The prevalence of incidental findings on pelvis MRI of 8-13-year-old children.

BACKGROUND: The prevalence and clinical relevance of incidental findings (IF(s)) on imaging assessing the pelvis in children has not been well documented. METHODS: Three-thousand two-hundred thirty-one children (mean age 10.2 (range 8.6-12.9) years) were evaluated with MRI of the hips, pelvis, and lumbar spine, as part of a prospective population-based pediatric cohort study. Scans were reviewed by trained medical staff for abnormalities. IFs were categorized by clinical relevance and need for further clinical evaluation. RESULTS: 8.3% (n = 267) of children featured at least one IF. One or more musculoskeletal IFs were found in 7.9% (n = 254) of children, however, only 0.8% (n = 2) of musculoskeletal IFs required clinical evaluation. Most frequent abnormalities were simple bone cysts 6.0% (n = 195), chondroid lesions 0.6% (n = 20), and perineural cysts 0.5% (n = 15). Intra-abdominal IFs were detected in 0.5% (n = 17) of children, with over half (n = 9) of these requiring evaluation. The three most common intra-abdominal IFs were a duplex collecting system 0.09% (n = 3), significant ascites 0.06% (n = 2), and hydroureteronephrosis 0.06% (n = 2). CONCLUSIONS: IFs on MRI of the lower abdominal and hip region are relatively common in children aged 8-13 years, most of these can be confidently categorized as clinically irrelevant without the need for additional clinical or radiologic follow up. IMPACT: Our research contributes greatly to the knowledge of the prevalence of (asymptomatic) pathology in children. We evaluated MR images of 3231 children, covering hip joints, pelvic skeleton, lower and mid-abdomen, and lumbar and lower thoracic spine as part of a population study. One or more musculoskeletal incidental finding were found in 7.9% of children. Most of these can be confidently categorized as clinically irrelevant without the need for additional follow up. However 0.8% of musculoskeletal findings required further evaluation. Intra-abdominal incidental findings were detected in 0.5% of children, with over half of the abdominal and urogenital findings requiring further evaluation.

Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis.

Sphingomyelinases generate ceramide from sphingomyelin as a second messenger in intracellular signaling pathways involved in cell proliferation, differentiation, or apoptosis. Children from 12 unrelated families presented with microcephaly, simplified gyral pattern of the cortex, hypomyelination, cerebellar hypoplasia, congenital arthrogryposis, and early fetal/postnatal demise. Genomic analysis revealed bi-allelic loss-of-function variants in SMPD4, coding for the neutral sphingomyelinase-3 (nSMase-3/SMPD4). Overexpression of human Myc-tagged SMPD4 showed localization both to the outer nuclear envelope and the ER and additionally revealed interactions with several nuclear pore complex proteins by proteomics analysis. Fibroblasts from affected individuals showed ER cisternae abnormalities, suspected for increased autophagy, and were more susceptible to apoptosis under stress conditions, while treatment with siSMPD4 caused delayed cell cycle progression. Our data show that SMPD4 links homeostasis of membrane sphingolipids to cell fate by regulating the cross-talk between the ER and the outer nuclear envelope, while its loss reveals a pathogenic mechanism in microcephaly.

Transcutaneous carbon dioxide monitoring during therapeutic hypothermia for neonatal encephalopathy.

BACKGROUND: In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCO2) monitoring during TH. METHODS: In this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCO2) values and tcPCO2 measurements during TH was determined. TcPCO2 levels during the first 24 h of hypothermia were tested for an association with ischemic brain injury on magnetic resonance imaging (MRI). RESULTS: Thirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCO2 and PaCO2 levels was 3.9 (-12.4-20.2) mm Hg. No relation was found between the body temperature and tcPCO2 levels. TcPCO2 levels differed significantly between patients with considerable and minimal damage on MRI; after 6 h (P = 0.02) and 9 h (P = 0.04). CONCLUSIONS: Although tcPCO2 provided a limited estimation of PaCO2, it can be used for trend monitoring during TH. TcPCO2 levels after birth could provide an early indicator of ischemic brain injury. This relation should be investigated in large prospective studies, in which adjustments for confounders can be made. IMPACT: Transcutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring. Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI. The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders. Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

Is the brain involved in patients with late-onset Pompe disease?

Our objective was to investigate brain structure, cerebral vasculature, and cognitive function in a cohort of patients with late-onset Pompe disease, with particular reference to the differences from those with the classic infantile phenotype, where extensive white-matter abnormalities (WMA) and impaired cognition on long-term enzyme treatment are reported in a subset of patients. Brain imaging (T1, T2, T2 fluid-attenuated inversion recovery, susceptibility-weighted images, and magnetic resonance angiography-time of flight) was combined with extensive cognitive testing of general intelligence (Wechsler IQ Test, Montreal Cognitive Assessment [MoCA]) and specific neuropsychological domains (verbal fluency, cognitive flexibility, attention, memory, and visuospatial abilities). We included 19 patients with late-onset Pompe disease (age range 11-56 years). Two patients showed mild punctate WMA within normal range for age, with a Fazekas score (FS) of 1 to 2. Magnetic resonance angiography revealed a slight vertebrobasilar dolichoectasia in two patients yet did not show any aneurysms or vascular dissections. Most patients had age-adjusted scores within the normal range for the Wechsler index scores (verbal comprehension, perceptual reasoning, working memory, and processing speed) and combined total intelligence (IQ) score (median 101, interquartile range 91-111; one patient had a below-average score for total IQ) as well as for the specific domains verbal fluency, attention, and memory. A subset of patients performed suboptimally on the Rey Complex Figure Test (9/14 patients) or cube-copying/clock-drawing test of the MoCA (8/10 patients). We therefore concluded that our study showed no brain abnormalities, other than minor microvascular lesions considered within normal range for age, nor general cognitive impairment in late-onset Pompe patients. These findings are in sharp contrast with the widespread WMA and cognitive problems found in some classic infantile patients.

Cerebral cortex maldevelopment in syndromic craniosynostosis.

AIM: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. METHOD: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo-24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log-transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. RESULTS: Mean ICV was greater in patients with FGFR (1519cm3 , SD 269cm3 , p=0.016) than in patients with TWIST1 (1304cm3 , SD 145cm3 ) or controls (1405cm3 , SD 158cm3 ). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61-0.76) in patients with FGFR compared to 0.81 (95% CI 0.50-1.12) in patients with TWIST1 and 0.77 (95% CI 0.61-0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42-0.59) and occipital (0.67, 95% CI 0.54-0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. INTERPRETATION: Despite adequate ICV in FGFR-mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR.

MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance.

To date, mutations in 15 actin- or microtubule-associated genes have been associated with the cortical malformation lissencephaly and variable brainstem hypoplasia. During a multicenter review, we recognized a rare lissencephaly variant with a complex brainstem malformation in three unrelated children. We searched our large brain-malformation databases and found another five children with this malformation (as well as one with a less severe variant), analyzed available whole-exome or -genome sequencing data, and tested ciliogenesis in two affected individuals. The brain malformation comprised posterior predominant lissencephaly and midline crossing defects consisting of absent anterior commissure and a striking W-shaped brainstem malformation caused by small or absent pontine crossing fibers. We discovered heterozygous de novo missense variants or an in-frame deletion involving highly conserved zinc-binding residues within the GAR domain of MACF1 in the first eight subjects. We studied cilium formation and found a higher proportion of mutant cells with short cilia than of control cells with short cilia. A ninth child had similar lissencephaly but only subtle brainstem dysplasia associated with a heterozygous de novo missense variant in the spectrin repeat domain of MACF1. Thus, we report variants of the microtubule-binding GAR domain of MACF1 as the cause of a distinctive and most likely pathognomonic brain malformation. A gain-of-function or dominant-negative mechanism appears likely given that many heterozygous mutations leading to protein truncation are included in the ExAC Browser. However, three de novo variants in MACF1 have been observed in large schizophrenia cohorts.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Saethre-Chotzen syndrome: long-term outcome of a syndrome-specific management protocol.

AIM: To assess the long-term outcomes of our management protocol for Saethre-Chotzen syndrome, which includes one-stage fronto-orbital advancement. METHOD: All patients born with Saethre-Chotzen syndrome between January 1992 and March 2017 were included. Evaluated parameters included occipital frontal head circumference (OFC), fundoscopy, neuroimaging (ventricular size, tonsillar position, and the presence of collaterals/an abnormal transverse sinus), polysomnography, and ophthalmological outcomes. The relationship between papilledema and its associated risk factors was evaluated with Fisher's exact test. RESULTS: Thirty-two patients (21 females, 11 males) were included. Median (SD) age at first surgery was 9.6 months (3.1mo) for patients who were primarily referred to our center (range: 3.6-13.0mo), the median (SD) age at last follow-up was 13 years (5y 7mo; range: 3-25y). Seven patients had papilledema preoperatively, which recurred in two. Two patients had papilledema solely after first surgery. Second cranial vault expansion was indicated in 20%. Thirteen patients had an OFC deflection, indicating restricted skull growth, one patient had ventriculomegaly, and none developed hydrocephalus. Eleven patients had emissary veins, while the transverse sinus was aberrant unilaterally in 13 (hypoplastic n=10 and absent n=3). Four patients had mild tonsillar descent, one of which was a Chiari type I malformation. Four patients had obstructive sleep apnoea (two mild, one moderate, and one severe). An aberrant transverse sinus was associated with papilledema (p=0.01). INTERPRETATION: Single one-stage fronto-orbital advancement was sufficient to prevent intracranial hypertension for 80% of our patients with Saethre-Chotzen syndrome. Follow-up should focus on OFC deflection and venous anomalies.

Silent cerebral infarcts in patients with sickle cell disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Silent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences. METHODS: The databases of Embase, MEDLINE ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Trials via Wiley and Google Scholar were searched from inception to June 1, 2019. RESULTS: The search yielded 651 results of which 69 studies met the eligibility criteria. The prevalence of SCIs in patients with SCD ranges from 5.6 to 80.6% with most studies reported in the 20 to 50% range. The pooled prevalence of SCIs in HbSS and HbSß0 SCD patients is 29.5%. SCIs occur more often in patients with the HbSS and HbSß0 genotype in comparison with other SCD genotypes, as SCIs are found in 9.2% of HbSC and HbSß+ patients. Control subjects showed a mean pooled prevalence of SCIs of 9.8%. Data from included studies showed a statistically significant association between increasing mean age of the study population and mean SCI prevalence. Thirty-three studies examined the risk factors for SCIs. The majority of the risk factors show no clear association with prevalence, since more or less equal numbers of studies give evidence for and against the causal association. CONCLUSIONS: This systematic review and meta-analysis shows SCIs are common in patients with SCD. No clear risk factors for their development were identified. Larger, prospective and controlled clinical, neuropsychological and neuroimaging studies are needed to understand how SCD and SCIs affect cognition.

Cervical ribs and other abnormalities of the vertebral pattern in children with esophageal atresia and anorectal malformations.

BACKGROUND: In mammals the vertebral column has a constant pattern, particularly in the cervical region, which is likely the result of stabilizing selection. The prevalence of cervical ribs and extended vertebral pattern abnormalities is increased in deceased fetuses and neonates and associated with structural and chromosomal anomalies. The hypothesized close interaction between vertebral patterning and organogenesis in early embryogenesis could be studied in children with esophageal atresia and anorectal malformations by evaluating the radiographs of the vertebral column and the type and number of associated anomalies METHODS: The vertebral pattern of 367 children diagnosed with an esophageal atresia (n = 135), anorectal malformation (n = 215), or both (n = 17) was assessed on radiographs. RESULTS: The vertebral pattern was abnormal in 170/202 (84.2%) children in whom this could be assessed, and cervical ribs were present in 147/335 (43.9%). Extended vertebral pattern abnormalities became more frequent with an increasing number of associated structural abnormalities. Cervical ribs were particularly common in children with chromosomal and genetic abnormalities (18/20, 90.0%). CONCLUSIONS: Cervical ribs are frequent and abnormal vertebral patterns are more extended in the presence of associated anomalies. These findings support the hypothesized selection against vertebral patterning variations and emphasize the relevance of assessment of the vertebral pattern.

Intracranial hypertension and cortical thickness in syndromic craniosynostosis.

AIM: To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis. METHOD: ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes. RESULTS: In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo-34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682). INTERPRETATION: Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies. WHAT THIS PAPER ADDS: Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.

Hipertensión intracraneal y grosor cortical en craneosinostosis sindrómica OBJETIVO: Evaluar el impacto de los factores de riesgo de hipertensión intracraneal (HIC) en el grosor de la corteza cerebral en la craneosinostosis sindrómica. MÉTODO: La neuroimagen, y, los factores de riesgo para HIC que incluyeron papiledema, hidrocefalia, apnea obstructiva del sueño (SAOS), posición de la tonsila cerebelosa, edad de desviación de la curva de circunferencia occipitofrontal (CFO) y el sexo, se recogieron de los registros de pacientes con craneosinostosis sindrómica (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzensis). Las imágenes de resonancia magnética fueron analizadas y exportadas para análisis estadístico. Se desarrolló un modelo mixto lineal para determinar las correlaciones con los cambios en el espesor de la corteza cerebral. RESULTADOS: En total se evaluaron 171 exploraciones de 107 pacientes (83 varones, 88 mujeres [incluyendo escaneos repetidos], edad media 8 años 10 meses, rango 1 año 1 mes - 34 años, DE 5 años 9 meses). El espesor medio cortical en esta cohorte fue de 2,78 mm (DS 0,17). Los hallazgos anteriores de papiledema (p=0,036) y de hidrocefalia (p=0,007) se asociaron de forma independiente con el adelgazamiento cortical. El grosor cortical no varió significativamente por sexo (p=0,534), síndrome (p=0,896), SAOS (p=0,464), CFO (p=0,375), o posición tonsilar (p=0,682). INTERPRETACIÓN: La detección de papiledema o hidrocefalia en la craneosinostosis sindrómica, se asocia con cambios significativos en el grosor cortical. Esto apoya la necesidad de estrategias de tratamiento preventivo en lugar de tratamientos reactivos.

Hipertensão intracrianiana e espessura cortical na craniossinostose sindrômica OBJETIVO: Avaliar o impacto de fatores de risco para hipertensão intracraniana (HIC) na espessura cortical em craniossinostose sindrômica. MÉTODO: Fatores de risco para HIC incluindo papiloedema, hidrocefalia, apnéia obstrutiva do sono (AOS), posição das tonsilas do cerebelo, idade de deflexão da curva da circunferência occipitofrontal (COF), e sexo foram coletados dos registros de pacientes com craniossinostose sindrômica (síndromes de Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen) e imagens. As imagens de ressonância magnética foram analisadas e exportadas para análise estatística. Um modelo linear misto foi desenvolvido para determinar correlações com mudanças na espessura do córtex cerebral. RESULTADOS: No total, 171 imagens de 107 pacientes (83 do sexo masculino, 88 do sexo feminino [incluindo varreduras repetidas], média de idade 8a 10m, variação 1a 1m-34a, DP 5a 9m) foram avaliados. A espessura cortical média nesta coorte foi 2,78mm (DP 0,17). Achados prévios de papiloedema (p=0,036) e de hidrocefalia (p=0,007) foram independentemente associados com a redução cortical. A espessura cortical não variou significativamente com o sexo (p=0,534), síndrome (p=0,896), AOS (p=0,464), COF (p=0,375), ou posição tonsilar (p=0,682). INTERPRETAÇÃO: A detecção do papiloedema ou hidrocefalia na craniossinostose sindrômica se associa com mudanças significativas na espessura cortical, sustentando a necessidade de estratégias de tratamento preventivas e não reativas.

A Systematic Review of Neuromonitoring Modalities in Children Beyond Neonatal Period After Cardiac Arrest.

OBJECTIVES: Postresuscitation care in children focuses on preventing secondary neurologic injury and attempts to provide (precise) prognostication for both caregivers and the medical team. This systematic review provides an overview of neuromonitoring modalities and their potential role in neuroprognostication in postcardiac arrest children. DATA RESOURCES: Databases EMBASE, Web of Science, Cochrane, MEDLINE Ovid, Google Scholar, and PsycINFO Ovid were searched in February 2019. STUDY SELECTION: Enrollment of children after in- and out-of-hospital cardiac arrest between 1 month and 18 years and presence of a neuromonitoring method obtained within the first 2 weeks post cardiac arrest. Two reviewers independently selected appropriate studies based on the citations. DATA EXTRACTION: Data collected included study characteristics and methodologic quality, populations enrolled, neuromonitoring modalities, outcome, and limitations. Evidence tables per neuromonitoring method were constructed using a standardized data extraction form. Each included study was graded according to the Oxford Evidence-Based Medicine scoring system. DATA SYNTHESIS: Of 1,195 citations, 27 studies met the inclusion criteria. There were 16 retrospective studies, nine observational prospective studies, one observational exploratory study, and one pilot randomized controlled trial. Neuromonitoring methods included neurologic examination, routine electroencephalography and continuous electroencephalography, transcranial Doppler, MRI, head CT, plasma biomarkers, somatosensory evoked potentials, and brainstem auditory evoked potential. All evidence was graded 2B-2C. CONCLUSIONS: The appropriate application and precise interpretation of available modalities still need to be determined in relation to the individual patient. International collaboration in standardized data collection during the (acute) clinical course together with detailed long-term outcome measurements (including functional outcome, neuropsychologic assessment, and health-related quality of life) are the first steps toward more precise, patient-specific neuroprognostication after pediatric cardiac arrest.

Posterior Distraction Using Springs in Syndromic and Multisuture Craniosynostosis: Improving the Technique.

INTRODUCTION: Posterior distraction is the preferred surgical treatment for particularly Apert and Crouzon syndrome in most craniofacial centers, using either external distractors or springs. The authors prefer the use of springs and have adapted their technique to further improve outcomes. METHODS: All patients who were treated with the adapted technique for occipital expansion using springs were included. The most significant adaption that the authors introduced in 2017 is using a bony hinge at the top of the vault instead of at the caudal edge of the occiput. RESULTS: A total of 8 posterior expansions with springs were performed. No complications occurred and the springs were also successfully applied in cases with extremely thin bone. If indicated, a simultaneous foramen magnum decompression was performed and this was easier to combine with a hinge at the top of the vault. CONCLUSIONS: Posterior distraction with springs is a safe and effective procedure and allows a simultaneous foramen magnum decompression. Planning the hinge at the vault allows intracranial volume gain at the site of the posterior skull base.

Added value of arterial spin labeling magnetic resonance imaging in pediatric neuroradiology: pitfalls and applications.

Arterial spin labeling is a noninvasive, non-gadolinium-dependent magnetic resonance imaging (MRI) technique to assess cerebral blood flow. It provides insight into both tissue metabolic activity and vascular supply. Because of its non-sensitivity toward blood-brain barrier leakage, arterial spin labeling is also more accurate in cerebral blood flow quantification than gadolinium-dependent methods. The aim of this pictorial essay is to promote the application of arterial spin labeling in pediatric neuroradiology. The authors provide information on artifacts and pitfalls as well as numerous fields of application based on pediatric cases.

Traumatic Spinal Injury in Children; Time to Revise Pre-Hospital and Diagnostic Protocols?

Background: Traumatic spinal injury in children is a rare but serious life event. Predicting pediatric patients at risk for spinal injury remains difficult. This study focuses on the cause of the injury and predictors to identify children at risk and appropriate diagnostic procedures. Methods: Retrospective chart review from the Landelijke Trauma Registratie of patients with spinal injury from 2010 to 2021 in a level 1 pediatric trauma center. Results: We included 114 children with spinal injury, 79.8% of whom were aged 12-17 years. In the overall trauma population, the incidence of spinal injury was 10% in children aged 12-17 years, 2.3% in children aged 6-11 years, and 0.4% in children 0-5 years of age. Neurological deficits were present in 27.2% of patients in the emergency department, with permanent deficits in 14.0%. Spinal fractures were present in 91.2% of 12-17-year-olds, 43.8% in 6-11-year-olds, and 71.4% in 0-5-year-olds. ISS was 23 (SD 14) in children with spinal injury compared to 8 (SD 9) for children without spinal injury. Conclusions: In children 0-11 years old, spinal injury is very rare compared to the overall trauma population, and there are more non-osseous injuries. Clinicians should consider MRI as the next step after conventional X-ray to diagnose or exclude spinal injuries in this group. In older children aged 12-17 years, the incidence of spinal injury is much higher, at 10%. Although ISS is higher in children with spinal injury, a low ISS does not exclude spinal injury. If one fracture is found, more fractures in other regions of the spine may be present.

Eye and Orbital Anatomy in Metopic Synostosis.

Background: Metopic synostosis patients have a high prevalence of orthoptic anomalies, including hyperopia, astigmatism, and amblyopia. We hypothesized altered orbital anatomy contributes to suboptimal visual outcomes by adversely affecting eye anatomy and growth from early life onward. Therefore, we aimed to investigate eye and orbital anatomy in metopic synostosis. Methods: We conducted a retrospective study in nonsyndromic metopic synostosis patients (n = 134, median age 0.43 years [IQR 0.45]) with nonsyndromic sagittal synostosis patients (n = 134, median age 0.27 years [IQR 0.23]) as controls. Primary analyses focused on eye dimensions (axial length, width, and globe height) and orbital dimensions, correcting for sex and age. Measurements were obtained from preoperative computed tomography scans. Results: Axial length and width in metopic synostosis patients did not differ from sagittal synostosis patients, but globe height was significantly smaller (P = 0.0002). Lateral wall interorbital length, lateral orbital wall length, anterior medial interorbital length, and maximal medial interorbital length were significantly smaller, and anterior vertical orbital height and maximal vertical orbital height were significantly larger (P < 0.001). The central orbital axis and interorbital angle were significantly narrower, and medial-to-lateral orbital wall angle was wider (P < 0.001). Conclusions: Metopic synostosis patients have more shallow, wider, and higher orbits. Eye dimensions are similar in sagittal synostosis patients, although globe height was smaller. Altered orbital and eye dimensions in metopic synostosis probably have a causal relation with an unknown order of development. How these dimensions relate to future orthoptic anomalies (eg, refractive error) needs further investigation.

The Influence of Nonaerated Paranasal Sinuses on DTI Parameters of the Brain in 6- to 9-Year-Old Children.

BACKGROUND AND PURPOSE: DTI is prone to susceptibility artifacts. Air in the paranasal sinuses can cause field inhomogeneity, thus affecting measurements. Children often have mucus in their sinuses or no pneumatization of them. This study investigated the influence of lack of air in the paranasal sinuses on measurements of WM diffusion characteristics. MATERIALS AND METHODS: The study was embedded in the Generation R Study, a prospective population-based birth cohort in Rotterdam (the Netherlands). Brain MR imaging studies (1070 children, 6-9 years of age) were evaluated for mucosal thickening of the paranasal sinuses. Nonaeration of the paranasal sinuses (modified Lund-Mackay score) was compared with that in a randomly selected control group. The relationship between nonaerated paranasal sinuses and fractional anisotropy and mean diffusivity in the DTI fiber tracts was evaluated using ANCOVA and independent t tests. RESULTS: The prevalence of mucosal thickening was 10.2% (109/1070). The mean modified Lund-Mackay score was 6.87 (SD, 3.76). In 52.3% (57/109), ≥ 1 paranasal sinus was not pneumatized. The results are reported in effect sizes (Cohen's d). Lower mean fractional anisotropy values were found in the uncinate fasciculus (right uncinate fasciculus/right frontal sinus, d = -0.60), superior longitudinal fasciculus (right superior longitudinal fasciculus/right ethmoid sinus, d = -0.56; right superior longitudinal fasciculus/right sphenoid sinus, d = -2.09), and cingulate bundle (right cingulum bundle/right sphenoid sinus, d = -1.28; left cingulum bundle/left sphenoid sinus, d = -1.49). Higher mean diffusivity values were found in the forceps major/right and left sphenoid sinuses, d = 0.78. CONCLUSIONS: Nonaeration of the paranasal sinuses is a common incidental finding on pediatric MR imaging brain scans. The amount of air in the paranasal sinuses can influence fractional anisotropy and, to a lesser degree, mean diffusivity values of WM tracts and should be considered in DTI studies in pediatric populations.

Pre-Operative Ocular Findings and Long-Term Follow-Up in a Large Cohort of Non-Syndromic Unicoronal Craniosynostosis.

(1) Background: Non-syndromic unicoronal craniosynostosis (UCS) is associated with a high prevalence of ocular anomalies. Currently, the etiology of this association remains obscure, however, it is presumed to be primarily attributed to their orbital malformations and/or secondary to craniofacial surgery. We assessed pre-operative ophthalmological examinations of non-syndromic UCS patients and compared them with their postoperative outcomes and long-term follow-up. (2) Methods: A retrospective case series was conducted on medical records of patients with non-syndromic UCS at Sophia Children's Hospital, Rotterdam. Ophthalmologic examinations were collected at different time periods: T1 (first visit), T2 (<1 year after cranioplasty), and T3 (long-term follow-up at last visit). The McNemar's test was used for statistical analysis. (3) Results: A total of 101 patients were included, for whom examinations were available at T1 and T3. Patients had a mean age of 2.8 years (±2.7) and 9.5 (±4.9) at T1 and T3, respectively. At T1, 52 patients (51.5%) were diagnosed with strabismus, and 61 patients (60.4%) at T3. Vertical strabismus increased significantly from 23 patients (22.8%) at T1 to 36 patients (35.6%) at T3 (p = 0.011). Followed by astigmatism, which increased significantly from 38 (37.6%) at T1 to 59 (58.4%) patients at T3 (p = 0.001). T1 was available in 20 patients prior to fronto-orbital advancement (FOA), therefore, a sub-analysis was conducted on these patients, which was followed shortly after FOA at T2. Prior to FOA, strabismus was present in 11 patients (55.0%) and in 12 patients (60.0%) at T2. After FOA, strabismus worsened in two patients. (4) Conclusions: This study showed the high prevalence of ocular anomalies in patients with non-syndromic UCS before and after cranioplasty and at long-term follow-up. The findings of this study show that ophthalmic and orthoptic examinations are an important part of the optimal treatment of patients with non-syndromic UCS.

Comparing Smartphone Virtual Reality Exposure Preparation to Care as Usual in Children Aged 6 to 14 Years Undergoing Magnetic Resonance Imaging: Protocol for a Multicenter, Observer-Blinded, Randomized Controlled Trial.

BACKGROUND: A magnetic resonance imaging (MRI) procedure can cause preprocedural and periprocedural anxiety in children. Psychosocial interventions are used to prepare children for the procedure to alleviate anxiety, but these interventions are time-consuming and costly, limiting their clinical use. Virtual reality (VR) is a promising way to overcome these limitations in the preparation of children before an MRI scan. OBJECTIVE: The objective of this study is (1) to develop a VR smartphone intervention to prepare children at home for an MRI procedure; and (2) to examine the effect of the VR intervention in a randomized controlled trial, in which the VR intervention will be compared to care as usual (CAU). CAU involves an information letter about an MRI examination. The primary outcome is the child's procedural anxiety during the MRI procedure. Secondary outcomes include preprocedural anxiety and parental anxiety. We hypothesize that the VR preparation will result in a higher reduction of the periprocedural anxiety of both parents and children as compared to CAU. METHODS: The VR intervention provides a highly realistic and child-friendly representation of an MRI environment. In this randomized controlled trial, 128 children (aged 6 to 14 years) undergoing an MRI scan will be randomly allocated to the VR intervention or CAU. Children in the VR intervention will receive a log-in code for the VR app and are sent cardboard VR glasses. RESULTS: The VR smartphone preparation app was developed in 2020. The recruitment of participants is expected to be completed in December 2022. Data will be analyzed, and scientific papers will be submitted for publication in 2023. CONCLUSIONS: The VR smartphone app is expected to significantly reduce pre- and periprocedural anxiety in pediatric patients undergoing an MRI scan. The VR app offers a realistic and child-friendly experience that can contribute to modern care. A smartphone version of the VR app has the advantage that children, and potentially their parents, can get habituated to the VR environment and noises in their own home environment and can do this VR MRI preparation as often and as long as needed. TRIAL REGISTRATION: ISRCTN Registry ISRCTN20976625; https://www.isrctn.com/ISRCTN20976625. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41080.