Fatal Insomnia

Unlike insomnia, which is a sleep disorder that affects millions of adults, fatal insomnia is an extremely rare and serious disease. Fatal insomnia affects sleep behavior, cognitive abilities, hormone production, and a range of bodily functions.

Fatal insomnia is a type of prion disease. In prion diseases, the brain becomes damaged by the buildup of abnormally shaped proteins. The breakdown of nerve cells in prion diseases causes extensive symptoms and eventually results in death.

Prion diseases are quite rare, with a frequency of only 1 to 1.5 cases for every one million people. About 350 combined cases of all prion diseases are found in the United States each year. Among prion diseases, fatal insomnia is even rarer.

When it occurs, fatal insomnia usually affects middle-aged adults. Unfortunately, fatal insomnia is irreversible, ending in death an average of 18 months after symptoms first emerge.

Despite its name, fatal insomnia is not linked to the more common sleep disorder of insomnia. Learning the details about fatal insomnia, including its symptoms and causes, can help you understand this incredibly rare disease and how it is distinct from other kinds of sleep problems, including insomnia.

There are two types of fatal insomnia: fatal familial insomnia and sporadic fatal insomnia. The two types are distinguished by whether or not they have a link to an inherited genetic mutation.

Fatal Familial Insomnia

Fatal familial insomnia (FFI) is the inherited form of fatal insomnia. This means that specific gene mutations associated with FFI are passed down from one generation to another. These mutations trigger the production of abnormally shaped proteins that harm the brain and are associated with other prion diseases besides FFI.

FFI is extraordinarily uncommon. The genetic mutation that causes FFI has only been found in around 70 families in the entire world.

Sporadic Fatal Insomnia

Sporadic fatal insomnia (sFI) occurs when normal prion proteins spontaneously transform into abnormally shaped proteins. There is no genetic cause or family history. However, sFI has essentially the same symptoms and outcomes as FFI.

sFI appears to be even more rare than FFI. As of 2018, studies reported only 25 published cases of sFi.

Symptoms of fatal insomnia include sleep disturbances, changes in mood or behavior, irregular body functions, and decreased muscle strength. Most people with fatal insomnia also experience weight loss. It’s important to remember that this disease is extremely rare and most people experiencing these symptoms do not have fatal insomnia.

Sleep disturbances caused by fatal insomnia include:

• Insomnia: Insomnia is difficulty falling asleep or staying asleep at night. This symptom gets worse over time as fatal insomnia progresses. 
• Vivid or Lucid Dreaming: During the brief time that a person with fatal insomnia sleeps, they may experience very vivid dreams or lucid dreams in which they recognize that they are asleep.
• Wakeful Dreaming and Dream Enactment: Due to insufficient sleep, people with fatal insomnia may suddenly experience a dream-like state while they are still awake. They may also act out their dreams.
• Diminished Deep Sleep: Slow wave sleep, also called stage 3 sleep or deep sleep, is critical for feeling refreshed each day. As fatal insomnia worsens, slow wave sleep decreases or stops, and separate sleep stages may become indistinguishable.
• Reduced Sleep Time and Daytime Sleepiness: The total amount of time spent sleeping drastically decreases throughout the progression of the disease. This lack of sleep often leads to daytime sleepiness.

People with fatal insomnia typically experience changes in mood and behavior, such as:

• Depression 
• Panic attacks
• Hallucinations, phobias, or paranoia
• Short-term memory loss
• Worsened concentration

However, despite these changes, most people with fatal insomnia maintain cognitive abilities for most of the course of the disease. Dementia is rare and only occurs during the last stages of fatal insomnia.

Fatal insomnia also affects the autonomic nervous system, which controls involuntary body functions. This can lead to symptoms like:

• Excessive sweating
• Significant crying
• Episodes of rapid breathing
• Unusually high body temperature
• Abnormally fast heartbeat
• High blood pressure
• Sexual dysfunction
• Constipation

Muscles tend to weaken as fatal insomnia progresses, which can cause physical symptoms such as:

• Difficulty swallowing 
• Uncontrollable muscle twitching
• Decreased muscle tone
• Loss of muscle coordination
• Slowed movements, stiffness in the limbs, and body tremors
• Trouble speaking

Stages of Fatal Insomnia

After the onset of fatal insomnia symptoms, the disease progresses over time. The changes in symptoms are sometimes categorized in four stages.

• Stage 1: Insomnia begins during this stage and may be accompanied by changes in mood and behavior, such as panic attacks and paranoia.
• Stage 2: During stage 2 of the disease, the insomnia and psychiatric symptoms worsen. Involuntary functions such as breathing and heart rate may be affected.
• Stage 3: The sleep-wake cycle is fully disrupted during this stage, which involves a complete inability to fall asleep or stay asleep.
• Stage 4: This stage may last several months and involves losing the ability to speak and move, followed by coma and death. Death is typically caused by disease complications, such as an infection in the lungs or bladder.

The length of each stage of fatal insomnia varies among individuals. The full course of the disease can range from 8 to 72 months. On average, though, the disease progresses over 18 months. 

The cause of fatal insomnia depends on the type of the disease. Familial fatal insomnia is genetically inherited, while sporadic fatal insomnia occurs spontaneously with no known cause or inherited link.

Both types of fatal insomnia are prion diseases. In these very rare diseases, the body creates an abnormal prion protein. Prion proteins are found in the brain. Researchers hypothesize that normal prion proteins serve a number of important functions, including protecting brain cells.

In fatal insomnia and other prion diseases, though, prion proteins become abnormally shaped. When these abnormal proteins build up over time, they damage nerve cells and create tiny holes in the brain.

FFI is caused by inheriting an altered prion protein (PRNP) gene. This mutated PRNP gene gives the body’s cells incorrect instructions for making prion proteins, which leads to the creation of misshapen proteins. Different alterations of the PRNP gene can affect how these damaging proteins are produced.

In FFI, the mutated PRNP gene typically comes from one parent. However, in some cases, the gene mutation occurs in the egg or sperm. The PRNP gene change can also happen in the early formation of an embryo. When this occurs, the mutation can later be passed on to future children.

sFI is not inherited, and people with this type have no family history of fatal insomnia. Instead, prion proteins spontaneously change to the abnormal protein. The reason for this change is unknown. The occurrence of sFI is extremely rare.

Fatal insomnia is primarily diagnosed based on symptoms and an assessment of cognitive and physical ability. Additional tests, studies, and scans can help provide a clearer picture of the disease and confirm a diagnosis.

Sleep Study

Although not always necessary for a diagnosis, sleep studies of people suspected to have fatal insomnia can provide a clearer picture of their sleep stages and total time spent asleep. A sleep study records brain waves, muscle movements, breathing patterns, and heart rate during sleep.

Sleep studies of people with fatal insomnia typically show little or no stage 3 sleep. As the disease progresses, distinct stages of sleep may not be detectable.

Genetic Testing

Genetic testing for fatal familial insomnia is recommended in cases where FFI is suspected. The test examines the prion protein (PRNP) gene for mutations linked to FFI.

People with sporadic fatal insomnia do not have a mutated PRNP gene. However, testing may show other genetic characteristics that could suggest sFI in people who have symptoms of fatal insomnia.

Brain Scans and Imaging

Signs of fatal insomnia typically do not appear on computed tomography (CT) scans and magnetic resonance imaging (MRI) exams. However, such imaging of the brain can be useful in ruling out other conditions that may cause similar symptoms. As fatal insomnia gets worse, an MRI may show part of the brain reducing in size.

An imaging test called fluorodeoxyglucose positron emission tomography (FDG-PET) can show reduced uptake of glucose in the brain, which may be an early sign of fatal insomnia and other conditions that affect the brain.

Brain biopsies do not help diagnose fatal insomnia. But, like other tests, they may help doctors rule out other brain conditions.

Fluid Analysis

A spinal fluid analysis may find signs of nerve cell destruction that can occur in people with fatal insomnia. However, because this cell damage can result from many conditions, this test is not specific enough to diagnose fatal insomnia.

There is no cure for fatal insomnia and no known way of slowing the progression of the disease. Therefore, treatment focuses on palliative care, which is designed to reduce symptoms and improve comfort.

Although it does not treat the disease, comfort care can improve quality of life. Patients may be advised to stop using medications that contribute to insomnia, cause confusion, or make other symptoms worse. A feeding tube may be suggested for people with fatal insomnia who have difficulty swallowing.

Counseling for both the person with fatal insomnia and their family may be a beneficial part of palliative care. Hospice care can also support the person with the disease and their family by providing quality end-of-life care.

No drug therapies have yet been proven to help people with fatal insomnia. Studies have investigated several medications, but the results have been inconclusive.