United States

Background and Aims: Subpial hemorrhages (sPH) were first described in infants in 1972, but they remain underrecognized on neuroimaging and the clinical implications of sPH are poorly understood. The aim of this study is to describe the etiologies, risk factors, clinical presentations, and imaging findings of sPH in neonates. Methods: Institutional Neonatal Intensive Care Unit database was queried for presence of sPH. All infants recorded to have intracranial hemorrhage on brain MRI were reviewed by a pediatric neuroradiologist. Through retrospective chart review, data on pregnancy/birth history, comorbidities, and clinical concerns that led to imaging were collected. Results: Twenty-six infants with sPH were identified: 13 (50%) were preterm, 11 (42%) had low birthweight. Comorbidities included hypoxic-ischemic encephalopathy (n=1, 42%), birth trauma (n=6, 23%), cardiopulmonary disease (n=6, 23%), coagulopathy (n=6, 23%), ventricular shunt (n=3, 12%), severe congenital brain anomalies (n=1, 4%), and chromosomal anomaly (n=1, 4%). MRI acquisition was at a median of 5 days of life (range 1 to 41 days). sPH frequently accompanied intraparenchymal (n=17, 65%), subdural (n=16, 62%), intraventricular (n=13, 50%), and subarachnoid hemorrhage (n=8, 31%). In addition, 7 children (27%) had ischemic stroke. All children with sPH had either another form of hemorrhage, ischemic stroke, or both. In addition, 9 patients (34%) had follow-up MRIs. Development of adjacent encephalomalacia was consistently demonstrated in children with large subpial hemorrhages. Sixteen infants with sPH (62%) had clinical and/or electrographic seizures. Conclusions: sPH are associated with multiple comorbid medical conditions, other types of intracranial hemorrhage, and ischemic strokes. Further studies to evaluate long-term clinical implications of subpial hemorrhages are needed.

IPSO 2021

A new kind of bleed: Subpial hemorrhages in the neonatal intensive care unit

hemorrhagic stroke

ICPR 2020 is the premier international conference on Pattern Recognition, gathering leading researchers from around the world to present their latest achievements in Pattern Analysis and Recognition, applied Artificial Intelligence and Machine Learning. The topic of the year is " Putting Artificial intelligence to work on Patterns". 
For the first time, ICPR has employed a two-round review process similar to journal submissions, with new papers allowed to be submitted in either the first or second round and papers submitted in the first round and not accepted allowed to be revised and re-submitted for second round review. 

In this edition of the **ICPR 2020** Conference, there are 1407 Oral/Poster presentations organized in five Tracks: 
- Artificial Intelligence, Machine Learning for Pattern Analysis; 
- Biometrics, Human Analysis and Behavior Understanding; Computer Vision, Robotics and Intelligent Systems; 
- Document and Media Analysis; and 
- Image and Signal Processing. 

The **ICPR 2020** Main Conference program also includes 7 Keynotes from prominent world-renowned scientists, 8 Tutorials, 28 Demos, 8 Challenges, 2 Panels, as well as an Industry/Sponsor Exhibition. In addition, 41 Workshops on a range of important current and emerging research topics complete the ICPR 2020 program. 


ICPR 2020

poster

**[Download Full Agenda](https://drive.google.com/file/d/1Dm9lJyTfJrvd7-StaHFmUmhXC-J_UgTj/view?usp=sharing)**

Dear IPSO Virtual Conference Attendees:

Welcome to IPSO’s first-ever conference! We are delighted to bring together experts from <u>multiple disciplines</u> and <u>six continents</u> to provide a diverse perspective on pediatric cerebrovascular disease.  

A few quick words about what to expect.  Two important goals of this conference are to (1) foster a sense of community and (2) identify global priorities for our field. Hence, the program includes short presentations on an array of clinical controversies and dedicates more time to panel discussions with a live chat function so that everyone can participate. We are excited to announce IPSO is able to offer 8.75 CME units for the virtual conference. If you would like to claim CME credits, please email  <membership@internationalpediatricstroke.org>. 

We want to hear from you!  Planning for the [IPSO Founding Members’ Congress](https://internationalpediatricstroke.org/2022-congress/) in Vienna, April 24-26, 2022, will commence as soon as the Virtual Conference ends. Let us know your priorities through the live chat function, via email, or by submitting a symposium idea. Based on your input, the Scientific Program Committee will select the topics that we will address in greater depth when we meet again in the spring.

We hope you find the Virtual Conference both interesting and educational, and hope to see you in person in Vienna, or at another IPSO meeting in the future.  

Warm regards,

Heather Fullerton, IPSO President

Adam Kirton, IPSO Vice-President

Lori Jordan, IPSO Secretary & Treasurer


![](https://assets.underline.io/uploads/markdown_image/1/image/1c71a0aebc49947c923a7920d9f28857.jpg)



  
    
  


  



*Header Photo Credit: Helen Carlson, Ph.D, Alberta Children's Hospital*

To access IPSO 2021, you must pre-register for the conference.  Instructions on how to access the event will be provided directly to attendees and included on the IPSO 2021 conference website. [Register now](https://internationalpediatricstroke.org/2021-congress/registration/).

Welcome to the first IPSO Virtual Conference. The mission of the virtual conference is to unify the global community of professionals engaged in research and clinical care for children with cerebrovascular diseases, and chart a path forward for multinational, multidisciplinary efforts.  Please go here to access the virtual conference platform- <a href="https://underline.io/events/157/reception">Reception page</a>. 



Introduction: Moyamoya disease (MMD) in children commonly presents as cerebral ischemia (80%) rather than hemorrhage (20%) as well as headaches, seizures, involuntary movements and progressive decline in intellectual ability. We present a pediatric patient with MMD presenting with worsening migraines, anxiety, fatigue and nonspecific subcortical signal abnormalities on brain imaging. Case: A 7-year-old French-Canadian girl presented with a 2-year history of monthly, bifrontal headaches, associated with nausea, vomiting, photo- and phonophobia. An initial brain-MRI at 5 years of age showed non-specific subtle bifrontal subcortical millimetric white matter hyperintensities on T2/FLAIR, a finding often seen in pediatric migraine patients. She was treated with daily Vitamin B2 and NSAIDs as-needed, with a good initial response. At 7 years of age, her headaches occurred 3-4 times/month. She also complained of increasing anxiety, fatigue as well as 2-3 episodes of paroxysmal confusion, right-handed clumsiness, and expressive aphasia lasting minutes, triggered by stress or crying. The patient nevertheless continued to have a normal development and exam. A repeat MRI at 6-years-of-age showed mild progression of the bifrontal subcortical white matter hyperintensities. An MRI at 7-years-of-age showed further progression of the same signal changes, with prominent tortuous signal voids within the deep grey matter, mostly the basal ganglia and non-visibility of the M1 and M2 segments of the MCA bilaterally, confirming the diagnosis of MMD. Discussion: Approximately 90% of pediatric patients with MMD are diagnosed solely after a cerebral ischemic infarct. Early symptoms and neuroimaging can often be subtle or misleading. The worsening of migraine-like headaches, along with anxiety, fatigue, and paroxysmal self-resolving episodes of aphasia should prompt re-investigation. Conventional angiography is the gold-standard imaging modalities for the diagnosis of MMD. Conventional nonquantitative brain-MRI, while limited, may provide useful clues to obtain an early diagnosis in patients, such as in our case. It allows visualization of late sequelae of previous strokes, including silent strokes, appearing as T2/FLAIR hyperintensities, brain atrophy and ventriculomegaly. Abnormal vasculature can appear as multiple tortuous flow voids in deep structures on T1 and T2 sequences. The "ivy sign", due to leptomeningeal engorgement, can be seen on postcontrast-MRI or FLAIR-MRI.

Subclinical pediatric moyamoya disease preceded by non-specific brain-MRI signal changes, anxiety, fatigue and recurrent migraines

Introduction Moyamoya disease (MMD) is a malignant cause of childhood stroke characterized by occlusion of the distal internal carotid arteries and branches by neointimal cells staining positive for smooth muscle cell (SMC) markers. ACTA2 encodes smooth muscle α-actin (α-SMA). A subset of ACTA2 mutations that predispose to thoracic aortic aneurysms and dissections including mutations altering arginine 179 are also associated with bilateral MMD-like occlusions. This study aims to elucidate the molecular pathogenesis of this disease to potentially inform the etiology of large vessel disease in stroke patients in the general population. Hypothesis We hypothesize that Acta2SMC-R179C/+ mice have disrupted differentiation of SMCs in cerebrovascular arteries, and thus the cells are primed to proliferate and migrate excessively, leading to MMD-like disease. Methods 
We generated patient-derived ACTA2 R179C and control induced pluripotent stem cell (iPSC) lines, and the Acta2SMC-R179C/+ mouse model, which expresses the Acta2 R179C mutation in SMCs via the SM-22-Cre-Lox system. Phenotypic differences between mutant and WT brains are characterized using micro CT, non-invasive cuff blood pressure measurements, and echocardiography. SMC phenotype is evaluated by protein expression of contractile genes, BrdU ELISA proliferation assay, Transwell migration assay, and immunofluorescence. Results/Anticipated Results: Patient-derived ACTA2 R179C iPSC-derived SMCs from patients show de-differentiation, continued expression of stem cell markers, and increased proliferation and migration. rt-PCR and sequencing of genomic DNA performed in aortic tissue and explanted SMCs confirms the presence of the mutation in the mutant mice and absence in mice with only the floxed allele (WT). Two-dimensional gel confirms presence of mutant α-SMA. Acta2SMC-R179C/+ mice display straightened and narrowed cerebral arteries at 8 weeks of age and hypotension but no aortic disease between 2 and 12 months of age. Explanted SMCs from Acta2SMC-R179C/+ mice exhibit decreased levels of differentiation markers and increased proliferation and migration. Acta2SMC-R179C/+ SMCs also show less robust and disrupted α-SMA filaments. Conclusion Acta2SMC-R179C/+ mice display MMD-like cerebrovascular disease and Acta2SMC-R179C/+ SMCs exhibit stem cell-like characteristics including de-differentiation, increased proliferation and migration.

Characterization of vascular disease in Acta2 SMC-R179C/+ mice

Introduction: Digital subtraction angiography (DSA) is commonly performed post pial synangiosis to establish the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. Our study aimed to identify whether arterial spin labelling (ASL) can predict post-operative angiogram grading. In addition, we aimed to identify whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared to patients who received ASL imaging and post-operative DSA. Methods: The medical records of patients undergoing pial synangiosis at a single institution were reviewed during a 10-year period. Results: Twenty-two patients were identified. Twenty-one hemispheres of 13 patients with "ASL only" and 14 hemispheres of 9 patients with "ASL + DSA" were analyzed. Both groups had similar rates of MRI evidence of acute or chronic stroke preoperatively; 61.9% in the ASL only group and 64.3% in the ASL + DSA group. All symptoms improved in frequency after intervention except categories of hemorrhage and non-chronic headaches. We found a significant correlation between revascularization observed on the DSA and the ASL graded by 3 neuroradiologists. The ASL grades in patients with a postoperative Matsushima grade indicating robust neovascularization were significantly higher than the ASL grades of patients with a poor postoperative Matsushima grade. Conclusions: Non-invasive ASL perfusion imaging had an association with post-operative DSA neoangiogenesis following pial synangiosis surgery. There were no significant stroke-risk differences between ASL and ASL + DSA cohorts. Both cohorts show significant improvement in pre-operative symptoms after surgery. Providers may consider obtaining a postoperative ASL MRI imaging in lieu of a catheter angiogram.

Arterial-spin labeling imaging for assessment of neoangiogenesis after pial synangiosis in pediatric moyamoya patients

Background and Aims: There are few retrospective studies describing clinical-radiological features and outcomes of children with Down Syndrome (DS) and Moyamoya (MM). Our aims are to present three cases of DS/MM from our institution, perform a review of the literature to compile similar case reports, determine if there is a clinical-radiological syndrome specific to DS/MM, and determine if this association is related to different outcomes. Methods: Our clinical database was reviewed between 2017-2019 for patients with DS/MM and cross-referenced with our radiology PACS database. We then reviewed the clinical data, imaging, treatment, and outcomes of previously 38-reported cases in English world literature with DS/MM from 1977 to 2018 using PubMed, Ovid, Medline, and Embase. Results: Case 1: Six year-old girl with focal status epilepticus, left MCA infarction and bilateral MM. Case 2: Three year-old boy with right hemiparesis, left MCA infarction and bilateral MM. Case 3: Thirteen year-old boy with right leg monoparesis, MRI-A: left ACA infarction and left ICA-MCA incipient MM. Case 1 & 2: managed with multiple burr holes (MBH). Case 1: surgery was performed 5 days after initial stroke due to rapid progression. Case 3: treated conservatively. On follow-up, all children had minimal deficit and continued on ASA. We reviewed 38 DS/MM cases found in the literature: 30 children presented with hemiparesis and 12 were treated surgically. Conclusions: Our findings are suggestive that DS/MM presentation and severity is variable with relatively good outcomes post-surgery. To our knowledge, Case 1 is the first reported child with DS/MM treated with urgent surgical MBH revascularization.


Stroke in children with moyamoya and down syndrome; 3 cases and review of the literature

Introduction: Moyamoya is a progressive steno-occlusive arteriopathy affecting the distal internal carotid artery and its branches. Associated to an underlying condition such as neurofibromatosis type 1 (MMS-NF1) or sickle cell disease (MMS-SCD), it is called moyamoya syndrome (MMS) while an isolated arteriopathy is referred to as moyamoya disease (MMD). It remains unknown whether the associated condition impacts its evolution. Objective: We hypothesize that MMD presents and evolves differently compared to MMS. Methods: We performed a single-center chart review of patients with moyamoya followed between 2003 and 2019. Clinical and radiographic features at diagnosis were obtained. Subsequent stroke or neurosurgery clinic visits were reviewed to identify ischemic event occurrence. Evidence of disease progression or new infarction was sought on follow up MRI studies. Group comparisons between children with MMD and MMS and between MMD and MMS subgroups (MMS-NF1 and MMS-SCD) were conducted using Pearson's Chi-squared, Fisher's Exact, Mann-Whitney U, or t test, as appropriate. Survival analysis by cerebral hemisphere using Cox regression were conducted to assess ischemic event occurrence, disease progression and silent infarction at follow-up. A false discovery rate (FDR) p-value adjustment for multiple comparisons with a q-value< 0.05 was applied. Results: One hundred and eleven patients were identified (MMD=49; MMS-NF=23; MMS-SCD=21). MMD presented more with TIA than MMS (22.45% vs MMS 4.84%, q=.02), while MMS-NF1 presented less with a stroke compared to the other groups (MMD 46.94% vs MMS-NF1 8.7% vs MMS-SCD 42.86%; q=0.0032). MMS-NF1 had more frequently unilateral disease (MMD 26.53% vs MMS-NF1 78.26% vs MMS-SCD 33.33%; q=.0003) and less infarcts (MMD 67.35% vs MMS-NF 26.09% vs MMS-SCD 80.95%; q=.0008) at diagnosis, while MMS-SCD were less likely to have an ivy sign (MMD67.35% vs MMS-NF1 52.17% vs MMS-SCD 9.52%, q=.0003). At follow-up, MMD patients were more likely to suffer another ischemic event compared to MMS patients (OR 1.92, p=.019), these events were mainly TIA (OR 2.5, p=.004). However, compared to the other groups, MMS-NF1 were less likely to have another TIA (OR 0.43, p=.045). Conclusion: MMS has varying phenotypes. MMS-NF1 tends to be unilateral with a lower burden of infarction at presentation, while an ivy sign is not a common feature of MM-SCD. Compared to MMS-SCD and MMD, MMS-NF1 is less likely to have further ischemic events.


Distinct clinical and radiographic presentation and evolution in childhood moyamoya syndrome

The symptoms of Cerebral Autosomal Disorder Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) do not typically manifest until midlife, but it has been diagnosed in a few children. Although she appeared healthy as a young child, BV had a heterozygous NOTCH3 gene mutation, and she experienced previously undetected strokes in the left frontal area. At 4 years 9 months, BV exhibited sudden onset aphasia and left hemiparesis, and she was found to have had acute ischemic strokes involving the right anterior cerebral artery (ACA) and left middle cerebral artery (MCA) territories. Extensive vascular disease involving the internal carotid arteries, right ACA, and left MCA was also observed. Within days, BV experienced new strokes in the right centrum semiovale, left interior frontal white matter, and right parietal lobe. She underwent encephaloduroarteriosynangiosis (EDAS) procedures in the left brain hemisphere at 5 years 0 months and in the right brain hemisphere at 5 years 3 months. BV experienced brain edema following the second procedure, and she was diagnosed with an acute ischemic stroke in the right MCA area affecting the majority of the temporal, parietal, and occipital lobes approximately 1 week following that procedure. BV had neuropsychological evaluations at 5 years 1 month, 5 years 10 months, and 7 years 1 month. At the time of her first evaluation, BV's visuospatial processing was average, but her verbal abilities were generally low average. She also exhibited severe inattention and impulsivity. After revascularization surgery and additional strokes, BV's language processing was stable, but her visuospatial processing had declined and was generally low average to mildly impaired. BV's cognitive functioning had remained generally stable with some areas of modest development at the time of her third neuropsychological evaluation at 7 years of age.

Neuropsychological function across time in a child with NOTCH3 mutation and CADASIL

Introduction: After sustaining brain injury, children have unique challenges to their activities of daily living compared to their healthy peers. These barriers are especially notable in the classroom, where a combination of physical, emotional, social, and cognitive skills is required to allow optimal performance. Medical staff and educational professionals share a common mandate to facilitate a child's best future. When injury interferes with a child's function, the achievement potential is threatened. Methods:This presentation is a review of return to school initiatives in place for children in the USA and medical provider utilization of these systems. We will present comparative models of educational inclusion services, identifying strengths and opportunities for expansion. Preliminary results from a survey of pediatric brain injury care providers will detail utilization of these services. Results: We describe a continuum of services divided into 4 discrete paradigms: brain injury-specific classroom, transitional school model, day rehabilitation program, and school outreach/community-based services. Programs vary dramatically in cost, payer, service coverage, and geographic availability. There is minimal data on efficacy and little agreement on endpoints to demonstrate successful intervention. A wide variation in access to and utilization of services is reflected in healthcare provider experience. Conclusions: There is a clear need to develop robust, available, and successful programs to return children to their education after brain injury.

 A review and survey of school inclusion after acquired brain injury

Background:Stroke is an important cause of mortality and morbidity in children. Aim:The aim of the study was to evaluate long-term neurological outcome in children with arterial ischemic stroke (AIS) and explore predictive factors that affect poor outcome. Patients:56 patients aged between one month and 17 years who were treated at M.Iashvili Children Central Hospital, Tbilisi, Georgia, with an onset of stroke from 2007 to 2017 were included. Methods:To explore predictive factors of outcome, the following data were collected: demographic characteristics, risk factors, the presenting signs, radiological features, and presence of stroke recurrence. Neurological status at discharge and long-term neurological outcome at least 1 year after stroke was evaluated according to Pediatric Stroke Outcome Measure (PSOM) subscale. Results: The reported outcome after childhood stroke was variable with long-term neurological deficits in one-third of patients (30.4%). The neurological outcome was worse in males, in patients with multiple stroke episodes, and in those with infractions involving a combination of cortical and subcortical areas. Conclusion:Pediatric AIS carries the risk of long-term morbidity, and neuroimaging has a predictive influence on outcome.

Predictors of neurological outcome of arterial ischemic stroke in children

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

Introduction Neurogenesis occurs after perinatal brain injury as a result of gene expression changes. DNA methylation and demethylation is one mechanism by which gene expression is regulated. Recent work has elucidated a role for Gadd45 proteins in mediating gene demethylation. Hypothesis We hypothesize that Gadd45 is responsible for active demethylation after perinatal hypoxia/ischemia and promotes neurogenesis as part of the regenerative response to injury. Methods We induced perinatal HI in 10 day old C57BL/6 pups by ligation of the right common carotid artery followed by exposure to hypoxia (8% O2/92% N2) for 45 minutes. The pups were sacrificed at 4 or 24 hours for molecular biology or immunohistochemistry. We used quantitative RT-PCR to study gene expression of Gadd45 family and TET family proteins. We evaluated targeted gene methylation status with methylation specific PCR and in situ DNA modifications using immonhistochemistry. Neurogenesis was quantified by 5-ethinyl-2'-deoxyuridine (EdU) incorporation in wild type and Gadd45b knockout mice. Results Gadd45 family mRNA is rapidly upregulated by 14-fold in the subventricular zone (SVZ) by 4 hours following perinatal HI, and remains upregulated at 24 hours. Small transient increases in expression were seen for Gadd45a and Gadd45g at 4 hours. There is no significant change in the expression of TET mRNA. Preliminary suggest specific demethylation of the BDNF promoter by 24 hours. Immunohistochemistry revealed increased expression of 5-hydroxymethylcytosine specifically within the SVZ progenitor cells, and neurogenesis was reduced in Gadd45-/- mice. Conclusion Perinatal HI induces upregulation of Gadd45b, which may contribute to demethylation of growth promoting genes in the neurogenic niche, driving the neurogenic response to perinatal hypoxic-ischemic brain injury.

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