Term
| What are the defining characteristics of the 4 major forms of MS? |
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Definition
1) Primary Progressive (10%)
- slow and steady worsening from onset
- no good treatment
2) Relapsing-remitting (85%)- Acute episodes followed by partial recovery, with no progression in between
3) Secondary Progressive- Relapsing-remission followed by progressive (90% of relapsing-remitting cases)
4) Progressive- Relapsing- Steady worsening from onset with later exacerbation (RARE) |
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Term
What epidemiological features define MS?
1) Prevalence
2) Genetics
3) Environment |
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Definition
Genetically susceptible individuals exposed to environmental trigger prior to critical age. 1:800 in Pitt
1) 3:1 female to male with 95% Caucasian
- mean age of onset at 28 (median 22)
- if you move after 15, you carry previous risk
2) Immune genes (HLA DRB1 1501-DR2 haplotype)
- first-degree relatives have 2-3% risk
- if both parents have it, kids at 10-30%
3) Diet, sunlight exposure (want vitamin D), sanitation levels, affluence, EBV |
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Term
| What is the basic pathogenesis of MS? |
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Definition
"Patchy" demyelination of white matter tracts in CNS and optic nerve, with inflammation in the perivascular spaces
1) Activated lymphocytes and macrophages enter CNS and attack CNS myelin
2) Conduction slowing and blockage causes loss of nerve function (paralysis, blinding, double vision, anesthesia)
3) Electrical "cross talk" can cause dystonic spasms, flashes of light or electric-like pains (neuralgia)
4) Repaired nerve (re-myelination and membrane modification) is prone to conduction failure when body temperature rises (Uhtoff's phenomenon) or repetitive use. |
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Term
| What is "Uhtoff's Phenomenon" as it relates to MS? |
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Definition
Increased body temperature exacerbates symptoms.
Was originally exploited by "hot bath test" as a diagnostic procedure. |
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Term
A patient presents with Extreme fatiguability and reports feeling an "electric like feeling" with neck flexion.
What should be on your differential? |
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Definition
This is Lhermitte's Phenomenon and it is seen in MS, cervical spine degeneration and vitamin B12 deficiency (subacute combined degeneration of SC).
Extreme fatiguability is characteristic of MS |
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Term
| What features when observed should cause a physician to immediately think of MS? |
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Definition
1) Optic neuritis (sudden unilateral visual loss and pain with eye movement that tends to improve over a period of weeks)
** look for pupillary defect
2) INO from demyelination of MLF
3) Partial myelitis (focal demyelination of SC that often causes bladder control problems) |
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Term
| How does Devic's Disease differ from MS? |
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Definition
You see Transverse Myelitis (entire SC) with bilateral optic neuritis ("neuromyelitis optica")
In MS, it is partial myelitis with unilateral optic neuritis. |
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Term
| What do you look for on MRI with MS? |
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Definition
1) supratentorial and infratentorial lesionswith periventricular and juxtacortical distribution that are >5 mm
2) Bright on T2 and FLAIR and "black holes" on T1
3) "Dawson's fingers" in perivenular regions
4) Global brain leads to cognitive issues with SC/brainstem leading to physical issues |
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Term
| What diagnostic procedures should be followed when considering MS? |
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Definition
1) MRI for lesions (sensitive)
2) CSF to look for increase IgG (inflammation and rule out ischemia)- VARIABLE but specific
3) Evoked Potentials for ocult or subtle lesions (won't give you causation) |
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Term
| What is the typical differential diagnosis of a patient presenting with symptoms consistent with MS? |
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Definition
MANY MORE ALSO
1) Vascular
-cardiogenic emboli
- anticardiolipid antibody syndrome
- CADASIL
2) Inflammatory Disorders
- Sjogren's
- Sarcoidosis
3) Infections
- Lyme
- Syphillis
- Papovavirus (PML)
- Retrovirus (HTLV)
- Mitrochondrial
3) Rheumatological disorders
4) Infections |
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Term
| What is the prognosis for a patient with MS? |
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Definition
1) 85-90% untreated patients will develop severe ambulatory dysfunction within 30 years
2) High lesion loads are predictive of early disability risk (remember, 10X as many lesions as clinical relapses)
3) Risk of suicide and other complications (mildly shorter lifespan overall) |
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Term
| What external factors influence MS progression? |
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Definition
1) Heat exposure
2) Mild viral load
3) Exercise
4) Vaccinations?
** Gets better during pregnancy, but then worsens afterwards** |
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Term
| What treatment options are available for MS? |
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Definition
$$$$ aimed at modifying specific immune response (with no treatment effective for primary progressive form)
1) Interferon Beta (1/3 reduction in relapse rate, decreased risk of progression and decreased occurrence of novel MRI lesions)
- Decrease T-cell proliferation and activation
- Decrease MMPs that open BBB
- Side effects of fever and myalgia, miscarriage, leukopenia, thrombocytopenia
2) Glatiramer acetate (Copaxone) (similarly effective)
- synthetic protein that binds MHC molecules and competes with myelin antigens for presentation to T cells
- incude Th2 suppressers for in situ immunosuppression
- Side effects is benign, but frightening chest pain.
3) Natalizumab (67% reduction in relapse rate- BEST)
- antibody against VLA-4 that prevents lymphocyte adhesion to vascular epithelium
- Can cause PML (1:1,000)
4) Mitoxantrone
- Chemotherapteutic drug with broad immunosuppresion
- Second-line agent because of risk of cardiomyopathy and leukemia
- Single dose every 3 months vs. every day or few days for others! |
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Term
| Other then then 4 primary drugs to treat MS (IFN-b, Glatiramer acetate, Natalizumab, Mitoxantrone), what alternative therapies are available? |
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Definition
1) Diet (low saturated fat)
2) Steroids for exacerbations
3) Symptomatic treatment
- muscle relaxants for spasticity (Difampridine)
- exercise for strength
- ect. |
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Term
| Where can patients and their families access important information about MS treatment and education? |
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Definition
| National Multiple Sclerosis Society (NMSS) |
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Term
| How can you definitively diagnose the MS? |
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Definition
| Need 2 CNS lesions separated in time (month) |
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Term
| What % of MS patients present with sensory, motor and/or cognitive features? |
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Definition
| 1/3 of population presents with each (some combined) |
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Term
| What autonomic functions are effected in MS? |
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Definition
1) Bladder control
2) Sexual
3) Bowel |
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Term
| What sensory symptoms are seen in MS? |
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Definition
1) MS "hug"
2) Lhermitte's
3) V neuralgia
4) Hemibody paresis |
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Term
| What Brain stem symptoms are seen in MS? |
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Definition
1) Dysarthria
2) Dysphagia
3) Vertigo
4) V. neuralgia |
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Term
| What features of MS is most disabling for most patients? |
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Definition
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Term
| Which inherited disorders of myelin function should be on your differential when considering MS? |
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Definition
1) Adrenoleukodystrophy (adrenal gland or CNS dysfunction evident in young men)
2) Metachromatic leukodystrophy (Autosomal recessive with psychiatric dysfunction |
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Term
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Definition
Symptomatic treatment of muscle weakness in MS
- K channel blocker that improves conduction for weakness.
- Risk of seizures |
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Term
| What is the concern with using Fingolimod to treat MS? |
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Definition
| Cause susceptibility to HSV infection |
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