Multiple Sclerosis Treatment

Email: enquiry@medicyatra.
com
Multiple Sclerosis:
Principles,& treatment Presented By: Medic Yatra
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Email: enquiry@medicyatra.com
1-Overreview
Multiple Sclerosis
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
Email: enquiry@medicyatra.com 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
http://www.spermbankcal Youre not alone ifornia.com/buy-sperm Worldwide, 2.5 million people have MS online.h
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 factors Environmental factors
MS
Immunological factors
3-The Biology of MS
The Biology Email: enquiry@medicyatra.com of MS
What does the central nervous system do?

The central nervous system (CNS) consists of the:1
Brain Spinal cord Optic nerves
The CNS is the bodys command center. It interprets sensory information and sends commands to muscles3
Spinal cord
Brain
Copyright @
How does the CNS work?

Nerve Cell
Messages travel to and from the CNS through nerve cells3
Myelin surrounds the nerve fibers, protecting them like the coating of a wire1
Myelin Cell body
Nerve fibers (or axon)
Nerve fibers (or axon)
Myelin
How could autoimmune responses cause MS?
How does MS affect the CNS?

In MS, cells of the immune system attack myelin and can cause permanent damage3
Nerve Cell
Areas where myelin has been damaged interrupt communication Exposed nerve fibers are severed, causing permanent damage
Axonal Transection in Acute MS Lesions
.
. How is MS monitored?
MRI showing no signs of damage MRI showing an active lesion* MRI showing 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
*The exact relationship between MRI findings and the clinical status of patients is unknown.
is located
4-Pathophysiology
mechanism
NORMAL CONDUCTION
ABNORMAL CONDUCTION
Inflammation and Axonal Transection

Disease Stage
Early Late
Main Component
Inflammation and demyelination Atrophy, axonal loss, and increasing tissue destruction (less Gd-defined inflammation, demyelination ongoing)
Main Clinical Outcome

Relapses Disability
MS Email: enquiry@medicyatra.com pathophysiology
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
What does the effect in central nervous system
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 Natl MS Society www.nationalmssociety.org/Sourcebook-Early.asp. Accessed May 17, 2006.
Current Therapies:
Immunosuppressant's and Immunomodulators
Corticosteroids Interferons :
Betaseron (interferon -1b) Avonex (interferon -1a) Rebif (interferon -1a)
Immunosuppressants and immunomodulators:

Copaxone (glatiramer acetate) Novantrone (mitoxantrone)
Symptomatic management@ Forever Medic Online Copyright

Pvt. Ltd
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 inflammation by:
Reduce the production of the TNFa , known to induce damage to myelin

Switching cytokine production from type 1 (proinflammatory) 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 :
Avonex (Interferon -1a)

Indication: relapsing forms of MS Dose: 30 mcg IM once weekly Reduces rate of clinical relapse Reduces the development of new lesions
Avonex-lyo-vial
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 :
Rebif
Interferon -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
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
May delay progression of disability
Interferons :
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 Chills Fever Muscle aches Asthenia (weakness) Betaseron and Rebif have injection site reactions
Severe depression Suicide Seizures Cardiac effects Anemia Elevated liver enzymes
Severe hepatic
injury, including cases of hepatic failure, has been This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark. reported in patients Copyright @ Forever Medic Online taking Avonex
Pvt. Ltd
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
Auto Injectors
autoject 2 for glass syringe Dispenses Copaxone
Rebiject Dispenses Rebif
autoject 2.25 Dispenses Betaseron
All provided free from manufacturer. Rebiject and Copaxone need a prescription. This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
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
Spasticity
Symptoms
Management
Painful spasms in the lower Remove irritating factors and upper limbs Physical therapy, baclofen, diazepam, dantrolene Trigeminal neuralgia, pain, tonic seizures Feeling tired (morning or early afternoon) Common, occurs in high percentage of patients carbamazepine, Neurontin, phenytoin Energy conservation, amantidine Anti-depressants
Paroxysmal phenomena Fatigue Depression Sexual dysfunction Urinary dysfunction
Inability to produce/ sustain Behavioral therapy an erection Viagra, Muse Urgency, frequency and retention Detrol, Ditropan, Botox
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
Email: enquiry@medicyatra.com Conclusion
Conclusion
1-Multiple sclerosis is not a common Disease 2-Its 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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Email: enquiry@medicyatra.

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Email: enquiry@medicyatra.com MS Overview

What is Multiple Sclerosis (MS)?

Copyright @ Forever Medic Online Pvt. Ltd

Piere Marie Charcot

This disease without his

His descriptions about

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Risk is higher in siblings

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

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

1. Research into the Causes of MS

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

The Biology Email: enquiry@medicyatra.com of MS

What does the central nervous system do?

The Biology Email: enquiry@medicyatra.com of MS

How does the CNS work?

Messages travel to and from the CNS through nerve cells3

Nerve fibers (or axon)

Nerve fibers (or axon)

Copyright @ Forever Medic Online Pvt. Ltd

How could autoimmune responses cause MS?

Copyright @ Forever Medic Online Pvt. Ltd

The Biology Email: enquiry@medicyatra.com of MS

How does MS affect the CNS?

Copyright @ Forever Medic Online Pvt. Ltd

Axonal Transection in Acute MS Lesions

The Biology Email: enquiry@medicyatra.com of MS

Active lesion Permanent damage

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Inflammation and Axonal Transection

Main Clinical Outcome

Copyright @ Forever Medic Online Pvt. Ltd

MS Email: enquiry@medicyatra.com pathophysiology

What does the effect in central nervous system

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Copyright @ Forever Medic Online Pvt. Ltd

Immunosuppressants and immunomodulators:

Symptomatic management@ Forever Medic Online Copyright

Interferon Beta Mechanism of Action

Reduce the production of the TNFa , known to induce damage to myelin

Decrease antigen presentation, to reduce the attack

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

Copyright @ Forever Medic Online Pvt. Ltd

Avonex (Interferon -1a)

May delay progression of disability

Copyright @ Forever Medic Online Pvt. Ltd

Betaseron (interferon beta-1b)

Copyright @ Forever Medic Online Pvt. Ltd

Side Effects of Interferons

Copyright @ Forever Medic Online Pvt. Ltd

Copaxone Mechanism of Action

Copyright @ Forever Medic Online Pvt. Ltd

autoject 2 for glass syringe Dispenses Copaxone

Rebiject Dispenses Rebif