1. Multiple sclerosis (MS) PROF.SHKROBOT

2. 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)

3. 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.

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

5. 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

6. 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)

7. 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

8. 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.

9. 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

10. 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

15. 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

16. 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

19. ROMBERG TEST

20. 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

21. 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

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

23. Dysmetry

24. Finger-nose test

25. Heel to knee test

26. Kinds of ataxias:

28. Multiple sclerosis (MS)

29. PATOLOGICAL REFLEXES

31. 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

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

33. 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

35. 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.

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

37. 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

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

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

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

41. 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 200-300 m.  IV – patient can’t to walk without help  V – patient can’t to walk or has blindness

42. Клінічні прояви РС

43. 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.

44. 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.

47. mri

48. ЗМІНИ НА МРТ

49. 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.

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

51. 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

52. 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.

53. 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.

54. 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

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

56. 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

57. 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

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

59. 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

60. 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.

61. Acute multiple encephalomyelitis (AMEM)

62. 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 - 1.5 – 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.