The Prognostic Value of Brain Extracellular Fluid Nitric Oxide Metabolites After Traumatic Brain Injury.

BACKGROUND: Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF) adjacent to neurons becomes possible. We investigate the prognostic value of brain ECF NO metabolites in patients with traumatic brain injury (TBI). METHODS: A prospective case cohort of 195 ECF samples collected from 11 cases over 4 days following TBI was collected. Nitrate and nitrite concentrations ([NO( x )]) were quantified using a vanadium-based colorimetric assay. RESULTS: Early ECF [NO( x )] (<48 h post TBI) were significantly higher in non-survivors (median 59.2 μmol/l, n = 7) compared to survivors (23.3 μmol/l, n = 4) (P = 0.04). Late (48-96 h) ECF [NO( x )] remained higher in non-survivors (47.9 μmol/l) compared to survivors (23.0 μmol/l) but this was not significant (P = 0.29). Receiver operator characteristic analysis shows an optimized cutoff level for ECF [NO( x )] of 26.5 μmol/l measured <48 h post TBI for predicting non-survival (sensitivity 100%, specificity 75%). CONCLUSION: Early ECF NO( x ) concentrations are of prognostic value after TBI. ECF NO( x ) may be a useful biomarker for treatment trials targeted at nitric oxide metabolism

Planning stereoelectroencephalography using automated lesion detection: Retrospective feasibility study

OBJECTIVE: This retrospective, cross-sectional study evaluated the feasibility and potential benefits of incorporating deep-learning on structural magnetic resonance imaging (MRI) into planning stereoelectroencephalography (sEEG) implantation in pediatric patients with diagnostically complex drug-resistant epilepsy. This study aimed to assess the degree of colocalization between automated lesion detection and the seizure onset zone (SOZ) as assessed by sEEG. METHODS: A neural network classifier was applied to cortical features from MRI data from three cohorts. (1) The network was trained and cross-validated using 34 patients with visible focal cortical dysplasias (FCDs). (2) Specificity was assessed in 20 pediatric healthy controls. (3) Feasibility of incorporation into sEEG implantation plans was evaluated in 34 sEEG patients. Coordinates of sEEG contacts were coregistered with classifier-predicted lesions. sEEG contacts in seizure onset and irritative tissue were identified by clinical neurophysiologists. A distance of <10 mm between SOZ contacts and classifier-predicted lesions was considered colocalization. RESULTS: In patients with radiologically defined lesions, classifier sensitivity was 74% (25/34 lesions detected). No clusters were detected in the controls (specificity = 100%). Of the total 34 sEEG patients, 21 patients had a focal cortical SOZ, of whom eight were histopathologically confirmed as having an FCD. The algorithm correctly detected seven of eight of these FCDs (86%). In patients with histopathologically heterogeneous focal cortical lesions, there was colocalization between classifier output and SOZ contacts in 62%. In three patients, the electroclinical profile was indicative of focal epilepsy, but no SOZ was localized on sEEG. In these patients, the classifier identified additional abnormalities that had not been implanted. SIGNIFICANCE: There was a high degree of colocalization between automated lesion detection and sEEG. We have created a framework for incorporation of deep-learning-based MRI lesion detection into sEEG implantation planning. Our findings support the prospective evaluation of automated MRI analysis to plan optimal electrode trajectories

Challenging undue influence?:Rethinking children’s participation in contested child contact

Despite the widespread ratification of the United Nations Convention on the Rights of the Child, children continue to struggle to have their participation rights recognised and supported. This is evident within family law, where despite sometimes progressive and strong legislation, children’s views are often not heard, nor given due weight, when parent-child contact is contested within the courts. This paper explores barriers to children’s participation rights being realised. It uses Scotland as the example, due to its strong legal safeguards and mechanisms that aim to support participation rights. The paper draws on recent empirical research with legal professionals, combined with an analysis of reported case law and relevant literature, to explore the barriers ‘on the ground’ for children’s participation rights. Through our analysis, we offer new ways to conceptualise the notion of influence in children’s participation rights in family actions. We offer the conceptual devices of ‘the influenced child’ and ‘the influential child’ to elucidate how children’s participation rights are restricted

Achieving responsible medicines use at practice and farm level

Medicines use in farm animals and the potential for antimicrobial resistance development and transfer to humans is of increasing scientific, public and political concern. Veterinary surgeons must take the lead in driving change: challenging the currently accepted norms of prescribing and administration, advocating and adopting an evidence-based approach to therapeutic decision making, and monitoring patterns of medicines use to identify opportunities for intervention and measure impact, while at the same time partnering with farmers to improve herd health management. This article discusses how such a multifaceted, collaborative approach, which involves the whole practice team working in partnership with farm staff, can be highly successful in achieving and sustaining more responsible medicines use on farm and improving animal health

Exploring student participation across different arenas of school life

Much has now been written on student participation at school. Yet a lack of conceptual clarity, contestation over purpose and benefits, and uncertainty about how to culturally embed and effectively facilitate participation in school contexts continue to pose considerable challenges. This article reports the qualitative findings from a large‐scale, mixed‐method study that sought to explore how participation is perceived and practised in schools. The qualitative phase involved students from Years 7–10 (n = 177) and staff (n = 32) across 10 government and Catholic secondary schools in New South Wales (NSW), Australia. The data demonstrate that considerable efforts are being made in NSW schools to expand opportunities through which students might ‘participate’, with these explored across three key arenas of school life: the classroom; co‐curricular activities, including formal participatory structures; and informal relational spaces. Although participatory opportunities were largely ad hoc and often dependent upon the approach of individual teachers or school initiatives, differing enactments of childhood and adulthood were identifiable between the three arenas, along with varying expectations in this regard. The classroom emerged as a positive arena at present, and one in which adult–child relations are beginning to become reconfigured. The co‐curricular arena was much more contested, with the breadth of potential participatory opportunities perhaps distracting from the need to address underlying intergenerational issues. However, informal relational encounters between students and teachers were becoming increasingly egalitarian, and these offer scope for creating the cultural preconditions such that student participation might expand more evenly across school life

Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study

BACKGROUND AND PURPOSE: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. MATERIALS AND METHODS: We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. RESULTS: A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). CONCLUSIONS: Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values

Proportion of resected seizure onset zone contacts in pediatric stereo-EEG-guided resective surgery does not correlate with outcome

Objective: We aimed to determine whether the proportion of putative seizure onset zone (SOZ) contacts resected associates with seizure outcome in a cohort of children undergoing stereoelectroencephalography (SEEG)-guided resective epilepsy surgery. / Methods: Patients who underwent SEEG-guided resective surgery over a six-year period were included. The proportion of SOZ contacts resected was determined by co-registration of pre- and post-operative imaging. Outcome was classified as seizure free (SF, Engel class I) or not seizure-free (NSF, Engel class II-IV) at last clinical follow-up. / Results: Twenty-nine patients underwent resection of whom 22 had sufficient imaging data for analysis (median age at surgery of 10 years, range 5–18). Fifteen (68.2%) were SF at median follow-up of 19.5 months (range 12–46). On univariate analysis, histopathology, was the only significant factor associated with SF (p < 0.05). The percentage of defined SOZ contacts resected ranged from 25-100% and was not associated with SF (p = 0.89). In a binary logistic regression model, it was highly likely that histology was the only independent predictor of outcome. / Conclusions: The percentage of SOZ contacts resected was not associated with SF in children undergoing SEEG-guided resective epilepsy surgery. / Significance: Factors such as spatial organisation of the epileptogenic zone, neurophysiological biomarkers and the prospective identification of pathological tissue may therefore play an important role

Drug-resistant focal epilepsy in children is associated with increased modal controllability of the whole brain and epileptogenic regions

Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function