Sequence of metabolic, clinical, and histological events in experimental thiamine deficiency.

The [14C]deoxyglucose technique was used to determine local cerebral glucose utilization (LCGU) in the rat at various times in two models of thiamine deficiency: pyrithiamine administration in addition to dietary deprivation, and dietary deprivation alone. In the pyrithiamine model most of the 40 structures examined showed a gradual decline in LCGU, reaching the lowest metabolic activity at day 11. A statistically significant rise in LCGU (p less than 0.05) was then noted between day 11 and day 12 or 14 in 18 structures, followed by the autoradiographic appearance of focal areas of centrally depressed glucose utilization in many of these same 18 structures. Only then did ambulatory difficulty, opisthotonus, and other advanced clinical sequelae of thiamine deficiency become evident, usually around day 18, followed by the appearance of focal histological lesions in the same distribution. On a different time scale, rats that were only deprived of thiamine in their diet over a prolonged period, but not their pair-fed controls, revealed the same metabolic and autoradiographic events, but the deprivation was not sufficiently prolonged to result in clinical or histological abnormalities. We believe that the selective rise in LCGU may set into motion a chain of events that leads to the subsequent clinical and histological consequences of thiamine deficiency.