By
Dateline NBC
updated 1/14/2005 10:00:38 PM ET 2005-01-15T03:00:38

Imagine what a nightmare it would be to never have a nightmare, to never again have a dream, to be banished forever from the topsy-turvy realm of sleep. Just imagine what it would be like one day to wake up and never fall asleep again, to be tortured in a twilight world of perpetual insomnia, lying in bed, exhausted but with eyes wide open, listening to the groans and whispers of the night -- sleepless, until death mercifully claims you.

It's not a lost Gothic chiller from Edgar Allen Poe but a very real, and very rare, disease called "fatal insomnia." We might have never heard of it without the medical detective work of an Italian family, which, it turns out, was stalked for centuries by a terrifying fate.

As clinical tapes show, insomnia has become an all-too waking reality for this family. But as difficult as their experience has been, it has pushed the outer boundaries of what we know about sleep and expanded our understanding of human disease itself. This family's illness might lead to breakthroughs in curing diseases like Alzheimer's and Parkinson's. 

Dr. Ignazio Roiter: “The first person to fall ill was my wife's aunt. They said she was depressed.”

Dr. Ignazio Roiter is a country doctor. His wife, Elisabetta, is a descendant of a prominent Italian family with roots in Venice since the 1600s. Roiter's medical training hadn't prepared him for the sad and puzzling ailment that was suddenly overtaking Elizabetta's aunt, a woman in her 40s.

Dr. Roiter: “She appeared to be sleeping all the time, but then she claimed she had insomnia. The doctors were confused.”

Sleeping pills were useless. The two could only watch in horror as the aunt's health deteriorated. After a few months she could no longer walk, even speaking was an effort.

Dr. Roiter: “The disease progresses very rapidly. Death comes suddenly.”

The aunt was dead one year after the onset of her mysterious sleepless condition. Then a year later, in 1979, it struck again. A second aunt became suddenly sleepless.

Elisabetta: “The symptoms were the same. Exactly the same.”

Dennis Murphy: “This has to be terrifying.”

Elisabetta: “It was shocking at first.”

The mind of both women remained crisp as their bodies failed them.

Dr. Roiter: “That's the worst aspect of the disease.”

Stages of sleepThe second aunt died in 1979, a year after the first. What had struck them down? The medical experts were perplexed, but Elisabetta's mother remembered vaguely seeing the dreadful symptoms before. It happened to Elizabetta's grandfather in 1944. He too had been cursed by the waking nightmare, sleepless, then quickly dead.

Elisabetta: “We started to understand that there was a hereditary disease in our family.”

Dr. Roiter, desperate to find a diagnosis and a cure, turned to the dusty record books of the local church where the births and deaths in Elizabetta's family had been dutifully recorded down through cobwebbed generations. He was like a cop working a cold case back through time. And he was finding clues, causes of death listed as "epilepsy," "fever," and "mental illness". A vague pattern was emerging.

Gradually, he built a family tree and encountered long-lost family members who told him that yes, they remembered relatives dying of the nameless affliction. But Dr. Roiter needed stronger clinical evidence of a family link. His search brought him here to an island off Venice, San Servolo, the site of Europe's first mental asylum. Some of his wife's ancestors had been warehoused here, and like hundreds of other patients, observed and catalogued. He found ancestors' medical records, and compelling evidence.

Murphy: “Confusion, apathy. So this is years before the diagnosis, but doctors are observing these same traits.”

Dr. Roiter: “Yes.”

There it was in the yellowed records. Elizabetta's ancestors had been dying of sleeplessness for centuries. Now Dr. Roiter had to convince the medical establishment that he had stumbled across a new, family-borne disease -- his own family's disease. But before his investigation could continue, its urgency was made apparent when Elisabetta's Uncle Silvano came for a visit

Dr. Roiter: “He seemed depressed, anxious. His behavior changed, his character changed.”

Elisabetta's uncle agreed to be examined. He was determined to help them find a cure

Elisabetta: “He said, do it quickly. He knew he was going to die within a short time.”

Dr. Roiter: “I wanted to save him.”

Dr. Roiter contacted Dr. Elio Lugaresi, a world-renowned sleep expert, in Bologna, Italy.

Dr. Elio Lugaresi: “I realized immediately that this might be an important case.”

Uncle Silvano was admitted to the clinic in the spring of 1984.

Dr. Lugaresi: “I'd studied sleep for more than 30 years and I'd never seen anything like it!”

Over several months Dr. Lugaresi videotaped Uncle Silvano's decline.

Tapes recorded his semi-awake state. His eyes rarely stay closed. Then after 6 months, he begins miming in his half-dreams - combing his hair, buttoning his shirt. Though he may look conscious, he isn't. He's lost in a passageway between sleep and the wakeful world. In time, he finds it difficult to walk. Insomnia caused his body to shut down and he died, exhausted, at 52. 

His brain was removed, sped through customs and rushed to a specialist in America.

Dr. Pierluigi Gambetti: “If we had lost that brain, we would have lost the key to the understanding of the disease.”

The brain was delivered intact to Dr. Pierluigi Gambetti, a neuropathologist at Case Western Reserve University in Cleveland. He studied it and found that it was full of small holes - like a sponge. It looked suspiciously similar to the brain of patients with Creutzfeldt-Jacob, the human form of mad cow disease. 

Dr. Gambetti: “It gave us really a direction we're to move to try to identify the type of disease we are dealing with.”

The doctor in Cleveland contacted a scientist in Los Angeles who'd done ground-breaking work on the transmission of disease.

Dr. Stanley Pruisner, the California scientist, believed that some diseases are caused by proteins in our brains. Abnormal proteins can hijack healthy proteins that in turn declare war on other proteins in the brain – a whole new system of infection that leads to death. But it was just an unproven theory.

Labwork on Uncle Silvano's brain turned out to be the key that researchers had been looking for, their proof. Uncle Silvano, indeed all of Elizabetta's sleepless relatives and ancestors, had died of a hereditary disease caused by rogue protein disorder in the brain.

In 1997 Dr. Prusiner was awarded the Nobel Prize in medicine for his discovery of rogue protein disorders. His discovery was partly the result of an Italian country doctor's crusade to cure his family

But diagnosing the disease wasn't curing it. As Dr. Gambetti in Cleveland continued his research into fatal familial insomnia, he actually located the genetic mutation in Elizabetta's line that causes the disease. He tested 50 members of the Italian family and found that 50 percent of them were carriers. Carrying the mutated gene doesn't mean that it will bloom into the fatal insomnia but if it does, no cure is known.

Now those onetime long-list family members reunited by Dr. Roiter's medical detective work face an awful dilemma. They've seen fathers disintegrate before their eyes, and their loved ones turned into sleepless zombies.

Elizabetta's distant cousin Lucia has lost her father, an uncle and a sister to the disease.

Murphy: “Lucia, the doctors would be able to say with some precision whether or not you or your family member have it or don't have it. It's an awful decision. Would you want to know, or not know?”

Lucia: ”No, I wouldn’t want to know it. My aim in life is to find a cure, fund research.”

Some scientists predict a cure will be found within the next 10 or 15 years. And scientists believe that a cure for fatal familial insomnia, rare as it is, may open the door to cures for other rogue protein diseases, and similar maladies like Alzheimer's and Parkinson's. 

Lucia: “My strength comes from the people who've died. Wherever they are now, they help me along this road, which won't cure them anymore, but will help people in the future. We've lost some battles, but I haven't lost the war.”

It’s a war for a cure that would allow this family and others always to be able to sleep, perchance to dream. Perchance to live.

In recent years, 27 other families around the world have been found to be carriers of fatal familial insomnia, five of those in the United States. The Roiters’ extended family has formed an association to help find a cure, and raise the money for research.

© 2013 MSNBC Interactive. Reprints

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