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Human immunodeficiency virus within the brains of children with AIDS
C A Wiley1, A L Belman, D W Dickson
1Department of Pathology, University of California San Diego, La Jolla 92093.
Insights
In children with symptomatic human immunodeficiency virus (HIV) infection, progressive neurologic disease is linked to detectable HIV in the brain. A plateau in neurologic development suggests limited HIV presence or clearance within the central nervous system.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Neuroimmunology
Background:
- Symptomatic human immunodeficiency virus (HIV) infection in children often leads to significant neurologic complications.
- Neurologic manifestations include microcephaly, developmental delays, encephalopathy, and motor deficits.
- Clinical courses of HIV-associated neurologic disease in children are variable.
Purpose of the Study:
- To investigate the relationship between HIV presence in the brain and the clinical course of neurologic disease in children with HIV.
- To differentiate the neuropathogenesis of progressive versus plateau neurologic decline in pediatric HIV.
Main Methods:
- Classification of pediatric HIV-associated neurologic disease into progressive and plateau categories based on developmental milestones.
- Utilized immunocytochemistry to detect and localize human immunodeficiency virus (HIV) antigen within brain tissue samples.
- Correlated the presence and location of HIV antigen with the observed clinical neurologic course.
Main Results:
- Children with a progressive neurologic course exhibited readily detectable HIV antigen in their brain tissue.
- Children with a plateau neurologic course showed minimal to no detectable HIV antigen in the brain.
- HIV antigen was detected in both deep white matter and gray matter in progressive cases.
Conclusions:
- Progressive neurologic deterioration in pediatric HIV is associated with the continued presence of HIV within the central nervous system.
- A plateau in neurologic development may result from initial HIV-induced damage with subsequent limited viral entry or clearance from the CNS.
- These findings highlight the importance of viral load and central nervous system penetration in determining the outcome of pediatric HIV-associated neurologic disease.
Abstract:
Infants and children with symptomatic human immunodeficiency virus (HIV) infection frequently develop neurologic disease with symptoms and signs of acquired microcephaly, developmental delays, encephalopathy, pyramidal tract signs, and less often, movement disorders and ataxia. However, clinical courses vary and, based upon progression of neurologic findings, we have classified them into 2 broad categories; progressive (loss of previously acquired language and cognitive skills) and plateau (failure to acquire additional developmental skills). We have used immunocytochemistry to localize HIV within the brains of neurologically involved children with AIDS. Interestingly, the brains of those children with a progressive neurologic course showed readily detectable HIV antigen, while those with a plateau course showed little or no detectable HIV. These findings suggest that in children with symptomatic HIV infection, the progressive neurologic deterioration is due to continued presence of HIV within deep white matter and gray matter, while the plateau neurologic course is due to HIV induced damage followed by either limited penetration of virus into the central nervous system, or clearance of virus below detectable limits.