HIV-associated Neurologic Dysfunction/Dementia

Question 1

Pathophysiology of HIV-associated dementia

Answer 1

• Multifactorial
• HIV-infected monocytes enter the brain and infect microglia, astrocytes, neurons, and oligodendrocytes. Then, the virus may replicate within these cells.
• Toxins and HIV proteins produced by or in response to the presence of HIV may have neurotoxic properties
• The incidence of opportunistic infections and tumors secondary to HIV also plays a role

Question 2

Neuropsychological testing

Answer 2

A battery of tests to evaluate cognitive impairment more extensively than the MMSE

Question 3

Effect of HAART on HAD

Answer 3

HAART reduces the incidence and severity of HAD, as one might expect

But, it does not bring these to zero.

Question 4

Since HAART was only introduced in 1992, and HAART reduces the incidence of HAD . . .

Answer 4

. . . older patients / patients who have had HIV for longer are more likely to have HAD

Question 5

Presentation/Natural history of HAD

Answer 5

• Early symptoms:
  
  • Difficulty concentrating and with mentation
  • Forgetfulness
• As the disease progresses:
  
  • Personality change (apathy, social withdrawal, quietness)
  • Psychomotor dysfunction (imbalance, mild ataxia)
    
    • Most common motor symptoms are tripping/falling and poor handwriting
• Late stage disease:
  
  • Disabling ataxia with inability to walk
  • Myoclonic jerks, postural tremor
  • Bowel and bladder dysfunction

Question 6

One thing that is NEVER seen in HAD

Answer 6

Focal neurologic deficits

It is a strictly subcortical dementia

Question 7

Physical exam findings in early vs late HAD

Answer 7

• Early:
  
  • Mostly normal neurologic exam without glaring deficits
  • Difficulties in concentration, fine motor manipulation, motor speed
  • Mild word finding difficulties and impaired retrieval
  • Subtle impairment of rapid limb and eye movements
• Late:
  
  • Hyperreflexia, spasticity, and frontal release signs (UMN signs)
  • Apraxia
  • Akinetic mutism (severely decreased motor-verbal output)

Question 8

Imaging findings typical of HAD

Answer 8

Diffuse cerebral atrophy

Sometimes white matter changes and abnormalities are present in the thalamus and basal ganglia

Question 9

Typical ddx for HAND

Answer 9

• Other forms of dementia (especially FTD and subcortical dementias)
• CNS lymphoma
• PML
• CNS infection
• Toxic-metabolic (B12, thyroid, alcoholism, medication effect, illicit substance use)

Question 10

Management of HAND is essentially limited to. . .

Answer 10

. . . viral suppression by HAART

HAART can not only protect against, but can also lead to remission of HAND

Antiretrovirals with good CNS penetration are preferred: lamivudine, indinavir, zidovudine

“LIZ, HAND me the HAART”

Question 11

Risk factors for HAD

Answer 11

• Low CD4 count
• High viral RNA
• Low BMI
• Anemia
• Low level of education