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

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Abstract 51: The Incidence of Perinatal Stroke is 1:1200 Live Births: A Population-Based Study in Alberta Canada

Stroke ◽

10.1161/str.51.suppl_1.51 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Mary J Dunbar ◽

Adam Kirton

Keyword(s):

Ischemic Stroke ◽

Hemorrhagic Stroke ◽

Tertiary Care ◽

Population Based ◽

Stroke Incidence ◽

Perinatal Stroke ◽

Live Births ◽

Cerebral Sinovenous Thrombosis ◽

Southern Alberta ◽

Disease Specific

Introduction: Perinatal stroke encompasses six cerebrovascular syndromes which occur between the 20 th week of gestation and the 28 th post-natal day. Morbidity is significant including motor, language, behavioral, and cognitive challenges, as well as epilepsy. Acute presentations include neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis (CSVT), and neonatal hemorrhagic stroke (NHS). Delayed presentations include arterial presumed perinatal ischemic stroke (APPIS), periventricular venous infarction (PVI), and presumed perinatal hemorrhagic stroke (PPHS). Inconsistent terminology and lack of population-based cohorts 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, Canada (population ~2.1 million). Leveraging universal health care at a single tertiary care pediatric center facilitated true population-based epidemiology. Patients included had neuroimaging-confirmed perinatal stroke. Case acquisition included exhaustive retrospective hospital and ICD code searches (1990-2008) and prospective enrollment from all NICU and neurology/stroke clinics (2008-2018). Live birth rate denominators were determined from the provincial census. Results: The overall incidence of perinatal stroke in Southern Alberta from 2008-2018 was 81 cases per 100,000 live births, or 1 case per approximately 1200 live births. The incidence of NAIS was 31 per 100,000 (~1/3000), APPIS was 11 per 100,000 (~1/9000), PVI was 18 per 100,000 (~1/5500), and CSVT was 10 per 100,000 (~1/9800). The incidence of NAIS increased after implementing prospective case identification, from 8.5 (95% CI 5.3-11.6) per 100,000 to 31 per 100,000 (95% CI 24.4-38.2), p<0.00001, the remainder of stroke subtypes were stable over time. 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.

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Abstract 29: Common Thrombophilias are not Associated With Specific Perinatal Stroke Diseases

Stroke ◽

10.1161/str.47.suppl_1.29 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Colleen Curtis ◽

Michael Leaker ◽

Patti Massicotte ◽

Amalia Floer ◽

Aleksandra Mineyko ◽

...

Keyword(s):

Ischemic Stroke ◽

Factor V Leiden ◽

Population Based ◽

Factor V ◽

Arterial Ischemic Stroke ◽

Chi Square ◽

Perinatal Stroke ◽

Potential Contributor ◽

Prothrombin Gene ◽

Disease Specific

Background: Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, including arterial and venous ischemic injuries, but pathophysiological mechanisms are poorly understood. Thrombophilia has long been considered a potential contributor but population-based, controlled, disease-specific studies are limited. Hypothesis: Thrombophilia is uncommon in children with perinatal stroke. Methods: Subjects were recruited from the Alberta Perinatal Stroke Project, a population-based cohort with MRI-classified perinatal strokes: neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), and fetal periventricular venous infarction (PVI). Standardized thrombophilia evaluations were performed prospectively (2008-2015) after 12 months of age on stroke cases and matched controls. Measures included protein C and S, antithrombin III, factors VIII/IX/XI, fibrinogen, lipoprotein a, lupus anticoagulant, and antiphospholipid antibodies. Groups were compared (ANOVA, chi-square), corrected for multiple comparisons. Results: A total of 252 children were studied (58 NAIS, 48 APPIS, 69 PVI, 77 controls). Of 14 parameters, no differences were observed in 12 including all common thrombophilias. Prothrombin times were shorter in arterial strokes compared to controls (p<0.001). Factor XI levels were higher in arterial and PVI strokes compared to controls (p=0.004). Rates of genetic thrombophilias including factor V Leiden, prothrombin gene, and MTHFR were low and comparable to population rates. Conclusion: Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated.

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Perilesional Gliosis Is Associated with Outcome after Perinatal Stroke

Journal of Pediatric Neurology ◽

10.1055/s-0041-1728687 ◽

2021 ◽

Author(s):

Sabrina Yu ◽

Charissa Lam ◽

Siddharth Shinde ◽

Andrea M. Kuczynski ◽

Helen L. Carlson ◽

...

Keyword(s):

Ischemic Stroke ◽

Brain Injury ◽

Motor Function ◽

Developmental Plasticity ◽

Infarct Volume ◽

Population Based ◽

Arterial Ischemic Stroke ◽

Cross Sectional ◽

Perinatal Stroke ◽

Focal Brain Injury

AbstractPerinatal ischemic stroke results in focal brain injury and life-long disability. Hemiplegic cerebral palsy and additional sequelae are common. With no prevention strategies, improving outcomes depends on understanding brain development. Reactive astrogliosis is a hallmark of brain injury that has been associated with outcomes but is unstudied in perinatal stroke. We hypothesized that gliosis was quantifiable and its extent would inversely correlate with clinical motor function. This is a population-based, retrospective, and cross-sectional study. Children with perinatal arterial ischemic stroke (AIS) or periventricular venous infarction (PVI) with magnetic resonance (MR) imaging were included. An image thresholding technique based on image intensity was utilized to quantify the degree of chronic gliosis on T2-weighted sequences. Gliosis scores were corrected for infarct volume and compared with the Assisting Hand and Melbourne Assessments (AHA and MA), neuropsychological profiles, and robotic measures. In total, 42 children were included: 25 with AIS and 17 with PVI (median = 14.0 years, range: 6.3–19 years, 63% males). Gliosis was quantifiable in all scans and scores were highly reliable. Gliosis scores as percentage of brain volume ranged from 0.3 to 3.2% and were comparable between stroke types. Higher gliosis scores were associated with better motor function for all three outcomes in the AIS group, but no association was observed for PVI. Gliosis can be objectively quantified in children with perinatal stroke. Associations with motor outcome in arterial but not venous strokes suggest differing glial responses may play a role in tissue remodeling and developmental plasticity following early focal brain injury.

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Population-based study of ischemic stroke risk after trauma in children and young adults

Neurology ◽

10.1212/wnl.0000000000004708 ◽

2017 ◽

Vol 89 (23) ◽

pp. 2310-2316 ◽

Cited By ~ 5

Author(s):

Christine K. Fox ◽

Nancy K. Hills ◽

David R. Vinson ◽

Adam L. Numis ◽

Rochelle A. Dicker ◽

...

Keyword(s):

Ischemic Stroke ◽

Stroke Risk ◽

Motor Vehicle ◽

Care Delivery ◽

Population Based ◽

Young Cohort ◽

Trauma Patients ◽

Arterial Ischemic Stroke ◽

Vascular Abnormality ◽

Stroke Incidence

Objective:To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort.Methods:We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997–2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression.Results:From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0–5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1–14.9) and neck (OR 5.6, CI 1.03–30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation).Conclusions:Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected.

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Epidemiology of neonatal stroke: A population-based study

Paediatrics & Child Health ◽

10.1093/pch/pxy194 ◽

2019 ◽

Vol 25 (1) ◽

pp. 20-25

Author(s):

Breanna Clive ◽

Michael Vincer ◽

Tahani Ahmad ◽

Naeem Khan ◽

Jehier Afifi ◽

...

Keyword(s):

Nova Scotia ◽

Standardized Testing ◽

Hemorrhagic Stroke ◽

Population Based ◽

Imaging Features ◽

Arterial Ischemic Stroke ◽

Stroke Subtype ◽

Neurodevelopmental Outcomes ◽

Neonatal Stroke ◽

Cerebral Sinovenous Thrombosis

Abstract Objective The goal of this study was to obtain population-based data on the incidence, clinical presentation, management, imaging features, and long-term outcomes of patients with all types of neonatal stroke (NS). Methods Full-term neonates with NS born between January 2007 and December 2013 were identified through the Nova Scotia Provincial Perinatal Follow-up Program Database. Perinatal data and neonatal course were reviewed. Neurodevelopmental outcomes were assessed at 18 and 36 months of age using standardized testing. Results Twenty-nine neonates with NS were identified during the study period, giving an incidence of 47 per 100,000 live births in Nova Scotia. Arterial ischemic stroke was the most common stroke type (76%), followed by neonatal hemorrhagic stroke (17%), then cerebral sinovenous thrombosis (7%). The majority of neonates presented with seizures (86%) on the first day of life (76%). At 36 months of age, 23 (79%) of the children had a normal outcome, while 3 (10%) were diagnosed with cerebral palsy (2 with neonatal arterial stroke and one with neonatal hemorrhagic stroke) and 3 (10%) had recurrent seizures (1 patient from each stroke subtype group). Conclusion The incidence of NS in Nova Scotia is higher than what has been reported internationally in the literature. However, the neurodevelopmental outcomes at 3 years of age are better. Further studies are required to better understand the reasons for these findings.

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Pediatric Stroke: Clinical Findings and Radiological Approach

Stroke Research and Treatment ◽

10.4061/2011/172168 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Giuseppe Lanni ◽

Alessia Catalucci ◽

Laura Conti ◽

Alessandra Di Sibio ◽

Amalia Paonessa ◽

...

Keyword(s):

Ischemic Stroke ◽

Magnetic Resonance ◽

Hemorrhagic Stroke ◽

Clinical Findings ◽

Pediatric Stroke ◽

Arterial Ischemic Stroke ◽

Venous Circulation ◽

Cerebral Sinovenous Thrombosis ◽

First Choice ◽

Sinovenous Thrombosis

This paper focuses on radiological approach in pediatric stroke including both ischemic stroke (Arterial Ischemic Stroke and Cerebral Sinovenous Thrombosis) and hemorrhagic stroke. Etiopathology and main clinical findings are examined as well. Magnetic Resonance Imaging could be considered as the first-choice diagnostic exam, offering a complete diagnostic set of information both in the discrimination between ischemic/hemorrhagic stroke and in the identification of underlying causes. In addition, Magnetic Resonance vascular techniques supply further information about cerebral arterial and venous circulation. Computed Tomography, for its limits and radiation exposure, should be used only when Magnetic Resonance is not available and on unstable patients.

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Perinatal thrombosis: implications for mothers and neonates

Hematology ◽

10.1182/asheducation-2015.1.48 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 48-52 ◽

Cited By ~ 3

Author(s):

Sarah H. O'Brien

Keyword(s):

Ischemic Stroke ◽

Treatment Strategies ◽

Perinatal Period ◽

Clinical Equipoise ◽

Arterial Ischemic Stroke ◽

Perinatal Stroke ◽

Behavioral Challenges ◽

Cerebral Sinovenous Thrombosis ◽

Sinovenous Thrombosis

Abstract Stroke is more likely to occur in the perinatal period than any other time in childhood, and these events can lead to a lifetime of intellectual and motor disabilities, epilepsy, and behavioral challenges. This review describes the epidemiology and natural history of perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT), risk factors for these complications, recent evidence regarding treatment strategies, and current gaps in knowledge. Existing evidence demonstrates the multifactorial etiology of symptomatic ischemic stroke in neonates, which includes a combination of maternal, delivery, and neonatal factors. The importance of inherited thrombophilia in the pathophysiology and long-term outcomes of perinatal stroke requires additional study. At this time, there is no evidence to support routine extensive thrombophilia screening outside of a research setting. Despite the frequency of perinatal stroke and its association with substantial morbidity, treatment strategies are currently limited, and prevention strategies are nonexistent. Anticoagulation is rarely indicated in PAIS, and more work needs to focus on neuroprotective prevention and alternate treatment strategies. Anticoagulation does appear to be safe in CSVT and may prevent thrombus progression but clinical equipoise remains, and clinical trials are needed to obtain evidence regarding short- and long-term efficacy outcomes.

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Neurocognitive outcome in a 6-year-old girl with a history of perinatal stroke

European Psychiatry ◽

10.1016/s0924-9338(11)72805-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1100-1100

Author(s):

A. Matos-Pires ◽

N. Cardoso-Pereira

Keyword(s):

Working Memory ◽

Ischemic Stroke ◽

Verbal Learning ◽

Arterial Ischemic Stroke ◽

Intellectual Performance ◽

Perinatal Stroke ◽

Intellectual Outcome ◽

History Of ◽

Perinatal Arterial Ischemic Stroke

Perinatal Stroke involves an often poorly understood neurocognitive events affecting the fetus and the new born with a potential for serious intellectual outcome.Our aim is to present a case study on the issue of neurocognitive defects on domains such as intellectual performance, attention and vigilance, executive functioning, visual perception, speed of processing, verbal learning and memory, and working memory on a 6 year old girl with perinatal arterial ischemic stroke.

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Head circumference trajectory in children with perinatal stroke

Journal of Child Neurology ◽

10.1177/0883073821996103 ◽

2021 ◽

pp. 088307382199610

Author(s):

Amanda Leong ◽

Amalia Floer ◽

Adam Kirton ◽

Aleksandra Mineyko

Keyword(s):

Ischemic Stroke ◽

Head Circumference ◽

Developmental Outcomes ◽

Normal Growth ◽

Fisher Exact Test ◽

Arterial Ischemic Stroke ◽

Neurodevelopmental Outcomes ◽

Perinatal Stroke ◽

Head Growth ◽

Poor Outcome

Background: Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes. Methods: Patients with magnetic resonance imaging (MRI)–confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed t test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference. Results: Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories ( P < .05) with a large effect size (Cohen d >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference ( P < .05). Conclusion: Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome.

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Symptom patterns in childhood arterial ischemic stroke: Analysis of a population-based study in Germany

Klinische Pädiatrie ◽

10.1055/a-0684-9794 ◽

2018 ◽

Vol 230 (06) ◽

pp. 319-325

Author(s):

Lucia Gerstl ◽

Raphael Weinberger ◽

Rüdiger von Kries ◽

Florian Heinen ◽

Andreas Sebastian Schroeder ◽

...

Keyword(s):

Ischemic Stroke ◽

Clinical Symptoms ◽

Population Based ◽

Case Definition ◽

Childhood Stroke ◽

Older Children ◽

Arterial Ischemic Stroke ◽

Focal Neurological Deficit ◽

Symptom Patterns ◽

Specific Symptoms

Hintergrund Die zeitliche Verzögerung zwischen Symptombeginn und Diagnose ist eine Herausforderung in der Behandlung von Kindern mit arteriell ischämischem Schlaganfall. Frühere Studien zur klinischen Präsentation beschäftigten sich v. a. mit kumulativen Symptomen. Zielsetzung Ziel dieser Studie ist es, mögliche Symptommuster aufzuzeigen. Methoden In einer aktiven Beobachtungsstudie zwischen 01/2015 und 12/2016 (ESPED-Studie) wurden Kinder mit Erstdiagnose eines arteriell ischämischen Schlaganfalls eingeschlossen. Isoliert auftretende Erstsymptome wurden verschiedenen Symptomkombinationen gegenübergestellt. Zudem wurde untersucht, inwieweit ein als „akut“ oder „progredient“ klassifiziertes Auftreten der Symptome Rückschlüsse auf die zugrundeliegende Ätiologie erlaubt. Ergebnisse Es wurden 99 Kinder in die Studie eingeschlossen. Unabhängig vom Alter traten überwiegend fokale Symptome auf (86%). Krampfanfälle als Initialsymptom wurden insbesondere bei Säuglingen beschrieben (67%), wohin-gegen diffuse, unspezifische Symptome vor allem bei Vorschulkindern (38%) und älteren Kindern (59%) auftraten. Isoliert traten fokale Symptome bei 37 Kindern auf, 48 Kinder zeigten zusätzlich unspezifische Symptome, darunter auch 9 Kinder mit Krampfanfällen. Isolierte unspezifische Symptome zeigten sich lediglich bei 7 Kindern, 2 Kinder wurden nur mit Krampfanfällen symptomatisch. Die Akuität des Symptombeginns wurde bei 53/78 als „akut“ und bei “25/78 Fällen als „progredient“ klassifiziert, lieferte jedoch keinen Hinweis auf die zugrundeliegende Ätiologie. Schlussfolgerung Jedes neue fokal neurologische Defizit sollte unabhängig vom Auftreten (isoliert oder kombiniert, akut oder progredient) an einen kindlichen Schlaganfall denken lassen. Background Time delay between onset of clinical symptoms and diagnosis is a challenge in childhood arterial ischemic stroke. Most previous studies reported cumulative symptoms. Objective We attempted to identify typical symptom patterns and assessed their emergence in childhood stroke. Methods Prospective active surveillance in ESPED, a hospital based Pediatric Surveillance Unit for rare diseases in Germany, between January 2015 and December 2016. Case definition: first diagnosis of a radiologically confirmed arterial ischemic stroke. Symptom patterns were identified as occurring in isolation or in combination. We distinguished acute vs. progressive onset. We ascertained risk factors to identify the possible etiology. Results 99 children with childhood arterial ischemic stroke were reported. Focal symptoms were the predominant presenting feature (86%), independent of age. Seizures were more often seen in infants < 1 year (67%), whereas diffuse symptoms were more present in pre-school children (38%) and older children (59%). 37 children had focal features alone and 48 additional non-specific features, including 9 with seizures. Isolated non-specific features accounted for 7 cases, and 2 children had (focal) seizures as the only symptom. In 77% of all cases at least one risk factor was identified. The emergence of symptoms was acute in 53/78 cases and progressive in 25/78 cases. The pattern of emergence was unrelated to the underlying etiology. Conclusions Any new focal neurological deficit in isolation, or associated with seizures or further non-specific symptoms should alert to childhood stroke.

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