(What's the story) morning glory? MRI findings in morning glory disc anomaly.

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).

Diagnostic Ultrasound for Acute Appendicitis: The Gold Standard.

BACKGROUND: Acute appendicitis may present a diagnostic dilemma. The aim of this study was to review the accuracy of ultrasound in the diagnosis of paediatric acute appendicitis. METHOD: Ultrasound studies performed for investigation of appendicitis during 2015-2021 were retrieved from a tertiary paediatric hospital database and reviewed. Medical records were reviewed to determine operative intervention, further imaging, and final diagnosis. Diagnostic accuracy was assessed by sensitivity, specificity, predictivity, and overall accuracy. All appendicectomy specimens underwent histopathological confirmation. This study was approved by the local Human Research Ethics Committee. RESULTS: A total of 8555 consecutive ultrasound examinations were performed during the study period. Mean patient age was 10.8 years ( ± 3.7). Overall diagnostic accuracy was 96.1% (8221/8555) with a visualisation rate of 91.0%. Sensitivity and specificity were 96.2% (CI 95.3-97.0%) and 96.1% (CI 95.6-96.5%), respectively. When limited to positive/negative scans, sensitivity was 99.6% (CI 99.2-99.8%) and specificity 99.0% (CI 98.7-99.3%). Positive and negative predictive values were 96.9% and 99.9%, respectively. Repeat ultrasound following a non-diagnostic scan led to a definitive diagnosis in 76.1%. Negative appendicectomy rate was 5.5% overall in children who had undergone pre-operative ultrasound (107/1938), and 4.4% when other surgical pathologies were excluded. CONCLUSION: Ultrasound examination provides gold-standard accuracy in the diagnosis of paediatric appendicitis and reduces rates of negative appendicectomy. Given the disadvantages of computed tomography and magnetic resonance imaging, ultrasound should be considered the first-line investigation of choice in the diagnosis of acute appendicitis in children. LEVEL OF EVIDENCE: III.

Neuroimaging Findings in Axenfeld-Rieger Syndrome: A Case Series.

Axenfeld-Rieger syndrome is an autosomal dominant condition associated with multisystemic features including developmental anomalies of the anterior segment of the eye. Single nucleotide and copy number variants in the paired-like homeodomain transcription factor 2 (PITX2) and forkhead box C1 (FOXC1) genes are associated with Axenfeld-Rieger syndrome as well as other CNS malformations. We determined the association between Axenfeld-Rieger syndrome and specific brain MR imaging neuroradiologic anomalies in cases with or without a genetic diagnosis. This case series included 8 individuals with pathogenic variants in FOXC1; 2, in PITX2; and 2 without a genetic diagnosis. The most common observation was vertebrobasilar artery dolichoectasia, with 46% prevalence. Other prevalent abnormalities included WM hyperintensities, cerebellar hypoplasia, and ventriculomegaly. Vertebrobasilar artery dolichoectasia and absent/hypoplastic olfactory bulbs were reported in >50% of individuals with FOXC1 variants compared with 0% of PITX2 variants. Notwithstanding the small sample size, neuroimaging abnormalities were more prevalent in individuals with FOXC1 variants compared those with PITX2 variants.

Neuroimaging of Ocular Abnormalities in Children.

In this article, we will discuss the essential MR imaging protocol required for the assessment of ocular abnormalities including malignancies. Then we will describe relevant anatomy, ocular embryogenesis, and genetics to establish a profound understanding of pathophysiology of the congenital ocular malformations. Finally, we will discuss pediatric ocular malignancies, benign mimics, and the most common congenital ocular malformations with case examples and illustrations and give tips on how to distinguish these entities on neuroimaging.

Ultrasound guided hydrostatic enema reduction of ileocolic intussusception: a safe and effective technique.

BACKGROUND: Currently, the primary management of ileocolic intussusception in children is usually by non-operative image-guided enema reduction. In most centres around the world especially in Australasia the predominant technique is the pneumatic reduction under fluoroscopic guidance. At our institution, we have been performing ultrasound-guided hydrostatic reduction since 2012.This is an audit to determine the efficacy and safety of ultrasound-guided hydrostatic reduction for intussusception. METHODS: Following ethics approval, a retrospective review of all patients presenting to our institution with intussusception and subsequently undergoing hydrostatic reduction over a period of 9 years (2012 to-2020) was performed. The parameters studied included (i) successful reduction, (ii) recurrence, (iii) need for surgery and (iv) lead point at surgery. RESULTS: The mean age at presentation was 12 months. One hundred and eight children were diagnosed to have ileocolic intussusception. One hundred and six underwent ultrasound-guided hydrostatic reduction with successful reduction in 96 (90.5%) patients. Reduction was unsuccessful in 10 patients (9.5%). Of these eight were noted to have a pathological lead point (four-Meckel's diverticulum and four-Lymphoma) at the time of the surgery. The intussusception recurred in six patients (6.25%) within 24 h. No reduction related perforation occurred during the study period. CONCLUSION: Ultrasound-guided hydrostatic reduction is a safe and effective technique for managing intussusception as it allows continuous monitoring of the reduction of the intussusception without exposing the children to ionizing radiation.

Current and future funding streams for paediatric postmortem imaging: European Society of Paediatric Radiology survey results.

BACKGROUND: Perinatal and childhood postmortem imaging has been accepted as a noninvasive alternative or adjunct to autopsy. However, the variation in funding models from institution to institution is a major factor prohibiting uniform provision of this service. OBJECTIVE: To describe current funding models employed in European and non-European institutions offering paediatric postmortem imaging services and to discuss the perceived barriers to future postmortem imaging service provision. MATERIALS AND METHODS: A web-based 16-question survey was distributed to members of the European Society of Paediatric Radiology (ESPR) and ESPR postmortem imaging task force over a 6-month period (March-August 2021). Survey questions related to the radiologic and autopsy services being offered and how each was funded within the respondent's institute. RESULTS: Eighteen individual responses were received (13/18, 72.2% from Europe). Only one-third of the institutions (6/18, 33.3%) have fully funded postmortem imaging services, with the remainder receiving partial (6/18, 33.3%) or no funding (5/18, 27.8%). Funding (full or partial) was more commonly available for forensic work (13/18, 72%), particularly where this was nationally provided. Where funding was not provided, the imaging and reporting costs were absorbed by the institute. CONCLUSION: Increased access is required for the expansion of postmortem imaging into routine clinical use. This can only be achieved with formal funding on a national level, potentially through health care commissioning and acknowledgement by health care policy makers and pathology services of the value the service provides following the death of a fetus or child. Funding should include the costs involved in training, equipment, reporting and image acquisition.

Loss of non-motor kinesin KIF26A causes congenital brain malformations via dysregulated neuronal migration and axonal growth as well as apoptosis.

Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA sequencing in KIF26A knockout organoids revealed transcriptional changes in MAPK, MYC, and E2F pathways. Our findings illustrate the pathogenesis of KIF26A loss-of-function variants and identify the surprising versatility of this non-motor kinesin.

Ultrasound diagnosis of hypertrophic pyloric stenosis - Time to change the criteria.

Introduction: Ultrasound is the examination of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). A correct diagnosis is dependent on the technique and measurement accuracy. However, in the world literature there is a wide range of values suggested for the diagnosis of this condition. The current minimum measurements used to diagnose HPS seem excessively large, and therefore, we set out to redefine these values. Methods: A retrospective study was performed on 607 patients (615 scans) being investigated for HPS. The length and transverse diameter of the pyloric canal, and thickness of the pyloric muscle were measured. All results were correlated with clinical and surgical findings. Results: In this study, the muscle thickness in the normal group was <2.0 mm than in HPS infants having a muscle thickness of 2.0-5.0 mm. All the pyloric canal lengths in the normal group were <5.0 mm than in those with HPS having a length of 10.0-24.0 mm. The transverse diameters ranged from 6.0 to 11.0 mm in the normal group compared with those with HPS having a diameter between 8.0 and 16.0 mm. Conclusions: The current criteria for sonographic diagnosis of HPS should be redefined. The canal length is the single most important discriminator, with a clear separation between normal and abnormal. The commonly used 16.0-mm measurement is too long and should be reduced to 10.0 mm (without the risk of false positives). In many cases, the muscle thickness in those with HPS is as low as 2.0 mm, considerably less than the 3.0 mm that is currently used. The transverse diameter is not a useful discriminator for HPS. The use of current values will delay the diagnosis and timely treatment of this condition.

Multi-suture craniosynostosis in c.1570C>T (p.Arg524Trp) mutated TRAF7: a case report.

Craniosynostosis is a condition of premature fusion of the cranial sutures. Multi-suture craniosynostosis has been found to be associated with a number of syndromes and underlying gene mutations. Tumour necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins interacting with cell surface receptors or other signalling molecules. TRAF7 is one of the factors involved in multiple biologic processes, including ubiquitination, myogenesis and toll-like receptor signalling. Here, we report a child who presented with multi-suture craniosynostosis and had the uncommon c.1570C>T (p.Arg524Trp) variant of TRAF7.

Neuroradiological Mimics of Periventricular Leukomalacia.

AIM: Periventricular leukomalacia (PVL) is a term reserved to describe white matter injury in the premature brain. In this review article, the authors highlight the common and rare pathologies mimicking the chronic stage of PVL and propose practical clinico-radiological criteria that would aid in diagnosis and management. METHODS AND RESULTS: The authors first describe the typical brain MRI (magnetic resonance imaging) features of PVL. Based on their clinical presentation, pathologic entities and their neuroimaging findings were clustered into distinct categories. Three clinical subgroups were identified: healthy children, children with stable/nonprogressive neurological disorder, and those with progressive neurological disorder. The neuroradiological discriminators are described in each subgroup with relevant differential diagnoses. The mimics were broadly classified into normal variants, acquired, and inherited disorders. CONCLUSIONS: The term "PVL" should be used appropriately as it reflects its pathomechanism. The phrase "white matter injury of prematurity" or "brain injury of prematurity" is more specific. Discrepancies in imaging and clinical presentation must be tread with caution and warrant further investigations to exclude other possibilities.

Fibrodysplasia ossificans progressiva: Diagnosis with ultrasound.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare connective tissue disease, diagnosed by genetic testing. This is the first report in English literature wherein an ultrasound examination suggested this specific diagnosis. In this case, a two month old girl presented with bi-parieto-occipital swellings that were being managed as subgaleal haematoma. The parents were anxious that there was no resolution of the swellings. The suspicion of FOP was raised during the ultrasound examination where a review of the images prompted a questioning of the parents about other lesions in the body. Ultrasound examination of a lump in the thigh revealed calcifications in the vastus lateralis muscle. The appearances on the ultrasound combined with the presence of hallucis valgi suggested a diagnosis of FOP. The diagnosis was subsequently confirmed by genetic studies. This case highlights the need for good communication between the physician, patient and the imaging department.

Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders.

Primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders (MCPH-SCKS) include a heterogeneous group of autosomal recessive inherited diseases characterized by primary (congenital) microcephaly, the absence of visceral abnormalities, and a variable degree of cognitive impairment, short stature and facial dysmorphism. Recently, biallelic variants in the nuclear pore complex (NPC) component nucleoporin 85 gene (NUP85) were reported to cause steroid-resistant nephrotic syndrome (SRNS). Here, we report biallelic variants in NUP85 in two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS, thereby expanding the phenotypic spectrum of NUP85-linked diseases. Structural analysis predicts the identified NUP85 variants cause conformational changes that could have an effect on NPC architecture or on its interaction with other NUPs. We show that mutant NUP85 is, however, associated with a reduced number of NPCs but unaltered nucleocytoplasmic compartmentalization, abnormal mitotic spindle morphology, and decreased cell viability and proliferation in one patient's cells. Our results also indicate the link of common cellular mechanisms involved in MCPH-SCKS spectrum disorders and NUP85-associated diseases. In addition to the previous studies, our results broaden the phenotypic spectrum of NUP85-linked human disease and propose a role for NUP85 in nervous system development.

Ultrasound imaging as the first line of investigation to diagnose intestinal malrotation in children: Safety and efficacy.

BACKGROUND: Upper gastrointestinal contrast study is considered the gold standard investigation to diagnose intestinal malrotation and midgut volvulus which is potentially devastating condition. Ultrasound imaging is an alternative but has been considered unreliable due to significant false negative results. At our institution we have been using ultrasound imaging as the first line investigation to diagnose malrotation since 2008 with a preliminary study of 139 patients published in 2014. This is an ongoing audit of a further much larger cohort of patients to determine the efficacy and safety of ultrasound imaging in the diagnosis of intestinal malrotation. MATERIALS AND METHODS: Following ethics approval, a retrospective analysis of a prospectively collected patient database undergoing ultrasound scans to exclude malrotation at our centre was performed from 2012 to 2019. RESULTS: 539 patients underwent ultrasound to assess for malrotation. The mean age of presentation was 365 days (median 30 days, mode 1 day). Malrotation was diagnosed in 17 with 5 having volvulus, with findings confirmed at surgery. 12 had equivocal findings and subsequent contrast studies ruled out malrotation. The remaining 510 patients with no evidence of malrotation were managed conservatively. CONCLUSION: We have shown ultrasound to be a safe and effective tool to assess intestinal malrotation without exposure to ionizing radiation. LEVEL OF EVIDENCE: Level IV.

Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia.

BACKGROUND: Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. CASE PRESENTATION: We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. CONCLUSION: We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

Neuroimaging manifestations of epidermal nevus syndrome.

Epidermal nevus syndrome (ENS) represents a diverse group of rare neurocutaneous diseases associated with the presence of characteristic epidermal nevi (EN) in the skin and extracutaneous manifestations in the eyes, skeletal, urogenital and central nervous systems. We present a case series of 7 children with ENS, with specific attention to the neuroradiological characteristics of this entity.

Current state of perinatal postmortem magnetic resonance imaging: European Society of Paediatric Radiology questionnaire-based survey and recommendations.

BACKGROUND: Postmortem magnetic resonance imaging (MRI) in perinatal and childhood deaths is increasingly used as a noninvasive adjunct or alternative to autopsy. Imaging protocols vary between centres and consensus guidelines do not exist. OBJECTIVE: Our aim was to develop practical, standardised recommendations for perinatal postmortem MRI. MATERIALS AND METHODS: Recommendations were based on the results of two surveys regarding local postmortem MRI practices sent electronically to all 14 members of the European Society of Paediatric Radiology (ESPR) Postmortem Imaging Task Force and 17 members of the International Society of Forensic Radiology and Imaging Task Force (25 different centres). RESULTS: Overall, 11/14 (78.6%) respondents from different institutions perform postmortem MRI. All of these centres perform postmortem MRI for perinatal and neonatal deaths, but only 6/11 (54.5%) perform imaging in older children. CONCLUSION: We propose a clinical standard for postmortem MRI sequences plus optional sequences for neuroimaging and cardiac anatomy depending on available scanning time and referral indications.