Multiple sclerosis Multiple sclerosis (MS)(MS)

PROF.SHKROBOTPROF.SHKROBOT

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)

EpidemiologyEpidemiology

Age of onset is between 20 – 40 Age of onset is between 20 – 40 years. Usually it is 21 – 25 years, in years. Usually it is 21 – 25 years, in women – 2 – 3 years earlier. In women women – 2 – 3 years earlier. In women the incidence of MS is 1.5 – 2 times the incidence of MS is 1.5 – 2 times higher than in men.higher than in men.

Nowadays there are about 2 mln Nowadays there are about 2 mln people with MS all over the worldpeople with MS all over the world

. The geographic distribution is . The geographic distribution is uneven. Most of northern USA, uneven. Most of northern USA, southern Canada, northern Europe, southern Canada, northern Europe, southern Australia and New Zealand southern Australia and New Zealand are areas of high prevalenceare areas of high prevalence. .

EpidemiologyEpidemiology

In Ukraine the incidence of MS is In Ukraine the incidence of MS is 15 per 100 000 people. But it is 15 per 100 000 people. But it is much more higher in western much more higher in western regions (25 per 100 000 people) regions (25 per 100 000 people) than in eastern and southern than in eastern and southern ones (6 – 8 per 100 000 people).ones (6 – 8 per 100 000 people).

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

The main cause of the increased The main cause of the increased growth of the diseasegrowth of the disease

Better diagnosisBetter diagnosis Unitary diagnostic scalesUnitary diagnostic scales Increasing possibilities of treatment that Increasing possibilities of treatment that

leads to the growth of percentage of the leads to the growth of percentage of the patients with long lasting course of the patients with long lasting course of the diseasedisease

True growth of MS incidenceTrue growth of MS incidence

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

PathogenesisPathogenesis

Different etiologic agents provoke Different etiologic agents provoke autoimmune mechanisms. The autoimmune mechanisms. The result of this process is myelin result of this process is myelin destruction. At the beginning of the destruction. At the beginning of the process auto-allergic processes process auto-allergic processes prevail over the other ones. Then prevail over the other ones. Then immunodeficiency is developed.immunodeficiency is developed.

PathogenesisPathogenesis

The typical features of MS pathogenesis are:The typical features of MS pathogenesis are: 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 balance suppressing 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

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

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

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

The beginning of the The beginning of the diseasedisease

Oculomotor n. disordersOculomotor n. disorders (diplopia and (diplopia and cross eye)cross eye)

Pelvis disordersPelvis disorders (retention of urine, (retention of urine, micturition)micturition)

Acute vestibular syndromeAcute vestibular syndrome Cerebellar disordersCerebellar disorders – ataxia, disorders – ataxia, disorders

of coordinationof coordination

ROMBERG TESTROMBERG TEST

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

Motor disordersMotor disorders Hemiparesis, lower paraparesis and Hemiparesis, lower paraparesis and

monoparesis are common symptoms of MSmonoparesis are common symptoms of MS Upper extremities are injured very seldomUpper extremities are injured very seldom The typical signs of these symptoms are low The typical signs of these symptoms are low

muscle strength, the presence of pathological muscle strength, the presence of pathological reflexes and low abdominal reflexesreflexes and low abdominal reflexes

There are also changes of muscle tonus – There are also changes of muscle tonus – spastic hypertonus, hypotonus or dystonusspastic hypertonus, hypotonus or dystonus

Hypotonus can be the sign of cerebellum and Hypotonus can be the sign of cerebellum and spinal cord posterior columns lesionspinal cord posterior columns lesion

Disorders of coordinationDisorders of coordination

Ataxia:Ataxia:

Cerebellar dynamic and static ataxiaCerebellar dynamic and static ataxia

Vestibular Vestibular

Sensitive Sensitive

Mixed Mixed Dysmetry, hypermetryDysmetry, hypermetry Intention tremorIntention tremor Asynergy Asynergy

DysmetryDysmetry

Finger-nose testFinger-nose test

Heel to knee testHeel to knee test

Kinds of ataxias:Kinds of ataxias:

Kinds of ataxias:Kinds of ataxias:

Multiple sclerosis (MS)Multiple sclerosis (MS)

PATOLOGICAL REFLEXESPATOLOGICAL REFLEXES

PATOLOGICAL REFLEXESPATOLOGICAL REFLEXES

Sensory disordersSensory disorders

Subjective sensory disturbances are Subjective sensory disturbances are early signs of MSearly signs of MS

Then conductive sensory disorders are Then conductive sensory disorders are joined to themjoined to them

Muscle – joint sense usually suffers at Muscle – joint sense usually suffers at the fifth year of the disease and laterthe fifth year of the disease and later

The loss of vibration sense points on The loss of vibration sense points on posterior columns lesionposterior columns lesion

Brain stem disturbancesBrain stem disturbances

There is vestibular symptom with:There is vestibular symptom with: dizzinessdizziness nystagmus nystagmus vestibular ataxia;vestibular ataxia; Sometimes trigeminal pains are observedSometimes trigeminal pains are observed

Visual and eye movements Visual and eye movements disordersdisorders

The typical features of MS are: The typical features of MS are: retrobulbar neuritisretrobulbar neuritis subatrophy of optic nerve discsubatrophy of optic nerve disc decoloration of disc’s temporal partdecoloration of disc’s temporal part Eye movement disorders mean that there Eye movement disorders mean that there

are syndromes of ophthalmoplegia are syndromes of ophthalmoplegia

Autonomic (pelvic) disordersAutonomic (pelvic) disorders

Syndrome of m. Detrussor hyperreflexion. That Syndrome of m. Detrussor hyperreflexion. That means urine bladder inability to accumulate means urine bladder inability to accumulate urine. The main symptoms are:urine. The main symptoms are:

micturitionmicturition increased frequency of urinationincreased frequency of urination incontinence of urineincontinence of urine retention of urine.retention of urine.Incomplete urine bladder emptiness. Dyssynergy Incomplete urine bladder emptiness. Dyssynergy

of m. Detrussor and Sphincter. of m. Detrussor and Sphincter.

Nonspecific symptomsNonspecific symptoms

General weaknessGeneral weakness Cognitive disordersCognitive disorders MemoryMemory Attention disturbancesAttention disturbances Behavioral disordersBehavioral disorders Depression, euphoria and fatigue Depression, euphoria and fatigue

syndrome syndrome

Paroxysmal symptomsParoxysmal symptoms Tonic muscles spasm (painful and short lasting)Tonic muscles spasm (painful and short lasting) Dysarthria and ataxia attacksDysarthria and ataxia attacks Lermitt symtom – it is a short lasting feeling of electrical Lermitt symtom – it is a short lasting feeling of electrical

current along the spinal cordcurrent along the spinal cord Paroxysmal trigeminal painsParoxysmal trigeminal pains Atypical pains in extremitiesAtypical pains in extremities Paroxysmal itchingParoxysmal itching Paroxysmal choreoatetosisParoxysmal choreoatetosis Paroxysmal nystagmusParoxysmal nystagmus Paroxysmal facial hemispasmParoxysmal facial hemispasm Epileptic attacks (focal and general)Epileptic attacks (focal and general) Pains are very often observed at MS. They can be Pains are very often observed at MS. They can be

paroxysmal or chronic ones paroxysmal or chronic ones Uthoff’s symptoms – it is the worsening of patients state Uthoff’s symptoms – it is the worsening of patients state

after the hot bathroom or hot meal after the hot bathroom or hot meal

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 – patient has difficulty to walk only after I – patient has difficulty to walk only after physical training physical training

II – patient has difficulty to walk and weakness II – patient has difficulty to walk and weakness on 2-3 km on 2-3 km

III – patient has spastic-paretic gait, difficulty to III – patient has spastic-paretic gait, difficulty to walk and weakness on 200-300 m. walk and weakness on 200-300 m.

IV – patient can’t to walk without helpIV – patient can’t to walk without help V – patient can’t to walk or has blindness V – patient can’t to walk or has blindness

Клінічні прояви РСКлінічні прояви РС

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.

MRIMRI To put veridical MS we have to reveal in patient at To put veridical MS we have to reveal in patient at

least 2 focuses of lesion and 2 exacerbations, or 2 least 2 focuses of lesion and 2 exacerbations, or 2 exacerbations of 1 clinical focus and 1 paraclinical exacerbations of 1 clinical focus and 1 paraclinical supposed focus. supposed focus.

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

mrimri

ЗМІНИ НА МРТЗМІНИ НА МРТ

Method of evoked Method of evoked potentialspotentials

This is a method that reveals bioelectrical This is a method that reveals bioelectrical brain activity in response to the brain activity in response to the stimulation. stimulation.

This method is not a specific one for MS This method is not a specific one for MS diagnosis. diagnosis.

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 has neither toxic nor treating activity.activity.

γ - Interferonumγ - Interferonum activates immune system and activates immune system and that’s why it provokes exacerbations. that’s why it provokes exacerbations.

β - Interferonumβ - Interferonum inhibits production of γ – inhibits production of γ – interferonum, increases activity of T – suppressors, interferonum, increases activity of T – suppressors, has antiproliferative, antiviral and immune has antiproliferative, antiviral and immune modulating properties. modulating properties.

Rebif Rebif – is a modern human β – interferonum – is a modern human β – interferonum produced by “Serono” production. It is used in dose produced by “Serono” production. It is used in dose 6 – 12 mln s/c 6 – 12 mln s/c 33 times per week. It is one of the most times per week. It is one of the most effective modern medicines in MS patients, but effective modern medicines in MS patients, but unfortunately it is very expensiveunfortunately 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.

Basic therapyBasic therapy Vitamins B groupVitamins B group Desensibilizative medicinesDesensibilizative medicines Amino acidsAmino acids NootropsNootrops ATP, CocarboxylasaATP, Cocarboxylasa BiostimulantsBiostimulants Entero and hemosorptionEntero and hemosorption AntiplateletAntiplatelet AntioxydantsAntioxydants AngioprotectorsAngioprotectors Inhibitors of proteolytic enzymesInhibitors of proteolytic enzymes Regeneration stimulantsRegeneration stimulants

Symptomatic treatmentSymptomatic treatment Pelvis disordersPelvis disorders Proserinum, Halantaminum decrease m. Proserinum, Halantaminum decrease m.

Detrussor hyperreflexion.Detrussor hyperreflexion. α - Adrenoblockers decrease dysynergy of α - Adrenoblockers decrease dysynergy of

Sphincter and Detrussor. Sphincter and Detrussor. SpasticitySpasticity Baclofen 5 mg 3 times per dayBaclofen 5 mg 3 times per day Sirdalude 4 mg 3 times per daySirdalude 4 mg 3 times per dayTremorTremor β - Adrenoblockers are used at postural tremorβ - Adrenoblockers are used at postural tremor Clonasepam, Carbamasepam are used at Clonasepam, Carbamasepam are used at

intentionintention

Symptomatic treatmentSymptomatic treatment

Hyperkinetic formHyperkinetic form AdrenoblockersAdrenoblockers AntidepressantsAntidepressants

AstheniaAsthenia PsychostimulantsPsychostimulants Dopaminergic medicinesDopaminergic medicines

Paroxysmal signsParoxysmal signs Carbamasepinum, FilepsinCarbamasepinum, Filepsin

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.

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

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.