Howard A. Moss

The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia.

Receptive and expressive language function of children with symptomatic HIV infection and relationship with disease parameters: a longitudinal 24-month follow-up study.

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.

Relation between stage of disease and neurobehavioral measures in children with symptomatic HIV disease.

ObjectiveTo 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. DesignConsecutive case series. SettingGovernment medical research center. PatientsEighty-six previously untreated children with symptomatic HIV-1 disease. ResultsCD4% 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). ConclusionsDegree 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.

Psychologic adjustment of human immunodeficiency virus-infected school-age children

We investigated the psychosocial adjustment of school-aged, human immunodeficiency virus-positive children and factors associated with level of adjustment. Participants were primarily transfusion-infected children living in middle-class families. We administered measures of depression, anxiety, and self-concept to children, and measures of behavior problems, social functioning, personality characteristics, and life events to parents. An index of disease stage was also collected. Children reported experiencing low levels of depressive and anxious affect and generally felt positively about themselves. By contrast, parents saw their children as more anxious and less socially active than respective standardization samples. A greater than expected proportion of these children, as reported by their parents, scored in the maladaptive range on measures of social functioning, anxiety, and conduct problems. Experience of adversive life events and progression of the disease were associated with more behavioral and social problems. Findings are discussed in terms of their generalizability and implications for future research.

Communication in Mother-Infant Interaction

Observations of mother-infant dyads yield a host of impressions, both to the eyes of the naive, casual observer and to the scrutiny of the trained student of interpersonal interactions. Familiar reactions of a mother relating to her infant range from viewing the mother as warm and sensitive, the infant as wide-eyed and alert, and the dyad as exhibiting rapport to the other extreme, at which the mother is regarded as rejecting and obtuse, the infant as unresponsive and difficult, and the dyad as uncommunicative and disconnected. Observations of this sort are often stated with a deep sense of conviction and immutable certainty. The generally held agreement as to what the state of affairs is between a mother and infant, based on certain prototypical qualities of the interaction, suggests some level of consensual validation as to what constitute positive or negative attributes in a mother-infant interaction. Certainly, artists for centuries have found mothers engaging in positive types of contact with their infants to be a favorite subject matter, and there seems to be good reason to believe that viewers of these works of art concur with what the respective artists were attempting to depict.

Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.