Tragedy of the insomnia family to death

In the world, there are people who are faced with the dreaded "insomnia" that makes them suffer for months before they die.

Silvano's family lives in fear of fatal insomnia.(Artwork: BBC)

Mr. Silvano, 53, is enjoying the fun on a luxury cruise ship, showing the initial symptoms of the disease.

Initially sweating all over the shirt, Silvano blurted out that the pupils of the eyes were shrinking like a needle, making their eyes go blank, just like the symptoms that father and two sisters had. His ever suffered.

Silvano knows for sure that he will also have to suffer from the following symptoms, such as shaking his body, helplessness and even persistent constipation, but more frightening is chronic insomnia , which will make He stayed up all night for months, eventually falling into a coma and dying.

Silvano did not fool himself that this dreaded disease would be cured when contacted with the sleep research department of the University of Bologna.

" I will lose my sleep completely and only eight or nine months later, I will definitely die, " Silvano told Dr. Pietro Cortelli, and gave proof of the Silvano family 's genealogy from the 18th century, each The system has members who died of the disease.

Just as Silvano predicted, he died a few years after getting sick, but there was a wish to leave his brain for scientific research, hoping this could help clarify his family's strange disorders. and finding a treatment, preventing the same tragic fate that happens to other members.

The Silvano family almost kept their struggle with "family lethal insomnia " (FFI), except for the one time history mentioned by DT Max in the book "The Family people who do not sleep, " reveals the overall picture of people living in the immediate fear of their own genome .

Investigation

Looking for the genealogy of these " hopeless patients ", Max found the first case of the disease that could be traced as a scholar in the late 18th century Venice.

Medical records describe patients falling into paralysis and lethargy for months . Soon after, Giuseppe's nephew suffered from the same condition, then two sons Angelo and Vincenzo, passed down through the great generations to Pietro, Silvano's father, died during World War II.

Despite repeated lingering losses, the whole family did not seem to mention the disease due to the fear of fate, but Silvano wanted to change this and cooperate with a doctor-in-law. , scientist Ignazio Roiter , found out what happens inside the brain and body of people with this strange disease .

Efforts to understand the disease cannot save Silvano and the other two family members, but extensive trials eventually find the culprit: a deformed protein in the brain called prion - toxic protein, caused by a small genetic mutation. For some reason, just in middle age, prions began to multiply in an unorganized way, gathering into a group that poisoned nerve cells.

At a certain time in the night, people with FFI can enter an unconscious coma - not completely sleep, but not fully conscious, in that they imitate unconsciously. normal daily rhythm.(Artwork: BBC)

This finding shows that the disease is related to Creutzfeldt-Jakob disease (CJD) and mad cow disease - two other prion-related diseases known as TSE (transmissible spongiform encephalopathies), which attract attention. the attention of the scientific world at that time.

Creutzfeldt-Jakob disease (CJD) is a toxic protein that causes the brain's surface to become like a cheese block, while Silvano's insomnia (FFI) causes a tendency towards the thalamus (thalamus). ) in the center of each brain hemisphere. Researching images shows that the thalamus in Silvano's brain, which is sized and shaped with a walnut, is punctured like a worm.

After years of intensive research, scientists have been able to explain why the damage caused to this tiny neuropathy leads to such confusing symptoms.

Scientific explanation

We all know that the brain center regulates all activities that our bodies "automatically" respond to environmental impacts such as air conditioning, blood pressure, heart rate, simultaneously, resolution. Release some hormones to help the body work smoothly.

There seems to be no effective treatment for fatal insomnia.(Artwork: BBC)

When this coordination center is broken, everything will really become chaotic, so the sweat that is profoundly uncontrollable, the eyed pupils shrink, appear helpless and constipated. .

The unstable control of the central brain region may also contribute to insomnia , as the body of the sick person is not prepared to sleep at night.

Normally, normal human blood pressure will decrease before going to sleep, but patients with FFI blood pressure are unusually high, making patients feel that their bodies are still in high alert.

" If the sympathetic nervous system is not in equilibrium, of course the patient will experience insomnia," Cortelli presented his idea in a recently organized seminar on history. sleeping pills

Influenced by the problems mentioned above, the normal rhythm of the brain will be in complete turmoil. A seemingly normal night's sleep also includes various stages, followed by periodic cycles of rapid eye movement and emphasized by the "submerged wave" state. makes sleep deeper.

During this period, oscillation at low frequencies of electrical activity ripples on the cerebral cortex - through the bark, bark-like tissue on the surface of the brain.

This state of sleep seems to be able to reduce the excitement of the usual conscious coordination of the brain when awake, while also performing important maintenance tasks such as consolidate, classify, gather memories collected during the day to put into long-term memory.

The small brain region that is extremely important to coordinate all these delicate rhythmic activities is the thalamus (thalamus). Without a central switch that controls this state of change, people with FFI will always be in a state of alertness and unable to get regular sleep, sleep brings recovery to brain activity.

It was the statement of Angelo Gemignani at the University of Pisa, Italy, who demonstrated that FFI patients lost this crucial stage of brain activity.

There is no "sinking " state - the slow period of brain activity, the closest to normal sleep that FFI patients reach is a kind of unconscious lethargy - not entirely sleep, but not fully conscious, in that they imitate unconsciously the usual rhythm of daily life.

A well-known patient with FFI has suggested that some unusual ways can be used to minimize suffering. Psychologist at New York's Touro College, Joyce Schenkein tells about Daniel who is a wonderful, intelligent and extremely funny guy, after which Daniel begins conversations with timbre and intonation. somewhat confused, vague.

"There were times, he said 'forgive me if my voice was interrupted, discrete, but I didn't sleep for the last five days'," Schenkein said.

A medical test showed that Daniel was carrying a genetic mutation that caused FFI, and there were some people with FFI-related illnesses in Daniel's father's family, but sadly, the disease was inherited to Daniel again. growing very fast.

Enjoy life

Instead of collapsing or desperate, Daniel chose to live actively, traveling all over the United States, not just sitting and waiting to die. Meanwhile, Daniel also tested many potential treatments, ranging from vitamin supplements, exercise to general fitness, to local anesthesia with drugs such as ketamine and nitrous oxide. , along with sleeping pills like diazepam - anything can help you take a nap, even if it's only a few minutes.

Daniel even bought a dedicated soundproof chamber, because found that even after using anesthesia, his fragile sleep could still be interrupted by very small noises or switching. Surprise.

Lying in an egg-shaped cocoon, bathing in warm salt water, Daniel found some rest and enjoyed a sleep full of happiness lasting four and a half hours. However, when he regained consciousness, he faced a very scary illusion - including a feeling of uncertainty about whether he was alive or dead.

There are times when Daniel loses consciousness throughout the day.(Artwork: BBC)

Despite certain successes, Daniel still faces frequent relapses, becoming more and more stressful when the disease goes bad.

" When the symptoms of the disease became severe, Daniel could not do anything," Schenkein said. "There were times when he lost his whole consciousness all day. He just sat there, there was no active movement at all; at that time, he seemed to be frozen."

Daniel even tried to use an electric shock therapy that affected the brain to try to see if a strong electric shock caused him to faint. Although there was some effect, the side effect of this therapy caused Daniel to suffer from dementia, so he could not use this therapy for further treatment. Finally, after a few years of struggling against the fatal disease, Daniel also left.

New Hope

Although there is no treatment to prove a long-term effect, Daniel has lived a few years more than the initial diagnosis.

Scientists hope the new drug will cure the underlying disease in the genetic genes of FFI patients.(Artwork: BBC)

Schenkein points out that recent studies provide evidence that sleep's "sinking waves" cause the flow of cerebrospinal fluid to wash away, carrying debris through channels between cells. Brain. This, perhaps alleviating chronic insomnia, while cleaning and preventing further disintegration of the brain.

Along with Italian neuroscientist Pasquale Montagna (who worked with other cases of "family death-inducing" insomnia ), Schenkein published research papers on this case in a single issue. Medical releases, in the hope that it could inspire other scientists in their search for ways to prolong the lifespan of a life-threatening insomnia patient - FFI.

The hope of FFI-affected families in Venice is focusing on a new research direction. After decades of working with people with FFI, Dr. Roiter and his colleagues in Milan, along with Treviso, are confident that they have nearly succeeded in finding ways to cure the disease when announcing the trials. Clinically a new drug hopes to prevent or at least reduce the rate of formation of toxic prions (toxic proteins).

The drug in question, doxycycline, has previously shown promise of therapeutic potential in Creutzfeldt-Jakob disease trials (CJD), originally of an antibiotic, it seems to have the ability to prevent prions from sticking together into blocks and even support the division of prions through the brain's natural enzymes.

Indeed, in a small clinical trial of people with early signs of FFI, 21 people took the medication to drink, twice as long (averaging 13 months) compared to 78 subjects observed.

But sadly, studies conducted on patients who have been taking doxycycline and showing good signs of progress do not produce satisfactory results for FFI. Roiter and his colleagues suggest that at the time of the disease, the use of treatment is too late, with no therapeutic effect.

For this reason, they propose a method of whether doxycycline can be used as a preventive treatment for people at risk of FFI, before prions begin to accumulate.

"It may delay or completely disrupt the development of the disease," said Gianluigi Forloni, head of the project at Mario Negri's Pharmaceutical Research Institute in Milan.

Long-term testing is conducted with families with FFI patients in anxiety. First, the scientists tested the family members' chromosomes to see who brought the mutation, and therefore needed to use the appropriate drugs. Then, they selected 10 members aged 42 to 52, who will see the impact of the disease in the next decade.

The problem is that many of the family members with FFI do not want to know the results of the test, because they fear it will be like a horrifying dark cloud covering every minute of their awakening.

For this reason, an additional 15 members who are not at risk will also be treated with counterfeit drugs. This means that each member will have no way to find their test results.

Without aggressive treatment, Forloni predicts that at least four of the 10 subjects with the mutation will die in the next decade. Therefore, if more than 6 people get out of this disease at the end of the trial period, they are considered successful - it is possible to consider using this treatment more widely.

Although the experiment brought many glimmer of hope, the controversy surrounding it continued to take place in the doctor's world to closely monitor this family disease. Because even if family members have escaped the disease at the end of the trial period, it is not ruled out that there are just a few individuals who are simply lucky; some mutants still live up to 80 years old and no one knows why their genes carry the disease.

Although very anxious and bewildered, families with FFI patients still decided to bet their lives on treatment gamble: this is an opportunity to cancel the death penalty written in their DNA in centuries.

If the drug being studied actually works, it will be the end of this nightmare - and the beginning of a new future in which a good night's sleep will be welcomed. Receive without fear that it could be the last sleep.