Patient 2. This 68-year-old malnourished chronic alcoholic was found wandering in
a state of confusion and disorientation. In the emergency department, he demonstrated
a severe disturbance of memory in which new information could not be stored. The normal
temporal sequence of his established long-term memories was disrupted. When asked to
recall events of the past week, he was easily suggestible and gave a semi-fictionalized
account of the circumstances (i.e., he demonstrated confabulation). A diagnosis of
Korsakoff syndromesecondary to chronic thiamine deficiency was made. His mental
state responded partially, but incompletely, to prolonged thiamine administration.
Patient 3. This 24-year-old male presented with a recent increase in seizures (arising
from an exacerbation of his underlying epilepsy) as well as “pins and needles” and
“uncomfortable numbness” in his feet, lower legs, and hands. Based on “advice” that
he had obtained from an internet chatroom on the World-Wide Web, he had decided to
take “megadoses” of pyridoxine for several months and then to stop his regular anti-
convulsant drugs. A diagnosis of peripheral neuropathy secondary to pyridoxine toxicity
was made. He ultimately returned to normal following discontinuation of the pyridoxine
and reinstitution of his carbamazepine anticonvulsant drug.
Patient 4. This 79-year-old male presented with marked agitation and bloody urine.
In the previous week, he had experienced a spontaneous nosebleed. A diagnosis of
Alzheimer’s disease had been made 18 months previously and the patient was being
“managed” by his four children, a family physician, and a geriatrician. He was receiv-
ing donepezil (cholinesterase enzyme inhibitor), Vitamin E (2000 IU/day), acetylsali-
cylic acid (325 mg/day) and Gingko biloba (“as a complementary alternative therapy”).
A diagnosis of a urinary tract hemorrhage, possibly precipitated by the administration of
large doses of vitamin E, was made. The family refused to reduce the dose of vitamin E,
since “everyone knows it is a harmless vitamin.” The patient died of a brain hemorrhage
three months later.
Patient 5. This 74-year-old female presented with three identical episodes of sudden-
onset left-sided body paralysis lasting 5–10 minutes, occurring over the past 24 hours.
Over the past four months she had experienced intermittent episodes of an “irregularly
irregular” heart rate. Multiple electrocardiograms over the past 12 weeks had demon-
strated an intermittent atrial fibrillation heart rhythm disorder. A diagnosis of transient
ischemic attacks (TIAs, “mini-strokes”) secondary to blood clots arising from atrial fib-
rillation was made. The patient had her blood “thinned” with warfarin, an anticoagulant
that works as a vitamin K antagonist. The TIAs subsequently resolved completely.
8.3 Proteins as Drugs and Drug Design Targets: Non-Enzymes
8.3.1 Protein Folding Disorders: Neurodegenerative DiseasesA number of neurodegenerative disorders are characterized by neuronal damage that is
induced by neurotoxic, aggregation-prone proteins. Various neurodegenerative dis-
eases, including Alzheimer’s disease (“caused” by β-amyloid deposits), prion disease
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