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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

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2
Q

In which space is CSF located?

A

Subarachnoidal space

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3
Q

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

A

T-cells, located in the perivascular space

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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
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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
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6
Q

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

A

Maternal faecal flora

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7
Q

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

A
  1. Pneumococci
  2. Meningococci
  3. Staphylococcus
  4. H. influenzae
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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
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9
Q

Via which spaces do inflammatory cells enter the subarachnoidal space?

A

Virchow-Robin spaces (perivascular space)

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10
Q

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

A

Waterhouse-Friedrichsen syndrome

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11
Q

What is Waterhouse-Friedrichsen syndrome? (3)

A
  1. Diffuse intravascular coagulation
  2. Bilateral haemorrhage of the adrenal glands
  3. Sepsis
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12
Q

What is cerebritis?

A

Encephalitis -> inflammation of brain tissue

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13
Q

What is the most common result of bacterial encephalitis?

A

Abcess formation

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14
Q

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

A
  1. Endocarditis
  2. Pneumonia/pulmonary infections
  3. Abdominal infections (peritonitis)
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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

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16
Q

Which bacterium causes syphilis?

A

Treponema pallidum

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17
Q

What kind of CNS infection does syphilis cause?

A

Meningo-vascular inflammation

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18
Q

How can neurosyphilis be prevented?

A

Antibiotics

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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

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20
Q

Which bacterium causes Lyme disease?

A

Borrelia burgdorferi

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21
Q

How is Lyme’s diseasae transmitted?

A

Ixodes ticks

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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
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23
Q

How does HSV1 enter the body?

A

Through mucous membranes

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24
Q

What is the genetic makeup of HSV1?

A

DNA virus

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25
Q

Where does HSV1 establish infection?

A

Dorsal ganglia

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26
Q

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

A

Basal side

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27
Q

What is the genetic makeup of rabies virus?

A

RNA virus

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27
Q

True or false: rabies virus only infects humans

A

False; rabies virus can affect all mammals

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28
Q

How is rabies virus transmitted?

A

Infected secretions (saliva)

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29
Q

How does rabies virus travel to the brain?

A

Retrograde axonal transport

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30
Q

To which viral family does poliomyelitis belong?

A

Enterovirus

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31
Q

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

A

Increases

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32
Q

How many % of polio-infected individuals are symptomatic?

A

5-8%

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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
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34
Q

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

A

Immunocompromised individuals

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35
Q

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

A
  1. Cryptococcus
  2. Amoeba
  3. Toxoplasma
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36
Q

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

A

Chronic meningitis

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37
Q

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

A

Vasculitis

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38
Q

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

A
  1. Systemic vasculitis
  2. Primary granulomatous vasculitis
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39
Q

What is ADEM? What triggers it?

A

Acute demyelinating encephalomyelitis -> caused by virus

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40
Q

What is immune privilege (definition)?

A

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

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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

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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
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43
Q

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

A

Prevent spontaneous passing of cells and molecules

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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

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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

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46
Q

By which 2 basal membranes is the perivascular space coverd?

A
  1. Basement membrane of the endothelium
  2. Glia limitans
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47
Q

What is the glia limitans?

A

Clutched together end feet of astrocytes

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48
Q

What is the function of the glia limitans?

A

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

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49
Q

The perivascular space is very [sterile/immunogenic]

A

Immunogenic -> contains a lot of immune cells

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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

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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

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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

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53
Q

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

A

Express inhibitory markers

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54
Q

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

A

False

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55
Q

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

A

Perivascular macrophages

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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
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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

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58
Q

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

A

Reactivation in the perivascular space

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59
Q

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

A

True

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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)

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61
Q

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

A

TGF-β

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62
Q

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

A

CD200

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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
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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
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65
Q

How do inflammatory cells recognize they are in the brain?

A

Brain endothelium contains a unique set of integrins

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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

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67
Q

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

A
  1. Sinuses
  2. Lymphatic vessels in the meninges
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68
Q

Where do lymphatic vessels in the meninges drain to?

A

Deep cervical lymph nodes

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69
Q

What is the most common cause of encephalitis?

A

Viral infection

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70
Q

What is the incidence of viral encephalitis?

A

5-10/100.000 persons/year

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71
Q

How many different viruses have been implicated in viral encephalitis?

A

~100

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72
Q

What is the difficulty in diagnosing viral encephalitis?

A

(Initial) symptoms are very aspecific

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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
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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
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75
Q

Which herpesviruses can cause viral encephalitis? (5)

A
  1. HSV1
  2. HSV2
  3. CMV
  4. EBV
  5. HHV6
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76
Q

Which enteroviruses can cause viral encephalitis? (3)

A
  1. Poliovirus
  2. Coxsackievirus
  3. EV71
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77
Q

Which paramyxoviruses can cause viral encephalitis? (3)

A
  1. Measles
  2. Mumps
  3. Rubella

(note: this is rare!)

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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?

A

HSV1

101
Q

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

A

11-22%

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?

A

> 70%

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?

A

5-15%

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?

A

500.000

117
Q

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

A

50.000

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?

A

Petechia

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?

A

Vaccines

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?

A

3:1

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?

A

EBV

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

A

85%

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?

A

Microglia

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

A

True

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?

A

19%

169
Q

What are the most important genes implicated in MS?

A

MHCII

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

A

Less

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?

A

38%

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

A

Lower

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)

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