Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study

Abstract

HIV infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤200cells/mm3, on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). 84% of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16% had mild cognitive impairment (HIVCI). Tract-Based Spatial Statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy (FA) decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.

White matter damage and effects of nadir CD4+ count on patients with asymptomatic HIV associated dementia complex–A DTI study

“…FA value and ADC value, which is more sensitive to changes of white matter in HIV þ patients is an contradiction at previous reports. We found HIV þ infection affects ADC to a greater extent than FA, which may suggest that alteration of ADC may reflect the prominent disease process in HIV þ patients, this is consistent with the findings of Zhu T et al [24], they reported that mean diffusivity (MD) increased significantly in the both hemispheres in HIV patients with neurologically asymptomatic compared to controls, no statistical significance was detected in any regions in FA.…”

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

“…In the HIV context and based on DTI acquisition parameters, we interpret FA as relating to the degree of axonal structural integrity primarily reflecting membrane and cytoskeleton integrity (Winston 2012) and possibly astrocytic structural integrity (Lentz et al 2014). MD reflects aspects of WM microstructure density (Winston 2012;Zhu et al 2013), such as degree of extracellular space between WM tracts (Lentz et al 2014) that may be affected by neuroinflammation including glial involvement and myelin loss to a lesser extent. In this case, myelin contribution to MD changes is debatable (Lentz et al 2014) as massive demyelination is not a common feature of HIV-related brain injury even in those who had severe HIV encephalopathy (Pelle et al 2008).…”

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

“…The findings that FA values within the genu, body, and splenium of the corpus callosum were reduced in HIV-positive adolescents are consistent with findings in previous studies on HIV-infected children and adults. For example, FA values for the genu, 10 body, 21 and splenium 8 of the corpus callosum 11,22 are significantly reduced in HIV-infected adults. Decreased FA of the body of corpus callosum is also reported in HIV-infected children.…”

“…25 Moreover, deceased FA is also found in the anterior and superior corona radiata in HIV-infected participants. 10,11 The anterior corona radiata is associated with functions of the executive network. 26 Previous studies have focused on HIV-infected children and found that the subjects displayed visual-spatial memory and motor developmental deficits and executive function disorders.…”

“…6 Recent DTI studies have identified abnormalities in the subcortical WM and corpus callosum, despite appearing normal on conventional MRI in HIV-infected adults. 7 Abnormal WM integrity, such as reduced fractional anisotropy (FA) or increased mean diffusivity (MD), was found in the splenium, 8 superior longitudinal fasciculus, 9 anterior and superior corona radiata, 10,11 and frontal and parietal WM 12 in HIVinfected adults. Similarly, neuroimaging studies have also demonstrated vast WM abnormalities in adolescents with vertically transmitted HIV infection.…”