Child's Nerv Syst (1990) 6:406-408 m6NS 9 Springer-Verlag 1990 How frequent and how early does the neurological involvement in HIV-positive children occur? Preliminary results of a prospective study A.M. Laverda 1, p. Cogo 1, A. Condini 1, C. Cattelan 1, C. Giaquinto 1, S. Cozzani 1, E. Ruga 1, E Viero 1, A. De Rossi 2, A. Del Mistro 2, L. Chieco Bianchi 2, and E Zacchello 1 1Department of Pediatrics and 2Institute of Oncology, University of Padua, Via Giustiniani, 3, 1-35128 Padua, Italy Received January 12, 1990 Abstract. To study the natural history of the neurological involvement in pediatric human immunodeficiency virus (HIV) infection, 77 children born to seropositive mothers have been followed up since birth. The median follow-up time has been 17.5 months. Fourteen children were classi- fied as infected, 34 as not infected, and 21 as indeter- minable. Only two children with full-blown acute im- mune deficiency syndrome had severe neurological man- ifestations. "Soft" neurological signs were found in six infected, and ten non-infected children ()~2, p < 0.05). The mean development quotient and IQ scores in the infected and the non-infected children were 82.22, and 93.15, re- spectively (Mann-Whitney test, P>0.05). These data suggest that neurological and developmental abnormali- ties do not occur early in the course of vertical HIV infec- tion and that they are associated with severe immunode- ficiency. Key words: Neurological manifestation - HIV infection - Children The reported incidence of neurological manifestations in children with human immunodeficiency virus (HIV) in- fection is high (50%-90%) [2, 4, 6]. A progressive en- cephalopathy, probably related to the primary HIV in- fection, has been noted as early as 2 months and as late as 5 years after birth in children with perinatally acquired infections [6]. However, some authors reported that the majority of these children become symptomatic before the age of 2 years [6]. Most of these results involve chil- dren who come under medical observation because they are symptomatic. For this reason, the true incidence of neurological manifestation cannot be estimated because of the bias introduced by the preselection of the popula- tion studied. In order to determine the natural history of neurological involvement in HIV infected children, in 1985 we initiated a prospective study of children born to Offprint requests to: A.M. Laverda HIV-seropositive mothers. Some of these children have also been admitted into the European collaborative study [5]. Patients and methods HIV-seropositive women were identified during the prenatal period, or at the time of delivery. Their children were clinically and neuro- logically evaluated at birth and at tri-monthly intervals. All children under 30 months of age were rated by the Brunet-Lezine scale, while the Termann-Merril test was used to rate the older patients. Only the infected children underwent a computed tomography (CT) scan, an EEG, and a cerebral spinal fluid study every year, or more frequently if clinically indicated. A blood sample was taken at each visit, and used to determine the presence of the HIV antibody by ELISA and Western blot. Virus cultures, antigen tests, in vitro antibody production [1] and the polymerase chain reaction (PCR) procedure were performed every 6 months. Other investigations included absolute lymphocyte count, immunoglobulin subset, and T4/T8 ratio. Infection was defined by the persistence of antibodies beyond the age of 15 months, clinicaly acute immune deficiency syndrome (AIDS) or AIDS related complex (ARC) and/or direct evidence of the virus. Children who lost antibodies and had negative cultures, negative PCR or antigen tests were presumed to be not-infected. Since maternal antibodies can persist up to 18 months after birth, the infection status of the antibody-positive/virus negative children under 15 months of age was considered indeterminable. Symptomatic children were classified according to the Centers for Disease Control classification system for HIV infection in child- hood [3]. Statistical analysis was performed by means of the )~a,and Mann-Whitney tests. Results By the end of November 1988, 77 children had been en- rolled in this study. All of the mothers except one were Caucasian; 85% of the mothers, and 15% of their sexual partners, had a history of intravenous drug abuse prior to or during the pregnancy. The median follow-up time of the children was 24 months (ranging 1-38 months); 14 children were infected, 34 were not infected, and 29 had indeterminate status.