Fatal Familial Insomnia: Causes, Symptoms And Treatment
Not all forms of insomnia are psychological in cause. Fatal Familial Insomnia is far from resembling a typical sleep disorder It is a neurodegenerative disease due to prions, which, as the name suggests, is transmitted genetically 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 common 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, which is why it is so fascinating to neurologists.
Fatal familial insomnia an autosomal dominant hereditary prion disease A mutation in the PRNP gene on chromosome 20 gives rise to an overproduction of prion proteins, which accumulate and have the ability to convert other proteins into prion proteins, ending with neurodegeneration of the area where they are located.
Location of lesions
The main neuropathological manifestation that we find in fatal familial insomnia is the degeneration of the thalamus, which is responsible for sleep, with selective involvement in the ventral anterior and dorsal medial regions of the thalamic nucleus. In addition, involvement is found in 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 an indicator 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 greater 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 is the mutation of the PRNP gene, or 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 do not simply die, but rather 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 approximately 50. Its onset is abrupt and continues to progress until causing 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 may sleep little or poorly. This is an absolute inability to fall asleep or to do so in an extremely superficial way
The disease progresses towards hallucinations, alterations of the autonomic nervous system such as tachycardia, hypertension, hyperhidrosis and hyperthermia, an increase in catecholamine levels in the brain, cognitive changes such as attention and short-term memory problems, ataxia and endocrine manifestations.
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 sooner due to the deregulation of other functions due to insomnia.
We know that sleep is a fundamental part of health since it is restorative on a physical and psychological 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 worsening of brain structures. For this reason, an intervention aimed directly at relieving 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 we measure it through a polysomnogram, without the patient being unable to fall asleep. This patient’s electroencephalogram predominantly shows delta wave activity, which is present during wakefulness, with brief instances of microsleep in which slow waves and K complexes, characteristic of phase 2 of sleep, are triggered.
The observed rhythms are not typical of someone awake or someone asleep, but rather he seems like someone who is in a limbo halfway between one side and the other. As the disease progresses, microsleeps become less and less frequent, and the slow waves and K complexes that mark these rest periods progressively disappear.
There is increasingly less metabolic activity in the thalamus, epileptic seizures begin to occur, alterations in the autonomic system worsen and cortisol increases. Finally, growth hormone, produced during the night, stops being produced, which allows the body to inhibit the use of glucose, causing rapid weight loss and premature aging characteristic of the disease.
For now we only have symptomatic treatments, that is, those that attack the symptoms, but do not stop the cause of neuronal deterioration. In fact, in many cases the treatment is not even symptomatic, but rather palliative. Worse still, patients with fatal familial insomnia respond poorly to conventional hypnotics and sedatives. In order to allow these people to sleep, a medication is needed that stimulates slow wave sleep.
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 pharmacological cocktail have occurred in a context of trial and error. More clinical trials are necessary with compounds specifically aimed at inducing sleep taking into account the barriers posed by thalamic deterioration.
