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Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

ABSTRACT: Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO2) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P<0.05). rScO2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO2 asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; P<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.

SUBMITTER: Wagenaar N

PROVIDER: S-EPMC6756254 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Wagenaar Nienke N van den Berk Daphne J M DJM Lemmers Petra M A PMA van der Aa Niek E NE Dudink Jeroen J van Bel Frank F Groenendaal Floris F de Vries Linda S LS Benders Manon J N L MJNL Alderliesten Thomas T

Stroke 20190808 10

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral ...[more]

PMID: 31390967

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Project description:ImportancePerinatal arterial ischemic stroke (PAIS) is a focal brain injury in term neonates that is identified postnatally but is presumed to occur near the time of birth. Many pregnancy, delivery, and fetal factors have been associated with PAIS, but early risk detection is lacking; thus, targeted treatment and prevention efforts are currently limited.ObjectiveTo develop and validate a diagnostic risk prediction model that uses common clinical factors to predict the probability of PAIS in a term neonate.Design, setting, and participantsIn this diagnostic study, a prediction model was developed using multivariable logistic regression with registry-based case data collected between January 2003, and March 2020, from the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and Alberta Pregnancy Outcomes and Nutrition study. Criteria for inclusion were term birth and no underlying medical conditions associated with stroke diagnosis. Records with more than 20% missing data were excluded. Variable selection was based on peer-reviewed literature. Data were analyzed in September 2021.ExposuresClinical pregnancy, delivery, and neonatal factors associated with PAIS as common data elements across the 4 registries.Main outcomes and measuresThe primary outcome was the discriminative accuracy of the model predicting PAIS, measured by the concordance statistic (C statistic).ResultsOf 2571 term neonates in the initial analysis (527 [20%] case and 2044 [80%] control individuals; gestational age range, 37-42 weeks), 1389 (54%) were male, with a greater proportion of males among cases compared with controls (318 [60%] vs 1071 [52%]). The final model was developed using 1924 neonates, including 321 cases (17%) and 1603 controls (83%), and 9 clinical factors associated with risk of PAIS in term neonates: maternal age, tobacco exposure, recreational drug exposure, preeclampsia, chorioamnionitis, intrapartum maternal fever, emergency cesarean delivery, low 5-minute Apgar score, and male sex. The model demonstrated good discrimination between cases and controls (C statistic, 0.73; 95% CI, 0.69-0.76) and good model fit (Hosmer-Lemeshow P = .20). Internal validation techniques yielded similar C statistics (0.73 [95% CI, 0.69-0.77] with bootstrap resampling, 10-fold cross-validated area under the curve, 0.72 [bootstrap bias-corrected 95% CI, 0.69-0.76]), as did a sensitivity analysis using cases and controls from Alberta, Canada, only (C statistic, 0.71; 95% CI, 0.65-0.77).Conclusions and relevanceThe findings suggest that clinical variables can be used to develop and internally validate a model to predict the risk of PAIS in term neonates, with good predictive performance and strong internal validity. Identifying neonates with a high probability of PAIS who could then be screened for early diagnosis and treatment may be associated with reductions in lifelong morbidity for affected individuals and their families.

Project description:Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126EC-/-), and miR-126 knockout control (miR-126fl/fl) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group). Cardiac hemodynamics and function were measured using transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after dMCAo. WT mice subjected to stroke exhibited significantly decreased cardiac ejection fraction and increased myocyte hypertrophy, fibrosis as well as increased heart inflammation, infiltrating macrophages, and oxidative stress compared to non-stroke animals. Stroke significantly decreased serum and heart miR-126 expression and increased miR-126 target genes, vascular cell adhesion protein-1, and monocyte chemotactic protein-1 gene, and protein expression in the heart compared to non-stroke mice. MiR-126EC-/- mice exhibited significantly decreased cardiac function and increased cardiomyocyte hypertrophy, fibrosis, and inflammatory factor expression after stroke compared to miR-126fl/fl stroke mice. Exosomes derived from endothelial cells of miR-126EC-/- (miR-126EC-/-EC-Exo) mice exhibited significantly decreased miR-126 expression than exosomes derived from miR-126fl/fl (miR-126fl/fl-EC-Exo) mice. Treatment of cardiomyocytes subjected to oxygen glucose deprivation with miR-126fl/fl-EC-Exo exhibited significantly decreased hypertrophy than with miR-126EC-/-EC-Exo treatment. Ischemic stroke directly induces cardiac dysfunction. Decreasing miR-126 expression may contribute to cardiac dysfunction after stroke in mice.

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Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Publications

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

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