White Matter Signal Abnormalities in Children With Suspected HIV-related Neurologic Disease on Early Combination Antiretroviral Therapy

Abstract

BACKGROUND The natural history and manifestation of HIV-related neurological disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging (MRI) in children with HIV-related neurological disease. METHODS We reviewed MRI scans of children with suspected HIV-related neurological disease despite early ART, and correlated with clinical, neurodevelopmental data, virological markers and time on ART. These children were also on the Children with HIV Early Antiretroviral (CHER) trial. RESULTS MRI scans were performed at a mean age 31.9 months (range 8-54) on 44 children: 10 on deferred and 34 on early 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%) white matter. No differences in neurodevelopmental scores comparing children with and without WMSA were found. Neither lesion load nor distribution showed significant correlation with neurodevelopmental scores or neurological examination. Normal head growth was more common in the WMSA group (p=0.01). There was a trend for association of WMSA and longer time on ART (p=0.13) and nadir CD4% (p=0.08). CONCLUSION Half of children referred with HIV-related brain disease had WMSA on T2/FLAIR. Our findings of the association with normal head growth and duration of ART require further study. We suspect that WMSA can occur early and that initiating ART by 8 weeks of life may be too late to prevent HIV from entering the CNS.

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing

“…Ten had WM signal abnormality on FLAIR. 39 Unfortunately, a limitation in the present study was an absence of FLAIR, thus an inability to assess interval WM signal change. However, absence of frontal and parietal involvement on FA does suggest interval improvement on ART.…”

“…Of interest, CC volume and thickness were similar to controls in a study by Andronikou et al which included the 20 HIV+ children previously reported. 39, 50 The CC genu demonstrates a variable growth spurt at 2 months of age, followed by similar growth in the splenium by 4-6 months, with myelination being visible on T1W MRI from 4-6 months. 51 Our data support early ART being neuroprotective for the CC.…”

“…We previously reported multi-focal WM signal abnormalities on standard T2W MRI sequences in frontal (91%) and parietal WM (82%) of HIV+ children at mean age 31.9 months. 39 Twenty of these children are also included in the present study. Ten had WM signal abnormality on FLAIR.…”

Of Mice and Monkeys: Can Animal Models Be Utilized to Study Neurological Consequences of Pediatric HIV-1 Infection?

“…Children in this study began ART by 8 weeks of life, suggesting that the white matter abnormalities manifest early during the infection, possibly due to early entry of HIV-1 into the central nervous system (CNS). 85 There is also an increased prevalence of cerebrovascular disease. 86 Diffusion tensor imaging also indicates reduced radial diffusivity, suggesting demyelination, 56 which is consistent with sparse reports of multiple-sclerosis-like disorders in HIV-1 infected children.…”

“…58 White matter abnormalities may occur very early in the infection, possibly within 8 weeks of life. 85 …”