Temporal trends of transport-related injuries on New Zealand roads.

AIM: This observational study aimed to investigate temporal trends in transport-related injuries in New Zealand by mode of transport and explore whether specific population groups and localities have a relatively higher incidence of injury. These trends provide insight into changes in injury patterns from road trauma. METHODS: A retrospective study of hospitalised road trauma in New Zealand was conducted between 1 July 2017 to 30 June 2021. Data were obtained from the National Minimum Dataset of hospital admissions, and the New Zealand Trauma Registry (NZTR). Road trauma was identified using ICD-10 coding, and major trauma using Abbreviated Injury Scale (AIS) coding. Analysis included road trauma by mode, ethnicity, rurality and population rates. Statistical analysis included Interrupted Time Series (ITS) analysis to account for the impact of COVID-19 on road trauma. RESULTS: Over the 4-year period there were 20,607 incidents of transport-related injury that resulted in admission to a New Zealand hospital. Of these, 14.5% (2,992) involved injuries that were classified as major trauma. Car occupants accounted for 62% of hospitalisations, followed by motorcyclists (23%), pedestrians (9%) and pedal cyclists (4%). Temporal trends showed no reduction in injuries from cars, pedal cyclists and pedestrian injuries, but an increase in motorcycling injuries. Maori had an age-standardised incidence rate almost 3.5 times higher than the rate for Asian peoples. CONCLUSION: The increases in motorcycling injuries and no changes in pedestrian and cycling injuries, as well as demographic variation, highlight the need to focus on vulnerable road users. Effective and targeted initiatives on vulnerable road users will support objectives to reduce deaths and serious injury on New Zealand roads. Enhanced exposure data is needed for vulnerable road users to account for mobility changes over time. Linked data across population-based datasets is an important asset that enhances our understanding of road traffic injuries and allows evidence-based countermeasures to be developed.

A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.

BACKGROUND: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. METHODS: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. RESULTS: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. CONCLUSION: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. TRIAL REGISTRATION: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246.

Correlation between whole body muscle MRI and functional measures in paediatric patients with facioscapulohumeral muscular dystrophy.

Symptoms and severity of facioscapulohumeral muscular dystrophy (FSHD) can vary greatly, even within the same family. Clinical trial readiness requires accurate and reliable methods of assessing disease stage and progression. MRI has not previously been assessed as a disease biomarker in paediatric FSHD. Eleven patients with FSHD1 underwent whole body muscle MRI. Pre-selected muscles were analysed by a paediatric radiologist using the semi-quantitative Mercuri/Kim method. Within each domain (oedema, fat replacement, atrophy) scores for each muscle were then summated to give each participant three cumulative domain scores. The same participants had functional measures scored: FSHD-CSS (Ricci), FSHD-CS (Lamperti), FSHD-COM, PUL2.0, MFM-32, 6MWT, myometry and manual muscle testing. Pearson coefficient was calculated to determine strength of correlation. The scores for atrophy and fat replacement showed strong correlation with functional outcome measures, particularly FSHD-CSS, FSHD-CS and FSHD-COM. In contrast, muscle oedema correlated poorly with all functional outcome measures, with no relationship seen to the 6MWT. This study of eleven children suggests that semi-quantitative visual Mercuri score utilising fat replacement or atrophy on whole body muscle MRI correlates strongly with disease-specific functional measures and may be a useful measure of disease severity in paediatric FSHD.

Karawun: a software package for assisting evaluation of advances in multimodal imaging for neurosurgical planning and intraoperative neuronavigation.

PURPOSE: The neuroimaging research community-which includes a broad range of scientific, medical, statistical, and engineering disciplines-has developed many tools to advance our knowledge of brain structure, function, development, aging, and disease. Past research efforts have clearly shaped clinical practice. However, translation of new methodologies into clinical practice is challenging. Anything that can reduce these barriers has the potential to improve the rate at which research outcomes can contribute to clinical practice. In this article, we introduce Karawun, a file format conversion tool, that has become a key part of our work in translating advances in diffusion imaging acquisition and analysis into neurosurgical practice at our institution. METHODS: Karawun links analysis workflows created using open-source neuroimaging software, to Brainlab (Brainlab AG, Munich, Germany), a commercially available surgical planning and navigation suite. Karawun achieves this using DICOM standards supporting representation of 3D structures, including tractography streamlines, and thus offers far more than traditional screenshot or color overlay approaches. RESULTS: We show that neurosurgical planning data, created from multimodal imaging data using analysis methods implemented in open-source research software, can be imported into Brainlab. The datasets can be manipulated as if they were created by Brainlab, including 3D visualizations of white matter tracts and other objects. CONCLUSION: Clinicians can explore and interact with the results of research neuroimaging pipelines using familiar tools within their standard clinical workflow, understand the impact of the new methods on their practice and provide feedback to methods developers. This capability has been important to the translation of advanced analysis techniques into practice at our institution.

Prospective Associations of Susceptibility-Weighted Imaging Biomarkers with Fatigue Symptom Severity in Childhood Traumatic Brain Injury.

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Assessment of intraoperative diffusion EPI distortion and its impact on estimation of supratentorial white matter tract positions in pediatric epilepsy surgery.

The effectiveness of correcting diffusion Echo Planar Imaging (EPI) distortion and its impact on tractography reconstruction have not been adequately investigated in the intraoperative MRI setting, particularly for High Angular Resolution Diffusion Imaging (HARDI) acquisition. In this study, we evaluated the effectiveness of EPI distortion correction using 27 legacy intraoperative HARDI datasets over two consecutive surgical time points, acquired without reverse phase-encoded data, from 17 children who underwent epilepsy surgery at our institution. The data was processed with EPI distortion correction using the Synb0-Disco technique (Schilling et al., 2019) and without distortion correction. The corrected and uncorrected b0 diffusion-weighted images (DWI) were first compared visually. The mutual information indices between the original T1-weighted images and the fractional anisotropy images derived from corrected and uncorrected DWI were used to quantify the effect of distortion correction. Sixty-four white matter tracts were segmented from each dataset, using a deep-learning based automated tractography algorithm for the purpose of a standardized and unbiased evaluation. Displacement was calculated between tracts generated before and after distortion correction. The tracts were grouped based on their principal morphological orientations to investigate whether the effects of EPI distortion vary with tract orientation. Group differences in tract distortion were investigated both globally, and regionally with respect to proximity to the resecting lesion in the operative hemisphere. Qualitatively, we observed notable improvement in the corrected diffusion images, over the typically affected brain regions near skull-base air sinuses, and correction of additional distortion unique to intraoperative open cranium images, particularly over the resection site. This improvement was supported quantitatively, as mutual information indices between the FA and T1-weighted images were significantly greater after the correction, compared to before the correction. Maximum tract displacement between the corrected and uncorrected data, was in the range of 7.5 to 10.0 mm, a magnitude that would challenge the safety resection margin typically tolerated for tractography-informed surgical guidance. This was particularly relevant for tracts oriented partially or fully in-line with the acquired diffusion phase-encoded direction. Portions of these tracts passing close to the resection site demonstrated significantly greater magnitude of displacement, compared to portions of tracts remote from the resection site in the operative hemisphere. Our findings have direct clinical implication on the accuracy of intraoperative tractography-informed image guidance and emphasize the need to develop a distortion correction technique with feasible intraoperative processing time.

Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.

Background and Purpose: Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. Methods: An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient <620×10−6 mm2/s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume <70 mL, mismatch volume ≥15 mL, and a mismatch ratio ≥1.8. Results: Twenty-nine children (median 8 years old, interquartile range, 4.4­14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3­11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5­25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small (<3.5 mL). Overall, 3 children, imaged at 3.75, 11, and 23.5 hours had favorable mismatch profiles. Conclusions: This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics.

One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia.

OBJECTIVE: To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD). METHODS: We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings in consecutively operated patients with drug-resistant focal epilepsy and MRI-positive BOSD, all of whom underwent corticectomy guided by MRI and ECoG. RESULTS: Thirty-eight patients with a median age at surgery of 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex in 15 patients. Eighty-seven percent of patients had rhythmic spiking on preresection ECoG. Rhythmic spiking was present in 22 of 24 patients studied with combined depth and surface electrodes, being limited to the dysplastic sulcus in 7 and involving the dysplastic sulcus and gyral crown in 15. Sixty-eight percent of resections were limited to the dysplastic sulcus, leaving the gyral crown. Histopathology was focal cortical dysplasia (FCD) type IIb in 29 patients and FCDIIa in 9. Dysmorphic neurons were present in the bottom of the sulcus but not the top or the gyral crown in 17 of 22 patients. Six (16%) patients required reoperation for postoperative seizures and residual dysplasia; reoperation was not correlated with ECoG, neuroimaging, or histologic abnormalities in the gyral crown. At a median 6.3 (IQR 4.8-9.9) years of follow-up, 33 (87%) patients are seizure-free, 31 off antiseizure medication. CONCLUSION: BOSD can be safely and effectively resected with MRI and ECoG guidance, corticectomy potentially being limited to the dysplastic sulcus, without need for intracranial EEG monitoring and functional mapping. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 1-stage, limited corticectomy for BOSD is safe and effective for control of seizures.

Airway closure is the predominant physiological mechanism of low ventilation seen on hyperpolarized helium-3 MRI lung scans.

Hyperpolarized helium-3 MRI (3He MRI) provides detailed visualization of low- (hypo- and non-) ventilated lungs. Physiological measures of gas mixing may be assessed by multiple breath nitrogen washout (MBNW) and of airway closure by a forced oscillation technique (FOT). We hypothesize that in patients with asthma, areas of low-ventilated lung on 3He MRI are the result of airway closure. Ten control subjects, ten asthma subjects with normal spirometry (non-obstructed), and ten asthmatic subjects with reduced baseline lung function (obstructed) attended two testing sessions. On visit one, baseline plethysmography was performed followed by spirometry, MBNW, and FOT assessment pre and post methacholine challenge. On visit two, 3He MRI scans were conducted pre and post methacholine challenge. Post methacholine the volume of low-ventilated lung increased from 8.3% to 13.8% in the non-obstructed group (P = 0.012) and from 13.0% to 23.1% in the obstructed group (P = 0.001). For all subjects, the volume of low ventilation from 3He MRI correlated with a marker of airway closure in obstructive subjects, Xrs (6 Hz) and the marker of ventilation heterogeneity Scond with r2 values of 0.61 (P < 0.001) and 0.56 (P < 0.001), respectively. The change in Xrs (6 Hz) correlated well (r2 = 0.45, p < 0.001), whereas the change in Scond was largely independent of the change in low ventilation volume (r2 = 0.13, P < 0.01). The only significant predictor of low ventilation volume from the multi-variate analysis was Xrs (6 Hz). This is consistent with the concept that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.NEW & NOTEWORTHY This study introduces a novel technique of generating high-resolution 3D ventilation maps from hyperpolarized helium-3 MRI. It is the first study to demonstrate that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.

Altered resting-state functional connectivity within the developing social brain after pediatric traumatic brain injury.

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting-state functional magnetic resonance imaging 12-24 months post-injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between-group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal-fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments.

Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study.

INTRODUCTION: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD. METHODS AND ANALYSIS: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria. ETHICS AND DISSEMINATION: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

MRπ: Inside the meat pie.

Meat pies have been adopted as one of Australia's favourite foods, and considered an icon by many. The hand-held convenience of the pie has made them a culinary necessity while watching sport, also beloved in Australia. An enduring question about the meat pie is what exactly is inside. This can be difficult to ascertain by digital, ocular or oral exploration. In this study we use MR imaging to study the contents of some of Australia's best loved pies.

Uncovering cortico-striatal correlates of cognitive fatigue in pediatric acquired brain disorder: Evidence from traumatic brain injury.

Cognitive fatigue is among the most profound and disabling sequelae of pediatric acquired brain disorders, however the neural correlates of these symptoms in children remains unexplored. One hypothesis suggests that cognitive fatigue may arise from dysfunction of cortico-striatal networks (CSNs) implicated in effort output and outcome valuation. Using pediatric traumatic brain injury (TBI) as a model, this study investigated (i) the sub-acute effect of brain injury on CSN volume; and (ii) potential relationships between cognitive fatigue and sub-acute volumetric abnormalities of the CSN. 3D T1 weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children (TBI: n = 103; typically developing - TD children: n = 34). 67 of the original 137 participants (49%) completed measures of cognitive fatigue and psychological functioning at 24-months post-injury. Results showed that compared to TD controls and children with milder injuries, children with severe TBI showed volumetric reductions in the overall CSN package, as well as regional gray matter volumetric change in cortical and subcortical regions of the CSN. Significantly greater cognitive fatigue in the TBI patients was associated with volumetric reductions in the CSN and its putative hub regions, even after adjusting for injury severity, socioeconomic status (SES) and depression. In the first study to evaluate prospective neuroanatomical correlates of cognitive fatigue in pediatric acquired brain disorder, these findings suggest that post-injury cognitive fatigue is related to structural abnormalities of cortico-striatal brain networks implicated in effort output and outcome valuation. Morphometric magnetic resonance imaging (MRI) may have potential to unlock early prognostic markers that may assist to identify children at elevated risk for cognitive fatigue post-TBI.

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery.

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery-related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI-based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530-3543, 2016. © 2016 Wiley Periodicals, Inc.

Developmental brain trajectories in children with ADHD and controls: a longitudinal neuroimaging study.

BACKGROUND: The symptom profile and neuropsychological functioning of individuals with Attention Deficit/Hyperactivity Disorder (ADHD), change as they enter adolescence. It is unclear whether variation in brain structure and function parallels these changes, and also whether deviations from typical brain development trajectories are associated with differential outcomes. This paper describes the Neuroimaging of the Children's Attention Project (NICAP), a comprehensive longitudinal multimodal neuroimaging study. Primary aims are to determine how brain structure and function change with age in ADHD, and whether different trajectories of brain development are associated with variations in outcomes including diagnostic persistence, and academic, cognitive, social and mental health outcomes. METHODS/DESIGN: NICAP is a multimodal neuroimaging study in a community-based cohort of children with and without ADHD. Approximately 100 children with ADHD and 100 typically developing controls will be scanned at a mean age of 10 years (range; 9-11years) and will be re-scanned at two 18-month intervals (ages 11.5 and 13 years respectively). Assessments include a structured diagnostic interview, parent and teacher questionnaires, direct child cognitive/executive functioning assessment and magnetic resonance imaging (MRI). MRI acquisition techniques, collected at a single site, have been selected to provide optimized information concerning structural and functional brain development. DISCUSSION: This study will allow us to address the primary aims by describing the neurobiological development of ADHD and elucidating brain features associated with differential clinical/behavioral outcomes. NICAP data will also be explored to assess the impact of sex, ADHD presentation, ADHD severity, comorbidities and medication use on brain development trajectories. Establishing which brain regions are associated with differential clinical outcomes, may allow us to improve predictions about the course of ADHD.

The surgically remediable syndrome of epilepsy associated with bottom-of-sulcus dysplasia.

OBJECTIVE: To determine clinical and EEG features that might help identify patients with epilepsy harboring small, intrinsically epileptogenic, surgically treatable, bottom-of-sulcus dysplasias (BOSDs). METHODS: Retrospective review of clinical records, EEG, MRI, and histopathology in 32 patients with drug-resistant epilepsy and MRI-positive (72% 3.0 tesla), pathologically proven (type 2B cortical dysplasia) BOSDs operated at our centers during 2005-2013. RESULTS: Localization of BOSDs was frontal in 19, insula in 5, parietal in 5, and temporal in 3, on the convexity or interhemispheric surfaces. BOSDs were missed on initial MRI at our centers in 22% of patients. Patients presented with focal seizures during infancy in 9, preschool years in 15, and school years in 8 (median age 5 years). Seizures were stereotyped, predominantly nocturnal, and typically nonconvulsive, with semiology referable to the fronto-central or perisylvian regions. Seizures occurred at high frequency during active periods, but often went into prolonged remission with carbamazepine or phenytoin. Intellect was normal or borderline, except in patients with seizure onset during infancy. Scalp EEG frequently revealed localized interictal epileptiform discharges and ictal rhythms. Patients underwent lesionectomy (median age 14 years) guided by electrocorticography and MRI, with prior intracranial EEG monitoring in only one patient. Twenty-eight patients (88%) became seizure-free, and 20 discontinued antiepileptic medication (median follow-up 4.1 years). CONCLUSIONS: In patients with cryptogenic focal epilepsy, this clinical presentation and course should prompt review of or repeat MRI, looking for a BOSD in the frontal, parietal, or insula cortex. If a BOSD is identified, the patient might be considered for single-stage lesionectomy.

Alterations in the optic radiations of very preterm children-Perinatal predictors and relationships with visual outcomes.

Children born very preterm (VPT) are at risk for visual impairments, the main risk factors being retinopathy of prematurity and cerebral white matter injury, however these only partially account for visual impairments in VPT children. This study aimed to compare optic radiation microstructure and volume between VPT and term-born children, and to investigate associations between 1) perinatal variables and optic radiations; 2) optic radiations and visual function in VPT children. We hypothesized that optic radiation microstructure would be altered in VPT children, predicted by neonatal cerebral white matter abnormality and retinopathy of prematurity, and associated with visual impairments. 142 VPT children and 32 controls underwent diffusion-weighted magnetic resonance imaging at 7 years of age. Optic radiations were delineated using constrained spherical deconvolution tractography. Tract volume and average diffusion tensor values for the whole optic radiations and three sub-regions were compared between the VPT and control groups, and correlated with perinatal variables and 7-year visual outcome data. Total tract volumes and average diffusion values were similar between VPT and control groups. On regional analysis of the optic radiation, mean and radial diffusivity were higher within the middle sub-regions in VPT compared with control children. Neonatal white matter abnormalities and retinopathy of prematurity were associated with optic radiation diffusion values. Lower fractional anisotropy in the anterior sub-regions was associated with poor visual acuity and increased likelihood of other visual defects. This study presents evidence for microstructural alterations in the optic radiations of VPT children, which are largely predicted by white matter abnormality or severe retinopathy of prematurity, and may partially explain the higher rate of visual impairments in VPT children.

Susceptibility weighted imaging and its relationship to outcome after pediatric traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) sustained during childhood can cause difficulties in a wide range of physical, neurological, cognitive, social and functional domains. However, the ability of health professionals and researchers to accurately predict the outcome of pediatric TBI remains limited. The advent of advanced neuroimaging techniques shows some promise in improving outcome prediction, as they contribute to greater sensitivity in characterizing intracranial lesions underlying many cognitive and functional deficits. In this study, the relationship between lesions identified on susceptibility weighted imaging (SWI) and cognitive and functional outcomes was investigated following childhood TBI. METHOD: Participants between 5 and 14 years of age with varying levels of TBI severity (mild, mild complicated, moderate, severe, n = 106) underwent susceptibility weighted scanning on average 1-month post-injury and completed an assessment of intellectual functioning, processing speed, and behavioral and adaptive skills 6-month post-injury. RESULTS: More severe TBI was generally associated with poorer intellectual functioning, greater behavioral problems and lower adaptive functioning. Number and volume of SWI lesions were significantly correlated with clinical outcome variables including Glasgow Coma Score (GCS), surgical intervention, length of hospital stay and length of intubation, as well as with intellectual functioning. Together, SWI and GCS accounted for a significant, though small, proportion of the variance in intellectual quotient (IQ). CONCLUSIONS: SWI is a sensitive technique for detecting brain lesions at all TBI severity levels and shows promise in contributing to prediction of cognitive outcomes in the initial stages post-injury.

Focal thinning of the posterior corpus callosum: normal variant or post-traumatic?

AIM: The corpus callosum (CC) can be affected by childhood traumatic brain injury (TBI), through focal lesions, reductions in size and arrested development. Little is known, however, about what constitutes normal CC shape and appearance and how it may be affected in the long-term after early TBI. METHODS: In this study, the appearance of the CC was investigated in individuals with TBI assessed 10 years post-injury (n = 52, mean age = 16.82 years, SD = 3.55 years, 24 male) and compared to age-matched healthy controls (n = 44, mean age = 15.77 years, SD = 1.21 years, 18 male). A simple visual analysis technique was used to code the appearance of the CC according to location of focal thinning and severity of thinning and results between groups were compared using Chi-square analysis. RESULTS: A significantly higher proportion of patients with childhood TBI had focal posterior thinning of the CC than age-matched controls (p = 0.001). CONCLUSIONS: The findings call into question previous conclusions that focal posterior thinning is a normal variant of development. Instead, attenuations of the posterior portion of the CC in the long-term may reflect altered cortical and callosal development as a result of early brain injury, although the functional significance of this remains to be determined.