Fatal familial insomnia: causes, symptoms and treatment

Not all forms of insomnia are psychological in origin. Fatal familial insomnia is far from the typical sleep disorder. It is a neurodegenerative prion disease which, as the name suggests, is transmitted genetically and ends in the death of the patient in a relatively short period of time which usually lasts less than two years.

Fortunately, it is not a common disease, but when it does appear it is synonymous with lethality.. It is one of the few diseases known to end life for lack of sleep, which is why it is so fascinating to neurologists.

What is fatal familial insomnia?

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

Location of lesions

The main neuropathological manifestation found in fatal familial insomnia is degeneration of the thalamus, responsible for sleep, with selective involvement in the anterior ventral and dorsal medial region of the thalamic nucleus. Additionally, there is involvement of the olive kernel and changes in the cerebellum, as well as spongiform changes in the cerebral cortex. The most affected areas of the cortex are mainly the frontal, parietal and temporal areas.

There is no clear relationship between neuronal dysfunction and the distribution of prions. Moreover, even the number of prions is not indicative of the degree of severity of disease or neuronal death. All patients present with similar levels of prions in the thalamus and subcortical structures. It is only in those with sufficiently advanced disease that prions are found in the cortex until there is a higher concentration than in the innermost areas of the brain.

In view of these data, two hypotheses arise: either the prions are not toxic and only appear at the same time as the disease and what causes neuronal death is the mutation of the PRNP gene, well the prions are toxic but different brain tissues have varying degrees of resistance to this toxicity. Either way, we know that the neurons in these patients don’t just die, but go through apoptosis, which means they program their own deaths guided by a signal.

How does this manifest itself? frequent symptoms

It is a disease that usually manifests around the age of 50. Its onset is brutal and continues to evolve until the patient’s death. 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 so in an extremely superficial manner.

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

Does Insomnia Cause Death?

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

We know that sleep is a fundamental part of health because it is physically and mentally restorative, helping to cleanse toxins from the brain. In animals, for example, sleep deprivation for a long time leads to death. Thus, it is possible that the insomnia of this disease, if not the direct cause of death, is likely to influence the rapid deterioration of brain structures. Therefore, an intervention aimed directly at relieving insomnia can dramatically extend the life expectancy of a person with life-threatening familial insomnia.

Sleep in the fatal family insomnia

In some cases, the insomnia itself does not occur. Instead, sleep can deteriorate in its architecture when measured by a polysomnogram, without the patient being unable to fall asleep. The electroencephalogram of this patient mainly shows delta wave activity, present on awakening, with brief examples of microsons in which slow waves and K complexes are triggered, characteristic of phase 2 of sleep.

The rhythms observed are not typical of a person awake or asleepBut it looks like someone who is in limbo halfway between one side and the other. As the disease progresses, the microphones become less frequent and the slow, complex K waves that mark these periods of rest gradually disappear.

There is less and less metabolic activity in the thalamus, seizures begin to occur, alterations in the autonomic system worsen, and cortisol increases. Eventually, it stops producing growth hormone, which is made overnight, which allows the body to inhibit the use of glucose, leading to rapid weight loss and premature aging characteristic of the disease.

treatment

At the moment, we only have symptomatic treatments, that is, those that tackle the symptomsBut don’t stop the cause of the neuronal deterioration. In fact, in many cases, treatment is not only symptomatic, but palliative. Worse yet, patients with fatal familial insomnia respond poorly to conventional hypnotics and sedatives. In order for these people to sleep, they need a drug that stimulates slow sleep.

Apparently, some drugs still in research seem to be able to do this, they have not yet been tested in people with thalamic lesions, only in normal insomniac patients. To date, all attempts to find an effective drug or pharmacological cocktail have been carried out in a context of trial and error. Further clinical trials with compounds specifically intended to induce sleep are needed given the barriers involved in thalamic deterioration.

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