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To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS). Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13–14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14–42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks. 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13–14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14–42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = −0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33). With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome. • Embedding a second randomisation in trials effectively provides additional information about trial treatments. • There was no significant difference between prednisolone and tetracosactide depot in those achieving early spasm cessation. • There was no significant difference between trial treatments in those free of epileptic seizures at 14 and 18 months. • Developmental outcome was similar in both treatment groups. • Either prednisolone or tetracosactide depot can be recommended when using hormonal treatment as monotherapy. [ABSTRACT FROM AUTHOR]

Focal cerebral arteriopathy (FCA), a major cause of childhood arterial ischemic stroke (AIS), can progress and lead to increased infarct size and/or recurrent stroke. Evaluating treatment options depends on the ability to quantify reliably the degree of stenosis in FCA. We validated the recently introduced FCA severity score (FCASS) in an independent cohort from the Swiss Neuro-Paediatric Stroke Registry (SNPSR). We included children with FCA who had MR or CT angiography and a Pediatric Stroke Outcome Measure (PSOM) at 6-months and 2-years post-stroke. A paediatric neuroradiologist applied the FCASS and the modified pediatric Alberta Stroke Program Early Computed Tomography Score (ASPECTS), a measure of infarct volume, to all available imaging. Two senior paediatric stroke neurologists and a neuroradiology fellow independently assigned FCASS scores to test interrater reliability. Pairwise correlations between FCASS, pedASPECTS, and PSOM were examined. Thirty-two children [median (IQR) age = 5.9 (1.8, 9.6), 19 males] were included. The median maximum FCASS score at any time was 9 (IQR 6, 12; range 3, 16). Larger infarct volume scores correlated with both higher maximum FCASS scores and worse post-stroke outcomes, although we found no direct correlation between FCASS and outcomes. Stroke neurologists tended to assign lower FCASS scores than the neuroradiologist, but interrater reliability was predominantly good. In this independent validation cohort, higher maximum FCASS correlated with greater infarct volume scores that also correlated with worse neurological outcomes. Scoring by non-imaging specialists seems to be valuable, although differences are present. • Treatment trials under development for Focal Cerebral Arteriopathy (FCA)—a unilateral anterior circulation arteriopathy that causes childhood arterial ischemic stroke—require a validated metric for FCA severity. The FCA Severity Score (FCASS) quantifies disease severity and extent. • The goal of the current study was to validate the FCA Severity Score in an independent cohort of FCA cases from the Swiss Neuro-Paediatric Stroke Registry (SNPSR). In this independent validation cohort, higher maximum FCASS correlated with greater infarct volume scores that also correlated with worse neurological outcomes. [ABSTRACT FROM AUTHOR]

Little is known about resilience after paediatric stroke (PS), or the factors that contribute to better outcomes. Rather, research emphasis has been on impairment, measured through cross-sectional or retrospective designs, often heavily weighted to children presenting for clinical or rehabilitation follow-up. Implementing a resilience framework, this study aimed to investigate cognitive recovery post-stroke and factors that contribute to cognitive resilience at 12 months following PS. In a single site, prospective, longitudinal study (baseline, 1, 6, 12 months post-stroke), 61 children (55.7% male) aged 0–18 years, with a diagnosis of acute arterial ischemic stroke were recruited. Neurological status, lesion and child characteristics were collected at diagnosis. Cognitive, language and motor skills were assessed directly using age-appropriate, standardised tools. Parents rated their mental health, and child social and adaptive abilities. Participants were classified as 'resilient' (74%) or 'vulnerable' based on 12-month cognitive scores. The resilient group demonstrated more intact acute neurological status and higher language and adaptive abilities 1-month post-stroke; 88% of the vulnerable group had strokes involving both cortical and subcortical regions. Neonatal stroke, large lesions, cortical-only lesions, and middle cerebral artery involvement were associated with poorer cognition over the 12 months post-stroke. Absence of seizures and older age at stroke predicted better cognitive outcomes. In summary, most children surviving PS are cognitively resilient at 12 months post-insult. Risk and protective factors identified may guide targeted clinical intervention for more vulnerable children. Future research is needed to explore cognitive resilience trajectories beyond 12 months post-stroke. • Most PS survivors show intact cognition at 12 months, suggesting resilience after such brain insult is unexpectedly common. • Risk and protective factors identified in the present study may provide a guide for targeting clinical follow-up and intervention. • Future research is needed to explore cognitive resilience trajectories beyond 12 months post-stroke. [ABSTRACT FROM AUTHOR]

Abstract Background To minimise the risk of patient harm from results, laboratories should establish QC strategies and monitor the performance of assays in line with the analytical and clinical risk. Methods Steady state errors were calculated from a distribution normalized for an Analytical Performance Specification expressed as Assay Capability (imprecision) minus Assay Stability (drift). Inverting this error rate gave QC run length containing one error. Multiplying by error detection of a critical shift gave a QC functional run length for stable and unstable situations. Suitability of this technique was examined using laboratory EQA imprecision and drift data against various analytical and clinical performance specifications. Results Steady state errors and error detection, and hence QC functional run length, were dramatically affected by worsening imprecision, drift or changing performance specifications. For a single analyser type, laboratory steady state errors against RCPAQAP performance specification ranged over five orders of magnitude, with contributions from Assay Capability and Assay Stability varying by laboratory. Conclusions Steady state errors accumulate for all assays. Our functional QC run length based on steady state error rate adjusted for error detection of the QC algorithm, amounts to a risk approach using the first two elements of FMEA-like calculation and allows laboratories to examine the suitability of their combinations of QC run length, algorithm, workload and timing of QC challenges. An appropriate common performance specification is critical when assessing and comparing risk. [ABSTRACT FROM AUTHOR]

We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene. [ABSTRACT FROM AUTHOR]

Purpose: Status epilepticus (SE) is a paediatric emergency with significant morbidity and mortality. Recommendations beyond first line care are not based on high quality evidence. Emergency physicians and neurologists are key stakeholders in managing this condition. A collaborative, widely consulted approach to identifying priorities can help direct limited research funds appropriately. The objectives of this study are to identify consensus research priorities in paediatric SE among experts and health consumers.Methods: A three-stage Delphi process was conducted. Paediatric Neurologists and Emergency Physicians in Australia and New Zealand participated. Round one asked participants to generate three research questions important for further research in paediatric status epilepticus. Responses were refined into unique individual questions. Rounds two and three required participants to rate questions on a seven point ordinal scale. Health consumers were invited to participate by providing up to three problem areas that could be addressed by research.Results: 54 experts and 76 health consumers participated in the process. Nine questions reached our definition of consensus "high priority", 21 questions achieved consensus "low priority" and seven questions did not achieve consensus. High priority areas included second line management including levetiracetam (efficacy, dose and timing), use of third line agents, induction of anaesthesia (timing and best agent), management of focal SE, and indicators of "subtle SE". Consumer priority areas included themes of treatment efficacy, aetiology, and community education.Conclusion: We identified nine priority research questions in paediatric SE, congruent with the health consumer theme of treatment efficacy. Future research efforts should be directed towards these priority areas. [ABSTRACT FROM AUTHOR]

Gaining a better understanding of Quality Control (QC) processes is a key requirement to improving performance and reducing patient risk. Detecting analytical error is dependent on a QC strategy that reliably detects a critical shift in a result away from the true value. Recently the concept of Six Sigma has been used by diagnostic laboratories to assess the performance of assays and to assist in the selection of QC rules. The sigma metric is one measure of an assay's ability to perform within specification. However an additional dimension to managing an assay is its stability in bias over time. The concept of long term stability is the same as measured QC drift (SE drift ) which is the effect of numerous calibrations, changes in reagent lots and other conditions i.e. a long term effect. This implies that the standard error budget is wrong because it is modelled on short term QC and misses this SE drift stability component. We show that SE drift provides a measure of Assay Stability that should be included in Quality Planning and that by including an allowance for this drift, determining target imprecision appropriate for matched QC algorithms that provide high error detection is as simple as dividing the Allowable Performance Specification by 4, 5 or 6. [ABSTRACT FROM AUTHOR]

Objectives We propose a simple way to reliably rank assays for improvement according to patient risk, based solely on EQA imprecision and biological variation data. Because the underlying technique aligns the imprecision class of an assay from EQA data, peer performance can be used to assess achievable imprecision and the risk ranking can not only prioritise improvement but also highlight laboratory QC operating parameters that are easy to manage and provide reliable, acceptable performance. Design and methods A modified Failure Modes Effects Analysis (FMEA) is applied to produce an analyte risk rating based on three factors, each of which is graded: 1) the ease of detecting analytical errors based on the ratio of allowable limits of performance to imprecision (Assay Capability) compared to absolute standards and to peers, 2) the predicted frequency of errors in patient monitoring based on the ratio of within-individual biological variation to laboratory imprecision, and 3) the clinical importance of the assay as a surrogate marker for harm arising from an error. Results We provide laboratory examples to illustrate these models. Conclusion The proposed models using only EQA data can objectively identify assays at risk of failing against biological variation goals for monitoring patients and suggest parameters for reliable performance. [ABSTRACT FROM AUTHOR]

Pediatric stroke is unfortunately not a rare condition. It is associated with severe disability and mortality because of the complexity of potential clinical manifestations, and the resulting delay in seeking care and in diagnosis. Neuroimaging plays an important role in the multidisciplinary response for pediatric stroke patients. The rapid development of adult endovascular thrombectomy has created a new momentum in health professionals caring for pediatric stroke patients. Neuroimaging is critical to make decisions of identifying appropriate candidates for thrombectomy. This review article will review current neuroimaging techniques, imaging work-up strategies and special considerations in pediatric stroke. For resources limited areas, recommendation of substitute imaging approaches will be provided. Finally, promising new techniques and hypothesis-driven research protocols will be discussed. [ABSTRACT FROM AUTHOR]

Study objective: Little is known about the presenting features of acute ischemic and hemorrhagic stroke in children presenting to the emergency department (ED). Yet, initial clinical assessment is a key step in the management pathway of stroke. We describe the presentation in the ED of children with confirmed acute ischemic and hemorrhagic stroke subtypes. Methods: We conducted a retrospective descriptive case series of consecutive patients aged 1 month to younger than 18 years and presenting to a single-center tertiary ED with radiologically confirmed acute ischemic stroke or hemorrhagic stroke during a 5-year period. Patients were identified by medical record search with International Classification of Diseases, 10th Revision codes for hemorrhagic stroke and through the hospital stroke registry for acute ischemic stroke. Signs, symptoms, and initial management were described. Results: Fifty patients with acute ischemic stroke and 31 with hemorrhagic stroke were identified. Mean age was 8.7 years (SD 5.2), and 51% were male. Fifty-six percent were previously healthy. Median time from onset of symptoms to ED presentation was 21 hours (interquartile range 6 to 48 hours) for acute ischemic stroke and 12 hours (interquartile range 4 to 72 hours) for hemorrhagic stroke. Acute ischemic stroke presented with symptoms of focal limb weakness (64%; 95% confidence interval [CI] 49% to 77%), facial weakness (60%; 95% CI 45% to 73%), and speech disturbance (46%; 95% CI 31% to 60%). Few patients with acute ischemic stroke presented with vomiting and altered mental status. Most patients with acute ischemic stroke had a Glasgow Coma Scale (GCS) score of 14 or greater (86%; 95% CI 73% to 94%) and presented with at least 1 focal neurologic sign (88%; 95% CI 73% to 98%). Hemorrhagic stroke presented with headache (73%; 95% CI 54% to 87%), vomiting (58%; 95% CI 40% to 75%), and altered mental status (48%; 95% CI 30% to 67%). GCS score in hemorrhagic stroke was less than 14 in 38% and less than 8 in 19% (95% CI 7% to 37%). Less than one third of patients had focal limb weakness, facial weakness, or slurred speech. Nineteen percent of patients with hemorrhagic stroke were intubated in the ED and admitted to the ICU. None of the acute ischemic stroke patients were intubated in the ED, and 4% were admitted to the ICU. Conclusion: Diagnosis of stroke in children with acute ischemic stroke and hemorrhagic stroke was delayed. Acute ischemic stroke presented mainly with focal findings; hemorrhagic stroke, with headache, vomiting, and mental status change. [Copyright &y& Elsevier]

Acute flaccid paralysis is associated with inflammation, infection, or tumors in the spinal cord or peripheral nerves. Melioidosis (Burkholderia pseudomallei infection) can rarely cause this presentation. We describe a case of spinal melioidosis in a 4-year-old boy presenting with flaccid paralysis, and review the literature on this rare disease. [ABSTRACT FROM AUTHOR]

Because of the nature of the Fontan physiology, patients are at an increased risk of thromboembolic complications. As such, warfarin or aspirin is generally prescribed lifelong for thromboprophylaxis. This study aimed to compare long-term rates of cerebrovascular injury, thrombosis, bleeding, bone mineral density, and quality of life in people living with Fontan circulation receiving warfarin compared with aspirin. This was a multicenter study of a selected cohort from the Australia and New Zealand Fontan population. Participants underwent cerebral magnetic resonance imaging to detect the presence of cerebrovascular injury (n = 84) and dual-energy X-ray absorptiometry to assess bone mineral density (n = 120). Bleeding (n = 100) and quality of life (n = 90) were assessed using validated questionnaires: Warfarin and Aspirin Bleeding assessment tool and Pediatric Quality of Life Inventory, respectively. Stroke was detected in 33 participants (39%), with only 7 (6%) being clinically symptomatic. There was no association between stroke and Fontan type or thromboprophylaxis type. Microhemorrhage and white matter injury were detected in most participants (96% and 86%, respectively), regardless of thromboprophylaxis type. Bleeding rates were high in both groups; however, bleeding was more frequent in the warfarin group. Bone mineral density was reduced in our cohort compared with the general population; however, this was further attenuated in the warfarin group. Quality of life was similar between the warfarin and aspirin groups. Home international normalized ratio monitoring was associated with better quality of life scores in the warfarin group. Cerebrovascular injury is a frequent occurrence in the Australia and New Zealand Fontan population regardless of thromboprophylaxis type. No benefit of long-term warfarin prophylaxis could be demonstrated over aspirin; however, consideration must be given to important clinical features such as cardiac function and lung function. Furthermore, the association of reduced bone health in children receiving warfarin warrants further mechanistic studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Information on the medium-term recovery of children with Bell palsy or acute idiopathic lower motor neuron facial paralysis is limited. We followed up children aged 6 months to <18 years with Bell palsy for 12 months after completion of a randomized trial on the use of prednisolone. We assessed facial function using the clinician-administered House-Brackmann scale and the modified parent-administered House-Brackmann scale. One hundred eighty-seven children were randomized to prednisolone (n = 93) or placebo (n = 94). At six months, the proportion of patients who had recovered facial function based on the clinician-administered House-Brackmann scale was 98% (n = 78 of 80) in the prednisolone group and 93% (n = 76 of 82) in the placebo group. The proportion of patients who had recovered facial function based on the modified parent-administered House-Brackmann scale was 94% (n = 75 of 80) vs 89% (n = 72 of 81) at six months (OR 1.88; 95% CI 0.60, 5.86) and 96% (n = 75 of 78) vs 92% (n = 73 of 79) at 12 months (OR 3.12; 95% CI 0.61, 15.98). Although the vast majority had complete recovery of facial function at six months, there were some children without full recovery of facial function at 12 months, regardless of prednisolone use. [ABSTRACT FROM AUTHOR]

• Diagnosis of stroke in children is delayed in patients who are sedated or unable to participate in the neurological exam. • EEG is a sensitive modality of neuromonitoring for the recognition of focal voltage attenuation associated with stroke. • The Correlate of Injury to the Nervous System (COIN) index provides a numerical trend and visualization of stroke territory. To describe and assess performance of the Correlate Of Injury to the Nervous system (COIN) index, a quantitative electroencephalography (EEG) metric designed to identify areas of cerebral dysfunction concerning for stroke. Case-control study comparing continuous EEG data from children with acute ischemic stroke to children without stroke, with or without encephalopathy. COIN is calculated continuously and compares EEG power between cerebral hemispheres. Stroke relative infarct volume (RIV) was calculated from quantitative neuroimaging analysis. Significance was determined using a two-sample t-test. Sensitivity, specificity, and accuracy were measured using logistic regression. Average COIN values were −34.7 in the stroke cohort compared to −9.5 in controls without encephalopathy (p = 0.003) and −10.5 in controls with encephalopathy (p = 0.006). The optimal COIN cutoff to discriminate stroke from controls was −15 in non-encephalopathic and −18 in encephalopathic controls with >92% accuracy in strokes with RIV > 5%. A COIN cutoff of −20 allowed discrimination between strokes with <5% and >5% RIV (p = 0.027). We demonstrate that COIN can identify children with acute ischemic stroke. COIN may be a valuable tool for stroke identification in children. Additional studies are needed to determine utility as a monitoring technique for children at risk for stroke. [ABSTRACT FROM AUTHOR]

Abstract: We report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one of the most significant obstacles to offering acute thrombolytic therapies in teenagers and children. Feasibility of treatment is further limited by a lack of dosage and safety data in the paediatric population. Improved community awareness and more rapid recognition of stroke may reduce lag time to diagnosis. [Copyright &y& Elsevier]

Introduction: Health informatics and digital health, two rapidly growing disciplines, are becoming increasingly important to the sustainability of health service provision, highlighted especially through the COVID-19 pandemic. To maximise the benefits of the adoption and growth of health informatics and digital health, health service managers play a critical role in leading and managing the implementation and transformation of the system, both strategically and operationally, whilst still needing to manage 'business as usual'.Objectives: The objectives of the paper are to present and discuss the findings from a scoping review identifying: 1) competencies required for health service managers leading the implementation and transformation of informatics and digital technology in the health sector; and 2) factors that are critical to building the management workforce capacity in the era of health informatics and digital health.Methods: A scoping review of the literature was conducted in 2020 focussing on identifying empirical articles published in the English language since the year 2000 using a number of keywords such as 'health informatics', 'digital health', 'electronic health', 'competencies', 'capability', 'proficiency', 'qualification', 'certification', 'health manager', 'health executive' and 'health administrator'. The literature search was guided by a PRISMA approach searching within eight databases: Scopus, ProQuest, Web of Science, ACM Digital Library, CINAHL, PubMed, Google Scholar and ProQuest Dissertations.Results: After duplicates were removed, 941 publications were included for title screening as the result of an initial review. Title screening selected 185 articles to be included for abstract screening by two reviewers confirming 19 papers relevant to the focus of the current paper which were included in data extraction and content analysis. The analysis identified the additional competency of 'information and data management' be included as a core competency for health service managers. The analysis also confirmed additional elements for the following four core management competencies that are important to health service managers working in the digital health context, including: 1) leadership; 2) operational and resource management; 3) personal, interpersonal and professional qualities, and 4) understanding the industry and environment. Factors that are critical to developing the system and organization capacity in the use of health informatics and digital health technology, and leading and managing the adoption in the healthcare organizations were identified in three categories: 1) policy/system; 2) organizational structure and processes; and 3) people factors.Conclusions: This paper has taken an important step in confirming the competency requirements for health services managers that are relevant to leading and managing in the health informatics and digital health space, consequently indicating the directions for developing a competent workforce in meeting the existing and emerging healthcare delivery challenges, both now and in the future. [ABSTRACT FROM AUTHOR]

Objective: We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease.Methods: We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared.Results: We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P < 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS.Conclusions: Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population. [ABSTRACT FROM AUTHOR]

Background: The association between left hemisphere stroke and acute speech and language impairment is well documented in adults. However, little is known about this association in childhood arterial ischemic stroke. Here we examined potential predictors of acute speech (dysarthria and apraxia) and language impairments after childhood arterial ischemic stroke, including site of lesion.Methods: Children with radiologically confirmed acute arterial ischemic stroke, admitted to a tertiary pediatric hospital from 2004 to 2012, were identified from an institutional registry. We examined the prevalence of dysarthria, apraxia, and language impairment within two weeks of the stroke. Associations with age at stroke event, lesion side (left, right, or bilateral), and arterial territory affected (anterior, posterior, or both) were assessed using logistic regression.Results: Sixty-two children with mean age eight years (range three to 17 years) were identified. Strokes were located in the left (32%), right (44%), or both hemispheres (24%). Dysarthria (74%) and language impairment (50%) were frequent. Verbal dyspraxia was less common (11%). There was little evidence that variables of interest, including site of lesion, were significantly associated with increased odds of dysarthria or language impairment (all P > 0.49).Conclusions: Regardless of age, children are at high risk of communication disorders after stroke. Unlike adults, left hemisphere stroke was not associated with either speech or language impairment in our cohort, suggesting there may be bihemispheric contribution to language function. Future studies are needed to examine whether the predictors examined here determine long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Infantile spasms constitutes a severe infantile epilepsy syndrome that is difficult to treat and has a high morbidity. Hormonal therapies or vigabatrin are the most commonly used treatments. We aimed to assess whether combining the treatments would be more effective than hormonal therapy alone.Methods: In this multicentre, open-label randomised trial, 102 hospitals (Australia [three], Germany [11], New Zealand [two], Switzerland [three], and the UK [83]) enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing electro-clinical outcome were masked to treatment allocation. Minimum doses were prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without vigabatrin 100 mg/kg per day. The primary outcome was cessation of spasms, which was defined as no witnessed spasms on and between day 14 and day 42 from trial entry, as recorded by parents and carers in a seizure diary. Analysis was by intention to treat. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 54363174, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2006-000788-27.Findings: Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (186) or hormonal therapy alone (191). All 377 infants were assessed for the primary outcome. Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone (difference 15·0%, 95% CI 5·1-24·9, p=0·002). Serious adverse reactions necessitating hospitalisation occurred in 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious adverse reaction was infection occurring in five infants on hormonal therapy alone and four on hormonal therapy with vigabatrin. There were no deaths attributable to treatment.Interpretation: Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The 4 week period of spasm cessation required to achieve a primary clinical response to treatment suggests that the effect seen might be sustained, but this needs to be confirmed at the 18 month follow-up.Funding: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, the BRONNER-BENDUNG Stifung/Gernsbach, and University Children's Hospital Zurich. [ABSTRACT FROM AUTHOR]

Background Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke. Results Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research. Conclusions There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke. [ABSTRACT FROM AUTHOR]

Abstract: Few reports address the role of decompressive craniectomy in children with space-occupying cerebral edema attributable to severe ischemic infarction of the posterior cerebral arterial circulation. We describe four children with posterior circulation arterial ischemic stroke who required decompressive craniectomy. These children accounted for 11% of all cases of posterior circulation ischemic stroke at our institution from 2002-2010. Three manifested large, cerebellar hemispheric infarcts, and one manifested a large, temporo-occipital posterior cerebral artery infarct. Deterioration occurred within 72 hours of stroke onset. Two patients demonstrated minimal functional deficits at follow-up, and two demonstrated moderate deficits with functional limitations. Because decompressive craniectomy can be lifesaving in children with severe posterior circulation arterial ischemic stroke, early neurosurgical referral should be considered. [Copyright &y& Elsevier]

Abstract: Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder. Seventeen patients with Alpers syndrome or polymerase-γ gene mutations were identified. Case records of 12 patients with Alpers syndrome and polymerase-γ mutations in both alleles were reviewed. All patients manifested developmental delay or regression, refractory epilepsy, and biochemical liver dysfunction. Liver failure occurred in three patients previously treated with valproate. Other signs included ataxia, visual disturbance, motor paresis, and tremor. Myoclonic and focal motor seizures were common, often manifesting as status epilepticus. Electroencephalograms demonstrated absent/slow posterior dominant rhythms. Interictal discharges were common, usually involving the occipital lobes. Rhythmic high-amplitude delta with (poly)spikes was evident in four patients. Magnetic resonance imaging showed migratory, cortical, and subcortical T2 hyperintensities in four children most often affected the parietal and occipital lobes. Developmental regression and refractory focal motor or myoclonic seizures are consistent clinical features of Alpers syndrome with polymerase-γ mutations. Liver dysfunction constitutes a late manifestation. Migratory T2/fluid attenuated inversion recovery signal abnormalities involving metabolically active occipital and sensorimotor cortical regions comprise characteristic imaging findings. Interictal and ictal electroencephalogram patterns are more variable than previously reported. Three common polymerase-γ mutations, in patients of European descent, can assist with rapid diagnosis, circumventing the need for liver biopsy. [Copyright &y& Elsevier]