There are suggestions that there is a hereditary factor in the susceptibility of Wernicke-Korsakoff disease and possibly explains why only a small proportion of nutritionally deficient alcoholic patients develop this disease. Candidates for this variability have been proposed to be in transketolase activity or in the thiamine transporter gene, possibly on an epigenetic basis, but other genetic regions have been studied and no consistent genetic associations have emerged.
Approximately half of patients with Wernicke-
Korsakoff disease show electroencephalographic (EEG) abnormalities, consisting of diffuse mild to moderate slow activity. Total cerebral blood flow and cerebral oxygen and glucose consumption may be reduced in the acute stages of the disease and may still be present after several weeks of treatment (Shimojyo et al). These observations indicate that significant reductions in brain metabolism need not be reflected in EEG abnormalities or in depression of the state of consciousness and that the latter is more a function of the location of the lesion than of the overall degree of metabolic defect.
Course of the Illness
The mortality rate in the acute phase of Wernicke disease was 17 percent in the series of patients collected by Victor et al (1989) many decades ago. The fatalities were attributable mainly to hepatic failure and infection (pneumonia, pulmonary tuberculosis, and septicemia being at that time the most common). Some deaths were undoubtedly a result of the cerebral or cardiac effects of thiamine deficiency that had reached an irreversible stage.
Most patients respond in a fairly predictable manner to the administration of thiamine, as detailed further on. The most dramatic improvement is in the ocular manifestations. Recovery often begins within hours or sooner after the administration of thiamine and practically always within several days. This effect is so constant that a failure of the nystagmus and ocular palsies to respond to thiamine should raise doubts about the diagnosis of Wernicke disease. Horizontal nystagmus sometimes disappears in minutes. Sixth-nerve palsies, ptosis, and vertical gaze palsies recover completely within a week or two in most cases, but vertical nystagmus may sometimes persist for several months. Horizontal gaze palsies usually recover completely, but in 60 percent of cases a fine horizontal nystagmus remains as a permanent sequela. In this respect, horizontal nystagmus is unique among the ocular signs.
In comparison with the ocular signs, improvement of ataxia is delayed. Approximately 40 percent of patients recover completely from ataxia. The remaining patients recover incompletely or not at all and are left with a slow, shuffling, wide-based gait and inability to walk tandem. The residual gait disturbances and horizontal nystagmus provide a means of identifying obscure and chronic cases of dementia as alcoholic-nutritional in origin. Vestibular function improves at about the same rate as the ataxia of gait, and recovery is usually but not always complete.
The early symptoms of apathy, drowsiness, and global confusion invariably recede, and as they do the defect in memory and learning stands out more clearly. However, the memory disorder, once established, recovers completely or almost completely in only 20 percent of patients. The remainder is left with varying degrees of permanent Korsakoff amnesia.
It is apparent from the foregoing account that