Facial Function in Bell Palsy in a Cohort of Children Randomized to Prednisolone or Placebo 12 Months After Diagnosis.

BACKGROUND: Information on the medium-term recovery of children with Bell palsy or acute idiopathic lower motor neuron facial paralysis is limited. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Pain in children with Bell's palsy: secondary analysis of a randomised controlled trial.

OBJECTIVE: To describe the prevalence and severity of pain experienced by children with Bell's palsy over the first 6 months of illness and its association with the severity of facial paralysis. METHODS: This was a secondary analysis of data obtained in a phase III, triple-blinded, randomised, placebo-controlled trial of prednisolone for the treatment of Bell's palsy in children aged 6 months to <18 years conducted between 13 October 2015 and 23 August 2020 in Australia and New Zealand. Children were recruited within 72 hours of symptom onset and pain was assessed using a child-rated visual analogue scale (VAS), a child-rated Faces Pain Score-Revised (FPS-R) and/or a parent-rated VAS at baseline, and at 1, 3 and 6 months until recovered, and are reported combined across treatment groups. RESULTS: Data were available for 169 of the 187 children randomised from at least one study time point. Overall, 37% (62/169) of children reported any pain at least at one time point. The frequency of any pain reported using the child-rated VAS, child-rated FPS-R and parent-rated VAS was higher at the baseline assessment (30%, 23% and 27%, respectively) compared with 1-month (4%, 0% and 4%, respectively) and subsequent follow-up assessments. At all time points, the median pain score on all three scales was 0 (no pain). CONCLUSIONS: Pain in children with Bell's palsy was infrequent and primarily occurred early in the disease course and in more severe disease. The intensity of pain, if it occurs, is very low throughout the clinical course of disease. TRIAL REGISTRATION NUMBER: ACTRN12615000563561.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study.

Objectives: The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design: Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results: Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section (p = 0.04), 5-min Apgar score <7 (p < 0.01), neonatal resuscitation (p < 0.01) and nulliparity (p < 0.01). Conclusions: Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.

Developing Health Management Competency for Digital Health Transformation: Protocol for a Qualitative Study.

BACKGROUND: Globally, the health care system is experiencing a period of rapid and radical change. In response, innovative service models have been adopted for the delivery of high-quality care that require a health workforce with skills to support transformation and new ways of working. OBJECTIVE: The aim of this research protocol is to describe research that will contribute to developing the capability of health service managers in the digital health era and enabling digital transformation within the Australian health care environment. It also explains the process of preparing and finalizing the research design and methodologies by seeking answers to the following three research questions: (1) To what extent can the existing health service management and digital health competency frameworks guide the development of competence for health service managers in understanding and managing in the digital health space? (2) What are the competencies that are necessary for health service managers to acquire in order to effectively work with and manage in the digital health context? (3) What are the key factors that enable and inhibit health service managers to develop and demonstrate digital health competence in the workplace? METHODS: The study has adopted a qualitative approach, guided by the empirically validated management competency identification process, using four steps: (1) health management and digital health competency mapping, (2) scoping review of literature and policy analysis, (3) focus group discussions with health service managers, and (4) semistructured interviews with digital health leaders. The first 2 steps were to confirm the need for updating the current health service management curriculum to address changing competency requirements of health service managers in the digital health context. RESULTS: Two initial steps have been completed confirming the significance of the study and study design. Step 1, competency mapping, found that nearly half of the digital competencies were only partially or not addressed at all by the health management competency framework. The scoping review articulated the competencies health service managers need to effectively demonstrate digital health competence in the workplace. The findings effectively support the importance of the current research and also the appropriateness of the proposed steps 3 and 4 in answering the research questions and achieving the research aim. CONCLUSIONS: This study will provide insights into the health service management workforce performance and development needs for digital health and inform credentialing and professional development requirements. This will guide health service managers in leading and managing the adoption and implementation of digital health as a contemporary tool for health care delivery. The study will develop an in-depth understanding of Australian health service managers' experiences and views. This research process could be applied in other contexts, noting that the results need contextualization to individual country jurisdictions and environments. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51884.

A quantitative EEG index for the recognition of arterial ischemic stroke in children.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: We demonstrate that COIN can identify children with acute ischemic stroke. SIGNIFICANCE: 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.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

BACKGROUND AND OBJECTIVES: Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. METHODS: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral 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 diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. RESULTS: Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. DISCUSSION: CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Paroxysmal Nonepileptic Events in Children With Epilepsy and Cerebral Palsy.

Objective: To determine the frequency of paroxysmal nonepileptic events in children with cerebral palsy due to brain injury who have epilepsy and to describe the factors associated with paroxysmal nonepileptic events. Methods: Retrospective, population-based study of children from the Victorian CP Register born 1999-2006. Neuroimaging, medical records, electroencephalograms (EEG), and EEG requests were analyzed. Results: Of the included 256 children, 87 had epilepsy. EEGs (with video correlation) were available for 82 of 87. Eighteen (18/82, 22%) had epileptic events captured on EEG. Twenty-one (21/82, 26%) had paroxysmal nonepileptic events captured on EEG. The majority (13/18, 77%) of children with epileptic events also had paroxysmal nonepileptic events captured. Ten parents and carers continued to report events as epileptic despite there being no ictal EEG correlate for specific events on multiple EEGs. There were no clear associations to identify which children would have ongoing paroxysmal nonepileptic events reported. Conclusions: Paroxysmal nonepileptic events were captured on EEG in one-fourth of children from this cerebral palsy cohort with epilepsy and available EEG. Half the parents and carers reported previously identified paroxysmal nonepileptic events as epileptic on subsequent EEGs, highlighting the need for clearer counseling so that parents better understand seizure semiology in children with EEG-proven paroxysmal nonepileptic events.

Cost-effectiveness of Prednisolone to Treat Bell Palsy in Children: An Economic Evaluation Alongside a Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Bell palsy is the third most frequent diagnosis in children with sudden-onset neurologic dysfunction. The cost-effectiveness of treating Bell palsy with prednisolone in children is unknown. We aimed to assess the cost-effectiveness of prednisolone in treating Bell palsy in children compared with placebo. METHODS: This economic evaluation was a prospectively planned secondary analysis of a double-blinded, randomized, placebo-controlled superiority trial (Bell Palsy in Children [BellPIC]) conducted from 2015 to 2020. The time horizon was 6 months since randomization. Children aged 6 months to <18 years who presented within 72 hours of onset of clinician-diagnosed Bell palsy and who completed the trial were included (N = 180). Interventions were oral prednisolone or taste-matched placebo administered for 10 days. Incremental cost-effectiveness ratio comparing prednisolone with placebo was estimated. Costs were considered from a health care sector perspective and included Bell palsy-related medication cost, doctor visits, and medical tests. Effectiveness was measured using quality-adjusted life-years (QALYs) based on Child Health Utility 9D. Nonparametric bootstrapping was performed to capture uncertainties. Prespecified subgroup analysis by age 12 to <18 years vs <12 years was conducted. RESULTS: The mean cost per patient was A$760 in the prednisolone group and A$693 in the placebo group over the 6-month period (difference A$66, 95% CI -A$47 to A$179). QALYs over 6 months were 0.45 in the prednisolone group and 0.44 in the placebo group (difference 0.01, 95% CI -0.01 to 0.03). The incremental cost to achieve 1 additional recovery was estimated to be A$1,577 using prednisolone compared with placebo, and cost per additional QALY gained was A$6,625 using prednisolone compared with placebo. Given a conventional willingness-to-pay threshold of A$50,000 per QALY gained (equivalent to US$35,000 or £28,000), prednisolone is very likely cost-effective (probability is 83%). Subgroup analysis suggests that this was primarily driven by the high probability of prednisolone being cost-effective in children aged 12 to <18 years (probability is 98%) and much less so for those <12 years (probability is 51%). DISCUSSION: This provides new evidence to stakeholders and policymakers when considering whether to make prednisolone available in treating Bell palsy in children aged 12 to <18 years. TRIAL REGISTRATION INFORMATION: Australian New Zealand Clinical Trials Registry ACTRN12615000563561.

Agreement of Clinician-Administered and Modified Parent-Administered House-Brackmann Scales in Children with Bell's Palsy.

Objective: Currently there is no parent administered scale for facial nerve function in children. We set out to assess the agreement between a newly developed parent-administered modified version of the House-Brackmann (HB) scale and the standard clinician-administered HB scale in children with Bell's palsy. Study Design: Secondary analysis of a triple-blind, randomized, placebo-controlled trial of corticosteroids to treat idiopathic facial paralysis (Bell's palsy) in children (6 months to <18 years). Setting: Multicenter study at pediatric hospitals with recruitment in emergency departments. Methods: Children were recruited within 72 hours of symptom onset and assessed using the clinician-administered and the parent-administered modified HB scales at baseline, and at 1, 3, and 6 months until recovered. Agreement between the 2 scales was assessed using intraclass coefficient (ICC) and a Bland-Altman plot. Results: Data were available for 174 of the 187 children randomized from at least 1 study time point. The mean ICC between clinician and parent HB scores across all time points was 0.88 (95% confidence interval, CI: 0.86, 0.90). The ICC for the data collected at baseline was 0.53 (95% CI: 0.43, 0.64), at 1 month was 0.88 (95% CI: 0.84, 0.91), at 3 months was 0.80 (95% CI: 0.71, 0.87) and at 6 months was 0.73 (95% CI: 0.47, 0.89). A Bland-Altman plot indicated a mean difference between the 2 scores (clinician-reported minus parent-reported) of only -0.07 (95% limits of agreement -1.37 to 1.23). Conclusion: There was good agreement between the modified parent-administered and the clinician-administered HB scales.

Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). SIGNIFICANCE: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome.

The incidence of pediatric ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Despite its importance in being among the top 10 causes of childhood death, there is limited data on the incidence of stroke in children and whether this has changed over time. AIMS: We performed a systematic review and meta-analysis to estimate the worldwide incidence rate of pediatric ischemic stroke, identify population differences, and assess trends in incidence. METHODS: We screened three databases (Medline, Embase, and Cumulative Index of Nursing and Allied Health Literature (CINAHL)) and a Google Search was performed up to October 2021. The protocol was pre-registered: PROSPERO: CRD42021273749. Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Stata SE17 to calculate the overall incidence rate. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. RESULTS: Out of 4166 records identified, 39 studies were included in the qualitative synthesis and the quantitative meta-analysis. The incidence rate for all ischemic strokes varied from 0.9 to 7.9 per 100,000 person-years, with a pooled incidence of 2.09 (95% confidence interval (CI): 1.57-2.76). The pooled incidence was 1.28 (95% CI: 0.75-2.19) per 100,000 person-years for arterial ischemic stroke, and 0.56 (95% CI: 0.31-1.02) per 100,000 person-years for cerebral venous sinus thrombosis. The incidence of arterial ischemic stroke was high in neonates, less than 28 days old (18.51, 95% CI: 12.70-26.97). Significant heterogeneity was observed in the initial analyses of stroke incidence estimates, and geographical region, cohort age upper limit, length of study, study quality, and study design could not explain this. The incidence rate of childhood stroke appeared remained relatively stable over time. CONCLUSION: Our review provides estimates of global stroke incidence, including stroke subtypes, in children. It demonstrates a particularly high stroke incidence in neonates.

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy.

Building health service management workforce capacity in the era of health informatics and digital health - A scoping review.

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.

Neuroimaging in Pediatric Stroke.

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.

Making waves: The changing tide of cerebral palsy.

Cerebral palsy (CP) is a broad diagnosis unbound by aetiology and is based on a clinical examination demonstrating abnormalities of movement or posture. CP represents a static neurological condition, provided that neurodegenerative conditions, leukoencephalopathies and neuromuscular disorders are excluded. In paediatrics, the genetic conditions associated with CP are rapidly increasing, with primary and overlapping neurodevelopmental conditions perhaps better categorised by the predominant clinical feature such as CP, intellectual disability, autism spectrum disorder or epilepsy. Progress in molecular genetics may challenge what constitutes CP, but a genetic diagnosis does not negate the CP diagnosis. As clinicians working in the field, we discuss the changing tide of CP. Neuroimaging provides essential information through pattern recognition and demonstration of static brain changes. We present examples of children where a layered clinical diagnosis or dual aetiologies are appropriate. We also present examples of children with genetic causes of CP to highlight the challenges and limitations of neuroimaging to provide an aetiological diagnosis. In consultation with a geneticist, access to genomic testing (exome or genome sequencing) is now available in Australia under Medicare billing for children under the age of 10 with dysmorphic features, one or more major structural organ anomalies, (an evolving) intellectual disability or global developmental delay. We encourage the uptake of genomic testing in CP, because it can be difficult to tell whether a child has an environmental or genetic cause for CP. A specific genetic diagnosis may change patient management, reduce guilt and enable more distinctive research in the future to assist with understanding disease mechanisms.

Efficacy of Prednisolone for Bell Palsy in Children: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND AND OBJECTIVE: Corticosteroids are used to treat the early stages of idiopathic facial paralysis (Bell's palsy) in children, but their effectiveness is uncertain. We set out to determine if prednisolone improves the proportion of children with Bell's palsy with complete recovery at one month. METHODS: We conducted a double-blind, placebo-controlled, randomised trial of prednisolone in children presenting to emergency departments with Bell's palsy. Patients aged 6 months to less than 18 years, recruited within 72 hours after symptom onset, were randomly assigned to receive 10 days of treatment with oral prednisolone (approximately 1 mg/kg) or placebo. The primary outcome was complete recovery of facial function at 1 month rated on the House-Brackmann scale. Secondary outcomes included facial function, adverse events and pain up to 6 months. Target recruitment was n=540 (270 per group). RESULTS: Between 13 October 2015 to 23 August 2020, 187 children were randomised (94 to prednisolone and 93 to placebo) and included in the intention-to-treat analysis. At 1 month, the proportions of patients who had recovered facial function were 49% (n=43/87) in the prednisolone group compared with 57% (n=50/87) in the placebo group (risk difference -8.1%, 95% CI -22.8 to 6.7; adjusted odds ratio [aOR] 0.7, 95% CI 0.4 to 1.3). At 3 months these proportion were 90% (n=71/79) for the prednisolone group versus 85% (n=72/85) for the placebo group (risk difference 5.2%, 95%, CI -5.0 to 15.3; aOR 1.2, 95% CI 0.4 to 3.0) and at 6 months 99% (n=77/78) and 93% (n=76/82) respectively (risk difference 6.0%, 95% CI -0.1 to 12.2; aOR 3.0 95% CI 0.5 to 17.7) There were no serious adverse events and little evidence for group differences in secondary outcomes. DISCUSSION: In children with Bell's palsy the vast majority recover without treatment. The study, although underpowered, does not provide evidence that early treatment with prednisolone improves complete recovery. REGISTRATION: Registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000563561, registered 1 June 2015, ://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368505&isReview=true CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for children with Bell's palsy, prednisolone does not significantly change recovery of complete facial function at one month. However, the study lacked the precision to exclude an important harm or benefit from prednisolone.

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition.

INTRODUCTION: Adolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. METHODS: Ninety-two participants with a Fontan circulation (aged 13-49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. RESULTS: Forty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were -0.63 (SD = 1.07) and -0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF-III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p < 0.01). Negative associations were identified between mean FA of the right arcuate fasciculus, right SLF-II and right SLF-III and processing speed (p ≤ 0.01). No significant associations were identified between DTI-based metrics and attention. CONCLUSION: Chronic hypoxemia may have long-term detrimental impact on white matter microstructure in people living with a Fontan circulation. Paradoxical associations between processing speed and tract-specific DTI metrics could be suggestive of compensatory white matter remodeling. Longitudinal investigations focused on the mechanisms and trajectory of altered white matter microstructure and associated cognitive dysfunction in people with a Fontan circulation are required to better understand causal associations.

Intravenous chlorpromazine for acute paediatric migraine.

OBJECTIVE: In paediatric migraine, ibuprofen, acetaminophen and triptans are safe, effective therapies but there is scant paediatric data informing second-line emergency treatment. METHODS: Retrospective cohort study of children diagnosed with migraine at a tertiary children's hospital ED. RESULTS: There were 207 children with migraine over a 1 year period. 46% received simple oral analgesia. 25% intravenous chlorpromazine, of whom 45% received further analgesia. CONCLUSIONS: While intravenous chlorpromazine as second-line agent was mostly safe, it had unclear efficacy given the requirement for further treatment and hospital admissions.

Parenteral Long-Acting Antiseizure Medications Are Used More Often to Treat Seizure Clusters Than Convulsive Status Epilepticus in the Pediatric Emergency Department.

Objective:Recent trials provide high-quality evidence for second-line treatment of convulsive status epilepticus (CSE) in children. However, the most effective medications for other seizure emergencies are poorly understood without established treatment algorithms. We investigated children presenting to the emergency department with repetitive or prolonged convulsions who required intravenous long-acting antiseizure medications, to determine the relative importance and treatment responsiveness of status epilepticus and seizure clusters. Methods: Retrospective observational study in the emergency department, Royal Children's Hospital, Melbourne, Australia (annual census 90 000) using hospital electronic medical records data of patients presenting with seizures in 2018. For patients receiving parenteral long-acting antiseizure medications, seizures were categorized as convulsive status epilepticus, nonconvulsive status epilepticus, and seizure clusters. Results: 1468 patients (2% of all visits) presented with seizures to the emergency department in 2018. Long-acting antiseizure medications were administered to 97 (7%) children for the emergency management of seizures. The majority presented with seizure clusters (n = 69; 71%). Only 11 (11%) were in convulsive status epilepticus and 17 (18%) in nonconvulsive status epilepticus. In convulsive status epilepticus, nonconvulsive status epilepticus, and seizure clusters, phenytoin was used in 27%, 53%, and 58% and levetiracetam in 73%, 47%, and 32%, respectively. Conclusions:Convulsive status epilepticus represents a small portion of patients requiring parenteral long-acting antiseizure medications. Seizure clusters accounted for >6 times the number of convulsive status epilepticus, yet evidence and treatment algorithms are lacking.