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Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

ABSTRACT: Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke.

SUBMITTER: Gu Y

PROVIDER: S-EPMC9434007 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

Gu Yuhang Y Zhou Chen C Piao Zhe Z Yuan Honghua H Jiang Huimin H Wei Huimin H Zhou Yifan Y Nan Guangxian G Ji Xunming X

Frontiers in neuroscience 20220818

Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in preventio ...[more]

PMID: 36061592

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Project description:IntroductionMalignant cerebral edema develops in a small subset of patients with hemispheric strokes, precipitating deterioration and death if decompressive hemicraniectomy (DHC) is not performed in a timely manner. Predicting which stroke patients will develop malignant edema is imprecise based on clinical data alone. Head computed tomography (CT) imaging is often performed at baseline and 24-h. We determined the incremental value of incorporating imaging-derived features from serial CTs to enhance prediction of malignant edema.MethodsWe identified hemispheric stroke patients at three sites with NIHSS ≥ 7 who had baseline as well as 24-h clinical and CT imaging data. We extracted quantitative imaging features from baseline and follow-up CTs, including CSF volume, intracranial reserve (CSF/cranial volume), as well as midline shift (MLS) and infarct-related hypodensity volume. Potentially lethal malignant edema was defined as requiring DHC or dying with MLS over 5-mm. We built machine-learning models using logistic regression first with baseline data and then adding 24-h data including reduction in CSF volume (ΔCSF). Model performance was evaluated with cross-validation using metrics of recall (sensitivity), precision (predictive value), as well as area under receiver-operating-characteristic and precision-recall curves (AUROC, AUPRC).ResultsTwenty of 361 patients (6%) died or underwent DHC. Baseline clinical variables alone had recall of 60% with low precision (7%), AUROC 0.59, AUPRC 0.15. Adding baseline intracranial reserve improved recall to 80% and AUROC to 0.82 but precision remained only 16% (AUPRC 0.28). Incorporating ΔCSF improved AUPRC to 0.53 (AUROC 0.91) while all imaging features further improved prediction (recall 90%, precision 38%, AUROC 0.96, AUPRC 0.66).ConclusionIncorporating quantitative CT-based imaging features from baseline and 24-h CT enhances identification of patients with malignant edema needing DHC. Further refinements and external validation of such imaging-based machine-learning models are required.

Project description:Background and Purpose- Cerebral edema (CED) develops in the hours to days after stroke; the resulting increase in brain volume may lead to midline shift (MLS) and neurological deterioration. The time course and implications of edema formation are not well characterized across the spectrum of stroke. We analyzed displacement of cerebrospinal fluid (ΔCSF) as a dynamic quantitative imaging biomarker of edema formation. Methods- We selected subjects enrolled in a stroke cohort study who presented within 6 hours of onset and had baseline and ≥1 follow-up brain computed tomography scans available. We applied a neural network-based algorithm to quantify hemispheric CSF volume at each imaging time point and modeled CSF trajectory over time (using a piecewise linear mixed-effects model). We evaluated ΔCSF within the first 24 hours as an early biomarker of CED (defined as developing MLS on computed tomography beyond 24 hours) and poor outcome (modified Rankin Scale score, 3-6). Results- We had serial imaging in 738 subjects with stroke, of whom 91 (13%) developed CED with MLS. Age did not differ (69 versus 70 years), but baseline National Institutes of Health Stroke Scale was higher (16 versus 7) and baseline CSF volume lower (132 versus 161 mL, both P<0.001) in those with CED. ΔCSF was faster in those developing MLS, with the majority seen by 24 hours (36% versus 11% or 2.4 versus 0.8 mL/h; P<0.0001). Risk of CED almost doubled for every 10% ΔCSF within 24 hours (odds ratio, 1.76 [95% CI, 1.46-2.14]), adjusting for age, glucose, and National Institutes of Health Stroke Scale. Risk of neurological deterioration (1.6-point increase in National Institutes of Health Stroke Scale at 24 hours) and poor outcome (adjusted odds ratio, 1.34 [95% CI, 1.15-1.56]) was also greater for every 10% increase in ΔCSF. Conclusions- CSF volumetrics provides quantitative evaluation of early edema formation. ΔCSF from baseline to 24-hour computed tomography is a promising early biomarker for the development of MLS and worse neurological outcome.

Project description:BackgroundCerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication.MethodsWe applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days).ResultsThe displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF).ConclusionsCerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

Dataset Information

Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

Publications

Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

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