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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 −6 mm 2 /s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume Results: Twenty-nine children (median 8 years old, interquartile range, 4.4–14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3–11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5–25.3). 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 ( 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. more...

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children. more...

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction. more...

This study aimed to investigate the prevalence of fractures and non-fracture injuries, including associated risk factors, in children with epilepsy prescribed antiseizure medications (ASM). A controlled, cross-sectional study was conducted in a hospital outpatient setting, comparing children with epilepsy prescribed ASMs with their non-epileptic siblings. Information was collected by questionnaire included history of fractures, non-fracture injuries and epilepsy, comorbidities and ASM use. 261 participants completed the questionnaire, 133 children with epilepsy (aged 10.7 ± 3.5 years, mean ± SD) and 128 siblings (10.1 ± 3.7 years). There were 49 non-seizure-related fractures in 34 ASM patients while prescribed ASMs, compared with 21 lifetime fractures in 15 controls, giving a 2.7 (95% CI 1.3-5.3, p = 0.007) times greater fracture prevalence in children treated with ASMs compared to healthy siblings. The rates of non-fracture injuries were similar across groups, except that concussion was more common in children taking ASMs (9.0% vs 1.6%, p = 0.026). Duration of ASM use and generalized tonic-clonic seizures (GTCS) were independent predictors of fractures (OR 1.55; 95% CI 1.03-2.31, p = 0.03; OR 2.50; 95% CI 1.05-5.94, p = 0.04, respectively). Fewer than 20% of participants and/or their families were aware that ASM use was related to bone health. Children with epilepsy treated with ASMs had a higher fracture prevalence than their sibling controls. Duration of ASM treatment and GTCS were associated with fracture risk. Longitudinal prospective studies are required to further explore risk and the direct impact of epilepsy on bone health. more...

Contains fulltext : 231688.pdf (Publisher’s version ) (Closed access) PURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. CONCLUSION: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants. more...

Background 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. Aims We validated the recently introduced FCA severity score (FCASS) in an independent cohort from the Swiss Neuro-Paediatric Stroke Registry (SNPSR). Materials and methods 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. Results 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. Conclusions 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. more...

ObjectiveTo determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.MethodsWe report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.ResultsOf 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy–inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.ConclusionSpecific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials. more...

Purpose of review Focal cerebral arteriopathy (FCA) is one of the most common causes of arterial ischaemic stroke in a previously healthy child. Distinguishing between different subtypes of arteriopathy is challenging and has significant management implications. Recent findings Recent studies have helped to define the subtypes of focal cerebral arteriopathies and improved understanding of their clinical and radiological features. In addition, they have reported new evidence for the association between viral infection and inflammation in the pathogenesis of FCA and proposed new radiological, serum and cerebrospinal fluid biomarkers to guide diagnosis and management. There is limited evidence to guide treatment of FCA but a role for steroids and antiviral therapies have been reported. Summary Despite the recent advances there is a limited knowledge of the pathophysiology and outcomes following FCA. Research priorities include the identification of biomarkers to improve accuracy of initial diagnosis and predict progression, and interventional trials to determine best treatments to reduce stroke recurrence risk. more...

We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease.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.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.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. more...

We sought to determine incidence, etiologies, and yield of genetic testing in infantile onset developmental and epileptic encephalopathies (DEEs) in a population isolate, with an intensive multistage approach. Infants born in Tasmania between 2011 and 2016, with seizure onset more...

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis.Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (Outcomes: The primary endpoint of Save ChildS Pro is the modified Rankin Scale score at 90 days post-stroke. Secondary endpoints will comprise the decrease of the Pediatric National Institutes of Health Stroke Scale score from admission to discharge and rate of complications.Discussion: Save ChildS Pro aims to provide high-level evidence for MT for pediatric patients with AIS, thereby improving functional outcome and quality of life and reducing the individual, societal, and economic burden of death and disability resulting from pediatric stroke.Clinical Trial Registration: Save ChildS Pro is registered at the German Clinical Trials Registry (DRKS; identifier: DRKS00018960). more...

Background and ObjectivesWe aimed to determine whether a modified pediatric Alberta Stroke Program Early CT Score (modASPECTS) is associated with clinical stroke severity, hemorrhagic transformation, and 12-month functional outcomes in children with acute arterial ischemic stroke (AIS).MethodsChildren (age 29 days–ResultsOne hundred thirty-one children were included; 91 were ≥2 years of age. Median time from stroke to MRI was 1 day (interquartile range [IQR] 0–1 day). Median modASPECTS was 4 (IQR 3–7). ModASPECTS correlated with PedNIHSS score (ρ = 0.40, p = 0.0001). ModASPECTS was associated with hemorrhagic transformation (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02–1.25, p = 0.018). Among children with follow-up (n = 128, median 12.2 months, IQR 9.5–15.4 months), worse outcomes were associated with higher modASPECTS (common OR 1.14, 95% CI 1.04–1.24, p = 0.005). The association between modASPECTS and outcome persisted when we adjusted for age at stroke ictus and the presence of tumor or meningitis as stroke risk factors (common OR 1.14, 95% CI 1.03–1.25, p = 0.008).DiscussionModASPECTS correlates with PedNIHSS scores, hemorrhagic transformation, and 12-month functional outcome in children with acute AIS. Future pediatric studies should evaluate its usefulness in predicting symptomatic intracranial hemorrhage and outcome after acute revascularization therapies.Classification of EvidenceThis study provides Class II evidence that the modASPECTS on MRI is associated with stroke severity (as measured by the baseline PedNIHSS score), hemorrhagic transformation, and 12-month outcome in children with acute supratentorial ischemic stroke. more...

Background: In adults, time since stroke onset correlates with efficacy and risk of recanalization therapies; beyond this temporal window there is increased risk of adverse events in particular hemorrhage with thrombolysis and decreased benefit of recanalization due to irreversible tissue injury. In adults the appearance of fluid attenuated inversion recovery (FLAIR) signal is a proxy for time, and is typically present by 6 hours. The time to FLAIR signal hyperintensity in childhood stroke is unknown but is of interest with potential utility due to the often greater uncertainty as to timing symptom onset. Methods: Time to FLAIR signal hyperintensity on brain MRI performed on children within 24 hours of stroke onset was studied with logistic regression. Results: A total of 68 MRIs with FLAIR imaging were available from 54 children (27 female), age 0.8 to 17.9 years, median 12.0 years. Seventy-four percent (40/54) of children and 72% (49/68) of scans had anterior circulation stroke. Interquartile range for time to FLAIR presence was 7.8 to 19.1 hours. The 90% probability of FLAIR change was reached at 11.2 hours for all strokes (Figure, dotted line; 80% highest density interval (HDI): 1.2-11.2 hours), and 9.3 hours for anterior circulation only strokes (Figure, solid line; 80% HDI: 3.3-9.3 hours), though nearly all had FLAIR change by 6 hours. FLAIR change was absent in 4 children after 6 hours, two with anterior circulation stroke (16 year-old at 6.1 hours, 10 year-old at 7.0 hours) and 2 with posterior circulation stroke (15 year-old at 7.3 hours, 9 month-old at 18.2 hours). Conclusion: Similar to adults, FLAIR hyperintensity can be used to estimate time since stroke ictus in childhood stroke. Children may have somewhat delayed time to FLAIR signal change compared with adults, suggesting that they may have a longer window for effective recanalization therapies. more...

Background: Neurocognitive outcomes beyond childhood in people with a Fontan circulation are not well defined. This study aimed to investigate neurocognitive functioning in adolescents and adults with a Fontan circulation and associations with structural brain injury, brain volumetry, and postnatal clinical factors. Methods: In a binational study, participants with a Fontan circulation without a preexisting major neurological disability were prospectively recruited from the Australia and New Zealand Fontan Registry. Neurocognitive function was assessed by using Cogstate software in 107 participants with a Fontan circulation and compared with control groups with transposition of the great arteries (n=50) and a normal circulation (n=41). Brain MRI with volumetric analysis was performed in the participants with a Fontan circulation and compared with healthy control data from the ABIDE I and II (Autism Brain Imaging Data Exchange) and PING (Pediatric Imaging, Neurocognition, and Genetics) data repositories. Clinical data were retrospectively collected. Results: Of the participants with a Fontan circulation who had a neurocognitive assessment, 55% were male and the mean age was 22.6 years (SD 7.8). Participants with a Fontan circulation performed worse in several areas of neurocognitive function compared with those with transposition of the great arteries and healthy controls ( P P P =0.01 and working memory, P =0.02). Structural brain injury was present in the entire Fontan cohort; the presence of white matter injury was associated with worse paired associate learning ( P P P P P ≤0.04). Conclusions: Neurocognitive impairment is common in adolescents and adults with a Fontan circulation and is associated with smaller gray and white matter brain volume. Understanding modifiable factors that contribute to brain injury to optimize neurocognitive function is paramount. more...

OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication. more...

Childhood stroke results in long-term, multifaceted difficulties, affecting motor, cognitive, communication, and behavioral domains of function which impact on participation and quality of life. The Childhood Stroke Consensus Rehabilitation Guideline was developed to improve the care of children with stroke by providing health professionals with recommendations to assist in their rehabilitative treatment. Clinical questions were formulated to inform systematic database searches from 2001 to 2016, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grade of Recommendation, Assessment, Development and Evaluation system was used to grade evidence as strong or weak. Where evidence was inadequate or absent, a modified Delphi consensus process was used to develop consensus-based recommendations. The guideline provides 56 recommendations (1 evidence-based recommendation and 55 consensus recommendations). These relate to the framework of rehabilitation service delivery as well as domain-specific rehabilitation treatment strategies for each domain of function. It is anticipated that this guideline will provide health professions with recommendations to improve the subacute care of children with stroke both in Australia and internationally. more...

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. more...

Background and Purpose— Focal cerebral arteriopathy (FCA)—a common cause of arterial ischemic stroke in previously healthy children—often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods— The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010–2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results— The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2–6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5–9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5–35.5) days poststroke; their median FCASS increase was 4 (2.5–6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P =0.037). Conclusions— Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development. more...

Stroke is among the top 10 causes of death in children and survivors carry resulting disabilities for decades, at substantial cost to themselves and their families. Children are not currently able to access reperfusion therapies, due to limited evidence supporting safety and efficacy and long diagnostic delays. The Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of Childhood Stroke was developed to minimize unwarranted variations in care and document best evidence on the risk factors, etiologies, and conditions mimicking stroke that differ from adults. Clinical questions were formulated to inform systematic database searches from 2007 to 2017, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grades of Recommendation, Assessment, Development, and Evaluation system (GRADE) was used to grade evidence as strong or weak. The Guideline provides more than 60 evidence-based recommendations to assist prehospital and acute care clinicians in the rapid identification of childhood stroke, choice of initial investigation, to confirm diagnosis, determine etiology, selection of the most appropriate interventions to salvage brain at risk, and prevent recurrence. Recommendations include advice regarding the management of intracranial pressure and congenital heart disease. Implementation of the Guideline will require reorganization of prehospital and emergency care systems, including the development of regional stroke networks, pediatric Code Stroke, rapid magnetic resonance imaging and accreditation of primary pediatric stroke centers with the capacity to offer reperfusion therapies. The Guideline will allow auditing to benchmark timelines of care, access to acute interventions, and outcomes. It will also facilitate the development of an Australian childhood stroke registry, with data linkage to international registries, to allow for accurate data collection on stroke incidence, treatment, and outcomes. more...

Aim To determine the role of inflammation in pediatric transient focal cerebral arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. Methods We measured 32 cytokine/chemokines in acute cerebrospinal fluid collected from children with stroke due to focal cerebral arteriopathy (n = 5) using multiplex immunoassay and compared with two patients with arterial ischemic stroke due to other causes (non-focal cerebral arteriopathy group, vertebral dissection, n = 1; cryptogenic, n = 1), pediatric encephalitis (n = 43), and non-inflammatory neurological disease controls (n = 20). Results Median age in the focal cerebral arteriopathy group was 9.3 years (range, 2.8–13 years). In the focal cerebral arteriopathy group (n = 5), four patients had middle cerebral ± distal carotid arteriopathy; one patient had posterior circulation arteriopathy. The median time from symptom onset to cerebrospinal fluid sampling was four days (range, 0.6–7 days). Only IL-6, IL-8, CXCL1, and CXCL10 levels were significantly higher in the acute cerebrospinal fluid of focal cerebral arteriopathy patients compared to non-inflammatory neurological disease controls and non-focal cerebral arteriopathy stroke. In contrast to focal cerebral arteriopathy, a broad array of Th1, Th2, Treg, Th17, B-cell related, and other broad spectrum cytokine/chemokines were elevated in encephalitis. Conclusion The elevated cerebrospinal fluid cytokine/chemokines support innate, T cell, and granulocyte inflammatory mechanisms in children with focal cerebral arteriopathy. This warrants larger cohort studies to discriminate primary inflammatory signals of the arteriopathy from secondary inflammation due to the stroke itself. more...

This review will discuss important developments in childhood arterial ischemic stroke over the past decade, focusing on improved understanding of the causes, consequences, and targets for intervention. Risk factors for childhood arterial ischemic stroke are different to adults. Infections, particularly herpes group viruses, are important precipitants for stroke. Non-atherosclerotic arteriopathies are the most common cause of childhood arterial ischemic stroke and an important predictor of recurrent events. Recent advances include the identification of serum biomarkers for inflammation and endothelial injury, and imaging biomarkers to monitor for vascular progression. Multicenter trials of immunotherapies in focal cerebral arteriopathies are currently in development. Recognition of clinical and radiological phenotypic patterns has facilitated the discovery of multisystem disorders associated with arterial ischemic stroke including ACTA2 arteriopathy and adenosine deaminase 2 deficiency. Identification of these Mendelian disorders provide insights into genetic mechanisms of disease and have implications for medical and surgical management. In contrast to adults, there are long diagnostic delays in childhood arterial ischemic stroke. Refinement of pediatric Code Stroke protocols and clinical decision support tools are essential to improve diagnostic certainty and improve access to reperfusion therapies. Children do not recover better than adults following arterial ischemic stroke, with more than half of survivors having long-term impairments. The physical, cognitive, and behavioral consequences of childhood arterial ischemic stroke are increasingly reported but further research is required to understand their impact on participation, quality of life, psychosocial, and family functioning. Longitudinal studies and the use of advanced imaging techniques, to understand neurobiological correlates of functional reorganization, are essential to developing targeted intervention strategies to facilitate recovery. more...

The aim was to describe clinical presentation, management, and outcomes of stroke in a tertiary emergency department (ED) of a developing country. Retrospective case series of patients aged 1 month to 18 years presenting to an ED with radiological confirmed acute stroke during a 7-year period were studied. Ninety-five patients were identified. Twenty-five patients were excluded because of incomplete records (8) or not presenting via ED (17). Thirty-four (48.5%) were diagnosed with hemorrhagic stroke (HS), 30 (42.8%) with arterial ischemic stroke (AIS), and 6 (8.5%) with sinus venous thrombosis (SVT). Mean age was 5.3 years, and 55.3% were male. The median time from onset of symptoms to ED presentation was 24 hours (mean, 55 hours; interquartile range [IQR], 14–72) for AIS, 24 hours (mean, 46.9 hours; IQR, 9–48) for HS, and 120 hours (mean,112 hours; IQR, 72–168) for SVT. Congenital cardiac disease was the most common risk factor (9%). For AIS, the most common symptoms were focal numbness 56.6% (95% confidence interval [CI], 37.8%–75.4%), focal weakness 56.6% (95% CI, 37.8%–75.4%), and seizures 50% (95% CI, 31%–68.8%). For HS, the most common symptoms were headache 64.7% (95% CI, 47.7%–81.6%), vomiting 79.4 (95% CI, 65–93.7), and altered mental status 64.7% (95% CI, 47.7–81.6). Computed tomography scan was done in 100% of the patients and magnetic resonance imaging in 54%. Twenty-five (36%) patients were admitted to intensive care unit and required intubation. Long-term deficit was identified in 24 (36%) patients based on medium-term follow-up. The spectrum of stroke in a developing country was similar to published series from developed countries in terms of final diagnosis, risk factors, and delay to ED presentation, neuroimaging, and long-term neurodeficits. No tropical diseases were identified as risk factors. more...

Background There is a lack of consensus regarding how best to screen children with facial port-wine stains for Sturge-Weber syndrome. Many favor brain magnetic resonance imaging, and adjunctive electroencephalography is increasingly used. However, the sensitivity, specificity, and negative and positive predictive value of magnetic resonance imaging and electroencephalography and whether screening improves seizure recognition is unclear. Methods A retrospective review of children with high-risk port-wine stains presenting consecutively to the outpatient laser clinic of a tertiary pediatric hospital between December 2015 and November 2016 was undertaken. Primary outcome measures were yield, accuracy, age of and protocols for screening magnetic resonance imaging and electroencephalography, type of and age at presenting seizure, and percentage referred to neurology. Results Of 126 patients with facial port-wine stains, 25.4% (32/126) were at high risk of Sturge-Weber syndrome (hemifacial, median, and forehead PWS phenotypes); 43.7% of these (14/32) underwent screening magnetic resonance imaging. Sturge-Weber syndrome was detected in 7.1% (1/14). Magnetic resonance imaging had false-negative results in 23.1% (3/13) of those screened. Screening magnetic resonance imaging had sensitivity of 25%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9% for the detection of Sturge-Weber syndrome (hemifacial, median and forehead PWS phenotypes). Only one-third of those with false-negative magnetic resonance imaging were referred to neurology. Mean age of first seizure in those with false-negative screening magnetic resonance imaging was 28 months, vs 14 months in those not screened. Abnormal electroencephalographic signs were detected in the two infants who underwent presymptomatic electroencephalography. Conclusions Findings from this small cohort of individuals with port-wine stains that put them at high risk of Sturge-Weber syndrome suggest that children with positive screening magnetic resonance imaging will almost certainly develop Sturge-Weber syndrome but that negative screening magnetic resonance imaging cannot exclude Sturge-Weber syndrome (in up to 23.1% of cases). False-negative magnetic resonance imaging may delay seizure recognition. Seizure education, monitoring, and consideration of adjunctive electroencephalography are important irrespective of magnetic resonance imaging findings. more...

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. more...

In this paper, the authors will describe the journey of registered nurses across a series of workshops as part of a research project that was undertaken in a regional aged care service in New South Wales, Australia. The aim of the project was to empower the participant registered nurses to positively influence the health care workplace culture within the residential care home by raising consciousness about their own practice. Registered nurses were actively involved in this reconnaissance phase of a participatory action research project through practice development principles and methods. Registered nurses determined the content and the outcomes of the overall program. The researchers evaluated the impact of a series of workshops, designed to develop skills and knowledge using nominal group technique. Results revealed registered nurses perceived they were empowered to flourish, and developed an understanding of the uniqueness of their role. A shared understanding of the role of the registered nurse in the aged care setting was fundamental in enabling them to feel empowered to lead their team and contribute positively to the workplace culture. Overall, the outcomes of this project have positively impacted workplace culture. more...

Background International clinical placements are being increasingly offered to expose students to different health settings internationally. Both nationally and internationally there is a need to build the primary health care nursing workforce to meet changing community needs. Exposure to specialty areas during clinical placement can impact career choices. Aim This paper explores the experiences of Australian undergraduate nursing students undertaking a primary health care clinical placement in Cambodia. Method This exploratory qualitative study used semi-structured interviews to gather experiential narratives. Eight Australian undergraduate nursing students from a single University in New South Wales, Australia participated in the study. Verbatim transcripts were analysed using thematic analysis. Results Interview data revealed four themes, namely; Preparation for placement, Challenges, "The experience is so, so worth it" and PHC "it's a lot more than words on a page now". Despite pre-placement preparation, students were challenged during the placement in ways that they never expected. These challenges saw them grow both professionally and personally from the experience. Additionally, exposing students to primary health care in practice helped to demonstrate the value and importance of this area of nursing. Conclusions International clinical placement experiences present undergraduate nursing students with unique challenges and facilitate both professional and personal growth. Enhanced appreciation of primary health care among participants has potentially positive implications as they enter the nursing workforce. However, future studies need to investigate the longer term impact of international placement experiences within the broader undergraduate preparation of nurses and into their future careers. more...

AIM: To estimate the strengths of association between clinical features and migraine or arterial ischaemic stroke (AIS) in children presenting to the emergency department. METHOD: Eighty-four children with migraine, prospectively recruited from 2009 to 2010, were compared with 55 children with AIS, prospectively/retrospectively recruited from 2003 to 2010. Odds ratios were calculated via logistic regression to measure associations between clinical features and process-of-care factors, and migraine and AIS. RESULTS: Median age was 13 years 5 months (interquartile range 12y 11mo-13y 10mo) for migraine and 5 years (interquartile range 3y 7mo-8y) for patients with AIS. All cases of AIS and 30% of migraine cases underwent neuroimaging. Over 40% of children with migraine had vomiting, numbness, or visual disturbance; other symptoms were uncommon. Fifty-five per cent had no signs on physician assessment. Weakness or speech disturbance were common in patients with AIS. Significant clinical features associated with increased odds of AIS included sudden symptom onset, weakness, seizures, speech disturbance, and ataxia, and signs of face, arm, or leg weakness, inability to walk, dysarthria, dysphasia, and altered consciousness (p more...

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. more...

At least half of childhood stroke survivors suffer long-term impairments. Rapid identification of stroke is essential to minimize the extent of injury by restoring perfusion to viable brain. Improving diagnosis of childhood stroke requires correct identification of stroke by prehospital and emergency physicians, rapid performance of appropriate neuroimaging to confirm infarction, and targeted investigations to determine underlying causes, which guide treatment decisions to reduce recurrence risk. Areas covered: This review will summarize the barriers to rapid stroke diagnosis in pre-hospital and emergency department settings, describe recent progress in understanding of the spectrum, presenting clinical features and differential diagnosis of childhood stroke, discuss clinical stroke recognition tools which improve diagnostic accuracy, and their application to children. Recent advances in the diagnostic evaluation of stroke will be presented, and the review will conclude by outlining priorities for future research. Expert commentary: Development of coordinated systems of acute care are essential to facilitate rapid diagnosis of childhood stroke. Recent advances in acute pediatric stroke care include consensus recommendations for primary pediatric stroke centers and implementation of standardized Pediatric Code Stoke protocols, which result in shorter time to diagnosis, selection of MRI as the initial imaging modality, and increased access to reperfusion therapies. more...

Background and Purpose— Focal cerebral arteriopathy accounts for up to 35% of arterial ischemic stroke (AIS) in children and is the most important predictor of stroke recurrence. The study objective was to compare outcomes for children with focal cerebral arteriopathy treated with combined corticosteroid antithrombotic treatment (CAT) to those receiving antithrombotic treatment (AT) alone. Methods— This multicenter retrospective Swiss/Australian cohort study analyzed consecutive children, aged 1 month to 18 years, presenting with first AIS because of a focal cerebral arteriopathy from 2000 to 2014. Children with CAT were compared with those treated with AT. Primary outcome was the presence of neurological deficits at 6 months post–AIS as measured by the Pediatric Stroke Outcome Measure. Secondary outcomes included resolution of stenosis and stroke recurrence. Analysis of covariance was used to adjust for potential confounders (baseline pediatric National Institute of Health Stroke Scale and concomitant acyclovir use). Results— A total of 73 children (51% males) were identified, 21 (29%) of whom received CAT. Mean (SD) age at stroke for the entire group was 7.9 years (4.7). Median (interquartile range) pediatric National Institute of Health Stroke Scale was 3 (2.0–8.0) in the CAT group and 5 (3.0–9.0) in the AT group ( P =0.098). Median (interquartile range) Pediatric Stroke Outcome Measure 6 months post-AIS was 0.5 (0–1.5) in the CAT group compared with 1.0 (0.5–2.0) in the AT group ( P =0.035), the finding was sustained after adjusting for potential confounders. Complete resolution of stenosis at last MRI was noted in 17 (81%) in the CAT group compared with 24 (59%) in the AT group ( P =0.197). Stroke recurrence occurred in 1 patient in each group. Conclusions— Corticosteroid treatment may provide additional benefit over AT for improved neurological outcome in childhood AIS because of focal cerebral arteriopathy. Larger prospective studies are warranted to further investigate these differences and understand mechanisms by which steroids modify outcome. more...

Objective Patients with third window syndrome and superior semicircular canal dehiscence (SSCD) symptoms whose surgical outcomes placed them as outliers were systematically studied to determine comorbidities that were responsible for their poor outcomes due to these confounding factors. Study Design Observational analytic case-control study in a tertiary referral center. Methods Twelve adult patients with clinical SSCD syndrome underwent surgical management and had outcomes that did not resolve all of their subjective symptoms. In addition to one of the neurotologists, 2 neurologists (one specializing in migraine and the other a neuro-ophthalmologist), and a psychologist clinician-investigator completed comprehensive evaluations. Neuropsychology test batteries included: the Millon Behavioral Medicine Diagnostic; Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7); Adverse Childhood Experiences Scale; the Wide Range Assessment of Memory and Learning, including the 3 domains of verbal memory, visual memory, and attention/concentration; Wechsler Adult Intelligence Scale; and the Delis-Kaplan Executive Function System. The control cohort was comprised of 17 participants who previously underwent surgery for third window syndrome that resulted in the expected outcomes of resolution of their third window syndrome symptoms and cognitive dysfunction. Results There was a high rate of psychological comorbidity (n = 6) in the outlier cohort; multiple traumatic brain injuries were also a confounding element (n = 10). One patient had elevated cerebrospinal fluid (CSF) pressure requiring ventriculoperitoneal shunting to control the recurrence of dehiscence and one patient with a drug-induced Parkinson-like syndrome and idiopathic progressive neurological degenerative process. Conclusions Components of the Millon Behavioral Medicine Diagnostic, PHQ-9 and GAD-7 results suggest that these instruments would be useful as screening tools preoperatively to identify psychological comorbidities that could confound outcomes. The identification of these comorbid psychological as well as other neurological degenerative disease processes led to alternate clinical management pathways for these patients. Level of Evidence 2b. more...

Background: The Objective Structured Clinical Examination (OSCE) is used increasingly in nursing education. The purpose of this article is to report on the qualitative evaluation of the first implementation of a medication administration OSCE within an Australian school of nursing. Method: A two-stage data gathering strategy was undertaken. The first stage was to survey participants' pre-OSCE and the second stage involved surveying the same participants' immediately post-OSCE. A constant comparison analysis method was used. Results: The first stage data analysis (pre-OSCE) were classified into three themes: (a) Student Anxiety, (b) Student Preparedness, and (c) The Effectiveness of This Style of Assessment. The three key themes from the second stage (post-OSCE) analysis were: (a) Feelings Toward the OSCE, (b) Assessor Interaction, and (c) The OSCE Environment. Conclusion: Although they found it stressful, the participants valued the OSCE experience. The OSCE gave the students confidence in their capabilities of medication management. [ J Nurs Educ. 2017;56(4):231–234.] more...

Purpose of review The past 20 years have seen a 35% increase in prevalence of pediatric stroke. Contrary to widely held views, children do not recover better than adults. This review explores the impact of pediatric stroke on cognitive domains, including intellectual and executive functions, memory and behavior, and the influence of age, lesion characteristics, and comorbidities on outcome. Recent findings Cognitive problems occur in up to half of ischemic and hemorrhagic stroke survivors. Single-center studies have shown intelligence quotient scores skewed to the lower end of the average range, with greater impairment in performance than verbal domains. Executive function, such as attention and processing speed are particularly vulnerable to the effects of pediatric stroke. Age at stroke, larger infarct size, cortical/subcortical lesion location, epilepsy, and comorbid physical deficits are associated with poorer cognitive outcomes. Summary Cognitive impairment occurs relatively frequently following pediatric stroke but the nature, severity, and predictors of specific deficits are not well defined. Improving understanding of outcomes following pediatric stroke is a key priority for families but a paucity of data limits the ability to develop targeted disease, and age-specific pediatric rehabilitation strategies to optimize cognitive outcomes following pediatric stroke. more...

Objectives: To investigate correlations between infarct topography on acute diffusion weighted MRI, using voxel-based lesion-symptom mapping (VLSM), and later development of cerebral palsy (CP) and neurological impairments, in neonatal arterial ischaemic stroke (AIS). Methods: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language or cognitive-behavioural impairments were assessed using the Pediatric Stroke Outcome Measure dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using axial DWI images, and coregistered to the Melbourne Children’s Regional Infant Brain 2.0 atlas. All lesions were projected to the left hemisphere to obtain binary union masks. VLSM was conducted using MATLAB SPM12 toolbox. A generalised linear model was used to correlate the lesion mask with outcomes. Voxel-wise t test statistics were calculated, and corrected for multiple comparisons using family-wise error rate (FWE). Results: 85 newborns (55 male) met inclusion criteria. Infarct lateralization was left hemisphere in 62%, right in 8% and bilateral in 29%. At median age 2.1 years (IQR1.9-2.6), 34% developed CP and 42% had neurological impairments. 54 ROIs were correlated with CP (t>4.33; FWE Conclusions: Cerebral palsy following neonatal AIS correlates predominantly with regions of acute infarction directly involved in motor control, or in functionally connected regions. Brain regions associated with language or cognitive-behavioural impairment are less clear. more...

ObjectiveTo compare risk factors, clinical presentation, and outcomes after posterior circulation arterial ischemic stroke (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children.MethodsIn this international multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), we compared clinical and radiologic features according to stroke location.ResultsOf 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% vs 22%, p < 0.001). Children with PCAIS were older than children with ACAIS (median age 7.8 [interquartile range (IQR) 3.1–14] vs 5.1 [IQR 1.5–12] years, p < 0.001), and more often presented with headache (54% vs 32%, p < 0.001) and a lower Pediatric NIH Stroke Scale score (4 [IQR 2–8] vs 8 [IQR 3–13], p = 0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% vs 8.5%, p < 0.001), while cardioembolic strokes were less frequent (19% vs 32%, p < 0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurologic examination at hospital discharge in 29% vs 21%, p = 0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates.ConclusionPCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older and have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS. more...

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is more...

Author(s): Fullerton, Heather J; Ganesan, Vijeya; Jordan, Lori C; Kirton, Adam; Mackay, Mark T; Steinlin, Maja

ObjectiveTo determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment.MethodsIdentification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD‐10).ResultsA total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi‐square 4.3, P = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P = .037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi‐square 0.35, P = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead‐time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy.SignificanceThis classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment. more...

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. more...

Background and objectives Neonatal arterial ischemic stroke (NAIS) can lead to long-term neurological consequences such as cerebral palsy (CP). The aim of this study was to evaluate the predictive value of acute diffusion-weighted imaging (DWI) for CP by analyzing stroke volume next to brain structure involvement. Methods We included 37 term-born infants with NAIS prospectively registered in a nationwide pediatric stroke registry. DWI was performed between 0 and 8 days (mean 3 days) after stroke manifestation. Participants were neurologically assessed at the age of 2 years. We calculated the stroke volume (in mm3) and the ratio of the stroke volume to the volume of the entire brain (relative stroke volume). The predictive value of the relative stroke volume was analyzed and an optimal threshold for classification of children with high- and low-rates of CP was calculated. Predictive value of brain structure involvements and the prevalence of CP in combinations of different brain structures was also assessed. Results Sixteen children (43.2%) developed CP. Relative stroke volume significantly predicted CP (p Conclusion In addition to determining the involvement of affected brain areas, the volumetric quantification of stroke volume allows accurate prediction of cerebral palsy in newborns with NAIS. more...

ObjectiveTo test the hypothesis that the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is useful in determining outcomes after neonatal arterial ischemic stroke (NAIS), we assessed accuracy of the modified pediatric ASPECTS (pedASPECTS) to predict cerebral palsy (CP), neurologic impairment, and epilepsy.MethodsCross-sectional study included newborns with acute NAIS whose outcomes were assessed at ≥18 months after stroke. PedASPECTS accuracy to predict outcomes was determined by sensitivity, specificity, and receiver operator characteristic (ROC) curves, and correlation between pedASPECTS and infarct volume was determined by the Spearman correlation coefficient.ResultsNinety-six children met the inclusion criteria. Median percentage infarct to supratentorial brain volume was 6.8% (interquartile range [IQR] 3.0%–14.3%). Median pedASPECTS was 7 (IQR 4–10). At a median age of 2.1 years, 35% developed CP, 43% had neurologic impairment, and 7% had epilepsy. Median pedASPECTS predicted outcomes of interest: CP (10, IQR 8–12) vs no CP (5, IQR 4–8) (p < 0.0001), poor (9, IQR 7–12) vs good (6, IQR 4–8) neurologic outcomes (p < 0.0001), and epilepsy (10, IQR 8–12) vs no epilepsy (7, IQR 4–10) (p = 0.033). PedASPECTS accuracy was good for CP (ROC 0.811) and fair for neurologic impairment (ROC 0.760) and epilepsy (ROC 0.761). A pedASPECTS ≥8 had ≥69% sensitivity and ≥54% specificity for clinical outcomes. PedASPECTS correlated with infarct volume (Spearman rank 0.701, p < 0.0001).ConclusionsThis study provides Class II evidence that pedASPECTS has fair to good accuracy for predicting CP, neurologic impairment, and epilepsy after NAIS and correlates with infarct volume. PedASPECTS may assist with early identification of babies requiring close developmental surveillance. more...

AIM There is a paucity of data from randomized controlled treatment trials in childhood arterial ischaemic stroke. Our objectives were to identify and plan a trial through use of a Delphi consensus process. METHOD The Delphi panel consisted of Australian, New Zealand, and European paediatric neurologists with interests in childhood stroke. Four rounds were conducted using a REDCap (Research Electronic Data Capture) Web-based application: the first consisted of open-ended questions; the second evaluated agreement for the most important trial; the third and fourth reached consensus on design. RESULTS Forty-seven out of 66 neurologists answered the first round. Eight areas of research for important and feasible trials were identified. In the second round, 43 paediatric neurologists ranked the three highest rated trials: (1) aspirin versus aspirin plus steroids in focal arteriopathy (n=31); (2) heparin versus aspirin (n=6); and (3) heparin versus aspirin versus modern anticoagulation (n=6). The third and fourth surveys reached consensus among 43 out of 44 respondents on design of the highest ranked trial, and allowed agreement on inclusion/exclusion criteria, clinical/neuroimaging data, and treatment protocols. CONCLUSION The Delphi consensus process is an efficient method of identifying and planning paediatric stroke trials. An international, multicentre trial is now in preparation. more...

Supplemental Digital Content is available in the text., Background and Purpose— Clinical identification of stroke in the pediatric emergency department is critical for improving access to hyperacute therapies. We identified key clinical features associated with childhood stroke or transient ischemic attack compared with mimics. Methods— Two hundred and eighty consecutive children presenting to the emergency department with mimics, prospectively recruited over 18 months from 2009 to 2010, were compared with 102 children with stroke or transient ischemic attack, prospectively/retrospectively recruited from 2003 to 2010. Results— Cerebrovascular diagnoses included arterial ischemic stroke (55), hemorrhagic stroke (37), and transient ischemic attack (10). Mimic diagnoses included migraine (84), seizures (46), Bell’s palsy (29), and conversion disorders (18). Being well in the week before presentation (odds ratio [OR] 5.76, 95% confidence interval [CI] 2.25–14.79), face weakness (OR 2.94, 95% CI 1.19–7.28), arm weakness (OR 8.66, 95% CI, 2.50–30.02), and inability to walk (OR 3.38, 95% CI 1.54–7.42) were independently associated with increased odds of stroke diagnosis. Other symptoms were independently associated with decreased odds of stroke diagnosis (OR 0.28, 95% CI 0.10–0.77). Associations were not observed between seizures or loss of consciousness. Factors associated with stroke differed by arterial and hemorrhagic subtypes. Conclusions— Being well in the week before presentation, inability to walk, face and arm weakness are associated with increased odds of stroke. The lack of positive or negative association between stroke and seizures or loss of consciousness is an important difference to adults. Pediatric stroke pathways and bedside tools need to factor in differences between children and adults and between stroke subtypes. more...

Contrary to commonly held views, children do not recover better than adults after a stroke.1 The lifelong individual, family, and societal burden of stroke is likely to be greater than in adults because infants and children surviving stroke face many more years living with disability. The key difference between children and adults is that childhood stroke (occurring during the perinatal period and beyond) results primarily in a changed ability to achieve, rather than lose, functional independence. The extent and severity of deficits across motor, sensory, cognitive, social, and behavioral domains may not be apparent in the short-term after stroke, particularly in newborns and preschool children, who typically grow into their deficits.2,3 The World Health Organization’s International Classification of Functioning (ICF), Disability, and Health can be applied to childhood stroke to describe its impact across health domains, including impairment in body structures and functions, activity limitations and participation restrictions at individual, institutional and social levels. This review will focus on childhood stroke, defined as stroke from 1 month to 18 years of age, and where possible use the ICF framework to describe outcome after arterial ischemic stroke (AIS) and hemorrhagic stroke (HS). ### Mortality After Childhood Stroke Stroke is among the top 10 causes of death in the pediatric population. The reported mortality for AIS ranges from 7% to 28%1,4 and from 6% to 54% for HS.5 In the US study reporting stroke mortality during a 10-year period from 1979 to 1998, 4881 deaths could be attributed to childhood stroke, giving average annual mortality rates of 0.09 per 100 000 person-years for AIS 0.14 for intracerebral hemorrhage and 0.11 for subarachnoid hemorrhage.6 Risk of death was higher in infants, males, blacks, and children living in the South-Eastern Stroke belt States.6,7 Declining mortality rates have … more...

Hereditary haemorrhagic telangiectasia, also known as Osler–Weber–Rendu disease, is a rare autosomal dominant multisystem disorder, characterised by mucocutaneous telangiectases and arteriovenous malformations affecting any organ. The physiological changes in pregnancy pose significant obstetric and anaesthetic challenges for women affected by the disease. The optimal timing and mode of delivery requires careful consideration; and the benefits and risks of both regional and general anaesthetic techniques must be carefully considered, depending on the organs affected. This case report describes the successful management of a patient with this disease and severe pulmonary involvement, who received both regional and general anaesthesia as a result of a complication in the initial anaesthetic plan. The report demonstrates the benefits of a multidisciplinary approach to a complex case, achieved through providing care in a tertiary centre with appropriate expertise and resources. more...

This chapter examines the problems of the most commonly used pest management technique, the use of synthetic pesticides. It explores some alternative approaches, and examines the difficulties of applying these alternatives in the Philippines. Pesticides required in small quantities are often repackaged in pop bottles and paper bags with no labels, stored near food and often reused as food containers. In order for the development of an improved pest management system there is a need for appropriate national policies. At the farm level, farmers continue to use a number of pesticides which are dangerous to their health. In order to implement the policies there will be a need for strong support from all segments of the agriculture sector, from the government, nongovernment, private sectors and most importantly from the men and women of the farming communities who bear the pain and suffering of the current over reliance on synthetic pesticides. more...