Comparative Analysis of Markers of Mass Effect after Ischemic Stroke

Ostwaldt, Ann-Christin; Battey, Thomas W.K.; Irvine, Hannah; Campbell, Bruce; Davis, Stephen M.; Donnan, Geoffrey A; Kimberly, W. Taylor

doi:10.1111/jon.12525

Cited by 23 publications

(28 citation statements)

References 24 publications

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“…1k). This is in accordance with the Monro-Kellie doctrine and correlations with previous reports of axial and coronal MLS in other animal models of stroke [38] as well as human stroke patients [48,49]. Additionally, axial measurements of MLS were correlated to coronal measurements of MLS (p < 0.0001; Fig.…”

Section: Acute Midline Shift Is Highly Correlated With Chronic Functisupporting

confidence: 91%

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

Spellicy

Kaiser

Bowler

et al. 2019

Transl. Stroke Res.

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Magnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell-derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EVadministration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV-treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.

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Section: Acute Midline Shift Is Highly Correlated With Chronic Functisupporting

confidence: 91%

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

Spellicy

Kaiser

Bowler

et al. 2019

Transl. Stroke Res.

View full text Add to dashboard Cite

show abstract

“…To our knowledge, this is the first study to quantify edema progression in ischemic lesions assessed in the subacute period after stroke onset. EVs are generally described using indirect and global imaging markers like midline shift-the gold standard for assessing edema, and hemispheric, lateral ventricular, or swelling volume (15)(16)(17). Broocks et al have developed a densitometry based NWU measure that relies on the relationship of increasing lesion volume due to water content and the associated density reduction on NCCT (18).…”

Section: Discussionmentioning

confidence: 99%

The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

et al. 2021

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Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

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“…In contrast, the proposed NEMMI score incorporates direct lesion diameters independent of the subterritorial location. As severity of brain swelling with mass effect is directly linked to baseline volume of edematous brain tissue, a score based on lesion dimensions rather than region involvement may be of advantage for MMI prediction ( 12 , 23 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Computed Tomography Based Score of Early Ischemic Changes Predicts Malignant Infarction

et al. 2021

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Background and Purpose: Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters.Methods: One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters.Results: The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p < 0.0001). Based on ROC curve analysis, a NEMMI score >10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56, p < 0.001), adjusted for recanalization status.Conclusion: The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters.

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Comparative Analysis of Markers of Mass Effect after Ischemic Stroke

Abstract: The ratio of ipsilateral to contralateral hemisphere volume, baseline lesion volume and lesional swelling volume best predicted poor outcome across a spectrum of stroke sizes.

Cited by 23 publications

References 24 publications

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

Computed Tomography Based Score of Early Ischemic Changes Predicts Malignant Infarction

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