Download - Multiple Sclerosis
![Page 1: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/1.jpg)
Multiple Sclerosis:Multiple Sclerosis:
Principles & treatment
Presented By:Sohaib Ashraf
Roll # 70
Second Year
SKZMDC, LHR.
![Page 2: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/2.jpg)
1-Overview1-Overview
![Page 3: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/3.jpg)
Multiple Sclerosis OverviewMultiple 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
![Page 4: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/4.jpg)
MS Overview
What is Multiple Sclerosis (MS)?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
You’re not alone 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 diagnosedin the US
![Page 5: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/5.jpg)
Piere Marie Charcot Piere Marie Charcot
This disease without his name is meaningless
His descriptions about disease is very precise
![Page 6: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/6.jpg)
![Page 7: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/7.jpg)
2-Ethiology2-Ethiology
![Page 8: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/8.jpg)
Is MS a Hereditary Disease?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
![Page 9: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/9.jpg)
MS plaques contain 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 base1-CSF changes (cells;oligoclonal bands) 2-Response to immunomodulators3-Specific HLA
![Page 10: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/10.jpg)
1. Research into the Causes of MS1. Research into the Causes of MS
Geneticfactors
Immunologicalfactors
Environmentalfactors
MS
![Page 11: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/11.jpg)
3-The Biology of MS3-The Biology of MS
![Page 12: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/12.jpg)
The Biology of MSWhat does the central
nervous system do?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 body’s command center. It interprets sensory information and sends commands to muscles3
Spinal Spinal cordcord
BrainBrain
![Page 13: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/13.jpg)
The Biology of MS
How does the CNS work?How does the CNS work?
Messages travel to and from the CNS through nerve cells3
Myelin surrounds the nerve fibers, protecting them like the coating of a wire1
Nerve Cell
Nerve fibers (or axon)
MyelinNerve fibers (or axon)
Cell body
Myelin
![Page 14: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/14.jpg)
How could autoimmune responses cause MS?How could autoimmune responses cause MS?
![Page 15: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/15.jpg)
MS is an Immune-Mediated Disease
BBB=blood-brain barrier; APC=antigen-presenting cell.Adapted from Miller et al. Continuum: Multiple Sclerosis (Part A). 1999;5:7.
![Page 16: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/16.jpg)
The Biology of MS
How does MS affect the CNS?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 damaged interrupt communication
Exposed nerve fibers are severed, causing permanent damageNerve Cell
![Page 17: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/17.jpg)
Axonal Transection in Acute MS LesionsAxonal Transection in Acute MS Lesions
Reprinted from Trapp BD et al. N Engl J Med. 1998;338:278-285. Copyright 1998 Massachusetts Medical Society. .
![Page 18: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/18.jpg)
The Biology of MS
How is MS monitored?How is MS monitored?Magnetic Resonance Imaging (MRI) detects areas of inflammation (active lesions) and areas of permanent damage in the brain1
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 itis located
*The exact relationship between MRI findings and the clinical status of patients is unknown.
![Page 19: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/19.jpg)
4-Pathophysiology4-Pathophysiology
![Page 20: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/20.jpg)
NORMAL CONDUCTIONNORMAL CONDUCTION
ABNORMAL CONDUCTION
mechanismmechanism
![Page 21: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/21.jpg)
Inflammation and Axonal TransectionInflammation and Axonal Transection
DiseaseStage
Main Component
Main Clinical Outcome
Early Inflammation and demyelination Relapses
Late Atrophy, axonal loss, and Disability increasing tissue destruction(less Gd-defined inflammation,
demyelination ongoing)
![Page 22: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/22.jpg)
MSpathophysiology
What does the effect in central nervous system 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
![Page 23: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/23.jpg)
Treatment GoalsTreatment Goals
Reduce (control) relapses
Delay disease progression
Delay disability
Alleviate symptoms
![Page 24: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/24.jpg)
Early TreatmentEarly 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.
![Page 25: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/25.jpg)
Current Therapies: Immunosuppressants and ImmunomodulatorsCurrent Therapies: Immunosuppressants and Immunomodulators
Corticosteroids
Interferons : Betaseron (interferon -1b)
Avonex (interferon -1a)
Rebif (interferon -1a)
Immunosuppressants and immunomodulators: Copaxone (glatiramer acetate)
Novantrone (mitoxantrone)
Symptomatic management
![Page 26: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/26.jpg)
CorticosteroidsCorticosteroids
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
![Page 27: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/27.jpg)
Interferon BetaMechanism of ActionInterferon BetaMechanism 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,
![Page 28: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/28.jpg)
Interferons : Avonex (Interferon -1a)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
May delay progression of disability
Avonex-lyo-vial
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 29: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/29.jpg)
Interferons : RebifInterferons : 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
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.
![Page 30: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/30.jpg)
Interferons : Betaseron (interferon beta-1b)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
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 31: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/31.jpg)
Side Effects of InterferonsSide Effects of Interferons
Common:
Flu-like symptoms
Chills
Fever
Muscle aches
Asthenia (weakness)
Betaseron and Rebif have injection site reactions
Uncommon:
Severe depression
Suicide
Seizures
Cardiac effects
Anemia
Elevated liver enzymes
Severe hepatic injury, including cases of hepatic failure, has been reported in patients taking Avonex
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 32: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/32.jpg)
Copaxone Mechanism of ActionCopaxone 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
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 33: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/33.jpg)
Auto InjectorsAuto Injectors
autoject® 2 for glass syringeDispenses Copaxone
Rebiject®
Dispenses Rebif
autoject® 2.25Dispenses 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.
![Page 34: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/34.jpg)
NovantroneMechanism of ActionNovantroneMechanism 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
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 35: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/35.jpg)
NovantroneSide EffectsNovantroneSide 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)
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
![Page 36: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/36.jpg)
ImmunosuppressantsImmunosuppressants
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.
![Page 37: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/37.jpg)
Symptomatic TreatmentsSymptomatic Treatments
Problem Symptoms Management
Spasticity Painful spasms in the lower and upper limbs
Remove irritating factors Physical therapy, baclofen, diazepam, dantrolene
Paroxysmal phenomena Trigeminal neuralgia, pain, tonic seizures
carbamazepine, Neurontin, phenytoin
Fatigue Feeling tired (morning or early afternoon)
Energy conservation, amantidine
Depression Common, occurs in high percentage of patients
Anti-depressants
Sexual dysfunction Inability to produce/ sustain an erection
Behavioral therapy Viagra, Muse
Urinary dysfunction Urgency, frequency and retention
Detrol, Ditropan, Botox
![Page 38: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/38.jpg)
ConclusionConclusion
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
![Page 39: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/39.jpg)
ChallengesChallenges
Challenges for the person with MS Physical difficulties
Financial concerns
Social issues
Emotional issues
![Page 40: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/40.jpg)
Resources and LinksResources 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
![Page 41: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/41.jpg)
5-Summary5-Summary
![Page 42: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/42.jpg)
ConclusionConclusionConclusion
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
![Page 43: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/43.jpg)
THANKYOU
![Page 44: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/44.jpg)
![Page 45: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/45.jpg)
![Page 46: Multiple Sclerosis](https://reader035.vdocuments.us/reader035/viewer/2022062320/55c1b26bbb61ebc67a8b47ff/html5/thumbnails/46.jpg)