Discirculatory encephalopathy: causes, symptoms, diagnosis

Classification of dyscirculatory encephalopathy ICD 10

The "I60-69" group collected cerebrovascular diseases. The International Classification of Diseases, Tenth Revision (ICD10) does not use the term “dyscirculatory encephalopathy.” Codes have been developed to describe various syndromes that occur with damage to blood vessels of various etiologies. Asymptomatic forms are designated "I65-66".

ICD codes for 10 types of dyscirculatory disorders of the brain:

• Chronic cerebral ischemia (I67.8) – develops over a long period of time, accompanied by progressive changes in the blood circulation of the brain;
• Hypertensive encephalopathy (I67.4) – pathology of intracerebral microcirculation in patients with hypertension;
• Vascular leukoencephalopathy (Binswanger syndrome) - pathological changes in the white matter against the background of amyloid angiopathy, arterial hypotension.

Brain MRI, electroencephalography, and Doppler ultrasound help determine the type of blood supply disorder.

Until recently, progressive multifocal leukoencephalopathy (PML) was considered a rare, rapidly progressive demyelinating disease of the central nervous system caused by activation of a ring virus of the genus Polyomavirus

family
Polyomaviridae
(polyomaviruses) - John Cunningham virus (John Cunninghamvirus - JC virus), named after the patient in whom it was first discovered in 1971 and the carriers of which are about 80% of the world's population [1–2]. Modern data indicate that PML develops in persons with reduced immunity (immunocompromised persons): with neoplastic diseases (leukemia, Hodgkin's disease, lymphosarcoma, myeloproliferative diseases), tuberculosis, sarcoidosis, with immunodeficiency, AIDS, drug immunosuppression with cytostatics during organ transplantation or neoplasms various localizations [3]. PML often occurs during the treatment of demyelinating diseases with monoclonal antibodies, and the development of PML as a dangerous complication of a systemic inflammatory rheumatic disease against the background of immunosuppressive therapy is also possible [4]. At the same time, in some cases, the development of PML occurs in the absence of severe immunodeficiency. PML is essentially an opportunistic viral infection. For neurologists, the relevance of studying PML is associated with the active use of immunosuppressive therapy and the widespread prevalence of HIV infection. After the introduction of highly active antiretroviral therapy (HAART), the incidence of PML increased and amounted to 1.3 per 1000 HIV-infected persons per year [5].

In clinical practice, early diagnosis of PML is difficult due to the lack of severe symptoms, since infection with the JC virus occurs in childhood and the virus remains in the body for life [6]. The exact location of its persistence has not been fully elucidated—presumably, it is the kidneys and bone marrow. When the immune system is weakened, the virus is transported by leukocytes to the central nervous system, where it begins its replication in the white matter of the brain, or more precisely, in oligodendrocytes. Destruction of the myelin sheaths is macroscopically manifested as multifocal demyelination. The white matter of the cerebral hemispheres is most often affected, but the cerebellum and gray matter may be affected.

Clinical manifestations of PML

Clinical manifestations of PML do not have a specific pattern. The onset of neurological and psychopathological symptoms is subacute (several days) or gradual (several weeks). The first to develop is a rapidly progressing psychotic syndrome. Later, mono- or hemiparesis, speech impairment and loss of visual fields (hemianopsia) appear. Headache, dizziness, ataxia and epileptic seizures are much less common. Characterized by the absence of general infectious and meningeal symptoms. In the early stages of the disease, progressive cognitive impairment occurs, but unlike dementia in HIV infection, it is accompanied by focal neurological symptoms [7]. Patients sometimes experience an atypical variant of the disease (spinal), which occurs without mental impairment [8]. The course is variable, death occurs within 6-12 months [9]. In the terminal stage of the disease, severe dementia, coma and death of the patient develop. The greatest diagnostic difficulties arise in AIDS, when the clinical picture and MRI signs are similar to PML and HIV-associated encephalopathy [10]. In these cases, only detection of JC virus in cerebrospinal fluid (CSF) and brain biopsy allows diagnosis to be made.

Diagnosis of PML

The diagnosis of PML is based on the criteria recommended by the American Academy of Neurology in 2013 [11] (Table 1).

Table 1. Clinical, laboratory and MRI criteria for diagnosing PML

Sometimes, to accurately confirm PML, a biopsy of brain tissue is performed to reveal the classic histopathological triad: an increase in oligodendrocyte nuclei, changes in the size and shape of astrocytes, which become large, bizarre in shape with hyperchromatic nuclei.

Thus, the doctor’s algorithm for suspected PML consists of several stages (Fig. 1)

Rice. 1. Algorithm for a doctor’s action in case of suspected PML. JCV - JC virus. [12].

Differential diagnosis of PML

The differential diagnosis of PML must first be made with infectious encephalopathies ( H erpes simplex

, CMV virus,
Varicella zoster
,
C r y ptocoсcus
,
A spergillus
), with lymphoma, with subacute sclerosing panencephalitis. Unlike the above infections, with PML there are no general infectious and meningeal symptoms.

Drug-induced PML

Taking into account the increasing number of risks under which optimal conditions are created for the proliferation of the JC virus under the influence of drug immunocorrection, the term “drug-induced PML” was proposed [13]. In patients with multiple sclerosis undergoing natalizumab therapy, it is necessary to exclude exacerbation of the underlying disease (with MRI control, the lesions will intensively accumulate the contrast agent) [14, 15]. Attention should also be paid to patients receiving rituximab. The risk of developing PML in patients receiving rituximab is 1:8000 [16]. Rituximab is a monoclonal antibody drug against CD20 precursors of B lymphocytes and mature B lymphocytes. Approved for use in cellular non-Hodgkin's lymphoma and resistant rheumatoid arthritis. Approved by the FDA in 2006 for the treatment of systemic lupus erythematosus. Currently, to monitor the effect of rituximab and identify the side effects of the drug, a special project has been created (Research on Advers Drag Events and Report - RADAR) with the participation of virologists, oncologists, neurologists and other specialists [17]. In early 2014, the Federal Service for Surveillance in Healthcare of the Russian Federation published a letter reporting 2 cases of PML in patients with systemic lupus erythematosus who received belimumab in the post-registration period.

In 2015, L. Calabrese et al. [18] proposed a conditional risk gradation developed for drug-induced PML. Class 1 included natalizumab and efalizumab (discontinued) as drugs with a high risk of developing PML (1/10,000-1/100). Class 2 (low risk) includes rituximab, belimumab, azathioprine, mycophenolate mofetil, methotrexate. Class 3 (very low risk) included tumor necrosis factor-α (TNF-α) inhibitors, abatacept, tocilizumab, anakinra, ustekinumab, and tofacitinib. The use of these drugs requires special careful monitoring of patients and the need to inform them about the risk of developing PML.

PML therapy

Specific therapy for PML has not yet been developed. The following drugs are used for treatment: antivirals, cytostatics, serotonin receptor antagonists, HAART therapy in HIV-infected patients [19]. With the development of this pathology, it is advisable to reduce the dose of glucocorticoids and cytostatic drugs as much as possible. A positive effect has been described from a combination of plasmapheresis (5 sessions every other day) followed by the aminoquinoline drug meflocin and mirtazapine (an antidepressant, a serotonin reuptake inhibitor, which slows the spread of the JC virus by blocking specific receptors) [19]. Symptomatic therapy (decongestant, neuroprotective, antioxidant) is very often carried out.

Thus, PML is a disease that can be encountered in the practice of a neurologist. It can simulate acute cerebrovascular accident (ACVA), chronic cerebral ischemia with severe cognitive impairment. The clinician should constantly remember that the development of this pathology is possible in patients with demyelinating diseases, HIV, and neuroinfections.

We present data from our own observations.

Observation 1.

Patient A.

, 35 years. Entered the City Clinical Hospital No. 15 named after. O.M. Filatov in the direction of emergency medical services (EMS) with a diagnosis of stroke. Upon admission, he complained of spatial disorientation, emotional lability, and decreased memory for current events.

Life history: married, has two healthy children. He has been smoking since he was 17 years old. Two years ago, after a business trip to Thailand, I lost weight sharply, which I attributed to the transition to a “healthy lifestyle”: a balanced diet, intense training. I began to get colds more often. I didn’t go to the doctors.

History of the disease: according to the patient and his wife, about 6 months ago he suffered from right-sided bronchopneumonia (diagnosed during a CT scan of the lungs).

The deterioration in health, according to the patient’s wife, began on January 12, 2017, when dizziness and decreased memory for current events occurred. According to the patient's wife, blood pressure (BP) ranged from 90/60 to 140/90 mm Hg. Hospitalized in the intensive care unit (ICU) for patients with stroke on January 19, 2017. After stabilization of his condition, on January 20, 2017 he was transferred for further treatment and examination to the neurological department.

The condition upon admission is of moderate severity, the skin and visible mucous membranes are of normal color and moisture. There is hard breathing in the lungs, no wheezing. Respiratory rate (RR) 16 per minute. Heart sounds are muffled, rhythmic, heart rate (HR) 76 beats/min, blood pressure 115/80 mm Hg. The abdomen is soft, painless on palpation in all parts. Self-urination. Urine is light and transparent.

Neurological status: conscious, contactable, oriented. Has difficulty finding words when answering simple questions. There are no meningeal signs. Palpebral fissures S

=
D
.
Pupils S
=
D.
_
Photoreactions and corneal reflexes are preserved. Full movement of the eyeballs. There is no nystagmus. The facial muscles are symmetrical. Swallowing is not impaired. Tongue in the midline. There are no paresis. Muscle tone D
=
S
, not changed.
Tendon reflexes D
=
S
, low. Babinski reflex on both sides. Coordinator tests are performed satisfactorily. There are no sensory disorders, the functions of the pelvic organs are controlled.

Complete blood count: lymphopenia up to 1.9-3.2·109.

Antibodies to hepatitis C (aHCV) were detected. Immunoblot (IB) + dated 01/26/17 No. 136240.

The electrocardiogram (ECG) shows normal sinus rhythm, heart rate 57 beats/min. Incomplete blockade of the right bundle branch. Ultrasound examination (ultrasound) of the abdominal organs and kidneys showed signs of splenomegaly and diffuse nonspecific changes in the liver. Electroencephalogram (EEG) without any features.

Multislice CT (MSCT) of the brain dated January 19, 2017: the picture may correspond to an ischemic zone in the right parieto-occipital region. MSCT of the brain dated January 20, 2017: The CT picture (compared to the MRI dated January 18, 2017, presented by the patient) more likely corresponds to leukoencephalopathy after a neuroinfection. Less likely is PML. MRI of the brain dated January 21, 2017: a picture of progressive multifocal leukoencephalopathy of the brain. Signs of intracranial hypertension. In Fig. 2

Rice. 2. MRI of the brain of patient A., 35 years old. a, b — Flair mode; c, d — T2 mode.

Rice. 2. MRI of the brain of patient A., 35 years old. (end) d, f - DVI mode. Tomograms are sequentially arranged in Flair, T2-weighted image and DVI modes.

Based on the clinical picture, positive IB and characteristic changes on MRI of the brain, the patient underwent a PCR test of the CSF for the JC virus to clarify the diagnosis, which turned out to be positive.

The patient was diagnosed with focal brain lesion (PML). IB (+) dated January 26, 2017 No. 136240.

Symptomatic treatment was carried out: Mexidol (ethylmethylhydroxypyridine succinate) 500 mg intravenously (iv); diacarb (acetazolamide) 500 mg/day; Cortexin (polypeptides of the cerebral cortex of cattle) 10 mg intramuscularly (i.m.); recognan (citicoline) 1000 mg i.v. Against the background of the therapy, the condition is showing positive dynamics. A.D.’s indicators have stabilized. There are no complaints of memory impairment. The patient is recommended to continue treatment in a specialized treatment and prevention facility. The described clinical case deserves special attention due to the fact that the socially prosperous patient did not know or deliberately concealed the cause of his health problems; upon entering the clinic, he received treatment for a vascular disease and the consequences of a neuroinfection. Unfortunately, enzyme-linked immunosorbent assay (ELISA) is a laboratory test that allows one to determine the presence of HIV antibodies in the blood and often gives false-positive results. To clarify the diagnosis, an immunoblot was performed for antibodies to HIV and HCV. According to WHO recommendations, immunoblotting (Western blot) is used in the diagnosis of HIV infection as an additional expert method, which should confirm the results of ELISA. Immunoblotting is an expensive and time-consuming technique. The results of this analysis were obtained almost before the patient was discharged from the hospital. At the same time, the prescription of symptomatic therapy made it possible to stabilize the patient’s condition and improve cognitive functions. The choice of drugs was based on the principles of treatment of vascular lesions of the brain.

Observation 2.

Patient R

., 52 years old. Entered the City Clinical Hospital No. 15 named after. O.M. Filatova with a diagnosis of stroke.

When I received the complaint, I could not formulate it due to speech impairments.

Life history: married. He has been abusing alcoholic beverages for a long time and has been smoking since he was 16 years old. Arterial hypertension for the last 10 years.

History of illness: considered himself practically healthy. In August 2016, he noticed dizziness and double vision. An outpatient MRI of the brain with contrast was performed, and he was consulted at City Clinical Hospital No. 24, where he was diagnosed with multiple sclerosis in question, mass formation of the brain, ischemic stroke. He was treated in a hospital with a diagnosis of transient ischemic attack. He completed a course of vascular and neurometabolic therapy with an unstable positive effect. He did not take recommended therapy (antiplatelet agents, statins, antihypertensive drugs). The deterioration of the condition was noted on November 16, 2016; at about 14:00 speech was impaired. Due to the lack of improvement in his condition, he was hospitalized by the ambulance team at City Clinical Hospital No. 15 named after. O.M. Filatova.

The condition upon admission is of moderate severity, the skin and visible mucous membranes are of normal color and moisture. There is hard breathing in the lungs, no wheezing. NPV 16 per minute. Heart sounds are muffled, rhythmic, heart rate 68 beats/min, blood pressure 160/90 mm Hg. The abdomen is soft, painless on palpation in all parts. Self-urination. Urine is light and transparent.

Neurological status: conscious, limited access to productive contact due to severe speech disorders. Cognitive functions cannot be assessed. There are no meningeal signs. Palpebral fissures S

=
D
.
Pupils S
=
D.
_
Photoreactions and corneal reflexes are preserved. Full movement of the eyeballs. Nystagmus and diplopia are absent. The facial muscles are symmetrical. Swallowing is not impaired. Tongue in the midline. In the test, Barre penetrates his right hand. There are no paresis. Muscle tone D
=
S
, not changed.
Tendon reflexes D
>
S
, low. There are no pathological foot signs. Sensitivity could not be reliably assessed due to speech impairments; the functions of the pelvic organs are monitored. No clear disturbances of sensitivity and coordination were identified. The Romberg test was not performed. Stroke scale score (NIHSS) - 2 points.

Laboratory research methods: without features, aHCV, hepatitis B virus surface antigen (HBsAg), antibodies to Treponema pallidum

not detected. ELISA method: aHCV - “+”, IB - “+” from 11/23/16.

The ECG shows a regular sinus rhythm, heart rate 78 beats/min. According to EEG data, against the background of moderate diffuse changes, there is dysfunction of nonspecific brain structures. No paroxysmal activity or focal pathology was detected. Ultrasound of the abdominal cavity and kidneys revealed signs of diffuse nonspecific changes in the liver, pancreas and left kidney cyst.

According to the speech therapist, the patient has amnestic-semantic aphasia, afferent motor aphasia, mixed agnosia, dyscalculia, a component of dysarthria, and a defect of moderate severity.

Neuroimaging: MSCT did not reveal any fresh areas of ischemia or hemorrhage at the time of the study. MRI of the brain shows a picture of subacute ischemia in the left parietal lobe of the brain, signs of central pontine myelinolysis. Encephalopathy. Signs of intracranial hypertension. If clinical and laboratory data are available, PML may be consistent. In Fig. 3

Rice. 3. MRI of the brain of patient R., 52 years old. a, b — DVI mode; c, d — Flair mode.

Rice. 3. MRI of the brain of patient R., 52 years old. (end) d, f - T2 mode; g, h — T1 mode. Tomograms are arranged sequentially in DVI, Flair, T2- and T1-weighted image modes.

PCR study of the CSF for the JC virus is positive.

Diagnosis: IB+ No. 131988 dated 11/23/16. Focal brain lesion (PML).

Symptomatic treatment was carried out: 25% solution of magnesium sulfate 10.0 ml + 0.9% solution of sodium chloride - 200.0 ml intravenous drip; heparin 5000 units 3 times a day subcutaneously; recognan (citicoline) 1000 mg IV; Cortexin (polypeptides of the cerebral cortex of cattle) 10 mg IM; bisoprolol 5 mg in the morning; enalapril 5 mg 2 times a day; atorvastatin 20 mg in the evening; aspirin 125 mg in the evening; omez (omeprazole) 20 mg 2 times a day; diacarb (acetazolamide) 500 mg. In order to prevent hypodynamic and hypostatic disorders and expand the motor regime, a complex of physical therapy was prescribed.

Against the background of the therapy, the condition is showing positive dynamics. Blood pressure levels were stabilized and antihypertensive therapy was adjusted. The focal neurological deficit partially regressed. Consciousness is clear. Speech disorders (amnestic-semantic aphasia, afferent motor aphasia, mixed agnosia, dyscalculia, dysarthria component) remain, the severity has decreased slightly. Facial expressions are symmetrical, there are no paresis of the limbs.

The patient had a typical vascular history, which most likely made it difficult to make a correct diagnosis. The positive effect of vascular therapy was short-term, but at the same time it made it possible to stabilize the patient’s condition before transfer to a specialized medical facility.

Discussion of the therapy performed

PML is a fairly common disease in patients with reduced immune status. The diagnosis is usually made on the basis of a typical clinical picture, MRI findings and a positive PCR test for JC virus in the CSF. Treatment has not been fully developed and is symptomatic.

Blocking excess CSF production is a pathogenetic approach to deciding on the treatment of a patient with neurological symptoms against the background of liquorodynamic disorders that were present in the patients. Given the presence of manifestations of intracranial hypertension, acetazolamide was used, a unique systemic carbonic anhydrase inhibitor, the only drug that blocks excess cerebrospinal fluid production [20]. The drug was historically classified as a diuretic, but, according to the instructions, the diuretic effect of acetazolamide is weak, and after 3 days it no longer has diuretic properties. The indication for use is intracranial hypertension. Acetazolamide allows long-term compensation of liquor circulation disorders. It should be remembered that correction of liquorodynamic disorders should not be episodic; long breaks in treatment are undesirable. Acetazolamide therapy fulfills all of these conditions in patients with PML. The duration of action of the drug is up to 12 hours. The recommended dosage for patients with intracranial hypertension is 1-3 tablets per day. There is no need for intervals in therapy2​᠎.

With encephalopathy of any origin, damage to the neurovascular unit occurs with the development of oxidative stress, to combat which ethylmethylhydroxypyridine succinate was used. This drug is an antioxidant that has antihypoxic, membrane-protective, nootropic, anticonvulsant and anxiolytic effects [21]. Ethylmethylhydroxypyridine succinates are approved for wide medical use for the treatment of stroke, encephalopathy of various origins (hypertensive, atherosclerotic, traumatic, etc.), neurotic and neurosis-like disorders with anxiety, for the relief of withdrawal syndrome in alcoholism, for the treatment of acute intoxication with neuroleptics and a number of others diseases. Derivatives of succinic acid have a pronounced stress-protective effect, which is manifested in the normalization of post-stress behavior, somatovegetative disorders, restoration of sleep-wake cycles, impaired learning and memory processes, and a decrease in dystrophic changes in various brain structures. The drugs are included in the Federal Guidelines for the Use of Medicines. A significant advantage of succinates is that they have few side effects and low toxicity. In patients with minimally expressed manifestations of cerebrovascular pathology, courses of the drug at a dose of 100 mg IM for 2 weeks are recommended as preventive therapy; the regimen can be repeated once every 6 months. It should be especially noted that these doses do not affect systemic hemodynamics, do not require adjustment of antihypertensive drugs, and are compatible with almost all drugs.

Cortexin (polypeptides of the cerebral cortex of livestock) is a drug with proven effectiveness at the clinical, biological, cellular, genetic and molecular levels [22]. It affects all stages of the pathological chain of molecular events leading to neuronal death. The central link in the pathological processes occurring in the brain against the background of hypoxia is a decrease in the ATP content in brain neurons. A decrease in synthesis and an increase in ATP consumption has been proven immediately after stimulation of glutamate receptors with toxic concentrations of glutamate. It is known that a decrease in ATP concentration in neurons during hyperstimulation of glutamate receptors can disrupt the intra- and intercellular signaling system in brain neurons, in particular ion homeostasis, the activity of glycolytic enzymes and oxidative phosphorylation, Ca2+ uptake by mitochondria and protein synthesis. These processes may underlie the death of neurons after hypoxia and the toxic effect of glutamate excessively present in the synaptic cleft. Cortexin is able to restore ATP content after exposure to toxic concentrations of glutamate in young and old neurons. The drug's peptides have a direct and indirect neurotrophic effect on cells, stimulating the growth of neurites or reducing the death of neurons cultured in a medium devoid of growth factors. The main mechanisms of this effect are probably based on changes in the expression of genes that regulate the synthesis of intrinsic neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The drug has multiple effects, including cascade regulation of apoptosis, expression of neurotrophic factors, activation of the energy supply of the nerve cell and mitochondrial potential, improves the functioning of glutamate receptors and regulates Ca concentration in the cell. Through a system of anti-inflammatory cytokines, cortexin improves the neurotrophic supply of nerve fibers and reduces autoimmune aggression, promoting the restoration and growth of axons. It is assumed that the positive effect of cortexin is explained not only by the action of polypeptide components, but also by the neurochemical activity of macro- and microelements, as well as vitamins (A, E, B1 and PP) [22]. Unlike many nootropic drugs, Cortexin has a stimulating effect on mental functions, and in some cases corrects abnormal bioelectrical activity of the brain (confirmed by psychological tests and EEG). The drug is also distinguished by the almost complete absence of adverse reactions and extremely favorable tolerability by patients of any age [22]. In 2009, The Open Neuropsychopharmacology Journal published a study on the use of the drug Cortexin and its effect on cognitive functions and behavioral reactions (under experimental conditions) [23]. Recently, new data have emerged on the indirect immunostimulatory effect of cortexin [24]. The balance of the drug’s peptides and the versatility of its subtle mechanisms of action explain not only the therapeutic effectiveness, but also the absence of side effects of the drug. The course of treatment ranges from 10 to 20 days.

However, if patients have severe neurological symptoms (acute stroke-like episodes with general cerebral and focal symptoms, cognitive impairment, episodes of dizziness or sudden falling, etc.) due to the use of chemically synthesized, foreign drugs at this stage, it is recommended to add other drugs. At the same time, natural metabolites of biochemical processes in the body make it possible, already in the early stages of the disease, to reduce the progression of the process and prevent further neuron degeneration. Priority is given to the administration of drugs that affect phospholipids and the products of their metabolism - since phospholipids are the main structural component of all cell membranes, numerous cell functions directly depend on them. In addition to phospholipids and cholesterol, various proteins are also built into the membrane, which are receptors for hormones, enzymes, and biologically active substances. The normal functioning of proteins, including peptide drugs, directly depends on the phospholipids surrounding them. From this point of view, research data on the use of citicoline are of undoubted interest. Recognan (citicoline) is a drug that has been well studied and widely used for various forms of cerebrovascular pathology in Western Europe, the USA and Japan over the past 30 years [25]. Citicoline is a natural metabolite of biochemical processes in the body, i.e. it is not a foreign chemical compound, a xenobiotic, like most drugs. It contains cytidine and choline linked by a diphosphate bridge and is a necessary intermediate in the synthesis of phosphatidylcholine, the major brain phospholipid, in the phospholipid synthesis pathway (Kennedy pathway). Citicoline reduces the loss of phosphatidylcholine, which is part of the cell membrane, is involved in the synthesis of the neurotransmitter acetylcholine, stimulates the activity of tyrosine hydroxylase and the secretion of dopamine. In experiments, citicoline reduced neuronal degeneration in the hippocampus of rats caused by injection of beta-amyloid protein [26]. Amyloid beta is a normal protein in the body. The degree of cognitive impairment is directly proportional to its accumulation. Choline in combination with cytidine stimulates the secretion of normal neurotrophic amyloid precursor protein by rat brain cells. Citicoline is able to reduce beta-amyloid deposition in the brain, which is clinically manifested in improving integral indicators of cognitive function. In addition to its effects on beta-amyloid, the neuroprotective effect of citicoline is likely due to the redistribution of the main glutamate transporter EAAT2 into lipid raft microdomains, which leads to increased glutamate uptake. Given these data, many clinical studies have been conducted to evaluate the effectiveness of citicoline in the treatment of cognitive disorders associated with brain aging, cerebrovascular diseases and dementia [27]. European clinical studies found that administration of the drug in different doses for different durations of treatment more significantly improved neurological functions and contributed to early recovery of motor and cognitive functions [28]. In the treatment of patients with PML, citicoline plays another important role: it has an immunomodulatory effect, which is based on a decrease in plasma levels of histamine, while simultaneously increasing TNF-α [29]. The course of treatment is long (up to 6-12 months).

Conclusion

PML is a disease that occurs in patients with various pathologies, including neuroinfections, rheumatoid arthritis, when using certain medications, so it is extremely important for a clinician to know the diagnostic criteria of this nosology, be able to make a correct diagnosis, and begin symptomatic therapy as early as possible. This will improve the patient's condition, given that there is still no effective treatment for PML. Until now, antiviral drugs, cytostatics, serotonin receptor antagonists, and plasmapheresis have been widely used. However, it should be noted that all of the above methods are possible only after the causes of PML have been established, while the patient needs emergency care. Therefore, it is advisable to use pathogenetic therapy regimens using drugs that have pleiotropic effects.

The authors declare no conflict of interest.

*e-mail

Letter of the Federal Service for Surveillance in Healthcare dated February 7, 2014 No. 02I-110/14 “On new data on the safety of the drug Benlysta.” . https://www.garant.ru/products/ipo/prime/doc/70485650/#ixzz3OWJlGxDT

Instructions for medical use of the drug Diacarb.

Causes of dyscirculatory encephalopathy

Pathology develops mainly in older people against the background of the following conditions:

1. Deposition of blood clots inside a vein, artery;
2. Angiospasm with a significant increase in blood pressure;
3. Atherosclerosis of the cerebral arteries;
4. Cholesterol plaques inside the vessel wall;
5. Damage to the vascular wall by bacterial toxins (botulism, streptococci);
6. Degenerative-dystrophic diseases of the cervical spine;
7. Vegetative-vascular dystonia (VSD);
8. Inflammatory processes of the arterial wall (vasculitis).

To predict clinical symptoms, it is rational to divide etiological factors into five categories:

• Venous;
• Hypertensive;
• Atherosclerotic;
• Neurological (VSD, rheumatism);
• Mixed.

The most common causes of nosology in older people are hypertension, atherosclerosis, and varicose veins.

Reasons for the development of the disease

There are many reasons for the development of mixed encephalopathy. It is worth highlighting the various groups and briefly characterizing each of them:

• Discirculatory processes. Described in detail in the article. They are almost always one of the factors leading to the disease.
• Dysmetabolic processes. Includes any endocrine and other metabolic disorders that pathologically affect brain tissue. The most common type is diabetes mellitus and endemic goiter. The word toxicodismetabolic can also refer to alcohol abuse.
• Consequences of traumatic brain injuries. Most often, the consequences remain after a brain contusion, however, multiple concussions can also be included when making a diagnosis.
• Residual encephalopathy, meaning any congenital malformation of the central nervous system.
• Hypoxic, this factor is set in the presence of severe obstructive pulmonary disease, uncontrolled bronchial asthma, lung tumors, including those operated on with existing insufficiency of external respiration.
• Consequences of ischemic and hemorrhagic strokes, especially in the presence of severe pyramidal insufficiency.
• Consequences of surgical interventions on the brain performed for any indication (cancer process, etc.).
• Toxic factors. Any poisoning, including alcohol substitutes, metals, carbon monoxide.

Symptoms of dyscirculatory encephalopathy

Let us describe the main symptoms of all forms of DEP:

• Disorders of the functioning of the cerebellum - fluency of speech, walking disorders, instability during movements;
• Affective disorders;
• Vascular dementia;
• Pyramidal spasticity;
• Pseudobulbar problems;
• Slow speech;
• Autonomic vestibular disorders;
• Instability of blood pressure;
• Smoothness and slowness of speech.

It is difficult to unambiguously determine the symptoms of dyscirculatory encephalopathy, since the manifestations are based on functional disorders of cerebral circulation.

The main signs of alcoholic encephalopathy:

1. Decreased memory for short-term events;
2. Mental and emotional disorders;
3. Apathy, lack of interest in favorite activities;
4. Severe headaches;
5. Weakness and dizziness;
6. Vomiting reflex;
7. Dizziness;
8. Multiple sclerosis;
9. Neurological focal symptoms.

Discirculatory encephalopathy is characterized by the appearance of symptoms closer to the night. In the first degree, initial symptoms occur after heavy physical activity:

• Unsteady walking;
• Decreased memory;
• Pathology of attention;
• Fall of self-criticism;
• Depressive syndrome;
• Dementia;
• Muscle tremors;
• Urinary incontinence;
• Pseudobulbar syndrome;
• Irritability;
• Ataxia.

The appearance of any sign requires MRI or CT angiography to verify changes in cerebral circulation.

Alcoholic encephalopathy - what is it?

The main pathogenetic manifestations of the disease are associated with a deficiency of vitamin metabolism. Metabolic products of ethyl alcohol damage vitamin B1, which is necessary for optimal functioning of the nervous and cardiovascular systems. The condition is aggravated by damage to the digestive organs.

A lack of B vitamins leads to impaired absorption of glucose by cells. A reduced energy balance leads to disruption of the functioning of intracellular organelles - mitochondria, lysosomal structures.

Deficiency of vitamins P and B6 disrupts cell division and damages the mechanism of genetic information exchange during mitosis. The process reduces the recovery ability of tissues after damage.

The most sensitive organ to glucose deficiency is the brain. Hypoxia leads to irreversible neuronal death. The mechanism ensures the formation of psychosis in people with alcohol dependence.

Degrees of dyscirculatory encephalopathy

The stages of DEP determine the clinical picture of the disease:

• First (I) degree – memory loss appears;
• Second (II) degree – personality changes occur, self-criticism decreases;
• Third (III) degree – several syndromes exist simultaneously, the ability to self-care is lost.

Stage 1 DEP is common among the population. Medical sources claim that every second resident has a nosology. Cerebral circulation disorders (dyscirculation) develop due to constant stress and air pollution.

Discirculatory encephalopathy of the 2nd degree occurs in old age. The development of nosology provokes cerebral infarctions and strokes. Depending on the symptoms, several clinical variants of the nosology are formed:

• Social maladjustment;
• Movement disorders;
• Polyneuropathy.

One of the common types of the disease is atherosclerotic dyscirculation. An imbalance of fat metabolism causes disturbances in the patency of cerebral arteries due to the presence of atherosclerotic plaques inside the lumen.

Venous discirculatory encephalopathy occurs due to stagnation of venous blood in the body. Congestion of the veins ensures the formation of blood clots. Migration of blood clots from the primary focus into the cerebral vessels provokes a stroke.

Clinic for Acute Encephalopathy Gaie-Wernicke

The rapid development (several weeks) of nosology poses a threat to health and life. Many mental, nervous, and somatic disorders arise:

• Speech impairment;
• Panic, anxiety, various types of fears;
• Apathy, reluctance to do usual work;
• Burning, numbness of the skin;
• Severe heart pain;
• Nightmares;
• Panic and anxiety;
• Coma or stupor.

The acute form of Guyre-Wernicke is accompanied by impaired functionality of internal organs due to concomitant polyneuropathy. With alcohol dependence in men, hepatitis (inflammation of the liver) and pancreatitis (inflammation of the pancreas) may occur.

Diagnosis of dyscirculatory encephalopathy

Primary assessment of the structure of the brain parenchyma and the nature of blood flow is carried out by clinical and instrumental methods:

1. Computed tomography (CT with contrast);
2. Positron emission tomography (PET);
3. Magnetic resonance imaging (MRI);
4. Electroencephalography (EEG);
5. X-ray of the cervical spine;
6. Blood chemistry.

The degree of dyscirculatory encephalopathy is determined by analyzing the symptoms. It is necessary to take into account the lack of self-criticism in the second and third forms of the disease.

Neuropsychological counseling is required for patients with suspected mental disorders.