MS Flashcards
what are the 4 demyelination mechanisms
- oligodentrocyte or schwann cell death
- interference with myelin synthesis
- interference with myelin replacement
- myelin destruction immune mediated
what is the composition of myelin?
70% lipids
30% proteins (myelin basic protein, myelin associated glycoprotein, oligodendrocyte glycoprotein)
what two things contain myelin?
schwann cells (PNS) oligodendrocytes (CNS)
both from neural crest
shwann cells and oligodendrocytes are components of what systems
schwann cells (PNS) oligodendrocytes (CNS)
how much does each schwann cell myelinate the axon?
1mm
how many axonal segments do oligodendrocytes myelinate
each oligo. myelinates 60 axonal segments
conduction velocity of an axon is proportional to its _________ and the ditance between________
diameter
distance between ranviers nodes
what is the speed of an action potential
120 m/s
perivascular and perivenulat immune infiltration/ plaques in white matter
demyelination
most common immune mediated inflammatory demyelinating disease of the CNS
MS
MS
age group affected
sex affected
most common neurologic disease among young adults
incidence is highest from ages 20-40 but can start in childhood or after 50
female to male 7:3 (2.3:1)
prevelance for MS decreases with?
proximity to equator
Genetic risk for MS for
general population?
one parent or 1st degree relative affected?
both parents?
0.1%
4%
20%
MS is associated with major __________
histocompatibility complex II (MHC II) and certain DR2 haplotypes
most frequent cause of permanent disability in young adults aside from trauma (among CNS disorders)
MS
mean age of ms
28-31
what is the best theory explaining the demyelination in MS
begins as an inflammatory immune mediated disorder characterized by autoreactive lymphocytes –> later the disease is dominated by microglial activation and chronic neurodegeneration
immunopath of ms/ inflammation in conjunction with BBB disruption –> inflammatory T cells, B cells, and macrophages are typically seen–> presence of IgG and IgM oligoclonal bands in ___________ but not in the ___________
Cerebrospinal fluid
serum
immunopath of ms/ myelin reactive ______ are found in MS _______ and in the ______ and the peripheral circulation of patients with MS
T cells
MS plaques
CSF
no direct proof that an autoimmune causes MS as ……
no specific autoantibodies or autorecessive T cells directed against self antigen in the CNS can passively transfer MS to experimental animals
how does MS appear or look like
multiple discrete pink or gray areas that have a hard or rubbery texture are id’d within the white matter of the brain and spinal cord
in MS lesions can occur at any site within the CNS, they have a predilection for involvement of the _______, _______, ______, and______
juxtacortical and periventricular white matter the corpus callosum optic nerves and the dorsal spinal cord brain stem cerebellum
the characteristic neuropathologic feature of MS is the presence of focal ____________ within the CNS accompanied by variable degrees of _______ and ______ with partial preservation of axons
focal demyelinated plaques
degrees of inflammation and gliosis
On MRI we can see that MS can cause diffuse damage of _____________ both of which are associated with a progressive loss of _______
normal appearing white matter (NAWM)
normal appearing gray matter (NAGM)
Loss of brain volume
what are the target proteins in MS
myelin basic protein (MBP)
Proteolipid proetin (PPL)
Myelin associated gycoprotein (MAG)
what paraclinical tests provide support in the diagnosis of MS
MRI
spinal fluid
evoked potentials
what are the diagnostic criteria in order to diagnose MS
dissemination in time and space: evidence that damage has occurred in at least two separate areas of the CNS at different points in time
There must be no other explination
what are the disease types in MS
clinically isolated syndrome
relapsing remitting MS 85%
primary progressive MS 15%
secondary progressive –> most people diagnosed with RRMS will eventually transition to SPMS
a first neurological event suggestive of demyelination in ms
clinically isolated syndrome
individuals with Clinically isolated syndrome are at high risk of __________
developing definite MS if the neurological event is accompanies by multiple clinically silent lesions on MRI typical of MS
inflammatory, demyelinating conduction that causes acute, usually mononuclear visual loss. highly associate with MS
optic neuritis
optic neuritis is a presenting feature of MS in ___% of patients and occurs in ___% during some course of disease
15-20
50
in optic neuritis due to MS _______ is identified at symptom onset and precedes changes in the cerebrospinal fluid
systemic T cell activation
B cell activation against myelin in MS is not seen in ________ but can be seen in ________
peripheral blood
cerebrospinal fluid
previously known as devic disase
neuromyelitis optica
inflammatory disorders of the CNS and axonal damage predominantly targeting optic nerves and spinal cord/ disease specific serum NMO-IgG antibody selectively binds aquaporin -4
neuromyelitis optica
traditionally considered a variant of MS, it is now recognized as a distinct clinical entity based on unique immunologic features
neuromyelitis optics
a water channel protein highly concentrated in spinal cord gray matter, periaqueductal and periventriculat regions, and astrocytic foot processes at the BBB
neuromyelitis optica :AQP4
target antigen of NMO-IgG
AQP4 in MS
vs
AQP4 in neuromyelitis optic (NMO)
in MS lesions the distribution of AQP4 protein expression depends upon the stage of demyelination
while in NMO lesions there is a loss of AQP4 expression that is unrelated to the stage of demyelation
what are inital symtpoms of MS
sensory disturbances, parenthesis, dysesthesias (burning, gritty, sandy, electrical, or wet sensations) , weakness, visial loss, abnormal gait, diminished dexterity, diplopia, ataxia, vertigo, or spinchter disturbances
Motor disturbances: weakness, spasticity, hyperreflexia babinski
non specific fatigue headache
a specific gaze abnormality characterized by impaired horizontal eye movements with weak adduction of the affected eye, and abduction nystagmus of the contralateral eye
IN MS
internuclear ophtalmoparesis
