1. 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)

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4. 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)

5. 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

6. Myelin function

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

16. 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

17. Visual field disorders of MS

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

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

20. The periods of the disease:  Exacerbation  Remission (complete, incomplete).  Stable period MS degree:  I, II, III, IV, V

21. Scale of MS disability (EDSS)

22. 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.

23.  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.

24. MRI of MS

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

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

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

31. Spinal form of MS

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

33.  A clinician presented with an MRI report that details a few "nonspecific white matter lesions" that are "compatible with MS" is often frustrated with the lack of sensitivity and specificity of such a description. For this reason, imaging findings need to be described in detail, and preferably referenced to one of the published set of diagnostic criteria such as those by Paty or Barkhof. Finally, the specific patient's neurologic history and clinical findings must be correlated with the imaging to establish an accurate diagnosis

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

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

36. 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

37. 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.

38. 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.

39. 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 and is used for MS treatment. 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 patients, but unfortunately it is very expensive

40. 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.

41. 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

42. 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.

43. 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.

44. Clinical symptoms of MS