PML disease. Progressive multifocal leukoencephalopathy

Pathology occurs against the background of suppression of immunity in patients with AIDS, hemoblastosis, hereditary immunodeficiencies, in patients receiving immunosuppressive therapy. Diagnostics is based on clinical data, results of brain tomography, PCR study of cerebrospinal fluid for viral DNA, histology of cerebral biopsy specimens. No specific therapy has been developed.

Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is associated with the JC virus (JCV) and occurs in immunocompromised patients, 85% of whom are HIV-infected. The disease belongs to opportunistic infections, 90% of humanity are carriers of the virus. Until the 90s of the twentieth century, the incidence of PML did not exceed 1 case per 100 thousand population. With the increase in the number of AIDS patients, this figure increased to 1 in 20 thousand people. Today, progressive leukoencephalopathy occurs in 5% of AIDS patients. Several authors have reported declines in the incidence over the past decade due to the successful use of antiretroviral therapy. At the same time, there is an increase in the prevalence of PML among people with autoimmune diseases, which is due to the use of aggressive immunotherapy in their treatment.

Causes of PML

Progressive multifocal leukoencephalopathy develops as a result of reactivation of the JC polyomavirus. The virus is ubiquitous. The source of infection is a person, the infection occurs by airborne droplets, alimentary. The vast majority of people become infected during childhood and are healthy carriers. During life, the virus is in a latent state, persists in the kidneys, spleen, and bone marrow. The reactivation of the pathogen occurs against the background of a sharply reduced immunity. The risk group for developing the disease includes the following conditions:

• HIV infection in the form of AIDS. It is accompanied by suppression of cellular immunity. It is the most common cause of PML.
• Hemoblastosis. Myeloproliferative (leukemia) and lymphoproliferative (lymphomas) processes lead to the development of immunodeficiency.
• Autoimmune pathology: systemic lupus erythematosus, scleroderma, rheumatoid arthritis... Immunodeficiency is formed against the background of active immunosuppressive treatment, especially with monoclonal antibodies.
• Hereditary diseases with immunodeficiency: Di Giorgi syndrome, Wiskott-Aldrich syndrome, ataxia-telangiectasia.
• Immunosuppression during organ transplantation.
• Secondary immunodeficiency as a result of cytostatic therapy for oncological diseases.

Pathogenesis

Disorder of cellular immunity provokes a rearrangement of the DNA sequence of the JC-virus, leading to its activation. The virus has a tropism for the cellular elements of neuroglia (oligodendrocytes, astrocytes), the defeat of which is accompanied by the destruction of myelin. As a result, multifocal progressive demyelination occurs in the brain substance with the growth and fusion of lesions. Microscopically, an increase in astrocytes, deformation of their nuclei are detected, staining of oligodendrocytes reveals nuclear inclusions - accumulations of JCV particles. The primary role in the immune antiviral response is played by cytotoxic T-lymphocytes, which kill cells infected with an active virus. The decrease in the production of specific T-lymphocytes due to immunodeficiency causes the development of PML.

PML symptoms

The onset of the disease is subacute (2-3 days) or gradual (1-3 weeks). Pathopsychological symptoms and focal neurological deficits come to the fore. In a typical variant, progressive multifocal leukoencephalopathy occurs without cerebral symptoms characteristic of neuroinfections, meningeal syndrome. Changes in behavior, aggressiveness, emotional lability, suspicion, progressive weakening of the cognitive sphere (memory, thinking, attention) are noted. Focal deficit is represented by muscle weakness of the limbs of one half of the body (hemiparesis), aphasia, hemianopsia, ataxia, paresthesias in the paretic limbs. Initially, hemiparesis may be absent, later it is observed in 75% of patients. 20% of cases occur with paroxysms of epilepsy. Mental disorders are noted in 38% of patients. The progression of cognitive deficits leads to dementia.

In rare cases, multifocal leukoencephalopathy occurs in an atypical form. Atypical variants include JC meningoencephalitis, JC encephalopathy, granular cell neuropathy. The meningoencephalitic form is characterized by the presence of meningeal symptoms. In JC encephalopathy, there is no focal neurological deficit. The clinical picture of the granular cell variant is presented by the isolated cerebellar syndrome.

Diagnostics

Progressive leukoencephalopathy is diagnosed by specialists in the field of neurology on the basis of clinical data, the results of neuroimaging studies, and the detection of specific DNA. The diagnostic algorithm includes:

• Examination by a neurologist. In the classical version, the neurological status is determined by hemiparesis, hemihypesthesia, unsteadiness, instability in the Romberg position, discoordination, sensorimotor aphasia, and cognitive impairment. Lability of the psyche, psychopathological symptoms, possibly inappropriate behavior are observed.
• Examination by an ophthalmologist. Most patients are diagnosed with decreased vision, perimetry reveals homonymous hemianopsia.
• MRI of the brain. Diffuse multifocal demyelination is found, the lesions are of different sizes, asymmetrically located in the white matter, thalamus, basal nuclei.
• PCR study. Aimed at detecting JC virus DNA in cerebrospinal fluid obtained by lumbar puncture. The specificity of the analysis is%, the sensitivity is 70-90%. Conducting antiretroviral therapy to AIDS patients reduces the sensitivity of the study to 58%, a negative result does not exclude the presence of the disease.
• Brain biopsy. An invasive technique, carried out in diagnostically difficult cases. Histological examination of cerebral tissue samples allows confirming morphological changes specific to leukoencephalopathy.

An accurate diagnosis of "progressive multifocal leukoencephalopathy" is justified when the classic clinical manifestations, MRI changes are combined with a positive PCR result or are confirmed by histology. The presence of only clinical and MRI signs allows us to interpret the diagnosis as probable. Differential diagnosis is carried out with primary neuro AIDS, neuro-rheumatism, viral encephalitis.

PML treatment

Currently, there are no proven drugs for the treatment of progressive leukoencephalopathy. Specific therapy is under development. Attempts to treat with interferon, immunostimulants, cytarabine, and their combinations were unsuccessful. Clinical trials of the drug cidofovir, showing anti-JC efficacy in experiments with mice, ended in failure. Recently, a radically new treatment was proposed with the antidepressant mirtazapine, which blocks the spread of JCV by binding to receptors through which the virus infects neuroglia cells. The method requires clinical trials.

Forecast and prevention

Progressive multifocal leukoencephalopathy is characterized by a steadily worsening course with an outcome in coma. Life expectancy varies from 1 month. (acute form) home. since the moment of illness. Prevention implies measures to prevent HIV infection, careful therapy autoimmune diseases, monitoring of neurological symptoms in patients receiving treatment with monoclonal drugs.

Progressive multifocal leukoencephalopathy - treatment in Moscow

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Leukoencephalopathy of the brain - what is it? Symptoms, treatment, prognosis

Leukoencephalopathy is a progressive type of encephalopathy, also called Binswanger's disease, which affects the white matter of the subcortical tissues of the brain. The disease is described as vascular dementia, and it is most susceptible to the elderly after 55 years. The defeat of the white matter leads to restriction and subsequent loss of brain functions, after a short time the patient dies. The ICD-10 code for Binswanger's disease is І67.3.

Varieties of leukoencephalopathy

There are the following types of the disease:

1. Leukoencephalopathy of vascular origin (small focal) is a chronic pathological condition in which the structures of the cerebral hemispheres are affected slowly. The risk category includes elderly people over 55 years old (mainly men). The cause of the disease is a hereditary predisposition, as well as chronic hypertension, which manifests itself in frequent attacks of high blood pressure. The consequence of the development of this type of leukoencephalopathy in old age can become dementia and death.
2. Progressive leukoencephalopathy (multifocal) is an acute condition in which, due to a decrease in immunity (including the progression of the immunodeficiency virus), the white medulla liquefies. The disease develops quickly, if the necessary medical care is not provided, the patient dies.
3. Periventricular leukoencephalopathy - the subcortical tissues of the brain are adversely affected due to prolonged oxygen deficiency and the development of ischemia. Pathological foci are most often concentrated in the cerebellum, brain stem, as well as structures responsible for the functions of movement.

Causes of the disease

Depending on the form of the disease, leukoencephalopathy can occur for a number of reasons that are not related to each other. So, a disease of vascular origin manifests itself in old age under the influence of the following pathological causes and factors:

• hypertonic disease;
• diabetes mellitus and other endocrine dysfunctions;
• atherosclerosis;
• the presence of bad habits;
• heredity.

The reasons for the negative changes occurring in the structures of the brain in periventricular leukoencephalopathy are conditions and diseases that provoke oxygen starvation of the brain:

• birth defects caused by genetic abnormalities;
• birth injuries arising from the entanglement of the umbilical cord, incorrect presentation;
• deformity of the vertebrae due to age changes or injury and impaired blood flow through the main arteries as a result.

Multifocal encephalopathy appears against the background of severely reduced immunity or its complete absence. The reasons for the development of this condition may be:

• HIV infection;
• tuberculosis;
• malignant formations (leukemia, lymphogranulomatosis, sarcodiosis, carcinoma);
• taking potent chemicals;
• taking immunosuppressants used during organ transplantation.

Determination of the reliable cause of the appearance of leukoencephalopathy allows doctors to prescribe adequate treatment and slightly extend the patient's life.

Symptoms and signs of leukoencephalopathy

The degree and nature of the manifestation of symptoms of leukoencephalopathy directly depends on the form of the disease and the location of the lesions. The symptoms characteristic of this disease are:

• permanent headaches;
• weakness in the limbs;
• nausea;
• anxiety, causeless concern, fear and a number of other neuropsychiatric disorders, while the patient does not perceive the condition as pathological and refuses medication;
• unsteady and wobbly gait, decreased coordination;
• visual disturbances;
• decreased sensitivity;
• violation of speaking functions, swallowing reflex;
• muscle spasms and cramps, turning over time into epileptic seizures;
• dementia, at the initial stage manifested in a decrease in memory and intelligence;
• involuntary urination, bowel movement.

The severity of the described symptoms depends on the state of human immunity. For example, patients with reduced immunity have more pronounced signs of damage to the medulla than patients with a normal immune system.

Diagnostics

If you suspect the presence of one of the types of leukoencephalopathy, the results of instrumental and laboratory examinations are fundamental in the diagnosis. After the initial examination by a neurologist and an infectious disease doctor, the patient is assigned a number of instrumental examinations:

• Electroencephalogram or Doppler ultrasound - to study the state of the vessels of the brain;
• MRI - to identify multiple lesions of the white medulla;
• CT - the method is not as informative as the previous one, but it still allows you to identify pathological disorders in the structures of the brain in the form of infarction foci.

Laboratory tests that can diagnose leukoencephalopathy include:

• PCR diagnostics is a "polymerase chain reaction" method that allows detecting viral pathogens in brain cells at the DNA level. To carry out the analysis, blood is taken from the patient, the information content of the result is at least 95%. This allows you to refuse biopsy and open intervention in the brain structures as a result.
• Biopsy - the technique involves the collection of brain tissue to identify structural changes in cells, the degree of development of irreversible processes, as well as the rate of the disease. The danger of biopsy is the need for direct intervention in the brain tissue for the collection of material and the development of complications as a result.
• Lumbar puncture - performed for research cerebrospinal fluid, namely, the degree of increase in the level of protein in it.

Based on the results of a comprehensive examination, the neurologist makes a conclusion about the presence of the disease, as well as the form and speed of its progression.

Leukoencephalopathy treatment

The disease leukoencephalopathy cannot be completely cured. When diagnosing leukoencephalopathy, the doctor prescribes supportive treatment aimed at eliminating the causes of the disease, relieving symptoms, inhibiting the development of the pathological process, as well as maintaining the functions for which the affected areas of the brain are responsible.

The main medication, which are prescribed to patients with leukoencephalopathy, are:

1. Drugs that improve blood circulation in the brain structures - Pentoxifylline, Cavinton.
2. Nootropic drugs that have a stimulating effect on brain structures - Piracetam, Phenotropil, Nootropil.
3. Angioprotective drugs that help restore the tone of the vascular walls - Cinnarizin, Plavix, Curantil.
4. Vitamin complexes with a predominance of vitamins of groups E, A and B.
5. Adaptogens that help the body to withstand such negative factors as stress, viruses, overwork, climate change - Vitreous, Eleutherococcus, Ginseng Root, Aloe Extract.
6. Anticoagulants, allowing to normalize vascular patency by thinning the blood and preventing thrombosis - Heparin.
7. Antiretroviral drugs in cases where leukoencephalopathy is caused by the immunodeficiency virus (HIV) - Mirtazipine, Acyclovir, Ziprasidone.

In addition to drug treatment, the doctor prescribes a number of procedures and techniques to help restore impaired cerebral functions:

• physiotherapy;
• reflexology;
• remedial gymnastics;
• massage treatments;
• manual therapy;
• acupuncture;
• classes with specialized specialists - rehabilitation therapists, speech therapists, psychologists.

Despite the extensive course of drug therapy and the work with the patient of a large number of specialists, the prognosis for survival with diagnosed leukoencephalopathy is disappointing.

Regardless of the form and speed of the pathological process, leukoencephalopathy always ends in death, while life expectancy varies in the following time interval:

• within a month - in the acute course of the disease and the absence of appropriate treatment;
• up to 6 months - from the moment the first symptoms of damage to brain structures are detected in the absence of supportive treatment;
• from 1 to 1.5 years - in the case of taking antiretroviral drugs immediately after the first symptoms of the disease appear.

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Multifocal encephalopathy

In these cases, we are talking about subacute spongiform encephalopathies that characterize prion diseases. Such diseases include, for example, Creutzfeldt-Jakob disease. They are distinguished by a rare family burden, a rapidly progressive course, often ending fatally within 6 months. A longer course of the disease is possible in some cases with familial forms of the disease, for example, with Gerstmann - Streussler - Schneaker syndrome.

<Агрессивное> the course of the disease reflects the rapid spread of the pathological process to various anatomical formations and functional systems, which determines the presence of a variety of neurological and psychological symptoms... Some patients have neurological symptoms at the onset of the disease, such as cerebellar damage, cortical blindness, sensory and motor impairments, myoclonus, and epileptic seizures. Focal psychological syndromes, such as aphasia and ataxia, can also be the first signs of disease. With the predominant involvement of thalamic structures, clinical signs of progressive somnolence (fatal insomnia) may be observed. Despite the obvious heterogeneity of symptoms, early stages diseases, there are also characteristic disorders that are rarely detected in other encephalopathies. The level of wakefulness in the patient is extremely variable and its pronounced fluctuations are determined (the so-called dramatic fluctuations). For long periods of time, the patient can remain practically motionless with his eyes open and directed into space and catatonic freezing of the limbs. During these periods (phases), contact with the patient is impossible. But then the patients begin to move and speak, the catatonic phenomena disappear and the patient can remember and analyze the events that took place during the described phase. The latter indicates that even during the period when contact with the patient was impossible, he was not in an unconscious state. With the progression of the disease, the restoration of contact with the patient takes place less and less, until signs of akinetic mutism become predominant.

Severe neurological and mental disorders accompanied by pronounced changes on the EEG with a gross slowing down of bioelectric activity and periodic three-phase complexes. On CT, there may be nonspecific signs of cerebral atrophy. According to SPECT data, there is a nested decrease in the absorption of the corresponding biochemical marker in the cortex. Autopsy reveals that the size and weight of the brain is normal. However, histological examination reveals changes characteristic of spongy (spongy) encephalopathies with loss of neurons, gliosis in the cerebral cortex and cerebellum, as well as in the gray matter of the basal ganglia in combination with amyloid and prion plaques.

Causes and symptoms of leukoencephalopathy of the brain

Leukoencephalopathy of the brain is a disease in which the white matter of the subcortical structures is affected. Previously, leukoencephalopathy was diagnosed quite rarely and mainly in people with HIV infection. But due to the improvement of medical equipment and thanks to the many studies that have been carried out on this issue, now it has become much easier to make a correct diagnosis. Most often, such a disease is found in elderly people.

It has been proven that leukoencephalopathy is caused by the presence of human polyomavirus. According to some data, carriers of the infection are about 80% of the world's population. But, despite this fact, cases of polyomavirus activation do not happen so often. Usually, the activation of the virus occurs under certain conditions, one and the main of which is the decline in the body's natural protective functions, that is, immunity.

In addition to HIV infection and AIDS, the predisposing causes for the development of this disease also include:

• leukemia and other blood pathologies;
• hypertension;
• tuberculosis;
• oncology;
• sarcoidosis;
• systemic lupus;
• rheumatoid arthritis;
• taking immunosuppressive drugs that are prescribed after organ transplantation;
• use of monoclonal antibodies;
• lymphogranulomatosis.

The disease has several forms:

1. 1. Small focal leukoencephalopathy of vascular genesis. It is a disease in which a chronic pathological state of the cerebral vessels is observed, which subsequently leads to damage to the cells of the white matter of the cerebral hemispheres. The predisposing factors for the development of this form of pathology is hypertension. Most often, this form is diagnosed in men who are older than years. Also at risk are people with a genetic hereditary predisposition to pathology. A complication of small-focal leukoencephalopathy of vascular genesis is the development of senile dementia.
2. 2. Progressive multifocal encephalopathy. With this form of the disease, the virus is damaged by the central nervous system, which, in turn, results in the destruction of the white matter of the brain. In most cases, progressive multifocal encephalopathy occurs against the background of human immunodeficiency. This pathology is one of the most dangerous, since its consequence can be a sudden death.
3. 3. Periventricular form. It develops against a background of chronic lack of oxygen and ischemia. The result of such circumstances is the defeat of the subcortical structures of the brain, mainly its trunk, cerebellum and those parts that are responsible for motor activity. The periventricular form is characteristic of newborn babies and can lead to the development of cerebral palsy.

Symptoms of the disease will depend on the area in which the brain is damaged and the form of the pathology. On the initial stages the development of the disease, the patient may feel symptoms such as fatigue, constant weakness, decreased thinking speed and other signs that are often confused with the usual manifestations of fatigue. As for neuropsychiatric symptoms, it develops in each patient at its own rate, from several days to several weeks.

The most common signs that characterize the development of leukoencephalopathy include:

• problems with coordination (its violation);
• decreased motor function;
• problems with speech;
• decreased quality of vision;
• dullness of some feelings, including pain;
• clouding of consciousness;
• emotional mood swings;
• intellectual degradation;
• violation of the swallowing reflex;
• frequent headaches;
• epileptic seizures.

In medicine, cases have been recorded when the foci of the disease affected by the virus were localized only in the spinal cord. These circumstances led to the fact that the patient had only spinal symptoms, while cognitive impairments (associated with mental performance) were completely absent.

The most effective way to diagnose leukoencephalopathy is magnetic resonance imaging. MRI allows you to identify foci of the disease at the initial stage of its development. The polymerase chain reaction (PCR) is also quite informative, which is a highly accurate method of molecular genetic diagnostics. This survey method is approximately 95% accurate. Another advantage is that it can replace diagnostics such as brain biopsy. But sometimes the latter can be recommended as a separate study, which will definitely confirm whether irreversible processes have already begun and what degree of disease progression has.

If a diagnosis of leukoencephalopathy of the brain was made, regardless of the form of pathology, it should be understood that today there is no medicine that could completely cure a person from this disease.

All therapeutic activities will only be supportive. They are aimed at reducing the progression of the pathological process and normalizing the functions of subcortical structures.

The patient may be prescribed corticosteroids, which will prevent the development of the inflammatory syndrome associated with the restoration of immunity.

When the disease develops against the background of HIV infection, the patient is prescribed antiretroviral drugs.

All medicines and their dosage are prescribed to each patient individually. In addition, in the course of treatment, some medications can be canceled, while others are prescribed, and the dosage of the drug used is periodically adjusted.

Even with early diagnosis and properly selected treatment, patients diagnosed with leukoencephalopathy are doomed. From the moment the first symptoms appear until death, it can take from 1 month (with a progressive form) to 1.5-2 years.

• avoid unprotected sex;
• selectively treats sexual partners;
• stop using drugs and alcohol;
• include in the diet a sufficient amount of vitamins and minerals;
• avoid frequent stressful situations.

There are no clear preventive measures, which could give a 100% guarantee that a person will not get sick with leukoencephalopathy. But given the fact that the activation of the virus occurs with reduced immunity, you need to try in every possible way to keep it normal.

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How and how long do people diagnosed with leukoencephalopathy live?

Leukoencephalopathy is a disease characterized by damage to the white matter of the subcortical structures of the brain.

This pathology from the very beginning has been described as vascular dementia.

Most often, elderly people suffer from a similar ailment.

Among the varieties of the disease, one can distinguish:

1. Small focal leukoencephalopathy of vascular genesis. Being by its nature a chronic pathological process of the cerebral vessels, it leads to a gradual damage to the white matter of the cerebral hemispheres. The reason for the development of this pathology is a persistent increase in blood pressure and hypertension. The risk group for morbidity includes men over 55 years old, as well as people with a hereditary predisposition. Over time, this pathology can lead to the development of senile dementia.
2. Progressive multifocal encephalopathy. This pathology means a viral lesion of the central nervous system, as a result of which there is a persistent resolution of the white matter. The impetus for the development of the disease can give the body's immunodeficiency. This form of leukoencephalopathy is one of the most aggressive and can be fatal.
3. Periventricular form. It is a lesion of the subcortical structures of the brain, against the background of chronic oxygen starvation and ischemia. The favorite place of localization of the pathological process in vascular dementia is the brain stem, cerebellum and parts of the hemispheres responsible for motor function. Pathological plaques are located in the subcortical fibers and sometimes in deep layers of gray matter.

Causes of occurrence

Most often, the cause of the development of leukoencephalopathy can be a state of acute immunodeficiency or against the background of infection with human poliomavirus.

Risk factors for this disease include:

• HIV infection and AIDS;
• malignant blood diseases (leukemia);
• hypertonic disease;
• immunodeficiency states during therapy with immunosuppressants (after transplantation);
• malignant neoplasms of the lymphatic system (lymphogranulomatosis);
• tuberculosis;
• malignant neoplasms of organs and tissues of the whole organism;
• sarcaidosis.

The main symptoms

The main symptoms of the disease will correspond to the clinical picture of damage to certain brain structures.

Among the most characteristic symptoms this pathology can be distinguished:

• impaired coordination of movements;
• weakening of motor function (hemiparesis);
• impaired speech function (aphasia);
• the appearance of difficulties in pronunciation of words (dysarthria);
• decreased visual acuity;
• decreased sensitivity;
• a decrease in a person's intellectual abilities with an increase in dementia (dementia);
• clouding of consciousness;
• personal changes in the form of fluctuations in emotions;
• violation of the act of swallowing;
• a gradual increase in general weakness;
• not excluded epileptic seizures;
• headache permanent nature.

One of the very first signs of the disease is the appearance of weakness in one or all of the limbs at the same time.

Diagnostics

For the accuracy of the diagnosis, and the determination of the exact localization of the pathological process, the following series of diagnostic measures should be carried out:

• getting advice from a neurologist as well as an infectious disease specialist;
• electroencephalography;
• computed tomography of the brain;
• conducting magnetic resonance imaging of the brain;
• in order to detect a viral factor, a diagnostic brain biopsy is performed.

Magnetic resonance imaging allows you to successfully identify multiple foci of the disease in the white matter of the brain.

But computed tomography is somewhat inferior to MRI in terms of information content, and can display the foci of the disease only in the form of foci of a heart attack.

In the early stages of the disease, these may be single lesions or a single lesion.

Laboratory research

Laboratory diagnostic methods include the PCR method, which allows you to detect viral DNA in brain cells.

With the help of PCR diagnostics, it is possible to avoid direct interference with the brain tissue in the form of taking a biopsy.

A biopsy can be effective if it is necessary to accurately confirm the presence of irreversible processes, and determine the degree of their progression.

Another method is lumbar puncture, which is rarely used today due to its low information content.

The only indicator may be a slight increase in the level of protein in the patient's cerebrospinal fluid.

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Supportive therapy

It is impossible to completely recover from this pathology, therefore any therapeutic measures will be aimed at curbing the pathological process, and normalizing the functions of the subcortical structures of the brain.

Considering that vascular dementia in most cases is the result of viral damage to the structures of the brain, treatment should first of all be aimed at suppressing the viral focus.

The difficulty at this stage may be overcoming the blood-brain barrier, through which the necessary medicinal substances cannot penetrate.

In order for a drug to pass this barrier, it must be lipophilic in structure (fat-soluble).

Today, unfortunately, most antiviral drugs are water-soluble, and this creates difficulties in their use.

Over the years, medical professionals have tried various medications with varying degrees of effectiveness.

These medications include:

• acyclovir;
• peptide-T;
• dexamethasone;
• heparin;
• interferons;
• cidofovir;
• topotecan.

The drug cidofovir, which is administered intravenously, can improve brain activity.

If the disease occurs against the background HIV infectionshould be treated with antiretroviral drugs (ziprasidone, mirtazipime, olanzapime).

The forecast is disappointing

Unfortunately, it is impossible to recover from leukoencephalopathy, in the absence of the above treatment, patients live no more than six months from the moment the first signs of CNS damage appear.

Antiretroviral therapy can increase life expectancy from one to one and a half years after the first signs of damage to the brain structures appear.

Cases of acute disease have been reported. With this course, the death occurred within 1 month from the onset of the disease.

Instead of output

Considering that leukoencephalopathy arises against the background of total immunodeficiency, any measures to prevent it should be aimed at maintaining the body's defenses and preventing HIV infection.

These measures include:

• selectivity in choosing a sexual partner.
• refusal to use narcotic drugs, and from their injecting form in particular.
• use of contraception during sexual intercourse.

The severity of the pathological process depends on the state of the body's defenses. The more the general immunity is reduced, the more acute the disease progresses.

And finally, we can say that at the moment, medical specialists are actively working to create effective methods of treating various forms of pathology.

But as practice shows, the best cure for this ailment is its prevention. Leukoencephalopathy of the brain refers to diseases that resemble a triggered mechanism that cannot be stopped.

This section was created to take care of those who need a qualified specialist, without breaking the usual rhythm of their own life.

Good day! The article mentions people of adults and old age, but how does such a disease develop in a teenager?

Leukoencephalopathy is a terrible, rapid disease. It is scary to watch a loved one die before our very eyes, and no one is able to help. My father's illness began very acutely (persistent hypertension preceded + work in the heat + lover of saunas and baths + drank coffee in large volumes). All the symptoms described above manifested themselves on the rise. He died 9 months after the onset of the disease. Doctors practically did not leave the apartment (therapists, neurologists, ambulance), ran to all relatives, helped my mother (psychosis, aggression, could not swallow or the pressure starts to jump, then the kidneys ..., for the last 2 months he screamed very strongly 24 hours a day, kicked , hands wherever possible). We were in the hospital three times. He died 9 months after the onset of the disease. As predicted for this disease. Nothing remained of a healthy man full of life after 9 months ...

Currently, there are no drugs that can stop the development of the disease.

Description

Leukoencephalopathy is a disease characterized by persistent destruction of the white matter in the brain. The disease develops quickly and is almost always fatal.

The pathology was first described by Ludwig Binswanger in 1964, therefore it is sometimes called Binswanger's disease.

The reasons

It is customary to distinguish 3 main reasons leading to leukoencephalopathy. This is hypoxia, stable high pressure and viruses. The following diseases and conditions provoke its occurrence:

• endocrine disorders;
• hypertension;
• atherosclerosis;
• malignant tumors;
• tuberculosis;
• HIV and AIDS;
• spinal pathology;
• genetic factor;
• birth injury;
• taking drugs that reduce the body's immune response.

The provoking effect of harmful factors leads to demyelination of the bundles of nerve fibers. The white matter decreases in volume, softens, changes its structure. Hemorrhages, lesions, cysts appear in it.

Demyelination is often caused by polyomaviruses. In an inactive state, they are constantly present in a person's life, remaining in the kidneys, bone marrow, and spleen. Weakening of the immune system leads to the activation of viruses. Leukocytes carry them to the central nervous system, where they find a favorable environment in the brain, settle in it and destroy it.

Usually only white matter undergoes irreversible changes. However, there is evidence that, probably, the periventricular type of leukoencephalopathy also leads to damage to the gray matter.

Classification

Determination of the main cause of the pathology and the nature of its course allows us to distinguish several types of leukoencephalopathy.

Dyscirculatory

The main reason for the appearance and development of small-focal leukoencephalopathy of vascular genesis is damage to the cerebral vessels caused by hypertension, trauma, the appearance of atherosclerotic plaques, endocrine diseases, and diseases of the spine. Blood circulation is impaired due to blood thickening and vascular blockage. The deteriorating factor is alcoholism and obesity. It is believed that the disease develops in the presence of aggravating hereditary factors.

This pathology is also called progressive vascular leukoencephalopathy. First, small foci of vascular lesions appear, then they increase in size, causing a deterioration in the patient's condition. Over time, signs of pathology are growing, which are noticeable to others. Memory deteriorates, intelligence decreases, psychoemotional disorders occur.

The patient complains of nausea, headache, constant fatigue. Small focal vascular encephalopathy is characterized by pressure surges. A person cannot swallow, chews food with difficulty. Tremor appears, which is characteristic of Parkinson's disease. The ability to control the processes of urination and defecation is lost.

Focal encephalopathy of vascular origin is recorded mainly in men after 55 years. Previously, this violation was included in the ICD list, but later it was excluded.

Progressive multifocal

The main feature of this type of violation is the appearance of a large number of lesions. Inflammation is caused by human polyomavirus 2 (JC polyomavirus). It is found in 80% of the world's inhabitants. In a latent state, it lives in the body for several years, but when immunity is weakened, it is activated and, getting into the central nervous system, causes inflammation.

Disease-provoking factors are AIDS, HIV infection, long-term use of immunosuppressants and drugs intended for the treatment of cancer. Progressive multifocal encephalopathy is diagnosed in half of patients with AIDS and 5% of people with HIV infection.

The defeat is often asymmetrical. Signs of PML are paralysis, paresis, muscle stiffness, and tremors that resemble Parkinson's disease. The face becomes a mask. Loss of vision is possible. Severe cognitive impairment, decreased attention are manifested.

Multifocal leukoencephalopathy is not curable. To improve the patient's condition, drugs that suppress immunity are removed. If the disease is caused by an organ transplant, it must be removed.

Periventricular

Leukopathy of the brain in a child is caused by hypoxia that occurs during childbirth. Instrumental methods diagnostics allow you to see areas of tissue death, mainly near the cerebral ventricles. Periventricular fibers are responsible for locomotor activity, and their damage leads to childhood cerebral palsy... The lesions appear symmetrically, in especially severe cases they are found in all central areas of the brain. The defeat is characterized by the passage of 3 stages:

• occurrence;
• development leading to structural change;
• formation of a cyst or scar.

Periventricular leukoencephalopathy is characterized by 3 degrees of the disease. A mild degree is characterized by a slight severity of symptoms. They usually go away within a week after birth. For an average degree, an increase in intracranial pressure is characteristic, convulsions occur. In severe cases, the child is in a coma.

Symptoms do not appear immediately, some of them can only be noticed 6 months after the baby is born. Most often, paresis and paralysis draw attention to themselves. Strabismus, lethargy, hyperactivity are observed.

Treatment includes massage, physiotherapy, special exercises.

Disappearing white matter leukoencephalopathy

The main cause of this disease is gene mutations that suppress protein synthesis. Most often appears in children, mainly between the ages of two to six years. The provoking factors include severe mental stress caused by trauma or severe illness.

Organic lesions of the brain have a common name - encephalopathy. The abnormal process is accompanied by degenerative changes in the brain tissue.

One of the types of pathology is called "progressive multifocal leukoencephalopathy" and can result in the death of the patient.

In order to understand what leukoencephalopathy is, one should consider the causes of its occurrence, classification and main methods of treatment.

The disease, as a result of which, under the influence of various factors, the white matter of the brain is affected is called leukoencephalopathy of the brain. Focal destruction of brain tissue occurs due to improper blood circulation in the vessels of the head, human infection with a virus. A hereditary predisposition contributes to the development of the disease.

The consequences of the disease are severe: dementia develops, vision is significantly reduced, seizures appear. The fatal outcome is recorded in most cases.

Several types of leukoencephalopathy have been identified depending on the location of the brain damage.

Encephalopathy

This disease develops due to damage to small arteries and arterioles in the brain tissue. Incorrect blood flow in the vessels of the brain leads to the destruction of the white matter of the brain tissue.

Dystrophic changes can occur due to various reasons: circulatory disorders, vascular pathology, traumatic brain injury. The main factor leading to the destruction of brain tissue is persistent hypertension, the presence of atherosclerotic deposits on the vascular walls.

Another name for the pathology is progressive vascular leukoencephalopathy. Over time, small lesions of the white matter of the brain grow, and therefore the patient's condition worsens. The following symptoms are observed:

• impairment of memory, mental abilities;
• the development of dementia;
• the appearance of signs of parkinson's syndrome;
• disorders of the vestibular apparatus: dizziness, nausea;
• difficulty eating: slow chewing, trouble swallowing;
• drops in blood pressure.

With the development of the process, the patient becomes unable to control the processes of defecation and urination.

Small focal leukoencephalopathy of vascular genesis is poorly expressed at first. The development of destruction of brain tissue is accompanied by mental disorders, chronic overwork, memory impairment, dizziness.

Progressive multifocal leukoencephalopathy

This type of pathology is characterized by the appearance of multiple foci, where brain damage is observed. Progressive multifocal leukoencephalopathy (PML for short) is caused by human polyomavirus 2, which usually occurs in childhood.

Despite the fact that this virus can be found in 80% of the population, multifocal brain damage is a rather rare disease.

Progressive multifocal leukoencephalopathy develops against the background of an almost complete loss of immunity, therefore it is most often affected by AIDS patients, people who have undergone immunosuppressive therapy, suffering from neoplasms of the lymphatic system.

Patients with a history of atherosclerosis are often treated with drugs that cause immunodeficiency.

Therefore, the risk of PML in patients with atherosclerosis is very high.

Progressive multifocal leukoencephalopathy begins acutely, progresses rapidly, its signs are:

• speech and vision disorders;
• significant hand motility disorder;
• severe headaches;
• paresis of the limbs on the right or left side of the body;
• sensitivity disorders.

As the disease progresses, memory loss and mental impairment occur.

No specific drug treatment for multifocal lesions of the brain tissue has been found. In cases where the lesion is caused by immunosuppressive therapy, it is stopped.

If the disease is the result of organ transplantation, it can be removed. All methods of treatment are aimed at restoring the protective functions of the body.

Unfortunately, if the immune system cannot be improved, the prognosis is poor. To the question of how long they live with this type of pathology, one can answer that it is very little. Death can occur within 2 years of diagnosis if treatment fails.

Periventricular leukomalacia

In this form of encephalopathy, brain damage occurs as a result of the appearance of foci of necrosis in the subcortical structures, most often around the ventricles. It is the result of hypoxia, and the diagnosis of periventricular leukoencephalopathy is often made in newborns who have experienced oxygen deprivation due to difficult labor.

The periventricular zones of the white matter are responsible for movement, therefore, the necrosis of their individual areas leads to cerebral palsy. Periventricular leukomalacia was studied in detail by the Soviet scientist V.V. Vlasyuk. He not only investigated the pathogenesis, etiology, stages of brain damage.

VV Vlasyuk came to the conclusion about the chronic form of the disease, over time, new ones join the affected areas.

Small focal necrosis (infarctions) are present in the white matter and are most often located symmetrically in the cerebral hemispheres. In severe cases, lesions can spread to the central regions of the brain.

Necrosis goes through several stages:

• development;
• gradual change in structure;
• the formation of a scar or cyst.

Several degrees of manifestation of leukomalacia have been identified.

Such as the:

• easy. Symptoms are observed up to a week after birth, are mild;
• average. Signs persist for 10 days, convulsions may occur, there is increased intracranial pressure;
• heavy. Very long time, the child falls into a coma.

Symptoms of periventricular leukomalacia are different:

• paresis;
• paralysis;
• the appearance of strabismus;
• developmental delay;
• hyperactivity or, conversely, depression of the nervous system;
• decreased muscle tone.

Sometimes neurological disorders in the first months of a child's life are not expressed and appear only after six months. Over time, symptoms of a disturbance in the activity of the nervous system appear, and convulsive syndrome may occur.

Treatment of periventricular leukoencephalopathy is carried out with the use of medications. An important role is played by physical procedures, massage, physiotherapy... Such patients require increased attention, systematic walks in the fresh air, games, communication with peers are required.

Disappearing white matter leukoencephalopathy

This type of damage is caused by gene mutations in the chromosome that suppress protein synthesis. Everyone is susceptible to the disease age categories, but the classic form of the disease occurs in children from 2-6 years old.

The impetus for its beginning is the experienced stress: severe infection, trauma, overheating, etc. Subsequently, the child is found to have severe hypotension, muscle weakening, he may fall into a coma, even die.

In adulthood, pathology can manifest itself after 16 years of the following symptoms:

• psychosis;
• dementia;
• depression.

A common symptom of this type of encephalopathy in adult women is ovarian dysfunction. In the blood, an increased content of gonadotropins and a reduced content of estrogen and progesterone are recorded.

Those suffering from this type of pathology have difficulties in learning, they have neurological disorders, muscle weakness and fine motor hand disorders.

There is no drug treatment that would directly correct the gene disorders. To prevent the onset of seizures, it is recommended to avoid head injuries, it is forbidden to overheat, if a temperature occurs, it is imperative to use antipyretic drugs.

Diagnostic methods

Before a diagnosis is made, a complete examination should be completed. This requires a specialist to examine the brain using special equipment. The following diagnostic methods are used:

• magnetic resonance imaging;
• cT scan;
• electroencephalography;
• dopplerography.

It is possible to conduct research using invasive methods of studying brain tissue. These include biopsy and lumbar puncture. The collection of material can lead to complications, since it is associated with direct penetration into the brain tissue. A lumbar puncture is performed when cerebrospinal fluid is required.

If you suspect a virus infection or the presence of gene mutations, PCR diagnostics (polymerase chain reaction method) can be prescribed. To do this, the laboratory examines the patient's DNA isolated from his blood. In this case, the accuracy of the diagnosis is quite high and amounts to about 90%.

Therapy

Treatment of encephalopathy associated with lesions of the white matter of the brain is aimed at eliminating the causes that caused it. Therapy includes taking medications and the use of non-drug methods.

For the treatment of vascular diseases that caused encephalopathy, funds are used to restore their normal functioning. They are designed to normalize blood flow in the brain tissues, to eliminate the permeability of the vascular walls. If necessary, blood thinners are prescribed.

The administration of nootropic drugs that stimulate the activity of the brain is shown. It is recommended to take vitamins, immunostimulating medicines. Non-drug methods include:

• remedial gymnastics;
• massage;
• physiotherapy;
• acupuncture.

It is possible to work with speech therapists, psychologists, chiropractors. It is possible to increase the patient's life expectancy, it depends on the intensity of therapy, the general health of the patient. But it is impossible to completely cure the pathology.

Conclusion

Telling why cerebral leukoencephalopathy occurs, what it is and what are its consequences, first of all it is necessary to mention the complexity of its diagnosis and treatment. The destruction of the white matter of the brain leads to serious consequences, including death.

With genetic pathologies that cause the destruction of brain tissue, regular monitoring of the patient's health is necessary. There are no specific drugs for correcting defective genes.

In most cases, the disease ends in death. You can only slow down the progression of the disease by increasing the body's immunity and eliminating external circumstances that aggravate brain damage.

At the heart of progressive multifocal leukoencephalopathy (PML), which is characterized by massive demyelination of the white matter, is the activation of the polyoma virus (JC virus) and viral replication in the brain. It is believed that the JC virus reaches the central nervous system via leukocytes and mainly affects the oligodendrocytes that form the myelin sheath. The destruction of the myelin sheaths is macroscopically manifested by multifocal demyelination. The white matter of the cerebral hemispheres is most affected, but the cerebellum and gray matter are also affected.

The JC virus (John Cunningham virus, John Cunningham virus) is a DNA-containing double-stranded circular virus of the genus Polyomavirus of the Polyomaviridae family (polyomaviruses). The JC virus gets its name from the initials of a patient in whom it was first detected in 1971. The virus capsid contains three viral proteins: VP1, VP2 and VP3. The predominant protein is VP1, which forms virus-like particles that induce the body's immune response. The genome of the virus is divided into early, late, and non-coding control regions (NCCRs). In accordance with the differences in the NCCR, two types of JC viruses are distinguished - the archetype (classic form) and prototype (invasive form). One of the receptors for the JC virus is a T-linked glycoprotein, which is present on the surface of most somatic cells. In addition, the JC virus is able to bind to serotonin receptors of the SNT type present on various cell types, including renal epithelium, B-lymphocytes, platelets, glial cells, and neurons. Most of these cells also detect viral DNA.

The JC virus is ubiquitous. Airborne and fecal-oral routes of infection are suggested. Primary infection occurs in early period life (in childhood) and is asymptomatic. From the tonsils and peripheral blood lymphocytes, the JC virus enters the epithelial cells of the kidneys, bone marrow and spleen, where it is in a state of persistence (asymptomatic carrier). The next stage of infection is the reactivation of the virus and its spread in the body with a presumably hematogenous route to the central nervous system. About 75 - 80% of adults are serologically positive for the virus, indicating a past infection [during childhood] (Love S., 2006).

The disease (PML) develops in persons with reduced immunity (in immuno-compromised persons): with neoplastic diseases (mainly chronic lymphocytic leukemia, Hodgkin's disease, lymphosarcoma, myeloproliferative diseases), tuberculosis, sarcoidosis, with immunodeficiency; can be combined with AIDS, detected during drug immunosuppression with cytostatics, immunoclonal antibodies (PML may develop as a dangerous complication and as part of systemic inflammatory rheumatic disease against the background of immunosuppressive therapy). (however, in some cases, the development of PML occurs in the absence of severe immunodeficiency). PML is thought to be essentially an opportunistic viral infection. Since monoclonal drugs are used to treat MS, PML can develop as a complication of this therapy. The table shows the clinical symptoms / signs (differential diagnosis) of exacerbation of MS and PML (according to L. Kappos et al. Lancet 2007; 6 (5): 431–441):

Solving the question of prescribing to the patient immunosuppressive drugs should be preceded by a study of the concentration of antibodies to the JC virus (Love S., 2006).

The clinical picture of PML is characterized by a galloping increase in neurological deficits in combination with personality changes and intellectual disabilities. Despite the variety of PML symptoms due to different localization of demyelination foci, a number of common features of the clinical picture can be distinguished. In addition to cognitive impairments (ranging from mild impairments to concentration to dementia), focal neurological symptoms are very common in PML. Mono- and hemiparesis, as well as speech and visual impairments, are more common; PML can lead to blindness. The defeat of the central nervous system is sometimes manifested at first by separate violations of coordination of movements, but at the same time it can quickly lead to severe disability. Some patients develop epileptic seizures (approximately 20% of patients). Numbness, fever, and headache are rare. In the final stages of the disease, dementia and coma are observed. The course is variable, death occurs within 3-6 to 10-12 months after the onset and even faster in patients with AIDS, if antiretroviral therapy is not carried out.

If PML is suspected, it is necessary to confirm the diagnosis as soon as possible beam methods diagnostics. It should be borne in mind that computed tomography (CT) of the head poorly detects foci of reduced density. Magnetic resonance imaging (MRI) is much more sensitive in terms of the number and size of lesions than CT. PML can develop anywhere in the brain; there is no typical localization. The lesions are often found in the parietal and occipital regions or periventricularly, but the cerebellum may also suffer.

The MRI picture is characterized by widespread demyelinating foci localized in the cerebral hemispheres, but sometimes in the brainstem and cerebellum, and rarely in the spinal cord. The lesions vary greatly in size: from microscopic foci of demyelination to massive multifocal zones of destruction of myelin and axonal cylinders, involving most hemisphere of the brain or (as mentioned above) the cerebellum.

However, the diagnosis based on the clinical picture and MRI data is not conclusive. CSF research is important. As a rule, if there are no concomitant infections, then there are no signs of nonspecific inflammation in the CSF, and the total protein level is slightly increased. Cytosis is rare; if it reaches 100 μL-1, the diagnosis of PML is unlikely. All patients should have CSF tested for JC virus. The sensitivity of new PCR-based studies is about 80%, the specificity is over 90%. However, a negative PCR result does not rule out PML. The amount of virus in the blood can fluctuate significantly and does not correlate with the size of the lesions. To date, laboratory diagnosis of the JC virus is not possible in all regions of Russia due to the lack of test systems, and therefore the diagnosis is often made during postmortem examination (histological examination of a brain biopsy is considered the standard for PML diagnostics).

Pathomorphological studies in the white matter of the brain reveal multiple foci of demyelination. On the border between the white matter of the brain and the cortex, small rounded foci of demyelination with good preservation of axons are revealed. Foamy macrophages are often predominant, and lymphocytes are rare. With the progression of the disease in the white matter of the brain, large confluent foci are observed, some with the formation of cavities in the center. Glial cells show significant abnormalities. At the periphery of the foci, the nuclei of oligodendrocytes are significantly enlarged and contain abnormal homogeneous amphiphilic inclusions; many of these cells are destroyed due to demyelination. In demyelinated foci, large astrocytes with pleomorphic, hyperchromic nuclei of irregular shape with mitotic figures can also be detected, which is more often characteristic of malignant glial tumors.

In accordance with the recommendations of the experts of the American Academy of Neurology (see table), the diagnosis of a specific PML is eligible in cases where there are typical clinical and neuroimaging data and JC-viral DNA is determined in the CSF or, in addition to clinical and MRI signs, typical morphological changes in the biopsy of brain tissue. The diagnosis of PML is interpreted as probable in the presence of only clinical and neuroimaging changes, or only the classical pathomorphological triad, or only the virus in oligodendrocytes by electron microscopy or immunohistochemical examination.

There is no specific treatment for PML. With the development of this pathology, it is advisable to minimize the dose of glucocorticoids and cytotoxic drugs... Some authors propose a combination of plasmapheresis (5 sessions every other day) followed by the administration of the aminoquinoline drug meflocine and mirtazipine (an antidepressant, serotonin reuptake inhibitor that slows down the spread of the JC virus by blocking specific receptors).

Literature:

1 ... article "Demyelinating diseases" by Yu.I. Stadnyuk, D.S. Lezina, O. V. Vorobiev (journal "Treatment of diseases of the nervous system" No. 2 (10), 2012, p. 14) [read];

2 . article "JC Virus Brain Infection (Review)" A.K. Bag, J.K. Curé, P.R. Chapman, G.H. Roberson, R. Shah (Department of Radiology, Department of Neuroradiology, University of Alabama at Birmingham Medical Center, Birmingham, Alabama) [read];

3 ... article "Progressive multifocal leukoencephalopathy and other neurological manifestations of JC virus reactivation" TE Schmidt, Department of Nervous Diseases and Neurosurgery, First Moscow State Medical University. THEM. Sechenov (Neurological journal, No. 4, 2014) [read];

4 ... article "Progressive multifocal leukoencephalopathy: rheumatological aspects (lecture)" BS Belov, FSBSI Scientific Research Institute of Rheumatology named after V.A. Nasonova, Moscow (magazine "Modern Rheumatology" No. 3, 2015) [read];

5 ... article "John Cunningham (JC) virus-associated brain damage in HIV infection" N.V. Mozgaleva, Yu.G. Parkhomenko, O. Yu. Silveistrova, T.S. Skachkova, O. Yu. Shipulina, Yu. Vengerov (journal "Clinical and Experimental Morphology" No. 1, 2015) [read];

6 ... article "A case of the development of progressive multifocal leukoencephalopathy (PML) in a patient with combined pathology of HIV and tuberculosis" L.V. Proskura, Pavlodar regional center for the prevention and control of AIDS, Pavlodar (magazine "Science and Health", No. 1, 2013) [read];

7 ... article "Progressive multifocal leukoencephalopathy (literature review)" M.N. Zakharova, Scientific Center of Neurology, Russian Academy of Medical Sciences, Moscow (Journal of Neurology and Psychiatry, 9, 2012; Issue 2) [read];

8 ... article "MRI diagnostics of progressive multifocal leukoencephalopathy" S.N. Kulikova, V.V. Bryukhov, A.V. Peresedova, M.V. Krotenkova, I.A. Zavalishin; Scientific Center of Neurology, Russian Academy of Medical Sciences, Moscow (Journal of Neurology and Psychiatry, No. 10, 2013) [read];

9 ... article "Progressive multifocal leukoencephalopathy as a complication of treatment with drugs that change the course of multiple sclerosis" M.N. Zakharova, E.V. Lysogorskaya, M.V. Ivanova, I.A. Kochergin, Yu.E. Korzhova; Federal State Budgetary Scientific Institution "Scientific Center of Neurology", Moscow (journal "Annals of Clinical and Experimental Neurology" No. 4, 2018 ) [to read ].

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