Objectives:To longitudinally assess the receptive and expressive language functioning of children with symptomatic HIV disease and to explore the relationship between immune status, computed tomography (CT) brain scan abnormalities, and language dysfunction over time. Methods:Children with symptomatic HIV infection were administered an age-appropriate standardized comprehensive language test and general cognitive measure prior to starting antiretroviral therapy (n = 44) and again after 6 months (n = 29) and 24 months (n = 17). CD4 percentage and CT brain scans were also obtained at each evaluation. Results:Expressive language was significantly more impaired than receptive language at the baseline, 6- and 24-month evaluations. No significant changes over time were found in receptive or expressive language from baseline to after 6 months of antiretroviral therapy, but despite treatment, language scores declined significantly between 6 and 24 months. Overall cognitive function, however, remained stable from baseline to 24 months. Age-adjusted CD4 percentage increased significantly over the initial 6 months, then remained stable. Overall CT brain scan severity ratings did not change significantly over 24 months. Conclusion:Expressive language was consistently more impaired than receptive language over 24 months, further supporting an earlier finding that expressive language was differentially affected by HIV in children with symptomatic disease. Both receptive and expressive language declined significantly after 24 months despite antiretroviral therapy, although overall cognitive function remained stable. Thus, functioning in some domains may be more vulnerable to the effects of HIV and global measures of cognitive ability may mask such differential changes in specific brain functions.

Central nervous system (CNS) abnormalities are significant and frequent complications of human immunodeficiency virus (HIV-1) infection in infants and children. Although the predominant cause of neurological and neuropsychological abnormalities appears to be related to HIV infection of the CNS, other factors including malnutrition may also play a role. We retrospectively evaluated the association of change in body weight with changes in neurocognitive function, ventricular brain ratio, and cerebrospinal quinolinic acid levels in a small cohort of children (n=15; mean age 6.3 years) with symptomatic HIV-1 disease before and after 6 months of antiretroviral therapy with continuous intravenous infusion of zidovudine (ZVD). Significant increases in weight and neurocognitive function as well as decreases in ventricular brain ratio and cerebrospinal quinolinic acid levels were noted after therapy. Only the relation between increase in weight and decrease in ventricular brain ratio was statistically significant (P<.01); contrary to expectations, an increase in weight seemed to correlate with a decrease in neurocognitive function (NS). Another group of children treated at the same time with oral intermittent ZVD, but otherwise receiving the same care did not show the same magnitude of improvement in neurocognitive function. These results seem to suggest that general supportive and medical care as well as nutritional factors may only play a limited role in the neurocognitive improvements after antiretroviral therapy with continuous infusion ZVD. Our sample size was, however, small and the nutritional measure rather global; thus these findings have to be considered as very preliminary.

Rated observations of videotapes were made of 16 variables representing 5 behavioral domains (task orientation, positive social-emotional, motor skills, expressive speech, and activity) on a sample of 83 HIV-infected children. Comparisons were made on the rated behaviors between children classified as either encephalopathic or nonencephalopathic. Analyses were conducted separately for infants (M age = 1.80 years) and older children (M age = 5.15 years). The nonencephalopathic infants exhibited higher activity levels and were superior in motor and verbal skills and showed more social and emotional responsiveness than did the encephalopathic group. The older nonencephalopathic children functioned in a more adaptive and appropriate manner than did the encephalopathic children in all domains of behavior. Independently made Q-sort ratings of behaviors during developmental testing were highly correlated with conceptually congruent ratings of the videotaped behaviors.

OBJECTIVE:To study the relationships between stage of HIV disease, reflected by CD4+ lymphocyte percentages and p24 antigen levels, and HIV-associated central nervous system (CNS) abnormalities, measured by computed tomography (CT) brain-scan ratings and neurobehavioral tests. DESIGN:Consecutive case series. SETTING:Government medical research center. PATIENTS:Eighty-six previously untreated children with symptomatic HIV-1 disease. RESULTS:CD4% measures correlated significantly with overall CT brain-scan severity ratings (r = -0.45; P < 0.001) as well as with its component parts (cortical atrophy, white matter abnormalities, and intracerebral calcifications); they were of comparable magnitude for vertically and transfusion-infected children. CD4% measures were also associated with the general level of cognitive function (r = 0.32; P < 0.005). Furthermore, patients with detectable serum p24 antigen levels (n = 39) had CT brain scans that were more abnormal than patients with undetectable p24 levels (n = 20; CT abnormality ratings of 21.3 versus 35.9; P < 0.02); similar differences were found for the cortical atrophy and calcification ratings. p24 levels also correlated with the overall CT brain-scan severity rating (r = 0.34; P < 0.01). CONCLUSIONS:Degree of CT brain-scan abnormality and level of cognitive dysfunction were significantly associated with the stage of HIV-1 disease, as reflected by either CD4 leukocyte measures or elevations of p24 antigen. The relation between the CT brain-scan lesions and markers of HIV disease (both CD4 and p24) suggest that these CNS abnormalities are most likely associated with HIV-1 infection, and further support the hypothesis that the interaction between systemic disease progression and CNS manifestations is continuous rather than discrete.

As more infants are infected with human immunodeficiency virus (HIV) and new medical treatments improve quality of life and lengthen survival time, the number of HIV-infected children attending school will continue to grow. Children with symptomatic HIV infection may develop a range of neuropsychological abnormalities associated with the direct effects of HIV on the central nervous system (CNS). Furthermore, behavioral and social-emotional difficulties may result from the indirect effects of HIV, which include the psychological reactions to living with the disease. Such cognitive and behavioral impairments may result in learning problems and academic difficulties. Thus, infants, children, and adolescents infected with HIV may require a range of developmental, rehabilitative, and special services. The purpose of this paper is to provide information about pediatric HIV infection to professionals working in educational settings. The primary focus is on the neurological, cognitive, motor, and behavioral impairments associated with the direct effects of HIV on the CNS, which may impede learning and school performance. The role of school psychology in pediatric HIV disease also is discussed.

Objectives. To investigate the effect of HIV disease on the receptive and expressive language of children and the relationship between CT scan brain abnormalities and language functioning.Methods. Thirty-six children (mean age, 5.5 years; range, 1 through 10 years; 75% vertical transmission; 58% classified as encephalopathic) with symptomatic HIV infection and 20 uninfected siblings (mean age, 7.8 years; range, 3 through 15 years) were administered an age-appropriate comprehensive language test assessing both receptive and expressive language (Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals-Revised). Each HIV-infected child had a CT scan of the brain as part of the baseline evaluation, which was rated independently and blindly by two neurologists, for presence and severity of brain abnormalities using a semiquantitative rating system.Results. Expressive language was significantly more impaired than receptive language in the overall sample of HIV-infected children. The encephalopathic children scored significantly lower than the non-encephalopathic children, however, the degree of discrepancy between mean receptive and expressive language scores was not significantly different between these two groups. The uninfected sibling control group did not have a significant discrepancy between receptive and expressive language, and they scored significantly higher than the infected patient group. Greater severity of CT scan abnormalities was significantly correlated with poorer receptive and expressive language functioning in the overall HIV-infected sample and a higher discrepancy between receptive and expressive language in the encephalopathic group.Conclusion. Pediatric HIV disease is associated with differential receptive and expressive language functioning in which expressive language is significantly more impaired than receptive language. The sibling data and CT scan correlations suggest that the observed language impairments are associated with the direct effects of HIV-related central nervous system disease.

Assessed longitudinally the effects of HIV infection and zidovudine on the adaptive behavior of 25 children with symptomatic disease (M age = 5.3 years; range = 1-12; 52% classified as encephalopathic) by parent report using the Vineland Adaptive Behavior Scales. Patients also were evaluated with an age-appropriate intelligence test and Q-sort Behavioral Rating Scale. Before treatment, encephalopathic children exhibited greater impairments in adaptive behavior than those without encephalopathy. After 6 months of zidovudine, all behavioral domains (communication, daily living, socialization) except for motor skills showed overall significant improvement. Children with or without encephalopathy showed a similar degree of change. Improvements in adaptive behavior correlated with increases in cognitive ability and decreases in severity of aberrant social-emotional behavior.

Developed a Q-sort procedure to assess social, emotional, and motivational behavior associated with central nervous system disease among 180 HIV-infected pediatric patients. These ratings were factor analyzed and scales were derived based on the factor structure. Younger (M age = 1.03 years) patients with HIV-associated encephalopathy were rated as more apathetic and nonsocial in their behavior than nonencephalopathic younger patients. Older (M age = 7.8 years) encephalopathic patients had significantly higher scores on scales measuring depression, autism, and irritability compared to nonencephalopathic patients from this age group. A subgroup (26 patients) showed a significant decrease in these elevated scores after a 6-month course of AZT.

Quinolinic acid (QUIN) is a neurotoxin implicated in the neurologic deficits associated with human immunodeficiency virus type 1 (HIV-1) infection. Forty children with symptomatic HIV-1 disease had elevated (P < .001) cerebrospinal fluid (CSF) QUIN levels (55.8 +/- 8.9 nM) compared with controls (14.9 +/- 3.0 nM). Age-adjusted CSF QUIN concentrations in HIV-1-infected children were predicted by the general index of mental abilities (GIMA, from an age-appropriate intelligence test; r = -0.45, P < .01). Zidovudine therapy reduced CSF QUIN from 64.1 +/- 16.3 to 19.7 +/- 5.2 nM (P < .01; N = 16) and increased GIMA from 76.8 +/- 5.2 to 87.2 +/- 6.3 (P < .001). Encephalopathic HIV-1-infected patients had higher CSF QUIN levels than patients without encephalopathy (79.6 +/- 16.1 vs. 32.7 +/- 6.7 nM, P < .01). CSF QUIN concentrations were also higher (P < .001) in patients who died < or = 3 years after their baseline assessment, compared with those who were still alive. These results warrant further investigation of CSF QUIN in HIV-infected children as a mediator of neurologic dysfunction and a supplemental marker of neurologic disease, particularly when combined with measures of neurocognitive functioning.