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Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children
Charlotte Blokhuis1, Henri J M M Mutsaerts, Sophie Cohen
1Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital/Academic Medical Center, University of Amsterdam Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Cognitive Neurology Research Unit, Sunnybrook Health Sciences Center, Toronto, Canada Department of Global Health, Academic Medical Center, University of Amsterdam, and Amsterdam Institute for Global Health and Development Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam, Academic Medical Center HIV Monitoring Foundation, Amsterdam, The Netherlands.
Insights
Pediatric HIV infection is linked to altered cerebral blood flow (CBF) in white matter and deep gray matter structures. Lower gray matter CBF in HIV-infected children correlated with white matter lesions, suggesting potential vascular contributions to brain injury.
Area of Science:
- Neurology
- Pediatrics
- Infectious Diseases
Background:
- Pediatric human immunodeficiency virus (HIV) infection can lead to neurological complications, including cognitive impairment.
- Cerebral blood flow (CBF) alterations may play a role in HIV-related brain injury.
- Understanding CBF changes in children with HIV is crucial for managing neurological sequelae.
Purpose of the Study:
- To evaluate cerebral blood flow (CBF) in children with perinatally acquired HIV.
- To investigate the association between CBF, HIV disease characteristics, and markers of cerebral injury.
- To determine the relationship between CBF and cognitive performance in pediatric HIV infection.
Main Methods:
- Cross-sectional observational study comparing 28 HIV-infected children (8-18 years) with 34 healthy controls.
- 3-Tesla magnetic resonance imaging with arterial spin labeling to measure CBF in gray matter (GM) and white matter (WM).
- Linear regression analysis to assess group differences and associations with clinical, imaging, and cognitive data.
Main Results:
- HIV-infected children exhibited higher CBF in WM, basal ganglia (caudate nucleus, putamen, nucleus accumbens), and thalamus compared to controls.
- Higher thalamus CBF was observed in children with CDC stage B or C disease.
- Lower GM CBF was significantly associated with a higher volume of WM lesions in HIV-infected children.
Conclusions:
- Perinatally HIV-infected children on combination antiretroviral therapy (cART) show elevated CBF in specific brain regions, but this was not linked to cognitive impairment or overall cerebral injury.
- The association between lower GM CBF and increased WM lesions suggests vascular disease may contribute to white matter injury in pediatric HIV.
- Longitudinal studies are needed to assess the long-term impact of HIV and cART on CBF, neuroinflammation, vascular function, and brain injury in children.
Abstract:
This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment.This cross-sectional observational study compared 28 perinatally HIV-infected children (8-18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance.HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = -0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found.CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.
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