What if sleep eluded you entirely? This is the grim reality for a family in Venice, Italy, who suffer from a genetic condition that manifests in mid-life. Their nights are stolen away, leading to severe brain deterioration and, tragically, untimely deaths.

Today, we delve into Fatal Familial Insomnia (FFI), an exceedingly rare genetic degenerative brain disorder, and address three common misconceptions about sleep.

The author of "The Family That Couldn’t Sleep: A Medical Mystery" portrays one family member's ordeal as follows:

“Silvano began to sweat excessively, his pupils constricted — it was time for his family to stop enduring in silence. He sought help at the University of Bologna, where researchers documented his final months. At times, his eyes barely opened, lost in a trance. Just as he seemed on the verge of sleep, he would abruptly awaken. He passed away at 53 in 1984.”

Fatal Familial Insomnia is categorized as a transmissible spongiform encephalopathy (TSE) or prion disease. To understand this, consider a pathogen that prompts normal proteins in the brain to misfold. These misfolded proteins are termed prion proteins. Here are some recognized human prion diseases:

• Fatal Familial Insomnia
• Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease
• Gerstmann-Straussler-Scheinker Syndrome
• Kuru

Animal prion diseases include:

• Bovine Spongiform Encephalopathy (BSE)
• Chronic Wasting Disease (CWD)
• Scrapie
• Transmissible mink encephalopathy
• Feline spongiform encephalopathy
• Ungulate spongiform encephalopathy

"Bovine" refers to cows, "spongiform" describes the spongy appearance of an infected cow's brain under a microscope, and "encephalopathy" indicates it is a brain disease. BSE is commonly known as "mad cow disease."

These conditions typically feature lengthy incubation periods during which abnormal prions accumulate, followed by rapid onset of symptoms leading to severe decline.

Symptoms may include sudden insomnia, panic attacks, weight loss, extreme body temperature fluctuations, hyperventilation, and other issues. As the condition worsens, individuals may experience uncoordinated movements, hallucinations, delirium, and ultimately an inability to sleep. But what causes these effects?

The term prion, introduced by Stanley B. Prusiner in 1982, is a blend of pr**otein and **i**nfecti**on. Prions originate as normal proteins but transform into an indestructible, abnormal form. Researchers believe that the aforementioned diseases result not from a viral or bacterial infection, but from a misfolded protein.

The durability of prions stems from their non-living nature and lack of DNA. If you ever need to destroy these resilient structures, it requires sustained extreme heat (around 900°F) for several hours to prevent them from causing normal proteins to misfold.

Returning to our family story, D.T. Max writes in "The Family That Couldn’t Sleep: A Medical Mystery":

“It’s been catastrophic. Excruciating suffering. [She] has lost numerous family members to this affliction, including her father, brother, and sister.”

A researcher from the University of Bologna remarks:

“Exactly what you might feel if you experience a sleep attack while driving. You begin to doze off, then suddenly awaken.”

Without restorative sleep, Silvano passed away in 1984. An American pathologist noted that much of his brain appeared normal during the autopsy, but a small central structure resembled a sponge. This finding led the pathologist to recognize a pattern akin to known prion-related diseases.

While we all possess similar proteins, an innocent protein can undergo transformation. This abnormal prion can then convert healthy proteins, creating duplicates. As these prion proteins spread, they cause brain cells to die along their path, revealing why this Italian family endures such tragedy.

The abnormal prion proteins primarily impact the thalamus, the brain region responsible for regulating the sleep-wake cycle. This structure also serves as a relay center, facilitating communication among various brain parts.

Unfortunately, the reasons behind the genetic mutation's preferential effect on the thalamus remain unclear. However, if one parent carries the dominant mutation, there is a 50% chance of passing it on. Currently, no cure exists. Some family members have tested positive for the gene. By the time they reach middle age, I hope gene therapy will be a viable option.

A family member and her spouse have shifted careers and are pursuing a doctorate in biology at Harvard Medical School. Their dedication and zeal give me chills. Thankfully, they utilized genetic testing and in vitro fertilization to ensure their daughter is free of the problematic gene.

How prevalent are prion disorders? Fortunately, they are exceedingly rare, affecting approximately 1 in a million individuals in the general population each year. Inherited prion diseases account for 15% of related illnesses.

Now, let's discuss three myths about sleep:

1. One can get by with only six hours (or less) of sleep. It is rare for someone to require fewer than six hours. While there is a gene mutation that allows for minimal sleep, it is uncommon.
2. Daytime naps are a terrible idea. Researchers found that “afternoon naps in individuals who are not sleep-deprived can lead to subjective and behavioral improvements, enhancing mood, alertness, and performance in tasks like addition, logical reasoning, and reaction time.”
3. More sleep is always better. A comprehensive study revealed a clear pattern indicating increased mortality risk at both ends of the sleep duration spectrum. Those sleeping less than 7 hours or more than 8 to 9 hours each night have a higher risk of dying than those who sleep 7 to 8 hours.

Sleep is crucial for overall health. Most adults should aim for 7 to 9 hours nightly (with older adults typically needing 7 to 8 hours). Teenagers require about 8 to 10 hours, while school-age children need 9 to 11 hours daily.

I’m Dr. Michael Hunter, and I appreciate your attention today. And yes, I am a habitual (short) napper.

References

• Gene identified in people who need little sleep. [NIH](www.nih.gov)
• Prion diseases. [Wikipedia](en.wikipedia.org)
• Prion Diseases. [CDC](www.cdc.gov)
• All About BSE (Mad Cow Disease). [FDA](www.fda.gov)
• Fatal Familial Insomnia - NORD (National Organization for Rare Disorders). [NORD](rarediseases.org)
• Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis. [Academic](academic.oup.com)
• Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience. [Wiley](onlinelibrary.wiley.com)
• The Family That Couldn't Sleep: A Medical Mystery. [Amazon](www.amazon.com)

Max, D. T. (2007). The Family that Couldn’t Sleep: A Medical Mystery. New York: Random House Trade Paperbacks.