HIV Dementia and the Basal Ganglia

Abstract

Infection with the human immunodeficiency virus frequently results in a dementing illness which manifests predominantly as a subcortical dementia. Parkinsonian features may be prominent in these patients and may on occasion be the presenting manifestation. These patients are exquisitely sensitive to dopaminergic blocking agents. Radiological studies, metabolic uptake studies and pathological examination of the brain suggest that the basal ganglia are the major target of this infection. Although further studies are necessary to determine appropriate treatment for this condition and to develop an understanding of the underlying pathophysiological mechanisms, available evidence suggests that the response to dopamine agonists may be variable and that viral strains and viral products may specifically target cells within the basal ganglia.

Acceleration of HIV dementia with methamphetamine and cocaine

“…Injection of Tat into the striatum, leads to loss of striatal N-acetyl aspartate peak by nuc lear magnetic resonance spectroscopy (Berger and Nath, 1997) and loss of niagrostiatal ® bers (Hayman e t a l, 1993). Consistent with these pathological observations, patients with HIV infection may develop a variety of movement disorders (reviewed in Berger and Nath, 1997). To date, however, the combination of motor abnormalities manifesting as focal dystonia, choreoathetosis and resting tremor abnormalities in a single patient have not been reported to the best of our knowledge.…”

Differential involvement of p38 and JNK MAP kinases in HIV-1 Tat and gp120-induced apoptosis and neurite degeneration in striatal neurons

“…The neurotoxic effects of HIV-1 proteins were explored in striatal neurons because the striatum is a major site of infection (Achim et al, 1994;Berger and Nath, 1997) and sustain highest viral loads in the CNS (Wiley et al, 1998;Avison et al, 2003). HIV dementia has been described as a subcortical dementia (Berger and Nath, 1997), aspects of which can include features of parkinsonism (Mirsattari et al, 1998) and dopamine dysfunction (Nath et al, 2000b).…”

“…HIV dementia has been described as a subcortical dementia (Berger and Nath, 1997), aspects of which can include features of parkinsonism (Mirsattari et al, 1998) and dopamine dysfunction (Nath et al, 2000b). Moreover, striatal neurons are unique in their response to neurotoxic insults (Miller et al, 1999;Mitchell et al, 1999;Calabresi et al, 2000;Whetsell, Jr., 2002;Goody et al, 2003).…”

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

“…The basal ganglia are especially vulnerable to HIV infection (Berger and Nath, 1997;Nath et al, 2001) and this may result from unique phenotypic characteristics of striatal neurons compared to other neuron types. For example, striatal neurons are quite susceptible to AMPA-receptor-mediated excitotoxic stimuli, but far less sensitive to NMDA-induced excitotoxicity Singh et al, 2003).…”