Long-term morphological changes of symptomatic lacunar infarcts and surrounding white matter on structural MRI

The contributing studies were funded by the Chief Scientist Office of the Scottish Executive (grant 217 NTU R37933), the Wellcome Trust (grants 075611 and WT088134/Z/09/A), and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE (Scottish Imaging Network, A Platform for Scientific Excellence) collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). This work was supported by European Union Horizon 2020 (EU H2020), PHC- 03 to 15, project No. 666881, SVDs@Target, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref No. 16 CVD 05. Dr Loos was supported by the Dutch Alzheimer Foundation.Peer reviewedPublisher PD

Tracer kinetic modelling for DCE-MRI quantification of subtle blood–brain barrier permeability

There is evidence that subtle breakdown of the blood–brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n = 201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a “sham” DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and KTrans estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible

The coping strategies used over a two-year period by HIV-positive women who had been diagnosed during pregnancy

Structured interviews were conducted with 224 HIV-positive women diagnosed during pregnancy, at antenatal clinics in Tshwane, South Africa, in order to investigate the use of coping strategies during the first two years after diagnosis. Interviews were conducted between one and four weeks after diagnosis during pregnancy, with three follow-up interviews conducted post-partum. Coping strategies were assessed with an adapted version of the Brief COPE. It was found that active coping was used more often than avoidant coping throughout the study period. Active coping increased over time, while avoidant coping decreased at first but increased again between 6 and 21 months after diagnosis. The most frequently used coping strategies included acceptance, direct action, positive reframing, religion and distraction. At first, women coped through internalised strategies. Over time, outwardfocused strategies developed. Avoidant coping patterns differed from previous research indicating that women diagnosed during pregnancy deal with the consequences of HIV after the baby is born. Recommendations for mental health services are made.National Institute of Child Health and Human Development (NICHD) grant R24HD43558http://www.tandfonline.com/loi/caic20hb201

Psychosocial variables associated with coping of HIV-positive women diagnosed during pregnancy

To identify psychosocial variables related to the use of coping strategies by HIV-positive South African women diagnosed during pregnancy, structured interviews were conducted with 224 HIV-positive women at antenatal clinics over a period of two years. Two coping styles, active and avoidant coping, were assessed using an adapted version of the Brief COPE. Psychosocial variables associated with changes in coping over time were identified with mixed linear analysis. Increases in active coping were associated with decreasing levels of internalized stigma and depression, increasing self-esteem and positive social support, knowing someone who is living with HIV, being physically healthy and living above the poverty line. Increases in avoidant coping were associated with increasing internalized stigma and depression, lower levels of self-esteem, HIV-knowledge and lower levels of education. Recommendations are made for psychological support services to strengthen women’s ability to cope and enhance their health and that of their infants.National Institute of Child Health and Human Development (NICHD) grant R24HD43558http://www.springer.com/public+health/journal/10461gv201

Lacunar stroke lesion extent and location and white matter hyperintensities evolution 1 year post-lacunar stroke

Lacunar strokes are a common type of ischemic stroke. They are associated with long-term disability, but the factors affecting the dynamic of the infarcted lesion and the brain imaging features associated with them, reflective of small vessel disease (SVD) severity, are still largely unknown. We investigated whether the distribution, volume and 1-year evolution of white matter hyperintensities (WMH), one of these SVD features, relate to the extent and location of these infarcts, accounting for vascular risk factors. We used imaging and clinical data from all patients [n = 118, mean age 64.9 (SD 11.75) years old] who presented to a regional hospital with a lacunar stroke syndrome within the years 2010 and 2013 and consented to participate in a study of stroke mechanisms. All patients had a brain MRI scan at presentation, and 88 had another scan 12 months after. Acute lesions (i.e., recent small subcortical infarcts, RSSI) were identified in 79 patients and lacunes in 77. Number of lacunes was associated with baseline WMH volume (B = 0.370, SE = 0.0939, P = 0.000174). RSSI volume was not associated with baseline WMH volume (B = 3.250, SE = 2.117, P = 0.129), but predicted WMH volume change (B = 2.944, SE = 0.913, P = 0.00184). RSSI location was associated with the spatial distribution of WMH and the pattern of 1-year WMH evolution. Patients with the RSSI in the centrum semiovale (n = 33) had significantly higher baseline volumes of WMH, recent and old infarcts, than patients with the RSSI located elsewhere [median 33.69, IQR (14.37 50.87) ml, 0.001 ≤ P ≤ 0.044]. But patients with the RSSI in the internal/external capsule/lentiform nucleus experienced higher increase of WMH volume after a year [n = 21, median (IQR) from 18 (11.70 31.54) ml to 27.41 (15.84 40.45) ml]. Voxel-wise analyses of WMH distribution in patients grouped per RSSI location revealed group differences increased in the presence of vascular risk factors, especially hypertension and recent or current smoking habit. In our sample of patients presenting to the clinic with lacunar strokes, lacunar strokes extent influenced WMH volume fate; and RSSI location and WMH spatial distribution and dynamics were intertwined, with differential patterns emerging in the presence of vascular risk factors. These results, if confirmed in wider samples, open potential avenues in stroke rehabilitation to be explored further

Support group processes : perspectives from HIV-infected women in South Africa

This study examined the experiences and perceived benefits of support group participation among HIV-infected women in South Africa. From a qualitative analysis of responses, key psychological processes through which support groups are potentially beneficial were identified. These processes included identification, modelling, acceptance, and empowerment. The participants’ consequent life changes were explored in order to associate these processes with the positive outcomes of support group participation. Through understanding the relationship between the psychological processes within a support group setting and the potential benefits, and by targeting these processes in the development and implementation of future support group interventions, a framework is provided for achieving positive outcomes associated with support group participation.NICHD grant R24HD43558http://www.tandfonline.com/loi/uqrp20gv201

A four-dimensional computational model of dynamic contrast-enhanced magnetic resonance imaging measurement of subtle blood-brain barrier leakage

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies

Impact of structured support groups for pregnant South African women recently diagnosed HIV positive

The authors of this study evaluated a structured 10-session psy- chosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p < 0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t = 2.68, p < 0.05) and lower levels of avoidant coping (t = -2.02, p < 0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t = 2.11, p < 0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one’s HIV status, but may not have sustainable benefits over time.http://www.tandfonline.com/loi/wwah2

Behavior and psychological functioning of young children of HIV-positive mothers in South Africa

Adults with HIV are living longer due to earlier diagnosis and increased access to antiretroviral medications. Therefore, fewer young children are being orphaned and instead, are being cared for by parents who know they are HIV positive, although they may be asymptomatic. Presently, it is unclear whether the psychological functioning of these young children is likely to be affected or, alternatively, whether it is only when a mother is ill, that children suffer adverse effects. We, thus, aimed to compare the behavior and psychological functioning of young children (aged 6 10 years) of HIV-positive and HIV-negative mothers. We also aimed to examine the association between HIV status disclosure and child outcomes. This study uses cross-sectional data from the baseline assessment of a randomized controlled trial conducted in Tshwane, South Africa. Participants (n 509) and their children were recruited from area health clinics. Among the 395 mothers with HIV, 42% reported symptoms of HIV disease. Multivariate linear regression models suggested that after adjusting for sociodemographic characteristics, children of HIV-positive mothers had significantly greater externalizing behaviors than children of HIV-negative mothers. Importantly, children whose mothers were symptomatic had greater internalizing and externalizing behaviors compared with children of HIV-negative mothers, but this was not true for children of asymptomatic mothers. Additionally, among children of HIV-positive mothers, those who had been told their mothers were sick compared with children who had been told nothing had less internalizing and externalizing behaviors and improved daily living skills. This study, therefore, provides evidence that maternal HIV disease can affect the behaviors of young children in South Africa but, importantly, only when the mothers are symptomatic from their disease. Furthermore, results suggest that disclosure of maternal illness but not HIV status was associated with improved behavior and psychological functioning among young children.National Institute of Mental Health (Grant 5R01HD057834)http://www.tandfonline.com/loi/caic20hb201

A randomized clinical trial of an intervention to promote resilience in young children of HIV-positive mothers in South Africa

OBJECTIVE : To assess the efficacy of an intervention designed to promote resilience in young children living with their HIV-positive mothers. DESIGN / METHODS : HIV-positive women attending clinics in Tshwane, South Africa and their children, aged 6 - 10 years, were randomised to the intervention (I) or standard care (S). The intervention consisted of 24 weekly group sessions led by community care workers. Mothers and children were in separate groups for 14 sessions, followed by 10 interactive sessions. The primary focus was on parent-child communication and parenting. Assessments were completed by mothers and children at baseline and 6, 12 and 18 months. Repeated mixed linear analyses were used to assess change over time.RESULTS : Of 390 mother-child pairs, 84.6% (I:161 & S:169) completed at least two interviews and were included in the analyses. Children’s mean age was 8.4 years and 42% of mothers had been ill in the prior three months. Attendance in groups was variable: only 45.7% attended >16 sessions. Intervention mothers reported significant improvements in children’s externalizing behaviors (ß=-2.8, P=0.002), communication (ß=4.3, P=0.025) and daily living skills (ß=5.9, P=0.024), while improvement in internalizing behaviors and socialization was not significant (P=0.061 and 0.052 respectively). Intervention children reported a temporary increase in anxiety but did not report differences in depression or emotional intelligence. CONCLUSIONS : This is the first study demonstrating benefits of an intervention designed to promote resilience among young children of HIV-positive mothers. The intervention was specifically designed for an African context, and has the potential to benefit large numbers of children, if it can be widely implemented.http://journals.lww.com/aidsonline2015-06-30hb201