When William Shakespeare wanted his witches in Macbeth to
utter a horrible curse, he had them deny their victim sleep. Nearly
400 years later, in the May 27 New England Journal of Medicine,
medical researchers from the University of Chicago and the University
of California at San Francisco describe the first case of a neurological
disorder that matches the witches curse: sporadic fatal insomnia
The symptoms and neuropathology of SFI are identical to an inherited
disorder described by Italian scientists in 1986. That disorder,
called fatal familial insomnia (FFI), is triggered by a tiny mutation
in a particular gene. The mutation prompts the protein made by that
gene to fold into an abnormal shape, like a deformed work of origami.
The misfolded proteincalled a prionnot only doesnt
function, it also cannot be chewed up by enzymes or eliminated from
the brain. Scientists are not sure why, but, as they gradually accumulate,
the prions disturb the normal functioning of the brain and cause
untreatable sleeplessness, loss of coordination, loss of mental
function, and eventually death, typically within less than two years.
SFI, the non-inherited version, occurs without the abnormal gene.
We found a disease that is indistinguishable from the genetic
disorder but lacks the disease gene, says James Mastrianni,
an assistant professor in neurology at Chicago and lead author of
the study. Sporadic fatal insomnia is an exact phenocopy,
but not a genocopy of fatal familial insomnia.
So far, FFI has been found in only 24 extended families worldwide.
But SFI, though still rare, may prove more common, say the researchers,
accounting for most or all cases of pure thalamic dementia.
The first SFI patient was documented two years ago when a previously
healthy 44-year-old California man developed increasing trouble
falling asleep. After about four months of sleeping an average of
one hour per night, the patient began to have trouble walking, lost
weight, and excessively produced tearsconsistent with the
witches curse to dwindle, peak, and pine. The
patient was referred to Mastrianniat that time, a clinical
instructor of neurology and medical director of Alzheimers
diagnostics at UCSFwho began the testing that led to the diagnosis.
Despite large doses of powerful drugs, the patient suffered progressive
loss of coordination and short-term memory, as well as difficulty
separating dreams from reality. One year after the onset of symptoms,
he was admitted to a long-term care facility, where he died four
months later. At autopsy, the patients brain showed damage
that was entirely consistent with FFI but revealed no evidence of
the abnormal gene in any tissue.John Easton