roop/raja Flashcards
1
Q
___are proteins called immunoglobulins. The presence of these proteins indicate inflammation of CNS.
A
oligoclonal IgG band
2
Q
what is oligoclonal IgG band useful in diagnosing?
A
MS, subacute sclerosing panencephalitis, herpes simplex encephalitis, bacterial meningitis, neurosyphilis, sarcoid and lupus
3
Q
___is used to enhance brain lesions in scans
A
gadolinium
4
Q
____is a contrast medium used in 1 in 3 MRI scans to improve the clarity of your bodys internal structures. This improves the diagnostic accuracy of MRI scan. For example it improves the visibility of inflammation, tumors, blood vessels and some organs blood supply
A
gadolinium
5
Q
___is immune mediated inflammatory disease. It attacks the myelinated axons in the CNS.
A
MS
6
Q
what is the hallmark for MS?
A
symptomatic episodes that occur months or years apart affecting different anatomic locations
7
Q
MS commonly begins between ____years of age and is more common in _____.
A
20-40; women
8
Q
in MS there is localized areas of demyelination called plaques with destruction of oligodendrocytes. Primarily in ____ Matter?
A
White
9
Q
in MS there is perivascular inflammation and chemical changes in ___ and ___ components of myelin
A
lipid and protein
10
Q
____ and ___ are damaged in MS
A
axons and cell bodies
11
Q
____are hardened areas
A
scleroses
12
Q
what happens to the speed of transmission in MS?
A
you would not have saltatory conduction
13
Q
____ is potential jumping from nodes of ranvier and because of this we have synchronized movements like walking
A
saltatory conduction
14
Q
in MS sensory loss occurs when?
A
early in disease
15
Q
spinal cord symptoms (motor): muscle cramping secondary to _____
A
spasticity
16
Q
what are spinal cord symptoms autonomic of MS?
A
bladder, bowel and sexual dysfunction
17
Q
what are cerebellar symptoms of MS?
A
dysarthria, nystagmus and intention tremor
18
Q
____inflammation of optic nerve
A
optic neuritis
19
Q
what are other symptoms of MS?
A
trigeminal neuralgia, heat intolerance, fatigue (70% of cases), dizziness
20
Q
episodes of acute exacerbations or relapses with recovery and stable course between relapses
A
relapsing remitting (RRMS)
21
Q
gradual neurologic deterioration and worsening of symptoms with or without relapses in a previous RRMS patient.
-follows RRMS
A
secondary progressive (SPMS)
22
Q
gradual, nearly continuous neurologic deterioration from onset of symptoms with no relapses or remissions
A
primary progressive (PPMS)
23
Q
gradual neurologic deterioration from onset of symptoms with subsequent relapses and no remissions
A
progressive relapsing (PRMS)
24
Q
what is the most common type of MS?
A
relapsing remitting (RRMS)
25
what are all the types of MS?
relapsing remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS) and progressive relapsing (PRMS)
26
what is the etiology of MS?
genetic and molecular factors
27
what is the etiology of viral infections have to do with MS?
EBV
28
low levels of vitamin ___ makes you at risk for developing MS
D
29
Histology of MS shows the ____as the myelin is destroyed
vacuolation
30
Histology of MS: the first step seems to be adhesion molecules interacting with ___, ___ and ____. Later the BBB endothelium is digested away and the cells enter.
T cells, B cells and macrophages
31
Histology of MS: ____ release immunoglobulins, ____ release inflammatory cytokines and chemokines; and ____ expose axons releasing NO, glutamate and oxygen free radicals
1. B cells
2. T cells
3. macrophages
32
what are the three categories of acute demyelination in MS?
1. phagocytic cells with perivascular and parenchymal T cell infiltration
2. everything in category 1 plus the presence of complement and antibodies
3. oligodendrocyte apoptosis
33
____responsible for myelin in CNS
oligodendrocyte
34
___responsible for myelin in PNS
schwann cell
35
-what determines remyelination or not, is not well understood
-remyelination with a thin myelin sheath
-chronic inactive
-smoldering
chronic MS
36
inflammation resolves without remyelination
chronic inactive
37
inflammation does not resolve and there is a slow demyelination
smoldering
38
what type of MS is smoldering most common?
progressive MS
39
what type of MS?
-recurrent attacks that resolve or almost completely resolve
-remission can last for month to years
-there is very little residual deficit. however, today it is theorized that there is progressive neuronal degeneration continuing even during periods of remission
RRMS
40
today treatment modalities slow progress of ___, but within 10-15 years of the onset of the disease, 50% of patients will convert to ___
1. RRMS
2. SPMS
41
____increasing disability with little response to todays drugs
SPMS
42
____ 10-15% of cases there is a steady decline in function. No remissions and no clear exacerbations
PPMS
43
___progressive decline with occasional relapses. Rare.
PRMS
44
methylprednisolone is used in MS for ____
acute exacerbations
45
disease modifying agents for MS (DMAMS)
-primarily for ____
-reduces frequency and severity of clinical attacks
-includes ____
1. RRMS
2. interferons, monoclonal antibodies
46
____ reduce the frequency of clinical exacerbations, decreases lesion volume and number
interferons
47
Frequency of disease: common
latitude gradient: present
female sex%: 70
ethnic variation: white people
age of onset: 20-40
progressive course: common
coexistent autoimmune disease: rare
multiple sclerosis (MS)
48
Frequency of disease: rare
latitude gradient: not proven
female sex%: 90
ethnic variation: africans and asians
age of onset: 40-60
progressive course: rare
coexistent autoimmune disease: MG, SLE, sjorens, thyroid, APL
neuromyelitis optica spectrum disorder (NMOSD)
49
NMOSD causes ____ (sometimes bilateral) resulting in loss of vision in the horizontal half of the visual field
optic neuritis
50
NMOSD causes demyelination of the _____ or _____
cervical or thoracic spinal cord
51
NMOSD causes muscle spasms, incontinence and ____ or ___
paraparesis or quadriparesis
52
___ is direct demyelination (primary)
MS
53
____ indirectly demyelinates myelin (secondary to astrocytic damage)
NMOSD
54
the pathophysiology of NMOSD: body produces antibodies against ____
aquaporin 4
55
aquaporin 4 is the most widely expresses water channel in the ___, ____ and ____ (also present in collecting ducts of kidney, parietal cells of the stomach, airways, secretory glands and skeletal muscles
brain, spinal cord and optic nerves
56
in the CNS aquporin 4 is found primarily in the ___
foot processes of astrocytes
57
in NMOSD antibodys get through BBB, bind to ____ on the astrocytes and intiate complement and inflammation
aquaporin 4 receptors
58
in _____
-neutrophils and eosinophils are abundant
-damaged astrocytes can no longer support neurons or oligodendrocytes and demyelination occurs
NMOSD
59
unlike MS, in NMOSD demyelination is secondary to ____
astrocytic damage
60
what is the target in NMOSD?
what is the NMOSD mediated by?
1. astrocytes
2. complement
61
-never fully recovers from relapses
-relapses accumulate in disability
NMOSD
62
-older onset than MS-primarily
-5:1 female to male ratio
-no cognitive changes
NMOSD
63
what is the target in MS?
oligodendrocytes and myelin
64
-can fully recover from relapses
-disability not always correlate with relapses
MS
65
-younger onset
-2:1 female to male ratio
-cognitive change over time
MS
66
-treatment for?
1. high dose steriods for acute attacks
2. immunosupressives
3. untreated, approximately 50% of NMOSD patients will be in wheelchair and blind
NMOSD
67
if untreated, 1/3 of ___patients die within 5 years of their first attack
NMOSD
68
In MS
1. unknown trigger sets up intitial focus of inflammation in brain and BB becomes locally permeable to ____ and ____
2. T cells specific for cns antigen and activated in peripheral lymphoid tissues reencounter antigen presented on ___ or ___ in brain
3. Inflammatory reaction occurs in brain due to ____, ___, ___ and ___
4. demyelination of neurons occurs
1. leukocytes and blood proteins
2. microglia or dendritic cells
3. mast cell activation, complement activation, antibodies and cytokines
69
risk factors for MS
- _____ and _____
-in pateints, increased serum levels of antibodies targeting EBV nuclear antigen 1 (EBNA1) strongly correlate with MS onset, and relapses are reported to associate with defective CD8 T cell mediated control of EBV reactivation
-high levels of IgG against HHV-6 are observed in patients with certain stages of MS
EBV and human herpesvirus 6 (HHV-6)
70
risk factors for MS
-____, ___ and ____: an individual immune system is strongly influenced by nutrition, both through the demand for engery and how nutrition shapes the gut microbiome
-obesity in adolescents and young adults, classified as having a body mass index of >30 kg/m2, is associated with the increase risk of MS
metabolism, diet and obesity
71
______, are found in active MS lesions within the CNS
CD4 TH cell in MS pathogenesis, IFN gamma producing TH1 cells and IL17 producing TH17 cells
72
____can weaken the integrity of the BBB and thereby, promote further neuroinflammation
TH17 cells
73
___ which can migrate to and damge neurons directly within the grey matter have been associated with neuronal decline and neurodegeneration
CD4 T cells
74
____ dominate the T cell infiltrates in active MS lesions and are reduced in criculation
CD8 T cells
75
____ in MS lesions exhibit tissue resident memory phenotype and show markers of activation, as well as expresssion of pro-inflammatory cytokine IL17
CD8 T cells
76
___ these clonally expanded and antigen experienced B cells recognize ubiquitos intracellular and seemingly non pathogenic self proteins
B cells
77
recruitment of ____ into the CNS is controlled by the presence of the growth factor GM-CSF, which is produced by autoreactive T cells
monocytes
78
conventional ___ show a dysregulated pro-inflammatory phenotype, enhanced production of IL12 and IL23, as well as increased expression of chemokine receptors CCR5 and CCR7, permitting their migration to the CNS
dendritic cells
79
The role of IL12 production by ____ and other APCS is pivotal for the generation of TH1 cells and cytotoxic CD8 t cell expansion, and in promoting autoreactive TH1 cell and CD8+ T cell populations in MS
dendritic cells
80
-targets for MS
_____ is generated against proteins of the CNS towards the myelin sheath that protects the axons of neurons
antigen specific immune response CD4 T cells
81
targets for MS
-components of the myelin sheath for example ____ are the main targets for autoimmune attacks
myelin basic protein (MBP), myeline oligodendrocyte glycoprotein (MOG) or proteolipid protein (PLP)
82
-targets for MS
________have been recognized to cross react with glial cell adhesion molecule (glialCAM), a protein expressed by CNS resident glial cells
antibodies against the Epstein Barr Virus (EBV) nuclear antigen 1 (EBNA1)
83
-targets for MS
___release and autoimmune brain inflammation can be induced independently of specific antigens
cytokine
84
unpredictable attacks which may or may not leave permanent deficits followed by periods of remission
relapsing remitting MS RRMS
85
steady increase in disability without attacks
primary progressive MS PPMS
86
intial relapsing remitting multiple sclerosis that begins to have decline without periods of remission
secondary progressive MS SPSM
87
steady decline since onset with super imposed attacks
progressive relapsing MS (PRMS)
88
-very early in disease
widespread inflammatory infiltrates, populations of ____
-the subsequent destruction of myelin producing oligodendrocytes by these cells leads to formation of acute lesions in early disease stages
-demyelinated axons and axonal damage occur and the neuronal body is affected. this indicates that neuronal loss, a defining feature of disease progression, is also present in early stages of disease
CD4 T cells, CD8 T cells, B cells and monocytes
89
_____
-S1 preceptor modulators
-agents that stop T cell, B cell proliferation
-prevent entry of lymphocytes into CNS
-push T cell into T-reg state
-interferons
disease modifying therapies for MS
90
what do S1 preceptor modulators do?
sequester lymphocytes in lymph nodes
91
___ binds Cd20 B cells, inducing cell death
ocrelizumab
92
____inhibits dihydro-orotate dehydrogenase, inducing cytostatis
teriflunomide
93
____binds CD52 lymphocytes, inducing cell death
Alemtuzumab
94
___affects proliferating lymphocytes DNA, inducing cell death
cladribine
95
___ binds a4 integrin subunit on lymphocytes. inhibits lymphocyte entry into the CNS
Natalizumab
