Disseminated encephalomyelitis: symptoms of the disease and treatment features

Acute disseminated encephalomyelitis is a single-phase autoimmune demyelinating disease in which the pathological process is localized in the central nervous system. Damage to the brain or spinal cord can occur after an infectious disease or vaccination. The reasons for the development of the idiopathic form of the disease are unknown. Rarely do neurologists diagnose recurrent or multiphasic acute disseminated encephalomyelitis.

The Yusupov Hospital has created optimal conditions for the successful recovery of patients:

• examination using the latest diagnostic equipment from leading global manufacturers;
• treatment with effective pharmacological drugs that have a minimal range of side effects;
• the use of innovative methods of restorative therapy by rehabilitation clinic specialists.

Severe cases of the disease are discussed at a meeting of the expert council with the participation of doctors and candidates of medical sciences, leading experts in the field of demyelinating diseases of the central nervous system. Doctors at the neurology clinic, who have extensive experience in treating acute disseminated encephalomyelitis, treat the patient according to an individual plan. At the same time, they comply with the recommendations of domestic and international neurological communities.

General information

Encephalomyelitis is an acute or subacute inflammatory process affecting the spinal cord and brain.
Lesions can be located in absolutely all parts of the nervous system. The most common form is acute disseminated encephalomyelitis (or disseminated). In many ways, the localization of the pathological process can be determined by the symptoms. Of utmost importance are proteins that are produced by the immune system in response to the inflammatory process and attack the nervous system’s own cells. The annual incidence is 0.4-0.8 people per 100 thousand population. Encephalomyelitis mainly affects children and young people with a pathological immune response. There is no gender predominance among patients.

Diagnostics of the electrical power supply

The diagnosis of ADEM is made by identifying characteristic symptoms, a detailed medical history, a thorough clinical evaluation, and various specialized tests, including imaging tests such as magnetic resonance imaging (MRI). MRI uses a magnetic field and radio waves to take cross-sections of individual organs and tissues in the body and can show characteristic brain lesions in people with the disease. Additional tests to rule out other conditions may also be performed. Such studies may include infectious disease, immunological and metabolic studies.

Pathogenesis

The pathogenesis is considered insufficiently studied. The main pathogenetic mechanisms of the development of the disease lie in the autoimmune response of activated humoral autoantibodies and T-lymphocytes to myelin in the central nervous system. In some cases, peripheral myelin is also affected. Today, 2 concepts of the development of the disease are being considered.

According to the first theory, the nervous system acts as a barrier to immunity . During the period of embryonic development in the fetus in the third month, the formation of the blood-brain barrier in the brain occurs. It is with its help that a separation is carried out between the general blood flow and the nervous system, which provides an optimal chemical composition and constant environment for full functioning.

The blood-brain barrier helps reduce the permeability that characterizes blood vessels in the nervous system. At the same time, an immune response is being formed. As they develop and mature, the two systems described above do not come into contact with each other. That is why, when the nervous system is damaged (for example, due to neuroinfection or trauma) and the permeability of the blood-brain barrier is disrupted, an immune response to antigens of one’s own nervous tissue is formed.

When pathogenic microflora or a virus enters the nervous system, brain-specific proteins are produced and released into the blood, and immune defense is activated. It is these autoantigens that, when in contact with immunocompetent cells (lymphocytes and macrophages), provoke the formation of brain-specific antibodies and activated T-lymphocytes. Antibodies and T-lymphocytes, after penetrating the blood-brain barrier, enter the nervous system and contribute to the maintenance of the autoimmune inflammatory process there.

With secondary encephalomyelitis , the causative agents of which are neurotropic viruses ( influenza , enteroviruses , polio ), glial cells and neurons are damaged by the infectious agents themselves, which also leads to the launch of an autoimmune response.

The second concept is based on the theory of molecular mimicry, which lies in the similarity of the myelin protein and the amino acid sequence of the genetic material of bacteria or viruses. The cascade of immune reactions is triggered by cross-reactivity, which means that the immune system initially reacts to a pathogenic agent, and then to its own tissues.

Acute reactive encephalomyelitis is characterized by the appearance of foci of demyelination together with foci of vascular reaction and involvement of glia. Around the ventricles in the substance of the brain, macrophages and lymphocytes are detected. Demyelination mainly affects veins of medium and small caliber.

The pathological process mainly affects the white matter of the cerebral hemispheres, the medulla, the cerebellum and the spinal cord. At the same time, lesions are detected in the myelin sheaths around the axons of peripheral nerves. In some cases, peripheral nerves and spinal roots are affected.

Classification

It is customary to distinguish acute disseminated encephalomyelitis - ADEM (in English literature known as ADEM - acute disseminated encephalomyelitis). There are 3 types of WECM:

• post-infectious;
• post-vaccination;
• spontaneous.

It is also customary to distinguish between primary (idiopathic) and secondary encephalomyelitis.

Classification by stream:

• Acute encephalomyelitis. Characterized by lightning-fast, rapid development and increase in neurological symptoms. It appears against the background or immediately after an infectious disease. Patients complain of cough, muscle pain, fever, chills, and shortness of breath.
• Subacute encephalomyelitis . The rate of development of symptoms is slower than in the acute form.
• Chronic encephalomyelitis . Characterized not only by the slow development of clinical symptoms, but also by episodes of relapse, which makes this form similar to multiple sclerosis . Exacerbation of the disease occurs very often (5-33% of cases). Multiphase cases account for 20% of the incidence, and recurrent forms account for 80%. Multiphase forms are characterized by periods of exacerbation after the apparent completion of the acute process and transition to the stage of residual manifestations. Recurrent cases are characterized by increased neurological symptoms during treatment in the first 3 months of the disease.

Variants of acute disseminated encephalomyelitis depending on clinical manifestations:

• diffuse encephalomyelitis;
• encephalomyelopolyradiculoneuritis;
• myelopolyneuritis;
• optoencephalitis.

There is also myalgic encephalomyelitis , a benign chronic fatigue syndrome. The pathology is characterized by long-term (at least 6 months), excessive, disabling fatigue and is accompanied by numerous infectious, articular and neuropsychic symptoms.

The diagnosis of “myalgic encephalomyelitis” is established if the patient has at least 4 of the 8 listed symptoms for 6 months:

• impaired concentration and memory;
• joint pain (without swelling or redness);
• pain on palpation of the axillary and cervical lymph nodes;
• pharyngitis;
• lack of feeling of vigor and freshness after sleep;
• muscle stiffness and soreness;
• headache;
• feeling of fatigue and exhaustion after mental or physical labor, lasting for 24 hours or more.

Causes

The reasons can be very diverse. Secondary encephalomyelitis of infectious origin develops against the background of bacterial and viral diseases:

• herpes;
• Lyme disease;
• syphilis;
• toxoplasmosis;
• HIV infection;
• tropical paraparesis.

Encephalomyelitis can also occur against the background of measles , rubella , chickenpox , zoster , mumps and other infections caused by enteroviruses.

Secondary disseminated encephalomyelitis of autoimmune origin:

• post-vaccination REM (after rabies vaccinations, etc.);
• REM in patients with diffuse connective tissue pathology ( rheumatism , systemic lupus erythematosus , undifferentiated connective tissue disease);
• lesions of the central nervous system in patients with oncological pathology;
• antiphospholipid syndrome and other vasculopathies;
• vasculitis with damage to the central nervous system;
• other autoimmune processes.

Encephalomyelitis develops much less frequently with sarcoidosis , after insect bites, and also with COVID-19 .

Causes and development factors

The disease is caused by infection or intoxication, but the exact reasons for its development are not fully understood. But there are some risk factors that can affect the patient’s health and provoke encephalomyelitis. These include:

1. Traumatic brain injuries, bruises and concussions.
2. Viral infections, mainly characterized by the appearance of various rashes on the human body (herpes, chickenpox, rubella, etc.).
3. Bacterial infections: toxoplasmosis, chlamydia, etc.
4. Colds, ARVI, flu, etc.
5. Various types of allergies.
6. Introduction of some vaccines, in particular against rabies, measles, diphtheria, etc.
7. Reduced immunity, regular stress, overwork, injuries.

The encephalomyelitis virus is believed to be contagious, and a healthy person can become ill after close contact with a sick person. The virus can also enter through the gastrointestinal tract or by droplets. Patients with a hereditary predisposition are also at risk.

Symptoms of encephalomyelitis

Acute disseminated encephalomyelitis is characterized by a rapid increase in symptoms:

• general weakness;
• increase in body temperature to 38-39℃;
• headache;
• pain in bones and muscles;
• sleep disturbances, apathy, general malaise.

Consequences in the form of severe damage to the nervous system appear 1-4 weeks after infection. The clinical picture depends on the area of ​​the central nervous system affected.

Symptoms of disseminated encephalomyelitis:

• epileptic seizures;
• vomiting, nausea;
• dizziness , headaches;
• impaired coordination of movements;
• limitation of movements in the limbs ( paresis , paralysis ), weakness in the arms and legs;
• drowsiness and disturbances of consciousness;
• impairment or complete loss of sensitivity;
• disturbances in the functioning of the pelvic organs (acts of defecation and urination);
• changes in muscle tone ( hypertonicity , atony );
• stupor, coma.

The disease can affect the optic pair of cranial nerves. In this case, retrobulbar neuritis , which is manifested by a narrowing of the visual fields and a decrease in its acuity. During diagnosis, facial paresis is detected on the affected side and impaired abduction of the eyeball.

Disorders of motor and sensory activity can manifest themselves as autonomic disorders in the form of:

• instability of blood pressure (hypo- or hypertension);
• orthostatic hypotension (a decrease in blood pressure by 20 or more units when changing body position);
• pathologies from thermoregulation.

In patients in serious condition with involvement of the trunk muscles involved in the act of breathing and brain stem structures in the pathological process, spontaneous breathing may be impaired, which requires cardiopulmonary resuscitation and artificial ventilation.

With secondary encephalomyelitis of viral and bacterial etiology, additional specific symptoms appear. For example, with neuroborreliosis, pronounced clinical symptoms appear only at the 3rd stage of the disease. At an early stage, there may only be indications of a tick bite or the appearance of ring-shaped erythema . In some cases, Bannwart syndrome (damage to the facial nerve) is registered, lymph nodes are enlarged, and the peripheral nervous system is affected.

In pediatric practice, encephalomyelitis develops against the background of infections that manifest as skin rashes ( chickenpox , rubella ). The pathological process develops either against the background of or immediately after an infection and has specific clinical features.

Chickenpox encephalomyelitis is characterized by cerebellar ataxia , which is manifested by impaired coordination of movements and balance. Additionally, nystagmus (jerky movement of the eyeballs), a drop in blood pressure, and tremors of the limbs when performing precise movements are recorded. As you recover, lost functions are gradually restored.

Mumps is characterized by symptoms of meningitis , in some cases cerebellar ataxia and polymyelitis-like syndrome develop, which is manifested by decreased or weak tendon reflexes and atrophy of muscle tissue. Cerebellar ataxia is manifested by impaired coordination of movements, unsteadiness of gait, scanned speech, changes in handwriting and other manifestations of cerebellar damage.

With rubella encephalomyelitis, the mortality rate reaches 20%. The disease is extremely severe and manifests itself:

• optic neuritis
• transverse myelitis;
• epileptic seizures;
• polyradiculoneuritis;
• coma.

Multiple encephalomyelitis (SEM) and multiple sclerosis (MS) are characterized by complete pathogenetic similarity. An important difference is that REM is acute, and the manifestations are reversible; in MS, the course is chronic, progressive, with alternating periods of exacerbations and remissions. The onset of multiple sclerosis can easily be confused with encephalomyelitis. REM can cause chronic demyelinating process and lead to multiple sclerosis .

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that develops acutely or subacutely in close temporal connection with an infectious disease or vaccination. The neurological picture of ADEM usually reflects multifocal but monophasic damage to the nervous system, with complete or marked clinical recovery in most cases (4, 6, 11, 12, 14, 15).

History of the study of ADEM. The clinical picture of the disease was first described by J. Lucas in the 18th century. At that time, ADEM was associated with measles, smallpox, and chickenpox and had a high mortality rate. In 1920–1930 The first experiments were conducted to create a model of inflammatory demyelination in animals. Monkeys were inoculated with brain extract and developed weakness and ataxia, with perivascular inflammation and demyelination histologically noted. The similarity between experimental and post-vaccination ADEM was obvious.

In 1931, D. McAlpine identified three variants of ADEM: post-infectious, post-vaccination and spontaneous (sporadic).

Postinfectious ADEM is usually associated with a previous or concomitant infection, usually a viral and nonspecific infection of the upper respiratory tract. A complete list of recognized causes of ADEM is presented in table. 1.

Patients can get the disease at any age, but children and adolescents are most susceptible to ADEM. The true incidence of ADEM is not known. The incidence of post-measles and post-varicella ADEM is estimated at 1:1000 cases [7].

Post-vaccination ADEM. Post-vaccination ADEM accounts for 5% of all ADEM cases. After the widespread introduction of the E. Jenner smallpox vaccine in 1853 and the L. Paster rabies vaccine in 1885, vaccinated individuals had o. Pasteur's "inoculum" caused a "neuroparalytic case" of ADEM in about 1 in 1000 people. The neurological symptoms were initially thought to be due to the viral component of the vaccine, although it was later recognized that this was the result of the presence of CNS tissue contaminating the vaccine. This hypothesis is confirmed by the decreased incidence of post-vaccination ADEM now that most vaccines are no longer prepared from in vivo infected CNS tissue [9, 10].

The incidence of ADEM is 1–2 cases per 1 million people when vaccinated with live measles vaccine. The most commonly associated with post-vaccination ADEM are measles, mumps and rubella vaccines.

Pathogenesis of ADEM . In terms of pathogenesis and clinical picture, ADEM is close to multiple sclerosis (MS). The most accepted theories are based on the concept that pathological findings in ADEM are similar to those obtained in experimental allergic encephalomyelitis (EAE): the agent attacks myelin, activating segregated antigens, in response to which an immune reaction is triggered [2, 8, 13, 16].

Exposure to any systemic infection is sufficient for the development of ADEM. The initiation of post-infectious ADEM is most likely due to molecular mimicry between the virus and myelin antigens. In the case of post-vaccination ADEM, the main cause of the development of the disease is directed immune reactivity to myelin basic protein (MBP).

It is now accepted that the primary systemic activation of T cells is monophasic and decreases with the disappearance of provoking factors, such as infection.

Histological changes in ADEM are in the form of perivascular demyelination and edema, while the axons are relatively unaffected. Myelin damage is expressed in its swelling, decay and disappearance due to the absorption of myelin breakdown products by phagocytes. Axial cylinders suffer less. As a rule, they exhibit swelling and, less frequently, fragmentation. In a later stage of the disease, the lesion is replaced by gliosis.

Pathologic findings correlate with disease duration and show an evolution from diffuse vascular involvement to widespread demyelination.

Clinical picture . The fact of a previous viral disease or vaccination is often within the 1st month preceding the appearance of neurological symptoms. When studying ADEM in children, documented evidence of a prodromal viral disease or vaccination was found in 75% of cases. The time of onset of symptoms varies depending on the etiology. Disease typically occurs 1 to 14 days after vaccination, a week or less after the appearance of the rash in exanthem diseases, and 1 to 3 weeks (or more) after inoculation of rabies vaccine.

The dependence of the clinical phenotype of ADEM on the previous disease was noted. Several variants of the ADEM phenotype have been described: post-measles ADEM often has a severe clinical course, while ADEM caused by chickenpox has a favorable prognosis. A peculiar phenotype of ADEM in children was presented with hemolytic streptococcal infection of group Ab [3]. 10 children aged 3 to 14 years developed typical clinical manifestations of ADEM, but with severe symptoms of extrapyramidal syndrome (70%), behavioral and speech disorders (50%). At the same time, “ADEM syndrome”, as a rule, followed acute pharyngitis, was clinically different from rheumatic chorea, and a high level of antibodies to the basal ganglia was noted in the blood serum of patients. The onset of ADEM can be acute (90–95%): “explosive” onset and progression of neurological symptoms within hours before peaking in days, and subacute (5–10%): with insidious onset, slow progression and maximum neurological deficit before day 30 from the moment of illness.

Regardless of the severity of the onset of the disease and the etiological cause, ADEM clinically manifests itself polysymptomatically. In the acute onset of the disease, the simultaneous appearance of infectious, cerebral symptoms in combination with focal symptoms is characteristic: symptoms of damage to the brain stem, cerebellum, and spinal cord.

Onset symptoms of ADEM often include fever, headache, and vomiting. Convulsions and meningeal symptoms are not typical, but if observed, they occur more often with post-infectious ADEM than after post-vaccination ADEM.

Neurological symptoms are mainly multifocal, heterogeneous (depending on the location and severity of the inflammatory demyelinating process in the central nervous system) and include changes in the level of consciousness, pyramidal disorders (monoparesis, hemiparesis), ataxia and symptoms of damage to the brain stem, cranial nerves (CN), including and bilateral optic neuritis.

In the clinical picture of ADEM, a significant place is occupied by symptoms of damage to the roots and peripheral nerves: pain, sensitivity disorders in the feet and hands, decreased tendon and periosteal reflexes, muscle wasting.

Isolated transverse myelitis is usually considered as an independent nosological entity, but in a quarter of all cases it can represent a clinical manifestation of ADEM.

In our studies (50 children aged 8 months to 14 years were examined, the average age of patients was 6.43 ± 0.59 years), the infectious prodrome occurred in 50% of cases of ADEM and included symptoms of intoxication (drowsiness, general weakness, anorexia), changes body temperature, respiratory syndrome (cough, pharyngitis, rhinitis). Body temperature was elevated to high levels in 23 cases (47%), in 2 (3%) - to low-grade levels. In 1/2 of all cases of ADEM (25 patients - 50%), body temperature did not change.

General cerebral symptoms were noted: headache in 15 children (30%), vomiting in 11 (22%), impaired consciousness in 5 (10%), generalized convulsions in 3 (12%). Respiratory failure, requiring artificial lung ventilation (ALV), due to depression of consciousness and cervical myelitis, appeared in 2 patients (4%). Symptoms of meningeal irritation - in 7 patients (14%).

In 71% of cases, spastic paresis and paralysis were observed, with asymmetric tetraparesis in 24 children (48%), lower paraparesis in 8 (16%), hemiparesis in 4 patients (8%) and 2 patients (4 %) - monoparesis. In 20 cases (40%) there was a combined lesion of the central and peripheral motor neuron (mixed paresis and paralysis). Polyneuritic syndrome was noted in 20 (40%) cases.

Cranial neuropathies manifested themselves in the form of symmetrical bilateral optic neuritis (ON) in 15 patients (30%), symptoms of lesions of III CN (divergent strabismus, ptosis) - in 12 (24%), V CN (impaired sensitivity on the face) - in 5 ( 10%), VI CN (convergent strabismus) - in 3 (6%), VII CN (peripheral paresis of facial muscles) - in 24 (48%), VIII CN (systemic vertigo, vomiting, vestibular nystagmus) - in 4 (8 %), IX, X, XII CN (bulbar syndrome) - in 23 (46%).

Decreased vision was observed in 16 patients (32%), all of them met the criteria for bilateral ON. In children with ON, the deterioration in visual acuity was often severe, up to persistent amaurosis.

Cerebellar symptoms in the form of ataxia, diffuse muscle hypotonia, and focal dysmetria were observed in 38 patients (76%).

Rare clinical symptoms were muscle rigidity - “cogwheel symptom” - in 1 patient (2%), hyperkinesis: resting tremor - in 1 (2%), athetosis - in 1 (2%) and myoclonus - in 3 (6%) ).

Sensory disturbances at the onset of the disease were characterized by pain, paresthesia in 10 patients (20%), decreased or loss of sensitivity in 22 children (44%), of which in 4 (8%) - of the conduction type, in 12 (24%) - of the polyneuritic type, in 6 (12%) - segmental-radicular type and in no case was monoanesthesia detected.

In 12 patients (24%) with ADEM, dysfunction of the pelvic organs was observed, of which 8 (16%) had a central type (urinary retention or imperative urge to urinate and defecate), 4 (8%) had a peripheral type ( urinary and fecal incontinence).

Disturbances of higher mental functions (HMF) in the acute period of ADEM were manifested by disturbances in the emotional-volitional sphere (12–24%) and cognitive disorders (8–16%). Partial epileptic seizures in the acute phase of the disease were noted in 3 patients (6%), subsequently the patients had symptomatic partial epilepsy.

Thus, the clinical picture of ADEM due to pronounced dissemination of the pathological process is polymorphic. All parts of the central nervous system and PNS (peripheral nervous system) can be affected, with hemispheric symptoms predominating in some cases and brainstem or spinal cord symptoms in others.

Multiphasic disseminated encephalomyelitis (MDEM). Although ADEM usually has a monophasic course without clinical relapses or new subclinical lesions in the future, there are reports in the medical literature of repeated cases of the disease and recurrent ADEM. Recurrent episodes are expected to occur over a period of several months and usually with similar clinical, laboratory, and radiological characteristics. The terminology is currently being clarified. Previously, the term “recurrent ADEM” was used. Recently, the term “biphasic disseminated EM” has been proposed.

Clinical course of ADEM: ADEM is characterized by the absence of new exacerbations, with the exception of rare recurrent forms. After the acute stage of the disease, rapid improvement almost always occurs without subsequent relapses, sometimes with a persistent neurological defect.

In our studies, in the vast majority of cases ADEM was monophasic (90%), in relatively rare cases ADEM recurred. During the observation period, 5 patients (10%) had a relapse. The number of relapses (relative to the entire group) averaged 0.16 ± 0.08. The period until the second relapse averaged 29.29 ± 15.24 days. Relapses occurred against the background of repeated acute respiratory viral infection (3 cases), previous traumatic brain injury (TBI) (concussion) and against the background of a sharp decrease in hormonal therapy (1 patient). In one case, the exacerbation was monosymptomatic (a sharp decrease in visual acuity to amaurosis) and in 4 cases polysymptomatic (ataxia, nystagmus, intention tremor, hemiparesis) and were relatively short in duration (10.5 ± 2.02 days). Subsequently, during the follow-up period (an average of 450.0 ± 270.0 days), no more relapses were observed in any child.

The duration of observation of children who suffered ADEM averaged 26.81 ± 3.94 months. 33 patients (66%) recovered completely; 5 children (10%) had mild motor impairments that could only be identified with a detailed neurological examination; 2 (4%) had behavioral disturbances and strabismus; 3 children (6%) had moderate weakness and ataxia; 5 (10%) had tetraparesis and ataxia, walking was possible only with support; 2 children (4%) had severe motor disorders (tetraplegia).

Diagnostics. The diagnosis of ADEM and MDEM is often made based on a typical clinical picture; unfortunately, there are no pathognomonic markers.

Analysis of cerebrospinal fluid (CSF) in 25% of cases reveals increased intracranial pressure and pleocytic cytosis with lymphocytes, neutrophils, and a significant number of erythrocytes, reflecting a microhemorrhagic process, but in 75% of cases there may be no changes. Oligoclonal IgG in the CSF is less common in children with ADEM than in MS. The frequency of detection of oligoclonal IgG in ADEM ranges from 3% to 29% of cases.

Neuroimaging. Multifocal lesions on brain MRI are similar to those seen in MS. But there are some differences that help distinguish MS from ADEM:

• ADEM lesions tend to be large and asymmetrically distributed in the cerebral and cerebellar white matter and basal ganglia. According to the results of our studies, patients with ADEM were significantly more likely to have lesions in the subcortical white matter with relatively spared periventricular white matter (93%, 36%, p < 0.001); in MS, lesions are localized both periventricularly (93%) and subcortically (92%); in ADEM, the cerebral cortex (28%–0%, p < 0.001), thalamus (23%–2%, p < 0.05) are often affected, while in MS, the corpus callosum is significantly often affected (38%–2% , p < 0.001), internal capsule (21%–4%, p < 0.01);
• Contrast-enhanced MRI reveals homogeneous lesions as opposed to heterogeneous temporal dissemination in MS. The presence of hypointensities or “black holes” on T1-weighted MRI is indicative of a previous destructive inflammatory demyelinating process, hence MS;
• mass effect and contrast enhancement, resulting from edema and dysfunction of the blood-brain barrier (BBB), are more often observed in the acute phase of ADEM, less common in MS;
• lesions in ADEM have poorly defined edges (marginations), while in MS they are more distinct.

Since lesions in ADEM have a mass effect, sometimes, to exclude a malignant disease of the central nervous system, a biopsy is suggested for diagnostic purposes. A necessary condition for diagnosing ADEM is the exclusion of infections, vasculitis or other autoimmune diseases.

Treatment. There is no standard treatment for ADEM. Therapy of the disease is based on a strategy that has an appropriate effect on the likely pathogenetic mechanisms of the disease. Treatment of ADEM is no different from relieving exacerbations of MS. The main therapeutic choice for ADEM is corticosteroids, intravenous immunoglobulins (IVIG), and plasmapheresis [1, 3].

Corticosteroids . The empirical evidence for their high effectiveness is quite convincing, despite the lack of case-control studies. The rationale for the use of corticosteroids is their ability to reduce inflammation, reduce swelling, and stabilize the blood-brain barrier, which reduces further influx of active immune cells and humoral factors that promote demyelination.

Modern data from the medical literature suggest the use of Metipred intravenously followed by a transition to oral prednisolone, but subject to the exclusion of bacterial meningoencephalitis.

IVIG . The main directions of action of IVIG are: binding to activated Th1 lymphocytes and slowing down their proliferation, which leads to a decrease in the level of pro-inflammatory cytokines; regulation of T cell apoptosis; restoration of suppressor T cells; suppression of complement-mediated myelin damage.

We analyzed the effectiveness of treatment in 10 children with ADEM who received pulse therapy with methylprednisolone (Solu-Medrol, Pharmacia, Belgium) at the rate of 20 mg/kg body weight per day intravenously, from 3 to 5 infusions, followed by switching to prednisolone at the rate of 1 mg /kg body weight per day per os for 6–8 weeks with a gradual dose reduction until complete withdrawal, in combination with IVIG: Octagam (Oktapharma), Intraglobin (Biotest Pharma), Pentaglobin (Biotest Pharma) at the rate of 2 g/kg body weight per course, intravenous drip. The use of combination therapy for ADEM: corticosteroid therapy and intravenous immunoglobulin had a pronounced and persistent clinical effect.

A retrospective analysis of the anamnestic data of patients with MDEM revealed that they received treatment with per os prednisolone during the first exacerbation for a short period of time and at a dose of 1 mg/kg body weight. It is possible that relapses of ADEM with a decrease in steroids occurred due to their premature withdrawal - in conditions when the inflammatory process was not yet completed.

Thus, corticosteroid therapy undoubtedly has a high effect, but its premature withdrawal (during the active period of the disease) can lead to a return of the original symptoms or to the development of new ones.

Given this fact, in our opinion, children with ADEM are advised to take a longer period of withdrawal from steroids—for 6–8 weeks. Another alternative for early withdrawal of corticosteroids is combination with immunomodulatory therapy (high doses of IVIG).

Based on our experience in treating ADEM, we can propose the following treatment tactics for patients with ADEM (Fig.).

Plasma exchange is recommended in patients who do not respond well to intravenous corticosteroids.

Cyclophosphamide has been used in the past and is not widely used. Although some studies still recommend the administration of cytostatics in the absence of effect from the therapy (41).

For questions regarding literature, please contact the editor.

Bembeeva R. Ts. , Doctor of Medical Sciences, Professor of Russian State Medical University , Moscow

Tests and diagnostics

The diagnosis is based on identifying the symptoms of multifocal damage to the nervous system. When interviewing the patient and collecting anamnesis, they must find out whether there were any infectious diseases the day before. Encephalomyelitis can also develop immediately after a tick bite or vaccination.

During the examination, the neurologist pays attention to the severity of paralysis, the presence of paresis, level of consciousness, autonomic disorders, changes in sensitivity and functional state of the pelvic organs.

In acute disseminated encephalomyelitis, laboratory tests reveal lymphopenia , leukocytosis and increased ESR.

If encephalomyelitis is suspected, a cerebrospinal fluid examination is required. Characteristic changes are observed in 60% of cases in the form of increased protein levels and moderate lymphocytic pleocytosis.

Quite often, oligoclonal immunoglobulins G, detected in multiple sclerosis , are absent, but in approximately every second adult and every third child they are detected, which greatly complicates differential diagnosis.

The main neuroimaging method for diagnosing ADEM is MRI. The study reveals asymmetric, multiple lesions involving the central and subcortical white matter. Also, affected areas are identified in the transition zone of cortical gray and white matter in the cerebellar hemispheres, cerebral hemispheres, spinal cord and brain stem. Quite often, the basal ganglia, thalamus and deep gray matter are involved in the pathological process. The lesions are characterized by a symmetrical arrangement. The corpus callosum is affected only in very large lesions.

Affected Populations

ADEM can develop at any age, but it is much more common in children than in adults. Men and women are affected in equal numbers, although a slight male predominance was noted in paired pediatric studies. In children, the disease is diagnosed on average at the age of 5-8 years. The exact incidence of ADEM among the Russian population as a whole is unknown. The disease appears to peak during the winter and spring months in studies conducted in the United States.

Treatment

In the acute course of ADEM, immunosuppressive therapy is prescribed. Also, as with multiple sclerosis, pulse therapy with corticosteroids is indicated (500-1000 mg administered intravenously, 3-5 times).

If there is no effect, glucocorticosteroids are prescribed orally at a dose of 1 mg of Prednisolone per 1 kg of body weight per day. Therapy is carried out until positive dynamics are achieved, followed by a gradual reduction in dose. The duration of treatment is 3-6 weeks. An oral course of corticosteroids with gradual withdrawal over 6 weeks can significantly reduce the risk of exacerbations.

Plasmapheresis and intravenous administration of immunoglobulins are prescribed only if glucocorticosteroids are ineffective.

Drugs from the group of cytostatics with an immunosuppressive effect, such as Cyclophosphamide and Mitoxantrone , are prescribed for severe disease with complications such as myelopolyneuropathy and encephalomyelopolyneuropathy.

In addition to pathogenetic therapy, which is aimed at suppressing and eliminating the causes of the disease, symptomatic, supportive therapy, as well as early rehabilitation, are indicated for encephalomyelitis.

Maintenance therapy:

• correction of water and electrolyte balance;
• artificial ventilation;
• taking naticonvulsants when diagnosing convulsive activity;
• the use of anticoagulants in patients at risk for the prevention of deep vein thrombosis.

Drugs prescribed during early rehabilitation:

• anticholinesterase drugs ( Galantamine , Ipidacrine );
• B vitamins
• metabolic agents (nootropics, neuroprotectors, vasoactive medications).

For muscle hypertonicity and increased activity of the tendon reflex, muscle relaxants are prescribed ( Baklosan , Tolperisone , Tizanidine ). botulinum toxin is injected .

Mandatory components of therapy during the recovery period are physical therapy classes, massage and balneotherapy.

Treatment of acute disseminated encephalomyelitis

There is no standard therapy for ADEM. Most treatments that have been used to treat acute disseminated encephalomyelitis have some effect of suppressing the activity of the immune system (immunosuppressive therapy). Such treatments include the use of:

• corticosteroid drugs;
• intravenous immunoglobulin therapy;
• plasmapheresis (the procedure for collecting blood, purifying it and returning it back into the bloodstream).

High doses of corticosteroids are commonly used to treat people with ADEM and are generally considered the mainstay of therapy. Corticosteroids resulted in improvement of symptoms in many cases. Methylprednisolone is the most common corticosteroid drug used to treat people with ADEM.

However, there are significant differences in the specific forms, routes of administration, dosage, and tapering schedule when treating patients with corticosteroids. In addition, high doses of corticosteroids can cause significant side effects in some patients.

Intravenous immunoglobuin therapy is used to treat some individuals with ADEM who do not respond to or cannot tolerate corticosteroid therapy. Intravenous immunoglobuin is a concentrated solution of antibodies extracted from the blood of healthy donors. This therapy is used to treat various autoimmune diseases because it can neutralize the effects of autoantibodies, which are antibodies that mistakenly attack healthy tissue.

Plasmapheresis has also been used to treat people who do not respond to other forms of therapy. However, its use has only been described in a few specific cases. Plasmapheresis is a procedure, a method of removing unwanted substances (toxins, metabolic substances and parts of plasma) from the blood. Blood is removed from the patient and the blood cells are separated from the plasma. The patient's plasma is then replaced with another person's plasma and the blood is returned to the patient.

Consequences of encephalomyelitis

The main complication after a severe form of disseminated encephalomyelitis is encephalomyelopolyradiculoneuropathy, as well as ascending Landry's palsy. Patients complain of weakness in the legs, and gradually the paralysis rises higher, affecting the arms and torso. Upon reaching the brain, bulbar syndrome develops, which is characterized by the following disorders:

• act of swallowing ( dysphagia );
• speech ( dysarthria );
• voice production ( dysphonia );
• breathing (if the respiratory center is involved in the pathological process).

All patients diagnosed with bulbar syndrome require emergency transfer to the intensive care unit, connection to a ventilator, and cardiopulmonary resuscitation. In case of dysphagia, it is necessary to organize nutrition through a tube (introduction of nutrients) or intravenous administration of special solutions.

The consequences of acute disseminated encephalomyelitis most often manifest themselves when the peripheral nervous system or spinal cord is involved in the pathological process and are manifested by dysfunction of the pelvic organs.

In some cases, in the acute period, acute urinary retention occurs, which requires the installation of a Foley catheter for up to 7 days.