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.

Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: Results from a European Collaboration.

OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.

Effects of hemodynamic alterations and oxygen saturation on cerebral perfusion in congenital heart disease.

BACKGROUND: Patients with severe congenital heart disease (CHD) are at risk for neurodevelopmental impairment. An abnormal cerebral blood supply caused by the altered cardiac physiology may limit optimal brain development. The aim of this study was to evaluate the effect of a systemic-to-pulmonary shunt, aortic arch obstruction and arterial oxygen saturation on cerebral perfusion in patients with severe CHD. METHODS: Patients with severe CHD requiring cardiac surgery within the first six weeks of life, who underwent pre- and/or postoperative brain magnetic resonance imaging (MRI), and healthy controls with one postnatal scan were included. Cerebral perfusion in deep and cortical gray matter was assessed by pseudocontinuous arterial spin labeling MRI. RESULTS: We included 59 CHD and 23 healthy control scans. The presence of a systemic-to-pulmonary shunt was associated with decreased perfusion in cortical (p = 0.003), but not in deep gray matter (p = 0.031). No evidence for an effect of aortic arch obstruction and arterial oxygen saturation on cerebral perfusion was found. After adjusting for hemodynamic and oxygen saturation parameters, deep (p = 0.018) and cortical (p = 0.012) gray matter perfusion was increased in patients with CHD compared to controls. CONCLUSION: We detected regional differences in compensation to the cerebral steal effect in patients with severe CHD. IMPACT: Patients with severe congenital heart disease (CHD) have altered postnatal brain hemodynamics. A systemic-to-pulmonary shunt was associated with decreased perfusion in cortical gray matter but preserved perfusion in deep gray matter, pointing towards regional differences in compensation to the cerebral steal effect. No effects of aortic arch obstruction and arterial oxygenation on cerebral perfusion were seen. Cerebral perfusion was increased in patients with CHD compared to healthy controls after adjusting for hemodynamic alterations and oxygen saturation. To improve neuroprotection and neurodevelopmental outcomes, it is important to increase our understanding of the factors influencing cerebral perfusion in neonates with severe CHD.

Treatment of NF1-Associated Optic Pathway/Hypothalamic Gliomas in Patients With Diencephalic Syndrome.

Diencephalic syndrome is usually associated with tumors in the hypothalamic region, rarely occurring in patients with neurofibromatosis type 1 (NF1)-associated gliomas. We describe the clinical presentation and response to treatment in 3 patients with NF1 presenting with diencephalic syndrome as first symptom of optic pathway/hypothalamic glioma (OPHG). Because of the rarity of this constellation, knowledge about the clinical course and best treatment options for patients with NF1-associated OPHG and diencephalic syndrome is still limited. All 3 patients showed good response to treatment with normalization of body mass index and decrease in tumor volume within 6 months.

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

BACKGROUND: 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.

Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant bilateral optic nerve hypoplasia.

Optic nerve hypoplasia (ONH) is a congenital optic nerve abnormality caused by underdevelopment of retinal ganglion cells (RGCs). Despite being a rare disease, ONH is the most common optic disk anomaly in ophthalmological practice. So far, mutations in several genes have been identified as causative; however, many cases of ONH remain without a molecular explanation. The early transcription factor atonal basic-helix-loop-helix (bHLH) transcription factor 7 (ATOH7) is expressed in retinal progenitor cells and has a crucial role in RGC development. Previous studies have identified several mutations in the ATOH7 locus in cases of eye developmental diseases such as non-syndromic congenital retinal non-attachment and persistent hyperplasia of the primary vitreous. Here we present two siblings with a phenotype predominated by bilateral ONH, with additional features of foveal hypoplasia and distinct vascular abnormalities, where whole-exome sequencing identified two compound heterozygous missense mutations affecting a conserved amino acid residue within the bHLH domain of ATOH7 (NM_145178.3:c.175G>A; p.(Ala59Thr) and c.176C>T; p.(Ala59Val)). ATOH7 expression constructs with patient single nucleotide variants were cloned for functional characterization. Protein analyses revealed decreased protein amounts and significantly enhanced degradation in the presence of E47, a putative bHLH dimerization partner. Protein interaction assays revealed decreased heterodimerization and DNA-binding of ATOH7 variants, resulting in total loss of transcriptional activation of luciferase reporter gene expression. These findings strongly support pathogenicity of the two ATOH7 mutations, one of which is novel. Additionally, this report highlights the possible impact of altered ATOH7 dimerization on protein stability and function.

The "Eyelet Sign" as an MRI Clue for Inflammatory Brown Syndrome.

BACKGROUND: Brown syndrome is characterized by a restrictive elevation deficit of the affected eye in adduction. Besides the well-known congenital form, different acquired etiologies including inflammation, trauma, and surgery may prevent the superior oblique (SO) tendon from gliding freely through the trochlea on attempted upgaze. We present MRI findings in pediatric and adult patients with inflammatory acquired Brown syndrome. METHODS: Retrospective review of clinical and MRI findings of 6 patients (4 children: median age 8.4 years [range 6.1-8.7]; 2 adults: age 46.4 and 51.1 years). Median follow-up was 23 months (range 1-52). RESULTS: In all 6 patients, orbital MRI demonstrated inflammatory changes of the SO tendon-trochlea complex. A striking feature was circumferential contrast enhancement of the trochlea with central sparing where the tendon passes, reminiscent of an eyelet. In all cases, the motility restriction improved either spontaneously or with systemic anti-inflammatory treatment. Although both adult patients had a history of known seronegative spondyloarthritis, there was no associated systemic condition in the children in our series. CONCLUSIONS: Both in children and in adults, MRI can provide evidence of inflammatory changes located at the trochlea-tendon complex in acquired Brown syndrome here referred to as the "eyelet sign," which may be helpful in confirming the clinical diagnosis and guide appropriate treatment.

Determination of Anatomical Levels in Spina Bifida Fetuses with Ultrasound and MRI.

PURPOSE: The goal of this study was to assess the accuracy of prenatal anatomical level determination by ultrasound (US) and magnetic resonance imaging (MRI) by analyzing the congruence with the "true" anatomical level identified by postnatal MRI. PATIENTS AND METHODS: The first 60 patients undergoing fetal myelomeningocele surgery at The Zurich Center for Fetal Diangosis and Therapy were included in this study. Anatomical levels (i. e., first dysraphic vertebra) determined by prenatal US and MRI were compared to postnatal MRI. The level of agreement between the imaging modalities was evaluated with a Cohen's kappa test. Results > 0.6 were interpreted as good agreement, > 0.8 as excellent. RESULTS: The exact congruence between prenatal US and MRI compared to postnatal MRI was 33 % and 48 %, respectively, for an accuracy within one level difference of 80 % and 90 %, and within two levels difference of 95 % and 98 %, respectively. The level of agreement of prenatal US and MRI compared to postnatal MRI was 0.62 and 0.79, respectively. Most of the prenatally incorrectly assigned levels were assigned too high (worse) than the "true" level (US 88 % vs. MRI 65 %). CONCLUSION: Reliable exact prenatal level determination by US and MRI is not possible. However, the prenatal determination of the anatomical level of the lesion is good within one level margin of error. Prenatal US as well as MRI demonstrate a systematic error towards higher levels. The above considerations must be integrated into prenatal counselling.

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.

BACKGROUND: Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known. OBJECTIVE: We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease. METHODS: Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids. RESULTS: Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes. CONCLUSION: ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

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.

Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia.

PURPOSE: This study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable. METHODS: We compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts. RESULTS: In 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient-derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. CONCLUSION: Taken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome.

Sinus pericranii with facial involvement-A great mimicker.

Sinus pericranii is a rare vascular anomaly characterized by an abnormal communication between the intra- and extracranial venous systems through a calvarial defect(s). We present three cases of congenital sinus pericranii with facial involvement, emphasizing its cutaneous presentation with diagnostic pitfalls and discuss the multidisciplinary management of this vascular anomaly.

Fetal surgery for spina bifida in Zurich: results from 150 cases.

PURPOSE: Over the past 10 years, over 150 fetal spina bifida surgeries were performed at the Zurich Center for Fetal Diagnosis and Therapy. This study looks at surrogates for success and failure of this approach. METHODS: We focused on key outcome parameters including hydrocephalus shunt rate at one year, bladder control at 4, independent ambulation at 3 years, and maternal, fetal, and neonatal complications. RESULTS: From the first 150 patients undergoing fetal surgery for spina bifida, 148 (98.7%) were included in the study. Maternal-fetal surgery was uneventful in 143/148 (97%) cases. Intraoperative problems included resuscitation in 4/148 fetuses (2.7%). 1/148 fetuses (0.7%) died on postoperative day 4. Maternal complications included chorioamniotic membrane separation in 22/148 (15%), lung embolism in 3/148 (2.1%), chorioamnionitis in 2/148 (1.4%), AV-block III and uterine rupture in 1/148 each (0.7%). 1/148 (0.7%) newborn death was recorded. Hindbrain herniation was identified preoperatively in 132/148 (90%) fetuses and resolved completely in 119/132 (90%). At one year, 39/106 (37%) children had required a CSF diversion. At 4 years, 4/34 patients (12%) had normal bladder control. At 3 years, 48/57 (84%) walked independently. CONCLUSION: A majority of patients benefitted from prenatal intervention, in that the shunt rate was lower and the rates of continent and walking patients were higher than reported with postnatal care.

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.

Pontocerebellar Hypoplasia: a Pattern Recognition Approach.

Pontocerebellar hypoplasias (PCH) represent a heterogeneous group of very rare disorders with reduced volume of pons and cerebellum. The term is purely descriptive and does not imply a genetic progressive disease. Currently (as of Jan 01, 2020), 13 different types are listed in OMIM (Online Mendelian Inheritance in Man), associated with 19 different genes. However, a large group of similar imaging patterns is known, and it is unclear why some are labeled as PCH, while others are not. The latter include CASK- and VLDLR-associated disorders, some tubulinopathies, certain dystroglycanopathies, a few congenital disorders of glycosylation (CDG) syndromes, several forms associated with rare variants (e.g., DCK1, WDR81, ITPR1), and "cerebellar disruption of prematurity"-an acquired etiology. The objective of this paper is to elaborate a pattern recognition approach, mainly imaging-based, to facilitate a timely and accurate diagnosis, to narrow the differential diagnosis, and to enable targeted additional (genetic) investigations. We describe magnetic resonance imaging (MRI) findings and offer "checklists" for infratentorial findings (e.g., non-lobulated vermis, dragonfly pattern of the cerebellum, cerebellar cysts, brainstem kinking, longitudinal grooves along the brainstem, flat pons) as well as for supratentorial anomalies (e.g., agenesis of corpus callosum, optic atrophy, simplified gyral pattern, and hypomyelination). The clinical context and laboratory investigations need to be considered as well. We also provide a "checklist" for clinical features. A systematic analysis of imaging and clinical features can assist in narrowing the differential diagnosis and permitting more targeted genetic testing. Some imaging patterns are diagnostic.

A single supratentorial high-grade neuroepithelial tumor with two distinct BCOR mutations, exceptionally long complete remission and survival.

Here, we present a patient with high-grade neuroepithelial tumors with mutations in the BCL6 corepressor BCOR (HGNET-BCOR), a rare, highly malignant brain tumor with poor prognosis. The patient underwent gross total tumor resection (GTR), high-dose chemotherapy, and, after local relapse, GTR, proton radiation, and chemotherapy. After a 7.5 year-long complete remission, the tumor recurred locally, was treated by GTR, and responded to temozolomide treatment. In addition to an internal tandem duplication in BCOR common to the majority of HGNET-BCOR cases, molecular analysis revealed a second BCOR mutation in this tumor: a frame shift mutation. The combination of these mutations was associated with relatively low BCOR expression compared to other HGNET-BCOR cases.

Left temporal plane growth predicts language development in newborns with congenital heart disease.

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age.

Spinal meningeal cyst in a child with Marfan syndrome: A potential cause for apparent dural puncture during caudal epidural block.

We report a complication from caudal epidural block for anesthesia in a 4-year-old child with Marfan syndrome who was undergoing lensectomy, orchidopexy, and circumcision resulting in apparent accidental dural puncture. Subsequent magnetic resonance imaging revealed a lumbosacral spinal meningeal cyst.

Microvascular perfusion of the placenta, developing fetal liver, and lungs assessed with intravoxel incoherent motion imaging.

BACKGROUND: In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. PURPOSE: To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). FIELD STRENGTH/SEQUENCE: In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. ASSESSMENT: Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. STATISTICAL TESTS: Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). RESULTS: Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. DATA CONCLUSION: Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.