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Transcript of Multiple Sclerosis Treatment
Multiple Sclerosis:Multiple Sclerosis:
Principles,& treatment
Presented By:
Medic Yatra
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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
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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
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Piere Marie Charcot Piere Marie Charcot
This disease without his name is meaningless
His descriptions about disease is very precise
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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
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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
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1. Research into the Causes of MS1. Research into the Causes of MS
Geneticfactors
Immunologicalfactors
Environmentalfactors
MS
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3-The Biology of MS3-The Biology of MS
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The Biology of MS
What 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
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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
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How could autoimmune responses cause MS?How could autoimmune responses cause MS?
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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
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Axonal Transection in Acute MS LesionsAxonal Transection in Acute MS Lesions
.
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The Biology of MS
How is MS monitored?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 itis located
*The exact relationship between MRI findings and the clinical status of patients is unknown.
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4-Pathophysiology4-Pathophysiology
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NORMAL CONDUCTIONNORMAL CONDUCTION
ABNORMAL CONDUCTION
mechanismmechanism
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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)
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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
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Treatment GoalsTreatment Goals
Reduce (control) relapses
Delay disease progression
Delay disability
Alleviate symptoms
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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.
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Current Therapies: Immunosuppressant's and ImmunomodulatorsCurrent 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
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CorticosteroidsCorticosteroidsSymptomatic 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
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Interferon BetaMechanism of ActionInterferon BetaMechanism of ActionReduce 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,
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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
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Interferons : RebifInterferons : RebifInterferon -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
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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
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Side Effects of InterferonsSide Effects of InterferonsCommon:
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
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Noninterferons: Copaxone (glatiramer acetate) PFSNoninterferons: 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
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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
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Auto InjectorsAuto Injectorsautoject® 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.
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Antineoplastics:Nonantrone 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)
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Antineoplastics: Novantrone (cont.)
Antineoplastics: Novantrone (cont.)
Reduces exacerbation rate
Prolongs time to first treated relapse
Improves EDSS scores versus baseline
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NovantroneMechanism of ActionNovantroneMechanism of ActionInhibits or prevents the development of any uncontrolled new or abnormal growth, such as a neoplasm or tumor
Suppresses B-cell and T-cell immunity
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NovantroneSide EffectsNovantroneSide EffectsModerate 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
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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)
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NovantroneContraindicationsNovantroneContraindicationsLVEF < 50%
CHF
Baseline neutrophil count < 1500 cells/mm3
Pre-existing myelosuppression
Abnormal LFT
Pregnancy, breastfeeding
Cumulative lifetime dose 140 mg/m2
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Immunosuppressant'sImmunosuppressant'sShow only slight evidence of benefit in MS
Used only for progressive MS
Associated with serious side effects Thiopurines (Imuran)
Methotrexate
Alkylating agents (Cytoxan)
Cyclosporine
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Symptomatic TreatmentsSymptomatic TreatmentsProblem 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
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ConclusionConclusionEarly 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
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ChallengesChallenges
Challenges for the person with MS Physical difficulties
Financial concerns
Social issues
Emotional issues
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Resources and LinksResources and LinksSupport/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
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Conclusion
ConclusionConclusion
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
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