Multiple sclerosis (MS) PROF.SHKROBOT

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

Epidemiology  Age of onset is between 20 – 40 years. Usually it is 21 – 25 years, in women – 2 – 3 years earlier. In women the incidence of MS is 1.5 – 2 times higher than in men.  Nowadays there are about 2 mln people with MS all over the world . The geographic distribution is uneven. Most of northern USA, southern Canada, northern Europe, southern Australia and New Zealand are areas of high prevalence.

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

Multiple sclerosis (MS) –  The main cause of the increased growth of the disease  Better diagnosis  Unitary diagnostic scales  Increasing possibilities of treatment that leads to the growth of percentage of the patients with long lasting course of the disease  True growth of MS incidence

Etiology The cause of MS is unknown. There are 2 groups of possible reasons of the disease:  Genetic susceptibility  Environmental factors  Infections (the virus can influence on nervous system directly or through the autoimmune mechanisms).  Geographical (ground, water properties, the number of light days in a year)  Toxic  Social conditions  Diet (domination of meat in the diet)  Other factors (trauma)

The typical features of MS pathogenesis  Clinical and immune signs are closely connected with each other in MS patients. Usually immune signs are the first ones  There is disturbance of activating and suppressing cytokines balance  The immunity is changed in the course of the disease  There are signs of immune suppression and immune modulation according to the stage of the disease – exacerbation or remission

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

Pathogenesis  The typical features of MS pathogenesis are:  Clinical and immune signs are closely connected with each other in MS patients. Usually immune signs are the first ones  There is disturbance of activating and suppressing cytokines balance  The immunity is changed in the course of the disease  There are signs of immune suppression and immune modulation according to the stage of the disease – exacerbation or remission

Pathology  There are multiple areas of Central Nervous System white matter inflammation, demyelination and glial scarring (sclerosis). The lesions are multiple in space. They are located in:  spinal cord  cerebellum  Optic n.  brain white substance

The beginning of the disease  Paresthesia. It is the feeling of numbness or tingling in one of the extremity. It can be spread during the next 3 – 4 days and lasts for about 1 – 2 weeks, then gradually disappear  Motor disorders - weakness in lower extremities. This symptom is much more common at the age of 25 – 40 years  Retrobulbar neuritis is a progressive loss of vision, colour vision disturbances. It lasts for about several weeks

The beginning of the disease  Oculomotor n. disorders (diplopia and cross eye)  Pelvis disorders (retention of urine, micturition)  Acute vestibular syndrome  Cerebellar disorders – ataxia, disorders of coordination

ROMBERG TEST

Typical clinical features  Motor disorders – 89 – 97%  Ataxia – cerebellar, sensitive and vestibular – 62 – 74%  Sensory disorders – pains and sensitive ataxia - 72 – 74%  Brain stem symptoms – vestibular syndrome, dysarthria, CN’s lesion – 47 – 58%  Visual and eye movements disorders – 42 – 52%  Autonomic disturbances – pelvic and sexual disorders – 46 – 60%  Nonspecific symptoms – cognitive, memory disturbances, loss of attention – 62%  Paroxysmal symptoms

Motor disorders  Hemiparesis, lower paraparesis and monoparesis are common symptoms of MS  Upper extremities are injured very seldom  The typical signs of these symptoms are low muscle strength, the presence of pathological reflexes and low abdominal reflexes  There are also changes of muscle tonus – spastic hypertonus, hypotonus or dystonus  Hypotonus can be the sign of cerebellum and spinal cord posterior columns lesion

Disorders of coordination  Ataxia: Cerebellar dynamic and static ataxia VestibularSensitiveMixed  Dysmetry, hypermetry  Intention tremor  Asynergy

Dysmetry

Finger-nose test

Heel to knee test

Kinds of ataxias:

Multiple sclerosis (MS)

PATOLOGICAL REFLEXES

Sensory disorders  Subjective sensory disturbances are early signs of MS  Then conductive sensory disorders are joined to them  Muscle – joint sense usually suffers at the fifth year of the disease and later  The loss of vibration sense points on posterior columns lesion

Brain stem disturbances There is vestibular symptom with:  dizziness  nystagmus  vestibular ataxia;  Sometimes trigeminal pains are observed

Visual and eye movements disorders The typical features of MS are:  retrobulbar neuritis  subatrophy of optic nerve disc  decoloration of disc’s temporal part  Eye movement disorders mean that there are syndromes of ophthalmoplegia

Autonomic (pelvic) disorders Syndrome of m. Detrussor hyperreflexion. That means urine bladder inability to accumulate urine. The main symptoms are:  micturition  increased frequency of urination  incontinence of urine  retention of urine. Incomplete urine bladder emptiness. Dyssynergy of m. Detrussor and Sphincter.

Nonspecific symptoms  General weakness  Cognitive disorders  Memory  Attention disturbances  Behavioral disorders  Depression, euphoria and fatigue syndrome

Paroxysmal symptoms  Tonic muscles spasm (painful and short lasting)  Dysarthria and ataxia attacks  Lermitt symtom – it is a short lasting feeling of electrical current along the spinal cord  Paroxysmal trigeminal pains  Atypical pains in extremities  Paroxysmal itching  Paroxysmal choreoatetosis  Paroxysmal nystagmus  Paroxysmal facial hemispasm  Epileptic attacks (focal and general)  Pains are very often observed at MS. They can be paroxysmal or chronic ones  Uthoff’s symptoms – it is the worsening of patients state after the hot bathroom or hot meal

Clinical forms Cerebral :  cortical (epileptic attacks, psychiatric disorders)  Visual  brain stem  cerebellar. Spinal:  Cervical  Thoracic  lumbar – sacral  pseudotabes. Cerebrospinal

The course of the disease  Acute  Subacute  Chronic:  – remittent,  - remittent – progressive  - progressive – remittent  - progressive

The periods of the disease:  Exacerbation  Remission (complete, incomplete).  Stable period

MS degree:  I – patient has difficulty to walk only after physical training  II – patient has difficulty to walk and weakness on 2-3 km  III – patient has spastic-paretic gait, difficulty to walk and weakness on m.  IV – patient can’t to walk without help  V – patient can’t to walk or has blindness

Клінічні прояви РС

MS diagnosis  Immune examinations of blood and CSF. Usually there are increased Ig G, M, A contents.  Insignificant increasing of protein content and moderate pleocytosis in CSF  Lymphocytosis, eosynophilia – in exacerbation stage; leukopenia, lymphopenia – in the period of remission.  Increased thrombocytes aggregation and fibrinogen content.  Increased Ig content in serum and decreased T – lymphocytes quantity.

MRI  To put veridical MS we have to reveal in patient at least 2 focuses of lesion and 2 exacerbations, or 2 exacerbations of 1 clinical focus and 1 paraclinical supposed focus.  According to the accepted criteria there should be at least 3 focuses in MRI (2 of them should be located paraventricularly, 1 – subtentorialy (that means in brain stem or cerebellum). The diameter of focuses should be at least 6 mm, or there should be 4 focuses, 1 of them periventricularly.

mri

ЗМІНИ НА МРТ

Method of evoked potentials  This is a method that reveals bioelectrical brain activity in response to the stimulation.  This method is not a specific one for MS diagnosis.

Treatment Pathogenetical treatment  Corticosteroids and ACTH  Cytostatics and immune modulators, non specific immune suppressors  Cytokines, interferones  Antigen – specific immune therapy

Corticosteroids and ACTH  Prednisone is used orally 1 – 1.5 mg/kg/day twice a day during 10 – 14 days. Then during the next 2 months we decrease the dose gradually.  One of the most popular schema for Methylprednisolone usage is 500 – 1000 mg per day i/v in 500 ml of physiological solution during 3 – 5 days. Then Prednisone is used in dose 0.5 – 1 mg/kg during 3 – 7 days with gradually decreasing of dose during the next 2 – 3 weeks. This way of usage has much more expressed and quick effectiveness and insignificant outside effects  Dexamethasone is used i/v or i/m according to the schema – 8 mg per day during 7 days, 4 mg – 4 days, 2 mg – 3 days. It is used at retrobulbar neuritis

The peculiarities of Corticosteroids usage:  Long lasting and frequent usage is undesirable  Usually H-2 blockers are used together with Corticosteroids  ACTH has immune suppressive activity, inhibits cellular and humoral immunity. It is used in dose 40 – 100 U i/m during 10 – 14 days.  Plasmapheresis is used in case of exacerbation.

Cytostatics and immune modulators, non specific immune suppressors  Asatioprine, Cyclophosfamidum, Cyclosporinum A. But all of these medicines have a lot of outside effects.  The representatives of immune modulators are - T – activinum, Timalinum, Myelopid, Levamisolum. They are prescribed at progressive forms of MS.  T – activinum is used in dose 100 mcg s/c every evening during 5 days, then 1 – 3 injections every 10 days.  Timalinum is used in dose 10 mg i/m twice a day during 5 days, then every 10 days 2 injections are used.

Interferones There are 3 types of Interferonum – α, β, γ.  α - Interferonum has neither toxic nor treating activity.  γ - Interferonum activates immune system and that’s why it provokes exacerbations.  β - Interferonum inhibits production of γ – interferonum, increases activity of T – suppressors, has antiproliferative, antiviral and immune modulating properties.  Rebif – is a modern human β – interferonum produced by “Serono” production. It is used in dose 6 – 12 mln s/c 3 times per week. It is one of the most effective modern medicines in MS patients, but unfortunately it is very expensive

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

Basic therapy  Vitamins B group  Desensibilizative medicines  Amino acids  Nootrops  ATP, Cocarboxylasa  Biostimulants  Entero and hemosorption  Antiplatelet  Antioxydants  Angioprotectors  Inhibitors of proteolytic enzymes  Regeneration stimulants

Symptomatic treatment Pelvis disorders  Proserinum, Halantaminum decrease m. Detrussor hyperreflexion.  α - Adrenoblockers decrease dysynergy of Sphincter and Detrussor. Spasticity  Baclofen 5 mg 3 times per day  Sirdalude 4 mg 3 times per day Tremor  β - Adrenoblockers are used at postural tremor  Clonasepam, Carbamasepam are used at intention

Symptomatic treatment Hyperkinetic form  Adrenoblockers  Antidepressants Asthenia  Psychostimulants  Dopaminergic medicines Paroxysmal signs  Carbamasepinum, Filepsin

Acute multiple encephalomyelitis (AMEM) It is an infectious – allergic disease that is characterized by acute multiple lesion of the brain and spinal cord It is an infectious – allergic disease that is characterized by acute multiple lesion of the brain and spinal cord

Clinical forms  Encephalomyelopoliradiculoneuritis – it is the most common form of the disease, which is characterized by the lesion of all parts of nervous system.  Polioencephalomyelitis – it is characterized by the lesion of CN’s nuclei and spinal cord gray substance.  Opticoencephalomyelitis and opticomyelitis – are characterized by optic nerve neuritis and symptoms of lesion of brain and spinal cord.  Disseminated myelitis – the spinal cord is damaged on different levels.

Acute multiple encephalomyelitis (AMEM)

Treatment  Corticoids: Prednisolone and Methylprednisolone in dose 10 – 15 mg per kg i/v by drops per day. Later we can use it in pills – 2 mg/kg every other day.  Together with this medicine we prescribe anabolics, K, Ca, vitamin C.  In acute stage we prescribe desensibilizating and dehydrating medicines. In case of severe bulbar disorders we include resuscitation measures.  Plasmapheresis and vitamin B are also used.  In residual period we prescribe massage, dibasol, KJ, biostomulants, Lidasa, Seduxen, sanatorium treatment.