Experimentally induced thiamine deficiency in beagle dogs: pathologic changes of the central nervous system.

Brain and spinal cord were examined in twenty-two 2- to 5-month-old Beagle dogs fed a purified thiamine-deficient ration for 84 +/- 42 (range, 32 to 134) days. Eleven dogs were used as principals, 6 were pair-fed controls, and 5 were controls fed ad libitum. Thiamine at 300 micrograms/kg of body weight was administered IM to control groups once a week. Lesions occurred in 2 topographic patterns in the brain of 8 of the principals. In pattern I, only the caudal colliculi were involved. In pattern II, the suprasplenial gyri of the cerebral cortex and the claustra, caudal colliculi, cerebellar nodulus, and medial vestibular nuclei were commonly involved. In both patterns I and II, gray matter was primarily involved, and in bilateral structures, the 2 sides were affected. Lesions were not limited to a given cerebral lamina or layer of the cerebellum, whereas sulcal areas were relatively spared, and the cingulate gyri were completely spared. Microscopic appearance of the lesions varied greatly among locations and individual principals. Collectively, regressive and reparative changes indicated that there was a progressive process which began with spongiosis and ended with tissue necrosis. These included hydropic vacuolation of the neuropil and myelin sheaths followed by demyelination, neuronal cell body necrosis, hypertrophy and hyperplasia of endothelial cells, necrosis of glia, neutrophil infiltration, disintegration of neuropil, and, finally, accumulation of lipid-containing phagocytes. Axonal degeneration was variable. Neuronal necrosis in the brain stem was characterized by acute swelling and lysis and by shrinkage of the cell body in cerebral and cerebellar cortex and basal ganglia.