New Insights Into the Spectrum of RASopathies: Clinical and Genetic Data in a Cohort of 121 Spanish Patients.

Noonan syndrome and related disorders are a group of well-known genetic conditions caused by dysregulation of the Ras/mitogen-activated protein kinase (RAS/MAPK) pathway. Because of the overlap of clinical and molecular features, they are now called RASopathies. In this study, we retrospectively analyzed the clinical data of 121 patients with a molecularly confirmed diagnosis of RASopathy, describing frequencies for clinical features in all organ systems as well as molecular data.

Parental or Trio Magnetic Resonance Imaging to Improve Prenatal Counseling in Brain Anomalies.

Objective: To assess whether targeted magnetic resonance of one or both of the progenitors could refine the diagnosis in cases of fetal brain anomalies with uncertain prognosis.

Methods: Single-center retrospective case series, where targeted magnetic resonance was performed on one or both of progenitors after a suspicion of fetal complex brain anomalies, and prognosis was unclear based solely on fetal tests (neurosonogram, fetal magnetic resonance, and genetic testing).

Results: Seven women were included.

Pituitary macroadenomas in childhood and adolescence: a clinical analysis of 7 patients.

Background: Pituitary adenomas (PPAs) are uncommon in childhood and adolescence, accounting for 2-6% of all intracranial neoplasms. Delayed puberty, growth retardation, galactorrhea and weight gain are common features at presentation in pediatric patients. Functional tumors constitute a vast majority (90%) of PPAs, with the most frequent being prolactinomas.

Myocardial tissue characterization by cardiovascular magnetic resonance T1 mapping and pericardial fat quantification in adolescents with morbid obesity. Cardiac dimorphism by gender.

Purpose: Changes in the myocardial extracellular matrix (ECM) identified using T1 mapping cardiovascular magnetic resonance (CMR) have been only reported in obese adults, but with opposite conclusions. The objectives are to assess the composition of the myocardial ECM in an obese pediatric population without type 2 diabetes by quantifying native T1 time, and to quantify the pericardial fat index (PFI) and their relationship with cardiovascular risk factors.

Methods: Observational case-control research of 25 morbidly obese adolescents and 13 normal-weight adolescents.

Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.

Background And Objectives: Genetic white matter disorders (GWMD) are of heterogeneous origin, with >100 causal genes identified to date. Classic targeted approaches achieve a molecular diagnosis in only half of all patients. We aimed to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD while identifying novel phenotypes and candidate genes.

Enterovirus-A71 Rhombencephalitis Outbreak in Catalonia: Characteristics, Management and Outcome.

Background: Between April and June 2016, an outbreak of rhombencephalitis (RE) caused by enterovirus (EV) A71 was detected in Catalonia, Spain-the first documented in Western Europe. The clinical characteristics and outcome of patients with this condition differed from those reported in outbreaks occurring in Southeast Asia.

Methods: Observational, multicenter study analyzing characteristics, treatment and outcome of patients with EV-A71 rhombencephalitis diagnosed in 6 publicly funded hospitals within the Catalonian Health Institute.

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix-intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old.

Perinatal outcomes and central nervous system abnormalities following intrauterine fetal transfusion: 17 years' experience in a tertiary center.

Background: This study aimed to describe the perinatal outcome and central nervous system (CNS) anomalies in fetuses undergoing red blood cell (RBC) intrauterine transfusion (IUT).

Methods And Materials: This was an observational single-cohort study carried out at Vall d'Hebron University Hospital in Barcelona, Spain, between 2002 and 2018 in women undergoing RBC IUT for suspected fetal anemia. Primary outcomes were adverse perinatal outcome (intrauterine or neonatal death and termination of pregnancy [TOP]), prenatal or postnatal CNS anomalies, and significant neurological impairment.

Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene.

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres.

Pediatric minor head injury imaging practices: results from an ESPR survey.

Purpose: Computed tomography (CT) for minor head injury exposes a large number of children to ionizing radiation, with an associated increased lifetime risk of malignancy. To study imaging practices for children with minor head injury and the level of awareness of radiologists of the current clinical decision rules for minor traumatic brain injury (TBI).

Methods: A questionnaire consisting of 17 questions was distributed electronically to 472 ESPR members.

Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies.

The main objective of this study was to evaluate the accuracy of prenatal ultrasound to diagnose corpus callosum alterations, compared to prenatal magnetic resonance imaging (MRI), postnatal image techniques (ultrasound and/or MRI), and post-mortem examination in terminated pregnancies. Retrospective review of 86 cases of prenatal ultrasound diagnosis of corpus callosum anomalies between January 2007 and December 2015 at a third level Maternal Fetal Medicine center. The study reviewed the findings of prenatal ultrasound and MRI, post-mortem examination in cases of termination of pregnancy (TOP) or stillbirths and postnatal ultrasound, and MRI in neonates.

Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.

Aim: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations.

Method: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts.

Results: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression.

Measurements of signal intensity of globus pallidus and dentate nucleus suggest different deposition characteristics of macrocyclic GBCAs in children.

Introduction: The safety of using GBCAs to enhance the visibility of body structures is currently discussed due to possible gadolinium retention in brain structures. The aim of the study was to evaluate the effect of multiple exposures to macrocyclic GBCAs in children.

Materials And Methods: This retrospective, single-center study included data from 43 patients who had received ≥4 injections of macrocyclic GBCAs during MRI examinations over performed over 8 to 84 months.

Brain lesion scores obtained using a simple semi-quantitative scale from MR imaging are associated with motor function, communication and cognition in dyskinetic cerebral palsy.

Purpose: To characterise brain lesions in dyskinetic cerebral palsy (DCP) using the semi-quantitative scale for structural MRI (sqMRI) and to investigate their relationship with motor, communication and cognitive function.

Materials And Methods: Thirty-nine participants (19 females, median age 21y) with DCP were assessed in terms of motor function, communication and a variety of cognitive domains. Whole-head magnetic resonance imaging (MRI) was performed including T1-MPRAGE, T2 turbo spin echo (axial plane), and fluid attenuated inversion recovery images (FLAIR).

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function.

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type.

Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions.

Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes.

Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings.

Mutations in the ACTA2 gene lead to a multisystemic smooth muscle dysfunction syndrome that causes vascular disease, congenital mydriasis, and variable presentation of urinary and gastrointestinal problems. The heterozygous Arg179 mutation is associated with a distinctive cerebrovascular phenotype. We report the cases of two newborn siblings with heterozygous ACTA2 Arg179Cys substitution and provide neuroimaging exams that demonstrate the distinctive cerebrovascular phenotype, also associated with variable degree of hypoplasia of the vertebro-basilar circulation as well as hypoxic-ischemic lesions.

Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates.

Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV).

Imaging abusive head trauma: why use both computed tomography and magnetic resonance imaging?

Abusive head trauma is the leading cause of death in child abuse cases. The majority of victims are infants younger than 1 year old, with the average age between 3 and 8 months, although these injuries can be seen in children up to 5 years old. Many victims have a history of previous abuse and the diagnosis is frequently delayed.

Recommendations for the radiological diagnosis and follow-up of neuropathological abnormalities associated with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic condition with multisystem involvement, characterized by the development of tumors and other abnormalities in organs such as the brain, retina, skin, heart, kidneys, and lungs. Most patients have neuropathological abnormalities such as cortical tubers, white matter radial migration lines, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). These lesions are associated with different neurological manifestations that are frequently associated with TSC.

Evolution of fetal subependymal cysts throughout gestation.

Subependymal cysts are secondary to brain germinal matrix hemorrhage or infarction and are associated with fetal chromosomal and metabolic conditions, as well as infections. They are found in 1-3% of neonates in the first days of life and have been described in fetuses, although much less frequently. We report the prenatal diagnosis of a case of subependymal cysts first visualized at 12 weeks' gestation and its evolution throughout pregnancy and after birth.

At-risk brain tissue identified with arterial spin labeling in neurotuberculosis.

A 13-year-old immunocompromised girl developed neurotuberculosis. Arterial spin labeling technique indicated areas of hypoperfusion in the vascular territories of the left posterior cerebral artery and superior cerebellar artery without restricted diffusion, suggesting early tuberculous arteritis. MR angiography confirmed vascular involvement, so adjunctive anticoagulant therapy was initiated.