Multiple sclerosis (MS)

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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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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)

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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

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Myelin function
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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

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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.

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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, CNs 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

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Visual field disorders of MS
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Clinical forms

• Cerebral
• cortical (epileptic attacks, psychiatric
  disorders)
• Visual
• brain stem
• cerebellar.
• Spinal
• Cervical
• Thoracic
• lumbar sacral
• pseudotabes.
• Cerebrospinal

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The course of the disease

• Acute
• Subacute
• Chronic
• remittent,
• - remittent progressive
• - progressive remittent
• - progressive

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

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Scale of MS disability (EDSS)
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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.

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• 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.

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MRI of MS
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MRI of MS
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Sagittal T1-weighted MRI depicts multiple
hypointense lesions in the corpus callosum this
finding is characteristic of MS
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Coronal fluid-attenuated inversion recovery
(FLAIR) MRI in a patient with multiple sclerosis
demonstrates periventricular highsignal
intensity lesions, which exhibit a typical
distribution for MS. FLAIR MRI is a highly
sensitive sequence for lesion detection,
particularly supratentorially.
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Axial T2-weighted MRI in a patient with multiple
sclerosis demonstrates numerous white matter
plaques in a callosal and pericallosal white
matter distribution.
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Spinal form of MS
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• 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.

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• 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

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• 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

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Treatment

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

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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

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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.

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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.

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Interferones

• There are 3 types of Interferonum a, ß, ?.
• a - Interferonum has neither toxic nor treating
  activity.
• ? - Interferonum activates immune system and
  thats why it provokes exacerbations.
• ß - Interferonum inhibits production of ?
  interferonum, increases activity of T
  suppressors, has antiproliferative, antiviral and
  immune modulating properties.
• Rebif is a modern human ß 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

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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.

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Acute multiple encephalomyelitis (AMEM)

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

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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 CNs 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.

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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.

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Clinical symptoms of MS