Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Module 2 > HIV and the brain > Flashcards

HIV and the brain Flashcards

1
Q

How does HIV penetrate through the BBB?

A

in mononuclear cells

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

What cells in the CNS does HIV infect?

A

perivascular macrophages and microglial cells

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

Which neurotransmitters are involved in the damage seen with HIV associated brain damage?

A

glutamate and NO

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

What is seen on imaging with HIV associated dementia?

A

subcortical white matter abnormalities; generalised atrophy/ventricular enlargement

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

What are the neuropathological features of HIV-associated dementia?

A

persistent astrocytosis and microglial activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the symptoms of HAD?

A

memory deficits; attention and mental slowing; mood distubrances; social withdrawal and apathy; slowness and loss of balance

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

Where is there a prediliction for HIV-encephalitis?

A

subcortical regions esp. the basal ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the pathological features of HIV encephalitis?

A

microglial activation, perivascular astrocytosis in the central white matter and leucoencephalopathy causing myelin/axonal damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Waht does the clinical severity of HAD correlate with?

A

severity of HIV -encephalitis

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

What are the menifestations of primary HIV infection in the brain

A

aseptic meningitis; meningo-encephalitis and encephalitis

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

What are the possible outcomes of the brain menifestations of primary HIV in the brain?

A

self-limiting or persistent neurological sequelae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why are the brain menifestations of primary HIV difficult to diagnose?

A

often presents to praimry care; recent negative HIV-Ab doesn’t exclude diagnosis

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

What are the conditions given by the BHIVA guidelines for starting ART ASAP due to risk of increased progression or morbidity?

A

neuro involvement; any AIDS-defining illness; CD4 <350; PHI diagnosed within 12 weeks of a pervious negative test

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

What has changed about neuropathology since the introduction of cART?

A

prevalence of CNS OI has reduced lots but HIV-encephalitis is still found in upto 25% of cases –persistent astrocytosis and microglial activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the factors invovled in the pathogenesis of HIV-associated cognitive impairment in the cART era?

A

lifestyle and comorbidities; persistent immune activation; sub-optimal CNS penetration of ART; ART toxicity; accelerated brain aging?; neurodegeneration

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

What is a clinical marker of persistent immune activation?

A

nadir CD4 coutn

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

What is a clinical marker of sub-optimal CNS penetration?

A

CSF HIV-1 escape

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

What virus is responsible for progressive multifocal leucoencephalopathy

A

JC virus

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

What type of virus is JC virus?

A

human polymovarius

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

What are the causes of PML?

A

HIV and other immunocompromise; steroids; chemo; efalizumab; rituximab; inflixumab

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

What is the pupose of the CPE score?

A

it is a CNS penetration effectiveness score- measure of the CSF exposure to an ART

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

Is there any clinical significance to the CPE score?

A

it was at the beginning of hte ART era, but now with more powerful ART regimens, there is no clinical signficance of hte CPE score

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the treatments of PML?

A

effective ART; steorids; adjunctive therapies- e.g mefloquine; mirtazapine

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

In whihc patients does cryptococcal meningitis remain common?

A

patients unaware of HIV serostatus

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

What are the symptoms of cryptococcal meningitis?

A

sub-acute: fever; HA; malaise; confusion; pneumonia; cryptococcaemia

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

What is the median number of days of symptoms of cryptococcal meningitis beore diagnosis?

A

30

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

What are the serological tests for cryptococcal meningitis?

A

antigen detection; cryptococcal latex agglutination

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

What are the CSF tests for cryptococcal meningitis?

A

cell count/protein; opening pressure; culture organism

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

How often is CSF cell coutn and protein abnormal with cryptococcal meningitis?

A

40%

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

Why is opening pressure often raised with cryptococcal meningitis?

A

organisms/ polysaccharide fungal antigen covers reabsorption of CSF in arachnoid villi increasing the ICP

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

What is seen on imaging with cryptococcal meningitis?

A

often normal

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

What is the recomended treatment for cryptococcal meningitis?

A

liposomal amphotericin B and 5-flucytosine then fluconazole

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

What are the 2 forms of IRIS?

A

unmasking and paradoxical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is unmasking IRIS?

A

OI appears for the first time in a patietn who, prior to commencing HAART did not have symtpoms of that OI

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

What is the cause of unmasking IRIS?

A

sub-clinical or unrecognised infections surface because of the emergence of pathogen-specific immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is paradoxical IRIS?

A

an individual with a previously diagnosed OI or malignancy experiences a clinical deterioration while on effective HAART

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

Which infections is paradoxical IRIS most common with?

A

mycobacterial and cryptococcal disease

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

Why is IRIS in the CNS such a big problem?

A

inflammation can be life-threatening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What are the infectious causes of CNS mass lesions?

A

toxoplasmosis; M. tb and PML

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

What are some of hte malignancy causes of mass lesions on CT?

A

primary cerebral lymphoma; CNS involvement with systemic lymphoma; glioma; breast ca

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

What are the common neurological presentations in HIV patietns on ART?

A

headaches; neuropsychiatric disorders and depression; cognitive complaints

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

What is seen on CT with toxoplasmosis?

A

ring-enhancing lesions particularly in the basal ganglia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What psychiatric disease is more prevalent in HIV?

A

depression

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

What may be a cause of increased depression in HIV?

A

social? - people more likely to get HIV are more lilkley to be depressed; or is it a symptom of HIV itself

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

What suggests that depression is more common in HIV patients because of social reasons?

A

there is reduced condom use in those with depression

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

What is the highest risk factor for suicide in those with HIV?

A

not being on ART

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is a common adverse effect iwth ART?

A

insomnia- common cause for ART discontinuation

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

What has changed in the causes of cognitive impairment after the introduction of ART?

A

reduced HIV-associated dementia but incrased minor neurocognitive disorders

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

What are the criteria for HIV associated dementia?

A

marked impairment (at least 2 SD below mean) involving at least 2 cognitive domains; impairs with day-to-day functioning

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

What is the criteria for HIV associated mild neurocongitive disorder?

A

cognitive impairment (1 SD below mean) in at least 2 domains which has mild interference with functioning

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

What is the criteria for HIV associated asymptomatic neurocognitive impairment

A

impairment >1 SD in 2 or more domains which doesn’t interfere with daily life

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

How does level of education affect the risk of HIV associated cognitive impairment?

A

increased in those with <13 years of education

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

What is one way of screening for HIV associated cognitive impairment?

A

with questions:

  • frequent memory loss?
  • slower when reasoning; planning activities or solving problems?
  • difficulties paying attention?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Who should be screened for HIV-associated congitive impairment?

A

HIV patients or their relatives reporting cognitive problems without obvious confounding condition

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

What tests should be done when HIV associated cognitive impairment is suggested?

A

further Ix to exclude confounding condition- MRI brain; CSF examination

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

Where are the main areas of damage with HIV-dementia?

A

basal ganglia and thalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What are the differences between the symptoms of alzhemiers and FTD and HIV dementia?

A

don’t get language problems/ aphasia; memory problems with HIV-dementia whereas do get personality and attention problems in HIV-demenita

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

What type of dementia is HIV-dementia most similar to?

A

parkinsons and huntingtons

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

What is N-acetyl aspartate a measure of

A

the integrity of neurones

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

What comorbidities are associated with an increased risk of poorer cognitive performance?

A

CVD and hypertension

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

What does the increased CVD associated with HIV-dementia suggest about its pathogenesis?

A

may be a result of unerlying cerebral vascular disease or may be the result of increased inflammatory resposnes

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

What suggests taht ART toxicity may be a cause of HIV-dementia?

A

efavirenz use is associated with HIv-dementia in some studies

63
Q

what class of ART are generally best at CNS penetration?

A

NRTIs

64
Q

What are the advantages of the CNS penetration effectivness score?

A

cART with optimal CNS exposure associated with lower CSF HIV VL and better CNS penetrating drugs (NRTIs) shown to protect against HAD

65
Q

What are the disadvantages of CNS penetration effectiveness score?

A

treatment intensification have failed to demonstrate HIV RNA reduction in the CSF; CNS targeted cART not superior for congitive improvement or virologic suppression

66
Q

Why should ART to started when a diagnosis of HIV-associated ognitive impairment is diagnosed?

A

its symptomatic of HIV disease; in general improvements in cognitive function are seen when starting ART; avoids further CD4 coutn decline - RF for cognitive impairment

67
Q

What are the virological definitions of CSF HIV RNA escape?

A

either CSF RNA detectable and plasma is undetectable OR both CSF and plasma RNA is detectable- at same or higher

68
Q

What should happen if there is a diagnosis of HIV-associated cognitive impairment and there is viral escape?

A

optimise ART based on plasma and CSF resistance testing

69
Q

What is the mx for HIV associated cognitive impairment with viral suppression?

A

reassess for other causes of cognitive impairment, condier ARt toxicity

70
Q

What is the function of empirical treatment of toxoplasma?

A

allows the distinction of toxoplasma encephalitis from priamry CNS lymphoma- imaging is often nondiagnostic

71
Q

Which OI should not be treated without prior confirmation?

A

cryptococcus

72
Q

What is the commonest systemic fungal infection with HIV?

A

cryptococcus

73
Q

How common was cryptococcosis pre-ARt?

A

5-10%

74
Q

Which stain can be used to detect cryptococcus in the CSF?

A

india ink

75
Q

What are the poor prognostic factors in cryptococcal meningitis?

A

blood culture positivity; low WBC count; high CSF cryptoccal antigen; confused state and raised ICP

76
Q

What is the benefit of 5-flucytosine added to amphotericin B when treating cryptococcal meningitis?

A

speeds the rate of sterilisation of CSF and reduces incidence of relapse in patients not on HAARt

77
Q

What is the problem with adding 5-flucytosine to amphotericin B?

A

increased toxicity in some studies and has not had an impact on early or late mortality– benefits are mostly in patients not on HAART

78
Q

Why should liposomal amphotericin B be used rather than standard amphotericin B?

A

to reduce renal toxicity

79
Q

What should be considered in any patient with cryptococcal meningitis who deteriorates or develops new neuro signs?

A

repeat LP- to reduce ICP

80
Q

What is the maintenance therapy for cryptococcal meningitis?

A

fluconazole

81
Q

What can treat isolated pulmonary cryptococcus?

A

fluconazole

82
Q

why is there no prophylaxis given or cryptoccoal meningitis?

A

although there is a reudction in incidence with prophylaxis, there is no effect on survival and there is a risk of resistance and is high cost

83
Q

When should HAART be started with cryptococcal disease?

A

after 2 weeks, when induction therapy has been completed- increased mortality in patients started on HAART within 72 hours of starting treatment for cryptococcal disease

84
Q

what is the commonest cause of mass lesions in the immunocompromised HIV postiive individual?

A

toxoplasma abscesses

85
Q

What is toxoplasma gondii?

A

obligate intracellular protozoan

86
Q

where does toxoplasma gondii complete its sexual cycle?

A

in feline intestinal tract

87
Q

How do humans acquire toxoplasma?

A

eating animals with disseminated infection or by ingestion of ooxytes shed in cat faces that have contaminated soil, crops and water

88
Q

What may be seen with primary toxoplasma infection in immunocompetent individuals?

A

mononucleosis-like syndrome

89
Q

What causes toxoplasmosis in immunodeficient patients?

A

reactivation of chronic infection acquired earlier in life

90
Q

what are manifestations of toxoplasma outside the brain?

A

chorioretinitis and pneumonia

91
Q

What type of imaging is preferred for toxoplasma?

A

MRI

92
Q

What is the differential for toxoplasma abscesses?

A

PCNSL; tuberculous disease and PML

93
Q

What would suggest taht a lesion is primary cerebral lymphoma rather than toxoplasma?

A

if lesion is single; have a periventricular location or show sub-ependymal spread

94
Q

What is the difference betweeen the lsions seen in toxoplasma and PML?

A

in PML tend to mainly involve white matter; are rarely contrast enhancing and don’t exhibit mass effect

95
Q

What is the use of serology with toxoplasma?

A

only indicates previous infeciton, rising IgG titres would be indicative of reactivation however this doesn’t happen in immunocompromised patietns so only useful as a risk marker

96
Q

What is the first line therapy for toxoplasma?

A

pyrimethamine; sulphadiazine and folinic acid

97
Q

When should anti-toxoplasma therapy be started empirically?

A

in any HIV patient with CD4 <200 and a brain mass lesion

98
Q

When should prophylaxis for toxoplasma be started?

A

in patients with CD4 <200

99
Q

When should primary and secondary prophylaxis for toxoplasma be discontinued?

A

when CD4 counts are repeatedly aboe 200

100
Q

Where does JC virus set up latent infection?

A

spleen; bone marrow; kidneys; B-cells

101
Q

How is JC virus transported to the brain ?

A

via B- cells

102
Q

What cells in the brain does JC virus infect?

A

oligodendrocytes

103
Q

What receptor does JC vrius use to infect oligodendrocytes?

A

serotonin receptor

104
Q

What causes the symptoms with PML?

A

demyelination of white matter

105
Q

What are the symptoms of PML?

A

progressive focal neurology- mainly motor; altered mental.mood; ataxia or cortical visual symptoms

106
Q

What symptom helps differentiate PML from HIV encephalopathy?

A

presence of focal features

107
Q

How is PML diagnosed?

A

MRI appearances and JC virus detection by PCR in CSF– avoids biopsy which was gold standard

108
Q

What is the only treatment which has improved clinical outcomes with PML?

A

HAART

109
Q

How many patients developed CMV disease pre-ART?

A

20-40%, with many more having evidence of disease at post-mortem

110
Q

Which site accounts for 3/4 of CMV disease?

A

retina

111
Q

What are the neurological presentations of CMV?

A

encephalitis and polyradiculitis

112
Q

What are the preferred diagnostic tests for CMV?

A

MRI scanning and CSF PCR

113
Q

what is the treatment for CMV disease?

A

ganciclovir with/without foscarnet

114
Q

What is seen with polyradiculitis?

A

rapidly progressive, painful bilateral ascending flaccid paralysis with saddle anaesthesia; arefelxia; sphincter dysfunctio nand urinary retention

115
Q

Should prophylaxis for CMV encephalitis/polyradiculitis?

A

no, only trials for retinitis - but HAART reduces the incidence of these conditions

116
Q

When does CMV end-organ disease typically occur?

A

CD4 <50

117
Q

Why should ART starting be delayed after opportunistic infections?

A

IRIS

118
Q

What is thought to be the important mediator of neurocognitive impairment in HIV?

A

synaptodendritic neuronal injury

119
Q

When does HIV enter the CNS?

A

in the earliest stages of infection

120
Q

How many patients develop neurocognitive impairment with HIV?

A

> 50%

121
Q

How has cART altered the character of the predominant neuro manifestation of hiv infection?

A

changed from a devastating, severe dementia to a chronic, milder degree of neurocognitive impairment

122
Q

What is the function of tight junctions between brain endothleial cells?

A

prevents the diffusion of polar molecules- lipophilicity is therefore a major determinant of CNS penetration

123
Q

Which parts of hte brain does HIV particularly affect?

A

those that govern executive functions - esp. striatum and hippocampus

124
Q

Give examples of the neural dysfunction caused by HIV?

A

axonal disruption; pruning or aberrant sprouting of synaptodendritic connections

125
Q

Which strain of HIV is predominant in the CNS?

A

R5

126
Q

what is the relationship between HIV encephalitis; neuronal apoptosis and synaptodendritic degenerative changes and cognitive impairment?

A

HIV encephalitis and neuronal apoptosis do not correlate with the degree of cognitive impairment whereas synaptodendritic changes correlate closely to the presence and severity of cognitive impairment

127
Q

What is the reuslt of synaptodendritic changes?

A

loss of normal neuronal communication and axoplasmic flow

128
Q

How can synaptodendritic injury be demonstated in preserved tissue?

A

immunostaining with antibodies to SYP and MAP2 is reduced in correlation with neurocognitive impairment

129
Q

What is SYP?

A

presynaptic synaptophysin

130
Q

What is MAP2?

A

expressed in neuronal cell bodies and dendrites- post synaptic microtubule-associated protein 2

131
Q

How can synaptodendritic injury be assessed during life?

A

meausre synaptodendritic proteins released from damaged neurons into the extracellular space- CSF and blood e.g neurofilament protein; neuroimaging

132
Q

What have studies with SIV shown about early and mid stage HIV disease?

A

cognitive, behavioural and electrophysiological abnormalities- infiltration of CD8 cells and upregulation of immune repsonse genes e.g CCL5

133
Q

What is thought to be the mechanism in HIV encephalitis?

A

infected/activated microglia and macropahges release toxic factors e.g viral products; excitotoxins and cytokines that damage neurons

134
Q

What is the result of homozygosity for the TNF2 allele (TNFa gene rpomoter region) in cerebral malaria?

A

marked increased risk of death and severe neurological sequelae

135
Q

How is gp120 invovled in neuronal injury?

A

interacts with cellular receptors to alter glutamate pathway siganlling –increases caspases and induce cytokine production that can injure neurons and affect the activation state of microglia and astrocytes

136
Q

What is the effect of gp41 on neuronal function?

A

disrupts glutamate signalling; increases iNOS generation

137
Q

What are the 3 calsses of genes that encode proteins in HIV?

A

structural; regulatory and accessory

138
Q

What are the strucutral HIV genes?

A

Gag, pol and env

139
Q

What are the regulatory HIV genes?

A

Tat; Rev

140
Q

What are the accessory HIV genes?

A

Vpu; Vpr; Vif; Nef

141
Q

What cements that role that gp120 plays in neurocognitive degeneration?

A

dendritic alterations seen in the brains of cognitively ipaired HIV patients that come to autopsy can be replicatedi n cultures of human nervous tissue exposed to gp120

142
Q

What do astrocytes infected with HIV release?

A

not whole virions, generate Tat

143
Q

What is the effect of Tat?

A

mitochondrial dysfunction; dendritic loss; neurotoxicity; glial cell activation; cell death

144
Q

What does abnormal activation of cytokine and chemokine receptors in the context of HIV result in?

A

dendritic beading and loss of dendritic spines

145
Q

What is the effect of HCV infection on HIV neurocognitive disorders?

A

increases the likelihood

146
Q

What is the effect of HIV on neurregeneration?

A

viral proteins or virally induced immune changes can intersect with the pathways invovled in trophic factor gene expression; protein production or signalling cascades

147
Q

Give examples of neurotrophic factors?

A

brain derived neurotrophic factor; insulin-like growth factor

148
Q

What is the effect of significant reductions in neurotrophic factors?

A

increases neurons vulnerability to injury and limits ability to undergo repair

149
Q

What was the prevalence of HIV-associated dementia in pts with advanced HIV?

A

arund 20%

150
Q

What can be used to identify HIV associated cognitive impairment before it becomes symptomatic?

A

before a breakdown in accuracy or speed of performance, functioanl imaging studies have shown that the HIV-infected brain recruits or activates more widespread regions to accomplish the same level of performance

151
Q

What are the treatment options for HIV-associated cognitive impairment?

A

optimising cART, however as not all patients get benefit from this- trophic factors supplied by gene therapy or drugs may reverse or arrest damage

152
Q

Give an example of a drug which may be useful in neurocognition in HIV?

A

lithium- prevents induction of dendritic spine loss by gp120– resulted in improved performance in patients with HAND

153
Q

What is the effect of minocycline?

A

reduces activation of macrophages and microglia; reduces influx of cytotoxic cells into brain- reudcing encephalitis severity; suppressing viral load and dampening expression of CNS inflam markers in SIV macaques

154
Q

Why are there fluctuations of cognitive impairment?

A

reflect disturbances in the dynamic balance between synaptodendritic injury and repair

Module 2 (38 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions