The Family That Can’t Sleep
What would happen if you could not sleep? We begin with the story of a family in Venice, Italy. Members suffer from an inherited condition, one that appears in middle age. In a phrase, they have their sleep stolen from them, developing holes in their brains and ultimately leading to their premature demise.
Today, we look at Fatal Familial Insomnia (FFI), a rare genetic degenerative brain disorder. We will then pivot to three myths about sleep.
Here is how the author of “The Family That Couldn’t Sleep: A Medical Mystery” describes one family member’s experience:
“Silvano began sweating profusely, with pinpoint pupils — he decided it was time for his family to stop suffering silently. Silvano traveled to the University of Bologna, where researchers filmed his last months. At times, his eyes are only half-open, staring off into space. Just as it seems he may fall asleep, he jerks to a half-wakefulness. In 1984, he died at 53 years of age.”
Fatal familial insomnia is a transmissible spongiform encephalopathy (TSE) or prion disease. Let’s break this down. Imagine a pathogen that induces normal proteins to fold abnormally in the brain. These abnormal proteins are then known as prion proteins. We’ll come to prions in a moment. First, here are the known human prion diseases:
- Fatal Familial Insomnia
- Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease
- Gerstmann-Straussler-Scheinker Syndrome
Animal prion diseases include:
- Bovine Spongiform Encephalopathy (BSE)
- Chronic Wasting Disease (CWD)
- Transmissible mink encephalopathy
- Feline spongiform encephalopathy
- Ungulate spongiform encephalopathy
“Bovine” means affecting cows, “spongiform” reflects how the brain from a sick cow appears spongy under a microscope, and “encephalopathy” indicates that it is a disease of the brain. BSE is commonly called “mad cow disease.”
Such conditions usually have long incubation periods in which the abnormal prions accumulate. Then come symptoms, with a rapid deterioration of the individual.
There are usually long incubation periods in which the abnormal prions accumulate. Then come symptoms, with a rapid deterioration of the individual. Many present with sudden-onset and rapidly progressing insomnia.
Others have panic attacks, weight loss, phobias, a body temperature that is either too high or too low, hyperventilation, or other problems. The situation can get considerably worse, with uncoordinated movements, hallucinations, delirium, and, ultimately, the inability to sleep. But why does this happen?
Zombie-like prions are nearly indestructible
The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau (a blend of words) derived from protein and infection, hence prion. Prions begin life as normal proteins, but become abnormal and near-impossible to destroy. Scientists hypothesize that the diseases described above are not the result of a viral or bacterial infection. Instead, they are secondary to a protein that has morphed into an abnormal form.
The indestructibility of prions is due mainly to prions not being alive and have no DNA. It sounds terrifying to me. Should you ever need to denature these zombie-like structures, try using sustained extreme heat (at least 900°F) for several hours. Then the prions can no longer cause normal proteins to fold badly.
Let’s turn back to our family that couldn’t sleep. Writes D.T. Max in “The Family That Couldn’t Sleep: A Medical Mystery”:
“It’s been a disaster. Brutal suffering. [She] has lost many relatives to the condition, including her father, brother, and sister.”
Observes a University of Bologna researcher:
“Exactly what you can feel if you get a sleep attack when you are driving. You are falling asleep, and then you wake up.”
With no restorative sleep, Silvano died in 1984. An American pathologist noted that while much of the brain seemed normal at autopsy, a small central structure looked like a sponge. This pathologist honed in on that pattern recognizing it as similar to a group of known diseases caused by prion proteins.
We all have similar proteins. But this innocent protein is capable of shapeshifting. This abnormal prion can then convert a healthy protein, creating a duplicate of itself. And so on. With the prion protein spread, brain cells die in their pathway. We now better understand why our Italian family experiences such tragedy.
The abnormal prion proteins affect the thalamus, the region of the brain that regulates our sleep-wake cycle. The structure also is a relay center, a kind of brain switchboard, of the brain, given it helps the various parts of the brain communicate with one another.
Unfortunately, we do not know why the genetic mutation causes the thalamus to be preferentially affected. But if your parent has the dominant mutation, you have a 50 percent probability of inheriting the troublesome gene. There is no cure. Some family members have tested positive for the gene. By the time they hit middle age, I hope that we have gene therapy as an option.
A family member and her husband changed careers and are aim for a doctorate in biology at Harvard Medical School. I get shivers thinking about their passion and commitment. Thankfully, they had the technology (in genetic testing and in vitro fertilization) to have a daughter free of the problematic gene.
How common are prion disorders? Fortunately, they are remarkably uncommon: Prion disorders affect about 1 in a million people in the general population per year. Inherited prion diseases account for 15 percent of the burden of illness.
Three sleep myths
I promised to end with three myths about sleep. Here they are:
- One can get by with only six hours (or less) of sleep. It is rare for an individual to need fewer than six hours of sleep. There is a gene mutation that allows for minimal rest, but it is rare.
- Daytime naps are a terrible idea. Here is what researchers said, after completing an extensive review: “Afternoon naps in people who are not sleep deprived can lead to ‘subjective and behavioral improvements’ and improvements in ‘mood and subjective levels of sleepiness and fatigue.’ Those who nap have improved performance in tasks, such as “addition, logical reasoning, reaction time, and symbol recognition.”
- More sleep is always better. The most comprehensive study showed “a clear pattern of increased risk of dying on either end of the distribution of sleep duration. Pooled analyses showed that short sleepers (commonly less than 7 hours per night, and often under 5 hours) have a 1.12-fold greater risk, and long sleepers (commonly more than 8 or 9 hours each night) have a 1.3-times higher risk of dying than those sleeping 7 to 8 hours each night.”
Sleep is essential for good health. Most adults should aim for 7 to 9 hours each day (with older adults typically getting 7 to 8 hours). Teenagers need about 8 to 10 hours, while school-age kids need 9 to 11 hours daily.
I’m Dr. Michael Hunter, and I thank you for joining me today. And yes, I am a chronic (short) napper.
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The Family That Couldn't Sleep: A Medical Mystery
The Family That Couldn't Sleep: A Medical Mystery [Max, D.T.] on Amazon.com. *FREE* shipping on qualifying offers. The…
Max, D. T. (2007). The Family that Couldn’t Sleep: A medical mystery. New York: Random House Trade Paperbacks.