Fatal familial insomnia: causes, symptoms and treatment

Not all forms of insomnia are psychologically caused. Fatal Familial Insomnia is far from resembling a typical sleep disorder. It is a neurodegenerative prion disease, which, as the name says, is genetically transmitted and ends with the death of the patient in a relatively short period of time that usually lasts less than two years.

Fortunately, it is not a frequent disease, but as soon as it appears it is synonymous with lethality. It is one of the few diseases known to end life through sleep deprivation, and this is why it is so fascinating to neurologists.

What is Fatal Family Insomnia?

Fatal familial insomnia an autosomal dominant inherited prion disease. A mutation in the PRNP gene on chromosome 20 leads to an overproduction of prion proteins, which accumulate and have the ability to convert other proteins into prions, ending the neurodegeneration of the area where they are place.

Location of lesions

The main neuropathological manifestation that we find in fatal familial insomnia is degeneration of the

thalamus, which is responsible for sleep, with selective involvement in the anterior ventral and medial dorsal region of the thalamic nucleus. In addition, there is involvement of the olivary nucleus and changes in the cerebellum, as well as spongiform changes in the cerebral cortex. The areas of the cortex most affected are mainly the frontal, parietal and temporal.

There is no clear relationship between neuronal dysfunction and prion distribution. What's more, not even the number of prions is indicative of the degree of severity of the disease or neuronal death. All patients show similar levels of prions in the thalamus and subcortical structures. Only in those in whom the disease has advanced sufficiently do we find prions in the cortex until there is a higher concentration than in the innermost areas of the brain.

Given these data, two hypotheses arise: either prions are not toxic and only appear at the same time as the disease and what causes neuronal death It is the mutation of the PRNP gene. Prions are toxic, but different brain tissues have different degrees of resistance to this toxicity. Be that as it may, we know that the neurons of these patients not simply die, but they undergo apoptosis, that is, they program their own death guided by a signal.

How does it manifest? Frequent symptoms

It is a disease that usually manifests itself around the age of 50. Its onset is abrupt and continues to progress until the death of the patient. Those who suffer from it begin to lose the ability to fall asleep. Not in the same way as insomniacs, who due to psychophysiological factors can sleep little or badly. It is an absolute inability to fall asleep or to do it in an extremely superficial way.

The disease progresses to hallucinations, autonomic nervous system disorders such as tachycardias, hypertension, hyperhidrosis and hyperthermia, an increase in the levels of catecholamines in the brain, cognitive changes such as short-term memory and attention problems, ataxia, and manifestations endocrine.

Does insomnia cause death?

The exact cause of death in fatal familial insomnia is unknown.. Although any neurodegenerative process ends in death, it is possible that in this disease death comes earlier due to the dysregulation of other functions due to the insomnia.

We know that sleep is a fundamental part of health since it is restorative on a physical and mental level, allowing the purification of toxins in the brain. In animals, for example, sleep deprivation for a long period causes death. Thus, it is possible that the insomnia of this disease, if it is not the direct cause of death, probably does influence the rapid deterioration of brain structures. For this reason, an intervention aimed directly at alleviating insomnia can greatly extend the life expectancy of someone with fatal familial insomnia.

Sleep in fatal family insomnia

In some cases, insomnia itself does not occur. Instead, sleep can deteriorate in its architecture when measured through a polysomnogram, without the need for the patient to be unable to fall asleep. The electroencephalogram of this patient shows predominantly delta wave activity, which is present during the wakefulness, with brief instances of micro-dreams in which the slow waves and K complexes, characteristic of phase 2 of the dream.

The observed rhythms are not typical of someone awake or someone asleepRather, it looks like someone who is in limbo halfway between one side and the other. As the disease progresses, microsleeps are less and less frequent, and the slow waves and K complexes that mark these rest periods progressively disappear.

There is less and less metabolic activity in the thalamus, epileptic seizures begin to occur, changes in the autonomic system worsen, and blood pressure increases. cortisol. Eventually growth hormone, made during the night, which allows the body to inhibit the growth hormone, stops being produced. glucose utilization, causing rapid weight loss and premature aging characteristic of the disease.

Treatment

For now we only have symptomatological treatments, that is, that attack the symptoms, but don't stop the cause of neuronal deterioration. In fact, in many cases the treatment is not even symptomatic, but palliative. Worse still, patients with fatal familial insomnia respond poorly to conventional hypnotics and sedatives. In order to allow these people to sleep, a drug that stimulates slow wave sleep is needed.

Apparently some drugs still under investigation seem to be able to do this, although they have not been tested in people with thalamic damage, only in normal insomniac patients. To date, all attempts to find an effective drug or drug cocktail have been in the context of trial and error. More clinical trials are needed with compounds specifically aimed at inducing sleep, taking into account the barriers posed by thalamic deterioration.