Longitudinal changes in acylated versus unacylated ghrelin levels may be involved in the underlying mechanisms of the switch in nutritional phases in Prader-Willi syndrome.

INTRODUCTION: Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. An elevated, more unfavorable ratio between acylated and unacylated ghrelin (AG/UAG ratio) might play a role in the underlying mechanisms of this switch. We aimed to assess the evolution of the appetite regulating hormones acylated ghrelin (AG) and unacylated ghrelin (UAG) and the AG/UAG ratio and their association with the change in eating behavior in children with PWS, compared to healthy age-matched controls. METHODS: Longitudinal study in 134 children with PWS and 157 healthy controls, from The Netherlands, France and Belgium. Levels of AG and UAG and the AG/UAG ratio were measured and nutritional phases as reported for PWS were scored. RESULTS: The AG/UAG ratio was in the first years of life lower in PWS than in controls and started to increase from the age of 3 years, resulting in a high-normal AG/UAG ratio compared to controls. The AG levels remained stable during the different nutritional phases (p=0.114), while the UAG levels decreased from 290 pg/ml in phase 1a to 137 pg/ml in phase 2b (p<0.001). The AG/UAG ratio increased significantly from 0.81 in phase 2a to 1.24 in phase 2b (p= 0.012). CONCLUSIONS: The change from failure to thrive to excessive weight gain and hyperphagia in infants and children with PWS coincides with an increase in AG/UAG ratio. The increase in AG/UAG ratio occurred during phase 2a, thus before the onset of hyperphagia.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

BACKGROUND AND PURPOSE: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book Pediatric Neuroimaging from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation. MATERIALS AND METHODS: This is a multicenter, international, retrospective study. We assessed the patients' medical records, prenatal ultrasounds, MR images, genetic findings, and postmortem results. We reviewed the medical literature for all studies depicting medullary malformations and evaluated cases in which a dorsal medullary protuberance was described. RESULTS: We collected 13 patients: 3 fetuses and 10 children. The medullary caps had multiple characteristics. Associated brain findings were a rotated position of the medulla, a small and flat pons, cerebellar anomalies, a molar tooth sign, and agenesis of the corpus callosum. Systemic findings included the following: polydactyly, hallux valgus, large ears, and coarse facies. Postmortem analysis in 3 patients revealed that the cap contained either neurons or white matter tracts. We found 8 publications describing a dorsal medullary protuberance in 27 patients. The syndromic diagnosis was Joubert-Boltshauser syndrome in 11 and fibrodysplasia ossificans progressiva in 14 patients. CONCLUSIONS: This is the first study to describe a series of 13 patients with medullary tegmental cap dysplasia. The cap has different shapes: distinct in Joubert-Boltshauser syndrome and fibrodysplasia ossificans progressive. Due to the variations in the clinical, imaging, and postmortem findings, we conclude that there are multiple etiologies and pathophysiology. We suggest that in some patients, the pathophysiology might be abnormal axonal guidance.

Common Neuroimaging Findings in Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant syndrome secondary to mutations in NR2F1 (COUP-TF1), characterized by visual impairment secondary to optic nerve hypoplasia and/or atrophy, developmental and cognitive delay, and seizures. This study reports common neuroimaging findings in a cohort of 21 individuals with BBSOAS that collectively suggest the diagnosis. These include mesial temporal dysgyria, perisylvian dysgyria, posterior predominant white matter volume loss, callosal abnormalities, lacrimal gland abnormalities, and optic nerve volume loss.

Diagnostic Accuracy of MRI for Detection of Meningitis in Infants.

PURPOSE: To determine the accuracy of MR imaging for diagnosis of meningitis in infants. MATERIALS AND METHODS: Retrospective review of infants less than 1 year of age who underwent a brain MR imaging for meningitis from 2010-2018. Gold standard for diagnosis of bacterial meningitis was a positive bacterial CSF culture or a positive blood culture with an elevated CSF WBC count, and diagnosis of viral meningitis was a positive CSF PCR result and elevated CSF WBC count. Sensitivity, specificity, PPV, NPV, and accuracy for MR imaging diagnosis of meningitis were calculated. RESULTS: Two hundred nine infants with mean age 80 days (range 0-347 days) were included. There were 178 true positives with the most common pathogens being: Group B Streptococcus (58), E. coli (50), Streptococcus pneumoniae (21), H. influenzae (4); Herpes simplex virus 1 or 2 (18); Enterovirus (4); and other (23). There were 31 true negatives. Range of sensitivity, specificity, PPV, NPV, and accuracy of MR imaging for detection of meningitis was 67.4-83.5%, 92.3-95.7%, 95.0-98.6%, 33.3-76.5%, and 71.3-86.5% respectively. MR imaging sensitivity decreased after 10 days from time of presentation while specificity remained stable. Among individual MR imaging findings, leptomeningeal enhancement was the most sensitive finding, while cerebritis, infarction, ventriculitis, abscess, and intraventricular purulent material were the most specific findings. CONCLUSIONS: MR imaging of the brain demonstrates high specificity and moderate sensitivity for diagnosis among infants presenting with signs and symptoms of meningitis. The results reflect current standard of care for imaging of infants with meningitis however a selection bias for imaging of more severe meningitis may affect these results.

Imaging Findings in Children Presenting with CNS Nelarabine Toxicity.

Nelarabine is a nucleoside analog critical for the treatment of patients with T-cell acute lymphoblastic leukemia/lymphoma. However, clinical peripheral and central neurologic adverse events associated with nelarabine administration have been reported. Neuroimaging of brain neurotoxicity has only been described in very few reports in pediatric patients so far. Six children with diagnosed T-cell acute lymphoblastic leukemia who clinically experienced possible, probable, or definite nelarabine-induced toxicity and underwent spine and/or brain MR imaging were reviewed. Neuroimaging findings showed a mixture of patterns including features of acute toxic leukoencephalopathy (seen in 6 cases), posterior reversible encephalopathy syndrome (2 cases), involvement of deep gray structures (1 case) and brainstem (2 cases), cranial and spinal neuropathy (2 cases each), and myelopathy (2 cases). Even though neuroimaging findings are nonspecific, the goal of this article was to alert the pediatric neuroradiologists, radiologists, and clinicians about the possibility of nelarabine-induced neurotoxicity and its broad neuroimaging spectrum.

Neuroimaging in Pediatric Patients with Juvenile Xanthogranuloma of the CNS.

BACKGROUND AND PURPOSE: Juvenile xanthogranuloma is a rare clonal, myeloid, neoplastic disorder. Typically, juvenile xanthogranuloma is a self-limited disorder of infancy, often presenting as a solitary red-brown or yellow skin papule/nodule. A small subset of patients present with extracutaneous, systemic juvenile xanthogranuloma, which may include the CNS. The goal of this retrospective study was to evaluate and categorize the neuroimaging findings in a representative cohort of pediatric patients with CNS juvenile xanthogranuloma. MATERIALS AND METHODS: The brain and/or spine MR imaging data of 14 pediatric patients with pathology-proven juvenile xanthogranuloma were categorized and evaluated for the location; the signal intensity of xanthogranulomas on T1WI, T2WI, DWI, and a matching ADC map for the pattern and degree of contrast enhancement; and the presence of perilesional edema, cysts, or necrosis. RESULTS: Fourteen pediatric patients (8 girls, 6 boys; mean age, 84 months) were included in the study. Patients presented with a wide variety of different symptoms, including headache, seizure, ataxia, strabismus, hearing loss, facial paresis, and diabetes insipidus. Juvenile xanthogranuloma lesions were identified in a number of different sites, including supra- and infratentorial as well as intracranial and spinal leptomeningeal. Five patients were categorized into the neuroradiologic pattern unifocal CNS juvenile xanthogranuloma; 8, into multifocal CNS juvenile xanthogranuloma; and 1, into multifocal CNS juvenile xanthogranuloma with intracranial and spinal leptomeningeal disease. In most cases, xanthogranulomas were small-to-medium intra-axial masses with isointense signal on T1WI (compared with cortical GM), iso- or hyperintense signal on T2WI, had restricted diffusion and perilesional edema. Almost all xanthogranulomas showed avid contrast enhancement. However, we also identified less common patterns with large lesions, nonenhancing lesions, or leptomeningeal disease. Four cases had an additional CT available. On CT, all xanthogranulomas were homogeneously hyperdense (solid component) without evident calcifications. CONCLUSIONS: CNS juvenile xanthogranuloma may demonstrate heterogeneous neuroimaging appearances potentially mimicking other diseases, such as primary brain neoplasms, metastatic disease, lymphoma and leukemia, other histiocytic disorders, infections, or granulomatous diseases.

An In-Depth Analysis of Brain and Spine Neuroimaging in Children with Abusive Head Trauma: Beyond the Classic Imaging Findings.

BACKGROUND AND PURPOSE: Abusive head trauma is the leading cause of morbidity and mortality in young children. Radiology provides valuable information for this challenging diagnosis, but no single neuroimaging finding is independently diagnostic of abusive head trauma. Our purposes were to describe the prevalence of brain and spine neuroimaging findings and to analyze the association of neuroimaging findings with clinical factors to determine which neuroimaging findings may be used as prognostic indicators. MATERIALS AND METHODS: Children with a confirmed abusive head trauma diagnosis between January 2018 to February 2021 were included in this single-center retrospective study. Patient demographics, survival, Glasgow Coma Scale score on admission, length of hospital stay, and intensive care unit stay were examined. Brain neuroimaging findings were categorized as classic and nonclassic findings. Spine MRIs were also assessed for spinal ligamentous injury, compression fracture, and hemorrhage. The χ2 test or the Wilcoxon rank-sum test was used for the analysis. RESULTS: One hundred two children (male/female ratio: 75:27; average age, 9.49; range, 0.27-53.8 months) were included. Subdural hematoma was the most common (83.3%) classic neuroimaging finding. Bridging vein thrombosis was the most common (30.4%) nonclassic neuroimaging finding. Spinal ligamentous injury was seen in 23/49 patients. Hypoxic-ischemic injury was significantly higher in deceased children (P = .0001). The Glasgow Coma Scale score was lower if hypoxic-ischemic injury (P < .0001) or spinal ligamentous injury were present (P = .017). The length of hospital stay was longer if intraventricular hemorrhage (P = .04), diffuse axonal injury (P = .017), hypoxic-ischemic injury (P = .001), or arterial stroke (P = .0003) was present. The intensive care unit stay was longer if intraventricular hemorrhage (P = .02), diffuse axonal injury (P = .01), hypoxic-ischemic injury (P < .0001), or spinal ligamentous injury (P = .03) was present. CONCLUSIONS: Our results may suggest that a combination of intraventricular hemorrhage, diffuse axonal injury, hypoxic-ischemic injury, arterial stroke, and/or spinal ligamentous injury on neuroimaging at presentation may be used as potential poor prognostic indicators in children with abusive head trauma.

Can MRI Differentiate between Infectious and Immune-Related Acute Cerebellitis? A Retrospective Imaging Study.

BACKGROUND AND PURPOSE: Acute cerebellitis is an acute neurologic condition attributable to a recent or concurrent infection or a recent vaccination or ingestion of medication, with MR imaging evidence of cerebellar edema. MR imaging can confirm an anatomic abnormality and may allow the radiologist to establish a differential diagnosis. The purpose of this research was to evaluate the MR imaging findings in children with acute cerebellitis due to infectious versus immune-related conditions, in particular whether MR imaging findings allow differentiation. MATERIALS AND METHODS: Electronic medical records were reviewed between 2003 and 2020 in our quaternary children's hospital. Data included demographics and clinical records: presentation/symptoms, final diagnosis including acute cerebellitis and immune-related acute cerebellitis, length of stay, treatment, condition at discharge, and laboratory findings. Retrospective independent review of all brain MR imaging studies was performed. RESULTS: Forty-three patients (male/female ratio, 28:15) were included in this study. Average age at presentation was 7.08 years (range, 0.05-17.52 years). Thirty-five children had infectious and 8 children had immune-related acute cerebellitis. Significant differences in neuroimaging were the following: 1) T2-FLAIR hyperintense signal in the brainstem (37.50% versus 2.85%, P = .016); 2) T2-FLAIR hyperintense signal in the supratentorial brain higher in the immune-related group (37.50% versus 0.00%, P = .004); and 3) downward herniation, higher in the infectious acute cerebellitis group (42.85% versus 0.00%, P = .03). CONCLUSIONS: Acute cerebellitis is a rare condition, and MR imaging is helpful in the differential diagnosis. T2-FLAIR hyperintense signal in the brainstem and supratentorial brain may be indicative of immune-related acute cerebellitis, and downward herniation may be indicative of infectious acute cerebellitis.

Neuroimaging Features of Ectopic Cerebellar Tissue: A Case Series Study of a Rare Entity.

Ectopic cerebellar tissue is a rare entity likely secondary to multiple, interacting, developmental errors during embryogenesis. Multiple sites of ectopic cerebellar tissue have been reported, including extracranial locations; however, an intracranial location is most common. We report on the MR imaging findings of a multi-institutional series of 7 ectopic cerebellar tissue cases (2 males, 4 females, 1 fetal) ranging from 22 weeks 5 days' gestational age to 18 years of age. All cases of ectopic cerebellar tissue were diagnosed incidentally, while imaging was performed for other causes. Ectopic cerebellar tissue was infratentorial in 6/7 patients and supratentorial in 1/7 patients. All infratentorial ectopic cerebellar tissue was connected with the brain stem or cerebellum. MR imaging signal intensity was identical to the cerebellar gray and white matter signal intensity on all MR imaging sequences in all cases. Ectopic cerebellar tissue should be considered in the differential diagnoses of extra-axial masses with signal characteristics similar to those of the cerebellum. Surgical biopsy or resection is rarely necessary, and in most cases, MR imaging is diagnostic.

Neuroimaging Offers Low Yield in Children Positive for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus disease 2 (SARS CoV-2) most commonly presents with respiratory disease, but neurologic complications are being reported. We aimed to investigate the rate of positive neuroimaging findings in children positive for SARS-CoV-2 referred for neuroimaging between March 18 and September 30, 2020. We found that 10% (n = 2) had acute findings. Our results may suggest that in children, neurologic involvement in COVID-19 is rare, neuroimaging has a low yield in diagnosis, and acute neuroimaging should involve careful risk-benefit analysis.

Oxytocin in young children with Prader-Willi syndrome: Results of a randomized, double-blind, placebo-controlled, crossover trial investigating 3 months of oxytocin.

CONTEXT: Prader-Willi syndrome (PWS) is characterized by hypothalamic dysfunction, hyperphagia and a typical behavioural phenotype, with characteristics of autism spectrum disorder (ASD) like stubbornness, temper tantrums and compulsivity. It has been suggested that the oxytocin system in patients with PWS is dysfunctional. In ASD, intranasal oxytocin treatment has favourable effects on behaviour. OBJECTIVE: To evaluate the effects of 3 months of twice daily intranasal oxytocin (dose range 16-40 IU/day), compared to placebo, on behaviour and hyperphagia in children with PWS. DESIGN: Randomized, double-blind, placebo-controlled, crossover study in the Dutch PWS Reference Center. PATIENTS: Twenty-six children with PWS aged 3-11 years. MAIN OUTCOME MEASURES: (Change in) behaviour and hyperphagia measured by Oxytocin Questionnaire and Dykens hyperphagia questionnaire. RESULTS: In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found. However, in boys, the Oxytocin Questionnaire scores improved significantly during oxytocin treatment, compared to a deterioration during placebo (4.5 (-0.8 to 15.3) vs. -4.0 (-11.3 to 0.8), P = .025). The Dykens hyperphagia questionnaire scores remained similar during oxytocin treatment, while there was a deterioration during placebo (0.0 (-0.8 to 4.3) vs. -3.5 (-6.0 to 0.0), P = .046). Patients with a deletion had significant improvements in both questionnaire scores during oxytocin treatment, but deteriorations during placebo. Oxytocin treatment was well tolerated, and there were no serious adverse events. CONCLUSIONS: Intranasal oxytocin treatment has positive effects on social and eating behaviour in 3-11 years aged boys with PWS and in children with a deletion without safety concerns. Intranasal oxytocin in children with PWS might be considered, but individual effects should be carefully evaluated and treatment discontinued if no effects are found.

Resonant Pumping of d-d Crystal Field Electronic Transitions as a Mechanism of Ultrafast Optical Control of the Exchange Interactions in Iron Oxides.

The microscopic origin of ultrafast modification of the ratio between the symmetric (J) and antisymmetric (D) exchange interaction in antiferromagnetic iron oxides is revealed, using femtosecond laser excitation as a pump and terahertz emission spectroscopy as a probe. By tuning the photon energy of the laser pump pulse we show that the effect of light on the D/J ratio in two archetypical iron oxides FeBO_{3} and ErFeO_{3} is maximized when the photon energy is in resonance with a spin and parity forbidden d-d transition between the crystal-field split states of Fe^{3+} ions. The experimental findings are supported by a multielectron model, which accounts for the resonant absorption of photons by Fe^{3+} ions. Our results reveal the importance of the parity and spin-change forbidden, and therefore often underestimated, d-d transitions in ultrafast optical control of magnetism.

Design of 3D-Printed Nasopharyngeal Swabs for Children is Enabled by Radiologic Imaging.

3D-printed nasopharyngeal swabs for COVID-19 molecular diagnostic testing address the national shortage of swabs. Swab designs for adult use were placed in the public domain in March 2020. Swabs for pediatric use, however, need to be smaller and more flexible to navigate delicate pediatric nasopharyngeal cavities. We describe a novel use of maxillofacial CT scans to aid in the design of pediatric nasopharyngeal swabs.

Neuroimaging Appearance of Cerebral Malignant Epithelioid Glioneuronal Tumors in Children.

Malignant epithelioid glioneuronal tumor is a rare high-grade, aggressive brain tumor that shows both glial and neuronal differentiation on histopathology but is not included in the current World Health Organization classification. The neuroimaging appearance is variable but may be secondary to the size of the mass and/or location of the tumor. In our series, all epithelioid glioneuronal tumors were encountered in the supratentorial space and included pineal, temporal, and extratemporal lobar cerebral hemisphere locations. When large, the tumors demonstrate cystic degeneration and necrosis, hemorrhage, contrast enhancement, and regions of low apparent diffusion coefficient scalars consistent with patterns seen with other high-grade pediatric brain tumors. The tumors also have a propensity to spread into the meninges at presentation and for distant CSF spread on follow-up imaging.

Accuracy of MR Imaging for Detection of Sensorineural Hearing Loss in Infants with Bacterial Meningitis.

BACKGROUND AND PURPOSE: Bacterial meningitis most commonly affects young children and can result in critical adverse outcomes, including sensorineural hearing loss (SNHL). The purpose of this study is to determine the diagnostic accuracy of MR imaging for predicting the development of SNHL among infants with bacterial meningitis. MATERIALS AND METHODS: A retrospective review was performed among infants (age <365 days) with bacterial meningitis (n = 115). Independent and consensus blinded review of brain MRIs (n = 239) performed less than 90 days from presentation were conducted. Abnormal appearance of the inner ear was defined as enhancement on postcontrast T1-weighted (T1-weighted+C) sequence and FLAIR hyperintensity. The consensus MR imaging appearance of the inner ear on FLAIR, T1-weighted+C, and combined evaluation was compared with criterion standard audiometric testing to determine the sensitivity and specificity of MR imaging for detecting SNHL. RESULTS: The mean age at diagnosis of bacterial meningitis was 50.6 days (range, 0-338 days) and 24.3% had SNHL. Sensitivity and specificity was 0.61/0.96, 0.50/0.94, and 0.61/0.94 for T1-weighted+C, FLAIR hyperintensity, and combined evaluation, respectively, for prediction of SNHL. There was excellent interobserver agreement for both the T1-weighted+C and FLAIR sequences and combined evaluation for presence of abnormal enhancement and hyperintense signal, respectively. Factors associated with abnormal MR imaging findings on T1-weighted+C and/or FLAIR in patients with SNHL included low CSF glucose (P = .04, .02) and high CSF protein (P = .04, .03). CONCLUSIONS: Abnormal enhancement and/or FLAIR hyperintensity of the inner ear demonstrate high specificity and average sensitivity for prediction of SNHL among infants with bacterial meningitis.

Brain MRI Findings in Pediatric-Onset Neuromyelitis Optica Spectrum Disorder: Challenges in Differentiation from Acute Disseminated Encephalomyelitis.

BACKGROUND AND PURPOSE: Differentiating pediatric-onset neuromyelitis optica spectrum disorder from acute disseminated encephalomyelitis could be challenging, especially in cases presenting with only brain manifestations. Our purpose was to investigate brain MR imaging features that may help distinguish these 2 entities. MATERIALS AND METHODS: We retrospectively examined initial brain MR imaging studies of 10 patients with pediatric-onset neuromyelitis optica spectrum disorder (female/male ratio, 7:3) and 10 patients with acute disseminated encephalomyelitis (female/male ratio, 2:8). The mean age of the patients was 10.3 ± 5.6 and 8.7 ± 5.3 years, respectively. Brain lesions were evaluated with respect to location, extent, expansion, T1 hypointensity, contrast enhancement/pattern, and diffusion characteristics. The χ2 test (Yates or Fisher exact χ2tests) was used to compare differences between groups. RESULTS: Cerebral subcortical ± juxtacortical and pons ± middle cerebellar peduncle were the most frequent locations involved in both neuromyelitis optica spectrum disorder (n = 5 and 4, respectively) and acute disseminated encephalomyelitis (n = 9 and 7, respectively). Thalamic lesions were more frequent in acute disseminated encephalomyelitis (P = .020) and were detected only in 1 patient with neuromyelitis optica spectrum disorder. None of the patients with neuromyelitis optica spectrum disorder had hypothalamic, internal capsule, or cortical lesions. The internal capsule involvement was found to be significantly different between groups (P = .033). There was no significant difference in terms of extent, expansion, T1 hypointensity, contrast enhancement/pattern, and diffusion characteristics. CONCLUSIONS: Although there is a considerable overlap in brain MR imaging findings, thalamic and internal capsule involvement could be used to differentiate pediatric-onset neuromyelitis optica spectrum disorder from acute disseminated encephalomyelitis.

Real-world multicentre experience of the pathological features of colonic ischaemia and their relationship to symptom duration, disease distribution and clinical outcome.

AIM: To determine the pathological features of colonic ischaemia (CI) and their relationship to symptom duration, disease distribution and clinical outcome in a real-world, clinical setting. METHOD: A retrospective, multicentre chart review was performed in patients diagnosed with CI at Montefiore Medical Center (January 2005 to July 2015), and Yale-New Haven Hospital (January 2005 to June 2010). Patients were included if clinical presentation, colonoscopic findings and colonic pathology were all consistent with CI. RESULTS: Six hundred and sixteen patients with pathologically proven CI were included. Common pathological findings included inflammation (51.1%), ulceration (38.2%), fibrosis (26.0%) and necrosis (20.4%). Infarction and ghost cells were seen in 1.6% and 0.2% of cases, respectively. There was a significant relationship between symptom duration and hyalinization of the lamina propria (P = 0.05) and cryptitis/crypt abscesses (P = 0.01). Patients with isolated right CI (IRCI) were more likely than patients with isolated left CI (ILCI) to exhibit necrosis (P < 0.01), cryptitis/crypt abscess (P < 0.01) and inflammation (P = 0.03). Patients with poor outcomes were more likely to exhibit necrosis (P < 0.01) and capillary fibrin thrombi (P < 0.01) and less likely to exhibit fibrosis (P < 0.01) and epithelial changes (P < 0.01). CONCLUSION: CI is accompanied by a broad spectrum of pathological findings. The traditional pathognomonic findings of CI are rare and cannot be relied upon to exclude the diagnosis. Patients with IRCI and/or poor outcomes were more likely to have pathological findings of necrosis than patients who had ILCI and/or nonpoor outcomes.