Family Matters:Trauma and Quality of Life in Family Members of Individuals With Prader-Willi Syndrome

BACKGROUND: Prader-Willi syndrome (PWS) is a potentially life threatening, genetic developmental disorder that requires lifelong medical treatment and behavioral management. PWS has a major impact on the patient's social environment. In this study, we have explored traumatic life events and symptoms of posttraumatic stress disorder (PTSD) in family members of individuals with PWS. We have also assessed quality of life in relation to trauma manifestations. In addition, we have evaluated demographic characteristics such as living setting of PWS patients as well as PWS symptom severity. METHODS: Data of this observational study were obtained by means of the Life Events Checklist DMS-5, the Posttraumatic Stress Disorder Checklist DSM-5, the abbreviated World Health Organization Quality of Life questionnaire, the Lancashire Quality of Life Profile questionnaire, and a short demographic inventory. The study sample includes 98 adults aged 19 to 80 years (M = 49, SD = 15), who are relatives of 69 individuals with PWS aged 0 to 58 years (M = 19, SD = 13). Participants were recruited via the two Dutch patient associations PWS and the Dutch Digital Center of Expertise PWS. RESULTS: Life time prevalence of traumatic events (93%) was higher in family members of PWS patients (“PWS relatives”) than in the general Dutch population (81%). Of those who reported any traumatic event, almost half reported PWS-related events. The prevalence of probable PTSD was higher in PWS relatives (12.1%) than the general lifetime prevalence of PTSD (worldwide, and in the Netherlands 7.4%). Predominant trauma symptoms in PWS relatives were “negative changes in arousal and reactivity” and “negative changes in cognition and mood;” both significantly negatively related to quality of life. Symptom severity of PWS individuals, as well as the associated trauma symptom severity of their relatives increased with age of the PWS individual. The presence of trauma symptoms was less frequent among relatives of PWS individuals living in a care facility. CONCLUSIONS: Having a relative with PWS is associated with higher prevalence of traumatic experiences and greater vulnerability to PTSD. Raising awareness in health care professionals of trauma symptoms in PWS relatives may contribute to effective treatment of their psychosocial stress. In addition, timely interventions might prevent family members from developing psychopathology like PTSD

Pictures of preterm infants elicit increased affective responses and reduced reward-motivation or perspective taking in the maternal brain

Preterm-birth increases the risk of several physical, cognitive, neuromotor, and psychosocial problems in children, and is also related to difficulties in the parent-child relationship. Research suggests that the development of early parent-child interactions in general is affected by deviations from typical infant facial characteristics, which may also be important in the case of small, preterm born infants. Therefore, we examined mothers' (N = 22, of whom 17 had no direct experience with preterm birth) neural responses to pictures of preterm and fullterm infants using functional magnetic resonance imaging (fMRI). We also explored whether neural responses to preterm and full-term infants correlated with mothers' self-reported tendencies to be nurturing and protective with children, and with mothers' ratings of affection or aversion toward pictures of preterm infants. Results revealed that, compared to pictures of full-term infants, those of preterm infants elicited more activity in specific areas of the brain (dmPFC, right insula, left caudate, hippocampi, parahippocampi, and PAG), that have previously been associated with processing of negative emotions and with empathy. In addition, less activity was seen in one area of the brain (vmPFC) known to be associated with reward-motivation or mental state understanding and perspective-taking. Higher self-reported maternal nurturance was associated with increased activity to pictures of preterm infants vs full-term infants in the caudate, which might reflect approach- or reward-related processing. To conclude, neural responses to preterm infants are related to reward-motivation, mentalizing, negative emotions, and empathy. Future studies should examine whether such neural processing of preterm infant stimuli might underlie difficulties in the parent-child relationship of parents with a preterm child

What a cute baby! Preliminary evidence from a fMRI study for the association between mothers ? neural responses to infant faces and activation of the parental care system

Infant facial characteristics, i.e., baby schema, are thought to automatically elicit parenting behavior and affective orientation toward infants. Only a few studies, conducted in non-parents, have directly examined the neural underpinnings of this baby schema effect by manipulating distinctiveness of baby schema in infant faces. This study aims to further our understanding of the intuitive nature of parenting, by studying the baby schema effect in mothers of young children (at least one child aged between 2 and 6 years old). Functional magnetic resonance imaging (fMRI) was used to examine mothers’ (N = 23) neural responses to unfamiliar infant faces varying in distinctiveness of baby schema. Also, it was studied how this neural activation to infant faces was associated with maternal nurturance. Results revealed that infant faces elicited widespread activation in bilateral visual cortices, the hippocampus, sensory-motor areas, parietal and frontal cortices, and the insula, which was not modulated by the distinctiveness of baby schema in the infant faces. Furthermore, higher self-reported maternal nurturance was related to increased neural responses to infant faces in the putamen and amygdala, brain regions known to be associated with reward and salience processing. These findings could suggest that in our small sample of mothers some of the core networks involved in reward and salience processing might be less sensitive to variation in distinctiveness of baby schema. Also, unfamiliar infant faces seem to be rewarding only for mothers who report high nurturance. These findings should be considered preliminary, because they need to be replicated in studies with larger samples

Decreased native renal T1 up to one week after gadobutrol administration in healthy volunteers

Background: Gadolinium-based contrast agents (GBCAs) are widely used in MRI, despite safety concerns regarding deposition in brain and other organs. In animal studies gadolinium was detected for weeks after administration in the kidneys, but this has not yet been demonstrated in humans. Purpose: To find evidence for the prolonged presence of gadobutrol in the kidneys in healthy volunteers. Study Type: Combined retrospective and prospective analysis of a repeatability study. Population: Twenty-three healthy volunteers with normal renal function (12 women, age range 40–76 years), of whom 21 were used for analysis. Field Strength/Sequence: Inversion recovery-based T 1 map at 3T. Assessment: T 1 maps were obtained twice with a median interval of 7 (range: 4–16) days. The T 1 difference (ΔT 1) between both scans was compared between the gadolinium group (n = 16, 0.05 mmol/kg gadobutrol administered after T 1 mapping during both scan sessions) and the control group (n = 5, no gadobutrol). T 1 maps were analyzed separately for cortex and medulla. Statistical Tests: Mann–Whitney U-tests to detect differences in ΔT 1 between groups and linear regression to relate time between scans and estimated glomerular filtration rate (eGFR) to ΔT 1. Results: ΔT 1 differed significantly between the gadolinium and control group: median ΔT 1 cortex –98 vs. 7 msec (P < 0.001) and medulla –68 msec vs. 19 msec (P = 0.001), respectively. The bias corresponds to renal gadobutrol concentrations of 8 nmol/g tissue (cortex) and 4 nmol/g tissue (medulla), ie, ~2.4 μmol for both kidneys (0.05% of original dose). ΔT 1 correlated in the gadolinium group with duration between acquisitions for both cortex (regression coefficient (β) 16.5 msec/day, R 2 0.50, P < 0.001) and medulla (β 11.5 msec/day, R 2 0.32, P < 0.001). Medullary ΔT 1 correlated with eGFR (β 1.13 msec/(ml/min) R 2 0.25, P = 0.008). Data Conclusion: We found evidence of delayed renal gadobutrol excretion after a single contrast agent administration in subjects with normal renal function. Even within this healthy population, elimination delay increased with decreasing kidney function. Level of Evidence: 3. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2020;52:622–631

Multiparametric Renal MRI: An Intrasubject Test-Retest Repeatability Study

BACKGROUND: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease. PURPOSE: To determine intrasubject test-retest repeatability of renal MRI measurements. STUDY TYPE: Prospective. POPULATION: Nineteen healthy subjects aged over 40 years. FIELD STRENGTH/SEQUENCES: T1 and T2 mapping, R2 * mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T. ASSESSMENT: Subjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model. STATISTICAL TEST: To assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated. RESULTS: CoVs for relaxometry (T1 , T2 , R2 */BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2 */BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP ), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP , respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively). DATA CONCLUSION: CoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1

Detection of Cardioembolic Sources With Nongated Cardiac Computed Tomography Angiography in Acute Stroke: Results From the ENCLOSE Study

BACKGROUND: Identifying cardioembolic sources in patients with acute ischemic stroke is important for the choice of secondary prevention strategies. We prospectively investigated the yield of admission (spectral) nongated cardiac computed tomography angiography (CTA) to detect cardioembolic sources in stroke. METHODS: Participants of the ENCLOSE study (Improved Prediction of Recurrent Stroke and Detection of Small Volume Stroke) with transient ischemic attack or acute ischemic stroke with assessable nongated head-to-heart CTA at the University Medical Center Utrecht were included between June 2017 and March 2022. The presence of cardiac thrombus on cardiac CTA was based on a Likert scale and dichotomized into certainly or probably absent versus possibly, probably, or certainly present. The diagnostic certainty of cardiac thrombus was evaluated again on spectral computed tomography reconstructions. The likelihood of a cardioembolic source was determined post hoc by an expert panel in patients with cardiac thrombus on CTA. Parametric and nonparametric tests were used to compare the outcome groups. RESULTS: Forty four (12%) of 370 included patients had a cardiac thrombus on admission CTA: 35 (9%) in the left atrial appendage and 14 (4%) in the left ventricle. Patients with cardiac thrombus had more severe strokes (median National Institutes of Health Stroke Scale score, 10 versus 4; P=0.006), had higher clot burden (median clot burden score, 9 versus 10; P=0.004), and underwent endovascular treatment more often (43% versus 20%; P<0.001) than patients without cardiac thrombus. Left atrial appendage thrombus was present in 28% and 6% of the patients with and without atrial fibrillation, respectively ( P<0.001). The diagnostic certainty for left atrial appendage thrombus was higher for spectral iodine maps compared with the conventional CTA ( P<0.001). The presence of cardiac thrombus on CTA increased the likelihood of a cardioembolic source according to the expert panel ( P<0.001). CONCLUSIONS: Extending the stroke CTA to cover the heart increases the chance of detecting cardiac thrombi and helps to identify cardioembolic sources in the acute stage of ischemic stroke with more certainty. Spectral iodine maps provide additional value for detecting left atrial appendage thrombus. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04019483

Validation of multiparametric MRI by histopathology after nephrectomy: a case study

OBJECTIVES: Renal multiparametric MRI (mpMRI) is a promising tool to monitor renal allograft health to enable timely treatment of chronic allograft nephropathy. This study aims to validate mpMRI by whole-kidney histology following transplantectomy. MATERIALS AND METHODS: A patient with kidney transplant failure underwent mpMRI prior to transplantectomy. The mpMRI included blood oxygenation level-dependent (BOLD) MRI, T1 and T2 mapping, diffusion-weighted imaging (DWI), 2D phase contrast (2DPC) and arterial spin labeling (ASL). Parenchymal mpMRI measures were compared to normative values obtained in 19 healthy controls. Differences were expressed in standard deviations (SD) of normative values. The mpMRI measures were compared qualitatively to histology. RESULTS: The mpMRI showed a heterogeneous parenchyma consistent with extensive interstitial hemorrhage on histology. A global increase in T1 (+ 3.0 SD) and restricted diffusivity (- 3.6 SD) were consistent with inflammation and fibrosis. Decreased T2 (- 1.8 SD) indicated fibrosis or hemorrhage. ASL showed diminished cortical perfusion (- 2.9 SD) with patent proximal arteries. 2DPC revealed a 69% decrease in renal perfusion. Histological evaluation showed a dense inflammatory infiltrate and fibrotic changes, consistent with mpMRI results. Most interlobular arteries were obliterated while proximal arteries were patent, consistent with ASL findings. DISCUSSION: mpMRI findings correlated well with histology both globally as well as locally

Mothers' neural responses to infant faces are associated with activation of the maternal care system and observed intrusiveness with their own child

Certain infant facial characteristics, referred to as baby schema, are thought to automatically trigger parenting behavior and affective orientation toward infants. Electroencephalography (EEG) is well suited to assessing the intuitive nature and temporal dynamics of parenting responses, due to its millisecond temporal resolution. Little is known, however, about the relations between neural processing of infant cues and actual parenting behavior in a naturalistic setting. In the present study we examined the event-related potentials (ERPs) of mothers (N = 33) watching infant faces of varying attractiveness, in relation to activation of the maternal care system and the mothers' observed parenting behavior (sensitivity, nonintrusiveness) with their own child (2-6 years old). The results revealed that, irrespective of the cuteness of the infant face, mothers' neural processing of infant faces involved both early P1 and P2 components (related to orienting/detecting processes) and late positive potentials (LPPs; related to more controlled cognitive evaluation/attentional engagement). Increased early detection and processing of infant faces (reflected by P1 and P2 activity) was related to increased activation of the parental care system. In later stages of face processing, increased attentional engagement with infant faces (as reflected by LPP activity) was associated with more intrusiveness of a mother with her own child during interaction. These findings suggest that individual variations in responses to infant stimuli are associated with individual differences in parental care system activation and parenting quality. Furthermore, the parental care system might be activated relatively automatically, but actual parenting and caregiving behavior requires more conscious control

Pictures of preterm infants elicit increased affective responses and reduced reward-motivation or perspective taking in the maternal brain

Preterm-birth increases the risk of several physical, cognitive, neuromotor, and psychosocial problems in children, and is also related to difficulties in the parent–child relationship. Research suggests that the development of early parent–child interactions in general is affected by deviations from typical infant facial characteristics, which may also be important in the case of small, preterm born infants. Therefore, we examined mothers’ (N = 22, of whom 17 had no direct experience with preterm birth) neural responses to pictures of preterm and full-term infants using functional magnetic resonance imaging (fMRI). We also explored whether neural responses to preterm and full-term infants correlated with mothers’ self-reported tendencies to be nurturing and protective with children, and with mothers’ ratings of affection or aversion toward pictures of preterm infants. Results revealed that, compared to pictures of full-term infants, those of preterm infants elicited more activity in specific areas of the brain (dmPFC, right insula, left caudate, hippocampi, parahippocampi, and PAG), that have previously been associated with processing of negative emotions and with empathy. In addition, less activity was seen in one area of the brain (vmPFC) known to be associated with reward-motivation or mental state understanding and perspective-taking. Higher self-reported maternal nurturance was associated with increased activity to pictures of preterm infants vs full-term infants in the caudate, which might reflect approach- or reward-related processing. To conclude, neural responses to preterm infants are related to reward-motivation, mentalizing, negative emotions, and empathy. Future studies should examine whether such neural processing of preterm infant stimuli might underlie difficulties in the parent–child relationship of parents with a preterm child

What a cute baby! Preliminary evidence from a fMRI study for the association between mothers’ neural responses to infant faces and activation of the parental care system

Infant facial characteristics, i.e., baby schema, are thought to automatically elicit parenting behavior and affective orientation toward infants. Only a few studies, conducted in non-parents, have directly examined the neural underpinnings of this baby schema effect by manipulating distinctiveness of baby schema in infant faces. This study aims to further our understanding of the intuitive nature of parenting, by studying the baby schema effect in mothers of young children (at least one child aged between 2 and 6 years old). Functional magnetic resonance imaging (fMRI) was used to examine mothers’ (N = 23) neural responses to unfamiliar infant faces varying in distinctiveness of baby schema. Also, it was studied how this neural activation to infant faces was associated with maternal nurturance. Results revealed that infant faces elicited widespread activation in bilateral visual cortices, the hippocampus, sensory-motor areas, parietal and frontal cortices, and the insula, which was not modulated by the distinctiveness of baby schema in the infant faces. Furthermore, higher self-reported maternal nurturance was related to increased neural responses to infant faces in the putamen and amygdala, brain regions known to be associated with reward and salience processing. These findings could suggest that in our small sample of mothers some of the core networks involved in reward and salience processing might be less sensitive to variation in distinctiveness of baby schema. Also, unfamiliar infant faces seem to be rewarding only for mothers who report high nurturance. These findings should be considered preliminary, because they need to be replicated in studies with larger samples