Infantile metastatic ependymoma with a novel molecular profile and favorable outcome to intensive chemotherapy without irradiation: Case-based review.

Ependymal tumors are the third most common brain tumor under 14 years old. Even though metastatic disease is a rare event, it affects mostly young children and carries an adverse prognosis. The factors associated with dissemination and the best treatment approach have not yet been established and there is limited published data on how to manage metastatic disease, especially in patients under 3 years of age. We provide a review of the literature on clinical characteristics and radiation-sparing treatments for metastatic ependymoma in children under 3 years of age treated. The majority (73%) of the identified cases were above 12 months old and had the PF as the primary site at diagnosis. Chemotherapy-based approaches, in different regimens, were used with radiation reserved for progression or relapse. The prognosis varied among the studies, with an average of 50%-58% overall survival. This study also describes the case of a 7-month-old boy with metastatic posterior fossa (PF) ependymoma, for whom we identified a novel SPECC1L-RAF1 gene fusion using a patient-centric comprehensive molecular profiling protocol. The patient was successfully treated with intensive induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic progenitor cell rescue (AuHSCR). Currently, the patient is in continuous remission 5 years after his diagnosis, without radiation therapy. The understanding of the available therapeutic approaches may assist physicians in their management of such patients. This report also opens the perspective of newly identified molecular alterations in metastatic ependymomas that might drive more chemo-sensitive tumors.

Correlation between the lateral and anteroposterior sacral ratios in anorectal malformations.

BACKGROUND: The sacral ratio has been used as a tool for evaluating sacral development in patients with anorectal malformations. Sacral ratios can be calculated by obtaining sacral radiographs in the anteroposterior (AP) and lateral planes. OBJECTIVE: The objective of the study was to determine the correlation and agreement in sacral ratio calculations. MATERIALS AND METHODS: In this single institution retrospective cohort study, we reviewed medical charts of all pediatric anorectal malformation patients treated between March 2014 and September 2018 who had both AP and lateral images of their sacrum. All sacral ratios were measured by three radiologists. Pearson's correlation coefficients and corresponding 95% confidence intervals (CIs) were used to assess the correlation between the AP and lateral radiographs. A weighted Kappa statistic was used to measure the agreement between how the AP and lateral sacral ratios categorized observations into risk groups. RESULTS: Our initial cohort consisted of 646 observations from patients with anorectal malformations who had radiographs obtained in both AP and lateral planes. We excluded all observations (n=76) where the radiographs were deemed to be inadequate or not appropriately centered to measure sacral ratio. For a given pair of measurements, the mean lateral sacral ratio was 0.07 units greater than the AP plane (95% CI 0.06-0.09, paired t-test P-value <0.0001). AP and lateral images had a moderate positive correlation (Pearson's r=0.76, 95% CI 0.73-0.79, P<0.0001) and moderate agreement in risk categorization (unweighted kappa = 0.60, P<0.0001). AP and lateral readings conducted by all three radiologists had excellent inter-rater reliability with intraclass correlations for AP and lateral sacral ratios of 0.88 and 0.84, respectively. CONCLUSION: Even though the AP and lateral sacral ratios had moderate positive correlation, the mean sacral ratio determined by images in the lateral plane was 0.07 units greater than the AP plane. AP and lateral sacral ratios concluded different risk categories relatively often. Future studies are needed to determine whether AP or lateral sacral ratios correlate better with continence in patients with anorectal malformations.

Post-contrast T1-weighted spine 3T MRI in children using a golden-angle radial acquisition.

PURPOSE: MRI methods that have reduced sensitivity to motion are attractive in pediatric applications. In spine imaging, physiologic motion such as respiration and cerebrospinal fluid pulsation can hamper diagnostic image quality. We compare a 3D T1-weighted non-Cartesian radial acquisition with a conventional Cartesian 2D turbo-spin-echo (TSE) acquisition in axial post-contrast spine imaging at 3T. METHODS: Thirty-two patients (mean age 12.2 ± 5.3 years) scheduled for routine clinical spine exams with contrast were enrolled. Three pediatric neuroradiologists compared the two sequences and assessed the presence of motion, the conspicuity of nerve roots, and whether one of the sequences was preferred in visualizing pathology using Likert scales. RESULTS: The Fleiss' kappa statistic for inter-rater agreement was 0.29 (95% confidence interval, 0.15-0.43) for the presence of motion, 0.30 (0.21-0.38) for conspicuity, and 0.37 (0.19-0.55) for sequence preference. Radial images were less sensitive to motion than TSE (p < 0.01). Motion and consequent artifacts were present in all TSE cases, while it was absent in 51% of the radial cases. In depicting nerve roots, radial images were superior in the cervical (p < 0.05), thoracic (p < 0.01), and lumbar spines (p < 0.01). Lastly, in 28 of the 32 patients who demonstrated contrast-enhancing pathology, radial images were preferred in 51% of the cases, while both sequences were equally preferred in 41% of the cases. CONCLUSION: We demonstrate the potential utility of radial MRI in post-contrast spine imaging. The free-breathing method is robust in generating diagnostic image quality and is superior in visualizing nerve roots and extramedullary metastases than traditional Cartesian TSE acquisitions.

Advanced neuroimaging in traumatic brain injury: an overview.

Traumatic brain injury (TBI) is a common condition with many potential acute and chronic neurological consequences. Standard initial radiographic evaluation includes noncontrast head CT scanning to rapidly evaluate for pathology that might require intervention. The availability of fast, relatively inexpensive CT imaging has fundamentally changed the clinician's ability to noninvasively visualize neuroanatomy. However, in the context of TBI, limitations of head CT without contrast include poor prognostic ability, inability to analyze cerebral perfusion status, and poor visualization of underlying posttraumatic changes to brain parenchyma. Here, the authors review emerging advanced imaging for evaluation of both acute and chronic TBI and include QuickBrain MRI as an initial imaging modality. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI, MR arterial spin labeling, and perfusion CT are reviewed as methods for examining cerebral blood flow following TBI. The authors evaluate MR-based diffusion tensor imaging and functional MRI for prognostication of recovery post-TBI. Finally, MR elastography, MR spectroscopy, and convolutional neural networks are examined as future tools in TBI management. Many imaging technologies are being developed and studied in TBI, and some of these may hold promise in improving the understanding and management of TBI. ABBREVIATIONS ASL = arterial spin labeling; CNN = convolutional neural network; CTP = perfusion CT; DAI = diffuse axonal injury; DMN = default mode network; DOC = disorders of consciousness; DTI = diffusion tensor imaging; FA = fractional anisotropy; fMRI = functional MRI; GCS = Glasgow Coma Scale; MD = mean diffusivity; MRE = MR elastography; MRS = MR spectroscopy; mTBI = mild TBI; NAA = N-acetylaspartate; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; UHF = ultra-high field.

A Retrospective Study of Cervical Spine MRI Findings in Children with Abusive Head Trauma.

BACKGROUND/AIMS: Increasing attention has been given to the possible association of cervical spine (c-spine) injuries with abusive head trauma (AHT). The aims of this study were to describe c-spine MRI findings in hospitalized AHT patients. METHODS: This is a retrospective study of children under the age of 5 years with AHT admitted to hospital in 2004-2013. Those with c-spine MRI were identified, and the images were reviewed. RESULTS: 250 AHT cases were identified, with 34 (14%) undergoing c-spine MRI. Eleven patients (32%) had 25 findings, including hematoma in 2, occiput-C1-C2 edema in 3, prevertebral edema in 6, facet edema in 2, and interspinous and/or muscular edema in 10. No patients had a clinically evident c-spine injury, a clinically unstable c-spine, or required c-spine surgery. CONCLUSIONS: C-spine MRI may identify abnormalities not apparent upon physical examination and the procedure should therefore be considered in cases of suspected AHT.

Symptoms of Persistent Behavior Problems in Children With Mild Traumatic Brain Injury.

OBJECTIVE: To investigate the effects of mild traumatic brain injury (mTBI) in children on symptom ratings of behavior problems across the first-year postinjury. SETTING: Emergency departments of 2 regional children's hospitals. PARTICIPANTS: Parents of 176 children with mTBI and 90 children with orthopedic injury aged 8 to 15 years. DESIGN: Group comparisons of postinjury parent and teacher ratings of child behavior problems controlling for background factors. MAIN MEASURES: Child Behavior Checklist and Teacher's Report Form. RESULTS: For younger but not older children in the sample, children with mTBI compared with children with orthopedic injury had higher postinjury ratings on the Child Behavior Checklist Total Behavior Problem scale (t264 = 3.34, P < .001) and higher rates of T-scores of 60 or more on this scale (odds ratio = 3.00; 95% confidence interval, 1.33-6.77; P = .008). For children with mTBI, hospitalization, motor vehicle accidents, loss of consciousness, and magnetic resonance imaging abnormality were associated with higher parent or teacher ratings. CONCLUSIONS: School-aged children with mTBI are at risk for persistent symptoms of behavior problems, especially if mTBI is more severe or occurs at a younger age. The findings justify monitoring of behavior long after injury and further research to identify risk factors for these symptoms and their association with clinical disorders.

New C2 synchondrosal fracture classification system.

BACKGROUND: Excessive cervical flexion-extension accompanying mild to severe impact injuries can lead to C2 synchondrosal fractures in young children. OBJECTIVE: To characterize and classify C2 synchondrosal fracture patterns. MATERIALS AND METHODS: We retrospectively reviewed imaging and medical records of children who were treated for cervical spine fractures at our institution between 1995 and 2014. We reviewed all fractures involving the five central C2 synchondroses with regard to patient demographics, mechanism of injury, fracture pattern, associated fractures and other injuries, treatment plans and outcome. RESULTS: Fourteen children had fractures involving the central C2 synchondroses. There were nine boys and five girls, all younger than 6 years. We found four distinct fracture patterns. Eleven complete fractures were further divided into four subtypes (a, b, c and d) based on degree of anterior displacement of the odontoid segment and presence of distraction. Nine of these 11 children had fractures through both odontoneural synchondroses and the odontocentral synchondrosis; one had fractures involving both neurocentral synchondroses and the odontoneural synchondrosis; one had fractures through bilateral odontoneural and bilateral neurocentral synchondroses. Three children had incomplete fractures, defined as a fracture through a single odontoneural synchondrosis with or without partial extension into either the odontocentral or the adjacent neurocentral synchondroses. All complete fractures were displaced or angulated. Four had associated spinal cord injury, including two contusions (subtype c fractures) and two fatal transections (subtype d fractures). Most children were treated with primary halo stabilization. Subtype c fractures required surgical fixation. CONCLUSION: We describe four patterns of central C2 synchondrosal fractures, including two unique patterns that have not been reported. We propose a classification system to distinguish these fractures and aid in treatment planning.

Neonatal deep white matter venous infarction and liquefaction: a pseudo-abscess lesion.

BACKGROUND: Deep white matter hemorrhagic venous infarction with subsequent cavitation due to necrosis and liquefaction has been described in neonates and may be associated with infection and meningitis. In our experience, the MRI pattern of these lesions is confused with the pattern seen with cerebral abscesses. OBJECTIVE: The purpose of our study was to characterize the MRI findings of post infarction necrosis and liquefaction after hemorrhagic deep white matter venous infarction in infants and to distinguish these lesions from cerebral abscesses. MATERIALS AND METHODS: An institutional review board approved a retrospective review of imaging records to identify all patients with cerebral venous infarction at a children's hospital during a 10-year period. Nine infants had deep white matter hemorrhagic venous infarction with white matter fluid signal cavitary lesions. A diagnosis of cerebral abscess was considered in all. The imaging and laboratory findings in these patients are reviewed and compared to descriptions of abscesses found in the literature. RESULTS: There were six female and three male infants. The mean age at presentation was 20 days (range: 0-90 days), while the corrected age at presentation was less than 30 days for all patients. Seven patients presented with seizures and signs of infection; one infant presented with lethargy and later proved to have protein C deficiency. MRI was performed 0-12 days from presentation in these eight patients. Another patient with known protein C deficiency underwent MRI at 30 days for follow-up of screening US abnormalities. There were a total of 38 deep cerebral white matter fluid signal cavitary lesions: 25 frontal, 9 parietal, 2 temporal, 2 occipital. Larger lesions had dependent debris. All lesions had associated hemorrhage and many lesions had evidence of adjacent small vessel venous thrombosis. Lesions imaged after gadolinium showed peripheral enhancement. Three lesions increased in size on follow-up imaging. Three patients, two with meningitis confirmed via microbiology and one with presumed meningitis by CSF counts, underwent surgical aspiration of a total of six lesions. All specimens were sent for pathology and culture and were negative for microorganisms. CONCLUSION: Recognizing the MR appearance of cavitary necrosis and liquefaction after deep white matter cerebral venous infarction in neonates can distinguish this entity from cerebral abscess and potentially avoid an unnecessary neurosurgical aspiration procedure.

Quality of life in pediatric mild traumatic brain injury and its relationship to postconcussive symptoms.

OBJECTIVES: Mild traumatic brain injury (TBI) and injury-related outcomes such as postconcussive symptoms (PCS) may influence health-related quality of life (HRQOL) in children. METHODS: We evaluated HRQOL in 186 8- to 15-year-old children with mild TBI and 99 children with orthopedic injuries (OI). Parents rated the frequency and severity of PCS at an initial assessment within 2-weeks postinjury and rated HRQOL at 3- and 12-months postinjury. RESULTS: The mild TBI and OI groups did not differ in psychosocial HRQOL, but the mild TBI group showed lower physical HRQOL at the 12-month follow-up. Somatic PCS were a significant predictor of physical HRQOL over time, and both cognitive and somatic PCS were significant predictors of psychosocial HRQOL over time. Children with higher PCS at the initial assessment had lower HRQOL scores at later time points. CONCLUSIONS: Effective management of PCS may be associated with improvements in HRQOL following pediatric mild TBI.

Cerebral perfusion and neurological examination characterise neonatal opioid withdrawal syndrome: a prospective cohort study.

OBJECTIVE: To test the hypothesis that cerebral blood flow (CBF) assessed with arterial spin labelling (ASL) MRI is increased and standardised neurological examination is altered in infants with neonatal opioid withdrawal syndrome (NOWS) compared with those without. DESIGN: Prospective cohort study. SETTING: Level IV neonatal intensive care unit and outpatient primary care centre. PARTICIPANTS: Infants with NOWS receiving pharmacological treatment and unexposed controls matched for gestational age at birth and post-menstrual age at MRI. MAIN OUTCOMES: CBF assessed by ASL on non-sedated 3-Tesla MRI and standardised Hammersmith Neonatal Neurological Examination (HNNE) within 14 days of birth. RESULTS: Thirty infants with NOWS and 31 control infants were enrolled and included in the final analysis. Global CBF across the brain was higher in the NOWS group compared with controls (14.2 mL/100 g/min±5.5 vs 10.7 mL/100 g/min±4.3, mean±SD, Cohen's d=0.72). HNNE total optimality score was lower in the NOWS group compared with controls (25.9±3.6 vs 28.4±2.4, mean±SD, Cohen's d=0.81). A penalised logistic regression model including both CBF and HNNE items discriminated best between the two groups. CONCLUSIONS: Increased cerebral perfusion and neurological examination abnormalities characterise infants with NOWS compared with those without intrauterine drug exposure and suggest prenatal substance exposure affects fetal brain development. Identifying neurological and neuroimaging characteristics of infants with NOWS can contribute to understanding mechanisms underlying later outcomes and to designing potential new treatments.

Coping strategies as a predictor of post-concussive symptoms in children with mild traumatic brain injury versus mild orthopedic injury.

This study examined whether children's coping strategies are related to post-concussive symptoms following mild traumatic brain injury (TBI) versus orthopedic injury (OI). Participants were 8- to 15-year-old children with mild TBI (n = 167) or OI (n = 84). They rated their current preferred coping strategies and post-injury symptoms at 2 weeks (baseline) and 1, 3, and 12 months post-injury. Children's reported use of coping strategies did not vary significantly over time, so their baseline coping ratings were examined as predictors of post-concussive symptoms across time. Self-ratings of symptoms were positively related to emotion-focused strategies and negatively related to problem-focused engagement after both mild TBI and OI. Higher problem-focused disengagement predicted larger group differences in children's ratings of symptoms, suggesting that problem-focused disengagement moderates the effects of mild TBI. Coping strategies collectively accounted for approximately 10-15% of the variance in children's post-concussive symptoms over time. The findings suggest that coping may play an important role in accounting for children's perceptions of post-concussive symptoms after mild TBI.

Do postconcussive symptoms discriminate injury severity in pediatric mild traumatic brain injury?

OBJECTIVES: To assess whether postconcussive symptoms (PCS) can be used to discriminate injury severity among children with mild traumatic brain injury (TBI). PARTICIPANTS: One hundred eighty-six children with mild TBI, divided into high and low injury severity depending on whether the injury was associated with a loss of consciousness (LOC), and a comparison group of 99 children with orthopedic injuries (OI), all aged 8 to 15 years at the time of injury. MAIN MEASURES: Parent-rated frequency and severity of PCS at initial assessment within 2 weeks postinjury and again at 3 and 12 months postinjury. RESULTS: Ratings of PCS obtained at the initial and 3-month assessments differentiated children with mild TBI from OI, although only ratings at the initial assessment discriminated among all 3 groups. Somatic PCS accounted for most of the discriminatory power. CONCLUSIONS: Overall, the accuracy of group classification was relatively modest, with a large proportion of misclassifications of children in the mild-TBI groups. Although children with mild TBI have more PCS than children with OI, PCS do not permit sufficiently accurate discrimination of mild TBI and injury severity to warrant diagnostic decisions at this time.

Deep Medullary Vein White Matter Injury Global Severity Score Predicts Neurodevelopmental Impairment.

AIM: To examine associations between the deep medullary vein white matter injury global severity scoring system and neurodevelopmental impairment. METHODS: This is a prospective observational cohort study of infants born at ≥32 weeks, diagnosed with deep medullary vein thrombosis and infarction on neuroimaging in the first month of life. Developmental testing was performed using validated measures for early, preschool, and school-age follow-up. RESULTS: Nineteen (37%) patients had major neurodevelopmental impairment. Global severity score was higher among patients with neurodevelopmental impairment (21.6 vs 13.4, P = .04). Overall, 78% of patients with epilepsy had neurodevelopmental impairment. A greater degree of asymmetry with right-sided injury predominance was associated with lower Bayley-III cognitive scores and presence of neurodevelopmental impairment (P < .01). CONCLUSIONS: Results suggest a need for targeted clinical surveillance for patients with a high global severity score and/or asymmetric, predominantly right cerebral white matter injury and for those who develop epilepsy.

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

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.

YAP1-FAM118B Fusion Defines a Rare Subset of Childhood and Young Adulthood Meningiomas.

Meningiomas are a central nervous system tumor primarily afflicting adults, with <1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2 may be found in ∼50% of meningiomas, with other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to NF2 wild-type tumors. NF2 is an upstream negative regulator of YAP signaling and loss of the NF2 protein product, Merlin, results in YAP overexpression and target gene transcription. This mechanism of dysregulation is described in NF2-driven meningiomas, but further work is necessary to understand the NF2-independent mechanism of tumorigenesis. Amid our institutional patient-centric comprehensive molecular profiling study, we identified an individual with meningioma harboring a YAP1-FAM118B fusion, previously reported only in supratentorial ependymoma. The tumor histopathology was remarkable, characterized by prominent islands of calcifying fibrous nodules within an overall collagen-rich matrix. To gain insight into this finding, we subsequently evaluated the genetic landscape of 11 additional pediatric and adolescent/young adulthood meningioma patients within the Children's Brain Tumor Tissue Consortium. A second individual harboring a YAP1-FAM118B gene fusion was identified within this database. Transcriptomic profiling suggested that YAP1-fusion meningiomas are biologically distinct from NF2-driven meningiomas. Similar to other meningiomas, however, YAP1-fusion meningiomas demonstrated overexpression of EGFR and MET. DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2 wild-type meningioma to include the YAP1-FAM118B fusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.

Cognitive reserve as a moderator of postconcussive symptoms in children with complicated and uncomplicated mild traumatic brain injury.

The occurrence of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children may depend on cognitive reserve capacity. This prospective, longitudinal study examined whether the relationship between mild TBI and PCS is moderated by cognitive ability, which served as a proxy for cognitive reserve. Participants included 182 children with mild TBI and 99 children with orthopedic injuries (OI), ranging from 8 to 15 years of age when injured. Mild TBI were classified as complicated (n = 32) or uncomplicated (n = 150) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging. PCS were assessed initially within 3 weeks of injury, and again at 1, 3, and 12 months post injury. The initial assessment also included standardized tests of children's cognitive skills and retrospective parent ratings of pre-injury symptoms. Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity. Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to children's self-ratings. Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents.

Relationships among post-concussive symptoms and symptoms of PTSD in children following mild traumatic brain injury.

PRIMARY OBJECTIVE: To investigate the occurrence of post-concussive symptoms (PCS) and symptoms of post-traumatic stress disorder (PTSD) in children following mild traumatic brain injuries (TBI). RESEARCH DESIGN: Longitudinal study comparing the outcomes of mild TBI and orthopaedic injuries (OI) in children aged 8-15. METHODS AND PROCEDURES: One hundred and eighty-six children with mild TBI and 99 with OI were recruited prospectively. Parents rated children's PCS and symptoms of PTSD at 2 weeks, 3 months and 12 months post-injury. One hundred and sixty-seven with mild TBI and 84 with OI completed all assessments. MAIN OUTCOMES AND RESULTS: Controlling for symptoms of PTSD, the mild TBI group demonstrated more PCS than the OI group, although the magnitude of group differences diminished with time. Controlling for PCS, the OI group displayed more symptoms of PTSD than the mild TBI group at baseline, but not thereafter. Symptoms of PTSD and PCS were correlated significantly, but more highly in the OI group than the mild TBI group. CONCLUSIONS: Although PCS and symptoms of PTSD are correlated, children with mild TBI are more distinguishable from children with OI based on PCS than on symptoms of PTSD. The latter symptoms, moreover, do not account for increased PCS following mild TBI in children.

Multidelay Arterial Spin Labeling MRI in the Assessment of Cerebral Blood Flow: Preliminary Clinical Experience in Pediatrics.

OBJECTIVES: We attempted to demonstrate the clinical applicability and utility of a three-dimensional multidelay arterial spin labeling magnetic resonance imaging technique in pediatric neuroimaging through a series of case studies. METHODS: Whole-brain three-dimensional multidelay arterial spin labeling data were acquired in five pediatric patients with different neurological conditions using 3 mm to 4 mm slices and a scan time of six to seven minutes. RESULTS: Three-dimensional multidelay arterial spin labeling provided complementary diagnostic information via quantitative cerebral blood flow and arterial transit time maps. CONCLUSIONS: Three-dimensional multidelay arterial spin labeling sequence provides simultaneous quantification of cerebral blood flow and arterial transit time and is feasible for pediatric patients.

Somatic SLC35A2 mosaicism correlates with clinical findings in epilepsy brain tissue.

OBJECTIVE: Many genetic studies of intractable epilepsy in pediatric patients primarily focus on inherited, constitutional genetic deficiencies identified in patient blood. Recently, studies have revealed somatic mosaicism associated with epilepsy in which genetic variants are present only in a subset of brain cells. We hypothesize that tissue-specific, somatic mosaicism represents an important genetic etiology in epilepsy and aim to discover somatic alterations in epilepsy-affected brain tissue. METHODS: We have pursued a research study to identify brain somatic mosaicism, using next-generation sequencing (NGS) technologies, in patients with treatment refractory epilepsy who have undergone surgical resection of affected brain tissue. RESULTS: We used an integrated combination of NGS techniques and conventional approaches (radiology, histopathology, and electrophysiology) to comprehensively characterize multiple brain regions from a single patient with intractable epilepsy. We present a 3-year-old male patient with West syndrome and intractable tonic seizures in whom we identified a pathogenic frameshift somatic variant in SLC35A2, present at a range of variant allele fractions (4.2%-19.5%) in 12 different brain tissues detected by targeted sequencing. The proportion of the SLC35A2 variant correlated with severity and location of neurophysiology and neuroimaging abnormalities for each tissue. CONCLUSIONS: Our findings support the importance of tissue-based sequencing and highlight a correlation in our patient between SLC35A2 variant allele fractions and the severity of epileptogenic phenotypes in different brain tissues obtained from a grid-based resection of clinically defined epileptogenic regions.