Multiple Sclerosis Flashcards
Is MS gender specific?
Yes, its more common in women (70%)
How is MS diagnosed?
Ultimately, its a clinical diagnosis; no definitive laboratory test exists. Clinical profile consists of symptomatic disease, abnormal exam, and white matter involvment.
eval should exclude other diagnoses (SLE, CNS tumors, vasculitis, endocrine distrubances)
What is included in the laboratory evaluation for MS? (3)
- MRI-imaging to identify lesions; reveals plaques
- CSF-evidence of intrathecal inflammation (thecal sac is a membrane of the dura mater that surrounds the spinal cord and cauda equina)
- Evoked potentials: evidence of altered conduction in a pattern consistent with demyelination
lumbar puncture shows increased lymphocytes, increased ig with oligoclonal IgG bands, and myelin basic proteins (because myelin is being destroyed)
What does an abnormal CSF consist of in MS?
- oligoclonal immunologbulin G (IgG) bands in CSF and not in serum
- elevated IgG index
Evidence of dissemination of lesions in space in time is key to making diagnosis. What is the criteria?
there must be atleast 2 distinct attacks affecting atleast _2 areas of the brain _
What is a metabolic condition that mimics MS?
Vitamin B12 and E deficiencies
What are the four disease types of MS?
Multiple sclerosis has been divided into 4 subtypes, based on the disease course1:
- *Relapsing-remitting**—characterized by relapses of neurological symptoms followed by periods of recovery when symptoms abate, with or without residual disability (50% progress to secondary-progressive)
- *Secondary-progressive**—initially has a relapsing-remitting course that changes over time such that patients have fewer relapses and a slower progression of symptoms
- *Primary-progressive**—characterized by slow and steady progression of symptoms, without asymptomatic periods
- *Progressive-relapsing**—initially has a progressive course, but an exacerbation occurs after establishment of the progressive course
50% of relapsing-remitting patients progress to what type of MS?
Secondary progressive: fewer relapses and a slower progression of symptoms
What is the pathology of MS?
Autoimmune-mediated disease in genetically susceptible indivudals against CNS MYELIN AND OLIGODENDROCYTES.
Inflammation and demyelination of the CNS (brain and SC).
Your body decides your myelin is foreign intermittently, and inflammation leads to the loss of myelin sheath/demyelination, which slows conduction along the nerve axon leading to neurological symptoms.
MS tends to occur in specific areas of the CNS. What areas? and why? (6)
Wherever there’s white matter:
- optic nerve
- periventricular white matter
- Brain stem
- Cerebellum
- cerebral cortex
- Spinal cord (small lesion is a larger volume of injury)
* the specific type of symptoms a pt experiences is related to the location of the lesions within the CNS!*
What are the 3 core components of MS pathogenesis?
- Inflammation: T cells leaking out of vein into perivenular area
- Demyelination: fragmented broken myelin
- axonal loss: broken axon, axon bulb breaking, spins up like a tape measure
What causes demyelination and axonal loss in MS?
Autoimmune in origin:
- preexisting autoreactive CD4+ Th1 cells in periphery become activated
- the BBB can be breached by lymphocytes if they are in a state of high activation
- in situ reactivation of myelin autoantigens stimulate an immune response
- Th1 secrete pro-inflammatory cytokines (interferon-gamma, IL-2) –> macrophages, T cells, and B cells
- acute attack: demyelination; resolution: reduction of inflammation w. partial remyelination
- axonal loss –> permanent disability
What are the periventricular plaques seen in MS?
areas of oligodendrocyte loss and reactive gliosis
does the inflammatory processes in MS occur early or late in MS?
EARLY. Which is why its improtant to intervene early when you can suppress the inflammation.
What does each type of MRI show in MS?
T2
FLAIR
T1
Gadolinium enhancement
T2: total burden of disease, may show new lesions, edema, inflammation, demyelination, and axonal loss
FLAIR: suppresses CSF, useful for subcortical and cortial lesion detection; white sports are inflammation
T1: shows hypo-intense lesions (black holes)
Gadolinium: highlights new or active lesions (Gd leaks into areas of inflammation)
How do you interpret T1 weighted lesions on MRIs?
Indicate irreversible axonal damage- they are permanent scars. There is a strong correlation between T2 and T1 hypointense lesion loads: a subset of T2 lesions become T1 hypo-intense.
What are acute relapses, and how are they treated?
- sometimes referred to as exacerbations, attacks, falre-ups. -Defined as focal distrubance of function, affecting a white matter tract, lasting >23 hours
- tx with high dose steroids: accelerate speed but not degree of recovery. Common option is methylprednisolone IV for 5 days followed by short course of prednisone. oral prednisone or dexamethason, subcutaneous ACTH (Acthar)
- note: oral prednisone is rarely used acutely, trials show increased risk of recurrents in pts with optic neuritis*
Two classes of disease-modifying medications
immunomodulators
immunosuppressants
3 nonspecific immunosuppression
corticosteroids
cyclophosphamide (Cytoxan)
Mitoxantrone
2 nonspecific immunomodulation
Interferon beta-1b (betaseron)
Interferon beta-1a (avonex)
2 selective immunomodulation
- Glatiramer acetate: shifts bad T cells to good cells
- Natalizumab: inhibts T cells from going into brain
What is one of the earliest, key steps in pathogenesis of MS?
T-cell and macrophage invasion of the brain
How does natalizumab (Tysabri) work?
thourght to block white blood cells from entering the brain and damaging nerves and myelin. (not fully known)
Immunomodulating treatments affect _______, which predominates in the ____ phases
INFLAMMATION, early.
3 main clinical features of MS
- scanning speech and vertigo (brainstem)
- internuclear opthalmoplegia (MLF is damaged, so can’t pull R eye to the left, but left eye can m ove left), incontinence (loss of bladder control), intention termor
- nystagmus
- blurred vision in one eye (optic)
SIN
common MS symptoms (7)
- Fatigue
- Depression
- Focal muscle weakness
- visual changes
- bowel/bladder/sexual dysfunction
- gait problems/spasticity
- cognitive dysfunction
Pain is a complex sensory phenomenon, and is a consequence of MS, but not the disease itself. What are some of the causes and types of pain? (5)
- Neuropathic
- Musculoskeletal
- Optic Neuritis (every time you move your eye your eyes hurt, at night you see flashing things in the dark because the nerve is sending off abnormal signals. Lose color vision first, then vision)
- Spasticity
- Dystonia
Pain symptom managment
- Tricyclic antidepressants
- Antiepileptic medications
- Antispasticity meds