiency associ- ated with alcohol misuse, the more usual presentation is as the Wernicke–Korsakoff syndrome, due to central nervous system lesions.
Initially, there is a confused state, Korsakoff’s psy-chosis, which is characterized by confabulation and loss of recent memory, although memory for past events may be unimpaired. Later, clear neurological signs develop: Wernicke’s encephalopathy. This is characterized by nystagmus and extraocular palsy. Post-mortem examination shows characteristic brain lesions.
Like shoshin beriberi, Wernicke’s encephalopathy can develop acutely, without the more gradual development of Korsakoff’s psychosis, among previously starved patients given intravenous glu-cose and seriously ill patients given parenteral hyperalimentation.