Diagnosis>Organ System>

PATHOGENS

• HIV is found in brain in macrophages, microglia, and multinucleated giant cells. 
• Neurons injured indirectly when infected cells release noxious substances. 

CLINICAL

• HAD is subacute decline in cognitive function due to HIV. 
• Also known as HIV encephalopathy or AIDS-dementia complex.
• Milder cognitive impairment is called HIV-associated cognitive/motor complex. The term HIV-associated neurocognitive dysfunction (HAND) is now frequently used and refers to neurocognitive dysfunction of any degree of severity, since severe forms (HAD) are now relatively rare and mild forms much more frequent.
• Dementia is AIDS-defining illness in 3%. 
• Incidence declining, but ultimately affects ~25% of AIDS patients.
• Early Sx: apathy, impaired memory, difficulty with reading and calculation, decreased libido, depressive symptoms, waning interest in work & hobbies causing social withdrawal, occasionally mania or psychosis. 
• Later Sx: psychomotor slowing, poor memory, slowed movement. At end-stage patients can be mute, bedbound, and incontinent. 
• Considered a "subcortical dementia" due to absence of signs like aphasia and apraxia seen in "cortical dementias" like Alzheimer disease.
• Motor symptoms like gait dysfunction, poor balance, and tremor may be present.
• Often accompanied by HIV-related myelopathy or neuropathy.
• Severity rated from 0 to 4: 0-normal, 0.5-subclinical, 1-mild, 2-moderate, 3-severe, 4-end stage.
• When untreated, mean survival ~6 months.

DIAGNOSIS

• DDx includes PML, CNS toxoplasmosis, primary CNS lymphoma, CMV encephalitis, neurosyphilis, vitamin B12 or thiamine deficiency, delirium, depression, medication/drug effect, or other causes of dementia. 
• Differs from delirium in that there is no alteration of consciousness or attention.
• Exam may show frontal release signs, hyperreflexia, and increased tone.
• Consider OI if focal signs or fever present. 
• Workup includes brain MRI, neuropsychological testing, serologic testing as needed to rule out vitamin deficiency, syphilis.
• MRI usually shows atrophy and ill-defined white matter hyperintensities on T2-weighted scans.
• CSF analysis not essential, but may be needed to rule out OI.
• CSF findings nonspecific: may be acellular or show a lymphocytic pleocytosis; protein elevated in 65%.

TREATMENT

• ART is mainstay of treatment.
• Drugs with greater CNS penetration, including AZT, d4T, 3TC, ABC, NVP, IDV, and LPV/r, are more effective at decreasing CSF viral load, but unclear whether this results in greater clinical benefit. 
• IRIS can occasionally be seen following initiation of ART-usually due to PML.
• No other adjunctive treatments have proven benefit.

•  Treatment of co-morbid depression, mania, or psychosis may be necessary.
•  HAD patients are sensitive to psychoactive medications.

Drug Comments

FOLLOW UP

• Monitor response to ART.
•  If neurologic deterioration, perform brain MRI to rule out IRIS or OI.
• Neuropsychological testing can be repeated to evaluate longitudinal change. 

REFERENCES