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Fatal Familial Insomnia: The Disease That Kills by Sleep Deprivation

fatal familial insomnia

Everybody suffers from a little insomnia once in a while, but what if you were unable to sleep for months?

Early studies conducted on dogs showed that the absence of sleep was fatal in a few days. In one brutal experiment conducted by a couple of Italian physiologists in the late 19th century, dogs were kept awake for two weeks by forcing them to walk, after which they died. Microscopic study of the dogs’ brain cells showed degenerative changes in the brain’s neurons.

In 1964, an American high school student, Randy Gardner, went a record eleven days without sleeping. Although Gardner, because of his remarkable fitness, was still able to play basketball his cognitive and sensory abilities suffered. As the days wore on, Gardner became increasingly moody, had difficulty concentrating, suffered from short term memory loss, hallucinated things that were not present and became consumed by paranoia. Gardner cut short his dangerous experiment before it ate into his health, but for a handful of families scattered across the world sleep is a luxury. They carry within their DNAs a very cruel gene that causes a very rare sleeping disorder called fatal familial insomnia.

The disease typically strikes in their middle ages, around fifty, and begins with sweating. A look in the mirror will show that the pupils have shrunk to pinpoints. Some victims experience tremors and constipation. Women suddenly enter menopause and men become impotent. The sufferer begins to have trouble sleeping, which becomes progressively worse as the days pass. He tries desperately to sleep, but never manages to catch beyond a few winks. This frightening symptom continues for months sapping away the energy of the individual, until the insomnia becomes total. Once the individual can no longer sleep, a downward progression ensues as the person loses the ability to walk or balance. There is profound weight loss. Forgetfulness and episodes of confusion and hallucinations are common. Some people even lose their speech. Finally, about fifteen months after the first symptoms began, the victim drops down dead out of sheer exhaustion. Some die sooner. Others suffer for as long as three years.

Randy Gardner

Randy Gardner. Photo: Don Cravens/Getty Images

Fatal familial insomnia is a genetic disease caused by mutation of the PRNP gene. This gene provides instructions for creating proteins that play critical roles in many functions of the body. But when the gene mutates, the protein produced becomes faulty—in other words, the protein misfolds. Depending on the position of the mutation, the gene can produce a variety of cognitive disorders and neurodegenerative diseases such as the mad cow disease in cattle, and Creutzfeldt–Jakob disease and fatal familial insomnia in humans. In FFI, the mutation causes an attack on the thalamus, which controls our sleep cycles and allows different parts of our brain to communicate with each other.

The disease can be traced back to the 18th century to a Venetian doctor who lived near the Jewish ghetto. He passed the disease to his nephew named Giuseppe, and from there, the illness passed through his sons to their children and great grandchildren, until there are about 40 families affected around the world now. But there could be as many as 200 families.

One of the strangest thing about these families is that they could have chosen not to procreate and ended the transmission of the disease, but they did not.

“Many lethal genetic diseases disappear on their own, because they bring about death before the carriers of the mutation can reproduce, but not FFI—at least not in this family. Because the disease usually stricken its sufferers after their childbearing years, and because most members of the family decide to have children, FFI will live on through them,” wrote D.T. Max in The Family That Couldn't Sleep, a book that provides a fascinating insight into this mysterious disease.

“The decision to bring a child into the world who may die a horrible death in the middle age is a difficult one,” Max continued.

Max writes about a family in Bologna, Italy, whose family members carries the fatal gene. Since the last 150 years, at least thirty members of the family had died from FFI. Nearly half of them in the last fifty years or so.

“To my knowledge no family member has terminated a pregnancy out of fear of passing the syndrome on,” Max observed.

One of the sufferers, a person known only as Silvano, presented himself to the University of Bologna hospital's sleep institute in 1983, just as he was experiencing the early symptoms of the disease. He told the doctors matter-of-factly, “I’ll stop sleeping, and within eight or nine months, I’ll be dead.”

Silvano died a couple of years later, but he left his brain to science. And thanks to Silvano’s generous contribution, neurologists now know that the disease is caused by a prion, a misfolded protein, that targets parts of the thalamus located just above the brain stem at the very center of the skull.

In a BBC article, David Robson explains:

After years of further research, the scientists can now explain why damage to this small nub of neural tissue unleashes such a puzzling constellation of symptoms. We know, for instance, that this hub orchestrates all our “autonomic” responses to the environment – things like temperature control, blood pressure, heart rate, and the release of hormones to keep the body ticking over comfortably. When it breaks down, it is as if your central heating is going haywire, your water pipes have sprung a leak, your windows are wide open and your loudspeakers are blaring at full volume – everything is in chaos. Hence the profuse sweating and shrunken pupils, the impotence and the constipation.

There is currently no cure to fatal familial insomnia, but there are medicines that can provide temporary relief for some. One patient, who we know only as Daniel, went to great lengths to alleviate his misery. Daniel took vitamin supplements and exercised to improve his general fitness. When the vitamins stopped working, he took anesthetics such as ketamine and nitrous oxide to induce short 15-minute periods of restful sleep, as well as sleep medications. Once, during treatment, Daniel suffered a mild stroke and slept for three days. He even bought a sensory deprivation tank, an egg-shaped chamber where the body floats in salt water at body temperature experiencing no pain, gravity, temperature, touch, or kinesthetic information. Eyes and ears are shielded from light and sound, and the lid is shut. The device, invented to promote muscular relaxation, was brutal. Most subjects, upon awakening, demanded immediate release. Those who remained experienced hallucinations. Daniel too suffered disturbing hallucinations, including a strange uncertainty as to whether he was alive or dead.

Although Daniel did eventually die (26 months later by cardiac arrest), he lived longer and functioned more efficiently than his diagnosis would have predicted, suggesting that at least some of these strategies warrant further study.

Leading image by Kleber Cordeiro/Shutterstock.com

References:
# Bentivoglio M, Grassi-Zucconi G., https://www.ncbi.nlm.nih.gov/pubmed/9322273
# BBC, https://www.bbc.com/future/article/20180118-the-boy-who-stayed-awake-for-11-days
# Rare Disease Database, https://rarediseases.org/rare-diseases/fatal-familial-insomnia/
# NPR, https://www.npr.org/templates/story/story.php?storyId=6503414
# BBC, https://www.bbc.com/future/article/20160118-the-tragic-fate-of-the-people-who-stop-sleeping
# Joyce Schenkein, Pasquale Montagna, https://www.medscape.com/viewarticle/542964_3

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