Multiple sclerosis Flashcards
What is the autoimmune theory?
Autoimmune attack on the CNS
Inflammatory process leads to disruption of the BBB
Migration of antigen-specific T cells into CNS
Cascade of immunologic events
Demyelination
What are the RFs for MS?
Age
US citizen
Environment (virus/bacteria, smoking, vit D deficiency)
Genetics (HLA, MHC< IL2/7alpha)
What are primary sx of MS?
Direct consequence of demyelination
What are secondary sx of MS?
Complications secondary to primary sx
What are tertiary sx of MS?
Sx that relate to the effect of the disease on the patients everyday life
What are the ways to measure MS progression?
EDSS
MSFC
MRI
What are the 4 classifications of MS?
RRMS
SPMS
PPMS
PRMS
What does RRMS stand for?
Relapsing remitting MS
What is RRMS?
Clearly defined exacerbations
Acute worsening of neurologic function
What is the most common MS form at diagnosis?
RRMS
What is the most common form of MS?
RRMS
What does SPMS stand for?
Secondary progressive MS
What can SPMS develop from?
RRMS
What is SPMS?
Steadily worsening w/ or w/o occasional flare ups
What does PPMS stand for?
Primary progressive MS
What is PPMS?
Slow but continuous worsening of disease from onset
Worse prognosis
No distinct relapse or remission
Variations in rates of progression
What does PRMS stand for?
Progressive relapsing MS
What is PRMS?
Steadily worsening disease from onset
Clear, acute relapses w/ or w/o recovery
Periods between relapses continue disease progression
What are factors that may lead to an exacerbation?
Infection Heat Sleep deprivation Stress Malnutrition Anemia Concurrent organ dysfunction Exertion Childbirth
What is the first exacerbation known as?
Clinically isolated syndrome (CIS)
How does MS affect mortality?
Does not directly decrease mortality
Increased mortality with secondary complications (pneumo, sepsis, decubitus ulcer, UTI)
What rate is 7x the normal population for MS?
Suicide
How is MS diagnosed?
2 episodes of neurologic disturbance
McDonald criteria
MRI
CSF (IgG)
What are the treatment categories for MS?
Tx of acute attacks
Disease-modifying therapies
Symptomatic therapy
What type of therapy are attack and disease-modifying therapies?
Immunotherapies
What are the goals of immunotherapy in MS?
Decrease frequency and severity of exacerbations
Diminish the progression of lesions
Slow progression of disability
What is the treatment of acute MS exacerbation?
HD IV methylprednisolone (500-1000) x 3-10d
What are the disease-modifying therapies?
Interferon beta Glatiramer (Copaxone) Natalizumab (Tysabri) Mitoxantrone (Novantrone) Fingolimod (Gilenya Teriflunomide (Aubagio) Dimethyl fumarate (Tecfidera) Alemtuzumab (Lemtrada) Ocrezlizumab (Ocrevus)
What are the 2 interferon B1b?
Betaseron
Extavia
What are the Interferon B1a?
Avonex
Rebif
Plegridy
How does interferon work?
Suppresses T-helper cell response, reducing T cell migration across the BBB into the CNS
What is the MOA of glatiramer?
Alteration of T cell activation and differentiation
What is the MOA of mitoxantrone?
Decrease the migration of T cells into the CNS by arresting cell cycle
What is the MOA of natalizumab?
Monoclonal antibodies of alpha4-integrin of the adhesion molecule VLA-4 on leukocytes. Inhibition of VLA-4 is responsible for blockade of T cells across the BBB
What is the MOA of fingolimod?
Reduces the infiltration of T lymphocytes into the CNS
What is the MOS of teriflunomide?
Inhibits pyrimidine synthesis thereby decreasing proliferation and inflammation
What is the MOA of dimethyl fumarate?
Thought to be protextive against damage to the brain and spinal cord secondary to antioxidant properties brought about by activation of the Nrf2 pathway
What is the MOA of alemtuzumab?
Monoclonal antibody directed at CD52, an antigen present on the surface of various types of immune cells
Results in depletion of circulating B and T lymphocytes
What is first line in PPMS?
Ocrelizumab
Which drugs are FDA approved for those with inadequate response or intolerance to other MS therapies?
Natalizumab
Alemtuzumab
Daclizumab
What can be considered in worsening RRMS, SPMS, and PRMS whether or not relapses are occurring?
Mitoxantrone
What are comorbidities with MS?
Cognitive dysfunction Depression Fatigue Paroxysmal sx Spasticity Sphincter dysfunction Gait impairment
How do we treat spasticity?
Baclofen
Tizanidine
How do we treat bladder sx?
Tolterodine
Oxybutinin
How do we treat sensory sx?
Gabapentin
How do we treat fatigue?
Amantadine
Modafanil
Methylphenidate
How do we treat gait impairment?
Dalfampridine
