Clinical comparison of adult and pediatric NeuroAIDS

Human Immunodeficiency Virus type-1 (HIV-1)-associated neurologic disease occurs as the initial presenting clinical manifestation of acquired immunodeficiency syndrome (AIDS) in 3–7% of infected patients, but in up to 18% of children and adolescents (Janssen, 1992; Janssen et al., 1992; Scott et al., 1989; Mintz et al., 1989a; Epstein et al., 1986). The overall prevalence of dementia in adult AIDS patients is 7.3–11.3% (Janssen, 1992), but up to 30–60% of children with AIDS manifest an analogous progressive encephalopathy (Epstein et al., 1986; Belman et al., 1988; Mintz, 1992; The European Collaborative Study, 1990). As a result of both direct and indirect effects of HIV-1 infection of the central nervous system (CNS), a distinct clinical and pathologic picture has emerged of insidious and severe neurologic deterioration, termed “AIDS Dementia Complex” (ADC) in adults, and “HIV-1-associated Progressive Encephalopathy” (PE) in children (Working Group, 1991) (see Table 1). In the severe manifestations of this pariah, there is little dispute as to the necessity of CNS HIV-1 infection for precipitating the cascade of adverse neurologic symptoms, although the pathogenic mechanisms of neurologic dysfunction and destruction— whether a result of direct cellular infection of HIV, secondarily produced and upregulated cytotoxic cytokines, or co-infection with opportunistic pathogens— remains an area of active research (Epstein and Gendelman, 1993; Fiala et al., 1993; Wiley and Nelson, 1988; Saito et al., 1994; Koenig et al., 1986; Sharer, 1992). Furthermore, the existence of systemic immune deficiency renders the CNS susceptible to opportunistic infection (OI), particularly in adult patients, adding further to morbidity and mortality (Clifford and Campbell, 1992). With the introduction of antiretroviral nucleoside analogues, there have been reports of a decreasing incidence of ADC (Portegies et al., 1989; Day et al., 1992), and amelioration—at least temporarily of PE in children (Pizzo et al., 1988; Mintz and Epstein, 1992; Brouwers et al., 1990; Mintz et al., 1990). This appends further evidence to the central precipitating role of CNS HIV-1 infection.

There is much debate whether there exists any subclinical neurologic dysfunction during the asymptomatic stages of systemic infection (Janssen et al., 1989; Karlsen et al., 1993; McArthur et al., 1989a; Selnes et al., 1990). Perplexities are injected from the many environmental confounders impacting on psychometric testing (McArthur et al., 1989a; Satz et al., 1993; Wilkins et al., 1990).

Although many analogies exist between ADC and PE, there are interesting differences and distinct contrasts between the two populations. Careful study and comparisons of these divergences are important for understanding pathogenic mechanisms, and in devising CNS specific, treatment approaches.