Transcript Multiple sclerosis (MS) –

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.
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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).
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:
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Genetic susceptibility
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Environmental factors
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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)
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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
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
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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
Vestibular
Sensitive
Mixed
 Dysmetry, hypermetry
 Intention tremor
 Asynergy
Dysmetry
Finger-nose test
Heel to knee test
Kinds of ataxias:
Kinds of ataxias:
Multiple sclerosis
(MS)
PATOLOGICAL REFLEXES
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
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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 :
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cortical (epileptic attacks, psychiatric disorders)
Visual
brain stem
cerebellar.
Spinal:
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Cervical
Thoracic
lumbar – sacral
pseudotabes.
Cerebrospinal
The course of the disease
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Acute
Subacute
Chronic:
– remittent,
- remittent – progressive
- progressive – remittent
- progressive
The periods of the disease:
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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 200-300 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
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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
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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.
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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
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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.
Basic therapy
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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
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 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.