Neurological and developmental effects of HIV and AIDS in children and adolescents

Abstract

HIV-related encephalopathy is an important problem in vertically infected children with HIV. Infected infants may manifest early, catastrophic encephalopathy, with loss of brain growth, motor abnormalities, and cognitive dysfunction. Even without evidence of AIDS, infected infants score lower than serorevertors on developmental measures, particularly language acquisition. Children with perinatal or later transfusion-related infection generally are roughly comparable developmentally to their peers until late in their course. Symptoms similar to adult AIDS dementia complex are occasionally seen in adolescents with advanced AIDS, including dementia, bradykinesia, and spasticity. Opportunistic CNS infections such as toxoplasmosis and progressive multifocal leukoencephalopathy are less common in children and adolescents than in adults. Increasing evidence suggests that aggressive antiretroviral treatment may halt or even reverse encephalopathy. Neuroimaging changes may precede or follow clinical manifestations, and include early lenticulostriate vessel echogenicity on cranial ultrasound, calcifying microangiopathy on CT scan, and/or white matter lesions and central atrophy on MRI. Differential diagnosis of neurological dysfunction in an HIV-infected infant includes the effects of maternal substance abuse, other CNS congenital infections, and other causes of early static encephalopathy. Initial entry of HIV into the nervous system occurs very early in infection. The risk of clinical HIV encephalopathy increases with very early age of infection and with high viral loads. Virus is found in microglia and brain derived macrophages, not neurons. The neuronal effect of HIV is probably indirect, with various cytokines implicated. Apoptosis is the presumed mechanism of damage to neurons by HIV.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa

“…DTI has been used successfully in pediatric populations to document injury to white matter tracts after prematurity (Feldman et al 2010), in multiple sclerosis (Vishwas et al 2013), and as a consequence of moderate-tosevere traumatic brain injury (Wu et al 2009). Reported neuroimaging findings in pediatric HIV include calcifying microangiopathy, atrophy, and ventricular dilatation on CT scan and white matter lesions and atrophy on MRI (Mitchell 2001). There are a number of reports describing the neurodevelopmental outcomes of vertically infected younger HIV-positive children; however, the neurologic features in older children are not as well described (Angelini et al 2000).…”

Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

“…A sensitive predictive marker of encephalopathy is critical [4,5] because early additional neuroprotective treatment may preserve brain integrity, slow deterioration or partially improve symptoms [3,5,6]. There is evidence that suggests that intensive antiretroviral therapy may halt or even reverse encephalopathy, leading to improved neurocognitive outcome and survival in children with HIV dementia [4,7,8].…”

“…Human immunodeficiency virus encephalopathy is an acquired immunodeficiency syndrome (AIDS) defining event [1] occurring in vertically infected infants and children with loss of brain growth, motor abnormalities and cognitive dysfunction [2,3]. A sensitive predictive marker of encephalopathy is critical [4,5] because early additional neuroprotective treatment may preserve brain integrity, slow deterioration or partially improve symptoms [3,5,6].…”

Human Immunodeficiency Virus Infection in Children

“…Encephalopathy was recognized early in the epidemic as a significant aspect of HIV disease that is particularly common in children (Mitchell, 2001), especially infants (Tardieu et al, 2000). Although opportunistic infections of the brain due to immunodeficiency are less common in children than in adults, the virus itself can enter the central nervous system.…”