Second edition

13.qxd 3/10/08 9:50 AM Page 469
delirium, dysarthria, cogwheel rigidity, gegenhalten, and
myoclonus (Ishii and Nishihara 1981; Jolliffe et al. 1940;
Serdaru et al. 1988).
Pellagra of gradual onset appears insidiously over many
months, and, when fully developed, is characterized by the
classic ‘three Ds’ of dementia, dermatitis, and diarrhea
(Spivak and Jackson 1977). The dementia may present
with apathy, depression, or anxiety; however, over time
typical cognitive deficits, such as decreased memory and
poor concentration, eventually appear. The dementia at
times may also be marked by delusions or hallucinations
(Pierce 1924). The dermatitis is characterized initially by
erythematous lesions in sun-exposed areas. Eventually, the
skin becomes hyperpigmented and roughened, and it is
from the Italian for rough (pelle) skin (agra) that the disease
gains its name. Diarrhea may be severe, and the fluid
may be blood tinged. It must be stressed that most cases of
pellagra do not, however, present with the full ‘three Ds’;
some patients with pellagrous dementia may have only one
of the other ‘Ds’, and in some cases there may only be
dementia, without any rash or diarrhea.
MRI scanning is unremarkable and the EEG shows generalized
slowing.
Although the serum niacin level is low, a more reliable,
if rarely ordered, test is a 24-hour urine test for niacin
metabolites.
Course
The encephalopathic form may be rapidly progressive, and
coma and death may occur in a matter of weeks. The
chronic form pursues a slower course, with death in a
matter of years.
Etiology
Niacin deficiency occurs most commonly as a result of
dietary deficiency. As noted earlier, in current practice in
developed countries this is seen primarily in malnourished
alcoholics as the encephalopathic form. The chronic form
of pellagra was endemic in the American South among
those individuals who subsisted primarily on corn. As corn
contains niacin in a bound, biologically less active form,
and also lacks tryptophan, these individuals very gradually
became niacin deficient. Since corn flour was ‘enriched’ with
niacin, however, the chronic form of pellagra has almost disappeared
in the United States. Other causes of niacin deficiency
include bowel resection, Crohn’s disease (Zaki and
Millard 1995), and anorexia nervosa (Rapaport 1985).
In addition to dietary lack, pellagra has also been noted
in conditions in which the normal endogenous conversion
of tryptophan to niacin is, for one reason or another,
impaired. Perhaps the most common example of this is in
patients treated with isoniazid. The normal enzymatic conversion
of tryptophan to niacin is dependent on the activated
13.4 Wernicke’s encephalopathy 469
form of pyridoxine (vitamin B6); isoniazid impairs the
conversion of the inactive form of B6 to the active form
and by this indirect mechanism reduces the endogenous
production of niacin (Ishii and Nishihara 1985). Another
example is in cases of carcinoid tumor, in which the gross
overutilization of tryptophan by the tumor leaves less
available for conversion to niacin.
Within the central nervous system (Hauw et al. 1988;
Ishii and Nishihara 1981; Langworthy 1931), neurons are
swollen and display chromatolysis with eccentric nuclei
and a loss of Nissl substance. These chromatolytic changes
may be seen in neurons of the cerebral cortex, basal
ganglia, dentate nuclei, brainstem motor nuclei, and the
anterior horn of the spinal cord.
Differential diagnosis
The acute encephalopathic form may be confused with
other disorders seen in chronic alcoholics, such as delirium
tremens or Wernicke’s encephalopathy. Prominent
tremor, of course, favors a diagnosis of delirium tremens.
Nystagmus, a sixth cranial nerve palsy, or ataxia favors
Wernicke’s encephalopathy. Cogwheel rigidity favors
encephalopathic pellagra. In practice, however, it may be
difficult to differentiate between these disorders, and
indeed they may appear concurrently (Serdaru et al. 1988).
The chronic form of pellagra is difficult to miss when all
three of the ‘Ds’ are present; however, as noted earlier,
many patients have only two of these, and some may have
only one. Consequently, a high index of suspicion is
required, and chronic pellagra should always be suspected
in any chronically malnourished patient who gradually
develops a dementia.
Treatment
Niacin may be given orally in doses from 250 to 500 mg
daily. In the encephalopathic form, the response is rapid
and often robust; in the chronic form recovery is slower
and may be incomplete. Once full benefit has occurred,
patients may be maintained on 50–100 mg of niacin daily.
In cases due to isoniazid, administration of pyridoxine, in
doses of 50 mg daily, is generally sufficient; however, in
some cases symptoms may persist and in these cases isoniazid
must be discontinued (Burke and Hiangabeza 1977).
13.4 WERNICKE’S ENCEPHALOPATHY
Wernicke’s encephalopathy, also known as Wernicke’s disease,
occurs secondary to thiamine (vitamin B1) deficiency
and, in its fully developed classic form, it presents with the
triad of delirium, nystagmus, and ataxia. It occurs most
frequently in malnourished alcoholics and is a common
cause of delirium in general hospital practice.