Flashcards in HIV Deck (30):
HIV-associated neurocognitive disorders (HAND)
CNS diseases progresses in disability from asymptomatic neurocognitive impairment (ANI) -->HIV-associated mild neurocognitive disorder (MND) -->HIV-associated dementia (HAD)
HAND and HAD
frequent complication of infection with HIV and is defined as a slowly progressive demyelinating disease with neuronal loss of the CNS
Epidemiology - Incidence of CNS disease: Pre-HAART
60% of advanced HIV/AIDS patients have neurological symptoms and 80→90% has evidence of neuropathology at autopsy
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. ??
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.)
The ?? of HIV-D has significantly decreased but its ?? has increased, as HIV-positive patients live much longer than before the HAART era
incidence (less pts developing HIV)
prevalence (more pts alive)
The prevalence of ?? seems to have increased, with reported prevalence between 20 and 50% of HIV-positive patients.
minor cognitive deficits
*unresolved, could be due to heterogeneity
Direct infection of ?? occur early in HIV infection, even during primary viremia
CNS and PNS systems
UNKNOWN: How infection occurs i.e., crosses BBB (free virus and/or in HIV-infected macrophages)
HAD pathology is due to HIV infection/replication in ??
does NOT infect ??
monocyte, macrophages, microglia in CNS
neurons or oligodendrocytes
Astrocytes and capillary endothelial cells may support ??
Most HIV in the CNS are ??
and utilize ?? as co-receptor
macrophage tropic (M-Tropic)
Neuronal damage may be due to ??
gp120 or Tat proteins
Numerous mechanisms for HAD:
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
HAD is not due to:
autoimmune disease (cross-reactive antibodies to HIV attack CNS)
opportunistic infection (i.e., cerebral toxoplasmosis, cryptococcal meningoencephalitis, progressive multifocal leukoencephalopathy).
*However, these diseases do occur in AIDS patients.
HAD is characterized by either few neuropathological changes? or:
Multinucleated giant cells (infected macrophages)
Astrocytosis - wide-spread, reactive astrocytosis.
*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).
acute and chronic peripheral neuropathies, (one form resembles Guillain-Barre’ syndrome)
HIV-1-associated cognitive/motor complex
vacuolar myelopathy (spinal column) – lower extremity spasticity.
painful sensory neuropathy (of feet).
Asymptomatic neurocognitive impairment (ANI)
Patient has neurocognitive impairment demonstrated by cognitive testing but are asymptomatic in their daily life
HIV-associated mild neurocognitive disorder (MND)
Patient has impairments causing mild disturbance of activities of daily living (ALDs)
ANI -→ MND
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
HAD is a diffuse or focal encephalitis: common or rare?
Now rare due to ART/HAART:
HAD early cognitive changes:
loss of concentration and memory.
long pauses before answering questions.
HAD early motor changes
loss of balance.
HAD early behavioral changes
decreased emotional responses
HAD late changes
Progression is predominantly abrupt, 3 → 6 months untill death.
incontinence and generalized spasticity
*Note: Much less common is a prolonged dementia lasting years.
EBV-associated primary CNS lymphoma (PCNSL) Primary or metastatic brain tumor.
CMV polyradiculopathy, encephalitis, myelopathy, etc.
HIV and AIDS pt. have one or more of:
abnormal CSF Ig,
recoverable HIV in the CSF
Use ?? dementia severity scale or HAD Scale.
Imaging studies should show
Decreased attenuation of deep white matter = demyelination
Absence of focal abnormalities.
tx: HAART has significantly reduced (@ 75%) the incidence of ??
Primary CNS lymphoma
There is an increased incidence of ?? and is likely due to ?? (part of the anti-HIV drug regimen)
sensory neuropathy (e.g., painful sensory symptoms of the feet)