Multiple Sclerosis
Epidemiology
Genetics, Environmental Factors
Treatment
Yvonne Benešová
Department of Neurology
Faculty od Medicine MU
University Hospital Brno
Multiple Sclerosis
• Multiple sclerosis is a chronic, autoimmune
demyelinating, degenerative disorder of the CNS
– brain, spine, optic nerve
– Typical sign of MS is repeating
demyelinaition, disseminated in spase
and time
– Axonal degeneration
– gliosis
• Affects around 2.5 millions people
• MS is the main cause of neurological disability in young people
Multiple Sclerosis
• Affects young people 20-40 years
rarely children, after 60
• Mostly female – 2.5:1
• Incidence and prevalence
in recent years increasing 1
• Autoimmune disease•
SLE incidence 90%
• 1Orton SM et al., Lancet Neurol , 2006
Multiple Sclerosis
• MS is a multifactorial disorder
• No single factor is responsible for conferring
susceptibility
• The aetiology is complex
• Involving both environmental and genetic factors
Multiple Sclerosis
• Environmental factors
• Evidence from geographical and migration studies
has suggested that environmental factors play
an important role in either increasing or decreasing
the risk of MS in patients with a genetic
susceptibility to the disease
• Genetic factors
• Population genetics and twin studies have shown
how important the genes are in conferring
susceptibility to MS
• Involved 200 small genes
Environmental factors
• There is evidence for playing roles
• both infection and the chemico-physical
environment
• infection, sunshine, vitamin D, geographical
gradient, race, hormonal influence, stress
• Additional data are needed to conclusively prove
which factors are the most important in MS
Geographical Distribution of MS
• The prevalence of MS increases with lalitude
• increasing from the equator
• Prevalence in CR 150/100 000 inh
• North USA, Canada and Europe
250-300/100 000
• South USA, Europe, Australia
50-100/100 000
Geographical Distribution of MS
• Lowest risk
Asia, Africa 5/100 000
• Latin America 29/100 000
Middle East
• For the geographical distribution of MS, an environmental
factors (relation infections, sunshine exposure,
vitamin D)
are a likely candidate
Geographical Distribution of MS
Prevalence Increases away from the Equator
• Study in France
confirms that MS
prevalence shows a
gradient increasing
from the equator
• in homogenous
populations
• 4 mil. farmers
• S-N
• 69% F
Vukusic S et al. J Neurol Neurosurg Psychiat 2007;78:707–709.
JNeurolNeurosurgPsychiat2007;78:707–9.Reproduced/amendedwith
permissionfromtheBMJPublishingGroups
53
55
70
47
76
7178
51 53 51
59
77
88
103
97
100
84
93
87
95
62
82
World Health Organisation
Atlas MS resources in the world 2008
World Health Organisation. Multiple sclerosis International Federation [on-line]. Atlas Multiple sclerosis resources in the world 2013. Dostupné
z WWW: <http://www.atlasofms.org/>.
World Health Organisation
Atlas MS resources in the world 2013
World Health Organisation. Multiple sclerosis International Federation [on-line]. Atlas Multiple sclerosis resources in the world 2013.
Dostupné z WWW: <http://www.atlasofms.org/>.
The Effect of Migration on MS Prevalence
• Individuals migrating after age of 15 have
the risk of the country of origin
• An environmental factor (an infectious agent
acquired during infancy/puberty is plausible for
the age-related migration effects, sunshine
exposure, vitamin D)
Population genetics
• MS prevalence varies with ethnic ancestry:
white populations are at greatest risk 1
(areas in which Nordic invasions took place)
• Black population 0.5 risk
• Oriental 0.1 risk
• Racial differences
may explain some of the geographic distribution
differences
Britain 200/100.000
Japan 1.4/100.000- Devic
although both countries lie at the same latitude
Genetics
• Genetic factors contribute
to the aetiology of MS
It is not classic Mendelian type of heridity
• Multiple small genes and their combination
confer susceptibility for development of
autoimmune process 1 200
• The first genetic investigations arised
from higher occurence of MS in families
• Ebers, G., 1995. Genetic factors in multiple sclerosis. MS Forum, Modern Management Workshop,
Boston.
Genetic susceptibility
• Studies of families and twins provide suport
• the life-time risk of developing MS
is about 1/1000 in the general population
• about 15% of patients with MS
have an affected relative
• children are at risk of about 5%
• about 30% risk in monozygotic twins
• 3-5% risk for same-sex dizygotic twins
Twin Studies
• High MZ versus DZ concordance rates reflect
genetic factors
• Concordance rates vary with background
prevalence:
– Canada, Denmark,
Finland, UK, USA1
– France1
– Italy2
MZ = 25–30% DZ = 3–5%
MZ = 5.9% DZ = 3%
MZ = 14.5% DZ = 4%
1Willer CJ et al. PNAS 2003;100:12877–12882; 2Ristori G et al. Ann Neurol 2006;59:27–34.
Cumulative Effect of Adding Shared Genes
• Baseline population rate of 1/1000 – add in the risk
of increasing gene sharing:
– Cousin has MS 7/1000
– Paternal half-sibling 13/1000
– Maternal half-sibling 24/1000
– Full sibling 35/1000
– MZ twin (all genes are common) 270/1000
• DZ twins have a higher MS risk than full siblings
• both share 50% of their genome
• suggesting the role of gestational and
environmental factors
Ebers GC. Unpublished data.
Genetics
• Regions of interest in MS identified on all
chromosomes, but only one confirmed1
• The major histocompatibility complex (HLA)
on chromosome 6 has been identified as one
genetic determinant for MS
• Positive results for HLA Class I/II, T-cell receptor ,
IL7-R, IL2-R, and cytotoxic T-lymphocyteassociated
protein 4
1Colhoun HM et al. Lancet 2003;361:865–872; 2Gregory SG, et al. Nat Genet 2007: published online: 29
July 2007. doi:10.1038/ng2103; 3Dyment DA et al. Lancet Neurol 2004;3:104–110.
Genetics
• I. and II. class HLA genes
• play a key role in the autoimmune
response and antigen presentation
for CD4+ and CD8+ lymphycytes
• I class genes (HLA-A, HLA-B, HLA-C)
Presentation for CD8+ lymphycytes
• II class genes (HLA-DP, HLA-DQ, HLA-DR)
expression on
B-, T-lymphocytes, macrophages
• Short arm of the 6. chromosome-most polymorphic
• Endode cell surface proteins
• Play essential role in initiating an immune response
• Presentation of antigens for CD8+, CD4+ ly
• Gene map of the HLA region. Expert Reviews in Molecular Medicine 2003 Cambridge University Press, 2003,
Cambridge University Press, 2003
HLA genes - I and II class
HLA-associated Diseases
Considerable data on HLA haplotype frequencies
and autoimmune diseases
DR2
DR3
DR4
DR4
B47
B27
0
50
100
MS CD RA IDDM CAH AS
Phenotypefrequency
coeliac disease; type 1 diabetes; congenital adrenal hyperplasia; ankylosing spondylitis
Patients
Healthy controls
Genetics
• Genome-wide association studies (GWAS)
• International MS Genetic Consortium (IMSGC)
• MS Genetics Group studies
• It was proved association with DR2 haplotype
in European population with MS
– HLA-DRB1*1501-DQA1*0102-DQB1*0602 1-5
• Carriers of this haplotype have a 3-fold increased
risk of developing disease, in homozygotes even
6-fold
Genetics
• Metaanalysis ass studies (GWAS) in group of 9.772 patients
from Europe, 17.376 2013
• Data were made by 23 research groups 15 countries, 465 434
polymorfisms
• Proved with HLA-DRB1*1501 risk allele
• (p=1x10–320, OR=3.1)
• Other populations Sweden- 61 % in MS compared to 31 %
in control group
• Other ethnic groups – Japan, Middle East
• Protective effect HLA-A*02 class HLA I
• It was proved next 101 suspect gene polymorphisms
• 1 International Multiple Sclerosis Genetic Consortium: Sawcer S et al. Genetic risk and a primary
role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 10:214-9
Genetics
• Non-HLA genes take part in the
development and progression of the disease
Several international studies
• Proved significant association with gene
polymorphisms for CD25 and CD 127
• encoding cytokines IL-7 and IL-2
• The whole genome of 931 families was examined
International MS genetic consorcium 1
• Hafler et al., 2007
Genetics
• It was proved association with MS
HLA A 02 and DRB1 15 have
23 times increase risk for development of MS
• Mutations in the genes encoding inflammatory
proteins may influence the expression level as
well as the stability of mRNA,
which could influence the aetiopathogenesis
of the MS process
• Brynedal-2007
Genetics
• Genes coding
• Cytokines CXCR5, IL2RA, iL7R, IL7, IL12RB1, L22RA2, IL12A,
• L12B, IRF8, TNFR
• Costimulation molecules CD37, CD40, CD58, CD80, CD86,
• CLECL1
• Signal molecules CBLB, GPR65,MALT1,TYK2
• Lack of genes take part in neurodegenerative process
Environmental Factors
• Infections
• Sunshine and Vitamin D3
• Stress
• Social and cultural factors
Multiple Sclerosis
Environmental Factors
Infections
Possible Candidate Microorganisms
• Chlamydia
• Herpesviruses
– HHV-6
– HSV
– CMV
– EBV
– Varicella zoster
• Canine distemper virus
• Measles virus
• Rubella
• HTLV-1
• HERV
• Corona virus
• Bordetella pertussis
• Mumps virus
Soldan SS et al. Nat Med 1997;3:1394–1397.
Infectious Aetiology of MS
Viruses all have been reported to be present
in patients with MS
Probable no single virus is the trigger
for demyelination in all patients with MS
Instead, several different viruses may
be involved
EBV and MS Risk –
Epidemiological Evidence
• EBV has a potential role in MS aetiology
in many sero-epidemiology studies 1–8
• MS risk very low in people never infected with EBV2
– >99% of MS patients infected with EBV
(~90% of controls)3
• Higher risk of developing MS following symptomatic
EBV infection- mononucl. than if no prior history
persists for 3 decades1
1Nielsen TR et al. Arch Neurol 2007;64:72–75; 2Thacker EL et al. Ann Neurol 2006;59:499–503;
3Ascherio A et al. Epidemiol 2000;11:220–224; 4Ascherio A et al. JAMA 2001;286:3083–3088;
5Levin LI et al. JAMA 2003;289:1533–1536; 6Levin LI et al. JAMA 2005;293:2496–2500;
7Sundstrom P et al. Neurology 2004;62:2277–2282; 8DeLorenze BN et al. Arch Neurol 2006;63:839–844;
9Munch K et al. Acta Neurol Scand 1998;98:395–399.
Potential Mechanisms of EBV
Involvement in MS
• As-yet unknown mechanisms
• Autoimmune
– Molecular mimicry1,2
– Cross reactivation between antigens EBV and PLP
• Oligodendrocyte infection
– New symptomatic MS lesions contain evidence
of extensive oligodendrocyte apoptosis 4
• Bystander activation
B-lymfocytes infected by EBV express
new antigen alfa B crysatllin, and
lead secondary to T-lymphocyte activation
1Lang HLE et al. Nat Immunol 2002;3:940–943; 2van Sechel AC et al. J Immunol 1999;162:129–135; 3
Pender MP. Trends Immunol 2003;24:548–588;
HHV-6
• Evidence to support HHV-6:
– Increased titres of HHV-6 in MS – association
controversial1–4
– HHV-6 showed a positive association in 29/37
MS studies5
– Positive association in 78% of studies (n=38) if
active and latent virus differentiated6
1Sanders VJ et al. J Neurvirol 1996;2:249–258; 2Soldan SS et al. Nat Med 1997;3:1394–1397;
3Ablashi DV et al. Mult Scler 1998;4:490–496;4Ablashi DV et al. J Clin Virol 2000;16:179–191;
5Ablashi DV. http://www.hhv-6foundation.org/febpressrelease.pdf; 6HHV Foundation. www.hhv-
6foundation.org;7 Munger KL et al. Epidemiology 2003;14:141–147; 8Munger KL et al. Neurology
2004;62:1799–1803; 9Bagos PG et al. Mult Scler 2006;12:379–411.
Multiple Sclerosis
Environmental Factors
Sunshine and Vitamin D3
Multiple Sclerosis
Sunshine and Vitamin D3
• Vitamin D3
is very important environmental factor
and a potent immunomodulator
• Hypothesis of relationship between chronic vitamin
D3 deficiency and increased risk for developing MS
in definite geographic distribution is in relation with
prevalence of this illness in temperate zone
The Main Biological Effects of Vitamin D3
• Calcium homeostasis
– Regulates Ca and phosphorus
– Promotes bone formation and mineralisation
• Vitamin D3 is a potent immune modulator
– Enhances macrophage phagocytosis
– Induces expression of cytokine IL-10 (anti inflammatory)
– Inhibits production and function of Th1-inducing proinflammatory
cytokines (IL-1)
– Inhibits transcription of IFNγ target genes
– Induces expression of antimicrobial peptides
The Main Biological Effects of Vitamin D3
• Neuroprotection
– Induces expression of nerve growth factor
– Protects against reactive oxygen species-induced
oxidative damage
• Immune system regulation
– Promotes immunosuppression, phagocytosis
by macrophages, anti-tumour activity
– vitamin D3 supplementation correlated
with reduced risk of some cancers
Sunshine and Vitamin D3
• Hypothesis of relation between chronic vitamin D3
deficiency and increased risk for developing MS in
definite geografical distribution is in link with
prevalence of this illness in temperate zonegeographical
gradient
• Insuficient production of vitamin D3
due to low sunlight exposure
• Calcitrol - active metabolit of vit D3
strong EAE inhibitor suplementation to severe disabled
mouse improvement of disability
Biological Effects of Ultraviolet Radiation
on Vitamin D3
• Vitamin D3
• Generated in skin when light energy
is absorbed by a precursor molecule
(7-dehydrocholesterol)
• Inactive until converted
to the hormonally-active form
(1,25(OH)2D3) calcitrol
25-hydroxycholecalciferol
(25-hydroxy vitamin D3)
cholecalciferol (vitamin D3)
HO
7-dehydrocholesterol
HO
1,25-dihydroxycholecalciferol
(1,25-dihydroxy vitamin D3)
HO
OH
HO
OH
OH
In liver
In kidney
In skin
ACTIVE
FORM
Sunshine and Vitamin D3
Months/year when sunshine cannot produce sufficient vitamin D3 in the skin1–3
1Jablonski NG, Chaplin G. J Hum Evol 2000;39:57–106; 2Jablonski NG, Chaplin G. Scientific American
2002;287:74–81; 3Chaplin G. Am J Phys Anthropol 2004;125:292–302.
No vit D for >6 m/y
No vit D for >6 m/y
No vit D for 1–6 m/y
No vit D for 1–6 m/y
Vit D all year
Theoretical skin colour based on environmental variables1–3
CourtesyofSarahChen
Prevalence of MS in Norway
• Prevalence data for counties in Norway (/105):
– A Finnmark1 (2003) >83
– B Troms1 (2003) >104
– C Nordland (1999) 106
– D Nord Trøndelag (1999) 164
– E Oppland2 (2002) 190
– F Hordaland (2003) 151
– G Oslo2 (2005) 154
• In Norway, MS prevalence does not rise
with increasing latitude, unlike other
northern European countries and the USA
• Lower incidences of MS in coastal fishing
areas than inland farming areas1 due to
higher nutrition intake of vitamin D3 -
fishing
1Kampman MT et al. J Neurol 2007;254:471-477. 2Personal communication.
A
B
C
D
E
F G
Sunshine Implicated in Several Diseases
Reduced sunlight exposure has been linked
to rickets and possibly to:
• Autoimmune diseases
– MS
– Rheumatoid arthritis
– Type 1 diabetes
• Cancer (other than skin cancers)
• Seasonal Affective Disorder
Holick MF. Am J Clin Nutr 2004;80:1678S–1688S.
Vitamin D3 in Humans: Supplementation
• Oral vitamin D3 supplementation should
be given strong consideration
• US Nutrition Guidelines: LOAEL for vitamin D3
in humans is 2000 IU/D
– Probably too low 200 IU/D
• The tolerable upper intake level for vitamin D3
should probably be raised from 2000 IU/D
to 10 000 IU/D3
• Vieth R et al. Am J Clin Nutr 2007;85:649–650; 3Hathcock JN et al. Am J Clin Nutr 2007;85:6–18.
Other factors
• There is no evidence that MS is worsened
by pregnancy
• Should be advised against routine influenza
vaccination
• Surgery, anaesthesia, and lumbar punctures
also have been implicated in MS, but controlled
studies failed to show any relation
Multiple sclerosis
Stress
• Stress is important factor for development and
progression of MS
• Play important role in activation of immune system
• Nervous, immune a endocrine systems
are influenced
Multiple Sclerosis
Genetics and Environmental Factors
How could the various factors interact to cause MS
Genetically susceptible individuals
(HLA haplotype)
Lack of sunlight or vitamin D3 during gestation
and/or early life (latitude- or skin tone-related)
Developmental alterations may result from deficiency in
sunlight interfering with the maturation of the nervous
and/or immune systems and the establishment of tolerance
Tolerance breakdown precipitated by viral infections and
non-specific immune stimulation (EBV?)
Course of Multiple Sclerosis
• Relapsing-remitting MS
• 85% of patients – the MS begins with
new clinical neurological signs
• Activation of inflamation- attack, relaps
24 hours
Complete remission of the first symptoms
occurs frequently, but during next attacks
remissions do not occur or are incomplete
then neurologic disability
increase gradually
Follow clinical remision- months, years (1-2)
Course of the disease
• Relapsing -remitting
(80-85%)
• Primary progressive
(10-15%)
• Sec. chronic-progressive
(30-40%) 15 years
• Relapsing-progressive
3%
Syptoms and signs
• MS varies from benign, largely symptom-free
disease to a rapidly progressive and disabling
disorder
• Clinical course extends for
many decades in most cases
• Rare are fatal within a few months of onset
• The optic nerve, chiasm, brain stem, cerebellum,
pyramidal tract and spinal cord, especially the
lateral and posterior columns - are involved
Syptoms and signs
Retrobulbar neuritis, a common manifestation
of MS-25%, is characterized by gradual decrease
of visual acuity (1-2 weeks), resolve 4-6 weeks,
residual impairment of color vision, dim …
Atrophy of the optic nerve
may not be associated with any fundoscopic
abnormality
35 to 50% of patients with optic neuritis
develop MS
Visual field defects ranging from a unilateral
scotoma or field contraction to homonymous
hemianopia, a central scotoma is the most
characteristic field loss
Syptoms and signs
Diplopia 15 %, VII, VIII
Limb weakness is the most common sign,
monoparesis, hemiparesis, 50 %
qvadriparesis may be present, an asymmetric
paraparesis
Spasticity and ataxia increase the gait disturbance
Slowly progressive spastic paraparesis
is particularly in patients with late onset
Dysarthria, gait ataxia, tremor, incoordination
of the trunk or limbs
Symptoms and sign
• tremor of the head
• urinary symptoms-urgent miction, incotinency
• paresthesias and sensory impairment
• Mental symptoms
• Depression is more common
than the euphoria
• Fatigue- chronic 85%
• Cognitive impairment
• monosymptomatic onset is most common
Disease course
• Two processes- inflammation, neurodegeneration
• In the beginning – predominate inflammation
• Attack-relaps- activation of inflammation
• Later – predominate neurodegneration
• Cause of neurological disability
Multiple sclerosis
• Chronic inflammatory disorder of the CNS
• Demyelination and axonal degeneration
• White matter plaques in the brain
periventricular regions
brainstem, spinal cord, optic nerve
• brain and spinal cord atrophy
• various neurological symptoms
• reversibile x irreversibilile neurological deficit
Multiple sclerosis
• White matter plaques
• in the brain
• Periventricular regions
brainstem, spinal cord,
optic nerve, juxtacortical
• Brain and spinal cord
atrophy
• Various neurological
symptoms
Source: MRI scans provided by Department of Radiology University Hospital Brno.
Patient with advanced demyelinating disease- Flair Dawson fingers.
Patient with advanced demyelinating disease with typical periventricular lesions.
Source: MRI scans provided by Department of Radiology University Hospital Brno.
Multiple sclerosis- pathogenesis
• Autoimmune response direct against CNS
antigens (MBP, MOG, MAG) and secondary
autoantigens
• Activation and clonal expansion of T-cells
CD-4+ and cytotoxic CD-8+
• Secrete immune mediatorscytokines,chemokines
TNF, IFN, IL
• Activation B-cells, synthethise antibodies
• Activated T-cells, B-cells,microglia,
macrophages migrate across BB barrier
Multiple sclerosis- pathogenesis
• Autoimmune response direct
against CNS antigens
(MBP, MOG,MAG) and
secondary autoantigens
• Recognition of ‘non-self’
antigen generally results in
an immune response.
• Similar aminoacid sequence
as in viruses-herpetic, EBV ..
Multiple sclerosis- pathogenesis
• Inflammation is a major contributor to the
formation of acute lesions
destruction of myelin sheats
axonal degeneration
demage of oligodendrocytes
• Degree of inflammation is in correlation with
the extent of axonal loss
• primarily axonal degeneration
• Four patterns of active MS lesions
Management
• Course can be modified
• No treatment completly
stops the disease
Approved therapies
• Interferon β-1a -Rebif® Avonex®, Plegridy®
(30ug i.m./weekly)
• Interferon β-1b Betaferon® 0,25 mg every other
day s.c.
• Glatiramer acetate- Copaxone® 40 mg/D s.c.
• Teriflunomide – Aubagio p.o.
• Slow accumulation of neurologic disablity
by 30-40%, reduction of number and the severity
of clinical attacks, and increasing MRI lesions
The first line therapy
Drug Admin Dose Frequency Name
INF beta- 1b s.c. 250 EOD Betaferon
INF beta- 1a s.c. 22, 44 3 x weekly Rebif 22
Rebif 44
INF beta- 1a i.m. 30 1x weekly
Every two
weeks
Avonex
Plegridy
Glatiramer
acetát
s.c. 40 3 x weekly Copaxone
Indication criteria for the initiation
of DMD therapy
• CIS
• RR-MS
2 attacks in the past year
3 attacks in the past 2 years
• Attack treatment
• methylprednisolonSolu-Medrol
3-5 grams
• It reduces inflammation activity
It will not affect the progression of the
disease even with repeated administration
• Interferon beta is an antiproliferative
multifunctional cytokine
• Complex immunomodulatory effect reduction
of activation and penetration
of autoaggressive T ly into the CNS
reduction of proinflammatory cytokine
production, interferon gamma
increased production of anti-inflammatory
cytokines
It reduces the permeability of the blood-brain
barrier
Glatiramer acetate- Copaxone
• Copolymer of four amino acids
(glutamate, lysine, alanine, tyrosine)
contained in the same ratio as MBP
Autoaggressive ly bind to GA
produce anti-inflammatory cytokines
and produce neuroprotective BDNF
• S.c. at a dose of 40 mg 3x week
Total reaction - histamine, redness, shortness
of breath, lasting a few minutes, local reactions
Second line treatment
• Patient treated with interferons or glatiramer
acetate
The persistent high activity of the disease
• Tysabri-Natalizumab
• Fingolimod- Gilenya
• Tecfidera-Dimethyl fumarate
• Ocrevus- Ocrelizumab
• Mavenclad- cladribinum
• Lemtrada-Alemtuzumab
Natalizumab - Tysabri
• Monoclonal antibody
It binds to the adhesion molecule VLA-4 on the
surface of white blood cells and blocks its binding
to vascular endothelial cells
Prevents white blood cells from penetrating
into the CNS
Reduces RR - up to 60%
It slows the progression of disability
Significantly reduces brain MR activity by up to 90%
Natalizumab - Tysabri
• It is given as monotherapy
This highly effective treatment is unfortunately
associated with the risk of developing Progressive
Multifocal Leukoencephalopathy – PML
• Unfortunately, at present, there are no screening
tests that would allow a reliable measure of risk
• Significant risk factors include duration of therapy
Previous treatment with immunosuppressants
The presence of ELISA antibodies detected in serum
JC virus
Natalizumab - Tysabri
• Risk of developing PML
Treatmen
duration
Anti-JCV Antibody
Negative
Anti-JCV Antibody
Positive
Immunosupressive
therapy -
Immunosupressive
therapy +
1-24 months <1/1.000 2/1.000
25-48 months 4/1.000 11/1.000
FINGOLIMOD- GILENYA
• It is a synthetic analog of myriocin, derived from
Isaria Sinclair's mushroom
It binds to four of the five subgroups of sfigosinephosphate
receptors in the human body
The S1P1 receptor is responsible for the
immunomodulatory effect of Fingolimod
Binding of this receptor on the surface of white
blood cells leads to their reduced travel from the
lymphatic tissue
FINGOLIMOD- GILENYA
• There is a significant reduction of MRI lesions
lower annual RR
up to 77% of patients are without an attack
Second line treatment
• Ocrelizumab- Ocrevus directed against CD 20
antigen on mature B cells, but not plasma cells
• for non-Hodkin´s lymphoma and RA
• fairly safe medication (market 2019)
• i.v. infusions, 2 weeks apart, every 6 months
• Alemtuzumab-Lemtrada
AB against CD 52,
antigen on most B and T ly (leukemia)
• Cladribine- Mavenclad
Generalized immunosupression
• Corticosteroids
• Methylprednisolon 1 g per day for 3-5 days
• Medrol 4mg/day
• Prednison 5 mg/day
Generalized immunosupression
• Azathioprine-modest effect
• Mitoxantrone- immunosupressant
(side effect cardiomyopathy, promyelocytic
leukemia)- in rapidly progressive MS
• Cyclophosphamide??
• Methotrexate-slight effect
• Cyclosporine A (renal side effects)
Symptomatic treatment
• Fatigue: Amantadine 2x100 mg (Viregyt)
• Spasticity: Baclofen, Sirdalud
• Spastic blader: Spasmex, Ditropan
• Amitriptyllin 25 mg
• Antineuralgic treatment: Lyrica, Gabapentin
Current treatment of RR-RS
• Long-term treatment slow the progression
of the disease
• Treatment of acute attack of the disease
• Disease modifying drugs - DMD
Slow progression
immunomodulatory and immunosuppressive
effect
• Anti-inflammatory effect
Current treatment
• At present, we have a range of therapeutic
options in MS treatment.
• These drugs have in particular an
anti-inflammatory effect.
Therefore, our primary goal remains the early
diagnosis of MS, the earliest initiation of
treatment and thus the prevention of the
development of the neurodegenerative process.
• To prevent the disability of the patients