Table of Contents
Send a Letter
Magazine Staff
Back Issues:
Editor's Notes
Chicago Journal
Books by Alumni

Class News


For the Record
Center Stage
College Report
Alumni Gateway
UofC Homepage

Life without sleep

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 (SFI).

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 protein—called a prion—not only doesn’t 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 tears—consistent with the witches’ curse to “dwindle, peak, and pine.” The patient was referred to Mastrianni—at that time, a clinical instructor of neurology and medical director of Alzheimer’s diagnostics at UCSF—who 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 patient’s brain showed damage that was entirely consistent with FFI but revealed no evidence of the abnormal gene in any tissue.—John Easton

Table of Contents | Send a Letter | Staff | Editor's Notes | Letters | Investigations | Journal | Class News | Books | Deaths