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 neurologic disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging in children with HIV-related neurologic disease.

Methods: We reviewed magnetic resonance imaging scans of children with suspected HIV-related neurologic disease despite early ART and correlated with clinical, neurodevelopmental data, virologic markers and time on ART. These children were also on the Children with HIV Early Antiretroviral (CHER) trial.

Results: Magnetic resonance imaging 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/fluid attenuated inversion recovery 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 neurologic 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).

Conclusions: Half of children referred with HIV-related brain disease had WMSA on T2/fluid attenuated inversion recovery. 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 central nervous system.

Figure 1

Axial FLAIR MRI: pin-point white matter signal abnormality (WMSA) (black arrows) in addition to larger measurable lesions (white arrow) of various shapes and sizes all less than 1cm in both of the superior frontal lobes. Axial FLAIR MRI: multiple bilateral pin point WMSA, involving predominantly subcortical (white arrows) and to a lesser degree deep white matter in the superior frontal lobes. Axial FLAIR MRI: Two right frontal sub-centimeter focal lesions. FLAIR MRI: Bilateral parietal WMSA, on the right larger than 1cm (white arrow) and on the left less than 1cm (black arrow) extending from the subcortical to the deep white matter. FLAIR: fluid attenuation inversion recovery MRI: magnetic resonance imaging WMSA: white matter signal abnormalities