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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Cerebral injury in perinatally HIV-infected children compared to matched healthy controls
Sophie Cohen1, Matthan W A Caan2, Henk-Jan Mutsaerts2
1From the Department of Pediatric Hematology, Immunology and Infectious Diseases (S.C., H.J.S., T.W.K., D.P.), Emma Children's Hospital AMC, Amsterdam; the Department of Radiology (M.W.A.C., H.-J.M., C.B.L.M.M.), the Department of Global Health and Amsterdam Institute of Global Health and Development (P.R.), and the Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA) (P.R.), Academic Medical Centre, University of Amsterdam; and HIV Monitoring Foundation (P.R.), Amsterdam, the Netherlands. s.cohen@amc.nl.
Insights
Children with HIV on antiretroviral therapy show reduced brain volumes and white matter integrity, impacting cognitive function. Further research is needed to understand these persistent neurologic deficits.
Area of Science:
- Neuroscience
- Pediatric Infectious Diseases
- Medical Imaging
Background:
- Perinatally HIV-infected children often experience persistent neurologic and cognitive deficits despite combination antiretroviral therapy (cART).
- Understanding the underlying brain changes is crucial for improving long-term outcomes.
Purpose of the Study:
- To evaluate the neurologic state of perinatally HIV-infected children on cART.
- To investigate the pathogenesis of persistent neurologic and cognitive deficits in this population.
Main Methods:
- 3.0 T MRI (3D-T1, FLAIR, DWI) was used to assess cerebral volumes, white matter hyperintensities (WMH), and white matter (WM) diffusion in HIV-infected children and controls.
- Linear regression models explored associations between neuroimaging findings and disease-related parameters, as well as cognitive performance.
Main Results:
- HIV-infected children (n=35) exhibited lower gray matter and WM volumes, increased WMH, and higher WM diffusivity compared to controls (n=37).
- Poorer clinical, immunologic, and virologic status in HIV-infected children correlated negatively with volumetric, WMH, and diffusivity markers.
Conclusions:
- Even with controlled HIV infection, children show reduced brain volumes, increased WMH, and impaired WM integrity versus controls.
- These structural brain differences are associated with poorer cognitive performance, highlighting the need for longitudinal studies on cerebral injury pathogenesis.
Objective:
The current study aims to evaluate the neurologic state of perinatally HIV-infected children on combination antiretroviral therapy and to attain a better insight into the pathogenesis of their persistent neurologic and cognitive deficits.
Methods:
We included perinatally HIV-infected children between 8 and 18 years and healthy controls matched for age, sex, ethnicity, and socioeconomic status. All participants underwent a 3.0 T MRI with 3D-T1-weighted, 3D-fluid-attenuated inversion recovery, and diffusion-weighted series for the evaluation of cerebral volumes, white matter hyperintensities (WMH), and white matter (WM) diffusion characteristics. Associations with disease-related parameters and cognitive performance were explored using linear regression models.
Results:
We included 35 cases (median age 13.8 years) and 37 controls (median age 12.1 years). A lower gray matter and WM volume, more WMH, and a higher WM diffusivity were observed in the cases. Within the HIV-infected children, a poorer clinical, immunologic, and virologic state were negatively associated with volumetric, WMH, and diffusivity markers.
Conclusions:
In children with HIV, even when long-term clinically and virologically controlled, we found lower brain volumes, a higher WMH load, and poorer WM integrity compared to matched controls. These differences occur in the context of a poor cognitive performance in the HIV-infected group, and larger, longitudinal studies are needed to increase our understanding of the pathogenesis of cerebral injury in perinatally HIV-infected children.
