Cerebral injury in perinatally HIV-infected children compared to matched healthy controls

Cohen, Sophie; Caan, Matthan W.A.; Mutsaerts, Henk‐Jan; Scherpbier, Henriëtte J.; Kuijpers, Taco W.; Reiss, Peter; Majoie, Charles B. L. M.; Pajkrt, Dasja

doi:10.1212/wnl.0000000000002209

Cited by 69 publications

(106 citation statements)

References 37 publications

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“…35 In HIV-infected patients, glial cells release inflammatory cytokines and chemokines, factors that often show stronger associations with cognitive performance than disease severity markers. 36,37 In agreement with this association between Cho:Cre and cognition, a previous study in our cohort detected increased WM diffusivity in HIV-infected children, which was associated with poorer working memory, 19 and might also be due to increased glial activation. In healthy participants, poorer performance on processing speed and executive functioning were related to lower NAA:Cre and Glu:Cre levels NAA enhances neuronal mitochondrial energy production from Glu, making it a marker for neuronal health.…”

Section: Discussionsupporting

confidence: 89%

“…As we previously detected poorer cognitive functioning and structural cerebral injury in these HIV-infected children, 18,19 we expected that neurometabolite levels in this group differ from those in matched healthy controls and will be associated with HIV-related characteristics, cognitive functioning and neurodegenerative markers.…”

Section: Introductionmentioning

confidence: 82%

“…Structural 3D echo gradient T1 with multiplanar reconstruction was conducted as previously reported. 19 MR spectra were acquired from 1 axial T1 slice positioned directly above the corpus callosum. Water was suppressed by applying 3 chemical shift-selective excitation pulses, using a Point Resolved Spectroscopy sequence (TE/TR = 37/2000 milliseconds).…”

Section: Methodsmentioning

confidence: 99%

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Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

et al. 2016

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Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36).Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses.HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. There were no associations between neurometabolites and neuronal damage markers in blood or CSF.Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

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Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

et al. 2016

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“…On both visual and auditory prepulse trials, HIV-1 Tg rats exhibited an insensitivity to ISI duration, suggesting a lack of perceptual sharpening after the adolescent period of development (Moran et al 2013a). There remains a critical need for longitudinal studies to understand the effect of pediatric HIV-1 infection on developmental processes (Cohen et al 2016; Crowell et al 2014)…”

Section: Introductionmentioning

confidence: 99%

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

2016

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Since the advent of combination antiretroviral therapy (cART), pediatric HIV-1 (PHIV) has evolved from a fatal disease to a chronic disease as children perinatally infected with HIV-1 survive into adulthood. The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes constitutively throughout development, was used to model the early development of chronic neurological impairment in PHIV. Male and female Fischer HIV-1 Tg and F344N control rats, sampled from 35 litters, were repeatedly assessed during early development using multiple experimental paradigms, including somatic growth, locomotor activity, cross-modal prepulse inhibition (PPI) and gap-prepulse inhibition (gap-PPI). Later eye opening was observed in HIV-1 Tg animals relative to controls. HIV-1 Tg animals exhibited a shift in the development of locomotor activity implicating alterations in the maturation of the forebrain cholinergic inhibitory system. Alterations in the development of PPI and perceptual sharpening were observed in both auditory and visual PPI as indexed by a relative insensitivity to the dimension of time (ms for ISI; days of age for perceptual sharpening) as a function of the HIV-1 transgene. Presence of the HIV-1 transgene was diagnosed with 97.1% accuracy using auditory and visual PPI measurements from PD 17 and 21. Early selective developmental alterations observed in the HIV-1 Tg rats provide an opportunity for the development of a point-of-care screening tool, which would permit for early diagnosis of PHIV and improve the long-term outcome for children perinatally infected with HIV-1.

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“…Regarding brain structure, investigations of the effects of HIV on the brain using neuroimaging and have discovered that HIV-infected adolescents have significant damage to neuronal microstructure 6–8 . The more recent of these types of investigations found that brain volume for both grey and white matter was lower and that white matter hyperintensities were higher in perinatally HIV-infected children 9 . Another recent study showed that neuronal damage was associated with altered neurometabolite levels 10 .…”

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confidence: 99%

HIV-Associated Cognitive Impairment in Perinatally Infected Children: A Meta-analysis

Phillips¹,

Amos²,

Kuo

et al. 2016

Pediatrics

114

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Context Research shows, conclusively, that perinatal HIV-infection has negative effects on cognitive functioning of children and adolescents. However, the extent of these cognitive impairments is unknown. Current literature does not document specific cognitive domains most affected in HIV-infected children and adolescents. Objective To systematically review and meta-analyse the degree of cognitive impairment, and the specific cognitive domains affected, in children and adolescents with perinatally acquired HIV-infection. Data Sources We systematically searched 5 electronic bibliographic databases namely: PubMed, PsychINFO, Academic Search Premier, Scopus, and WorldCat, using a search protocol specifically designed for this study. Study Selection Studies were selected on the basis of set a priori eligibility criteria. Titles, abstracts and full texts were assessed by two independent reviewers Data Extraction Data from included studies were extracted into Microsoft Excel by two independent reviewers. Results 22 studies were identified for inclusion in the systematic review and of this 6 studies were included in the meta-analysis. Results from the meta-analysis indicated that working memory and executive function were the domains most affected by the HIV-virus. Limitations Only 27% of the included studies were suitable to enter into the meta-analysis. There was significant geographic bias in published studies, with only 32% (7/22) of included studies from sub-Saharan Africa. Conclusions The evidence supports an association between HIV-infection in children and adolescents, and cognitive impairment in the domains of executive function and processing speed, with effect size estimates also providing some support for deficits in visual memory and visual spatial ability.

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Cerebral injury in perinatally HIV-infected children compared to matched healthy controls

Cited by 69 publications

References 37 publications

Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

Neurometabolite Alterations Associated With Cognitive Performance in Perinatally HIV-Infected Children

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

HIV-Associated Cognitive Impairment in Perinatally Infected Children: A Meta-analysis

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