Parallels Between AIDS Dementia and Parkinson's Disease
By Byron Young, M.D.
Clinical similarities between AIDS dementia
and Parkinson's disease are currently being studied at the Kentucky Neurosciences
Institute, in an effort to better understand the means by which the human
immunodeficiency virus (HIV) affects the brain. Before death, approximately
30 percent of all HIV- infected persons will develop an overt dementing
illness, evident on bedside neurological examination. This illness has
been referred to as AIDS dementia. An additional 30 percent of HIV-infected
persons will exhibit significant cognitive abnormalities that are evident
only with detailed neuropsychological testing. On physical examination,
these individuals often display abnormalities that are quite reminiscent
of Parkinson's disease. In very rare instances, an older person infected
with HIV may be misdiagnosed with Parkinson's disease until other AIDS-related
illnesses become apparent.
Among the most prominent findings in patients
with AIDS dementia resembling Parkinson's disease are slow thinking (bradyphrenia),
slow limb movements, altered gait, poor balance with frequent falls, stooped
posture, increased muscle tone (rigidity), diminished facial expression,
decreased eye blink rate, impaired smooth eye movements and abnormal speech.
Additionally, patients may exhibit seborrheic dermatitis-a greasy, scaling
rash often observed on the scalp, eyebrows and around the nose.
Clinical features which may prove helpful in
distinguishing these patients from those with Parkinson's disease include
the relative youthfulness of the HIV- affected population, the absence
of a typical "pill-rolling" tremor of the extremities at rest
(although a fine, fast tremor of the outstretched upper extremities is
frequently observed), the presence of a fairly dramatic dementing illness
from the onset of the illness, and the generally poor response to dopaminergic
agents, such as levodopa. These patients often have an exquisite sensitivity
to drugs that bind to the dopamine receptor or prevent its release. Small
doses of such drugs, which include haloperidol, thorazine, metoclopropramide
and reserpine, may leave a seemingly relatively unaffected individual bedridden
due to increased limb and trunk rigidity.
HIV and Brain Infection
HIV infects the brain very early after the
initial infection. It can be demonstrated in the brain within two weeks
of infection, although it rarely causes clinically apparent disorders at
this stage. The virus appears to have a predilection for deep nuclear structures,
such as the basal ganglia, including the substantia nigra. This latter
region of the brain is the region chiefly affected in Parkinson's disease.
The infection appears to result in decreased numbers of neurons in this
region and elsewhere. The content of dopamine (the neurotransmitter whose
deficiency is critical in the development of Parkinson's disease) in the
cerebrospinal fluid, as well as in the relevant, involved regions of the
brain, is significantly depressed in comparison to controls. Positron emission
tomography studies of the metabolism of these areas of the brain in affected
individuals has revealed an initial hyperactivity of the basal ganglia
early, followed in the late stages of the disorder by hypometabolism.
Research into AIDS Dementia
UK investigators are studying the activity
of the basal ganglia in normal subjects and patients with AIDS dementia,
using functional magnetic resonance imaging. In these studies, MRI is employed
to measure blood flow of the basal ganglia, providing a measure of the
metabolic activity of this region. When neurons in the basal ganglia are
activated, as occurs with limb movement, the blood flow increases. Comparisons
are possible of the degree of alteration from baseline assessment of neuronal
activity in this region. These changes can be compared between normal individuals
and HIV-infected persons with dementia and associated movement abnormalities.
The effects of various therapeutic strategies that enhance dopaminergic
activity will be assessed in the HIV study population to determine whether
these agents have any potential in relieving the illness.
to the AIDS Dementia Index