Neonatal Arterial Ischemic Stroke Research Articles

GNN-based structural information to improve DNN-based basal ganglia segmentation in children following early brain lesion

Analyzing the basal ganglia following an early brain lesion is crucial due to their noteworthy role in sensory–motor functions. However, the segmentation of these subcortical structures on MRI is challenging in children and is further complicated by the presence of a lesion. Although current deep neural networks (DNN) perform well in segmenting subcortical brain structures in healthy brains, they lack robustness when faced with lesion variability, leading to structural inconsistencies. Given the established spatial organization of the basal ganglia, we propose enhancing the DNN-based segmentation through post-processing with a graph neural network (GNN). The GNN conducts node classification on graphs encoding both class probabilities and spatial information regarding the regions segmented by the DNN. In this study, we focus on neonatal arterial ischemic stroke (NAIS) in children. The approach is evaluated on both healthy children and children after NAIS using three DNN backbones: U-Net, UNETr, and MSGSE-Net. The results show an improvement in segmentation performance, with an increase in the median Dice score by up to 4% and a reduction in the median Hausdorff distance (HD) by up to 93% for healthy children (from 36.45 to 2.57) and up to 91% for children suffering from NAIS (from 40.64 to 3.50). The performance of the method is compared with atlas-based methods. Severe cases of neonatal stroke result in a decline in performance in the injured hemisphere, without negatively affecting the segmentation of the contra-injured hemisphere. Furthermore, the approach demonstrates resilience to small training datasets, a widespread challenge in the medical field, particularly in pediatrics and for rare pathologies.

Risk factors of neonatal stroke from different origins: a systematic review and meta-analysis.

This study provides a succinct overview and comparative analysis of maternal, perinatal, and additional risk factors associated with neonatal cerebral artery ischemic stroke and neonatal hemorrhagic stroke, furnishing critical insights for healthcare practitioners involved in the diagnosis and prevention of neonatal stroke. This research also broadens the conceptual framework for future investigations. • Research indicates that prenatal, perinatal, and neonatal risk factors can elevate the risk of neonatal arterial ischemic stroke (NAIS). However, the risk factors for neonatal cerebral arterial ischemic stroke remain contentious, and those for neonatal hemorrhagic stroke (NHS) and neonatal cerebral venous sinus thrombosis (CVST) are still not well-defined. • This study is the inaugural comprehensive review and meta-analysis encompassing 19 studies that explore maternal, perinatal, and various risk factors linked to neonatal stroke of differing etiologies. Notably, our analysis elucidates eight risk factors associated with NAIS: gestational diabetes mellitus, a history of infertility, placenta previa, postdates, preterm birth, premature rupture of membranes, a prolonged second stage of labor, and chorioamnionitis. Furthermore, we identify six risk factors correlated with NHS: postdates, preterm birth, an abnormal CTG, the method of delivery, male gender, and vaginal delivery. Additionally, our systematic review delineates risk factors associated with CVST.

Abstract 109: Towards Individualised Prediction of Neurodevelopmental Outcomes After Neonatal Stroke: A Brain Lesion Network Mapping Study Leveraging Large-Scale Datasets

Introduction: Prediction of adverse neurodevelopmental outcomes after neonatal arterial ischemic stroke (NAIS) is challenging. We identified brain regions functionally connected to stroke lesions (lesion networks), and investigated whether such lesion networks are related to the development of cerebral palsy (CP) after NAIS. Methods: We performed a novel lesion network mapping approach, involving: 1. Creation of a normative connectome using the developing Human Connectome Project (dHCP) dataset. Resting state functional magnetic resonance imaging (MRI) scans of 518 neonates born at term (>36 weeks) from the dHCP were aligned to a template, built from T 2 -weighted scans of the same neonates; 2. Manual segmentation of lesions using diffusion MRI scans of 85 term-born neonates with NAIS, who were identified from Australian and Swiss pediatric stroke registries. Lesion masks were aligned to the template; 3. Construction of lesion network maps, by computing functional correlations between lesion masks and other brain grey matter regions, making use of the normative connectome; 4. Investigation of relationships between lesion networks and CP, diagnosed by clinical examination at least 18 months after NAIS. Lesion network maps were compared between those who did (n=28) and did not (n=57) develop CP after NAIS, with two sample t-tests. Results: In participants who developed CP after NAIS, lesions were more strongly functionally connected to the following regions: frontal (inferior and orbital frontal), temporal (pole, superior, and mesial temporal), insula, basal ganglia, thalamus and cerebellum (Figure 1). Conclusions: Leveraging large-scale datasets and innovative connectomic methods, we uncovered brain networks related to adverse outcomes after NAIS. This provided novel findings compared to past methods such as voxel-based lesion-symptom mapping. Our results point to differences in network vulnerabilities after stroke in neonates compared to adults.

Routine Echocardiography is not Required in Neonates with Arterial Ischemic Stroke.

Current guidelines suggest routine echocardiography (ECHO) in the acute phase to exclude a cardiac source for neonatal arterial ischemic stroke (NAIS). However, the commonly assumed embolic origin from a cardiac source for NAIS is challenged and the need for ECHO in NAIS remains questionable, especially during the era of standard fetal anomaly scanning. Our hypothesis is that any complex cardiac defects potentially causing NAIS would likely be detected during routine prenatal scans, thus possibly making routine postnatal ECHO redundant. This study aimed to determine the prevalence of significant cardiac risk factors and evaluate the necessity of routine postnatal ECHO in NAIS during the routine use of prenatal fetal sonography. Retrospective review of 54 infants diagnosed with NAIS via brain magnetic resonance imaging who underwent an ECHO evaluation during the acute period to exclude potential cardiac origins for NAIS. Postnatal ECHO revealed no intracardiac thrombus or vegetation, and only identified structural heart anomalies in three (5%) infants. Interestingly, these three cases had already been diagnosed with syndromic conditions or chromosomal malformations prenatally. In the remaining infants, postnatal ECHO was either normal or showed minor abnormalities unlikely to have contributed to the stroke. The detection rates of complex cardiac anomalies from prenatal scans and postnatal ECHO were statistically similar (p = 0.617). The probability of ECHO to exclude cardiac sources for NAIS is so low that in the era of standard fetal anomaly scanning, routine postnatal ECHO may not be necessary for all NAIS infants, except when chromosomal malformations are detected. · Guidelines recommend an acute phase ECHO to identify a cardiac source of NAIS.. · ECHO not effective at excluding NAIS's cardiac origin for infants with normal fetal scans.. · Routine postnatal ECHO is unnecessary in NAIS infants, except with genetic abnormalities..

Three-year incidence and acute setting predictors of epilepsy after neonatal and childhood arterial ischaemic stroke: a disease-based cohort study.

This study identified specific and reliable acute clinical and imaging predictors of PSE in paediatric patients, helping clinicians identify high-risk patients with potential implications for treatment decisions. • Numerous risk factors have been proposed for post-stroke epilepsy, but there is a lack of studies evaluating these variables while accounting for confounding factors and competing risks over time. • After adjustment for competing events, acute symptomatic seizures, both non-status and status epilepticus, abnormal mental status or motor neurological examination at hospital discharge, cortical involvement, and multifocal ischaemic lesions in small strokes are all independent predictors of post-stroke epilepsy. • Knowing the predictors of post-stroke epilepsy is essential for clinicians to make well-informed and effective decisions about treatment.

Contralateral Massive Neonatal Arterial Ischemic Stroke Secondary to Carotid Artery Dissection: A Case Report

Contralateral Massive Neonatal Arterial Ischemic Stroke Secondary to Carotid Artery Dissection: A Case Report

Long-term developmental condition following neonatal arterial ischemic stroke: A systematic review

BackgroundNeonatal arterial ischemic stroke (NAIS) is the most frequent subtype of perinatal stroke. Its elusive pathophysiology, its abrupt and unexpected occurrence, and the uncertainty of the post-NAIS developmental condition may lead to parental emotional distress and psychological difficulties. The aim of this study was to summarize the current data on long-term developmental conditions following NAIS to support parental information given within the neonatal unit. MethodsThis systematic review included clinical studies of term infants with NAIS, who had a developmental assessment at ≥5 years of age. Studies were identified from the Medline and Embase databases on June 1, 2022. The Joanna Briggs Institute (JBI) appraisal tool was used to assess the risk of bias. Results were synthesized using a narrative approach. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed to report this work. ResultsThree cohort studies enrolling 205 children assessed from 5 to 7 years after NAIS were included. Most of the children presented long-term developmental conditions allowing them to be integrated into a regular school program, to participate in physical activities, and to have a good quality of life. Global intellectual deficiency and moderate-to-severe cerebral palsy occurred in less than 10% of the children. ConclusionPhysicians should not overestimate the incidence of moderate-to-severe developmental outcome following NAIS when discussing the prognosis with parents. A parental information sheet about NAIS and its long-term developmental conditions is provided.

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

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). 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). 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. 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.

Massive Neonatal Arterial Ischemic Stroke

BackgroundMassive infarction in adults is a devastating entity characterized by signs of extreme swelling of the brain's parenchyma. We explored whether a similar entity exists in neonates, which we call massive neonatal arterial ischemic stroke (M-NAIS), and assess its potential clinical implications. MethodsProspective multicenter cohort study comprising 48 neonates with gestational age ≥35 weeks with middle cerebral artery (MCA) NAIS was performed. Diagnosis with magnetic resonance imaging (MRI) was performed within the first three days after symptom onset. The presence of signs of a space-occupying mass, such as brain midline shift and/or ventricular and/or extra-axial space collapse, was recorded. The volume of the infarct and brain midline shift were determined with semiautomatic procedures. Neurodevelopment was assessed at age 24 months. ResultsFifteen (31%) neonates presented MRI signs of a space-occupying mass effect and were considered to have an M-NAIS. The relative volume (infarct volume/total brain volume) of the infarct was on average significantly greater in the M-NAIS subgroup (29% vs 4.9%, P < 0.001). Patients with M-NAIS consistently presented lesions involving the M1 arterial territory of the MCA and showed more apneic and tonic seizures, which had an earlier onset and lasted longer. Moderate to severe adverse neurodevelopmental outcomes were present in most M-NAIS cases (79% vs 6%, P < 0.001). ConclusionsM-NAIS appears to be a distinctive subtype of neonatal infarction, defined by characteristic neuroimaging signs. Neonates with M-NAIS frequently present a moderate to severe adverse outcome. Early M-NAIS identification would allow for prompt, specific rehabilitation interventions and would provide more accurate prognostic information to families.

Chronic changes in oligodendrocyte sub-populations after middle cerebral artery occlusion in neonatal mice.

Neonatal stroke is common and causes life-long motor and cognitive sequelae. Because neonates with stroke are not diagnosed until days-months after the injury, chronic targets for repair are needed. We evaluated oligodendrocyte maturity and myelination and assessed oligodendrocyte gene expression changes using single cell RNA sequencing (scRNA seq) at chronic timepoints in a mouse model of neonatal arterial ischemic stroke. Mice underwent 60 min of transient right middle cerebral artery occlusion (MCAO) on postnatal day 10 (p10) and received 5-ethynyl-2'-deoxyuridine (EdU) on post-MCAO days 3-7 to label dividing cells. Animals were sacrificed 14 and 28-30 days post-MCAO for immunohistochemistry and electron microscopy. Oligodendrocytes were isolated from striatum 14 days post-MCAO for scRNA seq and differential gene expression analysis. The density of Olig2+ EdU+ cells was significantly increased in ipsilateral striatum 14 days post-MCAO and the majority of oligodendrocytes were immature. Density of Olig2+ EdU+ cells declined significantly between 14 and 28 days post-MCAO without a concurrent increase in mature Olig2+ EdU+ cells. By 28 days post-MCAO there were significantly fewer myelinated axons in ipsilateral striatum. scRNA seq identified a cluster of "disease associated oligodendrocytes (DOLs)" specific to the ischemic striatum, with increased expression of MHC class I genes. Gene ontology analysis suggested decreased enrichment of pathways involved in myelin production in the reactive cluster. Oligodendrocytes proliferate 3-7 days post-MCAO and persist at 14 days, but fail to mature by 28 days. MCAO induces a subset of oligodendrocytes with reactive phenotype, which may be a therapeutic target to promote white matter repair.

Abstract TP159: Association Of Lesion Characteristics And Neurological Outcomes In Neonatal Arterial Ischemic Stroke Patients

Background: Neonatal arterial ischemic stroke (NAIS) occurs as a result of an acute focal cerebral arterial infarction between birth and 28 days of life in nearly 1:2500 live births. As there are few studies examining the relationship between NAIS lesion characteristics and clinical outcomes, this study aims to determine if lesion volume and lesion location are associated with abnormal neurological outcomes in NAIS. Methods: Semi-automated lesion segmentation of co-registered multi-modal images was conducted using ITK-SNAP. Semi-automated lesion segmentations with manual corrections were performed using ITK-SNAP software. Lesion volumes were corrected for head size by dividing lesion volumes by total intracranial volume, and correlated (using Kendall's Tau-b [τ b ]) with neurological outcome that was assessed with the Pediatric Stroke Outcome Measure (PSOM). Results: Participants included N=20 NAIS patients (mean [M] weeks gestation=39.5, +/-1.64; 55% male, 70% single infarct, 75% left-sided lesions). Outcome was assessed an average of 312, +/-7.6 days post-stroke. Neurological deficits were present in 50% (with seizures in 85%) at time of stroke, and infarct locations most commonly involved supratentorial cortical structures (75%), however none were correlated with outcome. Larger lesion volumes (M=5.35 mm 3 , +/-0.069) were correlated with poor outcome (τ b =.444, p=0.02). Conclusion: We found larger lesion volume to be associated with atypical clinical outcomes following NAIS. Further analysis is in progress that include changes over time in lesion characteristics and outcome. These results demonstrate a need for better characterize the relationship between lesion characteristics and outcomes in NAIS.

Abstract TMP22: Exploring The Impact Of Material Deprivation, Clinical, And Radiological Features On Neurological Outcomes Of Neonatal Stroke

Introduction: Neonatal arterial ischemic stroke (AIS) is an important cause of neurologic disability in children. No research to date has examined the influence of determinants of health on outcomes in a neonatal AIS population. This study examined whether neighbourhood-level material deprivation was associated with long-term neurological outcomes in neonatal AIS patients, after accounting for the influence of clinical and radiological factors. Methods: Patients with neonatal AIS between 2004 and 2019 at a comprehensive stroke centre were included. The Ontario Marginalization Index (ON-Marg) was used to assess neighbourhood-level material deprivation. Participant postal codes were linked to census data and ON-Marg scores were reported. Neurological outcomes were assessed using the Pediatric Stroke Outcome Measure Severity Classification Scale (PSOM-SCS) at latest follow up (median = 49 months, range = 12 to 187 months). A poor outcome was defined as any neurologic deficit (i.e., mild, moderate, or severe). Univariable and multivariable logistic regression models were developed. Results: Amongst 154 participants, the majority of scores (66.23%) were within the normal range. Remaining participants demonstrated neurological deficits, including 25.97% mild and 7.79% moderate-to-severe. Predictors of poor outcome in the multivariable model included hemiparesis at stroke presentation (OR = 12.81, p &amp;lt; 0.05) and basal ganglia involvement (OR = 3.68, p &amp;lt; 0.05). Neighbourhood-level material deprivation was not significantly associated with poor outcome. Conclusions: Hemiparesis and basal ganglia involvement are important in determining long-term outcomes. Although material deprivation was not associated with poor outcomes in our study, it may be associated with neurological outcomes at later ages. Further research is needed to understand the role of socioeconomic factors in a neonatal stroke population, including the measurement of individual-level indicators and outcomes at later ages post-stroke. While outcomes after neonatal stroke are generally favourable, identifying predictors of poor outcomes may assist clinicians in developing a more precise risk evaluation regarding recovery after stroke.

Perinatal inflammation exposure and developmental outcomes 7 years after neonatal arterial ischaemic stroke.

To test the association between perinatal inflammation exposure and Full-Scale IQ (FSIQ) score 7 years after neonatal arterial ischaemic stroke (NAIS). We conducted a cross-sectional ancillary study nested in a multicentric longitudinal French cohort of infants born at term with NAIS between November 2003 and October 2006. Seventy-three children were included (45 males, 28 females). The a priori defined primary outcome measure was the FSIQ score assessed with the Wechsler Intelligence Scale for Children, Fourth Edition at 7 years of age. Seventeen (23%) of the included children were exposed to perinatal inflammation. Exposure to perinatal inflammation was independently associated with an increase of FSIQ score (coefficient 13.4, 95% confidence interval 1.3-25.4; p = 0.03). Children exposed to perinatal inflammation had a higher median cerebral volume, a lower median lesion volume, and less extensive lesion distributions compared to non-exposed children. We propose the existence of two NAIS categories: arteritis-associated NAIS in children exposed to perinatal inflammation and embolism-associated NAIS in children non-exposed to perinatal inflammation. Identifying these two NAIS categories would open the possibility for specific curative strategies: anti-inflammatory strategy in arteritis-associated NAIS and recanalization strategy in embolism-associated NAIS.

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

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. 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. 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). 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.

Neonatal Arterial Ischemic Stroke Secondary to Carotid Artery Dissection: A Case Report and Systematic Literature Review

BackgroundCarotid artery (CA) dissection is a rare etiology of neonatal arterial ischemic stroke (NAIS). MethodsWe describe one novel case and conduct a systematic literature review on NAIS attributed to CA dissection, to collect data on its clinical-radiological presentation, treatment, and outcome. ResultsEight published cases of NAIS attributed to CA dissection were identified and analyzed with our case. All patients (nine of nine) were born at term, and eight of nine experienced instrumental/traumatic delivery or urgent Caesarean section. None had fetal problems during pregnancy or thrombophilia. Signs and symptoms at presentation (between days of life 0 and 6) included seizures (eight of nine), respiratory distress or irregular breathing (five of nine), hyporeactivity, decreased consciousness or irritability (four of nine), and focal neurological signs (two of nine). At magnetic resonance imaging (MRI), stroke was unilateral in seven of nine and extensive in five of nine. CA dissection was documented by neuroimaging or at postmortem studies (seven of nine), and hypothesized by the treating physicians based on delivery and neuroradiology characteristics (in the remaining two of nine). Antithrombotic treatment was used in two of nine. According to available follow-up, one of eight died at age seven days, seven of eight had neurological/epileptic sequelae, and CA recanalization occurred in three of four. ConclusionsNAIS attributed to CA dissection is rarely identified in the literature, often preceded by traumatic/instrumental delivery, presenting with seizures and systemic signs/symptoms, and often characterized by extensive MRI lesions and neurological sequelae. Definite evidence and recommendations on antithrombotic treatment are lacking.

Effect of Age at Pediatric Stroke on Long-term Cognitive Outcome.

Background and ObjectivesTo investigate the effect of age at pediatric arterial ischemic stroke on long-term cognitive outcome in order to identify patients particularly at risk for the development of long-term cognitive sequelae.MethodsThis cross-sectional study included patients in the chronic phase of stroke (>2 years after stroke) previously diagnosed with neonatal or childhood arterial ischemic stroke and a control group. Participants with active epilepsy, severe learning difficulties, or behavioral problems hindering the cognitive assessment were excluded. Several cognitive domains, including intelligence, executive functions (working memory, inhibition, and cognitive flexibility), processing speed, memory, letter fluency, and visual-motor skills were assessed with neuropsychological tests. Cognitive long-term outcome was compared across patients after neonatal stroke (stroke between 0 and 28 days of life), early childhood stroke (stroke between 29 days and <6 years), and late childhood stroke (stroke between ≥6 and <16 years).ResultsFifty-two patients after neonatal or childhood arterial ischemic stroke (median age 15.3 years, interquartile range [IQR] 10.6–18.7) and 49 healthy controls (median age 13.6 years, IQR 9.8–17.2) met the inclusion criteria. Cognitive outcome was significantly worse in the pediatric stroke group compared to the control group. A nonlinear effect of age at stroke (irrespective of lesion size and lesion location) was found for cognitive flexibility, processing speed, and verbal learning with early childhood stroke (29 days to <6 years), showing significantly worse cognitive outcome compared to neonatal or late childhood stroke (p < 0.05, false discovery rate–corrected).DiscussionAge at stroke is an important factor for poststroke recovery and modulates long-term cognitive outcome irrespective of lesion size and lesion location. Children after early childhood stroke are at particular risk for long-term alterations in cognitive functions.

Cerebrospinal Fluid Ion Analysis in Neonatal Seizures

BackgroundThere is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. MethodsA descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl−, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxic-ischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. ResultsSixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl−]CSF, and [Ca2+]CSF were less consistent among subgroups. ConclusionsHere we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function.

Abstract 10072: Stroke Topology and Neurodevelopment in Infants with Congenital Heart Disease: Does it Differ by Cardiac Physiology?

Objectives: Vulnerability to brain injury in infants with congenital heart disease (CHD) may differ by CHD lesion. However, the link between arterial ischemic stroke (AIS) and neurodevelopment, and whether it differs by CHD lesion, is unknown. We sought to determine whether: (1) Stroke topology differs between infants with Transposition of the Great Arteries (TGA) and single ventricle physiology (SVP), and relationship with neurodevelopment;(2) Associations between stroke volume and neurodevelopment are CHD lesion specific. Methods: 64 of 312 CHD infants (TGA n=38, SVP n=26) studied prospectively with pre- and/or post-operative brain MRIs had AIS. AIS were segmented on 3DT1 and/or ADC images. 39 infants completed 18-month neurodevelopmental assessments with Bayley Scales (2 nd or 3 rd Edition); scores were adjusted to account for differences between versions. Adverse neurodevelopment was defined as &lt;85 points. We used multivariable linear regression models to study associations between AIS volume and neurodevelopment, stratifying by CHD lesion and adjusting for study site. Probability maps demonstrating areas vulnerable to AIS and odds ratio maps reflecting likelihood of a lesion predicting adverse outcomes were developed. Results: Most AIS were in MCA territories, with a left-sided predominance (Fig 1A). Stroke volume did not differ between CHD groups (p=0.8). Basal ganglia lesions were most predictive of cognitive (max OR=11) and motor (max OR=6) outcomes (Fig 1B). Stratifying by CHD lesion, AIS volume predicted 18-month cognitive outcomes in infants with TGA (β=-0.6, 95%CI -1.0-(-0.1), p=0.02) but not SVP (β=7.9, 95%CI -72-88). AIS volume did not predict motor outcomes in infants with TGA (β=-0.6, 95%CI -1.6-0.3) or SVP (β=-19.7, 95%CI -91-52). Conclusions: Neonatal AIS topology does not differ between infants with TGA and SVP. AIS location and size are important predictors of neurodevelopment at 18 months though this association differs by CHD lesion.

P.066 Hemispheric Reorganization of Functional Language Networks Following Neonatal Stroke Supports Language Outcome

Background: Neonatal Arterial Ischemic Stroke (NAIS) is a common form of paediatric stroke often affecting classical language areas. The post-stroke reorganization of functional language networks may provide insight into later-emerging language deficits and may help to identify at-risk children with NAIS. Methods: A cross-sectional study of fourteen children with left (n=8; 2M; 11.1±2.2 years) or right (n=6; 3M; 12.4±4 years) middle cerebral artery (MCA) NAIS, as well as seven neurotypical children (5M; 13.4±2.7 years), was conducted. Children listened to correct/incorrect syntactic sentences while MEG was recorded, and task-related functional connectivity in the time window and frequency band of interest was determined. Language outcomes were assessed using a battery of neuropsychological tests. Results: A network-based analysis of syntactic language processing (4-7 Hz, 1.2-1.4s) revealed a dysfunctional bilateral frontal-temporal network involving language areas in patients (p=0.01). Patients with right-MCA stroke exhibited a positive correlation between left hemispheric connectivity and measures of language skill (p&lt;0.01), resembling the neurotypical children. In left-MCA stroke patients, greater bilateral connectivity or right laterality in the language network is correlated with good outcome (p&lt;0.05). Conclusions: Depending on the hemispheric location of stroke, certain patterns of language network reorganization may account for impairments in a bilateral frontal-temporal language subnetwork and support language outcome.

B.3 The incidence of perinatal stroke is 1:1200 births in Southern Alberta: Population-based incidence of disease-specific perinatal stroke

Background: Perinatal stroke encompasses six cerebrovascular syndromes which occur between the 20th week of gestation and the 28th post-natal day. Subtypes are neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis (CSVT), neonatal hemorrhagic stroke (NHS), arterial presumed perinatal ischemic stroke (APPIS), periventricular venous infarction (PVI), and presumed perinatal hemorrhagic stroke (PPHS). Inconsistent terminology and lack of population-based case series has limited accurate measurement of disease-specific perinatal stroke incidence. Our objective was to define the incidence of the subtypes of perinatal stroke using a population-based cohort. Methods: The Alberta Perinatal Stroke Project is a research cohort established in 2008 in Southern Alberta. Case acquisition included retrospective hospital and ICD code searches (1990-2008) and prospective enrollment from all NICU and neurology/stroke clinics (2008-2017). Results: The overall incidence of perinatal stroke in Southern Alberta was 9.0 cases per 10,000 births, or 1:1200 births. Per 10,000 births, the incidence of each subtype was: NAIS = 3.2 (~1:3000), APPIS =1.2 (~1:8500), PVI = 1.5 (~1:6500), CSVT = 1.0 (~1:9900), NHS = 1.4 (~1/7300), PPHS = 0.1 (1/82,000). Conclusions: The overall incidence of perinatal stroke in Southern Alberta is 1:1200 live births. Population-based sampling of disease-specific states may explain why this rate is much higher than previous estimates