BACKGROUND: Objective MRI markers of central nervous system disease severity may precede subjective features of HIV encephalopathy in children. Previous work in HIV-infected adults shows that brain atrophy was associated with low CD4 and with neuropsychological impairment. Significant thinning of the corpus callosum (CC), predominantly anteriorly, was also found in HIV-infected adults and correlated with CD4 levels. These findings have not been tested in children. PURPOSE: The aim of this study was to determine if brain volume and midsagittal CC linear measurements (thickness and length) on MRI in children with HIV-related brain disease correlate with clinical and laboratory parameters of disease severity. METHODS: Retrospective MRI analysis in children with HIV-related brain disease used a volumetric analysis software and a semi-automated tool to measure brain volume and callosal thickness/length, respectively. Each measure was correlated with clinical parameters of disease severity including Griffiths Mental Development scores (GMDS), absolute CD4 counts (cells/mm(3)), nadir CD4 (the lowest CD4 recorded, excluding baseline), duration of HAART, and decreased brain growth. RESULTS: Thirty-three children with HIV-related brain disease were included. Premotor segment of the CC mean thickness correlated with age (p = 0.394). Motor CC maximum thickness correlated significantly with general developmental quotient (p = 0.0277); CC length correlated with a diagnosis of acquired microcephaly (p = 0.0071) and to CD4 level closest to date of the MRI scan (p = 0.04). CONCLUSIONS: Length of the CC and the "motor CC segment" may represent surrogate clinical biomarkers of central nervous system disease severity and with decreased level of immunity in HIV-infected patients that precede established HIV encephalopathy.
BACKGROUND: Objective MRI markers of central nervous system disease severity may precede subjective features of HIV encephalopathy in children. Previous work in HIV-infected adults shows that brain atrophy was associated with low CD4 and with neuropsychological impairment. Significant thinning of the corpus callosum (CC), predominantly anteriorly, was also found in HIV-infected adults and correlated with CD4 levels. These findings have not been tested in children. PURPOSE: The aim of this study was to determine if brain volume and midsagittal CC linear measurements (thickness and length) on MRI in children with HIV-related brain disease correlate with clinical and laboratory parameters of disease severity. METHODS: Retrospective MRI analysis in children with HIV-related brain disease used a volumetric analysis software and a semi-automated tool to measure brain volume and callosal thickness/length, respectively. Each measure was correlated with clinical parameters of disease severity including Griffiths Mental Development scores (GMDS), absolute CD4 counts (cells/mm(3)), nadir CD4 (the lowest CD4 recorded, excluding baseline), duration of HAART, and decreased brain growth. RESULTS: Thirty-three children with HIV-related brain disease were included. Premotor segment of the CC mean thickness correlated with age (p = 0.394). Motor CC maximum thickness correlated significantly with general developmental quotient (p = 0.0277); CC length correlated with a diagnosis of acquired microcephaly (p = 0.0071) and to CD4 level closest to date of the MRI scan (p = 0.04). CONCLUSIONS: Length of the CC and the "motor CC segment" may represent surrogate clinical biomarkers of central nervous system disease severity and with decreased level of immunity in HIV-infectedpatients that precede established HIV encephalopathy.
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