CNS Infections- HAD

Question 1

HIV-associated neurocognitive disorders (HAND) is the global term in which CNS diseases progresses in disability from

Answer 1

asymptomatic neurocognitive impairment (ANI) –> HIV-associated mild neurocognitive disorder (MND) –> HIV-associated dementia (HAD/HAND)

Question 2

HAD is a frequent complication of infection with HIV and is defined as

Answer 2

a slowly progressive demyelinating disease with neuronal loss of the CNS

Question 3

Risk factor for progression despite HAART (highly active antiretroviral therapy) is history of

Answer 3

IV drug abuse

Question 4

Good prognostic indicators of HAD progression are

Answer 4

Plasma and CSF viral load suppression

Question 5

Pathogenesis of HAD

Answer 5

Direct infection of CNS and PNS systems occur early in HIV infection, even during primary viremia. How infection occurs i.e., crosses BBB (free virus and/or in HIV-infected macrophages) is unknown

Question 6

HAD S/S are due to

Answer 6

HIV infection/replication in monocyte, macrophages, microglia in CNS

• *HIV does not infect neurons or oligodendrocytes**
• Astrocytes and capillary endothelial cells may support defective replication

Question 7

Most HIV in the CNS are macrophage tropic (M-Tropic), utilize _______ as a co-receptor

Answer 7

CCR5

Question 8

Neuronal damage may be due to _________

Answer 8

gp120 or Tat proteins

Question 9

Most likely mechanism of HAD is

Answer 9

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 10

HAD is NOT caused by

Answer 10

1. autoimmune disease (cross-reactive antibodies to HIV attack CNS
2. lymphoma
3. opportunistic infection (i.e., cerebral toxoplasmosis, cryptococcal meningoencephalitis, progressive multifocal leukoencephalopathy)

However, these diseases do occur in AIDS patients

Question 11

HAD is characterized by either few neuropathological changes or:

Answer 11

1. Multinucleated giant cells (infected macrophages)
2. Astrocytosis - wide-spread, reactive
3. Microglial nodules
4. 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).
5. Neuronal loss

Question 12

Possible neurological diseases associated with HIV infection of CNS include:

Answer 12

1. acute and chronic peripheral neuropathies, one form resembles Guillain-Barre’ syndrome.
2. aseptic meningitis
3. acute encephalitis
4. HAD
5. vacuolar myelopathy (spinal column) – lower extremity spasticity
6. painful sensory neuropathy (of feet)

Question 13

Asymptomatic neurocognitive impairment (ANI):

Answer 13

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

Question 14

HIV-associated mild neurocognitive disorder (MND)

Answer 14

Patient has impairments causing mild disturbance of ADLs

1. Patient has mild difficulties in concentration, attention, and memory may be present
2. Neurologic examination is unremarkable
3. Frequently, patient complains of reading difficulties due to poor concentration levels. They are easily distracted, lose their train of thought, and require repeated prompting.
4. Activities of daily living may take longer and become more laborious

Question 15

HAD can be either a diffuse or focal encephalitis, but is now rare due to

Answer 15

HAART

Question 16

Cognitive changes seen are

Answer 16

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

Question 17

Motor problems are

Answer 17

loss of balance and leg weakness

Question 18

Behavioral changes seen are

Answer 18

apathy, social withdrawal, decreased spontaneity, decreased emotional responses

Question 19

Late changes seen are

Answer 19

Progression is predominantly abrupt (3- 6 months until death) ,mutism, incontinence and generalized spasticity, death

-Much less common is a prolonged dementia lasting years

Question 20

HIV and AIDS pt. have one or more of the following in lab work:

Answer 20

1. pleocytosis,
   2. abnormal CSF Ig
   3. recoverable HIV in the CSF

Question 21

Imaging studies would show

Answer 21

1. Cortical atrophy
2. Enlarged ventricles
3. Decreased attenuation of deep white matter = demyelination of deep white matter
4. Absence of focal abnormalities

Question 22

Treatment for HAD

Answer 22

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

	a. HAD
	b. Cryptococcal meningitis
	c. CNS toxoplasmosis
	d. Primary CNS lymphoma

Question 23

There is an increased incidence of sensory neuropathy (e.g., painful sensory symptoms of the feet) and is likely due to

Answer 23

double dideoxynucleoside, anti-HIV drug regimen

Question 24

Problem with antiviral drugs

Answer 24

BBB has poor penetration of antiviral drugs, hence the CSF HIV population can differ from the serum population in terms of resistance

Question 25

HAART/ARV must consist of drugs capable of

Answer 25

penetrating the CNS