**Abstract authors:**

Moran Hausman-Kedem¹, Stephanie Libzon¹, Aviva Fattal-Valevski², Gustavo Malinger³, Shlomi Constantini², Nina Kreiden², Jonathan Roth², Liat Ben Sira², Shelly Shiran²

¹Tel Aviv Sourasky Medical Center, ²Dana Children's Hospital, Tel Aviv Sourasky Medical Center, ³Lis Maternity Hospital, Tel Aviv Sourasky Medical Center

**Abstract body:**

OBJECTIVE: to characterize clinical, neuroimaging data and etiology of spontaneous perinatal intracranial hemorrhage (spICH) in non-preterm. METHODS: a prospective, single-center study of 102 consecutive cases with spICH identified in the fetal/neonatal period between 2014-2022. RESULTS: Fifty-nine cases (58%) were diagnosed antenatally (termination of pregnancy-n=22). Intraventricular hemorrhage (IVH) was the most common hemorrhage type (73%), followed by periventricular hemorrhagic venous infarction (PVHI) (54%), parenchymal (13%), subdural (12%) and subpial (10%) hemorrhage. IVH was more commonly diagnosed prenatally (p=0.003), whereas subpial hemorrhage was exclusively diagnosed postnataly (p<0.001). Of the 73 born neonates, those with prenatal diagnosis were less likely to show symptoms in the perinatal period (p=0.005). There was no difference between prenatal versus postnatal cases or between types of hemorrhage in terms of maternal age, parity status, and mode of delivery. Intrauterine growth retardation was associated with parenchymal hemorrhage (p=0.039). Germinal matrix was the most common origin of hemorrhage (48%) and was more common in the prenatal group (65% vs. 28%, p<0.001), followed by choroid plexus (46%), hemorrhagic transformation of venous infarction (8%), bleeding diathesis (3%), vascular malformation (2%) and congenital tumor (1%). A family history of thrombophilia or coagulopathy was associated with subpial hemorrhage (p=0.033), and post-natal IVH (p=0.009). Genetic workup was performed in 42%, yielded a diagnosis in 35% of them, mostly with antenatal bleeding (p=0.003), and was associated with prenatal PVHI (p=0.029). Conclusion: Patterns of hemorrhage, as well as mechanisms, were different between the prenatal and postnatal cases, suggesting different disease mechanisms. Coagulopathy may contribute to spICH presenting in the postnatal period, whereas genetic factors play a major role in prenatal ICH.

Spontaneous perinatal intracranial hemorrhage-clinical, neuro-imaging and etiological correlates

**Abstract authors:**

Nicolas Serratrice¹, Andrea Bartoli¹, Kristof Egervari¹, Anne-Laure Rougemont-Pidoux¹, Eugénie Barras¹, Joël Fluss¹

¹HUG

**Abstract body:**

Introduction: Malignant neonatal arterial ischemic stroke concomitant with large vessel occlusion are rare and potentially life-threatening. Their origin is still controversial and very few cases reported in the literature. Case: The neonate was born full-term following an uneventful pregnancy without obstetrical maneuvers. Mild transient distress was noted at birth. Due to increasing lethargy, hypotonia and possible subtle seizures on day 2 of life, MRI was promptly conducted and showed an extensive left malignant hemispheric infarct with mass effect, left uncal herniation, right MCA infarct as well significant brainstem wallerian degeneration well visible on DWI and T2 sequences. Besides the ischemic lesions, the MRI angiography showed a complete occlusion of the left ICA, due a thrombus extending into the left MCA. Echocardiography demonstrated a PFO, normal anatomical structures, no intracardiac thrombus. The child rapidly deteriorated and was transferred to the NICU for reanimation. Given the very poor prognosis, and after multidisciplinary consensus as well as family approval, withdrawal of care was decided, and comfort measures initiated. The child died in parents' arms on day 3. Prothrombotic work-up was negative. On autopsy, thrombi were identified in the portal vein, the left iliac artery, the left MCA, and the left SCA. Large bilateral cerebral infarcts related mainly to the MCA territories were confirmed. A high grade fetal malperfusion syndrome with multiple thrombi within chorionic vessels was seen on placenta examination. Based on the various findings, it appears very likely that the severely abnormal placenta was the source of multiple thromboembolic stroke. Discussion: This case adds not only evidence of the presumed pathogenesis of perinatal arterial ischemic stroke, but also highlights the potential dramatic outcome of such situation, in particular when persistent occlusion of major neonatal cerebral vessel is still present on early imaging.

Fatal malignant neonatal arterial ischemic stroke with internal carotid occlusion: a pathological and clinic-radiological case study

**Abstract authors:**

Kathryn (Casey) Nesbit¹, Bryce Yale², Laura Hess³, Micah Mar², Alejandra Roque⁴, Dana Jacobs², Janice Brown³, Jordan Ng³, Reilly Todd³, Alyssa Vo³

¹Assistant Professor, ²UCSF/SFSU Graduate Program in Physical Therapy, ³Dominican University of California, ⁴NAPA Center, Inc

**Abstract body:**

Pediatric stroke has a significant impact on children and families. Outcome measures are essential to guide clinical management and inform research priorities, yet these instruments are highly varied in scope and application. Because pediatric stroke care and research is evolving, there is a need for a current review of pediatric stroke outcome measures. The purpose of this study was to systematically review the current literature for pediatric outcome measures, describe the studies using pediatric outcome measures, and describe the outcome measure characteristics. From an initial search of 1625 articles with duplicates removed, 116 articles met inclusion criteria. In those 116 articles, 95 distinct outcome measures were identified. Our review noted the most used outcome measures focused on deficits of the child whereas there was a paucity of outcomes used that included patient and family perspectives, recovery in natural contexts (e.g., home, school, community), and inadequate representation executive function and quality of life. We also found a lack of reliable and valid outcomes for the pediatric hemorrhagic stroke population, and a limited number of outcomes that measure recovery over time. The findings in this systematic review support recommendations for future development and use of pediatric stroke outcome measures, particularly for pediatric hemorrhagic stroke, that better capture the impacts to child and family life and contextually meaningful aspects of recovery over time.

Outcome Measures in Pediatric Stroke: A Systematic Review

From the ambient auditory environment, infants identify which communicative signals are linked to cognition. By 3 to 4 months of age, they have already begun to establish this link: listening to their native language and to non-human primate vocalizations supports infants’ core cognitive capacities, including object categorization. This study aims to shed light on the specific acoustic properties in these vocalizations which enable their links to cognition. We constructed a series of supervised machine-learning models to classify those vocalizations that support cognition from those that do not, based on classes of acoustic features derived from a collection of human language and non-human vocalization samples. The models highlight a potential role for spectral envelope and rhythmic features from both human languages and non-human vocalizations. Results implicate a potential role of underlying perceptual mechanisms relevant to spectral envelope and rhythmic features in infants’ establishment of the uniquely human language-cognition link.

Which acoustic features support the language-cognition link in infancy: A machine-learning approach

Infants experience the world through their actions with objects and their interactions with other people, especially their parents. Prior research has shown that school-age children with hearing loss experience poorer quality interactions with typically hearing parents, and difficulties in controlling their visual attention. In the current study, we used mobile eye-tracking to investigate parent-child interactions in toddlers with and without hearing loss. Parents and toddlers engaged in a goal-directed, interactive task that involved inserting coins into a slot and required joint coordination between the parent and the child. We examined the visual behaviors of the toddlers and the scaffolding behaviors of the parents. In contrast to previous work, preliminary findings reveal a pattern of potential similarities between deaf and hearing toddlers or their parents.

Joint Action in Deaf and Hearing Toddlers: A Mobile Eye-Tracking Study

The ability to rapidly recognize words and link them to referents in context is central to children's early language development. This ability, often called word recognition in the developmental literature, is typically studied in the looking-while-listening paradigm, which measures infants' fixation on a target object (vs. a distractor) after hearing a target label. We present a large-scale, open database of infant and toddler eye-tracking data from looking-while-listening tasks. The goal of this effort is to address theoretical and methodological challenges in measuring vocabulary development. We present two analyses of the current database (N=1,320): (1) capturing age-related changes in infants' word recognition while generalizing across item-level variability and (2) assessing how a central methodological decision -- selecting the time window of analysis -- impacts the reliability of measurement. Future efforts will expand the scope of the current database to advance our understanding of participant-level and item-level variation in children's vocabulary development.

Peekbank: Exploring children's word recognition through an open, large-scale repository for developmental eye-tracking data

Although infants can frequently observe others gathering information, it is an open question whether and how they make sense of such activities since the mental causes and intended effects of these are hidden and underdetermined by the available evidence. We tested the hypothesis that infants possess a naive theory that leads them to grasp the purpose of information-gathering actions when they serve as sub-goals of higher-order instrumental goals. We presented 14-month-old infants with actions that were inefficient with respect to the agent’s instrumental goal but could or could not be justified as information-seeking behavior via this theory. We expected longer looks in the condition where the detour could not be justified and the results were in line with our predictions. While this evidence is compatible with our hypothesis, further studies are in progress to rule out alternative interpretations of our findings.

Infants’ interpretation of information-seeking actions

Neuroprotection strategies for neonatal and childhood stroke - Kristin Guilliams

Background: Perinatal stroke occurs secondary to a focal disruption of blood flow in the brain occurring between 20 weeks' gestation and the 28th day of life. Current literature has associated perinatal stroke with adverse attention outcomes. Despite this, when parents of children with perinatal stroke were surveyed, very few recalled conversations with their clinician regarding their child's attentional outcome. There is therefore a need to evaluate the University Hospital Southampton (UHS) neurodevelopmental protocol to follow up attention outcomes in perinatal stroke. Aims: Firstly to evaluate adherence to the UHS neurodevelopmental protocol. Secondly, to evaluate the use of neuroimaging data and clinical data regarding neonatal seizures and post-natal epilepsy to identify children at risk of attention difficulties. Methodology: We conducted a service evaluation to determine whether the attention problem score from the Child Behavior Checklist (CBCL), was available from the parent reported questionnaire administered at the 2-year follow-up appointment. Neuroimaging data were analysed to identify cortical, white matter, basal ganglia, and thalamic involvement and to quantify infarct size. Presence of neonatal seizures and post-natal epilepsy were extracted from clinical notes. Chi-square was used to compare proportions. Results: CBCL data were only available for 35/63 patients. Reasons for missing CBCL data included patients not attending follow up, not returning questionnaires and inadequate data handling meaning data were not stored correctly. 13/35 children had attention scores in the borderline or clinical range. Basal ganglia and thalamic involvement (p=0.015), neonatal seizures (p=0.028) and post-natal epilepsy (p=0.042) were associated with borderline or clinically significant attention scores. Post-natal epilepsy predicted the highest relative risk of adverse attention outcomes. Conclusion: These clinical predictors could be used to identify children at high risk for attention difficulties to encourage parental adherence to the neurodevelopmental protocol, ensuring a complete clinical dataset and providing information to enable appropriate therapy and education.

A service evaluation of the University Hospital Southampton neurodevelopmental protocol to follow up and identify attention outcomes in children with perinatal stroke

Objective Perinatal intracranial hemorrhage (pICH) is a rare event that occurs during the fetal/neonatal period with potentially devastating neurological outcome. However, the etiology of pICH is frequently hard to depict. We investigated the role of rare genetic variations in unexplained cases of pICH. Methods We performed whole-exome sequencing (WES) in fetuses and term neonates with otherwise unexplained pICH and their parents. Variant causality was determined according to the American College of Medical Genetics and Genomics (ACMG) criteria, consistency between suggested genes and phenotypes, and mode of inheritance. Results Twenty-six probands (25 families) were included in the study (9 with a prenatal diagnosis and 17 with a postnatal diagnosis). Intraventricular hemorrhage (IVH) was the most common type of hemorrhage (n = 16, 62%), followed by subpial (n = 4, 15%), subdural (n = 4, 15%), and parenchymal (n = 2, 8%) hemorrhage. Causative/likely causative variants were found in 4 subjects from 3 of the 25 families (12%) involving genes related to the brain microenvironment (COL4A1, COL4A2, and TREX-1). Additionally, potentially causative variants were detected in genes related to coagulation (GP1BA, F11, Von Willebrand factor [VWF], FGA, and F7; n = 4, 16%). A potential candidate gene for phenotypic expansion related to microtubular function (DNAH5) was identified in 1 case (4%). Fifty-five percent of the variants were inherited from an asymptomatic parent. Overall, these findings showed a monogenic cause for pICH in 12% to 32% of the families. Interpretation Our findings reveal a clinically significant diagnostic yield of WES in apparently idiopathic pICH and support the use of WES in the evaluation of these cases

Whole-exome sequencing analysis in antenatal and perinatal intracerebral hemorrhage

Improving the accuracy of medical image interpretation is critical to improving the diagnosis of many diseases. Using both novices (undergraduates) and experts (medical professionals), we investigate methods for improving the accuracy of a single decision maker by aggregating repeated decisions from an individual in different ways. Our participants made classification decisions (cancerous versus non-cancerous) and confidence judgments on a series of cell images, viewing and classifying each image twice. We first applied the maximum confidence slating algorithm (Koriat, 2012), which leverages metacognitive ability by using the most confident response for an image as the `final response'. We also examined algorithms that aggregated decisions based on image similarity, leveraging neural network models to determine similarity. We found maximum confidence slating improves classification accuracy for both novices and experts. However, aggregating responses on similar images improves classification accuracy for novices and not experts, suggesting differences in the decision mechanisms of novices and experts.

Improving Medical Image Decision Making by Leveraging Metacognitive Processes and Representational Similarity

Retinopathy of Prematurity (ROP) is a disease affecting premature infants and may lead to childhood blindness. Due to lack of trained ophthalmologists, developing a fully automated ROP diagnostic system can significantly benefit the infants affected by ROP. Based on manually segmented features, previous work produces severity scores for ROP with excellent prediction accuracy. However, when automated segmentation employed, a significant accuracy drop is observed. In this paper, we show that U-Net segmentation, which is automated, comes at no accuracy loss.

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Spontaneous perinatal intracranial hemorrhage-clinical, neuro-imaging and etiological correlates

Fatal malignant neonatal arterial ischemic stroke with internal carotid occlusion: a pathological and clinic-radiological case study

Outcome Measures in Pediatric Stroke: A Systematic Review

Which acoustic features support the language-cognition link in infancy: A machine-learning approach

Joint Action in Deaf and Hearing Toddlers: A Mobile Eye-Tracking Study

Peekbank: Exploring children's word recognition through an open, large-scale repository for developmental eye-tracking data

Infants’ interpretation of information-seeking actions

Neuroprotection strategies for neonatal and childhood stroke - Kristin Guilliams

A service evaluation of the University Hospital Southampton neurodevelopmental protocol to follow up and identify attention outcomes in children with perinatal stroke

Whole-exome sequencing analysis in antenatal and perinatal intracerebral hemorrhage

Improving Medical Image Decision Making by Leveraging Metacognitive Processes and Representational Similarity

Automated ROP Diagnostic System based on Comparisons and U-Net Segmentation

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