Multiple sclerosis (MS) – Multiple sclerosis (MS) –

is a chronic disease that begins is a chronic disease that begins most commonly in young adults most commonly in young adults and is characterized pathologically and is characterized pathologically by multiple areas of central by multiple areas of central nervous system (CNS) white matter nervous system (CNS) white matter inflammation, demyelination, and inflammation, demyelination, and glial scarring (sclerosis)glial scarring (sclerosis)

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EtiologyEtiologyThe cause of MS is unknown. There are 2 groups ofThe cause of MS is unknown. There are 2 groups ofpossible reasons of the disease:possible reasons of the disease: Genetic susceptibilityGenetic susceptibility Environmental factorsEnvironmental factors

Infections (the virus can influence on nervous system Infections (the virus can influence on nervous system directly or through the autoimmune mechanisms).directly or through the autoimmune mechanisms).

Geographical (ground, water properties, the number Geographical (ground, water properties, the number of light days in a year)of light days in a year)

Toxic Toxic Social conditionsSocial conditions Diet (domination of meat in the diet)Diet (domination of meat in the diet) Other factors (trauma)Other factors (trauma)

The typical features of MS The typical features of MS pathogenesispathogenesis

Clinical and immune signs are closely Clinical and immune signs are closely connected with each other in MS patients. connected with each other in MS patients. Usually immune signs are the first onesUsually immune signs are the first ones

There is disturbance of activating and There is disturbance of activating and suppressing cytokines balancesuppressing cytokines balance

The immunity is changed in the course of the The immunity is changed in the course of the diseasedisease

There are signs of immune suppression and There are signs of immune suppression and immune modulation according to the stage of immune modulation according to the stage of the disease – exacerbation or remissionthe disease – exacerbation or remission

Myelin functionMyelin function

PathologyPathology

There are multiple areas of Central There are multiple areas of Central Nervous System white matter Nervous System white matter inflammation, demyelination and glial inflammation, demyelination and glial scarring (sclerosis). The lesions are scarring (sclerosis). The lesions are multiple in space. They are located in:multiple in space. They are located in:

spinal cordspinal cord cerebellumcerebellum Optic n.Optic n. brain white substance brain white substance

The beginning of the The beginning of the diseasedisease

ParesthesiaParesthesia.. It is the feeling of numbness or tingling in It is the feeling of numbness or tingling in one of the extremity. It can be spread during the next 3 – 4 one of the extremity. It can be spread during the next 3 – 4 days and lasts for about 1 – 2 weeks, then gradually days and lasts for about 1 – 2 weeks, then gradually disappear. disappear.

Motor disordersMotor disorders - weakness in lower extremities. This - weakness in lower extremities. This symptom is much more common at the age of 25 – 40 symptom is much more common at the age of 25 – 40 years.years.

Retrobulbar neuritisRetrobulbar neuritis is a progressive loss of vision, colour is a progressive loss of vision, colour vision disturbances. It lasts for about several weeks.vision disturbances. It lasts for about several weeks.

Oculomotor n. disordersOculomotor n. disorders (diplopia and cross eye). (diplopia and cross eye). Pelvis disordersPelvis disorders (retention of urine, micturition) (retention of urine, micturition) Acute vestibular syndromeAcute vestibular syndrome Cerebellar disordersCerebellar disorders – ataxia, disorders of coordination – ataxia, disorders of coordination..

Typical clinical featuresTypical clinical features Motor disorders – 89 – 97%Motor disorders – 89 – 97% Ataxia – cerebellar, sensitive and vestibular – 62 – Ataxia – cerebellar, sensitive and vestibular – 62 –

74%74% Sensory disorders – pains and sensitive ataxia - 72 – Sensory disorders – pains and sensitive ataxia - 72 –

74%74% Brain stem symptoms – vestibular syndrome, Brain stem symptoms – vestibular syndrome,

dysarthria, CN’s lesion – 47 – 58%dysarthria, CN’s lesion – 47 – 58% Visual and eye movements disorders – 42 – 52%Visual and eye movements disorders – 42 – 52% Autonomic disturbances – pelvic and sexual Autonomic disturbances – pelvic and sexual

disorders – 46 – 60%disorders – 46 – 60% Nonspecific symptoms – cognitive, memory Nonspecific symptoms – cognitive, memory

disturbances, loss of attention – 62%disturbances, loss of attention – 62% Paroxysmal symptoms Paroxysmal symptoms

Visual field disorders of MSVisual field disorders of MS

Clinical formsClinical forms

Cerebral :Cerebral : cortical (epileptic attacks, psychiatric disorders)cortical (epileptic attacks, psychiatric disorders) VisualVisual brain stembrain stem cerebellar.cerebellar.

Spinal:Spinal: CervicalCervical ThoracicThoracic lumbar – sacrallumbar – sacral pseudotabes.pseudotabes.

CerebrospinalCerebrospinal

The course of the diseaseThe course of the disease

AcuteAcute SubacuteSubacute ChronicChronic:: – – remittent, remittent, - remittent – progressive- remittent – progressive - progressive – remittent- progressive – remittent - progressive- progressive

The periods of the disease:The periods of the disease: ExacerbationExacerbation Remission (complete, incomplete).Remission (complete, incomplete). Stable periodStable period

MS degree:MS degree: I, II, III, IV, V I, II, III, IV, V

Scale of MS disability Scale of MS disability (EDSS)(EDSS)

MS diagnosisMS diagnosis Immune examinations of blood and CSF. Usually Immune examinations of blood and CSF. Usually

there are increased Ig G, M, A contents. there are increased Ig G, M, A contents. Insignificant increasing of protein content and Insignificant increasing of protein content and

moderate pleocytosis in CSFmoderate pleocytosis in CSF Lymphocytosis, eosynophilia – in exacerbation Lymphocytosis, eosynophilia – in exacerbation

stage; leukopenia, lymphopenia – in the period of stage; leukopenia, lymphopenia – in the period of remission. remission.

Increased thrombocytes aggregation and fibrinogen Increased thrombocytes aggregation and fibrinogen content.content.

Increased Ig content in serum and decreased T – Increased Ig content in serum and decreased T – lymphocytes quantity. lymphocytes quantity.

To put veridical MS we have to reveal in To put veridical MS we have to reveal in patient at least 2 focuses of lesion and 2 patient at least 2 focuses of lesion and 2 exacerbations, or 2 exacerbations of 1 clinical exacerbations, or 2 exacerbations of 1 clinical focus and 1 paraclinical supposed focus. focus and 1 paraclinical supposed focus.

According to the accepted criteria there According to the accepted criteria there should be at least 3 focuses in MRI (2 of them should be at least 3 focuses in MRI (2 of them should be located paraventricularly, 1 – should be located paraventricularly, 1 – subtentorialy (that means in brain stem or subtentorialy (that means in brain stem or cerebellum). The diameter of focuses should cerebellum). The diameter of focuses should be at least 6 mm, or there should be 4 be at least 6 mm, or there should be 4 focuses, 1 of them periventricularly.focuses, 1 of them periventricularly.

MRI of MSMRI of MS

MRI of MSMRI of MS

Sagittal T1-weighted MRI depicts multiple hypointense Sagittal T1-weighted MRI depicts multiple hypointense lesions in the corpus callosum; this finding is lesions in the corpus callosum; this finding is characteristic of MScharacteristic of MS

Coronal fluid-attenuated inversion recovery (FLAIR) MRI in a Coronal fluid-attenuated inversion recovery (FLAIR) MRI in a patient with multiple sclerosis demonstrates periventricular patient with multiple sclerosis demonstrates periventricular high–signal intensity lesions, which exhibit a typical high–signal intensity lesions, which exhibit a typical distribution for MS. FLAIR MRI is a highly sensitive sequence distribution for MS. FLAIR MRI is a highly sensitive sequence

for lesion detection, particularly supratentoriallyfor lesion detection, particularly supratentorially. .

Axial T2-weighted MRI in a patient with multiple sclerosis Axial T2-weighted MRI in a patient with multiple sclerosis demonstrates numerous white matter plaques in a callosal and demonstrates numerous white matter plaques in a callosal and pericallosal white matter distribution. pericallosal white matter distribution.

Spinal form of MSSpinal form of MS

One of the limitations of using MRI in patients One of the limitations of using MRI in patients with MS is the discordance occurring between with MS is the discordance occurring between lesion location and the clinical presentation. In lesion location and the clinical presentation. In addition, depending on the number and location addition, depending on the number and location of findings, MRI can vary greatly in terms of of findings, MRI can vary greatly in terms of sensitivity and specificity in the diagnosis of MS. sensitivity and specificity in the diagnosis of MS. This is especially true of primary progressive This is especially true of primary progressive MS, which may not show the classic discrete MS, which may not show the classic discrete lesions of relapsing-remitting MS.lesions of relapsing-remitting MS.

A clinician presented with an MRI report that details a A clinician presented with an MRI report that details a few "nonspecific white matter lesions" that are few "nonspecific white matter lesions" that are "compatible with MS" is often frustrated with the lack of "compatible with MS" is often frustrated with the lack of sensitivity and specificity of such a description. For this sensitivity and specificity of such a description. For this reason, imaging findings need to be described in detail, reason, imaging findings need to be described in detail, and preferably referenced to one of the published set and preferably referenced to one of the published set of diagnostic criteria such as those by Patyof diagnostic criteria such as those by Paty or Barkhof.or Barkhof.

Finally, the specific patient's neurologic history and Finally, the specific patient's neurologic history and clinical findings must be correlated with the imaging to clinical findings must be correlated with the imaging to establish an accurate diagnosisestablish an accurate diagnosis

Cerebrospinal fluid (CSF) analysis for Cerebrospinal fluid (CSF) analysis for oligoclonal banding or immunoglobulin G oligoclonal banding or immunoglobulin G (IgG) levels is no longer routine in the (IgG) levels is no longer routine in the investigation of MS, although this test investigation of MS, although this test may be of use when MRI is unavailable may be of use when MRI is unavailable or MRI findings are nondiagnosticor MRI findings are nondiagnostic

TreatmentTreatment

Pathogenetical treatmentPathogenetical treatment Corticosteroids and ACTHCorticosteroids and ACTH Cytostatics and immune modulators, Cytostatics and immune modulators,

non specific immune suppressors non specific immune suppressors Cytokines, interferonesCytokines, interferones Antigen – specific immune therapyAntigen – specific immune therapy

Corticosteroids and ACTHCorticosteroids and ACTH PrednisonePrednisone is used orally 1 – 1.5 mg/kg/day twice a day is used orally 1 – 1.5 mg/kg/day twice a day

during 10 – 14 days. Then during the next 2 months we during 10 – 14 days. Then during the next 2 months we decrease the dose gradually. decrease the dose gradually.

One of the most popular schema forOne of the most popular schema for MethylprednisoloneMethylprednisolone usage is 500 – 1000 mg per day i/v usage is 500 – 1000 mg per day i/v in 500 ml of physiological solution during 3 – 5 days. in 500 ml of physiological solution during 3 – 5 days. Then Prednisone is used in dose 0.5 – 1 mg/kg during 3 Then Prednisone is used in dose 0.5 – 1 mg/kg during 3 – 7 days with gradually decreasing of dose during the – 7 days with gradually decreasing of dose during the next 2 – 3 weeks. This way of usage has much more next 2 – 3 weeks. This way of usage has much more expressed and quick effectiveness and insignificant expressed and quick effectiveness and insignificant outside effectsoutside effects

DexamethasoneDexamethasone is used i/v or i/m according to the is used i/v or i/m according to the schema – 8 mg per day during 7 days, 4 mg – 4 days, 2 schema – 8 mg per day during 7 days, 4 mg – 4 days, 2 mg – 3 days. It is used at retrobulbar neuritismg – 3 days. It is used at retrobulbar neuritis

The peculiarities of The peculiarities of Corticosteroids usage:Corticosteroids usage:

Long lasting and frequent usage is undesirableLong lasting and frequent usage is undesirable Usually H-2 blockers are used together with Usually H-2 blockers are used together with

CorticosteroidsCorticosteroids ACTH has immune suppressive activity, ACTH has immune suppressive activity,

inhibits cellular and humoral immunity. It is inhibits cellular and humoral immunity. It is used in dose 40 – 100 U i/m during 10 – 14 used in dose 40 – 100 U i/m during 10 – 14 days. days.

Plasmapheresis is used in case of Plasmapheresis is used in case of exacerbation.exacerbation.

Cytostatics and immune modulators, Cytostatics and immune modulators, non specific immune suppressorsnon specific immune suppressors

Asatioprine, Cyclophosfamidum, Asatioprine, Cyclophosfamidum, CyclosporinumCyclosporinum A A. But all of these medicines . But all of these medicines have a lot of outside effects.have a lot of outside effects.

The representatives of immune modulators are - T – The representatives of immune modulators are - T – activinum, Timalinum, Myelopid, Levamisolum. They activinum, Timalinum, Myelopid, Levamisolum. They are prescribed at progressive forms of MS. are prescribed at progressive forms of MS.

T – activinumT – activinum is used in dose 100 mcg s/c every is used in dose 100 mcg s/c every evening during 5 days, then 1 – 3 injections every 10 evening during 5 days, then 1 – 3 injections every 10 days.days.

TimalinumTimalinum is used in dose 10 mg i/m twice a day is used in dose 10 mg i/m twice a day during 5 days, then every 10 days 2 injections are during 5 days, then every 10 days 2 injections are used.used.

InterferonesInterferonesThere are 3 types of Interferonum – α, β, γ.There are 3 types of Interferonum – α, β, γ.

α - Interferonumα - Interferonum has neither toxic nor treating activity. has neither toxic nor treating activity. γ - Interferonumγ - Interferonum activates immune system and that’s activates immune system and that’s

why it provokes exacerbations. why it provokes exacerbations. β - Interferonumβ - Interferonum inhibits production of γ – inhibits production of γ –

interferonum, increases activity of T – suppressors, has interferonum, increases activity of T – suppressors, has antiproliferative, antiviral and immune modulating antiproliferative, antiviral and immune modulating properties. properties.

Rebif Rebif – is a modern human β – interferonum produced – is a modern human β – interferonum produced by “Serono” production and is used for MS treatment. It by “Serono” production and is used for MS treatment. It is used in dose 6 – 12 mln s/c three times per week. It is used in dose 6 – 12 mln s/c three times per week. It is one of the most effective modern medicines in MS is one of the most effective modern medicines in MS patients, but unfortunately it is very expensivepatients, but unfortunately it is very expensive

Antigen – specific immune therapyAntigen – specific immune therapy

One of the representatives of these One of the representatives of these medications is medications is CopaxoneCopaxone,, made in Israel. made in Israel. Cost of treatment is about 7 000 $. It is Cost of treatment is about 7 000 $. It is used in dose 20 mg per day s/c during 6 – used in dose 20 mg per day s/c during 6 – 24 months. It has selective immune 24 months. It has selective immune modulating action.modulating action.

Acute multiple Acute multiple encephalomyelitis (AMEM)encephalomyelitis (AMEM)

It is an infectious – allergic It is an infectious – allergic disease that is disease that is characterized by acute characterized by acute multiple lesion of the brain multiple lesion of the brain and spinal cordand spinal cord

Clinical forms Clinical forms EncephalomyelopoliradiculoneuritisEncephalomyelopoliradiculoneuritis – – it is the it is the

most common form of the disease, which is most common form of the disease, which is characterized by the lesion of all parts of nervous characterized by the lesion of all parts of nervous system.system.

PolioencephalomyelitisPolioencephalomyelitis – – it is characterized by it is characterized by the lesion of CN’s nuclei and spinal cord gray the lesion of CN’s nuclei and spinal cord gray substance.substance.

Opticoencephalomyelitis and opticomyelitis –Opticoencephalomyelitis and opticomyelitis – are characterized by optic nerve neuritis and are characterized by optic nerve neuritis and symptoms of lesion of brain and spinal cord. symptoms of lesion of brain and spinal cord.

Disseminated myelitisDisseminated myelitis – – the spinal cord is the spinal cord is damaged on different levels. damaged on different levels.

Treatment Treatment Corticoids: Corticoids: Prednisolone Prednisolone and and

MethylprednisoloneMethylprednisolone in dose 10 – 15 mg per kg in dose 10 – 15 mg per kg i/v by drops per day. Later we can use it in pills - i/v by drops per day. Later we can use it in pills - 1.5 – 2 mg/kg every other day. 1.5 – 2 mg/kg every other day.

Together with this medicine we prescribe Together with this medicine we prescribe anabolics , K, Ca, vitamin Canabolics , K, Ca, vitamin C..

In acute stage we prescribe In acute stage we prescribe desensibilizatingdesensibilizating and and dehydratingdehydrating medicines. In case of severe medicines. In case of severe bulbar disorders we include bulbar disorders we include resuscitationresuscitation measures.measures.

Plasmapheresis and vitamin BPlasmapheresis and vitamin B are also used. are also used. In residual period we prescribe In residual period we prescribe massage, dibasol, massage, dibasol,

KJ, biostomulants, Lidasa, Seduxen, sanatorium KJ, biostomulants, Lidasa, Seduxen, sanatorium treatment. treatment.

Clinical symptoms of MSClinical symptoms of MS