Department of Paediatrics and Child Health

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    Neuro-imaging in paediatric HIV, a MRI/DTI study
    (Stellenbosch : Stellenbosch University, 2020-03) Ackermann, Christelle; Cotton, Mark F.; Andronikou, Savvas; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health.
    ENGLISH ABSTRACT: The HIV epidemic has been largely controlled by antiretroviral treatment (ART) which improves neurodevelopmental outcomes. Nevertheless, many HIV-infected (HIV+) children on long-term treatment may have HIV-related brain injury, ongoing cognitive impairment and treatment-related neurological complications. Magnetic resonance imaging (MRI) and in particular diffusion tensor imaging (DTI) are sensitive tools in assessing the integrity of white matter (WM) microstructure in HIV. The pictorial review describes common causes of HIV-related cerebral WM disease as well as the role of neuro-imaging in managing these patients. In the following chapters the characteristics of WM signal abnormalities on MRI and DTI (using DTI derived measures - fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusion (RD)) in children with HIV, recruited as part of the Children with HIV early antiretroviral (CHER) trial and who started ART within the first year of life, are described. In the CHER trial, infants were randomized to early limited or deferred continuous ART. Methods: Structural MRI scans of children at mean age 39.1 months were reviewed and correlated with clinical and neurodevelopmental data, virological markers and time on ART. DTI was acquired in a similar cohort (which included several children in the first study and control subjects) at mean age of 64.7 months. Voxel-based group comparisons were performed to determine regions where FA and MD differed between HIV+ and uninfected children. Associations of DTI parameters with timing of ART initiation and correlations of DTI parameters in abnormal WM with directed neurodevelopmental tests were examined. Results: MRI scans of 44 children were reviewed at mean age of 39.1 months: 10 on deferred and 34 on early CHER treatment arms, commencing ART at mean age of 18.5 and 8 weeks respectively. Multiple high signal intensity lesions on T2 /FLAIR were documented in 22 patients (50%), predominantly in frontal (91%) and parietal (82%) WM. There were no differences in neurodevelopmental scores in children with and without WM signal abnormalities. Neither lesion load nor distribution showed significant correlation with neurodevelopmental scores or neurological examination. There was a trend for association of WM signal abnormalities and longer time on ART (p=0.13) and nadir CD4% (p=0.08). 39 HIV+ children (15 male) and 13 controls (5 male) were imaged (using DTI) at mean age of 64.7 months. 2 Clusters with decreased FA and 7 clusters with increased MD were identified in the HIV+ group with symmetrical distribution predominantly due to increased RD, suggestive of decreased myelination. Children on early interrupted ART had lower FA compared to those receiving continuous treatment. The only neurodevelopmental domain with a trend of difference between the HIV+ children and controls (p=0.08), was personal social quotient which correlated to improved myelination of the forceps minor in the control group. As a combined group there was a negative correlation between visual perception and RD in the right superior longitudinal fasciculus and left inferior longitudinal fasciculus which may be related to these tracts, part of the visual perception pathway, are at a crucial state of development at age 5. Conclusion: Half of children at mean age of 39.1 months, referred with HIV-related brain disease had WM signal abnormalities on T2/FLAIR structural MRI. HIV+ children at 5 years have WM abnormalities measured by FA, despite early ART, confirming that early ART does not fully protect the WM either from peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum. Continuous early ART, however limits the extent of WM damage. Even directed neurodevelopmental tests will underestimate the degree of microstructural WM damage detected by DTI. The visual perception deficit detected in the HIV study population should be further examined as it persists in longitudinal follow up of these patients at age 7.