MR Imaging of Placenta Accreta Spectrum: A Comprehensive Literature Review of the Most Recent Advancements.

This article delves into the latest MR imaging developments dedicated to diagnosing placenta accreta spectrum (PAS). PAS, characterized by abnormal placental adherence to the uterine wall, is of paramount concern owing to its association with maternal morbidity and mortality, particularly in high-risk pregnancies featuring placenta previa and prior cesarean sections. Although ultrasound (US) remains the primary screening modality, limitations have prompted heightened emphasis on MR imaging. This review underscores the utility of quantitative MR imaging, especially where US findings prove inconclusive or when maternal body habitus poses challenges, acknowledging, however, that interpreting placenta MR imaging demands specialized training for radiologists.

The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.

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.

International Consensus Statement on the Radiological Evaluation of Dysraphic Malformations of the Spine and Spinal Cord.

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical weighting. This variability in radiologic practice risks unstructured decision making and increases the likelihood of suboptimal, less informed clinical management. In this manuscript, the first of a series of consensus statements, we outline a standardized international consensus statement for the radiologic evaluation of children with suspected DMSSC derived from a critical review of the literature, and the collective clinical experience of a multinational group of experts. We provide recommendations for plain radiography, sonography, CT, and MR imaging in the evaluation of DMSSC with an emphasis on technique of imaging and imaging protocols.

Dots and spots: A retrospective review of T2-hyperintense white matter lesions in pediatric patients with and without headache.

OBJECTIVE: We aimed to determine if T2-weighted hyperintense white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) occur more frequently in pediatric patients with migraine and other primary headache disorders compared to the general pediatric population. BACKGROUND: Small foci of T2 hyperintensity in the white matter are frequently identified on brain MRI during the workup of pediatric headache. Such lesions have been reported to be more common among adults with migraine versus adults without migraine; however, this association has not been well established in the pediatric population. METHODS: We performed a retrospective cross-sectional single-center study of electronic medical records and radiologic studies, examining pediatric patients from 3 to 18 years old who underwent brain MRI between 2016 and 2021. Patients with existing intracranial disease or abnormalities were excluded. Patients with reports of headache were categorized. Imaging was reviewed to determine the number and location of WMLs. Headache-associated disability scores (Pediatric Migraine Disability Assessment) were noted, when available. RESULTS: Brain MRI of 248 patients with a diagnosis of headache (144 with migraine, 42 with non-migraine primary headache, and 62 with headache that could not be further classified) and 490 controls were reviewed. WMLs were encountered commonly among all study participants, with a prevalence of 40.5% (17/42) to 54.1% (265/490). There was no statistically significant difference comparing the number of lesions between each of the headache groups and the control group: migraine group versus control group median [interquartile range (IQR)], 0 [0-3] versus 1 [0-4], incidence rate ratio [95% confidence interval (CI)], 0.99 [0.69-1.44], p = 0.989, non-migraine headache group versus control group median [IQR], 0 [0-3] versus 1 [0-4], 0.71 [0.46-1.31], p = 0.156, headache not otherwise specified group versus control group median [IQR], 0 [0-4] versus 1 [0-4], 0.77 [0.45-1.31], p = 0.291. There was no significant correlation between headache-associated disability and the number of WMLs (0.07 [-0.30 to 0.17], rho [95% CI]). CONCLUSION: T2 hyperintense WMLs are common within the pediatric population and are not encountered more frequently in pediatric patients with migraine or other primary headache disorders. Thus, such lesions are presumably incidental and unlikely related to headache history.

International Consensus Statement on the Radiological Screening of Contact Children in the Context of Suspected Child Physical Abuse.

Importance: Physical abuse is a common but preventable cause of long-term childhood morbidity and mortality. Despite the strong association between abuse in an index child and abuse in contact children, there is no guidance outlining how to screen the latter, significantly more vulnerable group, for abusive injuries. Consequently, the radiological assessment of contact children is often omitted, or variably performed, allowing occult injuries to go undetected and increasing the risk of further abuse. Objective: To report an evidence-based and consensus-derived set of best practices for the radiological screening of contact children in the context of suspected child physical abuse. Evidence Review: This consensus statement is supported by a systematic review of the literature and the clinical opinion of an internationally recognized group of 26 experts. The modified Delphi consensus process comprised 3 meetings of the International Consensus Group on Contact Screening in Suspected Child Physical Abuse held between February and June 2021. Findings: Contacts are defined as the asymptomatic siblings, cohabiting children, or children under the same care as an index child with suspected child physical abuse. All contact children should undergo a thorough physical examination and a history elicited prior to imaging. Contact children younger than 12 months should have neuroimaging, the preferred modality for which is magnetic resonance imaging, and skeletal survey. Contact children aged 12 to 24 months should undergo skeletal survey. No routine imaging is indicated in asymptomatic children older than 24 months. Follow-up skeletal survey with limited views should be performed if abnormal or equivocal at presentation. Contacts with positive findings should be investigated as an index child. Conclusions and Relevance: This Special Communication reports consensus recommendations for the radiological screening of contact children in the context of suspected child physical abuse, establishing a recognized baseline for the stringent evaluation of these at-risk children and providing clinicians with a more resilient platform from which to advocate for them.

Thromboembolic toxicity observed with concurrent trametinib and lenalidomide therapy.

The event-free survival of pediatric low-grade gliomas is poor, and patients often require multiple treatment strategies. While MEK and RAF inhibitors are efficacious in early-phase trials, not all patients respond, and many experience progression following completion of therapy. Evaluating combination therapies that may enhance efficacy or prolong disease stabilization is warranted. We report our institutional experience using concurrent trametinib and lenalidomide in the treatment of primary pediatric central and peripheral nervous system tumors. Two of four patients using this combination therapy experienced severe thromboembolic events, necessitating discontinuation of therapy. This combination requires further investigation, and we urge caution if used.

Imaging of pediatric brain tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper.

Tumors of the central nervous system are the most common solid malignancies in children and the most common cause of pediatric cancer-related mortality. Imaging plays a central role in diagnosis, staging, treatment planning, and response assessment of pediatric brain tumors. However, the substantial variability in brain tumor imaging protocols across institutions leads to variability in patient risk stratification and treatment decisions, and complicates comparisons of clinical trial results. This White Paper provides consensus-based imaging recommendations for evaluating pediatric patients with primary brain tumors. The proposed brain magnetic resonance imaging protocol recommendations balance advancements in imaging techniques with the practicality of deployment across most imaging centers.

Early outcomes of a myofascial repair technique for fetal myelomeningocele.

PURPOSE: Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP. METHODS: A single-center retrospective study of patients who underwent fetal MMC or myeloschisis repair between March 2013 and February 2022 was performed. Outcomes were evaluated (n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests (p < 0.05 significant). RESULTS: Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p < 0.0001). Myofascial closure was also associated with an increased rate of HBH improvement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group (n = 21), however this did not reach statistical significance (23.8% vs 41.9%, p = 0.19). CONCLUSIONS: We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herniation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.

Prevalence of cerebral sinovenous thrombosis in abusive head trauma.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) has been proposed in legal settings to be an atraumatic mimic of abusive head trauma (AHT). OBJECTIVE: The objective of this study was to determine the prevalence of CSVT and subdural hemorrhage (SDH) in a large AHT population. MATERIALS AND METHODS: This retrospective cohort study measured the prevalence of CSVT and SDH on magnetic resonance venograms in 243 patients diagnosed with AHT at a single center. We also reported additional intra- and extracranial injuries, head injury severity and length of hospital stay. RESULTS: Among 243 patients diagnosed with AHT, 7% (16/243) had CSVT. SDH was present in 94% (15/16) of the CSVT cases. Cytotoxic edema and subarachnoid hemorrhage were in 88% (14/16) and 69% (11/16) of the CSVT cases, respectively. Extracranial signs of abuse were also in 100% (16/16) of the patients with CSVT. Critical to maximal head injury severity (abbreviated injury scale >=5) was in 75% (12/16) of the CSVT population vs. 33% (82/243) in the total AHT population. Length of hospital and pediatric intensive care unit stay was greater in those with CSVT (10 vs. 21.9 and 3.5 vs. 7.3 days). CONCLUSION: These findings suggest that CSVT is uncommon in AHT and is associated with additional traumatic injuries and greater injury severity.

Response assessment in pediatric craniopharyngioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group.

BACKGROUND: Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized. METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively. RESULTS: Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor components. In certain clinical contexts, response to solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment. Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into craniopharyngioma response definitions. In most circumstances, the cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. CONCLUSIONS: Craniopharyngioma is a common pediatric central nervous system tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for craniopharyngioma assessment to uniformly define response in future prospective trials.

Refining the role of cervical spine immobilization and stabilization in pediatric non-accidental trauma, a retrospective series of 1008 patients.

INTRODUCTION: Prompt detection of traumatic cervical spine injury is important as delayed or missed diagnosis can have disastrous consequences. Given the understood mechanism of non-accidental trauma (NAT), it is reasonable to suspect that cervical spine injury can occur. Current management of young children being evaluated for NAT includes placement of a rigid collar until clinical clearance or an MRI can be obtained. Currently, there exists a lack of robust data to guide cervical bracing. Anecdotally, our group has not observed a single patient with a diagnosis of NAT who required operative stabilization for cervical spine instability. This study will be the largest series to date and aims to systematically investigate this observation to determine the likelihood that children with a diagnosis of NAT harbor cervical spine instability related to their injuries. METHODS: Patient data from the Children's Hospital Colorado Trauma Registry diagnosed with non-burn-only NAT were reviewed retrospectively. Children less than 4 years of age pulled from the registry from January 1, 2005, to March 31, 2021, were included. Demographic, admission/discharge, imaging, and clinic management data were collected for each patient and analyzed. RESULTS: There were 1008 patients included in the cohort. The age at presentation ranged from 5 days to 4 years (mean 10.4 months). No patient had X-ray or CT findings concerning for cervical instability. Three patients had MRI findings concerning for cervical instability. Two of these underwent external bracing, and the third died from unrelated injuries during their hospitalization. Only four patients were discharged in a cervical collar, and all were ultimately cleared from bracing. No patient underwent a spinal stabilization procedure. CONCLUSIONS: While the mechanism of injury in many NAT cases would seem to make significant cervical spine injury possible, this single-center retrospective review of a large experience indicates that such injury is exceedingly rare. Further study is merited to understand the underlying pathophysiology. However, it is reasonable to consider cervical collar clearance in the setting of normal radiographs and a reassuring neurological exam. Furthermore, if concerns exist regarding cervical spine instability on MRI, an initial trial of conservative management is warranted.

ACR Appropriateness Criteria® Ataxia-Child.

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.

Fetal MRI Neuroradiology: Indications.

Fetal MRI is a safe, noninvasive examination of the fetus and placenta, a complement to ultrasonography. MRI provides detailed CNS evaluation, including depicting parenchymal architecture and posterior fossa morphology, and is key in prenatal assessment of spinal dysraphism, neck masses, and ventriculomegaly. Fetal MRI is typically performed after 22 weeks gestation, and ultrafast T1 and T2-weighted MRI sequences are the core of the exam, with advanced sequences such as diffusion weighted imaging used for specific questions. The fetal brain grows and develops rapidly, and familiarity with gestational age specific norms is essential to MRI interpretation.

Perinatal Ischemic Stroke: Etiology and Imaging.

Perinatal ischemic stroke is a common cause of lifelong disability.

Imaging of Macrocephaly.

Macrocephaly is a common diagnosis in the pediatric population, particularly in the infantile time period. There is a wide range of causes of macrocephaly, from benign to malignant, for which imaging plays a key role in the diagnosis and clinical guidance. Our aim is to review the distinct and prevalent neuroimaging findings in the evaluation of the macrocephalic infant.

Thalamic Volume Loss Is Greater in Children Than in Adults Following Middle Cerebral Artery Territory Arterial Ischemic Stroke.

Background: Younger stroke patients may suffer worse outcomes than older patients; however, the extent to which age at stroke impacts remote areas of the brain remains unclear. The objective of this study was to determine thalamic volume changes ipsilateral to middle cerebral artery territory strokes based on age at acute ischemic stroke onset. Methods: Acute ischemic stroke patients <9 years, 9-18 years, and >18 years old were retrospectively recruited from a large quaternary care system. Each subject underwent an acute (<72 hours from AIS) and chronic (>90 days) magnetic resonance imaging (MRI) scan. Manual thalamic segmentation was performed. Results: Younger and older children had significantly greater stroke-side thalamic volume loss compared to adults (48.2%, P = .022; 40.7%, P = .044, respectively). Conclusions: Stroke-side thalamic volumes decreased across the age spectrum but to a greater degree in pediatric patients. This observation can affect functional and cognitive outcomes post stroke and warrants further research.

Visualization of the Anal Dimple by Fetal MRI: Is It Feasible?

INTRODUCTION: The aim of this study was to determine the feasibility of fetal MRI in identifying the normal anal dimple (AD) and compare it with prenatal ultrasound (US). METHODS: Retrospective review of 130 patients with both fetal MRI and US. The gestational age (GA) was stratified into four groups: (1) 16 to 21 weeks-6 days; (2) 22 to 27 weeks-6 days; (3) 28 to 33 weeks-6 days; and (4) 34 weeks and beyond. Steady-state free precession (SSFP) and single shot fast spin echo (SSFSE) axial T2 MRI and transverse US images of the fetal perineum were analyzed, and visualization of the AD was determined. Clinical indication, gender, single versus multiple gestation, best MRI sequence where it was seen, and postnatal AD information were recorded. RESULTS: The AD was visualized in 125/130 fetal MRIs, and visualization was independent of GA (p 0.230). US visualized the AD in 67/130 cases, and the best GA for visualization was in group 3 (p < 0.001). There was no difference in AD visualization between SSFSE and SSFP sequences (p 0.167). CONCLUSION: Prenatal visualization of the AD by MRI is feasible and superior to US, independent of GA. Adding AD visualization to routine screening prenatal US and MRI may increase recognition of anorectal malformation.

Torcular Dural Sinus Malformation: Fetal and Postnatal Imaging Findings and Their Associations With Clinical Outcomes.

BACKGROUND: Torcular dural sinus malformations (tDSMs) are rare vascular malformations that present in fetuses and infants. Existing data on prognostic imaging features, as well as the associated morbidity and mortality, are limited and variable. We therefore reviewed cases of tDSMs diagnosed on fetal magnetic resonance imaging (MRI) at our referral center to identify pre- and postnatal MRI imaging features associated with long-term outcomes. METHODS: We searched our imaging database for fetal and postnatal MRI reports of tDSM cases. The electronic medical record was then reviewed for pre- and postnatal clinical data, including follow-up imaging. Neurological outcomes were characterized using the previously reported scale based on the Bicêtre Score. Imaging features association with outcome scores were compared using the Fisher exact test. RESULTS: Sixteen cases of tDMS diagnosed by fetal MRI with postnatal clinical follow-up were identified, 11 of whom underwent postnatal MRI. The majority of cases of tDSM (73%) decreased in size or resolved on postnatal follow-up study without treatment. Restricted diffusion and parenchymal hemorrhage on fetal MRI were the only imaging features identified significantly associated with unfavorable neurological outcome or death, present in two patients with poor outcomes (two of two) and only one with a normal outcome (one of 14) (P = 0.025). CONCLUSIONS: Findings of tDSM on fetal MRI most often regress and/or resolve with normal or mild neurological outcomes, with the most significant predictor of poor outcome being the presence of parenchymal injury on fetal MRI. In addition, a subset will present with venolymphatic malformations.

Response assessment in paediatric intracranial ependymoma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric intracranial ependymoma vary historically and across different international cooperative groups. The Response Assessment in the Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, neuro-radiologists, radiation oncologists, and neurosurgeons, was established to address both the issues and the unique challenges in assessing the response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric ependymoma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric ependymoma to clinical trial therapy. For areas in which data were scarce or unavailable, consensus was reached through an iterative process. RAPNO response assessment recommendations include assessing disease response on the basis of changes in tumour volume, and using event-free survival as a study endpoint for patients entering clinical trials without bulky disease. Our recommendations for response assessment include the use of brain and spine MRI, cerebral spinal fluid cytology, neurological examination, and steroid use. Baseline postoperative imaging to assess for residual tumour should be obtained 24-48 h after surgery. Our consensus recommendations and response definitions should be prospectively validated in clinical trials.

Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.

AIM: To identify additional genes associated with infantile spasms using a cohort with defined infantile spasms. METHOD: Whole-exome sequencing (WES) was performed on 21 consented individuals with infantile spasms and their unaffected parents (a trio-based study). Clinical history and imaging were reviewed. Potentially deleterious exonic variants were identified and segregated. To refine potential candidates, variants were further prioritized on the basis of evidence for relevance to disease phenotype or known associations with infantile spasms, epilepsy, or neurological disease. RESULTS: Likely pathogenic de novo variants were identified in NR2F1, GNB1, NEUROD2, GABRA2, and NDUFAF5. Suggestive dominant and recessive candidate variants were identified in PEMT, DYNC1I1, ASXL1, RALGAPB, and STRADA; further confirmation is required to support their relevance to disease etiology. INTERPRETATION: This study supports the utility of WES in uncovering the genetic etiology in undiagnosed individuals with infantile spasms with an overall yield of five out of 21. High-priority candidates were identified in an additional five individuals. WES provides additional support for previously described disease-associated genes and expands their already broad mutational and phenotypic spectrum.