Multiple Sclerosis Treatment

Email: enquiry@medicyatra.com

Multiple Sclerosis:
Principles,& treatment
Presented By:
Medic Yatra

Copyright @ Forever Medic Online Pvt. Ltd


1-Overreview


Multiple Sclerosis Email: enquiry@medicyatra.com

Overview

- Chronic, inflammatory, demyelinating
disease its not common
- Affects the myelin sheath and axons
of the Central Nervous System (CNS)
- Progressive clinical or subclinical
course
- Common cause of disability
in young adults


MS Overview

What is Multiple Sclerosis (MS)?
MS causes nerve damage over time
 Ms is not a common disease

 MS is not considered fatal, but it affects
everyone differently
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 Worldwide, 2.5 million people have MS
 MS currently affects 400,000 Americans
 Incidence & prevalence in iran is not clear
 Every week, 200 new people are diagnosed
in the US



Piere Marie Charcot

 This disease without his
name is meaningless

 His descriptions about
disease is very precise



2-Ethiology



Is MS a Hereditary Disease?
Genetic factors
 First- and second-degree relatives are at
increased risk
 Risk is higher in siblings
– Nontwin siblings (2%)
– Monozygotic twins (30%)
– Dizygotic twins (2.3%)
Susceptibility gene
 Major histocompatibility
complex (MHC) on
chromosome 6

Source: http://www.msfacts.org/info/info_faq.html, http://www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm#54263215 and http://
www.nationalmssociety.org/Sourcebook-Epidemiology.asp. Accessed May 17, 2006



MS plaques contain
- Complement
- Immunoglobulins
- (These indicate disruption of BBB
and local production of Ig)
-TFN(gamma) TNF, IL-2

There is strong evidences that it has immunological base
1-CSF changes (cells;oligoclonal bands)
2-Response to immunomodulators
3-Specific HLA



1. Research into the Causes of MS

Genetic Environmental
factors factors
MS

Immunological
factors



3-The Biology of MS


The Biology
of MS

What does the central
nervous system do? Brain
The central nervous system (CNS)
consists of the:1
Spinal
 Brain cord
 Spinal cord
 Optic nerves

The CNS is the body’s command center. It
interprets sensory information and sends
commands to muscles3

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The Biology
of MS

How does the CNS work?
Messages travel to and from the CNS through nerve cells3
Nerve Cell

Myelin surrounds the nerve fibers, protecting
them like the coating of a wire1

Myelin
Nerve fibers (or axon)
Cell body

Nerve fibers (or axon) Myelin



How could autoimmune responses cause MS?


The Biology
of MS

How does MS affect the CNS?
In MS, cells of the immune system attack myelin and can
cause permanent damage3

Areas where myelin has been Exposed nerve fibers are severed,
Nerve Cell damaged interrupt communication causing permanent damage



Axonal Transection in Acute MS Lesions

.


The Biology
of MS

How is MS monitored?
.

MRI showing no signs MRI showing an active MRI showing
of damage lesion* permanent damage

Active
lesion

Permanent
damage
 These images may also help detect “silent” damage (lesions detected by MRI that do not
result in symptoms)1
 The impact of this damage depends on the destructiveness of the lesion and where it
is located
*The exact relationship between MRI findings and the clinical status of patients is
unknown.



4-Pathophysiology



mechanism
NORMAL CONDUCTION

ABNORMAL CONDUCTION



Inflammation and Axonal Transection
Main
Disease Main Clinical
Stage Component Outcome

Early Inflammation and demyelination Relapses

Late Atrophy, axonal loss, and Disability
increasing tissue destruction
(less Gd-defined inflammation,
demyelination ongoing)


MS
pathophysiology

What does the effect in
central nervous system
1-All the symptoms are upper motor
2-Dissamination in time & space
2-Conduction block is cause of fatigue
3-Agrravation with heat
4-remyelination is not perfect
5-plaques could be in silent areas

Immunological pathological physiologic clinical



Treatment Goals
Reduce (control) relapses
Delay disease progression
Delay disability
Alleviate symptoms



Early Treatment

The National MS Society recommends:
“Initiation of therapy with an
immunomodulator is advised as soon
as possible following a definite
diagnosis of MS with a relapsing
course, and may be considered for
selected patients with a first attack
who are at high risk for MS.”
Source: Recommendation of the Executive Committee of the Medical Advisory Board of the Nat’l MS Society www.nationalmssociety.org/
Sourcebook-Early.asp. Accessed May 17, 2006.



Current Therapies:
Immunosuppressant's and Immunomodulators
Corticosteroids
Interferons β :
 Betaseron® (interferon β-1b)
 Avonex® (interferon β-1a)
 Rebif® (interferon β-1a)
Immunosuppressants and
immunomodulators:
 Copaxone® (glatiramer acetate)
 Novantrone® (mitoxantrone)
Symptomatic management


Corticosteroids
Symptomatic management
Used in moderate-to-severe
exacerbations
IV methylprednisolone 500 mg/day for
five days followed by oral prednisone
(optional)
Hasten clinical recovery
Delay recurrence of neurologic events
Does not alter the course of MS



Interferon Beta
Mechanism of Action
Reduce the production of the TNFa ,
known to induce damage to myelin
Reduce inflammation by:
 Switching cytokine production from type 1 (pro-
inflammatory) to type 2 (anti-inflammatory) cells
 Decrease antigen presentation, to reduce the
attack on myelin

Reduce the ability of immune cells to
cross the blood-brain barrier,



Interferons β: Avonex-lyo-vial
Avonex (Interferon β-1a)

Indication: relapsing
forms of MS
Dose: 30 mcg IM
once weekly
Reduces rate of
clinical relapse
Reduces the development
of new lesions
May delay progression
of disability
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.



Interferons β:
Rebif
Interferon β-1a
Indication: relapsing/remitting forms of
MS
Dose: 22 or 44 mcg SC 3 times per
week
Decreases frequency of relapse
Delays the increase in the
volume of lesions
May delay progression
of disability


Interferons β:
Betaseron (interferon beta-1b)
Indication: Relapsing forms of MS
Dose: 8 million IU SC every other day
Reduces rate of clinical relapse
Reduces the development of
new lesions
Delays the increase in the
volume of lesions




Side Effects of Interferons
Common: Uncommon:
 Flu-like symptoms  Severe depression
 Chills  Suicide
 Fever  Seizures
 Muscle aches  Cardiac effects
 Asthenia (weakness)  Anemia
 Betaseron and Rebif  Elevated liver
have injection site enzymes
reactions
 Severe hepatic
injury, including
cases of hepatic
failure, has been
reported in patients
taking Avonex


Noninterferons:
Copaxone (glatiramer acetate) PFS

Indication: Reduction of frequency of
relapses in patients with RRMS
Dose: 20 mcg SC once daily
Reduces the frequency of
exacerbations
Moderately reduces the
development of new lesions




Copaxone Mechanism of Action
Synthetic chain of four amino acids
Structurally resembles the myelin basic protein
molecule
Believed to block the immune system from
attacking myelin




autoject® 2 for glass syringe Rebiject®
Auto Injectors Dispenses Copaxone Dispenses Rebif

autoject® 2.25
Dispenses Betaseron

All provided free from manufacturer.
Rebiject and Copaxone need a prescription.



Antineoplastics:Nonantrone
Indication:
Reduction of
relapse rate and
clinical disability in
patients with SPMS,
PRMS or worsening
RRMS
Dose: 12 mg/m2 as
short IV
infusion (five
minutes to 15
minutes every three
months)



Antineoplastics:
Novantrone (cont.)
Reduces exacerbation rate
Prolongs time to first treated relapse
Improves EDSS scores versus
baseline




Novantrone
Mechanism of Action
Inhibits or prevents the development
of any uncontrolled new or abnormal
growth, such as a neoplasm or tumor
Suppresses B-cell and T-cell immunity




Novantrone
Side Effects
Moderate to severe
 Bone marrow suppression
– Neutropenia (decreased WBC and ANC)
– Thrombocytopenia (decreased platelets)
– Acute myelogenous leukemia
 Cardiac toxicity
– Congestive heart failure (CHF)
– Decreased left ventricular ejection fraction (LVEF)
– Maximum cumulative dose 140 mg/m2




Novantrone
Side Effects
Moderate to severe
 Teratogenic effects
– Fetal growth retardation in rats
– Shortened gestation period
– Excreted in breast milk
Mild to moderate
 Increased liver enzymes
 Nausea
 Alopecia (hair loss - transient)




Novantrone
Contraindications
LVEF < 50%
CHF
Baseline neutrophil count < 1500 cells/
mm3
Pre-existing myelosuppression
Abnormal LFT
Pregnancy, breastfeeding
Cumulative lifetime dose ≥ 140 mg/m2



Immunosuppressant's
Show only slight evidence of benefit in
MS
Used only for progressive MS
Associated with serious side effects
 Thiopurines (Imuran)
 Methotrexate
 Alkylating agents (Cytoxan)
 Cyclosporine

This page contains prescription brand drugs that are registered or trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.



Symptomatic Treatments
Problem Symptoms Management
Spasticity Painful spasms in the Remove irritating factors
lower and upper limbs Physical therapy,
baclofen, diazepam,
dantrolene

Paroxysmal phenomena Trigeminal neuralgia, carbamazepine,
pain, tonic seizures Neurontin, phenytoin
Fatigue Feeling tired (morning or Energy conservation,
early afternoon) amantidine

Depression Common, occurs in high Anti-depressants
percentage of patients

Sexual dysfunction Inability to produce/ Behavioral therapy
sustain an erection Viagra, Muse

Urinary dysfunction Urgency, frequency and Detrol, Ditropan, Botox
retention



Conclusion
Early treatment may delay disability
and enhance recovery from relapses
Treatment must be a cooperative effort
between multidisciplinary team of
healthcare providers
Medications are not a cure for MS



Challenges
Challenges for the person with MS
 Physical difficulties
 Financial concerns
 Social issues
 Emotional issues



Resources and Links
Support/Information
 National MS Society (NMSS) 1-800-FIGHT-MS
 Consortium of MS Centers 1-201-837-0727
 MS Foundation 1-800-441-7055
 MS Association of America 1-800-833-4MSA



5-Summary


Conclusion

Conclusion
1-Multiple sclerosis is not a common Disease
2-It’s the result of Different mechanisms
3-the most probable mechanism is immunological

Its clear that effective treatments depends on better
undrestanding of mechanisms


Multiple Sclerosis Treatment

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Editor's Notes