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What is the pathophysiology of MS?
- Autoreactive T-cells activate an immune response against components of myelin
- Demyelination causes disruption of nerve conduction
- Neurologic sx depend on area damaged
- Scar tissue forms (lesions or plaques)
- Cumulative axonal damage leads to progressive, irreversible disabilities
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What is the clinical presentation of MS?
- Fatigue
- Depression
- Multitude of other neuron-based sx
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What is the definition of relapse in MS?
newly developed sx that continue for at least 24h and are at least 30d apart
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What is a Clinically isolated syndrome (CIS) in MS?
1st demyelinating event (relapse)
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What is the definition of remission in MS?
complete or incomplete resolution of sx
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What are the classifications of MS?
- Relapsing-remitting (RRMS)
- Secondary-progressive (SPMS)
- Primary-progressive (PPMS
- Progressive-relapsing (PRMS)
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What is are the characteristics of Secondary-progressive MS (SPMS)?
- Less frequent relapses than RRMS, but Less complete recover and gradual worsening of sx
- Significant accumulation of disability
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What are the characteristics of Primary-progressive MS (PPMS)?
- NO relapses
- Progressive worsening and accumulation of disability from disease onset
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What are the characteristics of Progressive-relapsing MS (PRMS)?
- Mixture of relapses and desease progression
- Rare
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What are the characteristics of Relapsing-remitting MS (RRMS)?
Relapses occur, but sx generally resolve until next exacerbation
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What is the treatment for relapse of MS?
- Mild relapse may not require drug tx
- High-dose CS for 3-5d with or without subsequent oral prednisone taper for 1-3wks
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What are the Disease Modifying Therapy drugs used in MS?
- IFN B-1a (Avonex)
- IFN B-1a (Rebif)
- IFN B-1b (Betaseron)
- IFN B-1b (Extavia)
- Glatiramer (Copaxone)
- Fingolimod (Gilenya)
- Natalizumab (Tysabri)
- Mitoxantrone (Novantrone)
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Which DMT drugs are given IM for MS?
IFNs (Avonex, Rebif, Betaseron, Extavia)
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Which DMT drugs are given SQ for MS?
- IFNs (Avonex, Rebif, Betaseron, Extavia)
- Glatiramer (Copaxone)
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Which DMT drug is given PO for MS?
Fingolimod (Gilenya)
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Which DMT drugs are given IV for MS?
- Natalizumab (Tysabri)
- Mitoxantrone (Novantrone)
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What type of MS is IFN B good for?
- RRMS
- Maybe CIS or SPMS if pt still having relapses
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What is the MOA of IFN B in MS?
- Unknown:
- Interfere with antigen presentation
- Anti-inflammatory
- Inhibition of pro-inflammatory cytokines
- Inhibition of T-cell proliferation and migration across BBB
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What type of MS is Glatiramer (Copaxone) good for?
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What is the MOA of Glatiramer (Copaxone) in MS?
- Unknown:
- Interfere with antigen presentation and T-cell activation by competing with MBP for binding at the MHC
- Induce a shift from TH1 (inflammatory to TH2 (anti-inflammatory)
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What type of MS is Fingolimod (Gilenya) good for?
Indicated to reduce frequency of exacerbations and delay accumulation of physical disability in relapsing forms of MS
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What type of MS is Natalizumab (Tysabri) good for?
Monotherapy for relapsing forms of MS
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What is the MOA of Natalizumab (Tysabri) in MS?
alpha-4 integrin inhibitor preventing activated lymphocytes from crossing the BBB
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What type of MS is Mitoxantrone good for?
SPMS, PRMS, and worsening RRMS
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What is the MOA of Mitoxantrone in MS?
Interferes with RNA and DNA synthesis and DNA repair
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What are the SE of IFN B?
- Flu-like sx
- Injection site reactions (mainly SQ)
- Neutralizing antibodies
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What are the SE of Glatiramer (Copaxone)?
- Injection site rxns
- Transient rxn (flushing, chest tightness, dyspnea, palpitations, anxiety - only occurs once, usually lasts <20min)
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What are the SE of Mitoxantrone?
- Cardiotoxicity
- Alopecia
- Amenorrhea
- Secondary AML
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What are the off-label tx for MS?
- Cyclophosphamide
- Azathioprine
- MTX
- IVIG
- Methylprednisolone
- Plasma exchange
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What is Dalfampridine used for in MS?
- to improve walking (ONLY!)
- Potassium channel blocker
- Dose-dependent seizure risk
- Do not cut, crush, or chew
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