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Matthew T Whitehead,1,2 Asim F Choudhri,1,2 Sarwat Salim31Department of Radiology, University of Tennessee Health Science Center, Memphis, TN, USA; 2Le Bonheur Neuroscience Institute, Le Bonheur Children’s Hospital, Memphis, TN, USA; 3Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USAAbstract: Axenfeld–Rieger syndrome (ARS) is a genetic disorder representing a disease spectrum resulting from neural crest cell maldevelopment. Glaucoma is a common complication from the incomplete formation of the iridocorneal angle structures. Neural crest cells also form structures of the forebrain and pituitary gland, dental papillae, aortic arch walls, genitalia, and long bones; therefore, patients with ARS manifest a wide range of systemic findings. To our knowledge, detailed magnetic resonance imaging findings have not been previously reported. We report a case of a 19-month-old Indian male diagnosed with ARS with emphasis on magnetic resonance imaging findings of the globes, brain, teeth, and skull base.Keywords: ARS, glaucoma, megalocornea, orbit MRI

Background and Purpose: In fetuses with lateral ventriculomegaly and normal posterior fossa cerebrospinal spaces, third ventricle distention is a compelling clue that supports a diagnosis of aqueductal stenosis. However, this association assumes normal ventricular anatomy. Structural constraints can impair pressure-induced compliance. We aimed to determine how thalamic massa intermedia size alterations may impact the size of the third ventricle in the setting of congenital aqueductal stenosis., Materials and Methods: This retrospective study was performed at a single academic pediatric hospital after institutional review board approval. We searched our brain MRI reports for all examinations describing aqueductal stenosis and included all the patients who had both fetal and postnatal examinations. Patients with interhypothalamic adhesions and hydrocephalus unrelated to congenital aqueductal stenosis were excluded from this study. We evaluated all the MRIs for the presence of thalamic massa intermedia and documented third ventricle diameters (supraoptic recess, central and suprapineal recesses) and the thalamic massa intermedia circumference. The Spearman correlation was used to identify the potential relationship between the thalamic massa intermedia circumference and third ventricle size in fetal and postnatal MRIs. Patients were also stratified into 2 groups based on the presence or absence of thalamic massa intermedia. Mann-Whitney U tests were used to compare third ventricle diameters between these groups., Results: The study included both fetal and postnatal studies from 59 patients. The overall third ventricle diameter was inversely proportional to the circumference of the thalamic massa intermedia in both groups (fetal: P = .001, ρ = -0.422; [95% CI, -0.628 to -0.181]; postnatal: P < .001, ρ = -0.653; [95% CI, -0.782 to -0.479]). Nonetheless, dilation of anterior and posterior recesses still occurred when the mid third ventricle was nondilated or less severely dilated in patients with an enlarged thalamic massa intermedia. Third ventricle dilation was most severe in patients lacking a thalamic massa intermedia compared with patients with a thalamic massa intermedia ( P < .001)., Conclusions: In patients with suspected congenital aqueductal stenosis, lack of marked third ventriculomegaly as conventionally measured can sometimes be explained by thickening of the thalamic massa intermedia. In this circumstance, it is important to evaluate the extreme recesses of the third ventricle for evidence of dilation on fetal MRI., (© 2024 by American Journal of Neuroradiology.)

Background and Purpose: Sotos syndrome is a rare autosomal dominant condition caused by pathogenic mutations in the NSD1 gene that presents with craniofacial dysmorphism, overgrowth, seizures, and neurodevelopmental delay. Macrocephaly, ventriculomegaly, and corpus callosal dysmorphism are typical neuroimaging features that have been described in the medical literature. The purpose of this study was to expand on the neuroimaging phenotype by detailed analysis of a large cohort of patients with genetically proved Sotos syndrome., Materials and Methods: This multicenter, multinational, retrospective observational cohort study systematically analyzed the clinical characteristics and neuroimaging features of 77 individuals with genetically diagnosed Sotos syndrome, via central consensus review with 3 pediatric neuroradiologists., Results: In addition to previously described features, malformations of cortical development were identified in most patients (95.0%), typically dysgyria (92.2%) and polymicrogyria (22.1%), varying in location and distribution. Incomplete rotation of the hippocampus was observed in 50.6% of patients and was associated with other imaging findings, in particular with dysgyria (100% versus 84.2%, P  = .012)., Conclusions: Our findings show a link between the genetic-biochemical basis and the neuroimaging features and aid in better understanding the underlying clinical manifestations and possible treatment options. These findings have yet to be described to this extent and correspond with recent studies that show that NSD1 participates in brain development and has interactions with other known relevant genetic pathways., (© 2024 by American Journal of Neuroradiology.)

Monochorionic twins are at risk for complications due to the presence of placental vascular anastomoses, including twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, and twin reversed arterial perfusion sequence. While ultrasound is the primary modality to screen for the development of these complications, MRI plays an important role in assessing monochorionic twin pregnancies for the development of other complications, such as neurologic injury. In this article, the authors review the ultrasound imaging findings associated with monochorionic twin complications, management options, and the role for MRI in these pregnancies., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%) and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%) and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%) and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P = 0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%), motor delay with non-ambulance (64%), and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P = 0.003), non-ambulance (P = 0.035), ongoing enteral feeds (P < 0.001) and cortical visual impairment (P = 0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs, provide insights into their neurological basis, and vitally, enable meaningful genetic counselling for affected individuals and their families., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Brain malformations represent a heterogeneous group of abnormalities of neural morphogenesis, often associated with aberrations of neuronal connectivity and brain volume. Prenatal detection of brain malformations requires a clear understanding of embryology and developmental morphology through the various stages of gestation. This expert panel review is written with the central aim of providing an easy-to-understand roadmap to improve prenatal detection and characterization of structural malformations based on the current understanding of normal and aberrant brain development. The utility of each available neuroimaging modality including prenatal multiplanar neurosonography, anatomical magnetic resonance imaging (MRI), and advanced MRI techniques, as well as further insights from post-mortem imaging have been highlighted for every developmental stage., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

NAA10-related (Ogden syndrome) and NAA15-related neurodevelopmental syndrome are known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations of NAA10 and NAA15 variants are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic (P) or likely pathogenic (LP) variants in the NAA10 cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with (L)P variants in the NAA15 cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in our NAA10 cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified in the prevalence of these conditions between the NAA10 and NAA15 variants. Our study includes novel neuroimaging of 13 NAA10 and 5 NAA15 probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: NAA10 -related (Ogden Syndrome) and NAA15 -related neurodevelopmental syndromes present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. While there is much data on the clinical manifestations of these conditions, there are few radiologic reports describing the neuroanatomical abnormalities present on imaging., Objective: Our goal was to provide neuroimaging analyses for a subset of probands with NAA10 - and NAA15 -related neurodevelopmental symptoms and assess severity, common radiologic anomalies, and changes over time to better understand the pathophysiology of these disease processes., Materials and Methods: Neuroimaging studies from 26 probands (18 with pathogenic variants in NAA10 , 8 with pathogenic variants in NAA15 ) were collected and analyzed. Size of the cerebrum, brainstem, and cerebellum, as well as myelination, brain malformations, globus pallidus hyperintensity, brain lesions, 4th ventricle size, tegmentovermian angle, cisterna magna size, pituitary size, olfactory tract, palate arch, and choroid plexus abnormalities were analyzed. In depth medical histories were also collected on all probands, including genetic testing results and social, cognitive, and developmental history. The Vineland 3 Adaptive Behavior Scale was also administered to the parents to assess functional status of the probands., Results: On average, individuals with Ogden Syndrome had 5.7 anatomical abnormalities (standard deviation (SD) = 3.0), whereas those with NAA15 related neurodevelopmental syndrome had 2.8 (SD = 2.3) (p = .02). Probands who had more anatomical abnormalities tended to score worse on Vineland assessments, suggesting a possible correlation between the two. Structural-functional anatomic differences seen were preserved such that individuals with greater defects on, for example, motor regions of their scans tested worse on motor portions of the Vineland. Probands followed longitudinally demonstrated several changes between scans, most commonly in the cerebellum, brainstem, and degree of myelination. Such changes were only observed for probands with NAA10 variants in our cohort., Conclusion: Despite clinical imaging being reported as being predominantly "normal" during routine clinical care, this analysis of a cohort of patients with NAA10 -related (Ogden Syndrome) and NAA15 -related neurodevelopmental syndrome by one neuroradiologist has established a range of subtle abnormalities. We hope these findings guide future research and diagnostic studies for this patient population., Competing Interests: Competing Interests The authors declare that they have no competing interests or personal relationships that could have influenced the work reported in this paper.

Background and Purpose: While classic brain MR imaging features of Alexander disease have been well-documented, lesional patterns can overlap with other leukodystrophies, especially in the early stages of the disease or in milder phenotypes. We aimed to assess the utility of a new neuroimaging sign to help increase the diagnostic specificity of Alexander disease., Materials and Methods: A peculiar bilateral symmetric hyperintense signal on T2-weighted images affecting the medulla oblongata was identified in an index patient with type I Alexander disease. Subsequently, 5 observers performed a systematic MR imaging review for this pattern by examining 55 subjects with Alexander disease and 74 subjects with other leukodystrophies. Interobserver agreement was assessed by the κ index. Sensitivity, specificity, and receiver operating characteristic curves were determined., Results: The identified pattern was present in 87% of subjects with Alexander disease and 14% of those without Alexander disease leukodystrophy ( P  < .001), 3 with vanishing white matter, 4 with adult polyglucosan body disease, and 3 others. It was found equally in both type I and type II Alexander disease (28/32, 88% versus 18/21, 86%; P  = .851) and in subjects with unusual disease features (2/2). Sensitivity (87.3%; 95% CI, 76.0%-93.7%), specificity (86.5%; 95% CI, 76.9%-92.5%), and interobserver agreement (κ index = 0.82) were high., Conclusions: The identified pattern in the medulla oblongata, called the chipmunk sign due to its resemblance to the face of this rodent, is extremely common in subjects with Alexander disease and represents a diagnostic tool that can aid in early diagnosis, especially in subjects with otherwise atypical MR imaging findings and/or clinical features., (© 2024 by American Journal of Neuroradiology.)

Abnormalities of dental development and anatomy may suggest the presence of congenital or acquired anomalies. The detection of abnormalities, therefore, is an important skill for radiologists to achieve. Knowledge of dental embryology and an understanding of the radiologic appearances of teeth at various stages of maturation are required for the appreciation of abnormal dental development. While many tooth abnormalities are well-depicted on dedicated dental radiographs, the first encounter with a dental anomaly may be by a radiologist on a computed tomographic (CT) or magnetic resonance (MR) exam performed for other reasons. This article depicts normal dental anatomy and development, describing the appearance of the neonatal dentition on CT and MRI, the modalities most often encountered by clinical radiologists. The radiology and dental literature are reviewed, and key concepts are illustrated with supplemental cases from our institution. The value of knowledge of dental development is investigated using the analysis of consecutive MR brain examinations. Finally, the anatomical principles are applied to the diagnosis of odontogenic infection on CT. Through analysis of the literature and case data, the contrast of dental pathology with normal anatomy and development facilitates the detection and characterization of both congenital and acquired dental disease.

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations included severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband's low levels of citrulline and lactic acidosis provoked by administration of Depakoke were evocative of a mitochondrial etiology. The proband's genotype-phenotype correlation remained undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provided evidence of a deficient oxidative-phosphorylation pathway responsible for adenosine triphosphate (ATP) synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis revealed metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirmed the suspected mitochondrial etiology, as the proband's mitochondria exhibited an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that suboptimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward oxidative phosphorylation (OXPHOS) leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of the fetal and postnatal brain.

Mitochondrial diseases, a diverse and intricate group of disorders, result from both nuclear DNA and mitochondrial DNA malfunctions, leading to a decrease in cellular energy (ATP) production. The increasing understanding of molecular, biochemical, and genetic irregularities associated with mitochondrial dysfunction has led to a wider recognition of varying mitochondrial disease phenotypes. This broadening landscape has led to a diverse array of neuroimaging findings, posing a challenge to radiologists in identifying the extensive range of possible patterns. This review meticulously describes the central imaging features of mitochondrial diseases in children, as revealed by neuroimaging. It spans from traditional imaging findings to more recent and intricate diagnoses, offering insights and highlighting advancements in neuroimaging technology that can potentially guide a more efficient and accurate diagnostic approach., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work., (Published by Elsevier Inc.)

Background and Purpose: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implications for clinical outcomes. In this article, we offer detailed information on the association of brainstem dysgenesis in a large, multicentric cohort of patients with the Dandy-Walker phenotype, defining different subtypes of involvement and their potential clinical impact., Materials and Methods: In this established multicenter cohort of 329 patients with the Dandy-Walker phenotype, we include and retrospectively review the MR imaging studies and clinical records of 73 subjects with additional brainstem malformations. Detailed evaluation of the different patterns of brainstem involvement and their potential clinical implications, along with comparisons between posterior fossa measurements for the diagnosis of the Dandy-Walker phenotype, was performed among the different subgroups of patients with brainstem involvement., Results: There were 2 major forms of brainstem involvement in patients with Dandy-Walker phenotype including the following: 1) the mild form with anteroposterior disproportions of the brainstem structures "only" (57/73; 78%), most frequently with pontine hypoplasia (44/57; 77%), and 2) the severe form with patients with tegmental dysplasia with folding, bumps, and/or clefts (16/73; 22%). Patients with severe forms of brainstem malformation had significantly increased rates of massive ventriculomegaly, additional malformations involving the corpus callosum and gray matter, and interhemispheric cysts. Clinically, patients with the severe form had significantly increased rates of bulbar dysfunction, seizures, and mortality., Conclusions: Additional brainstem malformations in patients with the Dandy-Walker phenotype can be divided into 2 major subgroups: mild and severe. The severe form, though less prevalent, has characteristic imaging features, including tegmental folding, bumps, and clefts, and is directly associated with a more severe clinical presentation and increased mortality., (© 2023 by American Journal of Neuroradiology.)

Infantile botulism is an uncommon diagnosis and rarer still in the neonatal period. We describe three cases of neonatal-onset botulism that presented with symptoms typically (hypotonia, constipation, facial diplegia) or atypically seen in older infants (encephalopathy, seizures, and hypothermia). Our series shows a wider spectrum of clinical presentations in patients with neonatal-onset botulism. Our report also suggests that neonatal-onset botulism should be considered more broadly in the hypotonic infant, especially as the condition is treatable with intravenous botulinum-specific immune globulin., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Fetal ventriculomegaly is a source of apprehension for expectant parents and may present prognostic uncertainty for physicians. Accurate prenatal counseling requires knowledge of its cause and associated findings as the differential diagnosis is broad. We have observed an association between ventriculomegaly and incomplete hippocampal inversion., Objective: To determine whether ventricular size is related to incomplete hippocampal inversion., Materials and Methods: We retrospectively evaluated pre- and postnatal brain MRIs in normal subjects (mean GA, 31 weeks; mean postnatal age, 27 days) and patients with isolated ventriculomegaly (mean GA, 31 weeks; mean postnatal age, 68 days) at a single academic medical center. Lateral ventricular diameter, multiple qualitative and quantitative markers of hippocampal inversion, and evidence of intraventricular hemorrhage were documented., Results: Incomplete hippocampal inversion and ventricular size were associated in both normal subjects (n=51) and patients with ventriculomegaly (n=32) (P<0.05). Severe ventriculomegaly was significantly associated with adverse clinical outcome in postnatal (P=0.02) but not prenatal (P=0.43) groups. In all additional cases of isolated ventriculomegaly, clinical outcome was normal over the time of assessment (mean 1±1.9 years; range 0.01 to 10 years)., Conclusion: Lateral ventricular atrial diameter and incomplete hippocampal inversion are associated. Less hippocampal inversion correlates with larger atria. For every 1-mm increase in fetal ventricular size, the odds of incomplete hippocampal inversion occurring increases by a factor of 1.6 in normal controls and 1.4 in patients with ventriculomegaly., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: None declared.

This review presents a practical approach to imaging the fetal brain by MRI. Herein, we demonstrate how to measure brain structures and fluid spaces, and discuss the importance of comparing measurements to normative biometric references at a corresponding gestational age. We present some common imaging dilemmas of the technical aspects of fetal MRI with regard to typical regions of abnormality including the cerebrum, the ventricular system, and the posterior fossa, and discuss how to resolve them.

Competing Interests: The authors disclose no conflicts of interest.

Background: Fetal magnetic resonance imaging (MRI) may reveal sonographically occult ocular abnormalities. When discovered, acquired causes and genetic associations must be sought., Objective: We aim to evaluate a fetal cohort with orbit and/or globe malformations to determine whether there are imaging patterns that suggest the underlying cause., Materials and Methods: We searched all fetal MRI reports performed at an academic children's hospital over 9 consecutive years for orbit and/or globe abnormalities. Each positive exam and all follow-up MRIs were evaluated for interocular distance, globe size, shape and signal, and brain malformations. Genetic and clinical diagnoses were recorded from the medical record., Results: Seventy-six of 3,085 fetuses (2.5%) were diagnosed with ocular and/or globe abnormalities; 50% had postnatal follow-up MR exams, all confirming the fetal MRI findings. Ninety-two percent (70/76) had concurrent brain malformations. Sixty-seven percent (51/76) were diagnosed with an underlying disorder and 39% of these were genetically proven. The most common diagnoses with ocular globe abnormalities included CHARGE (coloboma of the eye, heart anomaly, choanal atresia, retardation and genital and ear anomalies) syndrome, trisomy 13 syndrome, dystroglycanopathy, holoprosencephaly and diencephalic-mesencephalic junction dysplasia. Genetic diagnoses were more likely with ocular globe abnormalities than isolated orbital abnormalities (P=0.04). Sixty-seven percent of fetuses with ocular calcifications, hemorrhage and/or lens abnormalities had potential maternal risk factors (P=0.03)., Conclusion: Malformed ocular globes are associated with brain malformations and genetic abnormalities. Ocular calcifications, hemorrhage and/or lens abnormalities may be associated with maternal risk factors. Genetic work-up should be considered when an ocular globe size or shape abnormality is detected., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Childhood ataxia may be due to multifactorial causes of impairment in the coordination of movement and balance. Acutely presenting ataxia in children may be due to infectious, inflammatory, toxic, ischemic, or traumatic etiology. Intermittent or episodic ataxia in children may be manifestations of migraine, benign positional vertigo, or intermittent metabolic disorders. Nonprogressive childhood ataxia suggests a congenital brain malformation or early prenatal or perinatal brain injury, and progressive childhood ataxia indicates inherited causes or acquired posterior fossa lesions that result in gradual cerebellar dysfunction. CT and MRI of the central nervous system are the usual modalities used in imaging children presenting with ataxia, based on the clinical presentation. This document provides initial imaging guidelines for a child presenting with acute ataxia with or without a history of recent trauma, recurrent ataxia with interval normal neurological examination, chronic progressive ataxia, and chronic nonprogressive ataxia. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Focal cortical dysplasia (FCD) is the most common cause of surgically remediable epilepsy in children. Little is known about the risk factors for the timing and development of pharmacoresistance in this population. This study sought to evaluate the prevalence and risk factors for pharmacoresistance in pediatric FCD-related epilepsy., Methods: In this retrospective single-center cohort design, patients were identified from search of centralized radiology report database and a central epilepsy surgical database. Inclusion criteria consisted of 3T MRI-confirmed FCD from January, 2011, to January, 2020; ages 0 days to 22 years at MRI; and at least 18 months of documented follow-up after MRI, unless had single seizure or incidentally discovered FCD. Records were excluded if there was dual pathology (except for mesial temporal sclerosis), hemimegalencephaly, or tuberous sclerosis complex present in imaging or history., Results: One hundred forty-three patients with confirmed FCD met the inclusion criteria. One hundred twenty-four children had epilepsy (87% of patients with FCD) with median age at seizure onset 2.7 years (IQR 0.75-6 years, range 0-17 years). Twelve children (8.5%) had a single lifetime seizure (provoked or unprovoked) or recurrent provoked seizures. Seven children (4.9%) had incidental FCD. Ninety-two patients (74%) of those with epilepsy met criteria for pharmacoresistance. Of children with epilepsy of all types, 93 children (75%) were seizure-free at the last visit; 82 patients underwent epilepsy surgery, of whom 59 (72%) achieved seizure freedom. Seven percent (9/124) achieved seizure freedom with a second ASM and 5.6% (7/124) with a third or more ASMs. Failure of only 1 antiseizure medication is associated with enormous increased incidence and earlier development of pharmacoresistance (OR 346; 95% CI 19.6-6,100); Cox regression showed FCD lobar location, pathologic subtype, and age at seizure onset are not., Discussion: Failure of 1 antiseizure medication is associated with substantial risk of pharmacoresistance. These data support an operational redefinition of pharmacoresistance, for surgical planning, in FCD-related epilepsy to the failure of 1 antiseizure medication and support early, potentially curative surgery to improve outcomes in this patient population., (© 2022 American Academy of Neurology.)

Background and Purpose: The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development., Materials and Methods: In this multicenter study, retrospective MR imaging examinations from fetuses and children previously diagnosed with Dandy-Walker malformation or vermian hypoplasia were re-evaluated, using the choroid plexus/tela choroidea location and the fastigial recess shape to differentiate Dandy-Walker malformation from vermian hypoplasia. Multiple additional measures of the posterior fossa and cerebellum were also obtained and compared between Dandy-Walker malformation and other diagnoses., Results: Four hundred forty-six examinations were analyzed (174 fetal and 272 postnatal). The most common diagnoses were Dandy-Walker malformation (78%), vermian hypoplasia (14%), vermian hypoplasia with Blake pouch cyst (9%), and Blake pouch cyst (4%). Most measures were significant differentiators of Dandy-Walker malformation from non-Dandy-Walker malformation both pre- and postnatally ( P  < .01); the tegmentovermian and fastigial recess angles were the most significant quantitative measures. Posterior fossa perimeter and vascular injury evidence were not significant differentiators pre- or postnatally ( P  > .3). The superior posterior fossa angle, torcular location, and vermian height differentiated groups postnatally ( P  < .01), but not prenatally ( P  > .07)., Conclusions: As confirmed by objective measures, the modern Dandy-Walker malformation phenotype is best defined by inferior predominant vermian hypoplasia, an enlarged tegmentovermian angle, inferolateral displacement of the tela choroidea/choroid plexus, an obtuse fastigial recess, and an unpaired caudal lobule. Posterior fossa size and torcular location should be eliminated from the diagnostic criteria. This refined phenotype may help guide future study of the numerous etiologies and varied clinical outcomes., (© 2022 by American Journal of Neuroradiology.)

Objective: The purpose of this study was to evaluate if focal cortical dysplasia (FCD) co-localization to cortical functional networks is associated with the temporal distribution of epilepsy onset in FCD., Methods: International (20 center), retrospective cohort from the Multi-Centre Epilepsy Lesion Detection (MELD) project. Patients included if >3 years old, had 3D pre-operative T1 magnetic resonance imaging (MRI; 1.5 or 3 T) with radiologic or histopathologic FCD after surgery. Images processed using the MELD protocol, masked with 3D regions-of-interest (ROI), and co-registered to fsaverage&#95;sym (symmetric template). FCDs were then co-localized to 1 of 7 distributed functional cortical networks. Negative binomial regression evaluated effect of FCD size, network, histology, and sulcal depth on age of epilepsy onset. From this model, predictive age of epilepsy onset was calculated for each network., Results: Three hundred eighty-eight patients had median age seizure onset 5 years (interquartile range [IQR] = 3-11 years), median age at pre-operative scan 18 years (IQR = 11-28 years). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), front parietal control (52), ventral attention (32), dorsal attention (31), and visual (31). Larger lesions were associated with younger age of onset (p = 0.01); age of epilepsy onset was associated with dominant network (p = 0.04) but not sulcal depth or histology. Sensorimotor networks had youngest onset; the limbic network had oldest age of onset (p values <0.05)., Interpretation: FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor and visual) with earlier onset, and limbic latest onset. These variations may reflect developmental differences in synaptic/white matter maturation or network activation and may provide a biological basis for age-dependent epilepsy onset expression. ANN NEUROL 2022;92:503-511., (© 2022 American Neurological Association.)

Despite its vigorous ability to detect and measure metabolic disturbances, 1 H MRS remains underutilized in clinical practice. MRS increases diagnostic yield and provides therapeutic measures. Because many inborn metabolic errors are now treatable, early diagnosis is crucial to prevent or curb permanent brain injury. Therefore, patients with known or suspected inborn metabolic errors stand to benefit from the addition of MRS. With education and practice, all neuroradiologists can perform and interpret MRS notwithstanding their training and prior experience. In this two-part review, we cover the requisite concepts for clinical MRS interpretation including technical considerations and normal brain spectral patterns based on age, location, and methodology., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Proton MRS of the brain provides the ability to gather direct information regarding the metabolic status of the brain at the time of MRI. Although selective vulnerability of brain tissue may yield distinct imaging patterns in neurometabolic disorders, it is not uncommon for the brain MRI to be normal, nonspecific, or show ambiguous abnormalities among several possible diagnoses, metabolic, or otherwise. This review highlights childhood neurometabolic diseases in which 1 H MRS may show diagnostic or suggestive metabolic profiles without complicated acquisition or postprocessing techniques., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inborn errors of metabolism (IEM) are a group of disorders due to functional defects in one or more metabolic pathways that can cause considerable morbidity and death if not diagnosed early. While individually rare, the estimated global prevalence of IEMs comprises a substantial number of neonatal and infantile disorders affecting the central nervous system. Clinical manifestations of IEMs may be nonspecific. Newborn metabolic screens do not capture all IEMs, and likewise, genetic testing may not always detect pathogenic variants. Neuroimaging is a critical component of the work-up, given that imaging sometimes occurs before prenatal screen results are available, which may allow for recognition of imaging patterns that lead to early diagnosis and treatment of IEMs. This review will demonstrate the role of magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ( 1 H MRS) in the evaluation of IEMs. The focus will be on scenarios where MRI and 1 H MRS are suggestive of or diagnostic for IEMs, or alternatively, refute the diagnosis.

Objective: The purpose of this study was to investigate injury occurrence sustained by collegiate rodeo athletes during practice and competition., Design: Descriptive epidemiology., Setting: Eleven National Intercollegiate Rodeo Association member institutions across the United States., Participants: Participants included 264 male and female college rodeo athletes. Athletic trainers (ATs) from each institution reported injury and exposure data using the National Collegiate Athletic Association Injury Surveillance Program., Interventions: Institutional ATs reported athlete exposures (AEs) and injuries that occurred from collegiate rodeo practices and competitions., Main Outcome Measure: Injury and AEs from practices and competitions for one college rodeo season were analyzed. Injury rates and ratios were calculated for non-time loss (NTL) and time loss (TL) with 95% confidence intervals (CI)., Results: Data revealed a higher proportion of TL than NTL injuries [2.47 vs 1.77 per 1000 AE; injury rate ratios (IRRs) = 1.39; 95% CI: 0.93-2.08]. There was a higher injury rate during competition as compared with practice (10.98 vs 3.09 per 1000 AE; IRR = 3.56; 95% CI: 2.36-5.35), but more injuries were reported in practice (62.2%)., Conclusions: Although the injury rate during rodeo competition was significantly higher than during practice in this study, a greater number of injuries were reported during practice. This indicates all college rodeo athletes can potentially benefit from available medical care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to assess the association of clinical risk factors with severity of magnetic resonance imaging (MRI) brain injury in neonatal extracorporeal membrane oxygenation (ECMO) patients., Study Design: This is a single-center retrospective study conducted at an outborn level IV neonatal intensive care unit in a free-standing academic children's hospital. Clinical and MRI data from neonates treated with ECMO between 2005 and 2015 were reviewed. MRI injury was graded by two radiologists according to a modified scoring system that assesses parenchymal injury, extra-axial hemorrhage, and cerebrospinal fluid spaces. MRI severity was classified as none (score = 0), mild/moderate (score = 1-13.5), and severe (score ≥ 14). The relationship between selected risk factors and MRI severity was assessed by Chi-square, analysis of variance, and Kruskal-Wallis tests where appropriate. Combinative predictive ability of significant risk factors was assessed by logistic regression analyses., Results: MRI data were assessed in 81 neonates treated with ECMO. Veno-arterial (VA) patients had more severe injury compared with veno-venous patients. There was a trend toward less severe injury over time. After controlling for covariates, duration of ECMO remained significantly associated with brain injury, and the risk for severe injury was significantly increased in patients on ECMO beyond 210 hours., Conclusion: Risk for brain injury is increased with VA ECMO and with longer duration of ECMO. Improvements in care may be leading to decreasing incidence of brain injury in neonatal ECMO patients., Key Points: · Veno-arterial ECMO is associated with more brain injury by MRI compared with veno-venous ECMO.. · Longer duration of ECMO is significantly associated with severe brain injury by MRI.. · Risk for neurologic injury may be decreasing over time with advances in neonatal ECMO.., Competing Interests: None declared., (Thieme. All rights reserved.)

Magnetic resonance spectroscopy (MRS) is a valuable adjunct to structural brain imaging. State-of-the-art MRS has benefited greatly from recent technical advancements. Neurometabolic alterations in pediatric brain diseases have implications for diagnosis, prognosis, and therapy. Herein, the authors discuss MRS technical considerations and applications in the setting of various pediatric disease processes including tumors, metabolic diseases, hypoxic/ischemic encephalopathy/stroke, epilepsy, demyelinating disease, and infection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: We aim to evaluate the utility of the Round Window Angle (RWA) as a predictor of difficulty and operative time in cochlear implantation., Methods: A retrospective study of pediatric patients that underwent cochlear implantation and CT temporal bone imaging from January 2008 to November 2019. Correlation, univariate, and multivariate analysis were conducted., Results: 347 implantations met inclusion criteria. We found a difference in RWA for difficult (median: 101°, n = 5) and non-difficult (median: 74, n = 317) implantations (p < 0.0001). There was also a difference in RWA in patients with round windows visualized intra-operatively (p < 0.0197). When controlling for age and intraoperative round window visualization, logistic regression showed RWA was significantly associated with difficult insertion (OR: 1.687; p = 0.0246). Further, there was positive correlation between RWA and operative time (r = 0.1779, p = 0.0013) with patients with acute RWAs having shorter operative times (mean 115.7 ± 32.1 min) than those with obtuse RWA (mean 183.5 ± 97.0 min) (p = 0.0035). When accounting for surgeon and patient age, multivariate linear regression showed round window visualization (β = 3.456, p = 0.0006) and obtuse RWA (β = 6.172, p < 0.0001) was associated with an increase in operative time., Conclusion: Further research is needed to identify difficult cochlear implantations to increase the success and reduce risks associated with the surgery. Our study reports the possibility that an obtuse RWA both significantly increases difficulty and time of operation due to decreased round window visualization., (Copyright © 2021. Published by Elsevier B.V.)

Hearing loss in pediatric age group is associated with many congenital temporal bone disorders. Aberrant development of various ear structures leads into either conductive or sensorineural hearing loss. Knowledge of the embryology and anatomical details of various compartments of the ear help better understanding of such disorders. In general, abnormalities of external and middle ears result in conductive hearing loss. Whereas abnormalities of inner ear structures lead into sensorineural hearing loss. These abnormalities could occur as isolated or part of syndromes. Temporal bone disorders are a significant cause of morbidity and developmental delays in children. Imaging evaluation of children presented with hearing loss is paramount in early diagnosis and proper management planning. Our aim is to briefly discuss embryology and anatomy of the pediatric petrous temporal bones. The characteristic imaging features of commonly encountered congenital temporal bone disorders and their associated syndromes will be discussed., (Published by Elsevier Inc.)

Background: Dandy-Walker malformation and Blake pouch cysts can have overlapping imaging features. The choroid plexus and associated taenia-tela choroidea complex are displaced inferolaterally in Dandy-Walker malformation and below the vermis in Blake pouch cysts., Objective: To determine the normal fetal and postnatal MR appearance of the choroid plexus and taenia-tela choroidea complex, and whether their location can help distinguish Dandy-Walker malformation from Blake pouch cysts., Materials and Methods: In this retrospective study, we evaluated brain MR exams from normal-appearing fetuses (gestational age 19-38 weeks) and infants, fetal and postnatal exams in Blake pouch cysts and Dandy-Walker malformation, and ambiguous cases equivocal for mild Dandy-Walker malformation and Blake pouch cysts. We documented choroid plexus and the taenia-tela choroidea complex location and axial and sagittal angles in each case. Then we contrasted and compared the original and updated fetal diagnoses based on taenia-tela choroidea complex and choroid plexus positions., Results: The choroid plexus location and the taenia-tela choroidea complex location and angles varied significantly among normal exams, Blake pouch cyst exams and Dandy-Walker malformation exams (P<0.01). Dandy-Walker malformation showed inferolateral displacement of the taenia-tela choroidea complex and choroid plexus distant from the vermis. Adding the taenia-tela choroidea complex and choroid plexus into the assessment improved diagnostic accuracy, especially in ambiguous cases., Conclusion: The location of the taenia-tela choroidea complex and choroid plexus provided additional diagnostic neuroimaging clues that could be used in conjunction with other conventional findings to distinguish Dandy-Walker malformation and Blake pouch cysts. Normal, Blake pouch cyst, and Dandy-Walker malformation cases differed with regard to taenia-tela choroidea complex and choroid plexus position. Inferolateral taenia-tela choroidea complex displacement distant from the vermian margin was characteristic of Dandy-Walker malformation.

Background: Neuroimaging detection of sensorineural hearing loss (SNHL)-related temporal bone abnormalities is limited (20-50%). We hypothesize that cochlear signal differences in gray-scale data may exceed the threshold of human eye detection. Gray-scale images can be post-processed to enhance perception of tonal difference using "pseudo-color" schemes., Objective: To compare patients with unilateral SNHL to age-matched normal magnetic resonance imaging (MRI) exams for "labyrinthine color differences" employing pseudo-color post-processing., Materials and Methods: The MRI database at an academic children's hospital was queried for "hearing loss." Only unilateral SNHL cases were analyzed. Sixty-nine imaging exams were reviewed. Thirteen age-matched normal MR exams in children without hearing loss were chosen for comparison. Pseudo-color was applied with post-processing assignment of specific hues to each gray-scale intensity value. Gray-scale and pseudo-color images were qualitatively evaluated for signal asymmetries by a board-certified neuroradiologist blinded to the side of SNHL., Results: Twenty-six SNHL (mean: 7.6±3 years) and 13 normal control exams (mean: 7.3±4 years) were included. All patients had normal gray-scale cochlear signal and all controls had symmetrical pseudo-color signal. However, pseudo-color images revealed occult asymmetries localizing to the SNHL ear with lower values in 38%. Ninety-one percent of these cases showed concordance between the side of pseudo-color positivity and the side of hearing loss., Conclusion: Pseudo-color perceptual image enhancement reveals intra-labyrinthine fluid alterations on MR exams in children with unilateral SNHL. Pseudo-color image enhancement techniques improve detection of cochlear pathology and could have therapeutic implications.

Objective: Report a single-center 12-year experience in the fetal diagnosis of diencephalic-mesencephalic junction dysplasia (DMJD) to expand the phenotype with Magnetic resonance imaging (MRI)-based classification, evaluate genetic etiologies, and ascertain outcomes., Methods: Retrospective medical record and imaging review of all fetal MRI exams with DMJD were performed at our institution., Results: Thirty-three pregnancies with fetal MRI findings of DMJD at 24 (18-37) weeks gestational age were studied; 70% were referred for fetal hydrocephalus. Three fetal MRI patterns were recognized. Type A (butterfly/hypothalamus-midbrain union) was seen in two cases (6%), Type B (partial thalamus-midbrain union) in 22 fetuses (70%), and Type C (complete/near complete midbrain-thalamic continuity) in nine fetuses (24%). L1CAM mutations were identified in four cases, and biallelic VRK1 variants in another. Among 14 live-born cases, 11 survived infancy, and 10 underwent postnatal brain MRI which confirmed the fetal MRI diagnosis in all but one case. Development was delayed in all surviving infants, most with additional neurological sequelae., Conclusions: DMJD may be identified by prenatal MRI as early as 18 weeks gestation. We propose three distinct phenotypic forms of DMJD, Types A-C. Next-generation sequencing provides an underlying molecular diagnosis in some patients, but further studies on associated genetic diagnoses and clinical outcomes are indicated., (© 2021 John Wiley & Sons Ltd.)

Objective: Focal Cortical Dysplasias (CD) are a common etiology of refractory pediatric epilepsy and are amenable to epilepsy surgery. We investigated the association of lesion volume and location to age of seizure onset among children with CD who underwent epilepsy surgery., Methods: A retrospective study of epilepsy surgery patients with pathologically-confirmed CD. Regions of interest (ROI) determined preoperative lesion volumes on 1.5 T and 3 T T2 and SPGR MRIs, and location in 7 distributed neural networks. Descriptive and inferential statistics were used., Results: Fifty-five patients were identified: 35 girls (56.5 %). Median age of seizure onset: 19.0 months (range 0.02 months - 16.0 years). Median age of surgery: 7.8 years (range 2.89 months - 24.45 years). CD were frontal (n = 21, 38 %); temporal (n = 15, 27 %); parietal (n = 10, 18 %); occipital (n = 3, 5%); multilobar (n = 6, 11 %). Frontal FCD had seizure onset < 1-year-old (P = 0.10); temporal lobe CD seizure onset was more likely > 5-years-old (P= 0.06). Median lesion volume for CD was 23.23 cm 3 (range: 1.87-591.73 cm 3 ). Larger CD lesions were associated with earlier epilepsy (P = 0.01, r = -0.16). We did not find that lesions proximal to early maturing cortical regions were associated with earlier seizure onset. We found an association with CD location in the default mode network (DMN) and age onset < 5years old (P = 0.03). Age of seizure onset was negatively correlated with percent of CD overlapping motor cortex (P = 0.001, r =-0.794) but not with CD overlap of the visual cortex (P = 0.35). There was no effect of CD type on age of epilepsy onset., Significance: Larger CD lesions are associated with earlier onset epilepsy. CD most commonly occurs within the DMN and Limbic network, and DMN is associated with seizure onset before 5-years-old. Percent of CD overlapping motor cortex correlates with earlier seizure onset. These observations may reflect patterns of brain maturation or regional differences in clinical expression of seizures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In children, seizures represent an extremely heterogeneous group of medical conditions ranging from benign cases, such as a simple febrile seizure, to life-threatening situations, such as status epilepticus. Underlying causes of seizures also represent a wide range of pathologies from idiopathic cases, usually genetic, to a variety of acute and chronic intracranial or systemic abnormalities. This document discusses appropriate utilization of neuroimaging tests in a child with seizures. The clinical scenarios in this document take into consideration different circumstances at the time of a child's presentation including the patient's age, precipitating event (if any), and clinical and electroencephalogram findings and include neonatal seizures, simple and complex febrile seizures, post-traumatic seizures, focal seizures, primary generalized seizures in a neurologically normal child, and generalized seizures in neurologically abnormal child. This practical approach aims to guide clinicians in clinical decision-making and to help identify efficient and appropriate imaging workup. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The urea cycle disorders (UCD) are rare genetic disorder due to a deficiency of one of six enzymes or two transport proteins that act to remove waste nitrogen in form of ammonia from the body. In this review, we focus on neuroimaging studies in OTCD and Arginase deficiency, two of the UCD we have extensively studied. Ornithine transcarbamylase deficiency (OTCD) is the most common of these, and X-linked. Hyperammonemia (HA) in OTCD is due to deficient protein handling. Cognitive impairments and neurobehavioral disorders have emerged as the major sequelae in Arginase deficiency and OTCD, especially in relation to executive function and working memory, impacting pre-frontal cortex (PFC). Clinical management focuses on neuroprotection from HA, as well as neurotoxicity from other known and yet unclassified metabolites. Prevention and mitigation of neurological injury is a major challenge and research focus. Given the impact of HA on neurocognitive function of UCD, neuroimaging modalities, especially multi-modality imaging platforms, can bring a wealth of information to understand the neurocognitive function and biomarkers. Such information can further improve clinical decision making, and result in better therapeutic interventions. In vivo investigations of the affected brain using multimodal neuroimaging combined with clinical and behavioral phenotyping hold promise. MR Spectroscopy has already proven as a tool to study biochemical aberrations such as elevated glutamine surrounding HA as well as to diagnose partial UCD. Functional Near Infrared Spectroscopy (fNIRS), which assesses local changes in cerebral hemodynamic levels of cortical regions, is emerging as a non-invasive technique and will serve as a surrogate to fMRI with better portability. Here we review two decades of our research using non-invasive imaging and how it has contributed to an understanding of the cognitive effects of this group of genetic conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sen, Anderson, Whitehead and Gropman.)

Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms., Methods and Analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans., Ethics and Dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor., Trial Registration Number: NCT02811263; Pre-result., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Posterior fossa anomalies can be diagnostic dilemmas during the fetal period. The prognosis for different diagnoses of the posterior fossa varies widely. We investigated whether fetal magnetic resonance imaging (MRI) and prenatal neurology consultation led to an alternate prognosis for fetuses referred due to concern for a fetal posterior fossa anomaly and concordance between pre- and postnatal diagnoses., Methods: This is a retrospective study of cases referred to the Prenatal Pediatrics Institute at Children's National Hospital from January 2012 to June 2018 due to concern for posterior fossa anomaly. Each encounter was scored for change in prognosis based upon clinical and fetal MRI report. Postnatal imaging was compared with prenatal imaging when available., Results: In total, 180 cases were referred for fetal posterior fossa anomalies based on outside obstetric ultrasound and had both fetal MRI and a neurology consultation. Fetal MRI and neurology consultation resulted in a change in fetal prognosis in 70% of cases. The most common referral diagnosis in our cohort was Dandy-Walker continuum, but it was not often confirmed by fetal MRI. In complex cases, posterior fossa diagnosis and prognosis determined by fetal MRI impacted choices regarding pregnancy management. Postnatal imaging was obtained in 57 (47%) live-born infants. Fetal and postnatal prognoses were similar in 60%., Conclusions: Fetal diagnosis affects pregnancy management decisions. The fetal-postnatal imaging agreement of 60% highlights the conundrum of balancing the timing of fetal MRI to provide the most accurate diagnosis of the posterior fossa abnormalities in time to make pregnancy management decisions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Urea cycle-related brain disease may take on variable neuroimaging manifestations, ranging from normal to abnormal with or without a signature appearance. In the past, we have described the usefulness of multimodal imaging in identifying biomarkers of neuronal injury in UCD patients. In this study, we report unique findings in an adolescent male with neonatal-onset OTC deficiency after an episode of hyperammonemia., Materials and Methods: Multiplanar, multisequence MR imaging (T1WI, T2WI, T2 FLAIR, diffusion weighted images and gradient echo) of the brain was performed on seven separate occasions over the course following the acute illness; first five exams were performed within 28 days of admission and the final two exams were performed approximately 3 and 5 months later., Results: 1.The initial MR revealed increased signal on T2WI in the basal ganglia, claustrum and frontoparietal white matter; which remained stable over time. By the 5th exam, signal changes had developed in frontal cortex; reflecting permanent injury. 2. DTI tractography of the corticospinal tracts displayed revealed diminution of the number of projectional and commissural fibers over time. 3. Blood flow measurements demonstrated hypoperfusion on the fifth exams followed by hyperperfusion on the final two studies. 4. MR spectroscopy demonstrated that glutamine was elevated during hyperammonemia with myoinositol reduction, reflecting osmotic buffering., Conclusion: This particular multimodal magnetic resonance neuroimaging showed novel, temporally specific manifestations over the disease course in OTC deficiency. This prospective imaging study expands our understanding of the effect of hyperammonemia on the structure and biochemistry of the nervous system., (© 2020 – IOS Press and the authors. All rights reserved.)

Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy ( 1 H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated 1 H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury.

Background: The falx cerebelli is a retrocerebellar dural reflection. The MR spectrum of the fetal falx cerebelli has not been described., Objective: To determine the prevalence of falx cerebelli abnormalities in the context of posterior fossa malformations and compare them to age-matched normal fetal MRI exams., Materials and Methods: We reviewed all consecutive fetal MRIs performed over 1 year at a children's hospital. We assessed the falx cerebelli in each examination for location, morphology, size and number. Exams were grouped into (1) normal or non-brain/head abnormalities or (2) abnormal brain or craniofacial structures. We used chi square, linear regression and logistic regression analyses; P<0.05 was considered significant., Results: We included 424 examinations (223 controls, 201 malformations) from 378 patients (mean gestational age 27±6 weeks). In the control group, the mean falx size was 2.6±1.2 mm (anteroposterior) × 11.0±3.2 mm (craniocaudal), with 80% retrovermian centered; the falx was linear (23%), Y-shape (15%), V-shape (22%) or U-shape (21%); it was unusually multiplicated (17%) or absent (<2%). Falx cerebellar abnormalities were more common in abnormal exams (59%; 119/201) than in normal exams (19%; 43/223) (P<0.001). The falx was abnormal with Blake pouch cysts (9/9, 100%) and rhombencephalosynapsis (3/4, 75%), absent in all Chiari II (n=9) and most Dandy-Walker malformations (5/6, 83%), commonly multiplicated in mega cisterna magna (14/22, 64%), and deviated or absent in cases with arachnoid cysts (3/3, 100%) and adhesions (4/5, 80%)., Conclusion: Structural alterations of the falx cerebelli are more prevalent in fetuses with brain and craniofacial abnormalities. Specific changes offer clues to posterior fossa diagnoses.

Stroke is an uncommon but an important and under-recognized cause of morbidity and mortality in children. Strokes may be due to either brain ischemia or intracranial hemorrhage. Common symptoms of pediatric acute stroke include headache, vomiting, focal weakness, numbness, visual disturbance, seizures, and altered consciousness. Most children presenting with an acute neurologic deficit do not have an acute stroke, but have symptoms due to stroke mimics which include complicated migraine, seizures with postictal paralysis, and Bell palsy. Because of frequency of stroke mimics, in children and the common lack of specificity in symptoms, the diagnosis of a true stroke may be delayed. There are a relatively large number of potential causes of stroke mimic and true stroke. Consequently, imaging plays a critical role in the assessment of children with possible stroke and especially in children who present with acute onset of stroke symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Temporal bone dehiscence is an infrequent but clinically important phenomenon. Cochlear-facial dehiscence, the rarest type, has been described only in adults. We report cochlear-facial dehiscence in a child. Knowledge of this entity is imperative for radiologists searching for anatomical markers of inner ear pathology and for cochlear implant planning.