Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

I&I WC1 > Central nervous system > Flashcards

Central nervous system Flashcards

1
Q

Which cells are the primary cells forming the blood-brain barrier?

A

Astrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

In which space is CSF located?

A

Subarachnoidal space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which type of lymphocyte can be found in the brain? Where are they found?

A

T-cells, located in the perivascular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do T-cells migrate migrate out of the CSF? (2)

A
  1. Via lymphatic vessels in the meningeal spaces
  2. Via blood vessels to the deep cervical nodes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which bacterial CNS infections are commonly found in neonates? (4)

A
  1. E. coli
  2. L. monocytogenesis
  3. Staphylococci & enterococci -> in vulnerable children
  4. Pneumococci
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where do E. coli that cause CNS infections in neonates often come from?

A

Maternal faecal flora

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which bacterial CNS infections are commonly found in adults? (4)

A
  1. Pneumococci
  2. Meningococci
  3. Staphylococcus
  4. H. influenzae
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the mechanisms by which meningitis causes brain damage? (2)

A
  1. Inflammatory damage to the brain tissue
  2. Endothelium & astrocytes start to leak, causing oedema & brain compression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Via which spaces do inflammatory cells enter the subarachnoidal space?

A

Virchow-Robin spaces (perivascular space)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is a severe systemic complication of N. meningitidis meningitis?

A

Waterhouse-Friedrichsen syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Waterhouse-Friedrichsen syndrome? (3)

A
  1. Diffuse intravascular coagulation
  2. Bilateral haemorrhage of the adrenal glands
  3. Sepsis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is cerebritis?

A

Encephalitis -> inflammation of brain tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the most common result of bacterial encephalitis?

A

Abcess formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are common sources of bacteria causing brain abscesses? (3)

A
  1. Endocarditis
  2. Pneumonia/pulmonary infections
  3. Abdominal infections (peritonitis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens in case of m. tuberculosis infection of the brain?

A

Granulomatous infection with obstruction of blood vessels, leading to blockage of CSF ducts (increased intracranial pressure) and infarctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which bacterium causes syphilis?

A

Treponema pallidum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What kind of CNS infection does syphilis cause?

A

Meningo-vascular inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How can neurosyphilis be prevented?

A

Antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which part of the CNS is typically affected by syphilis? What is the effect of this?

A

Dorsal roots of the spinal chord -> disruption of sensory neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which bacterium causes Lyme disease?

A

Borrelia burgdorferi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How is Lyme’s diseasae transmitted?

A

Ixodes ticks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are acute symptoms of Lyme’s disease? (4)

A
  1. Fever
  2. Migratory bull’s-eye rash
  3. Muscular/joint pain
  4. Meningeal irritation, causing headaches
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does HSV1 enter the body?

A

Through mucous membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the genetic makeup of HSV1?

A

DNA virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Where does HSV1 establish infection?

A

Dorsal ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Where does HSV1 typically cause encephalitis, if it infects the brain?

A

Basal side

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the genetic makeup of rabies virus?

A

RNA virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

True or false: rabies virus only infects humans

A

False; rabies virus can affect all mammals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How is rabies virus transmitted?

A

Infected secretions (saliva)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How does rabies virus travel to the brain?

A

Retrograde axonal transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

To which viral family does poliomyelitis belong?

A

Enterovirus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Risk of paralysis due to polio [decreases/increases] with age

A

Increases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How many % of polio-infected individuals are symptomatic?

A

5-8%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are known neurological complications of COVID-19? (4)

A
  1. Cerebral haemorrhage
  2. Encephalitis
  3. Ischemic stroke due to increased coagulation
  4. Hypoxia & systemic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

In which patient group do parasitic infections of the CNS most often occur?

A

Immunocompromised individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are parasites that commonly cause infection of the CNS? (3)

A
  1. Cryptococcus
  2. Amoeba
  3. Toxoplasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What kind of disease does cryptococcal infection of the brain cause?

A

Chronic meningitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is a group of auto-immune diseases that commonly affects the brain?

A

Vasculitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Into which two groups can vasculitids that infect the brain be grouped?

A
  1. Systemic vasculitis
  2. Primary granulomatous vasculitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is ADEM? What triggers it?

A

Acute demyelinating encephalomyelitis -> caused by virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is immune privilege (definition)?

A

Permissiveness/proneness of tissue/anatomical site develop and sustain immune activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

By which features can malignancies avoid the immune system? (3) Why is this relevant for understanding CNS immunity?

A
  1. Modulation of cytokine environment
  2. Not displaying proteins/potential antigens on MHCII
  3. Seclusion in seperate compartments through a physical barrier

These mechanisms can also be found in CNS immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are the unique features of the blood-brain barrier? (4)

A
  1. Overlapping tight junctions between endothelial cells
  2. Active pumps that remove molecules from the CNS
  3. High amount of pericytes
  4. Presence of a perivascular space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

How do overlapping tight junctions between endothelial cells contribute to the blood-brain barrier?

A

Prevent spontaneous passing of cells and molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

How does the ratio of endothelial cells:pericytes in the CNS differ from the rest of the body?

A

Higher amounts of pericytes per endothelial cell in the CNS than in the rest of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is the function of pericytes in the blood-brain barrier?

A

Contribute to a controlled immune environment by producing pro- and anti-inflammatory cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

By which 2 basal membranes is the perivascular space coverd?

A
  1. Basement membrane of the endothelium
  2. Glia limitans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the glia limitans?

A

Clutched together end feet of astrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the function of the glia limitans?

A

Tight border that controls entry of cells & molecules into the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

The perivascular space is very [sterile/immunogenic]

A

Immunogenic -> contains a lot of immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Why is the perivascular space an opportune site for immune surveillance of the brain?

A

Contains a continuous flow of interstitial fluid towards the veins, to remove waste -> waste products = potential antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

How are waste products transported out of the perivascular space?

A

Interstitial fluid with waste products flows along the postcapillary venules, towards the veins and is drained from the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the structural makeup of the perivascular space. What is the function of this makeup?

A

Contains interstitial matrix & mesenchymal structures, allowing for the maintainance of resident and surveilling lymphocyte populations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is a characteristic of T-cells in the perivascular space?

A

Express inhibitory markers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

True or false: the perivascular space does not contain APCs under physiological substances

A

False

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Which APC population can mainly be found in the perivascular space?

A

Perivascular macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is the difference between perivascular macrophages & microglia when it comes to:
1. Phagocytosis
2. Activation threshold
3. Antigen-presentation
4. Expression of costimulation

A
  1. Both perivascular macrophages & microglia have phagocytic activity
  2. Perivascular macrophages are easily activated by IFN-γ, whereas microglia require multiple cytokines to be activated
  3. Perivascular macrophages are strong antigen-presenters, microglia are moderate antigen-presentors
  4. Perivascular macrophages express many costimulatory molecules, while microglia have few costimulatory molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the most important mechanism controlling the influx of inflammatory cells into the brain parenchyma?

A

Interaction between APCs and T-cells in the perivascular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is required for a T-cell to be able to enter the brain parenchyma?

A

Reactivation in the perivascular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

True or false: inflammatory mediators are only present in the PVS (and not in the parenchyma) under physiological circumstances

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Apart from restricting entry into the brain, which mechanism also prevents inflammation inside the brain parenchyma?

A

High expression of anti-inflammatory cytokines (TGF-β) & anti-inflammatory markers (CD200)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is an important anti-inflammatory cytokine of the brain parenchyma?

A

TGF-β

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is an important anti-inflammatory surface marker of the brain parenchyma?

A

CD200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Which two routes can cells take to enter the perivascular space?

A
  1. Meningeal vasculature
  2. Choroid plexus -> cells end up in the subarachnoid space, and eventually in the perivascular space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Why is knowledge on how (T-)cells enter the brain useful in diseases? (2)

A
  1. Can be used for prevention of cell entry in case of neuroinflammatory diseases
  2. Can be used to promote cell entry in case of infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

How do inflammatory cells recognize they are in the brain?

A

Brain endothelium contains a unique set of integrins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Why is knowledge on the integrins expressed by endothelium in the brain useful?

A

Can be used to block integrin interaction -> prevents extravasation of inflammatory cells specifically in the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Via which two routes do inflammatory cells leave the brain? (2)

A
  1. Sinuses
  2. Lymphatic vessels in the meninges
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Where do lymphatic vessels in the meninges drain to?

A

Deep cervical lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What is the most common cause of encephalitis?

A

Viral infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What is the incidence of viral encephalitis?

A

5-10/100.000 persons/year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

How many different viruses have been implicated in viral encephalitis?

A

~100

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What is the difficulty in diagnosing viral encephalitis?

A

(Initial) symptoms are very aspecific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What are symptoms of viral encephalitis? (6)

A
  1. Fever
  2. Headache
  3. Behavioural changes
  4. Altered level of consciousness
  5. Focal neurological deficits
  6. Seizures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Which groups of viruses are known to cause viral encephalitis? (5)

A
  1. Herpesviruses
  2. Enteroviruses
  3. Paramyxoviruses (rare)
  4. Zoonotic causes
  5. Rest group
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Which herpesviruses can cause viral encephalitis? (5)

A
  1. HSV1
  2. HSV2
  3. CMV
  4. EBV
  5. HHV6
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Which enteroviruses can cause viral encephalitis? (3)

A
  1. Poliovirus
  2. Coxsackievirus
  3. EV71
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Which paramyxoviruses can cause viral encephalitis? (3)

A
  1. Measles
  2. Mumps
  3. Rubella

(note: this is rare!)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Which zoonotic viruses can cause viral encephalitis? (3)

A
  1. Arboviruses: WNV/JEV
  2. Rabies virus
  3. Nipah virus
79
Q

What is an important characteristic of zoonotic viruses that can cause viral encephalitis?

A

They are geographically restricted

80
Q

What are the main routes of viral entry into the CNS? (2)

A
  1. Hematogenous
  2. Migration via peripheral nerves
81
Q

Which viral families reach the brain by hematogenous dissemination? (2)

A
  1. Enteroviruses
  2. Arboviruses
82
Q

Which viral families reach the brain by migration via peripheral nerves? (2)

A
  1. Rabies virus
  2. Herpesviruses
83
Q

What are the mechanisms of damage in viral encephalitis? (2)

A
  1. Direct cytopathic effect
  2. Immune responses
84
Q

Which two mechanisms contribute to immune-mediated damage to the brain parenchyma in viral encephalitis?

A
  1. Antiviral immune response kills infected cells
  2. Viral infection of microglia can exacerbate immune response
85
Q

Which viruses cause relatively mild encephalitis? (3)

A
  1. Enterovirus
  2. Mumps
  3. LCM
86
Q

Which viruses cause mild-fatal encephalitis?

A

Arboviruses

87
Q

Which kinds of viral encephalitis are always fatal? (2)

A
  1. Rabiesvirus
  2. Herpesviruses
88
Q

Which three major groups of arboboviruses can cause viral encephalitis?

A
  1. Flaviviridae
  2. Togaviridae
  3. Buyaviridae
89
Q

Which viruses that can cause viral encephalitis belong to the flaviviridae? (3)

A
  1. Japanese encephalitis
  2. Tick-borne encephalitis
  3. West Nile Virus
90
Q

Which viruses that can cause viral encephalitis belong to the togaviridae? (2)

A
  1. Eastern equine encephalitis
  2. Western equine encephalitis
91
Q

Which virus that can cause viral encephalitis belongs to the buyaviridae?

A

La Crosse encephalitis

92
Q

How many % of WNV infections experiences symptoms? What are the main symptoms?

A

20%, mainly experiencing flu-like symptoms

93
Q

What is the mortality of symptomatic WNV infections in the general population, and in the elderly?

A

General population: 10%
Elderly: up to 35%

94
Q

True or false: the majority of symptomatic WNV cases will experience rest symptoms

A

False; most cases will have complete recovery

95
Q

What are rest symptoms of WNV infection? (4)

A
  1. Fatigue
  2. Myalgia
  3. Residual tremor
  4. Parkinsonism
96
Q

Which group of the herpesviruses is neurotropic?

A

Alphaherpesviridae

97
Q

Where do (most) herpesviruses establish latency?

A

Trigeminal ganglion

98
Q

To which three regions can HSV disseminate from the trigeminal ganglion? What are the effects of this?

A
  1. Mouth -> cold sores
  2. Eyes -> herpes keratitis
  3. Brain -> encephalitis
99
Q

What is a unique property of neurons in the trigeminal ganglion that allows herpesviruses of the brain?

A

They are pseudobipolar -> allow for axonal transport in both directions

100
Q

Which virus most commonly causes herpes encephalitis?

101
Q

How many % of all viral encephalitis is caused by HSV1?

102
Q

What is the incidence of herpes encephalitis?

A

4/1.000.000/year

103
Q

What is the mortality of herpes encephalitis if untreated/treated?

A

Untreated: 70%
Treated: 30%

104
Q

What is the treatment of herpes encephalitis?

A

(Early) acyclovir

105
Q

How many % of cases of HSV encephalitis retain morbidity?

106
Q

What are the main rest symptoms of herpes encephalitis? (2)

A
  1. Neurological deficits
  2. HSV retinitis
107
Q

Which age groups are most at risk of herpes encephalitis?

A

Individuals at extremes of age

108
Q

Which brain lobes are mainly affected by herpes encephalitis?

A

Inferior frontal and anterior temporal lobes

109
Q

Which diagnostics should be used in case of suspected viral encephalitis? (3)

A
  1. Symptomatology
  2. PCR on CSF
  3. Local antibody production tests
110
Q

What should be the immediate treatment of suspected viral encephalitis?

A

Immediately start acyclovir in case it is HSE -> most common cause of encephalitis

111
Q

How many % of meningitis cases are caused by:
1. N. meningitidis
2. S. pneumoniae
3. H. influenzae

A

N. meningitidis = 20%
S. pneumoniae = 50%
H. influenzae = 5%

112
Q

Why is S. pneumoniae the bacterium causing most CNS infections, even if it preferentially infects the lungs?

A

Streptococcus infections are far more common than meningococcus infections

113
Q

Which local infections can S. pneumoniae cause? (3)

A
  1. Sinusitis
  2. Otitis media
  3. Other paranasopharyngeal infections
114
Q

How many % of people is asymptomatic carrier of n. meningitidis?

115
Q

What are diseases that can be caused by n. meningitidis? (5)

A
  1. Petechiae
  2. Pneumonia
  3. Meningitis
  4. Sepsis
  5. Shock
116
Q

How many global cases of meningococcal meningitis are there every year?

117
Q

How many global cases of mortality due to meningococcal meningitis are there every year?

118
Q

What are risk factors for S. pneumoniae meningitis? (3)

A
  1. Immunocompromised
  2. Splenectomy
  3. Genetic polymorphisms
119
Q

What are risk factors for meningococcal carriage? (2)

A
  1. Smoking
  2. Living in an infected household
120
Q

What are clinical features of bacterial meningitis? (10)

A
  1. Headache
  2. Nausea/vomiting
  3. Photophobia
  4. Fever
  5. Neck stiffness
  6. Altered mental status
  7. Rash/petechia
  8. Signs of local infection
  9. Neurological deficits
  10. Epileptic seizures
121
Q

What causes neck stiffness in bacterial meningitis?

A

Increased pressure on the meninges

122
Q

Which feature is characteristic for meningococcal meningitis?

123
Q

Which diagnostics are used to diagnose bacterial meningitis? (3) On which material?

A

Lumbar punction, determining:
1. Purulence
2. Leucocytes
3. Low glucose

124
Q

What are systemic complications of bacterial meningitis? (3) In how many % of cases do they occur?

A
  1. Cardiorespiratory failure: 30%
  2. Hyponatremia: 25%
  3. Disseminated intravascular coagulation: 8%
125
Q

What are neurological complications of bacterial meningitis? (7) In how many % of cases do they occur?

A
  1. Cerebrovascular complications = 25-30%
  2. Meningo-encephalitis = 15-20%
  3. Seizures = 15-25%
  4. Hearing loss = 15-20%
  5. Brain oedema = 5-10%
  6. Hydrocephalus = 3-8%
  7. Transtentorial herniation
126
Q

What causes cerebrovascular complications in bacterial meningitis? (2)

A
  1. Arteriitis
  2. Decreased cerebral perfusion
127
Q

What causes hydrocephalus in bacterial meningitis? (2)

A
  1. Purulent CSF
  2. Vein thrombosis
128
Q

What is the standard initial treatment for bacterial meningitis?

A

Ceftriaxone + amoxicillin & dexamethasone

129
Q

How many % of bacterial meninigitis result in:
1. Mortality
2. Moderate disability
3. No disability

A
  1. Mortality = 21%
  2. Moderate disability = 10%
  3. No disability = 66%
130
Q

Which kinds of disability can remain after bacterial meningitis? (5)

A
  1. Hearing loss
  2. Cognitive impairment
  3. Aphasia
  4. Hemiparesis
  5. Quadriparesis
131
Q

Which two strategies do bacteria employ to survive in the bloodstream and cause meningitis?

A
  1. Bacterial capsule protects them against complement-mediated bacteriolysis & phagocytosis
  2. Acquisition of iron from transferrin
132
Q

What is the most effective way of preventing bacterial meningitis?

133
Q

Which vaccines protect against bacterial meningitis? (3)

A
  1. HiB
  2. N. meningitidis A, C, W, Y
  3. S. pneumoniae
134
Q

What is the age of symptom onset of MS?

A

20-50 years

135
Q

What is the female:male ratio of MS patients?

136
Q

What is the prevalence of MS in Northern Europe?

A

1,5-2/1000

137
Q

What are known risk factors for MS? (4)

A
  1. EBV
  2. Smoking
  3. Low vitamin D
  4. Genetic makeup
138
Q

Which risk factor is always implicated in MS?

139
Q

Which three different disease patterns can be identified in MS?

A
  1. Relapsing-remitting MS (RRMS)
  2. Secondary progressive MS (SPMS)
  3. Primary progressive MS (PPMS)
140
Q

How many % of MS patients start with RRMS

141
Q

Which pathological processes are involved in MS? (3)

A
  1. CNS inflammation
  2. Demyelination
  3. Neurodegeneration
142
Q

True or false: demyelination in MS is irreversible

A

False; demyelination is reversible (this is also the cause of relapsing-remitting MS)

143
Q

Which processes constitute neurodegeneration in MS? (3)

A
  1. Loss of synapses
  2. Loss of axons
  3. Loss of neurons
144
Q

What is the hallmark of RRMS?

A

White matter flares

145
Q

What happens to microglia in white matter lesions in MS?

A

They are activated by T-cells and attain a macrophage phenotype

146
Q

Which cells are primarily responsible for direct damage to oligodendrocytes & neurons in RRMS?

A

Activated microglia

147
Q

Which model is used for the study of inflammatory white matter lesions in MS? What kind of response is present here?

A

Auto-immune encephalitis -> induced auto-immune response to myelin

148
Q

What is focal axonal degeneration?

A

Degeneration of axons due to macrophage attack

149
Q

What are the stages in focal axonal degeneration? (3)

A
  1. Normal axon
  2. Swelling & thinning
  3. Breakage
150
Q

True or false: focal axonal degeneration is reversible

A

True; focal axonal degeneration is PARTIALLY reversible

151
Q

What is the hypothesized role for Ca2+ in focal axonal degeneration?

A

Intra-axonal [Ca2+] drives focal axonal degeneration

152
Q

The further axons get damaged in focal axonal degeneration, the [lower/higher] the amount of Ca2+ in axons

A

The more axons get damaged, the higher [Ca2+] -> amount of Ca2+ predicts axonal fate

153
Q

What happens when extracellular Ca2+ is removed from axons undergoing focal axonal degeneration? What does this signify?

A

Axon is rescued -> calcium causing focal axonal degeneration is most likely from the extracellular space and not from the axolemma

154
Q

How does extracellular calcium enter axons during focal axonal degeneration?

A

Leaky membrane due to physical damage

155
Q

What is the main cause of progressive MS? Which three processes are involved?

A

Loss of brain tissue

  1. Demyelination
  2. Loss of synapses
  3. Loss of neurons
156
Q

What is the primary part of the brain in which neurons are lost in progressive MS?

A

Cerebral cortex

157
Q

True or false: in progressive MS, brain damage occurs due to presence of a high amount of inflammatory cells in the cortex

A

False; during PMS, inflamamtory cells are mostly absent form the cortex

158
Q

Where are inflammatory cells located in progressive MS? How do they hypothetically cause damage to brain tissue?

A

Meninges; they are involved in cortical pathology by secreting inflammatory factors that activate microglia

159
Q

What are the main pathogenic cells in progressive MS, responsible for damage to neurons?

160
Q

Which three types of microglia can be identified in (post mortem) brain tissue of MS patients?

A
  1. MS0
  2. MS1
  3. MS2
161
Q

What are MS0 microglia?

A

Microglia similar to healthy controls

162
Q

What are MS1 microglia?

A

Microglia with a classical microglial activation profile, expressing CD68 + MHCII, with low expression levels of homeostatic markers

163
Q

What are MS2 microglia?

A

MS-specific phenotype, with high branching & low expression of homeostatic & activation markers

164
Q

Where can MS1 and MS2 microglia be found in MS patients?

A

Adjacent to meningeal inflammation in PMS

165
Q

What is the animal model for progressive MS?

A

Chronic meningeal inflammation (CMI)

166
Q

True or false: MS1 stage of microglia precedes MS2 stage

167
Q

What is the current hypothesis on the pathology of PMS? (3)

A
  1. Meningeal (B-)cells secrete inflammatory factors
  2. Loss of microglia-mediated neuroprotection
  3. Impaired neuronal mitochondrial transport, leading to necroptosis
168
Q

How many % of MS can be genetically explained?

169
Q

What are the most important genes implicated in MS?

170
Q

How is MS diagnosed?

A
  1. Clinical picture
  2. Supportive evidence: MRI, CSF
  3. No better explanation
171
Q

Which tests can be performed on CSF to diagnose MS? (2)

A
  1. Oligoclonal bands
  2. Increased IgG index
172
Q

Which adaptive immune cells are physiologically present in the brain, and which aren’t?

A

T-cells are present, B-cells are absent

173
Q

The CSF contains [less/more] lymphocytes than blood

174
Q

How does the profile of lymphocytes in CSF differ from blood? (3)

A
  1. Blood contains naive cells, CSF does not
  2. Blood contains both T- and B-cells, CSF only T-cells
  3. Blood contains both CD4+ and CD8+ T-cells (CD4+>CD8+), CSF nearly exclusively CD4
175
Q

What is the predominant T-cell type found within the brain? Where are they found? Which characteristic markers do they express?

A

CD4+ tissue-resident memory T-cells, found in the perivascular unit and expressing CD68 & CD103

176
Q

Which three possibilities for the initiation of detrimental immune responses have been hypothesized?

A
  1. Cells get primed & activated by antigens in the periphery, then cross react to the CNS and cause focal inflamation
  2. Regulary T-cells patrolling the CNS get activated by local cues/mediators
  3. Disease starts within the brain parenchyma by presentation of antigens by microglia
177
Q

Tregs function [poorly/normally/strongly] in MS

A

Poor Treg function

178
Q

Which processes are targeted by current MS therapies? (5)

A
  1. APC-T-cell interaction
  2. Clonal expansion of T-cells
  3. Migration of T-cells
  4. Trafficking into the CNS of T-cells
  5. Inflammatory cell depletion
179
Q

Which therapeutic strategy is most potent in MS?

A

Inflammatory cell depletion

180
Q

What is the downside of current MS therapies, aimed at preventing T-cell activation/entry into the CNS?

A

Therapies are poor at stopping flares after they have aready began

181
Q

What is remarkable about circulating CD4+ T-cells in RRMS?

A

Increased amount of CD4+ T-cells with cytotoxic phenotype

182
Q

What is remarkable about B-cells in RRMS? What characterizes them?

A

B-cells with a phenotype prone to CSF-infiltration, express CXCR3

183
Q

How many % of patients with RRMS have grey matter lesions?

184
Q

Cells extravasate and enter the PVS. What needs to happen before they can enter into the CNS?

A

Activation in the PVS

185
Q

What are, very globally, the four pathogenic steps of RRMS?

A
  1. Cells activated in lymph nodes and enter the bloodstream
  2. Cells cross blood-brain barrier and enter the PVS
  3. Cells are activated in the PVS and enter the parenchyma
  4. Cells contribute to inflammation, loss of myelin & loss of axons
186
Q

True of false: during progressive MS, attacks are completely absent

A

False; although they are rare, they still can occur during progressive MS

187
Q

True or false: we currently have therapies that curb progressive MS

A

False; current therapeutics are only effective in RRMS

188
Q

Which cell types can be found in white matter lesions of people with progressive MS? (3)

A
  1. Myeloid cells
  2. T-cells
  3. B-cells
189
Q

Where do myeloid cells found in white matter lesions of patients with progressive MS come from?

A

They are the result of local expansion of macrophage-like cells

190
Q

What is thought to fuel progressive MS pathology?

A

Excretion of inflammatory mediators by (mainly) T-cells

191
Q

B-cells are present in [lower/higher] numbers than T-cells in progressive MS white matter lesions

192
Q

Presence of B-cells in white matter lesions in progressive MS is prognostically [favourable/unfavourable]

A

Presence of B-cells = unfavourable

193
Q

What is the presence of B-cells in white matter lesions in progressive MS correlated with? (4)

A
  1. Early mortality
  2. Higher amount of inflammatory lesions
  3. High number of T-cells in inflammatory lesions
  4. More intrathecal IgG production
194
Q

Why can presence of IgG/oligoclonal bands be used as a progression marker for progressive MS?

A

They point to the presence of B-cells, which are prognostically unfavourable

195
Q

How is presence of IgG against myelin in progressive MS important from a pathological point of view?

A

Can fuel breakdown of tolerance of microglia to myelin and activate demyelination

196
Q

In progressive MS, follice-like structures can form in the meninges. What is their presence associated with? (3)

A
  1. Earlier onset of disease
  2. Faster accumulation of disability
  3. Earlier death

I&I WC1 (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions