Term
multiple sclerosis
clinical hallmark |
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Definition
*multiple lesions separated in space and time*
multifocal, subacute process --> inflammatory
MS affects the spinal cord as a focal process |
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Term
MS symptoms
areas affected |
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Definition
typical lesion sites:
spinal cord - 50%
optic nerve - 25%
brainstem/cerebellum - 20% |
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Term
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Definition
numbness
paraesthesias (Lhermitte's)
pain
weakness
stiffness
clumsiness
bladder/bowel disturbance
impotence |
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Term
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Definition
paresthesia as a sense of electric shock precipitated by flexion at the neck
not a symptom to be ignored! |
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Term
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Definition
blurred vision
loss of vision
eye pain |
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Term
MS symptoms
brainstem/cerebellum |
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Definition
diplopia
dysarthria
dysphagia
clumsiness
vertigo
numbness
weakness |
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Term
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Definition
relapsing remitting
secondary progressive
primary progressive
progressive relapsing |
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Term
clinical course
relapsing-remitting |
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Definition
at onset, 85% of MS cases are relapsing remitting (with half of these evolving to secondary progressive after 10 years)
clearly defined attacks (relapses), with no disease progression during the periods between the attacks
patients typically recover from the attacks (but not always), and the recovery may be partial or complete |
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Term
clinical course
primary-progressive |
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Definition
continued disease progression from onset
may have occasional plateaus or temporary periods of minor improvement
(10% of cases at onset) |
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Term
clinical course
secondary-progressive |
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Definition
initial relapsing-remitting course, followed by continues progression
may be occasional plateaus, superimposed relapses, or temporary periods of minor improvement |
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Term
clinical course
progressive-relapsing |
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Definition
continued progression from onset, but with clear superimposed relapses followed by partial or full recovery
continuing progression during the periods between relapses
(5% of cases at onset) |
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Term
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Definition
demyelinating plaques = pathologic hallmark
affects white matter of the brain - see gray in the middle of white area, indicates demyelination
plaques of MS like to form near the ventricles
plaque = well-demarcated areas of discoloration that can occur anywhere in the white matter, but especially in the regions near the ventricles and cerebral aqueduct |
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Term
| microscopic pathology of MS |
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Definition
plaques appear as perivascular collections of macrophages and lymphocytes (CD4+ T cells)
reduction in number of axons, but axons themselves preserved, just demyelinated
preservation of neurons - neuron cell bodies remain intact
*demyelination
*inflammation |
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Term
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Definition
demyelination
axonal damage
lesions/inflammatory changes |
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Term
pathophysiology
demyelination |
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Definition
primary damage to oligodendrocytes causes slowed/interrupted nerve conduction
impaired function from decreased Na channels in previously myelinated axons
(axon remains intact, function can be restored as Na channels redistribute or axon gets remyelinated) |
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Term
pathophysiology
axonal damage |
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Definition
axonal transection is a consistent feature of MS lesions
number of transected axons correlates to degree of inflammation
lower axon density |
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Term
pathophysiology
inflammation - theories |
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Definition
T-cells may be sensitized to one or more components of myelin and trigger an immune cascade
may be a generalized problem with immune system regulation that affects primarily CNS neurons and oligodendrocytes
may be a primary pathologic process in oligodendrocytes, neurons, myelin, or axons, and the immune activation is just a response to this underlying pathology |
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Term
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Definition
circulating CD4+ Tcells activated in periphery and adhere to postcapillary venules in the brain and spinal cord
pass through endothelial cells and migrate to perivascular brain parenchyma, with monocytes
adhesion molecules on Tcells and endothelial cells important
now in the CNS, Tcells restimulated by microglial cells
cause direct and indirect damage to oligodendrocytes, myelin sheath, axons
upregulation of cytokines (interleukins, gamma interferon, TNF_alpha, TGF-beta) |
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Term
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Definition
exposure to large amounts of sunlight correlated with reduced risk
increased prevalence with increased distance from the equator ("hygiene hypothesis")
seems that environmental exposure early in life can affect subsequent risk of developing the disease
suggestive associations with mini-epidemics |
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Term
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Definition
no single Mendenlin locus
MZ twin concordance rate = 30% (200 times background rate)
5% for siblings and DZ twins
1st degree relatives have 25x higher risk of MS than general population
association with certain HLA types, IL-2 receptor alpha, IL-7RA genes |
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Term
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Definition
CLINICAL diagnosis based on multiple lesions separated in sapce AND time (without other risk factors; ie Lupus can mimic)
when necessary, supplementary tests may be ordered |
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Term
diagnosis
supplementary tests |
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Definition
brain MRI
spinal cord MRI
LP (CSF testing)
evoked potentials |
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Term
supplemental diagnostic tests
brain MRI |
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Definition
may show additional lesions that night not be presenting at the time
not 100% sensitive or specific
MRI scan can only be interpreted reliably in the context of history and examination |
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Term
supplemental diagnostic tests
MRI spinal cord |
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Definition
| white matter lesions in the spinal cord are rarely insignificant |
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Term
supplemental diagnostic tests
CSF testing via LP |
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Definition
oligoclonal bands: CSF marker of IgG production; from electrophoretic analysis of CSF
increased IgG index: presence of IgG antibodies in CSF as measured by a specific ratio
[IgGCSF/albuminCSF] / [IgGserum/albuminserum] |
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Term
supplemental diagnostic tests
evoked potentials |
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Definition
useful when the physical exam does not provide compelling evidence for more than one CNS lesion
measures of the speed with which sensory information reaches the brain (which is dependent on the function of myelinated pathways)
EEG recordings time-locked to different repeat stimuli: visual, auditory, somatosensory; averaged over multiple stimuli and compared to control or analogous waveform in same pt on opposite side
abnormal function of the sensory pathway results in a prolonged latency of the signal - may provide evidence of a clinical lesion not apparent on the neurologic exam |
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Term
| "diagnosis" of a single episode |
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Definition
by definition, a single episode is NOT MS
-very likely to be MS if: typical syndrome, diffuse MRI changes
differential:
-ADEM
-NMO |
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Term
acute disseminated encephalomyelitis
ADEM |
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Definition
condition that is difficult to distinguish from MS
multifocal
begins abruptly and progresses over hours
often associated fever, HA, neck stiff, decreased consciousness
typically a history of antecedent infection (sometimes vaccine) |
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Term
neuromyelitis optics (Devic's syndrome)
NMO |
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Definition
some patients develop optic neuritis and transverse myelitis separately or simultaneously but then never develop any other MS lesions
associated with a specific auto-antibody to aquaporin 4
spinal cord MRIsshow demyelinating lesions extending over more spinal segments that in a typical MS lesion (brain MRI's usually normal) |
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Term
MS management
disease modifying agents |
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Definition
6 medications approved for use in MS:
3 are different preps of interferon beta (2 of 1a, 1 of 1b) - AVONEX, REBIF, BETASERON
1 polypeptide synthetic analogue of myelin basic protein - GLATIRAMER
1 monoclonal antibody against a Tcell adhesion molecule - NATALIZUMAB
1 chemotherapeutic agent - MITOXANTRONE |
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Term
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Definition
AVONEX (1a) - low dose, IM 1/week
REBIF (1a) - high dose, subq 3/week
BETASERON (1b) - high dose, subq every other day
different preparations of interferon-beta
reduce frequency of relapses in patients with relapsing-remitting MS and reduce progression of MRI abnormalities in clincial disability
dose effect
patients may form neutralizing antibodies after dose
flu-like symptoms with each dose |
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Term
MS management
glatiramer acetate |
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Definition
polypeptide devleoped as a synthetic analogue of myelin basic protein
reduce relapse frequency in relapsing-remitting disease
may slow progression of disability
daily subq |
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Term
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Definition
monoclonal antibody against the Tcell adhesion molecule, alpha4 integrin
reduces frequency of relapse and degree of clinical progression in patients with relapsing-remitting disesase
risk of PML (fatal viral infection) in 1/1000
only when other treatments have failed
IV 1/month |
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Term
MS management
mitoxantrone |
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Definition
chemotherapeutic agent
reduce relapse frequency and rate of disease progression in relapsing-remitting AND secondary-progressive MS
cardiac toxicity limits treatment duration to 3 years
IV every 3 months |
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Term
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Definition
hard to know benefit of treatment on an individual basis
relapsing-remitted patients encouraged to start glatiramer or interferon as early as possible (poss in clinically isolated syndromes too)
decision of specific drug based on side effects, convenience of administration, cost |
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Term
MS management
role of steroids |
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Definition
glucocorticoids appear to accelerate the recovery from an acute MS replase
no consistent evidence for long-term benefit
should be considered for relapses that result in considerable discomfort or dysfunction (but not used too frequently because of high incidence of side affects |
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