Impact of Brain Malformations on Neurodevelopmental Outcome in Children with a History of Prenatal Surgery for Open Spina Bifida

INTRODUCTION This retrospective study investigates brain malformations and their impact on neurodevelopmental outcome in children after prenatal surgery for spina bifida (SB). METHODS Sixty-one patients were included. On neonatal MRI, SB-associated brain malformations were assessed. Ventricular size, ventriculo-peritoneal shunt (VPS), and endoscopic third ventriculostomy (ETV) were also documented. Neurodevelopment was assessed with the Bayley-III and correlated with brain malformations, ventricular size, and VPS/ETV placement. RESULTS Chiari II malformation was detected in all patients. Corpus callosum (CC) abnormality was noted in 40%, heterotopies in 35%, and cerebellar parenchymal defects in 11%. 96% had ventriculomegaly; in 46%, VPS/ETV was performed. Cognitive and language testing yielded results in the low-average range (Bayley-III: Cognitive Composite Score 93.6, Language Composite Score 89.7), motor testing was below average (Motor Composite Score 77.4). CC abnormalities, heterotopies, and cerebellar defects were not associated with poorer Bayley-III scores, whereas patients with severe ventriculomegaly performed poorer in all subtests, significantly so for the language composite score. Patients requiring intervention for hydrocephalus had significantly lower scores in motor testing. DISCUSSION/CONCLUSION Additional brain malformations in open SB do not seem to have an impact on cognitive function at 2 years of age. Severe ventriculomegaly is a risk factor for poorer cognitive outcome; hydrocephalus surgery adds an additional risk for delayed motor function

Intra-voxel incoherent motion MRI of the living human foetus: technique and test-retest repeatability

Background Our purpose was to test the within-subject (test-retest) reproducibility of the perfusion fraction, diffusion coefficient, and pseudo-diffusion coefficient measurements in various foetus organs and in the placenta based on the intra-voxel incoherent motion (IVIM) principle. Methods In utero diffusion-weighted IVIM magnetic resonance imaging (MRI) was performed in 15 pregnant women (pregnancy age 21-36 weeks) on 1.5-T and 3.0-T clinical scanners with b-factors in the range of 0-900 s/mm in 16 steps. A bi-exponential model was fitted on the volume-averaged diffusion values. Perfusion fraction (f), diffusion coefficient (d), and pseudo-diffusion coefficient (D*) were calculated. Within-subject reproducibility was evaluated as test-retest variability (VAR %) of the IVIM parameters in the foetal frontal cortex, frontal white matter, cerebellum, lungs, kidneys, liver, and in the placenta. Results For the foetal lungs, liver and the placenta, test-retest variability was in the range of 14-20% for f, 12-14% for d, and 17-25% for D*. The diffusion coefficients of the investigated brain regions were moderately to highly reproducible (VAR 5-15%). However, f and D* showed inferior reproducibility compared to corresponding measures for the lungs, liver, and placenta. The IVIM parameters of the foetal kidney were revealed to be highly variable across scans. Conclusions IVIM MRI potentially provides a novel method for examining microvascular perfusion and diffusion in the developing human foetus. However, reproducibility of perfusion and diffusion parameters depends greatly upon data quality, foetal and maternal movements, and foetal-specific image post-processing

Brain volumes in adults with congenital heart disease correlate with executive function abilities

Congenital heart disease is the most common birth defect, and patients are at risk for neurodevelopmental impairment and brain abnormalities. Yet, little is known about the link between brain volumes and cognitive function in adults with congenital heart disease. Forty-four patients and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive testing, assessed with an intelligence quotient and executive function global score. Associations between brain volumes and cognitive function were calculated using linear models. Cognitive function in patients was within the normal range (intelligence quotient: 97.74 (10.76)). Total brain volume was significantly smaller in patients compared to controls (1067.26 (113.53) vs 1113.04 (97.88) cm3, P 0.4). After adjusting for total brain volume, only corpus callosum volume remained significantly smaller (P = 0.03). Smaller total brain volume was associated with poorer overall executive functioning (P = 0.02) and inhibition (P < 0.01), in both patients and controls. The association between total brain volume and overall executive functioning was moderated by parental socioeconomic status (lower socioeconomic status was associated with a stronger association between brain volume and EF; interaction P = 0.03). In adults with congenital heart disease, despite normal intelligence quotient, brain volume alterations persist into adulthood and are related to executive functioning, in particular inhibitory control. Adults coming from low socioeconomic background and with altered brain volumes are especially vulnerable and should thus be followed-up during adulthood to ensure optimal social and educational support. Keywords: ACHD; Brain imaging; Brain volume; Congenital heart disease; Executive function

Bildgebung des Retinoblastoms : Aktueller Stand der Technik und Ausblick in die Zukunft

Hintergrund Das Retinoblastom ist der häufigste bösartige Augentumor im Kindesalter und in bis zu 40 % der Fälle mit einem Tumorprädispositionssyndrom assoziiert (RB1-Mutation). Die Bildgebung ist ein wichtiger Bestandteil der diagnostischen Evaluation von Kindern mit Retinoblastom zum Zeitpunkt der Diagnose und im Follow-up. Ziel der Arbeit Diese Übersichtsarbeit soll den aktuellen Stand der Technik und wichtige diagnostische Aspekte der radiologischen Bildgebung von Kindern mit Retinoblastom aufzeigen mit einem kurzen Ausblick in die Zukunft. Zusätzlich wird ein Überblick über die allgemeine klinische Diagnostik und die Therapiemöglichkeiten gegeben. Material und Methoden Basis der Arbeit ist die Recherche in verschiedenen Literaturdatenbanken sowie eigene Erfahrungen in der Bildgebung des Retinoblastoms. Schlussfolgerung Hochaufgelöste MRT-Bildgebung ist die Bildgebungsmodalität der Wahl bei Kindern mit Retinoblastomen zum Zeitpunkt der Diagnose (Abklärung der Diagnose/möglicher Differenzialdiagnosen, Evaluation der Tumorausdehnung okulär und intrakraniell) und im Follow-up. CT-Untersuchungen sind trotz der charakteristischen Verkalkungen zur Diagnostik nicht mehr indiziert. Da Retinoblastome bis zu 40 % mit Tumorprädispositionssyndromen assoziiert sind, sollte stets auch eine genetische Abklärung erfolgen. = Background Retinoblastoma is the most common malignant eye tumor in children and is associated with tumor predisposition syndrome (RB1 mutation) in up to 40% of cases. Imaging is an important part of the diagnostic workup of children with retinoblastoma both during the initial diagnosis and follow-up. Objectives The goal of this review is to present the current state-of-the-art regarding imaging of children with retinoblastoma, including technical background and diagnostic clues with a brief discussion of future prospects. In addition, we summarize the general clinical diagnostic workup and therapeutic options. Materials and methods Review of the literature and our own experience in the imaging of retinoblastoma. Conclusion High-resolution magnetic resonance imaging (MRI) is the imaging modality of choice in children with retinoblastoma for diagnosis (estimation of diagnosis/differential diagnosis, evaluation of local and intracranial tumor extension) and during follow-up. Despite the characteristic calcifications, computed tomography (CT) examinations are no longer indicated in these patients. Due to the high association with tumor predisposition syndrome, genetic counselling is recommended

Homozygosity for a Novel DOCK7 Variant Due to Segmental Uniparental Isodisomy of Chromosome 1 Associated with Early Infantile Epileptic Encephalopathy (EIEE) and Cortical Visual Impairment

Early infantile epileptic encephalopathy (EIEE) is a severe neurologic and neurodevelopmental disease that manifests in the first year of life. It shows a high degree of genetic heterogeneity, but the genetic origin is only identified in half of the cases. We report the case of a female child initially diagnosed with Leber congenital amaurosis (LCA), an early-onset retinal dystrophy due to photoreceptor cell degeneration in the retina. The first examination at 9 months of age revealed no reaction to light or objects and showed wandering eye movements. Ophthalmological examination did not show any ocular abnormalities. The patient displayed mildly dysmorphic features and a global developmental delay. Brain MRI demonstrated pontine hypo-/dysplasia. The patient developed myoclonic epileptic seizures and epileptic spasms with focal and generalized epileptiform discharges on electroencephalogram (EEG) at the age of 16 months. Genetic screening for a potentially pathogenic DNA sequence variant by whole-exome sequencing (WES) revealed a novel, conserved, homozygous frameshift variant (c.5391delA, p.(Ala1798LeufsTer59)) in exon 42 of the DOCK7 gene (NM_001271999.1). Further analysis by SNP array (Karyomapping) showed loss of heterozygosity (LOH) in four segments of chromosome 1. WES data of the parents and the index patient (trio analysis) demonstrated that chromosome 1 was exclusively inherited from the mother. Four LOH segments of chromosome 1 alternately showed isodisomy (UPiD) and heterodisomy (UPhD). In WES data, the father was a noncarrier, and the mother was heterozygous for this DOCK7 variant. The DOCK7 gene is located in 1p31.3, a region situated in one of the four isodisomic segments of chromosome 1, explaining the homozygosity seen in the affected child. Finally, Sanger sequencing confirmed maternal UPiD for the DOCK7 variant. Homozygous or compound heterozygous pathogenic variants in the DOCK7 (dedicator of cytokinesis 7) gene are associated with autosomal recessive, early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615,859), a rare and heterogeneous group of neurodevelopmental disorders diagnosed during early childhood. To our knowledge, this is the first report of segmental uniparental iso- and heterodisomy of chromosome 1, leading to homozygosity of the DOCK7 frameshift variant in the affected patient

Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry

Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

Objective: To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Methods: Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3h 8min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Results: Twelve out of 12 (100%) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50%). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80%). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. Conclusion: In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. Key Points : • The focal ictal brain regions show hyperperfusion in DSC MR-perfusion imaging. • SWI shows focally diminished cortical veins in hyperperfused ictal regions. • SWI has the potential to identify a focal ictal region in CSE/NCSE

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease:A European Collaboration

Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06–4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23–5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20–21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05–1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58–67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20–6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28–95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08–13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07–1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors