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

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

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.272 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S16-S16

Author(s):

M Dunbar ◽

J Hodge ◽

A Floer ◽

A Kirton

Keyword(s):

Ischemic Stroke ◽

Hemorrhagic Stroke ◽

Case Series ◽

Population Based ◽

Arterial Ischemic Stroke ◽

Stroke Incidence ◽

Perinatal Stroke ◽

Cerebral Sinovenous Thrombosis ◽

Southern Alberta ◽

Disease Specific

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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Factor V Leiden and Prothrombin Gene G 20210 A Variant in Children with Ischemic Stroke

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615355 ◽

1998 ◽

Vol 80 (11) ◽

pp. 763-766 ◽

Cited By ~ 83

Author(s):

Z. Bodó ◽

Jutta Plotho ◽

W. Streif ◽

Ch. Male ◽

G. Bernert ◽

...

Keyword(s):

Risk Factor ◽

Ischemic Stroke ◽

Acute Stroke ◽

Neonatal Period ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Exact Test ◽

Multicenter Survey ◽

Prothrombin Gene

SummaryObjective: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. Patients: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. Results: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer’s exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer’s exact test, p = 0.38). Conclusion: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.

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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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Factor V Leiden and Antiphospholipid Antibodies in Either Mothers or Infants Increase the Risk for Perinatal Arterial Ischemic Stroke

Stroke ◽

10.1161/strokeaha.108.527283 ◽

2009 ◽

Vol 40 (1) ◽

pp. 65-70 ◽

Cited By ~ 65

Author(s):

Michal J. Simchen ◽

Gal Goldstein ◽

Aaron Lubetsky ◽

Tzipi Strauss ◽

Eyal Schiff ◽

...

Keyword(s):

Ischemic Stroke ◽

Antiphospholipid Antibodies ◽

Factor V Leiden ◽

Factor V ◽

Arterial Ischemic Stroke ◽

Perinatal Arterial Ischemic Stroke

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The Factor V Leiden, Prothrombin Gene 20210GA, Methylenetetrahydrofolate Reductase 677CT and Platelet Glycoprotein IIIa 1565TC Mutations in Patients With Acute Ischemic Stroke and Atrial Fibrillation

Stroke ◽

10.1161/01.str.0000258076.04860.8e ◽

2007 ◽

Vol 38 (3) ◽

pp. 1069-1071 ◽

Cited By ~ 27

Author(s):

Eivind Berge ◽

Kari Bente Foss Haug ◽

Else Charlotte Sandset ◽

Kaia Kristine Haugbro ◽

Meliha Turkovic ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Methylenetetrahydrofolate Reductase ◽

Factor V Leiden ◽

Platelet Glycoprotein ◽

Factor V ◽

Glycoprotein Iiia ◽

Prothrombin Gene

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Clinical significance of factor V Leiden and prothrombin G20210A-mutations in cerebral venous thrombosis – comparison with arterial ischemic stroke

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-179207 ◽

2017 ◽

Vol 67 (3-4) ◽

pp. 261-266 ◽

Cited By ~ 3

Author(s):

Aida Beye ◽

Gerhard Pindur

Keyword(s):

Ischemic Stroke ◽

Venous Thrombosis ◽

Clinical Significance ◽

Cerebral Venous Thrombosis ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Arterial Ischemic Stroke

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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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Factor V Leiden Mutation in Cerebrovascular Disease

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960501100314 ◽

2005 ◽

Vol 11 (3) ◽

pp. 339-342 ◽

Cited By ~ 4

Author(s):

Nur Buyru ◽

Julide Altinisik ◽

Goksel Somay ◽

Turgut Ulutin

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Cerebrovascular Disease ◽

Smoking Status ◽

Factor V Leiden ◽

Restriction Enzyme Digestion ◽

Factor V ◽

Mutation Site ◽

Factor V Leiden Mutation ◽

High Prevalence

Several studies indicate a high prevalence of factor V Leiden mutation as the most frequent coagulation defect found in patients with venous thrombosis. The relationship between this mutation and cerebrovascular disease has not been established in adults. In this investigation, we studied 29 patients with ischemic stroke and 20 with intracerebral hemorrhage, all of whom were compared with 20 controls. A region of the factor V gene containing the Leiden mutation site was amplified with polymerase chain reaction and the presence of mutation was determined with restriction enzyme digestion. We found no evidence of an association between factor V Leiden mutation and ischemic stroke or intracerebral hemorrhage. There was no evidence of association in subgroup the analysis by age, smoking status, myocardial infarction, hypertension, diabetes mellitus, or coronary disease. Factor V Leiden mutation doesn’t seem to be associated with a risk of cerebrovascular disease.

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