United States

IPSO 2021

Embolectomy in pediatric stroke: who, when, where, why - Manoëlle Kossorotoff

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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>. 



technical paper

International Perspective: Pediatric Stroke in Nigeria

Introduction: Management after hemorrhagic stroke from cerebral arteriovenous malformation (AVM) rupture remains controversial due to strategies to prevent hemorrhagic expansion while maintaining cerebral autoregulation (CA). We investigated associations of hemodynamics on outcomes after pediatric AVM rupture. Hypotheses: Measures of CA, baroreflex sensitivity (BRs) and heart rate variability (HRV) are associated with outcome at 12 months after pediatric cerebral AVM rupture. Methods: Children (<18 years old) with ruptured cerebral AVMs at a single critical care unit over 5 years were retrospectively analyzed. Continuous measurements of data including arterial blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and heart rate (HR) were evaluated. CA measures include pressure reactivity index (PRx), weighted pressure-reactivity index (wPRx), pulse-amplitude index (PAx), and correlation coefficient between ICP pulse amplitude (AMP) and CPP (RAC). Model-based indices of HRV, BRs, CA and estimations of optimal CPP (CPP-Opt) were computed along with percent of time below lower limits of autoregulation (LLA). Outcomes were determined using Pediatric Glasgow Outcome Score - Extended (GOSE-Peds) at 12 months. Patients with scores below 5 were grouped as "unfavorable outcomes". Association of biomarkers with outcome was determined with Wilcoxon singed rank test. Results: 14 children who underwent multimodal monitoring (6 female; mean [IQR] age, 10.57 [1.5]) were included. 8/14 children underwent intraparenchymal ICP monitoring from which CA was measured. Unfavorable outcomes were associated with lower median BRs values as compared to favorable outcomes (p=0.001) and lower HRV as compared to favorable outcome (p=0.026). Favorable outcome was consistent with decreased percent time below LLA based upon PAx and RAC, although this study was not powered for statistical significance (p=0.057). Conclusion: Decreased BRs and HRV were associated with unfavorable outcomes in children after hemorrhagic stroke from AVM rupture. Prospective studies are warranted to understand CA and its impact on outcomes.

Multimodal assessment of cerebral hemodynamics after pediatric hemorrhagic stroke secondary to cerebral arteriovenous malformation rupture

Introduction: Understanding non-traumatic pediatric intracerebral hemorrhage (pICH) etiological spectrum is key to diagnostic work-up and care pathway orientation. We aimed to evaluate the etiologic spectrum of diseases underlying pICH. Patients and Methods Children treated at our institution for a pICH were included in an inception cohort initiated in 2008, retrospectively inclusive to 2000 and analyzed in October 2019. We then conducted a systematic review of relevant articles published between 1990 and 2019, identifying cohorts with pICH patient. Identified populations, and patients from our cohort were pooled in multi category diagnosis meta-analysis. Results A total of 243 children with pICH were analyzed in the cohort study. The final primary diagnosis was an intracranial vascular lesion in 190 patients (78.2%), a complication of a cardiac disease in 17 (7.0%), a coagulation disorder in 14 (5.8%). Hematologic and cardiologic etiologies were disproportionately more frequent in children younger than 2 years old (p<0.001). The systematic review identified 1309 children in 23 relevant records, pooled in meta-analysis. Overall there was important heterogeneity. The dominant etiology were vascular lesions, with an aggregate prevalence of 0.59 [95% confidence interval: 0.45-0.64, p=0,001 Q:302.8, I²: 92%]. In eighteen studies reporting detailed etiological spectrum, arterio-venous malformation represented the dominant etiology (68.3% of all vascular causes, [95%CI 64.2 - 70.9%), followed by cavernoma (15.7% [95%CI 13.0 - 18.2%]). Conclusion The most frequent etiology of pICH are brain arteriovenous malformations. The probability of an underlying vascular etiology increases with age, and conversely hematologic and cardiac causes are dominant causes in children younger than 2 years old.

Etiology of intracerebral hemorrhage in children:cohort study, systematic review & meta-analysis

Introduction: The clinical outcome of pediatric intracerebral hemorrhage (pICH) is scantly reported in a comprehensive way. In this cohort study of patients with pICH, systematic review and meta-analysis, we aimed at describing the basic clinical outcomes after pICH. Methods Children treated at our institution for a pICH were included in an inception cohort initiated in 2008, retrospectively inclusive to 2000 and analyzed in October 2019. We then conducted a systematic review of relevant articles published since 1990, Identified populations, and patients from our cohort were pooled in multi category diagnosis meta-analysis, and analyzed with regards to clinical outcomes. Results Amongst 243 children screened for inclusion, 231 patients were included and analysed. Median age at ictus was 9.6 years [interquartile range: 4.6 -12.5], and 128 (53%) patients were male. After a median of 33 months of follow-up (interquartile range 13-63), 132 patients (57.4%) had a favourable clinical outcome, of which 58 (44%) had no residual symptom. Amongst 2622 records screened, we retained 24 studies with available data for the final analyses. Overall, the aggregate proportion of children with complete recovery was 26% [95% confidence interval: 16.4-34.2%, Q:170, I²: 89%], and of those with residual deficits 52.7% [95% confidence interval: 39.7-60.3%, Q:170, I²: 89%]. When pooled with our cohort, the aggregate case fatality at last follow up was 15.3% [95% confidence interval: 11.2-19.9%, Q:191, I²: 87%]. Conclusion Here we showed that mortality affects 1 in 6 children after pICH, and that the majority of children have residual neurological deficits at latest follow up. Complementary data from the cohort study are to be presented.

Mortality and functional outcome after pediatric intracerebral hemorrhage: a cohort study, systematic review and meta-analysis

Introduction: Hemorrhage expansion (HE) is a known predictor of clinical deterioration, and poor clinical outcome following admission after an intracerebral hemorrhage (ICH) in adults, but remains poorly reported in children. In a large inception cohort of children with ICH, we aimed to explore the prevalence of HE, its associations with clinical outcomes and its clinical-imaging predictors. Patients and Methods The report is based on an inception registry of children presenting with an ICH at a single quaternary university pediatric hospital (Necker Enfants Malades, Paris, France), retrospectively inclusive to January 2000. The study sample was restricted to children with two CT scans within 72 hours of symptoms onset available for re-asessement, and a clinical follow-up duration of more than 12 months. Hemorrhage expansion was defined as being clinically significant if the difference between follow-up and baseline ICH volumes exceeded 12.5cc or 33% of the baseline volume. Results Fifty two children met inclusion criteria, amongst which 8 (15%) demonstrated hemorrhage expansion. Children with hemorrhage expansion had more frequent coagulation disorders (25,0% vs 2,3%, p=0,022), focal deficits at presentation (75,0% vs 43,2%, p=0,08) and infra-tentorial ICH (25,0% vs 9,1%, p=0,01). After adjustment for variables associated with HE in univariable analyses at a p<0.1, only the presence of coagulation disorders at baseline remained independently associated with HE (adjusted OR 14,4 95%CI [1,04-217], p=0,048). HE was independently associated with poor (KOSCHI < 5A, adjusted OR 5,77 95%CI [1,01-38,95], p=0,043) as well as severe (KOSCHI < 4A, aOR 20,22 95%CI [3,06-133,68], p= 0,002) clinical outcomes Conclusion Hemorrhage expansion frequency is unexpectedly high after a pediatric ICH, affecting over 15% of children in our sample, and was found to be strongly associated with poorer clinical outcome, regardless of its definition.

Hemorrhage expansion after pediatric intracerebral hemorrhage

Intro Cerebral sinus vein thrombosis (CSVT) is a type of stroke consisting in thrombosis of the dural sinus and/or cerebral veins. The estimated incidence in children is 0.6 per 100,000 children per year however the symptoms and presentations are variable among all age ranges raising the concern for missed diagnosis. Despite new progress on pediatric stroke, CSVT is under-recognized and its risk factors are not well established. Hypothesis To describe risk factors of pediatric CSVT together with its signs and symptoms at presentation. Methods A single-center review of pediatric patients (<18 years) with radiographically confirmed CSVT between 2008 and 2018, seen by the Hematology service at Cook Children's Medical Center were identified through the Cook Children's database. Results There were 87 patients identified. Symptoms at diagnosis were nausea/vomiting (33%), headache (32%), fever (29%) and neurologic deficits (25%). The most common neurologic deficits reported were altered mental status (9%) and increased intracranial pressure (9%) followed by focal weakness/hemiparesis (5%), cranial nerve palsy (5%), diplopia (4%), papilledema (4%) and ataxia (2%) (Table 1). Comorbidities included mastoiditis (26%), otitis media (24%), Lemierre's syndrome (10%), retropharyngeal abscess (5%) and severe anemia (hemoglobin < 7 g/dl; 5%) (Table 2). Results of thrombophilia work up and sinuses involved are included in Figure 1 and Figure 2, respectively. Conclusions Infectious causes such as otitis media, mastoiditis and Lemierre's syndrome can be common contributors of pediatric CSVT. Anemia is a little known independent risk factor for thrombosis, especially CSVT, and presented in 5% of our patients. Not all patients with CVST underwent a complete thrombophilia evaluation, but thrombophilia was still rare finding. We suggest that if these infections are diagnosed, there should be a high index of suspicion for CSVT even in the absence of neurological deficits/symptoms.

Risk factors for pediatric cerebral sinus vein thrombosis

Introduction: Children with congenital heart disease (CHD) may be at increased risk for cerebral sinus venous thrombosis (CSVT). The incidence of CSVT in neonates undergoing repair of congenital heart disease has been reported to be as high as 28%. Hypothesis: We hypothesize that the incidence of CSVT in this population is lower than previously described. Methods: Neonates who had CHD repair with cardiopulmonary bypass (CPB) in the first 30 days of life between 2013 and 2019 were identified from a prospective cardiac surgery database. Patients who had a post-operative brain MRI were identified from a prospective institutional database. Demographic, clinical, and surgical data were obtained from the cardiac surgery database and the medical record. Imaging was reviewed by a pediatric neuroradiologist. Results: One hundred eighty-four neonates who had repair of CHD using CPB between 2013 and 2019 had a post-operative brain MRI. CSVT was identified in 4.3% (n=8) and only in those with transposition of the great arteries with an intact ventricular septum (TGA-IVS), interrupted aortic arch (IAA), or coarctation of the aorta (CoA). TGA-IVS (p=0.007) and IAA (p=0.023) were associated with an increased risk for CSVT. Other risk factors for CSVT included longer cross-clamp time (98 minutes [interquartile range (IQR) 77.5-120] v. 67 minutes [IQR 44-102], p=0.03) and shorter time between surgery and MRI (10 days [IQR 7-12.5] v. 20 days [IQR 12-35], p=0.004). CSVT involved the transverse sinus in all patients. Five patients (62.5%) were treated with anticoagulation; four (80%) had complete resolution of their thrombus and one (20%) had partial resolution. Three patients were not treated, all of whom had at least partial resolution of their thrombus. No patient had complications of their thrombus or of anticoagulation. Conclusion: We identified a low incidence (4.3%) of CSVT in neonates with CHD undergoing surgery with CPB in the first 30 days of life. All CSVTs were asymptomatic and discovered on routine post-operative imaging. CSVT was found only in patients with TGA, IAA, or CoA and was associated with a shorter time between surgery and imaging. At least partial recanalization was universal, regardless of anticoagulation. Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in neonates undergoing CPB for repair of CHD.

Cerebral venous sinus thrombosis in infants after surgery for congenital heart disease

Introduction: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in children, presentation is variable but can include seizures and other neurologic symptoms. Anticoagulation is the cornerstone of treatment and endovascular interventions can also be used for management. Bivalirudin is a direct thrombin inhibitor used for the treatment of thrombosis in children especially as an alternative to heparin in heparin induced thrombocytopenia (HIT). It has not been well studied in children with CVT. Objectives: To report a case of successful treatment of CVT stroke in a pediatric patient with bivalirudin Case: 16-year-old female with polycystic ovarian syndrome on oral contraceptives as well as obesity with BMI of 43 who presented to the pediatric intensive care unit as a transfer from a local hospital. She presented there with altered mental status, seizures and acute respiratory failure. She arrived at our ICU intubated and sedated. MRI/MRA Brain/Neck were obtained that showed complete thrombosis of the left transverse sinus, sigmoid sinus and superior internal jugular vein down to the C1 level with partial thrombosis extending down to the C1-C2 level. She was started on bivalirudin after discussion with the Neurology, coagulation and neuro radiology teams. Neurologic exam after extubation was within normal limits. She continued bivalirudin for 6 days and was transitioned to rivaroxaban at discharge. She had no adverse effects while on anticoagulation. Thrombophilia work up revealed she is heterozygous for factor V Leiden. Discussion This case highlights the successful use of bivalirudin for treatment of CVT in a pediatric patient. In addition to its use for treatment of HIT, bivalirudin has been used in pediatric patients on extracorporeal membrane oxygenation (ECMO). However, this is the first documented case report of treatment of a pediatric patient with CVT with bivalirudin. Further prospective studies are needed to clarify its utilization in pediatrics.

Successful treatment of pediatric cerebral venous thrombosis stroke with Bivalirudin

Introduction: Direct oral anticoagulants (DOACs) are becoming an acceptable alternative to vitamin K oral antagonists and heparin derivatives in the treatment of thrombosis in adults. However, the recommended treatment for cerebral sinus venous thrombosis (CVT) remains coumadin or low molecular-weight heparin.1 Though there are no reports of DOAC use in pediatric CVT, they are appealing as drug levels do not have to be followed, food and medication interactions are minimal, and they are taken orally. We report two adolescents with CVT treated with apixaban. Case 1: A 16 year-old girl presented with three days of headache after an increase in estrogen content of oral contraceptive pills. Her head CT and CT angiogram were consistent with CVT of the majority of the superior sagittal sinus without venous infarct. She was started on enoxaparin before transitioning to apixaban 5 mg twice daily the next day. She tolerated the medication well. She had resolution of her CVT on MRA after 3 months, so her apixaban was discontinued. Case 2: An 18 year-old man with trisomy 21 and acute lymphocytic leukemia presented with headache and left-sided weakness 3 weeks after his 2nd PEG-asparaginase dose. Imaging showed a right parenchymal hemorrhage CVT of the left sigmoid, transverse and superior sagittal sinuses. He was initially treated with a heparin drip for 24 hours, then switched to apixaban 10 mg twice daily for 6 days, then 5 mg twice daily, which he has tolerated well. There was no progression of CVT after 6 months of treatment. Due to lack of recanalization and need for further PEG-aspariginase, he will remain on apixaban for one year. Discussion: We report two adolescents with CVT treated with apixaban, one with recanalization and the other with symptoms resolution and lack of clot progression. Apixaban was well-tolerated without bleeding. Prospective data are needed comparing heparin-based and oral vitamin K antagonist treatments to DOACs in this population. 1. Ferro JM, Bousser MG, Canhao P, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. European journal of neurology. 2017;24(10):1203-1213.

Apixiban therapy of adolescent cerebral sinus venous thrombosis

Introduction: Cerebral venous thrombosis is a rare cause of stroke in the neonatal and paediatric population. In the last 2 decades there has been significant growth in the study and diagnosis of this rare disease in pediatrics. We are interested in sharing our experience in the management of this pathology in order to contribute to the evidence of the effectiveness and safety of the treatment. Objective: to share our experience in the management of cerebral venous thrombosis in pediatrics. Method: A descriptive longitudinal, prospective and retrospective study was conducted from January 2015 to DEcember 2020 evaluating patients with cerebrovascular disease. Of 88 follow-up patients with cerebrovascular disease 14 patients had cerebral venous thrombosis. Children from 0 days of life to 18 years of life were included who had acute neurological signs (altered consciousness, headache, seizures or neurological focal signs) with radiological confirmation with resonance or tomography venography, where thrombus or interruption of venous flow was evident, or not by associating infarction or bleeding. Results: 14 patients were evaluated, 9 of whom were evaluated from baseline and 3 were evaluated after the acute period. The majority were male( 8/ 61.5%). More than 50% occurred in the neonatal period. Of the predisposing factors found: 2 patients associated with head and neck infections; 1 meningitis; 1 sepsis. 6 had heart disease, 1 ischemic hypoxic encephalopathy; 1 required respiratory ECMO. Most common clinical presentation were: impaired consciousness, headache, seizures, apnea. One patient was detected by prenatal eco Received treatment. 11/13. None had post-anticoagulant bleeding. 8 patients had treatment during 6 weeks or 3 month according to age; 2 followed was lost. 3 to die before assessing whether they managed to resolve thrombosis.; 1 required prolonging the anticoagulation time according to their age. Conclusions: so far there are few series of patients published with this pathology. It is important to communicate the experience in order to obtain strong information about the efficacy and safety of the treatment.

Embolectomy in pediatric stroke: who, when, where, why - Manoëlle Kossorotoff

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International Perspective: Pediatric Stroke in Nigeria

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Embolectomy in pediatric stroke: who, when, where, why - Manoëlle Kossorotoff

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Next from IPSO 2021

International Perspective: Pediatric Stroke in Nigeria

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Pediatric code stroke: a single center experience

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