In an attempt to investigate the neural mechanisms of acute ataxia in human Wernicke's disease, acute thiamine deficiency encephalopathy was produced in the rat by feeding them with a thiamine deficient diet in conjunction with daily subcutaneous injection of pyrithiamine, a thiamine antagonist. Between days 11-13, all of the rats fed on this regimen developed acute ataxic syndrome. It was classified into four stages according to the severity of the ataxia. The rats in stage one exhibited tremulousness of the head and body, restlessness and occasional ventral flexion posture. Stage two was manifest by widebased frank ataxic gait ; stage three, by inability to walk, although they could still right themselves on the floor. Stage four was manifest by inability to right themselves and with ventral flexion posture.
ENG analyses of the vestibulo-ocular nystagmus, provoked by the pendular rotation of the head, revealed suppression of nystagmus as early as in stage one. During stage 2-3, marked suppression of the vestibular nystagmus was evident. However, following intraperitoneal injection of thiamine, the nystagmus reappeared within a few hours. The compensatory horizontal head movements were disinhibited during stages 2-3 and abolished totally in stage 4. Also, anti-compenstatory head movements were observed, although the movement was quite slow. This was thought to be a postrotatory behavior and perhaps not a true anti-compenstatory movements. The labyrinthine righting was impaired during stage 2 and totally abolished in stage 3.
The pathological correlations of these observations were attempted by examining histological specimens of CNS in these animals. The impairment of vestibular nystagmus was attributable to the symmetrical lesions of the medial, superior, and less markedly the lateral vestibular nuclei and pontine reticular formation. Uninhibited compensatory head movements were perhaps due to the lesions of the pontine reticular formation, whereas the descending vestibular nucleus exhibited no significant pathology. The ventral flexion posture was in some way related to impaired otolith input at the level of the vestibular nuclei and/or medial reticular formation.
The ataxic syndrome in experimental Wernicke's encephalopathy appears to correlate well with the human syndrome in which the global confusional state, ocular motor disturbance and ataxia are the cardinal manifestations. We speculate that involvements of the vestibular nuclear complex and the medial pontine reticular formation in Wernicke's disease would play major roles in producing oculomotor as well as ataxic parts of the symptomatology. The animal model of human Wernicke's disease shown here would be useful not only in investigating the causes of deficiency encephalopathy, but also in evaluating the functions of the vestibular portion of the brainstem in performing locomotions and vestibulo-ocular integrations.
