HIV

Question 1

HIV-associated neurocognitive disorders (HAND)

Answer 1

CNS diseases progresses in disability from asymptomatic neurocognitive impairment (ANI) –>HIV-associated mild neurocognitive disorder (MND) –>HIV-associated dementia (HAD)

Question 2

HAND and HAD

Answer 2

frequent complication of infection with HIV and is defined as a slowly progressive demyelinating disease with neuronal loss of the CNS

Question 3

Epidemiology - Incidence of CNS disease: Pre-HAART

Answer 3

60% of advanced HIV/AIDS patients have neurological symptoms and 80→90% has evidence of neuropathology at autopsy

Question 4

Even with HAART, ?? occurs in 30% of people with AIDS and frank dementia occurs in 15% with an annual incidence after onset of AIDS of about 5%.

Risk factor for progression despite HAART ??

good prognostic indicators. ??

Answer 4

cognitive impairment

IVDA

Plasma and CSF viral load suppression

(persons >50-y-o-age with HIV infection (new or pre-existing) are “older.” 50% of all AIDS patients will fall within this group by 2015.)

Question 5

The ?? of HIV-D has significantly decreased but its ?? has increased, as HIV-positive patients live much longer than before the HAART era

Answer 5

incidence (less pts developing HIV)

prevalence (more pts alive)

Question 6

The prevalence of ?? seems to have increased, with reported prevalence between 20 and 50% of HIV-positive patients.

Answer 6

minor cognitive deficits

*unresolved, could be due to heterogeneity

Question 7

Direct infection of ?? occur early in HIV infection, even during primary viremia

Answer 7

CNS and PNS systems

UNKNOWN: How infection occurs i.e., crosses BBB (free virus and/or in HIV-infected macrophages)

Question 8

HAD pathology is due to HIV infection/replication in ??

does NOT infect ??

Answer 8

monocyte, macrophages, microglia in CNS

neurons or oligodendrocytes

Question 9

Astrocytes and capillary endothelial cells may support ??

Answer 9

defective replication

Question 10

Most HIV in the CNS are ??

and utilize ?? as co-receptor

Answer 10

macrophage tropic (M-Tropic)

CCR5

Question 11

Neuronal damage may be due to ??

Answer 11

gp120 or Tat proteins

Question 12

Numerous mechanisms for HAD:

Answer 12

Break down of BBB via increased production of human matrix metalloproteases

Production of cytokines, chemokines, neurotoxic products by macrophages

gp120 interaction with chemokine CXCR4 on the surface of neural progenitor cells

Question 13

HAD is not due to:

Answer 13

AI: 
autoimmune disease (cross-reactive antibodies to HIV attack CNS)

lymphoma

OI:
opportunistic infection (i.e., cerebral toxoplasmosis, cryptococcal meningoencephalitis, progressive multifocal leukoencephalopathy).
					*However, these diseases do occur in AIDS patients.

Question 14

HAD is characterized by either few neuropathological changes? or:

Answer 14

Multinucleated giant cells (infected macrophages)

Astrocytosis - wide-spread, reactive astrocytosis.

Microglial nodules.

Diffuse or focal myelin pallor (AKA demyelination AKA “dirty white matter”) primarily within the basal ganglia and the white matter (i.e., central white matter, frontal cortices, basal ganglia, thalamus, brain stem).

Neuronal loss.

Question 15

HAD Manifestations:

Answer 15

acute and chronic peripheral neuropathies, (one form resembles Guillain-Barre’ syndrome)

aseptic meningitis.
acute encephalitis.

HIV-1-associated cognitive/motor complex

vacuolar myelopathy (spinal column) – lower extremity spasticity.

painful sensory neuropathy (of feet).

Question 16

Asymptomatic neurocognitive impairment (ANI)

Answer 16

Patient has neurocognitive impairment demonstrated by cognitive testing but are asymptomatic in their daily life

Question 17

HIV-associated mild neurocognitive disorder (MND)

Answer 17

Patient has impairments causing mild disturbance of activities of daily living (ALDs)

Question 18

ANI -→ MND

Answer 18

Now common in era of ART/HAART:

mild difficulties in concentration, attention, and memory may be present.

reading difficulties due to poor concentration levels. easily distracted, lose their train of thought, and require repeated prompting.

ADLs may take longer and become more difficult

Question 19

HAD is a diffuse or focal encephalitis: common or rare?

Answer 19

Now rare due to ART/HAART:

Question 20

HAD early cognitive changes:

Answer 20

forgetfulness.
loss of concentration and memory.
confusion.
long pauses before answering questions.

Question 21

HAD early motor changes

Answer 21

loss of balance.

leg weakness

Question 22

HAD early behavioral changes

Answer 22

apathy
social withdrawal,
decreased spontaneity
decreased emotional responses

Question 23

HAD late changes

Answer 23

Progression is predominantly abrupt, 3 → 6 months untill death.
Mutism
incontinence and generalized spasticity
death.

*Note: Much less common is a prolonged dementia lasting years.

Question 24

ddx HAD

Answer 24

EBV-associated primary CNS lymphoma (PCNSL) Primary or metastatic brain tumor.
Toxoplasmosis encephalitis
PML
Cryptococcal meningoencephalitis
CMV polyradiculopathy, encephalitis, myelopathy, etc.

Question 25

HIV and AIDS pt. have one or more of:

Answer 25

pleocytosis,
abnormal CSF Ig,
recoverable HIV in the CSF

Question 26

Use ?? dementia severity scale or HAD Scale.

Answer 26

Memorial Sloan-Kettering

Question 27

Imaging studies should show

Answer 27

cortical atrophy
enlarged ventricles
Decreased attenuation of deep white matter = demyelination
Absence of focal abnormalities.

Question 28

tx: HAART has significantly reduced (@ 75%) the incidence of ??

Answer 28

HAD
Cryptococcal meningitis
CNS toxoplasmosis
Primary CNS lymphoma

Question 29

There is an increased incidence of ?? and is likely due to ?? (part of the anti-HIV drug regimen)

Answer 29

sensory neuropathy (e.g., painful sensory symptoms of the feet)

double dideoxynucleoside

Question 30

Problem: ??? has poor penetration of antiviral drugs, hence the CSF HIV population can differ from the serum population in terms of ??

HAART/ARV must consist of drugs capable of penetrating the ??

Answer 30

BBB

resistance

CNS