Prion disease: why Russia is not diagnosed, fatal proteins in meat and lack of treatment

With the advent of the Internet and free media, people began to learn more about fatal diseases -

infectious, viral, oncological andhereditary. But few have heard of fatal prion diseases. Despite clinical trials, at the moment there is no proven universal treatment of this group of diseases. Neurologist Richard Johnson at Johns Hopkins University says that if a patient’s prions become pathological, he dies and we cannot avoid it.

What is prion disease

Prion diseases - they are also calledtransmissible spongiform encephalopathies are a family of rare progressive neurodegenerative diseases that affect both humans and animals. They are distinguished by:

long incubation period;

characteristic spongy loosening of brain tissue associated with the loss of neurons;

the inability of the immune system to respond to infection, initiating an inflammatory process.

Prion diseases affect both humans and animals, progress rapidly and always lead to death.

Prions in the macro

Causative agent - prions - type of protein withabnormal tertiary structure, free of nucleic acids. The term itself refers to pathological pathogenic agents that can cause abnormal folding of specific normal cellular proteins, which are called just prion proteins, most commonly found in the brain. The functions of these normal prion proteins are still not fully understood.

Creutzfeldt-Jakob disease - CJD, pseudosclerosis, spastic syndrome, corticostero-spinal degeneration syndrome, transmissible spongioforne encephalopathy, mad cow disease.
This is a progressive dystrophic disease.cerebral cortex, basal ganglia and spinal cord. It is considered the main manifestation of spongiform encephalopathy (prion disease). Cure is impossible. CJD affects people of all nationalities and races, men and women, adults and children.

Prion proteins - normal proteins that are present ineach person. But there are certain groups of people who have a genetic mutation that predisposes them to the synthesis of pathogenic prion protein. Prion diseases can also be transmitted through direct infection, transmission can occur during surgical procedures, the use of human growth hormone, or the consumption of infected meat. This type of infection is called iatrogenic and it remains in the percentage minority relative to other forms of CJD.

The percentage of iatrogenic cases of Creutzfeldt-Jakob disease in the National CJD Research & Surveillance Unit study in 177 patients.

Growth hormone (somatotropin) - 53.1% (94 cases).

Dura mater (including eating) - 38.9% (69 cases).

Gonadotropic hormone - 2.25% (4 cases).

Neurosurgical instrumentation - 2.25% (4 cases).

Corneal transplantation - 1.69% (3 cases).

Electrodes for stereoelectroencephalography - 1.12% (2 cases).

Liver transplantation - 0.56% (1 case).

There are cases of infection that are notclassified for any of the two above-mentioned reasons, in which case they are considered sporadic, that is, they have arisen spontaneously and independently, due to circumstances independent of genetics or external factors.

Dr. Oybek Turgunhuzhaev, Headdirections for neurorehabilitation at the Interdisciplinary Rehabilitation Center (Moscow), says that the final diagnosis of a person with suspected any prion disease is based on an assessment of clinical signs and symptoms and a number of supporting studies. For a long time, the only method for confirming the diagnosis was electroencephalography. But since the overall sensitivity of this method is limited, the usefulness of this study was questioned.

Why in Russia do not put this diagnosis

Prion diseases are incurable, they are inevitablefatal. In addition, the problem is that in order to make a reliable diagnosis, an autopsy is necessary. Any autopsy is a risk for the pathologist, as there have been cases of iatrogenic infection by specialists from deceased patients.

By order of Rospotrebnadzor, that a personill with prion disease must be notified within two hours. At the same time, the establishment of such a diagnosis leads, according to Russian instructions, the disposal of all equipment with which the patient was in contact. That is why, when Medusa told the case of one of the patients with CJD, all the clinics said that they did not have the equipment to observe such patients. In fact, it’s just a way not to lose millions of rubles, even scrapping an MRI machine. If it were about hundreds of diagnoses of a prion disease (for example, in the USA 300 cases are registered annually, possibly more), then it would be about losing billions of rubles for Russian hospitals and the budget. That is why the diagnosis is not officially made, doctors do not want to talk about it, since there is no official order that a diagnosis cannot be made. As a result, it turns out that there is a disease, there is death, and there are no reasons for relatives and dying people.

Nobody will tell them that most likely relativesalready infected. No one will say that you can not try raw minced meat or eat raw meat, especially brains. Also, because a diagnosis is not made, it is possible to accidentally transplant the organ of a patient with a prion's disease, thereby infecting another person. It can also occur through a surgical instrument (there were such cases, more on this below).

When we asked anyone to tell us aboutPrion diseases, almost no one was willing to speak openly. So we spoke anonymously with a neurologist at one of the largest hospitals in Moscow. “There are two problems with prions. First, for a reliable diagnosis, an autopsy is necessary. Although formally (for Russian guidelines, for example), an autopsy can be performed, albeit under special conditions. Any autopsy is naturally an additional risk for pathologists, because cases of infection by pathologists from dead patients have been described. no one wants to transfer risk to them.

Secondly, since prion infections are hardflowing, incurable diseases (albeit with a rather complicated mode of transmission), in our country are pretty darn complicated laws for registering and managing such patients; cases must be reported in case of detection within almost two hours, after diagnosis, it is necessary to carry out the destruction of part of expensive equipment, which, as it may turn out, did not even lie next to the patient, reissue documents and so on.

Pretty sad, but nonetheless truthful, the fact is that the correct diagnosis does not matter to the patient. There is still no cure. ”

Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is onefrom varieties of prion diseases. It is a rapidly progressive, fatal neurodegenerative disease, which is believed to be caused by an abnormal isoform of the prion protein. CJD is found throughout the world, and according to statistics, 1 out of a million people are falling ill all over the world.

Prion diseases do not go the same way.scenario, people suffering from the same prion lesion may differ epidemiology and pathogenesis. Creutzfeldt-Jakob disease is divided into several types.

Sporadic form - sore from mutation, coughing, experiencing headache and memory lapses

Sporadic Creutzfeldt-Jakob Disease (SCAN) -the most common type of transmissible spongiform encephalopathy in humans, which accounts for about 85% of cases of registered diseases of prion nature. SBCYA has a very rapid course of the disease - the average life expectancy after the onset of symptoms is only six months. More than 90% of patients die within a year after the onset of symptoms. The peak incidence occurs in older people 60–70 years of age, in other age groups it happens much less frequently. One of the hypotheses of the origin of SCDM is the opinion that this is a spontaneous neurodegenerative disease resulting from a somatic mutation of the PRNP gene or an accidental structural change in the PrP protein, causing the formation of PrPSc2. Epidemiological studies did not reveal a connection between the sporadic form of CJD and environmental factors.

Snapshot mrt patient CJD

The first symptoms of SCAD are usually non-specific: headache, malaise, cough, dizziness, and changes in behavior, mood, or memory lapses. To confirm the diagnosis, time must pass in order for other reasons to appear to suggest prion nature. The classic clinical signs with CJD are:

rapid decline in cognitive abilities;

ataxia (violation of the coordination of the movement of various muscles);

myoclonus (rapid sudden contractions of individual muscles), ending in akinetic mutism (inhibition of all motor functions, except for fixing movements of the eyeballs).

The final diagnosis depends on the evaluation of the clinical manifestations and the results of laboratory tests.

Akinetic Mutism - a condition in which patients stopmove and follow the target’s eyes, with the exception of eye reaction to stimuli or long-term fixation of the gaze, their muscles independently or under the influence of external factors periodically rapidly contract. Patients suffer from incontinence, do not make any sounds or just inarticulate noises. If swallowing persists, patients can live in this state for several weeks, even years with other favorable factors, getting food intravenously or through a tube. In the sporadic form of CJD, patients reach this state during the first weeks of the disease. In the most rapid scenarios, 10% of patients reach this state in a year.

For a long time the most informative waydiagnosis was performed by diffusion-tensor MRI. This method is the most accessible, relatively non-invasive and effective for early changes in the cerebral cortex. SBKYa can be detected through markers in nasal mucous membranes, cerebrospinal fluid, urine or blood, but these tests often give false positive results - protein 14.3.3 is not specific without the appearance of a concomitant clinical picture. The proteinogram is a new optimal method for diagnosing SCD, as it is the most sensitive of all of the above.

Proteins 14-3-3 - family of regulatory molecules found inall eukaryotes. They bind to many other proteins, regulating their functions and thereby affecting a variety of processes, including cell cycle regulation, metabolic control, apoptosis, gene transcription control. They were discovered more than 40 years ago with the systematic classification of proteins of the nervous tissue, where their content exceeds 1% of all proteins. To date, more than 300 different target proteins that can interact with 14-3-3 have been described.

Proteinogram - A study that studies the quantitative ratio of protein varieties in the blood. The concept of total protein includes all possible proteins, despite their differences in structure and function.

Hereditary form of Creutzfeldt-Jakob diseaseand fatal familial insomnia associated with genetic mutations, constitute only 10% of all cases of prion diseases. Many studies indicate that the general pathway in the pathogenesis of a disease can be common for both sporadic and hereditary forms of prion disease, except that in the first case, protein transformation occurs without the participation of any factors, and is not predetermined by the presence of mutation in the genes.

(A) Sponge-like degeneration in the cortex of largehemispheres. Inset: neurons containing vacuoles. (B) The cerebellum bark with kuru plaques (PAS reaction), which consist of PrPsc aggregates. (B) Plaques in the cortical substance, surrounded by a spongy-shaped degeneration zone, with a new variant of Creutzfeldt-Jakob disease.

Studies of hereditary forms of CJD and fatalfamily insomnia provided scientists with the opportunity to study the course of phenotypic heterogeneity (a variety of “strains”) of prion disease. Although many other neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's chorea, are quite similar in phenotype, prion disease includes many clinically different symptoms.

Phenotype - a set of characteristics inherent in a certain stage of the disease. The phenotype is formed on the basis of the genotype.

Polymorphism - the ability of some organisms to exist in states with different internal structures or in different external forms.

With hereditary prion disease, phenotypediseases will be determined by the combined effect of pathogenic mutations, codon 129 polymorphism and PrP Sc type. Codon 129 polymorphism plays a dual role in predicting the outcome of a disease. Central to the understanding of the pathogenesis of prion disease is a detailed and accurate knowledge of the processes and conditions in vivo for the formation of PrPSc, which inevitably leads to the development and expression of the disease. This knowledge will allow you to develop a rational and effective strategy for therapeutic intervention.

New variant of CJD - to get infected by eating a piece of meat

New variant of Creutzfeldt-Jakob disease(nvCJD) was first identified in 1996. Subsequent studies have confirmed the hypothesis that this form is associated with bovine spongiform encephalopathy. Most likely, patients ate meat containing pathological prions in the brain of cows.

Unlike the sporadic form, the disease is nothas a clear age of infection. Psychiatric symptoms are often identified in patients with nBKYa, because sometimes she is mistakenly diagnosed as a mental, not a neurological disorder. The true cause of psychiatric symptoms lies in cognitive impairment, persistent pain in the limbs, impairment of sensory adequacy (paresthesia or dysesthesia), speech or vision disorders.

Vices develop within 6–8 monthsmanagement of the muscular system, but in some cases the development of the disease can last more than 18 months. Therefore, this diagnosis is difficult to make when the first signs of the disease appear. If a patient has uncontrolled movements, the likelihood of competent diagnosis of nBCD increases. Unlike the sporadic form, where sudden muscle spasms are characteristic during tension (myoclonus), dystonia (a syndrome in which constant spasmodic muscle contraction occurs) and chorea (a syndrome characterized by random, jerky, irregular movements) are possible in the case of a new form. .

The lethal stage of the new form is similar to the lethalthe stage of the sporadic form of Creutzfeldt-Jakob disease, it passes with a progressive loss of muscle control, often resulting in akinetic mutism.

Dementia and CJD: someone is sick and does not even know about it

Unlike the more common idiotconditions that usually develop over the years, rapidly progressing dementia can develop within a few months, weeks, or even days and lead to death. The sporadic form of CJD accounts for 46.9% of all reported cases of rapidly progressing dementia, the genetic form of prion diseases - 13.6%. 39% of all cases are fronto-temporal dementia (FTD), corticobasal degeneration (CBD), Alzheimer's disease (AD), Levi body dementia (DLB) and progressive paralysis.

As a rule, sporadic form of CJD is represented bya combination of dementia and neurodegenerative or psychiatric symptoms. In such patients, pyramidal, cerebellar and focal cortical dysfunction are common. One third of dementia patients are preceded by complaints of fatigue, headache, sleep disturbances, malaise, weight loss, pain, depression, or changes in behavior.

Neurological symptoms, including ataxia,dysesthesia, dementia or muscle disorders (chorea, myoclonus or dystonia) appear later. Most cases of rapidly progressing dementia without other associated symptoms occur in older people due to metabolic disorders or acute infections (pneumonia or urinary tract infections). Therefore, before passing laboratory tests, physicians, first of all, indicate rapidly progressing dementia without an explicit diagnosis. The final verdict will depend on the results of tests and examinations, the disease will differ depending on the clinical picture. An EEG may help eliminate convulsive activity in the brain and turn to the diagnosis of other conditions, such as CJD.

Rapidly progressive dementia presentone of the most difficult neurological problems. Differential diagnosis is widely used to confirm definitive diagnoses that may relate to neurodegenerative, autoimmune, infectious, and neoplastic diseases. Even with such a careful approach to the examination of patients, a small percentage of cases are diagnosed after death.

Fatal familial insomnia

Fatal familial insomnia is rare.prion disease, which literally deprives sleep and leads to a decrease in all neuro-motor and mental functions. Two forms of this disease can be distinguished: genetic and sporadic.

The genetic form is associated with a mutation that causesto the transformation of PrP protein into a prion protein. Sporadic appears spontaneously, without any prerequisites. This disease differs from other prion diseases in the area of damage - the transformation of prion proteins into pathological ones mainly occurs in one section of the brain - the thalamus, which is also responsible for sleep.

Mean age at onset of symptomsThe genetic form of fatal familial insomnia is 40 years. Early symptoms are expressed as minor difficulties in falling asleep and sleeping, muscle twitching, cramps, and torpor. During sleep, people can sleep restlessly: move their legs and arms, toss and turn. In the end, the sick stop sleeping. By virtue of this, mental activity decreases, muscular coordination (ataxia) is lost. Patients can be traced to increased blood pressure, increased heart rate and excessive sweating. Unlike other prion diseases with fatal familial insomnia, there is no spongy degeneration of the brain substance. The main signs of damage are the degeneration of neurons and reactive gliosis (the formation of "scars" on and in the brain tissue) in the nuclei of the thalamus, as well as the degeneration of neurons in the complex of nuclei of the medulla.

Brain Sick with Fatal Family Insomnia

The diagnosis of fatal familial insomniagenetic form is confirmed by genetic testing. In the case of sporadic cases, polysomnography and positron emission tomography (PET) can be detected in the structure of sleep and abnormalities in the thalamus. The average life expectancy since the beginning of the first symptoms of the disease is 3 years, there is no treatment.

Slow progressing dementia: symptoms over several years

Gerstmann-Straussler-Sheinker syndrome isA rare genetic form of transmissible spongiform encephalopathy, which was first described by Austrian neurologists in 1936. The syndrome is most often seen at the age of 40–50 years, and is caused by mutations of the PRNP prion protein genes on chromosome 20.

The clinical picture of the syndrome is similar tosporadic form of CJD, but it differs in duration and slowly progressive dementia, along with other symptoms. Gerstmann-Straussler-Sheinker syndrome can last for several months or several years, the average life expectancy is 5 years. It is possible to diagnose the disease even in the early stages through magnetic resonance imaging. MRI will show spongy changes in the cortex and proliferation of glial cells.

Glial cells or neuroglia - a set of auxiliary cells of the nervous tissue. It is about 40% of the central nervous system. The number of glial cells in the brain is approximately equal to the number of neurons.

Glial cells have common functions and, in part,origin (exception - microglia). They constitute a specific microenvironment for neurons, providing conditions for the generation and transmission of nerve impulses, as well as carrying out part of the metabolic processes of the neuron itself.

Detecting prion disease is enoughlabor-intensive, given that if the diagnosis is confirmed, the patient is no longer able to help, and hospitals lose millions of rubles. And the worst thing is that all people on Earth are at risk. Prions will not spare anyone. Therefore, do not try the stuffing after it has been salted. Do not eat the guts and brains of cows and pigs, and visit the doctor on time. In the end, an MRI will not lie.