Diagnosis criteria and types of multiple sclerosis. Radiological isolated syndrome (RIS) Radiological isolated syndrome

Definition. In on standing time The following two concepts have been introduced into clinical practice: radiological isolated syndrome[RIS] and clinically isolated syndrome [CIS] (you can read about CIS). RIS are lesions in the white matter of the brain on MRI that [given their appearance and location] can be interpreted as a demyelinating process and suggest multiple sclerosis (MS) in patients who do not have clinical history and neurological symptoms typical for MS (that is, these lesions are in no way associated with specific clinical symptoms).

Historical reference. The first mention of demyelinating lesions accidentally discovered during autopsy in a patient who had no clinical signs of MS dates back to 1959. Similar publications appeared in the future, and the frequency of such “finds” was about 0.1% of autopsies. Since 1993, in connection with the widespread introduction of MRI into clinical practice, the first mentions of demyelination foci that were accidentally detected during MRI scans in patients examined for other CNS diseases appeared. Then in 2008 in online publications, and in 2009 in printed literature by D. Ocuda et al. the above definition of RIS has been introduced. At the same time, they proposed criteria for RIS, and in 2011 the requirements for lesions in the spinal cord were clarified.

note! As follows from the definition, RIS, or “asymptomatic multiple sclerosis,” is detected incidentally using MRI (the availability of MRI of the brain in recent years has allowed its widespread use in neurology). With the advent of MRI in clinical practice, incidental tomographic findings of demyelination foci also began to be detected in individuals referred for MRI due to headache, traumatic brain injury, endocrine and psychiatric pathology, as well as in individuals who have family ties with patients suffering from definite MS. The incidence of RIS varies according to various sources from 1 to 10% and depends on the population of patients examined, as well as the technical characteristics of the MR tomographs used.

The diagnostic criteria for RIS according to D. Ocuda, 2009 include:

[1 ] the presence on MRI of incidentally detected abnormalities of the white matter of the brain, characterized as homogeneous ovoid foci, meeting the criteria of F. Barkhof (1997) and not corresponding to the vascular pattern;
[2 ] absence in the anamnesis of indications of remitting clinical symptoms suggesting neurological dysfunction;
[3 ] MRI findings are not associated with clinically obvious impairment of functioning in professional, everyday and social terms;
[4 ] exclusion of leukoaraiosis or white matter pathology;
[5 ] abnormal MR findings cannot be explained by another disease.

The criteria for spinal cord damage in RIS according to D. Ocuda, 2011 include:

[1 ] focal or multifocal lesion of the spinal cord with ovoid-shaped foci with clear boundaries;
[2 ] the length of the lesion along the length of no more than two segments of the spinal cord;
[3 ] presence of lesions on more than one MRI slice;
[4 ] MRI findings cannot be explained by another disease.

Note. Diagnostic MPT criteria for MS according to F. Barkhof (1997). For the purpose of even more accurate neuroimaging diagnosis of multiple sclerosis, F. Barkhof et al. proposed criteria according to which lesions must meet 3 of 4 conditions: [ 1 ] one lesion accumulating contrast, or 9 hyperintense lesions in T2 mode; [ 2 ] there must be at least 1 subtentorial lesion; [ 3 ] at least 1 lesion must be located near the cerebral cortex; [ 4 ] there must be at least 3 periventricular lesions. In this case, 1 lesion in the spinal cord is equivalent to 1 lesion in the brain. The lesions must be more than 3 mm in diameter.

Remember! Key and common features for lesions in the brain and spinal cord in RIS are their characteristics as demyelinating, asymptomatic, and the inability to explain the presence of these lesions by any other disease.

read also the article: Neuroimaging in multiple sclerosis(to the website)

read also the post: MRI criteria for multiple sclerosis(to the website)

RIS forecast. Since it is known that in many patients the development of demyelinating diseases of the central nervous system is preceded by an asymptomatic period, the issue of RIS transformation has gained widespread interest, since there are no established protocols in this area on the management of such patients and whether they need to receive (drugs that modify the course of multiple sclerosis). Considering that, according to modern concepts, on the one hand, the greatest effectiveness of disease-modifying drugs is achieved with their earliest administration, on the other hand, RIS is currently considered as a “pre-disease” and has no clinical manifestations and, accordingly, does not require treatment, the question of The prescription of DMTs for people with RIS remains controversial. There are no clinical studies confirming the effectiveness of DMTRS at the stage of RIS. In the current situation, it is of great interest to predict the course of RIS in order to identify the group of people with the highest risk of clinical conversion of the disease.

The incidence of definite MS in patients with RIS is about a third of cases within five years, although there may be risk factors suggesting an earlier transition to the clinical stage of the disease, however, these are currently not defined. It was found that in men in the younger age group, identified RIS is associated with an increased risk of developing clinical symptoms, and this risk is also higher in the presence of foci of demyelination in the cervical and thoracic regions spinal cord. Profile cerebrospinal fluid, ethnicity, and contrast accumulation in areas of demyelination were not significant in predicting future clinical manifestations. According to Totolyan N.A. (2009) when RIS is detected in most patients, new lesions are identified during observation, and in 25 - 30% of cases, significant RS develops, according to et al. (2005). Patients with RIS require dynamic monitoring.

Remember! To date, the clinical and prognostic significance of subclinical lesions in patients with RIS remains controversial. However, the irrefutable fact is that patients with RIS belong to a group with an increased risk of developing definite MS: about 2/3 of patients have progression according to MRI and about 1/3 of patients have the appearance of clinical symptoms within 5 years of follow-up. Predictors of faster transformation of RIS into CIS or clinically significant MS include: [ 1 ] a large number of hyperintense foci in T2 mode, [ 2 ] the presence of foci of infratentorial or spinal localization and [ 3 ] detection of oligoclonal IgG in the cerebrospinal fluid. Thus, the presence of foci in the cervical spinal cord, corresponding changes in the cerebrospinal fluid and a large number of T2 foci on MRI of the brain during the initial scan can serve as an indication for forming a group of patients with RIS for close dynamic observation in order to make a timely diagnosis of definite MS and the onset of pathogenetic therapy.

Materials used:

dissertation for the scientific degree of Candidate of Medical Sciences “The first attack of the demyelinating process (clinically isolated syndrome) in the population of the Rostov region” Tatyana Vasilievna Sycheva; Moscow, 2014 [read];

articles “Radiologically isolated syndrome (MRI criteria and patient management tactics)” by V.V. Bryukhov, E.V. Popova, M.V. Krotenkova, A.N. Boyko; FGBNU " Science Center Neurology", Moscow, Russia; Interdistrict department multiple sclerosis on the basis of the State Budgetary Healthcare Institution “GKB No. 24”, Moscow, Russia; Russian National Research Medical University named after. N.I. Pirogova, Moscow, Russia (Journal of Neurology and Psychiatry, No. 10, 2016) [read];

article “Radiologically isolated syndrome - a possible preclinical stage of primary progressive multiple sclerosis” E.V. Popova, V.V. Bryukhov, A.N. Boyko, M.V. Krotenkova; Interdistrict Department of Multiple Sclerosis, City Clinical Hospital No. 24, Moscow Health Department, Moscow; Federal State Budgetary Educational Institution of Higher Education "Russian National Research Medical University named after. N.I. Pirogov" Ministry of Health of the Russian Federation, Moscow; Federal State Budgetary Institution "Scientific Center of Neurology", Moscow (Journal of Neurology and Psychiatry, No. 8, 2018; Issue 2) [read]

The improvement of existing and introduction of new neuroimaging methods, as well as the development of new diagnostic criteria for multiple sclerosis (MS) have made it possible to sufficiently early detection. The clinical manifestation of MS does not always coincide with the actual time of its onset. In approximately 90% of MS cases, the first episode of demyelination occurs in the form of a so-called “clinically isolated syndrome”, when there are no signs of “dissemination in time”, and signs of “dissemination in space” are either present or absent.

Clinically isolated syndrome ( CIS)

[currently defined as] is a monophasic (i.e., for the first time with a relatively rapid onset) frolicking symptomatology, or more precisely, a frolicking individual clinical episode that is caused by a presumably inflammatory demyelinating disease. "CIS" has a synonym - "first demyelinating episode" (or "first episode of demyelination").

The most common manifestations of CIS are unilateral retrobulbar neuritis, trigeminal neuralgia, transverse myelitis, Lhermitte's sign, bilateral internuclear ophthalmoplegia, paroxysmal dysarthria/ataxia, paroxysmal tonic spasms, or sensory disturbances.

(! ) We should not forget that CIS is not always the first manifestation of MS, but can be a manifestation of diseases such as a tumor of the brain or spinal cord, cervical spondylosis, cerebral vasculitis, sarcoidosis, mitochondrial encephalopathy, etc.

The symptoms detected during CIS serve as objective [clinical] signs of one or more foci of demyelination in the brain or spinal cord (in 50-70% of cases of CIS, multiple subclinical foci of demyelination are detected already at the first MRI); sometimes with monosymptomatic CIS, it is also possible to identify clinically “silent” foci of demyelination (i.e., additionally, signs of multiple lesions of the central nervous system are detected, which confirms dissemination in space). Thus, in CIS, patients may present with different combinations of neurological symptoms and MRI findings; Moreover, despite the fact that it is possible to simultaneously detect multiple clinical/paraclinical manifestations [CIS], however, dissemination over time should not be obvious. In this regard, in modern classification The following types (variants) of CIS are distinguished:

type 1 - clinically monofocal; at least 1 asymptomatic MRI lesion;
type 2 - clinically multifocal; at least 1 asymptomatic MRI lesion;
type 3 - clinically monofocal; MRI may be without pathology; no asymptomatic MRI lesions;
type 4 -clinically multifocal; MRI may be without pathology; no asymptomatic MRI lesions;
type 5 - There are no clinical findings suggestive of demyelinating disease, but there are suggestive MRI findings.

Thus, The criterion for “CIS” is not the semiotic-topic (syndromic) isolation of clinical neurological symptoms, but its (i.e. symptoms) “temporary” A I am limited” - monophasic (i.e., absence of signs of dissemination over time); CIS can be monofocal or multifocal, but always without signs of dissemination over time, i.e. always limited in time - monophasic.

It is difficult to predict whether MS will develop after the first episode, but the currently used McDonald criteria (due to the widespread use of MRI and its increasing role in the diagnosis of MS) allow, in a certain percentage of cases of CIS, to establish a diagnosis of definite MS before the development of a second clinical attack. C. Dalton et al. (2003) found that the use of the McDonald criteria allows more than twice as often to diagnose MS within the first year after detection of CIS, without waiting for a second episode of demyelination. Identification of 9 (nine) or more lesions on a tomogram that do not accumulate contrast agent is an important prognostic sign of MS.

Note! [

INTERNATIONAL NEUROLOGICAL JOURNAL

INTERNATIONAL NEUROLOGICAL JOURNAL 1

INTERNATIONAL NEUROLOGICAL JOURNAL ORIGINAL RESEARCHES/

UDC 616-071+616.832-004.2+616-08+613.95

YEVTUSHENKO S.K.1, MOSKALENKO ML.2, YEVTUSHENKO I.S.3

1 Kharkov Medical Academy of Postgraduate Education

2 Regional Center for Demyelinating Diseases, Donetsk

3 DonNMU im. M. Gorky

FROM CLINICALLY ISOLATED SYNDROME TO RELIABLE DIAGNOSIS OF MULTIPLE SCLEROSIS AND ITS EFFECTIVE THERAPY IN CHILDREN

Summary. The article presents the results of 30 years of experience in the early diagnosis of multiple sclerosis in children using magnetic resonance imaging, visual and cognitive evoked potentials, biochemical and immunological studies of blood and cerebrospinal fluid. The authors describe variants of the onset of this intractable, disabling disease in children. Treatment regimens are presented, including pulse therapy with solu-medrol, plasmapheresis and intravenous immunoglobulin, as well as experience in the use of immunomodulators in children.

Key words: multiple sclerosis, children, diagnosis, treatment.

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the nervous system, which begins mainly at a young (including childhood) age, is characterized by multi-focal lesions of the white matter of the central nervous system, a remitting-progressive course, variability of neurological symptoms and leads to early disability and impairment of quality of life. This is what makes the MS problem socially significant. It is especially important to be wary of MS in neurological pediatric practice, since in recent years there has been a continuing trend towards an increase in the incidence of MS in children. From 1978 to 2005, 53 children aged 7 to 18 years were under our supervision (personal archive), and from 2006 to 2014, definite MS was diagnosed in 63 children in our clinic. The increase in the number of children with MS is associated

both with the increase in incidence and with the improvement of diagnostic capabilities. There are features of the course of the disease; there is a high risk of the formation of persistent irreversible neurological deficit and disability in childhood.

Unfortunately, even today there are many controversial, unclear and unresolved issues in the concept of the origin of multiple sclerosis. And yet, a giant breakthrough has been made in the discovery of the pathogenetic mechanisms of the development of the inflammatory-destructive process in this insidious disease. RS in na-

Evtushenko Stanislav Konstantinovich E-mail: [email protected]

Currently, it is considered as a multifactorial disease with a hereditary predisposition realized through a polygenic system responsible for the immune response and type of metabolism (HLA-BCG). The “trigger link” of the pathological process often includes infectious agents, primarily viruses (EVU, NNU type VI, JC viruses, retroviruses, measles, rubella viruses, etc.). In table 1 shows the homology of peptide 08P 114-120 with peptides of some viruses related to the etiology of multiple sclerosis.

Table 1. Homology of 114-120 peptide OBP with peptides of some viruses (Bronstein I.M. et al., 1999) related to the etiology of multiple sclerosis

Viruses/peptides Amino acid sequence

OSP 114-120 GVAKYRR

Epstein-Barr virus PVAKRRR

Coxsackie IN GVPKNRR

Human immunodeficiency virus I GVAKKLR

Human immunodeficiency virus II GLAKKRR

Herpes simplex virus II GSAKRRR

Geographical and environmental factors are important, having a long-term impact and shaping the characteristics of immunoregulation and metabolism. MS is more common in regions with humid, cool climates compared to wet, dry or cold, dry climates. There is a so-called latitude gradient - an increase in incidence from north to south and from west to east. It is known that the risk of development is associated not only with place of residence, but also with belonging to a particular race or ethnic group. The disease is more common among the white population of the Earth. It has been proven that increasing the level of vitamin D in the body reduces the risk of developing MS (possibly because of this, the incidence of the disease increases with distance from the equator and less exposure to sunlight). Vitamin B is a powerful regulatory factor that suppresses immunopathological reactions (excessive activity of CB3 + T cells, leading to damage to the myelin sheath of neurons).

The factor in the implementation of the pathological process (myelino- and axonopathy, neurodegeneration) are immunopathological and inflammatory mechanisms with the participation of activated T cells, CD25, CD95, cytokines, autoidiotypic antibodies. The basis of the disease is progressive demyelination of the pathways, called “exposed nerve disease,” with a clinical picture of multifocal damage to the brain and spinal cord. There are 5 main stages

immunopathogenesis of MS: activation of T cells and their differentiation into CD4 T cells; proliferation of activated T cells; involvement of B cells and monocytes in the pathological process; migration of T cells across the blood-brain barrier; reactivation of T cells in the CNS and induction of demyelination.

At the same time, axonal damage is the basis for the formation of neurological deficits in the early stages of MS. That is why the pathogenesis of primary and secondary progressive MS involves the progressive loss of axons and their receptors, while the production of cerebral trophic factor is impaired. Unfortunately, we rarely “catch” the first progressive inflammatory reaction that begins, because it initially damages the brain diffusely and manifests itself locally. But already at stage II of the progressive inflammatory-degenerative process, exposed axons become a target for glutamate-mediated cytotoxicity, which leads to axonal degeneration. Determining the level of excitotoxicity is today a marker of prognosis and choice of therapy for MS. Evidence of axonal degeneration is: atrophy of the brain and spinal cord (correlating with neurological deficit according to morphology and magnetic resonance imaging (MRI)), a decrease in the level of the neuronal marker K-acetylaspartate according to MR spectroscopy.

The most important clinical criteria Diagnosis of MS in the age aspect are: onset of the disease in childhood and young age, polymorphism of clinical manifestations, “flickering” of symptoms even throughout the day, wave-like course of the disease, the presence of clinical dissociations. The main (initial) clinical symptoms of MS, unfortunately not in demand by young neurologists, have not lost their significance either: Charcot’s tetralogy (not a triad) - nystagmus, intention tremor, scanned speech, lower paraparesis; Marburg pentad - nystagmus, intention tremor, absence or sluggishness of abdominal reflexes, blanching of the temporal halves of the optic nipples, spastic paresis of the legs; Markov sextad - visual disturbances with narrowing of the fields of vision for colors, vestibulopathy, oculomotor disorders (transient double vision), damage to the pyramidal system, isolated decrease in vibration sensitivity.

If a patient is suspected of having MS, we insist on examining classic clinical symptoms and reflexes that are clearly described reflex arcs, since this makes it possible to clearly identify diffuse organic damage to the nervous system. That is why all children need to undergo a thorough in-depth neurological examination with a study of cranial innervation, including an assessment of the symptoms of posterior and anterior internuclear ophthalmoparesis, supranuclear damage to the cranial nerves (symptoms of oral automatism: proboscis reflex, ankylosing spondylitis,

Oppenheim labial reflex, Karchikyan distance-oral reflex, Toulouse-Wurp reflex, Marinescu-Radovici palmar-submental reflex). In addition to the study of tendon, periosteal and abdominal reflexes, an assessment of surface and vibration sensitivity, muscle-articular sensation, a mandatory check of the Tom-Jumenti, Lhermitte symptom, carpal reflexes (Jacobson-Lask, Bekhterev, Zhukovsky, Rossolimo, Venderovich, Wartenberg) is required. pathological foot signs (Babinsky, Oppenheim, Chaddock, Puusep, Rossolimo), automatism reflexes (Chlenov - McCarthy, Astvatsaturov, Razdolsky), tests for ataxia and asynergia (simple

and sensitized Romberg test, knee-heel test, Stewart-Holmes test, Babinsky asynergy test).

The diagnosis of all patients was established according to the criteria of C.M. Poser, 1983, W.J. McDonald, 2001, 2005, 2010 (Tables 2, 3).

One of the most important signs Multiple sclerosis is a clinical dissociation. The main clinical dissociations in MS in children have been identified:

1. High reflexes with clonus with mild to moderate impairment of range of motion.

2. Impaired vibration sensitivity in the arms and legs with incoordination of dynamic performance

Table 2. Diagnosis criteria for multiple sclerosis (C.M. Poser et al., 1983)

Clinically reliable 2 exacerbations + 2 clinical lesions; 2 exacerbations + 1 clinical lesion + 1 paraclinical lesion (registered using MRI or evoked potentials)

Reliable, laboratory confirmed 2 exacerbations + 1 clinical focus or paraclinical focus + oligoclonal bands or increased synthesis of 1dO in the CSF; 1 exacerbation + 2 clinical lesions + oligoclonal bands or increased synthesis of 1dO in the CSF; 1 exacerbation + 1 clinical focus + 1 paraclinical focus + oligoclonal bands or increased synthesis of 1dO in the CSF

Clinically probable 2 exacerbations + 1 clinical focus; 1 exacerbation + 2 clinical lesions; 1 exacerbation + 1 clinical focus + 1 paraclinical focus

Probable, laboratory confirmed 2 exacerbations + oligoclonal bands or increased synthesis of 1dO in the CSF

Clinical picture Additional data

> 2 exacerbations, objective clinical data on the presence of > 2 lesions Not required

> 2 exacerbations, objective clinical evidence of the presence of 1 lesion and reasonable clinical evidence of a previous exacerbation in history Not required

> 2 exacerbations, objective clinical data about the presence of 1 lesion Dissemination in space, which can be confirmed by: - the presence of > 1 T2-hyperintense lesion located in at least 2 of 4 zones characteristic of MS (juxtacortical, periventricular, infratentorial, spinal cord) or - waiting for the next clinical exacerbation

1 exacerbation, objective clinical evidence of the presence of > 2 lesions Dissemination over time, which can be confirmed by: - the presence on a subsequent MRI of a new T2-hyperintense lesion and/or a lesion accumulating contrast, compared with the previous MRI, regardless of the timing of the baseline scan or - the presence on MRI of an asymptomatic lesion(s) accumulating contrast and a lesion not accumulating contrast or - waiting for the next clinical exacerbation

Table 3. Criteria for establishing a diagnosis of definite multiple sclerosis

(W.J. McDonald, 2010)

End of table. 3

1 exacerbation, objective clinical data about the presence of 1 lesion (clinically isolated syndrome - CIS) Dissemination in time and space: - > 1 T2-hyperintense lesion located in at least 2 of 4 zones characteristic of MS (juxtacortical, periventricular, infratentorial , in the spinal cord) or - anticipation of the next clinical exacerbation and - the presence on a subsequent MRI of a new T2-hyperintense lesion and/or a lesion accumulating contrast, compared with the previous MRI, regardless of the timing of the baseline scan or - the presence of an asymptomatic lesion on MRI ( ov), accumulating contrast, and a lesion that does not accumulate contrast, or - waiting for the next clinical exacerbation

Absence of exacerbations with gradual progression of neurological symptoms Progression of the disease over 1 year (retrospectively or prospectively) and the presence of at least 2 of 3 criteria: - 1 T2-hyperintense lesion located juxtacortical, or periventricular, or infratentorial; - > 2 T2 hyperintense lesions in the spinal cord; - characteristic changes in the CSF (presence of oligoclonal IgG groups in the CSF or increased IgG index)

mic tests while maintaining joint-muscular sensation (tuning fork 128 Hz).

3. Pathological reflexes with reduced knee and carporadial reflexes.

4. Pronounced pyramidal symptoms in the form of lower paraparesis with decreased muscle tone.

5. Varying degrees of hyperreflexia in the upper and lower extremities.

6. Dissociations between superficial and deep abdominal reflexes.

7. Pallor of the temporal half of the optic discs, atrophy with normal visual acuity or a drop in visual acuity with normal fundus.

8. The presence of pelvic disorders in mildly expressed pyramidal syndrome.

9. Diffuse decrease in muscle tone and identification of the “jackknife” symptom.

10. MRI-negative onset of MS (no changes on MRI with clear clinical manifestations of multifocal brain damage).

11. The presence of multiple lesions on MRI with a monosymptomatic onset.

12. The appearance of lesions on MRI and their regression do not coincide in time with the clinical stages of exacerbation and remission (discrepancy between the clinical severity and detected lesions of the brain).

13. Discrepancy between the clinical and neurological picture and the localization of identified foci of demyelination in the brain according to MRI data.

Typical clinical manifestations of MS in children are: motor and ataxic disorders, vibration sensitivity disorders, brainstem, visual and cortical symptoms, psychoneuro-

gical disorders and progressive cerebral and peripheral autonomic failure.

Based on 30 years of experience in monitoring children suffering from multiple sclerosis, we have identified 4 variants of its debut. These provisions, to a certain extent, distinguish MS in children from MS in adults.

Clinically isolated syndrome as the debut of multiple sclerosis in children with its monosymptomatic onset (according to our data, up to 50% of patients)

1. Retrobulbar optic neuritis (about 35%, according to our data).

2. Sensitive disorders in the form of a feeling of numbness of the trunk, limbs and/or face (about 25%).

3. Paresis of the upper or lower limb, including afferent paresis with the appearance of a feeling of awkwardness in the limb (about 15%).

4. Oculomotor disorders with diplopia (about 8%).

5. Ataxia (about 3%).

6. Facial nerve neuropathy (about 3%).

7. Cephalgia with cerebrospinal fluid hypertension syndrome (about 3%).

8. Dysfunction of the pelvic organs in the form of urinary retention (about 3%).

9. Dizziness (up to 2%).

10. Epileptic syndrome (up to 1%).

11. Neuropsychiatric disorders (acute psychotic states, aphasia, cognitive impairment) (up to 1%).

12. Dysarthria (as a manifestation of pseudobulbar syndrome) (up to 1%).

MRI can reveal both single and multiple foci of demyelination in the brain and/or spinal cord. According to our data, cerebral

Figure 1. Foci of demyelination in the brain and spinal cord

The monosymptomatic form of MS is observed in 33% of children, and the cerebrospinal form - in 67% of patients.

Initial symptoms of polysymptomatic debut of multiple sclerosis in children (according to our data, up to 44% of patients)

We observed in our patients a combination of ataxia, paresis in the limbs, sensory disorders, retrobulbar neuritis, oculomotor disorders, dizziness, dysarthria, dysfunction of the pelvic organs and cognitive impairment.

1. Opticomyelitis (optic neuropathy + lower paraparesis + dysfunction of the pelvic organs).

2. Retrobulbar optic neuritis + paraparesis.

3. Ataxia + retrobulbar optic neuritis + paraparesis.

4. Ataxia + lower paraparesis.

5. Ataxia + paraparesis + dysfunction of the pelvic organs.

6. Ataxia + paraparesis + cognitive impairment.

7. Ataxia + oculomotor disorders (usually in the form of abducens nerve neuropathy) + hemiparesis.

8. Ataxia + sensory disturbances (in the form of numbness of the trunk, limbs and/or face).

9. Ataxia + paraparesis + epileptic syndrome.

MRI can reveal both single and

multiple foci of demyelination in the brain and/or spinal cord. According to our data, the cerebral form of MS with a polysymptomatic onset is observed in 17% of children, and the cerebrospinal form - in 83% of patients.

Erased initial symptoms without a significant neurological picture and complaints, but with gross randomly detected demyelinating foci of brain damage on MRI (according to our data, up to 2% of patients)

At the time of the examination, the patients did not show any special complaints!

Examples of situations in which we diagnosed MS in children who had no complaints at the time of examination:

a) during a medical examination, the pediatric neurologist revealed high reflexes (without complaints!) and referred the child for consultation to the clinic. MRI shows periventricular confluent foci of demyelination;

b) the boy accidentally received a light blow to the head with a book. Moderate headaches appeared, which went away within a day. 20 days after that, I accidentally hit my head again. The headaches reappeared. Status: posterior nuclear ophthalmoparesis, Marinesko-Radovici symptom ++,

increased reflexes. MRI shows 4 foci of demyelination. After administration of Magnevist, MRI revealed active lesions (Fig. 1);

c) in a stuffy room, a 12-year-old girl lost consciousness. There were no further complaints. In the neurological status there is latent posterior ophthalmoparesis. Increased reflex, decreased vibration sensitivity up to 12 seconds. Studies were carried out: examination of the fundus, EEG, ECG, ultrasound examination of the vessels of the neck and head - no pathology was detected. MRI revealed foci of demyelination in both hemispheres of the brain and the spinal cord (Fig. 1).

MRI-negative onset of MS (typical symptoms of MS, but no pathology was detected on MRI at the time of examination) (according to our data, up to 4% of patients)

In such cases, it is necessary to study the cerebrospinal fluid with a polymerase chain reaction to detect the DNA of herpes group viruses and determine the intrathecal synthesis of immunoglobulin O. It is necessary to study visual evoked potentials and long-latency cognitive potentials to detect hidden foci. This form should be considered probable multiple sclerosis. For symptoms of manifest pyramidal and ataxic syndrome (or other manifestations), recommend treatment (corticosteroids, immunoglobulins for intravenous administration, acelysin, milgamma).

There are 4 types of MS, typical for both adults and children:

1. Relapsing-remitting. It is characterized by a wave-like course with clearly defined exacerbations and subsequent complete or partial restoration of impaired function without signs of progression during the period of remission. This type of course is observed in 90% of children with MS. early stages diseases.

2. Primary progressive (from the very beginning of the disease there is a steady progression, without clear periods of exacerbation and remission).

3. Secondary progressive (after the stage of exacerbations and remissions, the stage of chronic increase in neurological symptoms begins).

4. Progressive with exacerbations (against the background of constant progression, clear periods of exacerbation occur, after the relief of which there is a gradual increase in the symptoms of the disease).

We observed malignant forms of MS in children (in one case with a fatal outcome).

Clinical example.

Patient A., 11 years old, first came to our clinic with complaints of strabismus and double vision, which appeared about 3 weeks ago. Upon admission, the neurological status revealed posterior internuclear ophthalmoparesis, monocular nystagmus of the left eye, convergent strabismus due to the right eye, horizontal diplopia; decreased abdominal reflexes, knee, Achilles reflexes are high, S D, mild paresis of the left limbs. No pathological changes were noted in the fundus. A narrowing of the visual fields to colors was revealed. An MRI of the brain revealed no pathology. During therapy, diplopia resolved. The girl was discharged with a diagnosis of brainstem demyelinating encephalitis. A monosymptomatic onset of multiple sclerosis was suspected in the absence of changes on MRI of the brain.

Subsequently, the child begins to experience frequent (every 2-5 months) exacerbations of the disease in the form of retrobulbar neuritis (unilateral and bilateral), dysfunction of the pelvic organs, lower paraparesis and tetraparesis, ataxia; atrophy of the optic nerves develops. Dynamics of the MRI picture: a single small focus of demyelination appears on the right in the projection of the bridge, then foci of demyelination are determined in the area of the bridge on the right up to 0.5 cm, in the area of the corpus callosum up to 0.3 cm and periventricular zones of demyelination up to 0.45 cm wide. MRI of the cervical spinal cord revealed foci of demyelination ranging from 0.3 cm to 0.4 cm in width from the level of the C2 vertebral body to the upper edge of the C5 vertebral body. Subsequently, MRI of the spinal cord revealed multiple confluent lesions up to 1.0 cm throughout the cervical spine, as well as multiple zones of demyelination in the thoracic and lumbar regions. At the initial stages of therapy, an effect was observed in the form of a significant reduction in neurological symptoms, but the duration of remissions decreased, exacerbations were polysymptomatic, and after 4 years of illness the child died with clinical signs of cerebral edema. An autopsy revealed foci of demyelination. The main changes were noted in the cervical and upper thoracic spinal cord.

It should be noted that children more often (up to 75% of cases) have a benign form of MS.

The most typical features of the course of MS in children are the following:

1. In children, monosymptomatic initial manifestations of MS are more common (up to 65%).

2. The most vulnerable age is 11-14 years, more often in girls (m/d = 1: 3).

3. In children at the onset of the disease, even with severe polysymptomatic manifestations, full recovery neurological deficit.

4. At the initial stage, a remitting course prevails with frequent exacerbations and short-term remissions (2-4 months).

5. During the period of exacerbation, weakness in the lower extremities (pyramidal syndrome), ataxia, and headache are noted.

6. Only 20% of patients have complaints about disorders of the pelvic organs.

7. Almost all patients have a positive reaction to the administration of corticosteroids.

8. The prognosis (up to 75% of cases) can be favorable, without significant exacerbations for 5-10 years with proper therapy.

9. 20% of the entire population of children with MS have primary progressive forms that are difficult to treat.

Three degrees of PC recognition reliability according to McAlpin (2000):

Reliable MS - progressive lower paraplegia, a combination of pyramidal and cerebellar disorders, damage to the optic nerve, the presence of remissions;

Probable MS - multifocal onset with good remission and “flickering” of the same symptoms without signs of relapse and progression for a year or more;

Doubtful MS - progressive lower paraplegia, absence of clear remissions.

The following stages of MS are distinguished: exacerbation (exacerbation), remission, chronic progression, stabilization, debut of MS, pseudo-exacerbation (decompensation).

Functional systems are scored using the Kurtske scale (Expanded Disebility Status Scale, EDSS, 1983).

An example of a diagnosis: multiple sclerosis, cerebrospinal form, remitting course, acute stage with lower paraparesis, ataxia, partial atrophy optic nerves, decreased vibration sensitivity, with multiple foci of demyelination in both hemispheres of the brain according to MRI, severity according to EDSS 3.5 points (pyramidal system - 3 points, cerebellar functions - 3 points, brainstem - 2 points, sensory - 2 points, visual functions - 1 point, pelvic organ functions - 0 points, cerebral functions - 1 point).

The diagnosis of MS in children is more clinical than instrumental, and should be made by a council of competent doctors and researchers involved in this problem. Often, at the onset of MS, children are referred to us for examination with other diagnoses (retrobulbar neuritis, encephalitis, transient cerebrovascular accident, etc.).

It is always necessary to carry out a differential diagnosis of MS with other diseases of the nervous system. We diagnosed 87 (out of 203 referred to the clinic with suspected MS) children aged 7 to 17 years with the following diseases:

Disseminated encephalomyelitis - 33;

Brain tumors - 10;

Spinal cord tumors - 3;

Tuberous sclerosis - 4;

Neurofibromatosis type 1 with spinal cord compression - 2;

Paraplegia plus:

Strumpel's disease - 4;

Charleois - Sajenot - 2;

Vascular malformation of the spinal cord/brain - 3;

Dandy-Walker syndrome - 2;

Olivopontocerebellar degeneration - 4;

Adrenoleukodystrophy - 3;

Neuroborreliosis - 2;

Leber's disease - 2;

Hepatolenticular degeneration - 5;

HIV-associated leukoencephalopathy - 2;

Cerebral vasculitis - 3;

Mitochondrial encephalomyopathy (Leigh's disease) - 2;

Hereditary leukoencephalopathy with hyperkeratosis - 1.

The differential MRI diagnosis of foci of demyelination, dismyelination and metabolic disorders in children with the following diseases:

Subacute sclerosing panencephalitis Van Bogart;

Acute disseminated encephalomyelitis;

Neuroborreliosis;

Adrenoleukodystrophy;

Leber optoencephalitis;

Multifocal leukoencephalopathy;

Devic's optomyelitis;

Schilder's leukoencephalitis.

Diagnostic value of clinical instruments

tal indicators for multiple sclerosis:

1. Clinical manifestations - 75%.

2. Magnetic resonance imaging of the brain and spinal cord - 85% (Fig. 2).

The most common localization of demyelination foci in the brain in children observed in the clinic, according to MRI data:

Periventricular - 100% of cases;

Subcortically in the hemispheres of the brain - 83%;

In the cerebellum - 42%;

IN corpus callosum - 24 %;

In the cerebral peduncles - 22%;

In the trunk - 20%.

When only periventricular lesions are detected on MRI (especially in the absence of clinical manifestations of multifocal brain damage), there is often an assumption about the perinatal genesis of the lesions. This requires repeating the MRI examination with intravenous contrast (Gadovist, Magnevist) and mandatory MRI monitoring after 6 months.

Depending on the time of onset of the disease in the same patient, it is possible to distinguish three types of plaques based on MRI data:

Acute (active, new foci of demyelination), old (permanent, chronic, inactive foci);

Old chronic lesions with signs of temporary (immanent) activation along the periphery of the plaque, which can be regarded as a continuation of plaque growth;

Shadows of plaques (like penumbra in ischemic stroke) are an area of myelin thinning.

Figure 2. Foci of demyelination in the brain and spinal cord

Figure 3. Visual evoked potential study for chess pattern reversal

MRI studies show that the pathological process in MS exhibits slow but almost constant activity. According to MRI monitoring, it is possible to register new lesions or enlargement of old ones up to 10 times a year. That is why the factor of constant activity of the demyelinating process determines the need for continuous treatment of MS. The absence of new symptoms during the period of clinical remission of MS does not reflect the stabilization of the pathological process, but, more likely, is due to the absence of gross impulse conduction disturbances in the lesions or the localization of lesions in functionally insignificant areas of the brain. In this regard, it is mandatory to conduct an MRI with intravenous contrast and study evoked potentials, which will determine the degree of activity of the process.

However, correspondence between the severity of MS and the intensity of damage to the demyelinating process of the brain and spinal cord according to MRI data is observed only in 65-70% of cases.

3. Visual evoked potentials and long-latency evoked cognitive potentials to a significant stimulus - 80%.

Visual evoked potential testing for checkerboard pattern reversal can identify clinically silent lesions in patients with suspected demyelinating processes (Fig. 3).

The study of long-latency cognitive potentials to a significant stimulus allows for an objective quantitative assessment of the perception and processing of information by the brain (Fig. 4).

4. Reduction of vibration sensitivity (tuning fork 128 Hz) - 80%.

5. Transcranial magnetic stimulation allows you to determine not only the levels of damage pyramid path, but also the severity of the lesion (Fig. 5).

7. Laboratory research: oligoclonal IgO - 90%, FLC-c content - 95%, FLC-c index - 97%.

15-1-1-1-1-1-1-1-1-1-1

О 100 200 300 400 500 600 700 S00 900 1000

Figure 4. Study of long-latency cognitive potentials to a significant stimulus

Figure 5. Transcranial magnetic stimulation

Unfortunately, these studies are not readily available in medical practice. We consider an alternative to determine the permeability of the blood-brain barrier and intrathecal synthesis of IgO. We have introduced a method for determining albumin and immunoglobulin O, their ratio in the blood and cerebrospinal fluid, which is a definite neurogenic marker, and in some cases confirms the specificity of lesions of the nervous system, especially when autoimmune diseases are suspected. An increase in the IgO/albumin ratio is observed in 80% of cases of multiple sclerosis.

To a certain extent, the level of intrathecal synthesis of ]eO can be considered equivalent to oligoclonal IgO. Increased intrathecal

IgG synthesis indicates an inflammatory, predominantly autoimmune lesion of the central nervous system.

A mandatory examination pattern is to determine the degree of immune tension, as well as the severity of the autoimmune inflammatory process and demyelination. The most significant populations of CD cells in the study of cellular immunity in children with suspected MS:

CD3 (T-lymphocytes) - mature T-lymphocytes, total number;

CD4 (T-helpers) - are responsible for the maturation of T-killer cells, activation of the cytotoxic function of macrophages, secretion of interleukins and other cytokines;

CD8 (T-suppressors) - inducers that inhibit the immune response (inhibit the production of antibodies due to a delay in the proliferation and differentiation of B-lymphocytes);

CD4/CD8 - immunoregulatory index;

CD20 (B-lymphocytes) - participation in humoral immune reactions, antibody production;

CD16CD56+ (NK cells - natural killers) - destruction of cells lacking molecules of the major histocompatibility complex on the surface of malignant cells and cells modified by the virus;

CD3+CD25+ (activated T-lymphocytes) - stimulation of antibody formation and cytotoxicity;

CD22+CD25+ (activated B lymphocytes) - an indicator of the activity of the immune response during autoimmune and atopic inflammation;

CD14 (monocytes, macrophages) - binding of macromolecules in the early stages of inflammation;

CD95 (apoptosis factor) - activity of the apoptotic process;

HLA-DR (activated lymphocytes) are mature T lymphocytes.

The most frequently observed decrease in the level of CD4 and CD8, increase in the level of CD95 lymphocytes. Increased suppressor activity of lymphocytes (equivalent to T-autoreactivity of cells), activation of killer T cells, depression of immunoglobulin G in the blood, but with an increase in intrathecal synthesis of IgG and a decrease in the IgG/albumin index quite reliably indicate the activation of the inflammatory process. These indicators form the basis for choosing treatment regimens for MS in children.

7. A study of cerebrospinal fluid with a polymerase chain reaction to detect the DNA of herpes viruses (HSV types 1-2, HHV type 6, CMV, EBV) is necessary not from the point of view of clarifying the etiology of MS, but to determine the correct treatment tactics . According to our data, in 5-7% of cases in children with MS there is an association with viruses, which requires specific antiviral therapy. A technique has been mastered for determining the DNA of human polyomavirus 2 (JC virus, JCV) in blood and cerebrospinal fluid. This is of great importance for the correct choice of immunomodulatory therapy, taking into account the possible

the possibility of JCV activation with the development of progressive multifocal leukoencephalopathy.

Treatment of MS is a complex and sequential process, the stages of which are:

1) timely detection of the disease in the early stages and establishment of a reliable diagnosis of MS;

2) relief of exacerbations with corticosteroids;

3) prevention of exacerbations with the help of modern immunomodulators (long-term modified therapy);

4) carrying out symptomatic therapy and rehabilitation.

Therapy for the onset and exacerbation of MS in children

When DNA of herpes viruses is detected in the cerebrospinal fluid and/or blood using the polymerase chain reaction method (HSV type 1-2, HHV type 6, CMV, EBV) at the stage of diagnosing MS, it is advisable to conduct an intravenous course of acyclovir in a single dose of 10 mg/kg (no more than 250 mg) 3 times a day for 5-7 days.

At the onset of MS or exacerbation of the disease, therapy is carried out with solu-medrol (methylprednisolone) 10-20 mg/kg (no more than 1000 mg) intravenously drip every other day No. 3-5 in combination with plasmapheresis (2-3 procedures), especially if a high level is detected circulating immune complexes in the blood and increasing the permeability of the BBB. In case of incomplete restoration of functions, switch to oral administration of corticosteroids (metipred, medrol) 16-24 mg with a gradual dose reduction or a course of synacthen depot (0.5-1.0 mg IM once a week No. 8, then 1 once every 2 weeks No. 4).

Acelysin is used 0.5-1.0 g intramuscularly once a day No. 5-7 (reduces the production of prostaglandins and stimulates the synthesis of anti-inflammatory interleukins).

Intravenous immunoglobulins (IVIG) are used to treat patients with MS. IVIGs are a 100% biological blood product and are a fairly safe method of therapy approved for use in children.

Several mechanisms of action of IVIG in autoimmune diseases have been described: suppression of the complement system; inhibition of the production of proinflammatory cytokines by monocytes; stimulation of the production of anti-inflammatory cytokines by monocytes and macrophages; binding to antibodies to autoantigens and blocking them; decreased production of autoantibodies (as a result of binding of anti-idiotypic antibodies contained in IVIG to antigenic determinants and immunoglobulins G and M on B lymphocytes); induction of apoptosis of B and T cell lines; inhibition of superantigen-mediated T cell activation. IVIG also contains antibodies to variable and stable regions

CD4, which determines the immunoregulatory effect of the drug. IVIGs suppress the autoimmune process in MS by inhibiting excessively activated complement, stimulate anti-inflammatory interleukins, suppress antibodies to AMDA receptors, reduce the activity of the cytokine TNF and stimulate the proliferation of oligodendrocytes, which enhance myelin production. To date, several randomized, placebo-controlled studies have been conducted to evaluate the ability of IVIG to prevent exacerbations, disease progression, reduce MRI activity in various types of MS, as well as the ability of IVIG to stimulate remyelination in the central nervous system and restore lost functions in multiple sclerosis. It was shown that the frequency of exacerbations of MS with the use of IVIG decreased by 48-63% compared with placebo. Patients with a clinically isolated syndrome at high risk of developing MS who received IVIG for a year had a 64% reduction in the likelihood of developing definite MS. The effectiveness of IVIG in relapsing-remitting MS has been proven (evidence class I).

Studies have been conducted of MRI changes in patients using IVIG. A decrease in the number of new and active lesions, a slowdown in the increase in lesion volume, and a slowdown in brain atrophy were shown in patients receiving IVIG compared with placebo.

According to the Guidelines of the European Federation of Neurological Sciences, IVIG is recommended as 2nd or 3rd line therapy in patients with relapsing-remitting MS who are intolerant to other therapy, as well as during pregnancy and breastfeeding, when no other approved therapy exists. IVIG remains the only approved drug for the treatment of MS during pregnancy and while breastfeeding. The protocol of standards of care for patients with MS in Russia includes a course of IVIG (evidence class II). It is recommended to administer the drug once a month (dose 0.15-0.4 g/kg) for 2 or more years.

To treat our patients, we use immunoglobulin for intravenous administration produced in Ukraine (manufactured by Biopharma, Kiev) - bioven-mono (5% solution) or bioven (10% solution). The drug is administered at a dose of 0.4 g/kg every other day No. 3-5 (depending on the severity of MS), followed by repeating the course after 3-6 months.

The use of IVIG is an alternative to long-term immunomodulatory therapy with interferon-beta and glatiramer acetate.

Treatment regimens for children with MS at the onset of the disease and during exacerbations:

1. For moderate severity of exacerbation:

Pulse therapy (solu-medrol or methylprednisolone 500-1000 mg intravenously every other day No. 3-5).

2. In case of severe exacerbation with pronounced changes in the immunogram in combination with a high level of CEC:

Pulse therapy + plasmapheresis (2-3 procedures every other day)

Pulse therapy + plasmapheresis + intravenous administration of immunoglobulin 0.4 g/kg every other day No. 3-5.

3. In case of severe exacerbation with changes in the immunogram and an unexpressed increase in the level of CEC):

Pulse therapy + intravenous immunoglobulin.

In the initial stages of MS, it is especially difficult to predict the next exacerbation of the disease, especially in childhood. It is for this reason that the short-term and long-term prognosis of the disease can be difficult. The most informative indicator of MS prognosis is the course of the disease in the first 3-5 years, as well as the effectiveness of the treatment. According to the literature, among adults, a benign course of the disease with rare exacerbations is observed in 20% of patients, a remitting course with frequent exacerbations - in 30%, a progressive course - in 50%. Mortality 25 years after the onset of the disease ranges from 15 to 26%. Information on the incidence of mild and severe MS in children is extremely contradictory. But at the same time, severe MS in children is becoming more common. According to our data, a severe course of MS with frequent exacerbations and the rapid formation of a persistent neurological deficit in children is observed in 25% of cases, and the transformation of relapsing-remitting into a secondary progressive course in the first 2 years of the disease is observed in 13% of patients.

Today, a neurologist has a range of modern immunomodulatory drugs that can change the course of MS: reduce the frequency of exacerbations, slow down the increase in disability and prevent premature death. However, it has not yet been possible to radically solve the problem of treating this serious disease. Unfortunately, this is hampered by the insufficiently studied issue of early reliable diagnosis and treatment of children with MS. Currently registered drugs for the treatment of patients with MS are not always effective and are not without side effects.

The main principle of therapy for patients with MS today is the early administration of immunomodulators to prevent exacerbations, stabilize the condition, prevent transformation into a progressive course and slow down the increase in disability. For this purpose, it is currently generally accepted for the treatment of both adult patients and children to prescribe interferon beta-1b (Betaferon, Betfer-1b), interferon beta-1a (Rebif, Avonex, Betfer-1a) and glatiramer acetate (Copaxone , glatimer) (Table 4).

Table 4. Drugs for immunomodulatory therapy in patients with MS

IFN-ßnb (betaferon) 8 million IU 16 ml IU Every other day, subcutaneously

IFN-|-1a (Rebif) 22 mcg (6 million IU) 44 mcg (12 million IU) 3 times a week, subcutaneously

IFN-|-1a (avonex) 6 million IU once a week, intramuscularly

Glatiramer acetate (Copaxone) 20 mg Daily, subcutaneous

The main mechanisms of action of P-interferons (betaferon, Rebif, Avonex):

Inhibition and modulation of the activity of the cytokine gamma interferon (the main pro-inflammatory cytokine that contributes to exacerbations of MS);

Inhibition of costimulation molecules necessary for the activation of T lymphocytes and increased apoptosis of autoreactive T lymphocytes;

Strengthening the suppressor activity of T-lymphocytes;

Reduced expression of major histocompatibility complex molecules on antigen-presenting cells;

Blockade of matrix metalloprotease and adhesion molecules, which prevents the penetration of activated cells into the brain tissue through the blood-brain barrier.

This immunomodulatory effect allows us to weaken the effect of antibodies to the main components of myelin, which ultimately reduces the activity of the inflammatory process in MS.

The main mechanisms of action of glatiramer acetate (a standardized mixture of synthetic peptides of four amino acids: L-alanine, L-glutamine, L-lysine, L-tyrosine):

Formation of a close connection with the trimolecular complex of the membranes of antigen-presenting cells with the formation of a false target for T-lymphocytes;

Proliferation of specific T cells that suppress the activity of other autoaggressive cell lines and are able to penetrate the blood-brain barrier and create background suppression;

Apoptosis of activated T1 lymphocytes;

Suppression of the proinflammatory effect of γ-IFN and IL-2;

Stimulation of the production of neurotrophic factors (neuroprotective effect).

A number of randomized multicenter studies have been conducted to study the effectiveness and safety of immunomodulatory drugs in adults: BEYOND, BENEFIT, BECOME, EVIDENCE, INCOMIN, OVIMS, REGARD, BICC. In the clinic of nervous diseases of Donetsk National Medical University in 2001-2003. Clinical testing of betaferon was carried out in young people, including children. Results were obtained indicating good tolerability of the drug.

Over the past 6 years, 24 children under our supervision received immunomodulatory therapy:

Interferon-beta-1b (betaferon) - 10 patients;

Interferon beta-1a (Rebif, Avonex) - 6 children;

Glatiramer acetate (Copaxone) - 8 patients.

A positive effect in the form of lengthening was noted

remissions, satisfactory tolerability of therapy. Only 1 patient out of 10 receiving betaferon needed to discontinue the drug due to adverse reaction(cardiopathy). Because of allergic reaction In 2 children, immunomodulatory therapy was discontinued for Copaxone. In 6 patients (25%), despite the use of immunomodulators, the disease became secondary progressive. For the remaining patients, immunomodulatory therapy was continued after their transition to the adult category of patients.

Two children for whom immunomodulators were discontinued due to the transformation of the course of MS from relapsing-remitting to secondary progressive were given courses of immunostatic therapy with mito-xantrone (12 mg/m2 body intravenously):

In 1 child (a 17-year-old girl) there was a temporary deterioration in condition (up to 2 months) with subsequent stabilization;

The second patient (a 16-year-old girl) has a stable remission with a decrease in neurological deficit.

Based on literature data and our own experience, we consider it advisable to prescribe immunomodulatory therapy in childhood only after establishing a reliable diagnosis of MS and a preliminary thorough somatic examination. We have seen that starting therapy with minimal doses and slower (than in adults) dose titration provide better tolerability of immunomodulatory drugs.

IN Lately A number of new drugs have appeared for the treatment of patients with MS: tysabri (natalizumab), rituximab, alemtuzumab, teriflunomide, fingolimod (Gilenia), laquinimod, BG12. The testing of these drugs in children with MS is just beginning. And in adults, when using these drugs, not only side effects have been recorded, but also serious deterioration in health. In particular, during treatment with natalizumab, the development of progressive multifocal leukoencephalopathy due to activation of human polyomavirus 2 (JC virus) against the background of decreased immunity has been described.

Table 5. Symptomatic therapy for MS

Clinical symptoms Therapy

Spasticity ^rdalud, baclofen, valproates (Depakine, Konvulsofin, Konvulex), glycine Dysport (for severe spasticity) Therapeutic gymnastics

Imperative urges to urination, urinary incontinence and incontinence Oxybutin (driptan, sibutin) Adiuretin SD Pelvic floor muscle training

Difficulty urinating Galantamine, neuromidin Magnetic and electrical stimulation Bladder

Ataxia and tremor Milgamma, Magne-B6, glycine, tenoten, cognum Carbamazepine Therapeutic gymnastics

Dizziness Betaserc, Fezam, Thiocetam

Intracranial hypertension syndrome Diacarb, glycerin, L-lysine escinate

Syndrome chronic fatigue, neurosis-like conditions, cognitive impairment Semax, adaptol, noofen, glycine, stimol, gamalate-B6 Cognum

The registration of the drug Movectro (cladibrine) was canceled due to cases of cancer in patients receiving this drug.

After the exacerbation is relieved, neuroprotective therapy (Semax, Thiocetam, Cerebrolysine), Essentiale, Nucleo CMF forte (Keltican), treatment with nicotinamide, lipoic acid, cytoflavin, carnitine chloride (Carniel, Agvantar, Elkar) is carried out. Given the emotional and cognitive impairments characteristic of children with MS, the need injection drugs (which creates an additional stressful situation for the child), drugs that combine nootropic and sedative effects - hopantenic acid preparations (Cognum) - have recently been widely used. They have nootropic and anticonvulsant effects, increase the brain's resistance to hypoxia and the effects of toxic substances, stimulate anabolic processes in neurons, combine a sedative effect with a mild stimulating effect, and reduce the manifestations of extrapyramidal disorders and neurogenic urination disorders.

Symptomatic therapy is presented in table. 5.

The accumulated many years of experience of the staff of Donetsk National Medical University named after. M. Gorky on the diagnosis and treatment of children with MS and other demyelinating diseases made it possible to organize in 2011, on the basis of the neurological department of the regional children's clinical hospital, the Center for demyelinating and degenerative diseases of the nervous system in children. The goal of the center is to ensure timely diagnosis and improve the quality of treatment for children with demyelinating and degenerative diseases of the nervous system.

The center provides specialized assistance to children with multiple sclerosis, multiple

encephalomyelitis and other forms of acute, subacute and chronic disseminated demyelination; demyelinating polyradiculoneuropathy; hereditary neuropathies; myasthenia; hereditary ataxias; degenerative diseases with extrapyramidal disorders (including juvenile form of Parkinson's disease, dystonia), spinocerebellar degeneration and other degenerative diseases of the nervous system.

To diagnose these diseases, the Center, in addition to clinical ones, uses instrumental and laboratory examination methods:

MRI of the brain and spinal cord with intravenous contrast (Gyroscan Intera T10 device, Holland);

Study of evoked visual potentials for reversal of a chess pattern (computer diagnostic complex “Expert”, Tredex, Ukraine);

Study of long-latency cognitive potentials to a significant stimulus (computer diagnostic complex “Expert”, Tredex, Ukraine);

Electroencephalography (device "Tredex", Ukraine) and electroencephalographic monitoring during wakefulness and sleep (device "Axon M", Ukraine);

Electroneuromyography (Neuro-MVP-micro device, Russia);

Transcranial magnetic stimulation;

Studies of cellular and humoral immunity (laboratories of the CSTO, “New Diagnostics”, “Diagnostic Pasteur”);

Study of cerebrospinal fluid with polymerase chain reaction to detect DNA of cytomegalovirus, Epstein-Barr virus, herpes viruses types 1-2 and 6, JC virus (JCV, human polyomavirus type 2) and Rubella virus RNA (Novaya laboratories) diagnostics", "Diagnostician Pa-

erased"). In 2013, for the first time in Ukraine, a methodology for determining JCV was mastered;

Study of the permeability of the blood-brain barrier: level of albumin, immunoglobulin G, indicator of intrathecal synthesis of IgG (New Diagnostics laboratory).

A register of children in the Donetsk region with definite MS, as well as children being observed for probable MS, has been created. Since its founding, the center has been monitoring 33 children with definite MS.

In the treatment of demyelinating diseases, in addition to pulse therapy, plasmapheresis and intravenous administration of immunoglobulin (Bioven mono, Bioven) are widely used. Treatment regimens with intravenous immunoglobulin have been developed with the course repeated after 3-6 months. The technique of immunomodulatory therapy has been mastered in the treatment of children with MS using all groups of immunomodulators: interferon beta-1a (Rebif, betabioferon-1a, betfer-1a, Avonex), interferon beta-1b (betaferon, betabioferon-1b, betferon-1b). 1c, P-interferon-1c), glatiramer acetate (co-paxone, glatimer), including titration of drug doses and relief of exacerbations against the background of ongoing continuous immunomodulatory therapy.

The work of the center makes it possible to carry out early diagnosis of demyelinating and degenerative diseases of the nervous system in children, to introduce new modern treatment methods, which allows achieving a better effect of the therapy, longer remissions, delaying and sometimes preventing the disability of children with this severe neurological pathology.

We consider it necessary to implement educational programs on training pediatric neurologists in the diagnosis of reliable multiple sclerosis and methods of treating children with MS. Such training is carried out in thematic advanced training courses for doctors, and seminars are held for general practitioners and pediatric neurologists at the Center for Demyelinating Diseases. We also consider it extremely important to allocate state budget funds for examination (magnetic resonance imaging with the use of contrast agents, immunological studies, detection of viral DNA in the blood and cerebrospinal fluid) and treatment of these patients, including not only interferon-beta and glatiramer acetate, but and intravenous immunoglobulin.

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Received 01/04/15 ■

Svtushenko S.K.1, Moskalenko M.A.2, Svtushenko 1.S.3

1 Khark1all medical academician! I have completed my diploma

2 Regional center dem1el!n1zuyuchikh sick, Donetsk metro station

3 DonNMU 1m. M. Gorky

vGd CL|N|CHNO ¡ZOLOVAN SYNDROME to V|ROG1DNOT D1DIAGNOSTICS OF ROSATE SCLEROSIS AND EFFECTIVENESS OF THERAPY IN D|TEIRS

Summary. Statt has posted the results of the 30-year-old early diagnosis of pink sclerosis in Dggey from Wikoristan, magnetically resonant! tomography, visual and cognitive vi-clic potency, biochemical and immunological blood and spinal cerebrovascular! rshchini. The authors describe a variant of the onset of this important curable disease in children. Therapeutic regimens have been developed, which include pulse therapy with Solu-Medrol, plasmapheresis and intravenous immunoglobulin, as well as additional use of immunomodulators in days.

Key words: multiple sclerosis, child, diagnosis, medical treatment.

Yevtushenko S.K.1, Moskalenko M.A.2, Yevtushenko I.S.3

1 Kharkiv Medical Academy of Postgraduate Education, Kharkiv

2 Regional Center of Demyelinating Diseases, Donetsk, Ukraine

3 Donetsk National Medical University named after M. Horkyi, Donetsk

FROM CLINICALLY ISOLATED SYNDROME TO ACCURATE DIAGNOSIS OF MULTIPLE SCLEROSIS AND ITS EFFECTIVE THERAPY IN CHILDREN

Summary. Results of 30-year experience in the early diagnosis of multiple sclerosis in children using magnetic resonance imaging, visual and cognitive evoked potentials, biochemical and immunological studies of the blood and cerebrospinal fluid are described in the article. Different variants of the onset of this hard to treat, disabling disease in children are described by the authors. The schemes of therapy, including solu-medrol pulse therapy, plasmapheresis and intravenous immunoglobulin, as well as the experience ofusing immunomodulators in children, were specified.

Key words: multiple sclerosis, children, diagnosis, treatment.

(RIS) means the detection on MRI of changes characteristic of multiple sclerosis in asymptomatic (clinically silent) patients. Approximately 66% of patients with RIS experience radiological progression, and ~33% of patients develop neurological symptoms within 5 years. However, a significant number of patients did not subsequently progress to multiple sclerosis. Due to the lack of clear risk factors determining clinical conversion, treatment is usually not initiated.

Terminology

The incidental discovery in the brain/spinal cord of lesions characteristic of multiple sclerosis (in accordance with the 2010 McDonald criteria) during an examination performed for another reason is defined as a radiologically isolated syndrome. The development of neurological symptoms in patients with RIS is called conversion.
The phenomenon of asymptomatic, subclinical or clinically silent MS at autopsy has been known for a long time, but the increased availability of MRI and the increase in the number of studies conducted for reasons other than suspected MS have led to the need to isolate this syndrome.

Epidemiology

The exact prevalence is not known. The only large retrospective study put the rate at a very low 0.05%. The prevalence may be higher if there is a family history of MS.

Literature

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Dr Bruno Di Muzio and Dr René Pfleger et al. Radiologically isolated syndrome. Radiopedia.