The (extended) achondroplasia foramen magnum score has good observer reliability.

BACKGROUND: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed. OBJECTIVE: To assess the interobserver reliability of the achondroplasia foramen magnum score. MATERIALS AND METHODS: Base of skull imaging of children with achondroplasia under the care of Sheffield Children's Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability. RESULTS: Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62-0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing. CONCLUSION: The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.

Avoiding skull radiographs in infants with suspected inflicted injury who also undergo head CT: "a no-brainer?"

OBJECTIVES: To assess whether head CT with 3D reconstruction can replace skull radiographs (SXR) in the imaging investigation of suspected physical abuse (SPA)/abusive head trauma (AHT). METHODS: PACS was interrogated for antemortem skeletal surveys performed for SPA, patients younger than 2 years, SXR and CT performed within 4 days of each other. Paired SXR and CT were independently reviewed. One reviewer analysed CT without and (3 months later) with 3D reconstructions. SXR and CT expert consensus review formed the gold standard. Observer reliability was calculated. RESULTS: A total of 104 SXR/CT examination pairs were identified, mean age 6.75 months (range 4 days to 2 years); 21 (20%) had skull fractures; two fractures on CT were missed on SXR. There were no fractures on SXR that were not seen on CT. For SXR and CT, respectively: PPV reviewer 1, 95% confidence interval (CI) 48-82% and 85-100%; reviewer 2, 67-98% and 82-100%; and NPV reviewer 1, 95%, CI 88-98% and 96-100%; reviewer 2, 88-97% and 88-98%. Inter- and intra-observer reliability were respectively the following: SXR, excellent (kappa = 0.831) and good (kappa = 0.694); CT, excellent (kappa = 0.831) and perfect (kappa = 1). All results were statistically significant (p < 0.001). CONCLUSIONS: CT has greater diagnostic accuracy than SXR in detecting skull fractures which is increased on concurrent review of 3D reconstructions and should be performed in every case of SPA/AHT. SXR does not add further diagnostic information and can be omitted from the skeletal survey when CT with 3D reconstruction is going to be, or has been, performed. KEY POINTS: • Head CT with 3D reconstruction is more sensitive and specific for the diagnosis of skull fractures. • Skull radiographs can be safely omitted from the initial skeletal survey performed for suspected physical abuse when head CT with 3D reconstruction is going to be, or has been, performed.

Benefits and Limitations of the Minimally Invasive Postmortem: A Review of an Innovative Service Development.

INTRODUCTION: Pediatric postmortem (PM) rates have significantly declined, creating a need for effective minimally invasive alternatives to correlate with parental wishes. We review the use of a minimally invasive fetal and neonatal PM service further to preliminary findings published in 2015. MATERIALS AND METHODS: Cases taken from the mortuary electronic database from 2012 to 2017 are analyzed. The minimally invasive service consisted primarily of external examination, magnetic resonance imaging (MRI), and placental examination. Any significant conditions found noted. All pathology reports include a Relevant Condition at Death (ReCoDe) obstetric classification. Reports analyzed to determine which aspects of the service provided positive information. RESULTS: Of 1498 perinatal postmortems, 105 (7%) were PM MRI, of which 75.24% were intrauterine fetal deaths. Relevant conditions were identified in 94 cases (89.52%), and ReCoDe categories in 80 cases (76.19%). Moreover, 90% of cases had a ReCoDe condition, with 10% unclassified. Seven cases had more than 1 ReCoDe. Main conditions related to placenta (32.5%) and umbilical cord (27.5%). The most informative elements were placental examination and MRI. CONCLUSION: Minimally invasive PMs are a viable alternative to traditional autopsy when this option is refused. However, further case analysis is needed to determine potential bias toward certain classification codes.

Complete Laryngo-Tracheo-Oesophageal Cleft masquerading as Oesophageal Atresia and Tracheo-oesophageal Fistula: A Potential Diagnostic and Management Challenge.

Newborn babies presenting with difficulties related to the aerodigestive tract (ADT) are often provisionally diagnosed and managed as having oesophageal atresia +/- tracheo-oesophageal fistula. Continuing difficulties with management and abnormal findings on investigations should lead to the consideration of other congenital anomalies of the ADT, including complete larnygo-tracheo-oesophageal cleft (LTOC). We present two patients who were eventually diagnosed with complete LTOC and care was withdrawn. We discuss the inherent difficulties in reaching this diagnosis and present an algorithm to help manage these rare and challenging situations.

Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient.

WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.

Isolated congenital facial nerve agenesis.

An otherwise healthy 2-month-old boy was referred to ENT for a congenital right facial palsy, with a birth history of difficult ventouse delivery. Initially, a traumatic cause was suspected, however subsequent MR 3D-FIESTA (T2 weighted) imaging demonstrated a right facial nerve agenesis with normal appearances of the remainder of the brain parenchyma, cranial nerves and parotid glands. There were no syndromic features or hearing difficulties. Isolated congenital nerve agenesis is a rare condition, with very few case reports available in the literature. Pre-natal 4D ultrasound imaging further supports the diagnosis. To our knowledge, this is the first published pre-natal ultrasound image of congenital facial nerve palsy. The infant has been referred for consideration of nerve reconstruction surgery, and is receiving multi-disciplinary input from ENT, Physiotherapy and Ophthalmology, the latter for prevention of exposure keratitis.

Craniospinal abnormalities and neurologic complications of osteogenesis imperfecta: imaging overview.

Osteogenesis imperfecta is a rare genetic disorder that leads to progressive skeletal deformities due to deficits in type I collagen, the main pathophysiologic effect of the disease. In addition, it may lead to a wide range of associated neurologic abnormalities: The central nervous system is usually involved because of softening of bone at the base of the skull, with resultant upward migration of the upper cervical spine and odontoid process into the skull base. Upward migration of the spine may cause compression of the brainstem, mechanical impingement of the spinal canal with restriction of cerebrospinal fluid circulation, and impingement of the cranial nerves. Osteogenesis imperfecta also may directly involve neurovascular structures, leading to cavernous fistulas of the carotid artery, dissection of the cervical arteries, and cerebral aneurysms. The brain parenchyma is frequently affected by the disease, with manifestations including cerebral atrophy, communicating hydrocephalus, and cerebellar hypoplasia. The imaging features of the disorder vary as widely as its clinical manifestations, depending on the severity of disease. Severe forms accompanied by debilitating skeletal fractures and progressive neurologic impairments may lead to perinatal death, whereas milder asymptomatic forms might cause only a modest reduction in life span. The most important advance in medical therapy for osteogenesis imperfecta has been the introduction of bisphosphonate therapy to slow the resorption of bone in patients with moderate to severe forms of the disease (ie, type III or IV). In some patients, neurosurgery may be necessary to correct the effects of severe basilar invagination by the odontoid process.

The use of MR imaging and spectroscopy of the brain in children investigated for developmental delay: what is the most appropriate imaging strategy?

OBJECTIVES: Developmental delay is a common problem in paediatric practice and many children with developmental delay are referred for MR imaging. Our study was performed as part of a continuing audit process to optimise our MR protocol and case selection. MATERIALS AND METHODS: We performed MR imaging and spectroscopy protocol on 157 children with developmental delay. We analysed the effect of these interventions by looking at the overall detection rate of relevant pathology and in particular subgroups of the children. RESULTS: 71% of the children had normal MR imaging, 10% had non-specific findings and 19% had specific abnormalities on MR imaging. The overall risk of having a specific structural abnormality with isolated developmental was 7.5% but if other neurological symptoms/signs were present the risk was 28%. Two children had abnormal spectroscopic findings, one with tuberous sclerosis and the other with absent brain creatine. CONCLUSION: Case selection for MR imaging is important in children with developmental delay. The best strategies for selecting children for MR are either; not performing MR with developmental delay in one domain only or performing MR with developmental delay in three or four domains or if there are other neurological features.

Celiac Plexus Block to Treat Refractory Feed Induced Dystonia in Children with Severe Neurodisability: A Single Center Case Series.

This observational study describes the procedure technique, safety outcomes, and patient responses to celiac plexus blockade (CPB) in children with severe neurodisability with refractory feed intolerance, feed induced pain or feed induced dystonia (FID). Method: A review of the pathophysiological response to feeding in children with significant neurodisability and the effect on the neuroenteric system. A 2-stage CT-guided temporary celiac plexus blockade followed by neurolysis technique is described. We compile a case series of 5 patients with life limiting conditions and significant disability undergoing CPB in a single tertiary pediatric hospital. Results: A total of 10 separate procedures in 5 children were completed. A positive outcome was observed in 3 out of 4 cases of pediatric FID. Two of the three patients on parenteral nutrition had improved feed tolerance postprocedure. All children tolerated the procedure well, no postprocedure complications were documented. Conclusions: In selected cases, children with life-threatening feed induced dystonia or effective intestinal failure can be safely treated with celiac plexus blockade when other therapies have failed.

Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.

Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. An Achondroplasia Foramen Magnum Score will be used to identify infants at risk of requiring decompression surgery. This is a 2-year open label randomized controlled trial of vosoritide in infants with achondroplasia ages 0 to ≤12 months. Approximately 20 infants will be randomized 1:1 to either open label once daily subcutaneous vosoritide combined with standard of care or standard of care alone. The primary and secondary aims of the study are to evaluate the safety and efficacy of vosoritide in children with cervicomedullary compression at risk of requiring decompression surgery. The trial will be carried out in specialized skeletal dysplasia treatment centers with well established multidisciplinary care pathways and standardized approaches to the neurosurgical management of cervicomedually compression. After 2 years, infants randomized to standard of care alone will be eligible to switch to vosoritide plus standard of care for an additional 3 years. This pioneering trial hopes to address the important question as to whether treatment with vosoritide at an early age in infants at risk of requiring cervicomedullary decompression surgery is safe, and can improve growth at the foramen magnum and spinal canal alleviating stenosis. This in turn may reduce compression of surrounding structures including the neuraxis and spinal cord, which could alleviate future morbidity and mortality.Trial registrations: ClinicalTrials.gov, NCT04554940; EudraCT number, 2020-001055-40.

Intracranial non-Langerhans cell histiocytosis presenting as an isolated intraparenchymal lesion.

Non-Langerhans cell histiocytosis in the absence of cutaneous or other organ involvement is very rare. A Caucasian boy age 3 years 11 months presented with episodes of recurrent right-side seizures over 2 weeks. Brain CT and MR imaging showed a single enhancing left frontal lobe lesion. Stereotactic biopsy was performed and histological examination showed diffuse infiltrate of macrophages with foamy cytoplasm. Four months later there was recurrence of seizure activity despite anti-epileptic medication and a repeat MR scan showed a persistent enhancing lesion in the left frontal lobe. Histological examination of the resection specimen resembled juvenile xanthogranuloma (JXG) involving the central nervous system. In the absence of skin lesions a diagnosis of non-Langerhans cell histiocytosis was made. The child made a full recovery following surgery with resolution of his symptoms.

Visualisation of fetal meconium on post-mortem magnetic resonance imaging scans: a retrospective observational study.

BACKGROUND: Less invasive techniques for fetal post-mortems are increasingly used to correlate with parental wishes. With the use of post-mortem magnetic resonance imaging (MRI), normal appearance of the organs must be established. PURPOSE: To investigate the after death appearance of the fetal meconium throughout gestation using the hyperintense appearance of meconium on T1 weighted MRI. MATERIAL AND METHODS: This was a retrospective study that took place in a tertiary referral centre radiology department. Sixty-two fetal body post-mortem MRI scans (January 2014 to May 2018) between 12 and 41 weeks gestation were reviewed. Signal intensity of meconium at the rectum, sigmoid colon, splenic flexure and hepatic flexure was evaluated and correlated with gestational age. Interrater reliability was calculated. RESULTS: Meconium did not consistently have high signal intensity on T1 scans and was not always obvious. Rectal meconium had the highest intensity, and the more proximal the bowel the lower the intensity. The meconium had higher intensity at earlier gestations. Interrater reliability for rectal meconium gradings was excellent. CONCLUSION: This study provides the first published primary research on the appearance of fetal meconium on post-mortem MRI. Overall, results were variable and suggest an alteration of bowel contents after death, but further investigation is needed to effectively inform practice.

Biometric analysis of the foetal meconium pattern using T1 weighted 2D gradient echo MRI.

OBJECTIVES: Foetal MRI is used to assess abnormalities after ultrasonography. Bowel anomalies are a significant cause of neonatal morbidity, however there are little data concerning its normal appearance on antenatal MRI. This study aims to investigate the pattern of meconium accumulation throughout gestation using its hyperintense appearance on T 1 weighted scans and add to the current published data. METHODS: This was a retrospective cohort study in a tertiary referral clinical MRI centre. Foetal body MRI scans of varying gestational ages were obtained dating between October 2011 and March 2018. The bowel was visualised on T 1 weighted images. The length of the meconium and the width of the meconium at the rectum, sigmoid colon, splenic flexure and hepatic flexure was measured. Presence or absence of meconium in the small bowel was noted. Inter- and intrarater reliability was assessed. RESULTS: 181 foetal body scans were reviewed. 52 were excluded and 129 analysed. Visualisation of the meconium in the large bowel became increasingly proximal with later gestations, and small bowel visualisation was greater at earlier gestations. There was statistically significant strong (r = 0.6-0.8) or very strong (r = 0.8-1.0) positive correlation of length and width with increasing gestation. Interrater reliability was moderate to excellent (r = 0.4-1.0). CONCLUSION: This study provides new information regarding the pattern of meconium accumulation throughout gestation. With care, the results can be used in clinical practice to aid diagnosis of bowel pathology. ADVANCES IN KNOWLEDGE: The findings of this study provide further information concerning the normal accumulation of foetal meconium on MR imaging, an area where current research is limited.

Fluoroscopy-guided insertion of nasojejunal tubes in children - setting local diagnostic reference levels.

BACKGROUND: Little is known about the radiation burden from fluoroscopy-guided insertions of nasojejunal tubes (NJTs) in children. There are no recommended or published standards of diagnostic reference levels (DRLs) available. OBJECTIVE: To establish reference dose area product (DAP) levels for the fluoroscopy-guided insertion of nasojejunal tubes as a basis for setting DRLs for children. In addition, we wanted to assess our local practice and determine the success and complication rates associated with this procedure. MATERIALS AND METHODS: Children who had NJT insertion procedures were identified retrospectively from the fluoroscopy database. The age of the child at the time of the procedure, DAP, screening time, outcome of the procedure, and any complications were recorded for each procedure. As the radiation dose depends on the size of the child, the children were assigned to three different age groups. The sample size, mean, median and third-quartile DAPs were calculated for each group. The third-quartile values were used to establish the DRLs. RESULTS: Of 186 procedures performed, 172 were successful on the first attempt. These were performed in a total of 43 children with 60% having multiple insertions over time. The third-quartile DAPs were as follows for each age group: 0-12 months, 2.6 cGy cm(2); 1-7 years, 2.45 cGy cm(2); >8 years, 14.6 cGy cm(2). High DAP readings were obtained in the 0-12 months (n = 4) and >8 years (n = 2) age groups. No immediate complications were recorded. CONCLUSION: Fluoroscopy-guided insertion of NJTs is a highly successful procedure in a selected population of children and is associated with a low complication rate. The radiation dose per procedure is relatively low.

Surfer's exostosis in a child who does not surf.

Surfer's exostoses are more commonly seen in adults who frequently participate in aquatic activities with repeated exposed to cold water and wind. However, this entity has not been previously reported in the pediatric population. Most patients can be managed conservatively, particularly considering that surgical removal of external auditory canal exostosis can be challenging.

SLC35A2-related congenital disorder of glycosylation: Defining the phenotype.

We aim to further delineate the phenotype associated with pathogenic variants in the SLC35A2 gene, and review all published literature to-date. This gene is located on the X chromosome and encodes a UDP-galactose transporter. Pathogenic variants in SLC35A2 cause a congenital disorder of glycosylation. The condition is rare, and less than twenty patients have been reported to-date. The phenotype is complex and has not been fully defined. Here, we present a series of five patients with de novo pathogenic variants in SLC35A2. The patients' phenotype includes developmental and epileptic encephalopathy with hypsarrhythmia, facial dysmorphism, severe intellectual disability, skeletal abnormalities, congenital cardiac disease and cortical visual impairment. Developmental and epileptic encephalopathy with hypsarrhythmia is present in most patients with SLC35A2 variants, and is drug-resistant in the majority of cases. Adrenocorticotropic hormone therapy may achieve partial or complete remission of seizures, but the effect is usually temporary. Isoelectric focusing of transferrins may be normal after infancy, therefore a congenital disorder of glycosylation should still be considered as a diagnosis in the presence of a suggestive phenotype. We also provide evidence that cortical visual impairment is part of the phenotypic spectrum.

Thoracic Kyphosis is Now Uncommon Amongst Children and Adolescents with Cystic Fibrosis.

Historically, thoracic kyphosis has been reported to be common amongst patients with cystic fibrosis (CF). The mechanisms leading to the development of this abnormality of the chest wall are not fully understood. In order to explore the prevalence of the condition amongst children with CF in the early twenty-first century and to explore factors that might be contributing to its development, a retrospective cross sectional study was undertaken in a regional CF unit. Data were obtained from 74 children with CF aged 8-16 years attending for their annual review. Thoracic kyphosis was measured from lateral chest X-ray using an alternative Cobb method. Lung function, disease severity, and nutritional status were also recorded. Correlations between measures were explored using a multiple linear regression model. The range of Cobb angles measured was 5.4-44.3° with thoracic kyphosis identified in only two subjects. There was no correlation between age and thoracic kyphosis, however, there was a significant correlation between lung function and thoracic kyphosis (p = 0.004). Regression coefficient (b) was -0.26 (95% CI: -0.44, -0.08). The prevalence of thoracic kyphosis is significantly less amongst children with CF than previously reported. This appears likely to be associated with the overall improvements in pulmonary status. Studies of older populations may bring further understanding of increasing thoracic kyphosis in people with CF.

Blue rubber bleb naevus syndrome and Chiari malformation: high risk of peroperative haemorrhage.

Blue rubber bleb naevus syndrome is an uncommon disorder whereby patients possess cutaneous vascular malformations. Cranial malformations have been rarely reported in the literature. We report the first ever case of a patient with blue rubber bleb naevus syndrome (BRBNS), who was found to have a symptomatic Chiari malformation and prominent subcutaneous vascular malformations in communication with the intracranial venous sinuses. In our case, a routine operation for Chiari malformation was complicated by significant blood loss. The operative hazards are presented along with suggested peri-operative management strategies when carrying out neurosurgical operations on patients with BRBNS. A brief literature review is included.

Dynamic pelvic floor ultrasound for lower urinary tract symptoms in children--initial report on normative values.

PURPOSE: Lower urinary tract symptoms (LUTS) are common in children. The aim of this study was to determine normal values for pelvic floor movement in asymptomatic controls to allow comparison with symptomatic children with dysfunctional voiding (DV) in the next phase of the study. MATERIAL AND METHODS: One hundred children between the ages of 5-17 years were recruited prospectively as controls. All were asked to perform a voluntary pelvic floor contraction manoeuvre with a full bladder. All scans were performed on a Vivid I GE ultrasound machine with a 4-9 MHz curvilinear probe. M Mode was used to determine the direction of pelvic floor (levator plate-LP) movement, the distance in cms and the endurance in seconds. Each measurement was taken 3 times. RESULTS: Six children were unable to understand and perform the manoeuvre and were excluded. The median age was 10 years (range 4-17). The median LP movement was 0.3 cm (range 0.1-1.6) and cranial in 86/94 (91%). The median endurance time was 5.8 s (range 2.3-15.5). For the (n = 59) younger children aged 4-11, the 95% normal reference range for LP movement was 0.1 cm-1.4 cm and for endurance was 2.5-13.5 s. For the (n = 33) older children aged 12-17, the 95% normal reference range for LP movement was 0.2 cm-1.2 cm and for endurance was 2.3-15.5 s. There was a significant correlation (Pearson r = 0.39, P = 0.001) between average LP movement and endurance. CONCLUSIONS: This study gives the normal reference ranges for the variables measured. A further study is currently underway examining the same variables in children with dysfunctional voiding (DV) and comparing these with the reference range.

Childhood moyamoya disease and moyamoya syndrome: a pictorial review.

Moyamoya disease is an uncommon chronic cerebrovasculopathy, characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches, in association with the development of compensatory collateral vessels at the base of the brain. The etiology is unknown, and was originally considered exclusive to East Asia, with particular prevalence in Japan. Moyamoya disease is increasingly diagnosed throughout the world, and represents an important cause of childhood stroke in Western countries. In some cases, similar angiographic features are evident in children with other medical conditions, such as sickle cell disease and Down syndrome. In these instances, the term "moyamoya syndrome" is used. Diagnosing the vasculopathy, excluding possible associated conditions, and planning treatment and follow-up imaging comprise important aspects of clinical management. We review the key imaging features of childhood moyamoya disease and syndrome, present examples of its associations, and discuss new neuroradiologic methods that may be useful in management.