Intraoperative MRI in pediatric epilepsy and neuro-oncology: a systematic review and meta-analysis.

OBJECTIVE: Intraoperative magnetic resonance imaging (iMRI) use is becoming increasingly widespread in neurosurgical practice, and most of the data reporting its use are in adult populations. There is less evidence on the use of iMRI in pediatric neurosurgery. The aim of this paper was to synthesize the available literature into a systematic review and meta-analysis to evaluate the evidence for iMRI in pediatric neurosurgery, with a particular focus on neuro-oncology and epilepsy surgery. METHODS: This review was registered on PROSPERO and conducted according to PRISMA guidelines. A comprehensive search strategy of Medline via Ovid and Embase was conducted with predetermined key terms. Studies in English reporting the outcomes of patients < 21 years of age who underwent neuro-oncological or epilepsy surgery with the use of iMRI were included in the study. The types of studies eligible for inclusion were observational case-control and cohort studies, randomized clinical trials, cross-sectional studies, editorials, case series, and commentaries. Articles were de-duplicated and abstracts independently screened for inclusion by two reviewers. Full texts were screened, and data on demographic characteristics, etiology, outcome (extent of resection for neuro-oncology and Engel class for epilepsy), and technical iMRI data were extracted. RESULTS: Thirty-five articles were included in the review, 25 of which were observational cohort studies. Four articles were suitable for meta-analysis. In total, 1217 patients underwent iMRI-guided neuro-oncology surgery in 26 studies, most commonly for gliomas (n = 443). A total of 148 patients underwent iMRI-guided epilepsy surgery in 9 studies, with focal cortical dysplasia being the most common diagnosis (n = 95). The mean ± SD operating time was 357 ± 94 minutes (12 studies), with a mean of 1.32 scans per patient. There was a mean re-entry rate into the operative field of 42% (across 20 studies). Complications were noted in 21% of epilepsy surgery patients and 11% of neuro-oncology surgery patients. Meta-analysis of 4 eligible studies revealed that iMRI was more likely to lead to better Engel outcomes in terms of seizure freedom (OR 3.84, 95% CI 1.38-10.68, p = 0.69) and complete tumor resection (OR 3.19, 95% CI 0.28-36.92, p = 0.06). CONCLUSIONS: iMRI appears to be a useful adjunct in optimizing resective pediatric epilepsy and neuro-oncology surgery, with a low complication rate.

ESR Essentials: imaging of suspected child abuse-practice recommendations by the European Society of Paediatric Radiology.

The goal of this paper is to provide a useful desktop reference for the imaging of suspected child abuse with clear, age-specific pathways for appropriate evidence-based imaging and follow-up. We aim to provide a road map for the imaging evaluation and follow-up of this important and vulnerable cohort of patients presenting with signs and symptoms concerning for inflicted injury. As the imaging recommendations differ for children of different ages, we provide a flowchart of the appropriate imaging pathway for infants, toddlers, and older children, which allows ease of selection of which children should undergo skeletal survey, non-contrast computed tomography (CT) brain with 3-dimensional (D) reformats, and magnetic resonance imaging (MRI) of the brain and whole spine. For ease of review, we include a table of the common intracranial and spinal patterns of injury in abusive head trauma. We summarise search patterns, areas of review, and key findings to include in the report. To exclude skeletal injury, infants and children under 2 years of age should undergo a full skeletal survey in accordance with national guidelines, with a limited follow-up skeletal survey performed 11-14 days later. For children over 2 years of age, the need for skeletal imaging should be decided on a case-by-case basis. All infants should undergo a non-contrast-enhanced CT brain with 3-D reformats. If this is normal with no abnormal neurology, then no further neuroimaging is required. If this is abnormal, then they should proceed to MRI brain and whole spine within 2-5 days. Children older than 1 year of age who have abnormal neurology and/or findings on skeletal survey that are suggestive of inflicted injury should undergo non-contrast CT brain with 3-D reformats and, depending on the findings, may also require MRI of the brain and whole spine. We hope that this will be a helpful contribution to the radiology literature, particularly for the general radiologist with low volumes of paediatrics in their practice, supporting them with managing these important cases when they arise in daily practice. KEY POINTS: The choice of initial imaging (skeletal survey and/or brain CT) depends on the age of the child in whom abuse is suspected. A follow-up skeletal survey is mandatory 11-14 days after the initial survey. If an MRI of the brain is performed, then an MRI of the whole spine should be performed concurrently.

An international study presenting a federated learning AI platform for pediatric brain tumors.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.

Cortically-based Brain Tumors in Children: A Decision-tree Approach in the Radiology Reading Room.

Cortically-based brain tumors in children constitute a unique set of tumors with variably aggressive biological behavior. As radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flowchart for the differential diagnoses of these complex brain tumors is essential.This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes using current molecular understanding.ABBREVIATIONS: Astroblastoma=AB) Angiocentric glioma (AG) Atypical teratoid rhabdoid tumor (ATRT) Central Nervous System tumor (CNS) CNS neuroblastoma FOXR2-activated (NB-FOXR2) Desmoplastic infantile glioma/astrocytoma (DIG/DIA) Diffuse hemispheric glioma, H3 G34-mutant (DHG) Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) Dysembryoplastic neuroepithelial tumor (DNET) Embryonal Tumors with Multilayered Rosettes (ETMR) Ependymoma (EP) Focal cortical dysplasia (FCD) Ganglioglioma/gangliocytoma (GG) Infant-type hemispheric glioma (IHG) Intracranial pressure (ICP) Long-term epilepsy-associated tumors (LEATs) Pediatric diffuse low-grade gliomas (pLGG) MR spectroscopy (MRS) Multinodular and vacuolating neuronal tumor (MVNT) Overall survival (OS) Pediatric diffuse high-grade gliomas (pHGG).

Sotos Syndrome: Deep Neuroimaging Phenotyping Reveals a High Prevalence of Malformations of Cortical Development.

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.

Birth-related subdural hemorrhage in asymptomatic neonates: evolution over time and differentiation from traumatic subdural hemorrhage.

BACKGROUND: Intracranial birth-related subdural hemorrhage frequently occurs in asymptomatic newborns and has no adverse long-term sequelae. It is medically and medicolegally important to differentiate birth-related subdural hemorrhage from other pathological causes of intracranial hemorrhage. There is limited literature available on the incidence of birth-related subdural hemorrhage, its imaging features, and evolution over time, mainly because asymptomatic infants do not routinely undergo cranial MRI. OBJECTIVE: To establish the incidence and distribution of birth-related subdural hemorrhage and evaluate their association with various modes of delivery, identify associated features, and evaluate the sequential evolution of signal changes of the birth-related hemorrhages on MRI. MATERIALS AND METHODS: A total of 200 healthy term neonates and young infants were included in this retrospective review study. All infants underwent MRI of the brain and cervical spine at postnatal age of 0-2 months with acquisition of a 3D T1-weighted (T1W), 3D or 2D T2-weighted (T2W), and axial diffusion-weighted imaging (DWI) sequences. The scans were evaluated for the presence and distribution of subdural hemorrhages, other intracranial hemorrhages, and associated injuries. Prevalence of intracranial hemorrhage in various modes of delivery was analyzed. Relationship between the signal intensities of the bleeds on T1W, T2W, and DWI scans and the age of the infants was analyzed. Appropriate tests were applied to test for statistical significance of the data. RESULTS: Out of 200 neonates, 66 (33%) had detectable intracranial hemorrhage on MRI with an age range of 11-25 days, including 31 (47%) males and 35 (53%) females. All of them had subdural hemorrhages, 54 (81.8%) of which were in the posterior fossa. Additional parenchymal hemorrhages were present in a few, but no subarachnoid hemorrhages, cervical spinal canal hemorrhages, cortical bridging vein injury, or cervical spinal ligamentous injury were identified within the limitations of the study. No detectable intracranial hemorrhage was found in subjects above 25 days of age. Overall incidence of subdural hemorrhage by mode of delivery was 8/68 (11.8%) in babies born by cesarean section and 58/132 (43.9%) in babies born by vaginal delivery. Among the vaginal deliveries, the highest incidence was observed in assisted vaginal delivery (19/30, 63.3%). Subjects with birth-related subdural hemorrhage were categorized into three age groups: <13 days, 13-21 days, and >21 days. All detected hemorrhages were T1W hyperintense. In the <13 days group, all bleeds were T2W hypointense. In the 13-21 days group, 73.1% were T2W hypointense, while 26.9% were T2W mixed. All bleeds in the >21 days group were T2W hypointense. All DWI hyperintense bleeds were found in the 13-21 days group. CONCLUSION: Birth-related subdural hemorrhage occurs in over a third of normal deliveries and has a characteristic distribution, predominantly in the posterior fossa. Associated cervical spinal subdural hemorrhages, cervical spinal ligamentous injury, or cortical bridging vein injury, which are concerning for traumatic etiology, were not identified. Birth-related subdural hemorrhages follow a characteristic pattern of signal changes on MRI. Although not completely reliable, this can help in differentiating them from traumatic intracranial hemorrhages which usually occur postnatally. No birth-related subdural hemorrhages were seen after 25 days of age in our cohort.

Prenatal assessment of brain malformations on neuroimaging: an expert panel review.

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.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

AIMS: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality. METHODS: As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology-related findings, we conducted a result-evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro-oncology specialists. RESULTS: The MDT identified key determinants impacting decision-making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high-risk nature. From this experience, we developed a decision-making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. CONCLUSIONS: Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy-related pathology, genetic disorders and degenerative diseases.

Enzyme replacement therapy for CLN2 disease: MRI volumetry shows significantly slower volume loss compared to a natural history cohort.

BACKGROUND AND PURPOSE: Neuronal ceroid lipofuscinoses (NCL) are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for CLN2, a subtype of NCL. The aim of this study was to quantify brain volume loss in CLN2 disease of patients on ERT in comparison to a natural history cohort using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nineteen (13 female, 6 male) patients with CLN2 disease at one UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1 to 9 years). Brain segmentation was done using FreeSurfer. Volume measurements for supratentorial grey and white matter, deep grey matter (basal ganglia/thalami), lateral ventricles, and cerebellar grey and white matter were recorded. The volume change over time was analyzed using a linear mixed-effects model excluding scans before treatment start. Comparison was made to a published natural history cohort of 12 patients (8 female, 4 male) which was reanalyzed using the same method. RESULTS: Brain volume loss of all segmented brain regions was much slower in treated patients compared to the natural history cohort. For example, supratentorial grey matter volume in treated patients decreased by 3±0.74% (p<0.001) annually compared to an annual volume loss of 16.8±1.5% (p<0.001) in the natural history cohort. CONCLUSIONS: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared to a natural history cohort in several anatomical regions. Our results complement prior clinical data which found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease. ABBREVIATIONS: NCL = Neuronal Ceroid Lipofuscinosis, CLN2 = Neuronal Ceroid Lipofuscinosis type 2, TPP1 = tripeptidyl peptidase 1, ERT = enzyme replacement therapy, EMA = European Medicines Agency, ICV = intra-cerebro-ventricular reservoir.

Approaches to supratentorial brain tumours in children.

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by the neuroradiology community. The purpose of this article is to provide guidance to residents and fellows new to the field of paediatric neuroradiology on how to evaluate an MRI of a patient with a newly diagnosed supratentorial tumour. Six different approaches are discussed including: 1. Tumour types, briefly discussing the main changes to the recent WHO classification of CNS tumours, 2. Patient age and its influence on incidence rates of specific tumour types, 3. Growth patterns, 4. Tumour location and how defining the correct location helps in narrowing down the differential diagnoses and 5. Imaging features of the tumour on DWI, SWI, FLAIR and post contrast sequences.

Using diffusion MRI to understand white matter damage and the link between brain microstructure and cognitive deficits in paediatric medulloblastoma patients.

PURPOSE: Survivors of medulloblastoma face a range of challenges after treatment, involving behavioural, cognitive, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain resulting from both the tumour and the treatment. Diffusion magnetic resonance imaging (MRI) has been used to investigate the microstructure of the brain. In this review, we aim to summarise the literature on diffusion MRI in patients treated for medulloblastoma and discuss future directions on how diffusion imaging can be used to improve patient quality. METHOD: This review summarises the current literature on medulloblastoma in children, focusing on the impact of both the tumour and its treatment on brain microstructure. We review studies where diffusion MRI has been correlated with either treatment characteristics or cognitive outcomes. We discuss the role diffusion MRI has taken in understanding the relationship between microstructural damage and cognitive and behavioural deficits. RESULTS: We identified 35 studies that analysed diffusion MRI changes in patients treated for medulloblastoma. The majority of these studies found significant group differences in measures of brain microstructure between patients and controls, and some of these studies showed associations between microstructure and neurocognitive outcomes, which could be influenced by patient characteristics (e.g. age), treatment, radiation dose and treatment type. CONCLUSIONS: In future, studies would benefit from being able to separate microstructural white matter damage caused by the tumour, tumour-related complications and treatment. Additionally, advanced diffusion modelling methods can be explored to understand and describe microstructural changes to white matter.

Validation of the 2023 International Diagnostic Criteria for MOGAD in a Selected Cohort of Adults and Children.

BACKGROUND AND OBJECTIVES: To test the performance of the 2023 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) criteria in adults and children with inflammatory demyelinating conditions who were tested for MOG antibodies (Abs). METHODS: This was a retrospective study of patients tested for MOG-Abs from 2018 to 2022 in 2 specialist hospitals. The inclusion criteria comprised ≥1 attendance in an adult or pediatric demyelinating disease clinic and complete clinical and MRI records. The final clinical diagnosis of MOGAD, made by the treating neurologist, was taken as the benchmark against which the new criteria were tested. The international MOGAD diagnostic criteria were applied retrospectively; they stipulate at least 1 clinical or MRI supporting feature for MOGAD diagnosis in positive fixed MOG cell-based assay without a titer. The performance MOG-Ab testing alone for MOGAD diagnosis was also assessed and compared with that of MOGAD criteria using the McNemar test. RESULTS: Of the 1,879 patients tested for MOG-Abs, 539 (135 pediatric and 404 adults) met the inclusion criteria. A clinical diagnosis of MOGAD was made in 86/539 (16%) patients (37 adults, 49 children), with a median follow-up of 3.6 years. The MOGAD diagnostic criteria had sensitivity of 96.5% (adults 91.9%, children 100%), specificity of 98.9% (adults 98.8%, children 98.9%), positive predictive value of 94.3% (adults 89.4%, children 98%), negative predictive value of 99.3% (adults 99.2%, children 100%), and accuracy of 98.5% (adults 98.3%, children 99.2%). When compared with MOG-Ab testing alone, a difference was seen only in adults: a significantly higher specificity (98.9% vs 95.6%, p = 0.0005) and nonstatistically significant lower sensitivity (91.9% vs 100%, p = 0.08). DISCUSSION: The international MOGAD diagnostic criteria exhibit high performance in selected patients with inflammatory demyelinating diseases (who had a high pretest probability of having MOGAD) compared with best clinical judgment; their performance was better in children than in adults. In adults, the MOGAD criteria led to an improvement in specificity and positive predictive value when compared with MOG-Ab testing alone, suggesting that the requirement of at least 1 clinical or MRI supporting feature is important. Future work should address the generalizability of the diagnostic criteria to cohorts of greater clinical diversity seen within neurologic settings.

Added value of postmortem mri in sudden unexpected infant death cases.

We aimed to investigate the potential added value of postmortem MRI (PMMRI) in sudden unexpected infant death (SUID) cases referred to our center between September 2020 and June 2023. Ultimately, 19 SUID cases underwent PMMRI alongside standard autopsy procedures, which included technical examinations such as postmortem CT (PMCT). Four radiologists, two with prior PMMRI experience, provided structured reports following consensus. For each case, the responsible forensic medicine specialist documented the cause of death before and after reviewing the PMMRI report. Additionally, they assessed the overall impact of the PMMRI report and had the opportunity to provide written comments. The results of our study indicate that none of the PMMRI reports altered the prior determined cause of death, which included cases of infection, asphyxia, and sudden infant death syndrome (SIDS). However, we observed a moderate impact in one case and a low impact in 10 cases. The moderate impact arose from the PMMRI report identifying hypoxic-ischemic changes, where histologic examination of the brain was perceived as normal. Conversely, in the 10 cases with a low impact, the PMMRI reports supported the autopsy findings, specifically indicating brain injury and intra-alveolar cellular infiltrates. In conclusion, our study suggests that while PMMRI may not be pivotal in determining the cause of death in SUID cases, it could aid in detecting hypoxic-ischemic changes and reinforcing brain and lung observations. However, distinguishing genuine lung pathology from postmortem changes using PMMRI remains challenging. Further research is warranted to clarify the role of PMMRI in forensic SUID investigations.

Diagnostic pathway and management of first seizures in infants with Sturge-Weber syndrome.

AIM: Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment. METHOD: A single-centre case series of 49 infants explored early SWS care. Ninety-two per cent of children developed seizures aged 0 to 3 years; 55% of cases were before diagnostic magnetic resonance imaging (MRI) or tertiary referral. Delay in SWS diagnosis affected 31% of infants because of a lack of gadolinium enhancement for initial MRI. First seizures were frequently prolonged, with phenytoin administration necessary in 46%. Presymptomatic antiseizure medication prophylaxis (n = 8/49) decreased seizure burden. No patients on antiseizure medication prophylaxis suffered status epilepticus for longer than 30 minutes, and half of them (n = 4) had not developed seizures at last follow-up (aged 2-10 years). RESULTS: A parental survey enabled further service evaluation. Eighty-three per cent of parents considered local clinicians' understanding of SWS inadequate: 61% felt insufficiently informed about SWS and 81% received no epilepsy education before seizures. INTERPRETATION: To overcome the identified shortfalls, guidelines towards improving and standardizing SWS management are proposed.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

(What's the story) morning glory? MRI findings in morning glory disc anomaly.

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).

Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition.

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor regrowth can occur during therapy due to drug resistance, off treatment as tumor recurrence, or as reported in some patients as a rapid rebound growth within 3 months of discontinuing targeted therapy. Definitions of these patterns of regrowth have not been well described in pLGG. For this reason, the International Pediatric Low-Grade Glioma Coalition, a global group of physicians and scientists, formed the Resistance, Rebound, and Recurrence (R3) working group to study resistance, rebound, and recurrence. A modified Delphi approach was undertaken to produce consensus-based definitions and recommendations for regrowth patterns in pLGG with specific reference to targeted therapies.

Human mutations in SLITRK3 implicated in GABAergic synapse development in mice.

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved in controlling neurite outgrowth and inhibitory synapse development and that has an important role in brain function and neurological diseases. Using primary cultures of hippocampal neurons carrying patients' SLITRK3 variants and in combination with electrophysiology, we demonstrate that recessive variants are loss-of-function alleles. Immunostaining experiments in HEK-293 cells showed that human variants C566R and E606X change SLITRK3 protein expression patterns on the cell surface, resulting in highly accumulating defective proteins in the Golgi apparatus. By analyzing the development and phenotype of SLITRK3 KO (SLITRK3-/-) mice, the study shows evidence of enhanced susceptibility to pentylenetetrazole-induced seizure with the appearance of spontaneous epileptiform EEG as well as developmental deficits such as higher motor activities and reduced parvalbumin interneurons. Taken together, the results exhibit impaired development of the peripheral and central nervous system and support a conserved role of this transmembrane protein in neurological function. The study delineates an emerging spectrum of human core synaptopathies caused by variants in genes that encode SLITRK proteins and essential regulatory components of the synaptic machinery. The hallmark of these disorders is impaired postsynaptic neurotransmission at nerve terminals; an impaired neurotransmission resulting in a wide array of (often overlapping) clinical features, including neurodevelopmental impairment, weakness, seizures, and abnormal movements. The genetic synaptopathy caused by SLITRK3 mutations highlights the key roles of this gene in human brain development and function.