Excitotoxicity and Dopaminergic Dysfunction in the Acquired Immunodeficiency Syndrome Dementia Complex

HIV Dementia and the Basal Ganglia

“…In HIV dementia, bradyphrenia, forgetfulness, apathy and poor sequential processing [22,23], cognitive distur bances which parallel those seen in Parkinson's disease, are observed. Impaired psychomotor speed is often the first manifestation of AIDS dementia [24], Other parkin sonian features include bradvkinesia [25], impaired man ual dexterity [25], postural instability [25], gait abnormal ities [25], rigidity, hypomimetic facies, hypophonia, poor ly articulated speech and seborrheic dermatitis.…”

“…observations] which is characteristic of lesions in the striatum [28], Indeed, on rare occasions. HIV-infected patients may present with an illness virtually identical to Parkinson's disease [23,[29][30][31] that is variably responsive to dopa minergic medication [23], On rare occasions, elderly per sons not previously known to be HIV-infected may be mislabelled as having parkinsonism and dementia when first presenting with HIV dementia [Berger, pers. observa tion], It is estimated that 5% of patients presenting to the neuro-AIDS clinic have parkinsonism and another 10% have parkinsonian features [Mirsattari and Nath, unpubl.…”

“…These patients may also have an associated psychosis which may be precipitated by the use of dopamine agonists. The use of dopamine agonist in pediatric patients with HIV infection and parkinsonian features has produced consistent improvement in motor function [36] but results in adults are variable [23].…”

Movement disorders with cerebral toxoplasmosis and AIDS

“…Positron emission tomography of the brain shows that the basal ganglia is one of the earliest structures to be affected (30). Movement disorders may be unmasked in asymptomatic HIV-I -infected patients with low-dose neuroleptics (31)(32)(33). Autopsy studies confirm that the basal ganglia is invariably infiltrated by HIV-I-infected microglia and multinucleated giant cells (34- The apparent lack of response of the movement disorder to antitoxoplasmosis therapy despite resolution of the abscesses could be due to persistent gliosis.…”

The Role of Host Genetics in the Susceptibility for HIV-associated Neurocognitive Disorders

“…Clinical studies have also shown HIV to have particular adverse impact upon dopaminergic (DA) neurons and/or systems, and there is some evidence to connect this impact to specific cognitive, motor, and behavioral deficits in affected persons. Indeed, since the early days of the epidemic, investigators have reported Parkinsonian signs and symptoms, including hypersensitivity to DA-blocking drugs, apathy, and motor slowing/ incoordination in AIDS (Arendt and von Giesen 2002;Edelstein and Knight 1987;Kieburtz et al 1991;Koutsilieri et al 2002;Navia et al 1986). Structural MRI studies of individuals with HAD have found reduced basal ganglia volume (Aylward et al 1993) and evidence for increased blood-brain barrier permeability in this region (Berger et al 2000), findings supported by a recent MRS study (Avison et al 2004a, b).…”