DEMYELINATING DISEASE Flashcards
Structures affected by MS
where pial veins lie next to or within the white matter
In old lesions with interruption of axons, there
may be descending and ascending __________of long fiber tracts in the spinal cord
wallerian degeneration
four histologic subgroups of MS
Type 1-4
- T cells and macrophages
alone (pattern I); - an autoantibody lesion mediated
by immunoglobulin and complement (pattern II); - apoptosis of oligodendrocytes
and absence of immunoglobulin, complement, and with
partial remyelination (pattern III); - oligodendrocyte dystrophy and no remyelination
(pattern IV)
Most data suggest that antibody and_________ are the dominant mechanism
of demyelination in MS
complement mediated
myelin phagocytosis
Approximately _______percent of MS patients have an affected
relative, with the highest risk of concurrence being
observed in the patient’s siblings
15
The strongest association in MS is with
the DR locus on______
chromosome 6
infectious agents associated with MS
The bacterial agents Chlamydia pneumoniae
and Borrelia burgdorferi (the agent of Lyme disease) and
herpesvirus type 6
Autoantibodies have been found inconsistently that
are directed against _____ and ___
myelin oligodendrocyte glycoprotein
(MOG) and MBP
Another typical feature of MS is the temporary ind uction,
by heat or exercise, of symptoms such as unilateral
visual blurring ______
(the Uhthoff phenomenon)
A
rise of only ________) can block electrical transmission
in thinly myelinated or demyelinated fibers
0.5 C (0.9°F
__________ are all
capable of briefly worsening neurologic functioning and
are easily confused with relapses of disease.
Smoking, fatigue, hyperventilation,
and a rise in environmental temperature
These common modes of onset are
are: (1) optic
neuritis, (2) transverse myelitis, (3) cerebellar ataxia, and
(4) brainstem syndromes
When these are unaccompanied
by other features of MS, they are termed_______
“clinically
isolated syndrome” (CIS)
It is probably attributable to an increased sensitivity
of demyelinated axons to the stretch or pressure
on the spinal cord induced by neck flexion, but it occurs
in other conditions such as cervical spondylosis
Lhermitte sign
The typical relapsing-
remitting pattern of disease is more likely to appear
in patients who are younger than ______
40 years of age.
In approximately _______ of all MS patients (and
possibly in a larger proportion of children), the initial
manifestation is an episode of optic neuritis .
25 percent
ONTT findings
_______ generally taking
the form of a perceived desaturation of colors, frequently
persists as does the
______ wherein an object
such as a pendulum that is swinging perpendicular to
the patient’s line of sight, appears to moving in a threedimensional,
circular motion.
Dyschromatopsia,
Pulfrich effect,
More than ______of adult patients who present
with optic neuritis will eventually develop other signs of
MS
one-half
Clinically, the illness is characterized by a rapidly
evolving (several hours or days) symmetrical or asymmetrical
paraparesis or paraplegia, ascending paresthesia,
loss of deep sensibility in the feet, a sensory level on
the trunk, sphincteric dysfunction, and bilateral Babinski
signs.
TM
Another relatively isolated syndrome,
occurring mainly in _________ is a slowly progressive
cervical myelopathy with weakness and ataxia
older women,
The combination of nystagmus, scanning speech, and
intention tremor is known as the______
Charcot triad
A predominantly cerebellar or brainstemcerebellar
form occurs in approximately _____ percent of cases
5
It has become evident that some degree of cognitive
impairment, and probably a progressive decline,
is present in perhaps _____ of patients with longstanding
MS
one-half
Dementia in MS
As mentioned above,
the cognitive impairment is in keeping with what has
been ascribed to “subcortical dementia
MC Precipitants of MS
The most common are infection,
trauma, and pregnancy.
many plaques are of the same age and the confluence of
Acute a n d Tu m o r- L i ke (Tu m efactive) M u l t i p l e
S c l e ro s i s ( M a r b u rg Va r i a nt)
Usually the CSF shows a cellular response but no
oligoclonal bands.
True
_____ has as its distinguishing
feature the occurrence of alternating bands of destruction
and preservation of myelin in a series of concentric
rings that represent alternating areas of myelin loss, and
preservation.
Some
studies have found a high incidence in the Philippines.
The concentric sclerosis of Balo
large, well demarcated
areas of demyelination in the white matter of
both cerebral hemispheres, as well as a number of smaller
demyelinating foci, resembling the common lesions of
MS.
diffuse sclerosis
CSF test_____ may in fact be the only measure
of activity of the disease.
pleocytosis
The presence
of _____in a first attack of MS is predictive of a chronic
relapsing course,
bands
IgG index considered positive
a
positive test is considered to be greater than 12 percent of
the total protein.
I t i s now widely appreciated that ____ is the most helpful
ancillary examination in the diagnosis of MS, by virtue
of its ability to reveal symptomatic and asymptomatic
plaques in the cerebrum, brainstem, optic nerves, and
spinal cord
MRI
The ______sequence is particularly sensitive in detecting
lesions in the brainstem, cerebellum, and spinal cord.
T2
The presence of T1 hypointensity depends on the extent
of _____ of the lesion
remyelination
T1 hypointensity
was inversely proportional to the degree of ______
remyelination
MRI pattern that differentiates MS from abscess
C-shaped partial or open ring of abnormal
enhancement;
This change probably reflects both the loss of glial
cells and, importantly, wallerian degeneration and loss
of axons triggered acutely by inflammation and more
chronically by other neurodegenerative stimuli
cortical atrophy
Abnormalities of visual
evoked responses have been found in approximately
____ percent of patients with the clinical features of
definite MS
70
____ is a technique for
creating two- and three-dimensional images of the optic
nerve and retina.
Optical coherence tomography (OCT)
Measures degree of disability inMS
Kurtzke Disability Status Scale
in approximately _______ percent of cases,
the clinical course lacks periodic relapses and is almost
evenly progressive from the beginning (primary progressive
MS;
10
Highest rate of relapse in pregnancy
first trim, 1.2 attacks
effect of methylprednisolone administered at 1 g/ d
for 5 days per month over 5 years
there was a reduction
in disability as well as in the
degree of brain atrophy and
total volume of hypodense lesions on Tl-weighted MRI
T or F
A randomized
trial comparing oral and intravenous methylprednisolone
in acute relapses of MS demonstrated no clear
advantage of the intravenous regimen
t
Oral methylpredinsolone loading
48 mg in a single daily
dose for 1 week, followed by 24 mg daily for 1 week, and
finally 12 mg daily for 1 week)
methylprednisolone 500 mg orally for
5 days had a beneficial effect on visual function at ________ However, at 8 weeks, no effect could be shown
1 and
3 weeks.
True or False
In
this study, it was found that the use of intravenous methylprednisolone
followed by oral prednisone did, indeed,
speed the recovery from visual loss,
although at 6 months
there was little difference between patients treated in this
way and those treated with placebo
T
subcutaneous injection
of this agent every second day for up to 5 years decreases
the frequency and severity of relapses by almost one-third
and also the number of new or enlarging lesions (“lesion
burden”) in serial MRis.
IFNB
Dose of IFN B
The dose
currently used is 30 meg, or 6.6 million units
longer term administration of
interferon is the development of _____ to the drug.
antibodies
After a period of years,
_____ of patients demonstrate antibodies with daily
administration,
30 percent
Overall, the side effects of these interferon agents are
modest, consisting mainly of _____ sweating,
and malaise beginning several hours after the injection
and persisting for up to 14 h;
flu-like symptoms,
Complication in patients with a monoclonal gammopathy who receive
interferon
“systemic capillary leak syndrome
in patients with a first episode of optic neuritis
and at least two lesions on MRI that were compatible with MS.
Over 3 years, there was a modest reduction in clinical
progression or relapse from 37 percent to 28 percen
Controlled
High Risk Subjects Avonex Multiple Sclerosis Prevention
Study (CHAMPS
synthesized to mimic the actions of myelin basic
protein, a putative autoantigen in MS, is given daily in
subcutaneous doses of 20 mg
Copolymer I (glatiramer acetate),
_______
a drug with broad immunosuppressant and cytotoxic
activity, has attracted interest because one study has
shown a slight beneficial effect on the progressive form
of the disease
mitoxantrone,
_____is directed against alpha-integrin in order to
block lymphocyte and monocyte adhesion to endothelial
cells and their migration through the vessel
were able to demonstrate a reduction in
the number of relapses and a slowing of the accumulation of MRI lesions
Natalizumab
Nataluzimab study
showed a 68 percent reduction
in relapses, an 80 percent reduction in new or enlarging
T2 cerebral lesions and a 96 percent reduction in
gadolinium-enhancing lesions on MRI after a year
AFFIRM
Anaphylaxis in Natalizumab
2%
side effect of Nataluzimab
PML
CX of plasma exchange to rapidly clear natalizumab has
reversed PML
IRIS
____ is a monoclonal antibody that targets
CD-52 antigen expressed on T and B lymphocytes,
reduces the number of circulating B cells and, for a
longer period, T cells.
Alemtuzumab
SE of Alemtuzumab
The drug can produce idiopathic
thrombocytopenic purpura and autoimmune thyroiditi
__________ a B-cell-depleting monoclonal antibody
that targets CD20 lymphocytes, has been tested in several
trials and found to be effective in reducing relapses and
the accumulation of MRI lesions in a trial of relapsingremitting
cases over 4 years, but long-term safety is still
being established
Rituximab,
One immunosuppressive drug that interferes with
egress of lymphocytes from lymph nodes,_______
has had a short-term effect on MRI lesion burden and
relapse rate that is comparable or slightly superior to
inject able agents
It causes a lymphopenia by restricting
lymphocytes to the lymph nodes and causes adenopathy.
fingolimod,
Fatigue, a common complaint
of MS patients, particularly in relation to acute attacks,
responds to some extent to ____ (100 mg morning
and noon), ______ (200 to 400 mg/ d), or pemoline
(20 to 75 mg each morning), ________, or ______
amantadine
modafinil
methylphenidate
dextroamphetamine.
acute to
subacute onset of blindness in one or both eyes, preceded
or followed within days or weeks by a severe transverse
or ascending myelitis
DEVIC
Receptor affected in devic
autoantibody to the aquaporin-4 water channel
protein
In certain parts of the world, this form of aggressive
and usually monophasic demyelinating disease is
more common than is typical MS
“Asian optic-spinal MS”
Difference of MS and Devic
a failure to develop cerebral demyelinating
lesions typical of MS even after years of illness;
theabsence of oligoclonal bands in the CSF;
a tendency toCSF pleocytosis more so than in MS,
and the necrotizingand cavitary nature of the spinal cord lesion, affecting white and gray matter alike with prominent thickening
of vessels but with minimal inflammatory infiltrates
This has led to the conclusion that the Devic process
is a _____ disease in contrast to the ______ mechanism
that is proposed for MS
immunoglobulin (Ig) G antineural antibody directed
against aquaporin-4, (NMO antibody)
humoral
cellular
Distribution of antibodies in DEVIC
astrocytic end
feet adjacent to capillaries, pia, and Virchow-Robin spaces
acute inflammatory
and demyelinating disease, distinguished pathologically
by numerous foci of demyelination scattered throughout
the brain and spinal cord
ADEM
viruses associated with ADEM
measles, rubella, smallpox, or chickenpox
ADEM in adults
most adults make good recoveries
T or F
ADEM is a humoral disease
T
