Focal Cerebral Arteriopathy: Do Steroids Improve Outcome?

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

Pediatric ASPECTS predicts outcomes following acute symptomatic neonatal arterial stroke

Objective: To 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. Methods: Cross-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. Results: Ninety-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). Conclusions: This 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

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

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 neonatal arterial ischemic stroke (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-test statistics were calculated, correcting for multiple comparisons using family-wise error rate (FWE). RESULTS Eighty-five newborns met inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%) and bilateral (30%). At median age 2.1 years (IQR 1.9-2.6), 33% developed CP and 42% had neurological impairments. 54 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. CONCLUSIONS CP following NAIS correlates with infarct regions directly involved in motor control and, or in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear

Association of Pediatric ASPECTS and NIH Stroke Scale, Hemorrhagic Transformation, and 12-Month Outcome in Children With Acute Ischemic Stroke.

OBJECTIVE We 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 AIS. METHODS Children (29 days to <18 years) with acute AIS enrolled in two institutional prospective stroke registries at Children's Hospital of Philadelphia and Royal Children's Hospital Melbourne, Australia were retrospectively analyzed to determine whether modASPECTS, in which higher scores are worse, correlated with acute Pediatric NIH Stroke Scale (PedNIHSS) scores (children ≥2 years of age), was associated with hemorrhagic transformation on acute MRI, and correlated with 12-month functional outcome on the Pediatric Stroke Outcome Measure (PSOM). RESULTS 131 children were included; 91 were ≥2 years of age. Median days from stroke to MRI was 1 (interquartile range [IQR] 0-1). Median modASPECTS was 4 (IQR 3-7). ModASPECTS correlated with PedNIHSS (rho=0.40, P=0.0001). ModASPECTS was associated with hemorrhagic transformation (OR 1.13 95% 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). CONCLUSIONS ModASPECTS 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 EVIDENCE This study provides Class II evidence that the modified pediatric ASPECTS on MRI is associated with stroke severity (as measured by the baseline pediatric NIH Stroke Scale), hemorrhagic transformation, and 12-month outcome in children with acute supratentorial ischemic stroke

Australian Clinical Consensus Guideline: the diagnosis and acute management of childhood stroke

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

The Australian Stroke Clinical Registry Annual Report 2022

The Australian Stroke Clinical Registry (AuSCR) is a collaborative national effort to monitor and support improvements to the quality of acute care for patients with stroke. Since 2009, the AuSCR has provided national data on consecutive patients admitted to hospital with acute stroke, which has been used to inform improvements to the health system.In 2022, 61 hospitals contributed data to the AuSCR: 48% from Victoria; 34% from Queensland; 5% each from South Australia, Tasmania and Western Australia; and 3% from the Australian Capital Territory.Information is presented on 17,184 episodes of acute stroke for 15,880 patients.This Annual Report highlights the ongoing variation in stroke care in Australia. Many patients are missing out on the best available, evidence-based care. For example, one in four patients are not treated in a dedicated stroke unit, which is known to improve care in hospital, and outcomes after discharge, and two in three patients are treated with thrombolysis outside the recommended 60 minutes from arrival. We report essential, standardised evidence in support of national clinical guidelines, standards of care expected for acute stroke. We highlighted areas where Australian hospitals have made improvements, and others that should be improved including the urgent need to improve the quality of care for people experiencing intracerebral haemorrhage. Collectively, these findings underpin the continued importance of actively addressing practice gaps and ensuring access to evidence-based care. The benefits of stroke units were highlighted and we must ensure that all patients with stroke are treated in stroke units.It is essential that quality improvement programs are supported and that the data from AuSCR are used proactively. We have innovated in different areas of data feedback methods to support clinicians to understand their data, and have informed conversations with hospital executives. In 2022, the AuSCR pioneered the development of new, interactive data dashboards. These dashboards allow hospital clinicians to securely access their data in near real-time to explore opportunities to improve stroke care in greater detail. Through co-design with clinicians, a series of prototypes and features were initially prioritised to guide the dashboard development. We also welcome the recent announcement of National Stroke Targets be achieved by 2030. The AuSCR looks forward to working with organisations, such as the Stroke Foundation, Australian and New Zealand Stroke Organisation, the Australian Stroke Coalition and state health departments, to support hospitals to achieve these targets. The AuSCR data will continue to provide the essential evidence to monitor progress against the new national stroke targets. In this Annual Report, for the first time we report performance against these National Stroke Targets. In future Annual Reports, comparisons against these baseline values will be undertaken to track progress in meeting these targets.We acknowledge and gratefully respect the important contributions from patients, caregivers, and hospital clinicians.</p