Fatal familial insomnia

Fatal or fatal familial insomnia (FFI) is a rare genetic neurodegenerative disease that affects very few people worldwide. It is a prion disease, caused by prions, which are proteins that have undergone a mutation and accumulate to form deposits in brain tissue, thereby causing neurological damage. The mutation that causes a prion protein to become harmful in IFF is the D178N mutation.

It is the third prion disease in frequency, the first being Creutzfeldt-Jakob disease, but there are only about 40 diagnosed cases in the world, concentrated in 28 families. The inheritance pattern is autosomal dominant, which implies that there is a 50% risk that the patient transmits the mutation and, therefore, the disease to their descendants, regardless of their sex.

Cases have been diagnosed in the United States, Germany, France, Spain, Italy, the United Kingdom, and Japan. The cases diagnosed in Spain are mainly located in the Basque Country.

The mean age of onset of the disease is around 50 years and once established, the average life expectancy is about 18 months (between 2 and 36 months), as the disorder inevitably leads to a coma that leads to the death of the patient.

How it manifests

When the disease manifests itself, prions have been accumulating for years and causing damage to an area of ​​the brain, the thalamus, which controls, among other functions, the sleep and wake cycles, as well as the autonomic nervous system, which is responsible for regulating functions unconscious of the body, such as heart rate or blood pressure.

Sleep has certain phases and it is in the deep sleep phases during which brain information is reorganized, damage is repaired and real rest is achieved. In patients with IFF, this cycle is altered and a state of deep sleep is never reached, at most a stupor that is not restorative at all. Due to this lack of sleep, episodes of sudden daytime sleep can occur, as in the case of patients suffering from narcolepsy.

Insomnia is progressive as the disease progresses and does not respond to treatment with the usual hypnotic drugs. It is also accompanied by behavioral disturbances, delusions and hallucinations at night. Before insomnia itself manifests itself, the patient may present anxiety, irritability, lack of interest in the environment, lack of concentration and daytime sleepiness.

Since the thalamus, affected by the prions in IFF, also controls the autonomic nervous system, these patients may also present other disorders (dysautonomia):

-Arterial hypertension -Tachycardia –Diaphoresis (profuse sweating) –Hyperthermia (increased body temperature) -Constipation –Urinary difficulties –Miosis (very constricted pupils)

With the evolution of the disease, other severe alterations occur, such as loss of muscle tone, increased tendon reflexes, tremors and stiffness of the muscles, weakness, muscle atrophy, alterations in the ability to speak, involuntary contractions of groups muscles (myoclonus), slow and involuntary twisting of the limbs (athetosis), very marked weight loss and visual disturbances that can even lead to total blindness.

Diagnosis

The diagnosis of IFF is established through medical history and family history. In imaging tests such as CT or MRI, anatomical alterations will not be seen, while positron emission tomography (PET) will show a decrease in activity at the level of the thalamus. The electroencephalogram will show an alteration in brain activity and the polysomnography will determine the marked alteration of the phases of the sleep cycle, this being superficial and lasting only a few minutes.

Treatment

Currently, this disease has no cure and people who suffer from it end up dying in a short period of time after the symptoms appear. The risk of transmission to offspring is 50%, so if offspring are desired it would be necessary to carry out a genetic counseling to establish which members of the family are carriers of the gene. A clinical study has been carried out for a possible treatment of IFF that slows its evolution, but at the moment the results are unknown.

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• Those who suffer IFF never reach a state of deep sleep. Insomnia is progressive and does not respond to the usual hypnotic drugs.
• With the evolution of the disease, other severe alterations occur, such as loss of muscle tone, tremors, visual disturbances, weight loss ...
• The risk of transmission to descendants is 50%, there is no cure and those who suffer from it die in a short period of time after the symptoms appear.