Tuesday, July 3, 2007

Wernicke–Korsakoff syndrome

The Wernicke–Korsakoff syndrome is a vitamin B1 defi
ciency disease particularly associated with chronic
alcoholics who derive more than half their daily calories
from ethanol every day. Binge drinkers who eat
normally between bouts and who are in a reasonable
state of health are not prone to the disease. Alcoholic
beverages contain water, ethanol, variable amounts of
carbohydrate, and little else of nutritive value. Apart
from beers, protein and vitamin content of these
beverages is extremely low. Vitamin B1 defi ciency in
the alcoholic is a combination of several factors. The
main factor is reduced food intake due to depressed
consciousness during inebriation and hangover. Suppression
of appetite by alcohol has been postulated,
but not studied much. Gastritis and diarrhoea caused
by alcohol will impair digestion and absorption, and
alcoholic pancreatitis results in decreased secretion of
digestive enzymes. Impairment of thiamin absorption
has been reported in severely alcoholic patients
(Tomasulo et al., 1968). In cases of alcoholic cirrhosis
of the liver, there may be a decreased conversion of
thiamin to TPP and a decreased capacity of the liver to
store vitamin B1 (Leevy & Baker, 1968). The mortality
of the Wernicke–Korsakoff syndrome is 90% without
therapy, heart failure being the usual cause of death.
The Wernicke–Korsakoff syndrome has two components,
Wernicke’s encephalopathy (or Wernicke’s
disease) and Korsakoff ’s psychosis. The former is
specifi c to vitamin B1 defi ciency, whereas the latter
may be seen in association with other disorders of the
nervous system.

Wernicke’s disease is characterized by a triad of
clinical signs: eye abnormalities, incoordination and
altered state of consciousness. They occur simultaneously,
or one may precede the other by days or weeks.
The eye signs are caused by paralysis of one or more
of the eye muscles (ophthalmoplegia). Typical signs
are photophobia, nystagmus (oscillation of the eyeballs),
strabismus (crossed eyes) and diplopia (double
vision). In advanced cases, there may be complete loss
of eye movement and the pupils may become non-reactive.
The disorder of coordination is seen as a broadbased
stance and ataxia (staggering gait). Common
mental signs are listlessness, inattentiveness, apathy
and confusion. There is sometimes delirium and, in
extreme cases, stupor and coma.

Following the administration of thiamin, the
symptoms of Wernicke’s disease are alleviated and the
features of Korsakoff ’s psychosis become evident. The
most notable features are a form of amnesia in which
events of ordinary daily life are forgotten as quickly
as they occur but events in the distant past are well
remembered. The patient is alert and can converse,
think and solve problems, but is unable to memorize
new information. The symptom of confabulation
(story-telling) is an attempt by the patient to hide the

Neuropathological changes are seen as brain lesions
distributed in a bilaterally symmetrical fashion
in the mammillary bodies, superior vermis of the
cerebellum, hypothalamic nuclei and other diencephalic
structures (Reuler et al., 1985). Histology
shows necrosis of neurons and glial cells. There is also
capillary damage with endothelial proliferation and
pin-point haemorrhages. Damage to specifi c regions
of the brain can account for the clinical features of
286 Vitamins: their role in the human body
Wernicke–Korsakoff syndrome. Thus, for example,
the nystagmus is due to damage of the sixth cranial
nerve; the ataxia is related to loss of neurons in the
superior vermis of the cerebellum; and the amnesia is
associated with atrophy of the mammillary bodies.
Although the Wernicke–Korsakoff syndrome results
from a lack of dietary vitamin B1, two clinical observations
suggest that genetic factors are important
in its pathogenesis: it develops in only a small majority
of alcoholics and other chronically malnourished
persons, and it occurs much more frequently among
Europeans than among Asians. The possibility of
a genetic effect was investigated by Blass & Gibson
(1977) who found that transketolase in tissue-cultured
cells from patients with Wernicke–Korsakoff
syndrome was abnormal in that the binding of TPP
to the apoenzyme was diminished. The abnormality
persisted through more than 20 generations of
culture in medium containing excess thiamin and no
ethanol, and therefore appeared to be genetic rather
than dietary. Thus the abnormal enzyme appears to
be a structural mutant. Persistent aberrations had
previously been found in erythrocyte transketolase
from these patients, even after they had been treated
with thiamin for months while in hospital. The abnormality
appeared to be specifi c for transketolase as
pyruvate dehydrogenase and α-ketoglutarate dehydrogenase
were unaffected.

Because the symptoms of Wernicke’s disease can be
alleviated following the administration of thiamin,
the abnormal transketolase is presumably clinically
unimportant if the diet is adequate. This type of genetic
abnormality is an example of an inborn predisposition
to metabolic disorders. Unlike inborn errors
of metabolism, inborn predispositions are likely to
be clinically silent unless the person with the predisposition
faces an appropriate stress. In cases of Wernicke–
Korsakoff syndrome, the stress is a defi ciency of
vitamin B1. Nixon et al. (1984) demonstrated a highly
signifi cant association between a particular variant
of erythrocyte transketolase and the Wernicke–Korsakoff
syndrome, supporting the concept that the
syndrome has a genetic as well as a dietary origin.

Beriberi is treated with a proprietary thiamin
preparation, the dosage and route depending on the
patient’s condition. To prevent further recurrences,
a good diet containing all of the B-group vitamins
should be instituted. Severe cardiac (shoshin) beriberi
and Wernicke–Korsakoff syndrome constitute
medical emergencies requiring immediate treatment
with thiamin, given intravenously. Treatment of Wernicke–
Korsakoff syndrome will eradicate the symptoms
of encephalopathy (with abstinence of alcohol),
but the psychosis is irreversible.

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