MedicYatra provides the safe & best Multiple Sclerosis Treatment and procedure at its affiliate & trusted hospitals & clinics in various metro cities of India, like Mumbai, Delhi, Bangalore, Chennai, Pune etc.Our Associate Board certified doctors are extensively trained and vastly experienced and have performed hundreds of such cases at our state of the art JCI accredited hospitals & Clinics. Our aim is to provide you the best of the services at the most affordable costs. Don't forget to say hi at info@medicyatra.com
3. 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
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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
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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?
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
- 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
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1. Research into the Causes of MS
Genetic Environmental
factors factors
MS
Immunological
factors
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11. The Biology
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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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12. The Biology
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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
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14. The Biology
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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
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16. The Biology
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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.
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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)
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20. MS
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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
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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.
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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
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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,
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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
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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
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of disability
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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
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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
This page contains prescription brand drugs that are registered or registered trademarks of pharmaceutical manufacturers that are not affiliated with Caremark.
reported in patients
taking Avonex
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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
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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
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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.
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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.)
Reduces exacerbation rate
Prolongs time to first treated relapse
Improves EDSS scores versus
baseline
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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
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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
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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)
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Novantrone
Contraindications
LVEF < 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'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.
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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
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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
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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
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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
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Editor's Notes
Importance of early treatment : the ability to slow the frequency of relapses and the accumulation of disability diminishes as the disease progresses It is most beneficial to reduce the relapse rate at the earliest possible stage of the disease, because relapses represent severe short-term disability and contribute to accumulated long-term disability Early treatment of patients with limited disability with therapeutic agents that slow the demyelination process may help maintain patients in a less disabled state for a longer period of time. No therapy has been shown to reverse more advanced disability or arrest disease progression
Recommendation of the Executive Committee of the Medical Advisory Board of the Nat’l MS Society (www.nationalmssociety.org/Sourcebook-Early.asp) Immunomodulators include beta interferon 1b, beta interferon 1a, glatiramer acetate
These therapies are the cornerstones of MS treatment
Glucocorticoids - anti-inflammatory agents, reduce the inflammation and edema at the site of the myelin attack. With the inflammation calmed down, normal function returns more rapidly and the duration of the attack is reduced. To treat attack: the agent is typically given at high doses 3-5 days then tapered down for 1-3 weeks Commonly used steroids: Prednisone (PO) decadron (PO), solumedrol (IV) and ACTH (IM) (synthetic hormone to produce anti-inflammatory effects) *IV methyl prednisone is the treatment of choice during relapses but does not prevent relapses Side effects: osteoporosis, peptic ulcer, glucose intolerance and hypertension
No one knows what is totally going on with the activity of the immunomodulators, but we have some general understanding of what is happening at different times. (Interferon-beta ) helps to slow MS by reducing target recognition, repairing the damaged BBB, and reducing pro-inflammatory cytokines. BBB=blood brain barrier
Interferons (alpha, beta, gamma & others) are naturally occurring proteins produced by the body. Interferons have been found to have immunoregulatory, antiviral and antiproliferative properties. In general, interferons protect the body by inhibiting the multiplication of viruses It has been postulated that MS may be due to an immune disorder triggered by a viral infection. Since both viral infections and the immune system are modulated by interferons, the use of interferons has been studied in MS. The antiviral properties of interferons act to suppress background viral infection. The overall mechanism in beneficial effects of beta interferons is not established. Avonex is manufactured by Biogen. None of the INFs available today are approved for progressive disease. Studies are currently underway to evaluate INFs in these patients. The recently completed trial demonstrated that Avonex reduced the progression of disability by 27% vs. placebo in patients with SPMS. Full analysis still is pending.
Interferons (alpha, beta, gamma & others) are naturally occurring proteins produced by the body. Interferons have been found to have immunoregulatory, antiviral and antiproliferative properties. In general, interferons protect the body by inhibiting the multiplication of viruses It has been postulated that MS may be due to an immune disorder triggered by a viral infection. Since both viral infections and the immune system are modulated by interferons, the use of interferons has been studied in MS. The antiviral properties of interferons act to suppress background viral infection. The overall mechanism in beneficial effects of beta interferons is not established. Avonex is manufactured by Biogen. None of the INFs available today are approved for progressive disease. Studies are currently underway to evaluate INFs in these patients. The recently completed trial demonstrated that Avonex reduced the progression of disability by 27% vs. placebo in pts with SPMS. Full analysis is pending.
Berlex - chemical makeup: not glycosylated and the amino acid sequence is not identical to naturally occurring human form. Packaged as 8.6 million unit vial. Recommended dose is 250mcg = .25 mg or (1ml). The vial has overfill. When reconstituted with 1.2ml diluent, it equals .3mg. Need for lab tests: prior to beginning therapy and at periodic intervals thereafter (hgb, CBC & diff, platelet counts and blood chemistries including liver tests Side effects: most common is injection site reaction & occurs in approx. 50% of people (inflammation, pain, hypersensitivity) “flu-like symptoms” (only 3%-8% experience after 1st year)/ (pre-med with Tylenol) Depression has been reported Not recommended in pregnancy Neutralizing Abs developed. Betaseron produced in E.coli. Betaseron was approved in Canada and Europe for the treatment of SPMS. Two large multicenter clinical trials demonstrated that Betaseron delayed disease progression in patients with SPMS and reduced the frequency of relapses. Not approved in the U.S. for this indication as of today.
Side effects such as flu-like symptoms start about 3 to 6 hrs after the injection. The flu-like reactions usually resolve within the first 3 mo of therapy. To reduce the side effect, therapy may be started with a half-dose for 4 to 6 weeks and give injection at night. Pretreatment with ibuprofen or acetaminophen. Many patients can experience transient worsening in MS symptoms (increased spasticity) especially within the first 12 wks. CBC with dif and LFTs should be done monthly for the first 3 mo, then quarterly. Side effects may be depression, lack of interest, reduced appetite and pessimistic hopelessness. Suicide is the No. 3 reason for death for those with MS according to Dr. Kaplan a psychologist focusing on MS related depression that was interviewed on Larry King March 2004 NABS (neutralizing antibodies) have been a hot topic with the interferons. To date most physicians do not measure or rely on NABS to determine treatment. The American Academy of Neurology and the MS Council state that the utility of measuring NABs in uncertain. FDA and Biogen notified healthcare professionals of revisions to the WARNINGS, PRECAUTIONS/Drug Interactions and ADVERSE REACTIONS/Post-Marketing Experience sections and Medication Guide. Severe hepatic injury, including cases of hepatic failure, has been reported in patients taking Avonex. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of Avonex used in combination with known hepatotoxic drugs or other products (e.g. alcohol) should be considered prior to Avonex administration, or when adding new agents to the regimen of patients already on Avonex .
Teva Neuroscience Copaxone-formerly known as copolymer-1 ( now comes in a pre-filled syringe and requires refrigeration). Medication can be left out of the refrigerator for seven days. The first nonsteroidal, noninterferon agent Designed to modify the immune processes Exact mechanism unknown (fools the body). May inhibit the immune response to myelin basic protein and possibly other myelin antigens. Side effects: Most common is injection site reaction (usually mild)- (redness, pain, inflammation, itching, lump at site). People using the autojector report less injection site reactions. Less common side effects, flushing, chest pain, nausea, anxiety and dizziness. No neutralizing antibody development. Drug of choice if the person is choosing to get pregnant. Treatment option for patients who don’t respond or don’t tolerate interferon
All three of the manufacturer’s of the SQ injectible medications now provide free self injector’s for their patients. Berlex’s research demonstrates added comfort for the patient. Rebiject and the Autoject 2 for glass syringe for Copaxone both require a prescription.
Distributed by Serono. Traditionally used for various cancers such as ANLL, therapy of patients with pain related to hormone refractory prostate cancer. Very potent immunomodulator and immunosupressor. NOVANTRONE is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary progressive, progressive relapsing and worsening relapsing-remitting MS. NOVANTRONE is not indicated for primary progressive MS. Novantrone is not recommended for MS patients with a certain blood cell count, liver function test, or cardiac abnormalities; or for women who plan to become or are pregnant. Inhibits DNA replication by inhibiting topoisomerase II and reduces the number of B-cells, inhibits T-cell function and augmenting T-cell supressor activity.
Distributed by Serono. Traditionally used for various cancers such as ANLL, therapy of patients with pain related to hormone refractory prostate cancer. Very potent immunomodulator and immunosupressor. Inhibits DNA replication by inhibiting topoisomerase II and reduces the number of B cells, inhibits T-cell function and augmenting T-cell supressor activity. The only agent currently approved for progressive forms of MS.
5/25/05 The Food and Drug Administration and Serono Inc. notified healthcare professionals in a letter that Serono's multiple sclerosis treatment Novantrone(mitoxantrone for injection concentrate) is associated with an increased risk of cardio-toxicity. The letter states that &quot;cardiac monitoring of MS patients should be performed at baseline and prior to administration of every dose of Novantrone.&quot; According to the letter, post-marketing surveillance reports &quot;have shown that diminished cardiac function may occur early on in the treatment with Novantrone.&quot; The new label also provides supplemental information about secondary acute myelogenous leukemia reported in patients who take the drug. The label says, &quot;In a cohort of [Novantrone]-treated MS patients followed for varying periods of time, an elevated leukemia risk of 0.25 percent(2/802) has been observed.&quot;
Immunosuppressants - since MS is thought to be primarily of autoimmune origin, it is thought suppressing the immune system might be helpful. This is usually only used for chronic-progressive patients (show only slight evidence of benefits) Thiopurines: azathioprine(Imuran) Alkylating agents: Cyclophosphamide, Chlorambucil Methotrexate-being investigated for use, currently used for therapy in rheumatoid arthritis and cancer Note: IGIV-study between 1992-1996 showed that monthly administration seems to be at least as effective as therapy with interferon-B or copolymer 1 in improving clinical disability and reducing the rate of relapse for MS patients with relapsing-remitting MS .
Botox for urinary dysfunction is still considered Off Label.
Summary: People face many challenges in living with multiple sclerosis. The following organizations offer variety of services and programs to help cope with MS. National MS Society- network of 140 chapters and branches, offering programs and services including local referrals, information and education, professional and peer counseling, self-help groups, equipment assistance and more. (1.800.FIGHT.MS-New York, NY) Consortium of MS- a unique multi-disciplinary organization providing networking for all healthcare professionals specializing in the care of MS.(201.837.0727-New Jersey) MS Assoc. of America- provides day-to-day assistance through programs such as newsletter, social and support activities, barrier-free housing, free therapeutic equipment loans, and toll-free hotline., symptom management therapies and research, support groups, and public awareness. (800.833.4MSA Cherry Hill, NJ) MS Foundation(MSF) -offers information about both traditional and alternative options for treating MS.(800.441.7055 Fort Lauderdale, FL)
Summary: People face many challenges in living with multiple sclerosis. The following organizations offer variety of services and programs to help cope with MS. National MS Society- network of 140 chapters and branches, offering programs and services including local referrals, information and education, professional and peer counseling, self-help groups, equipment assistance and more. (1.800.FIGHT.MS-New York, NY) Consortium of MS- a unique multi-disciplinary organization providing networking for all healthcare professionals specializing in the care of MS.(201.837.0727-New Jersey) MS Assoc. of America- provides day-to-day assistance through programs such as newsletter, social and support activities, barrier-free housing, free therapeutic equipment loans, and toll-free hotline., symptom management therapies and research, support groups, and public awareness. (800.833.4MSA Cherry Hill, NJ) MS Foundation(MSF) -offers information about both traditional and alternative options for treating MS.(800.441.7055 Fort Lauderdale, FL)