Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization – When “tissue clock” and “time clock” are desynchronized

2019 ◽  
pp. 174749301988452 ◽  
Author(s):  
Jawed Nawabi ◽  
Fabian Flottmann ◽  
Andre Kemmling ◽  
Helge Kniep ◽  
Hannes Leischner ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Acute Stroke ◽  
Water Uptake ◽  
Quantitative Imaging ◽  
Receiver Operating Curve ◽  
Imaging Biomarker ◽  
Poor Clinical Outcome ◽  
Similar Time ◽  
Poor Outcome ◽  
Malignant Infarction

Background Ischemic water uptake in acute stroke is a reliable indicator of lesion age. Nevertheless, inter-individually varying edema progression has been observed and elevated water uptake has recently been described as predictor of malignant infarction. Aims We hypothesized that early-elevated lesion water uptake indicates accelerated “tissue clock” desynchronized with “time clock” and therefore predicts poor clinical outcome despite successful recanalization. Methods Acute middle cerebral artery stroke patients with multimodal admission-CT who received successful thrombectomy (TICI 2b/3) were analyzed. Net water uptake (NWU), a quantitative imaging biomarker of ischemic edema, was determined in admission-CT and tested as predictor of clinical outcome using modified Rankin Scale (mRS) after 90 days. A binary outcome was defined for mRS 0–4 and mRS 5–6. Results Seventy-two patients were included. The mean NWU (SD) in patients with mRS 0–4 was lower compared to patients with mRS 5–6 (5.0% vs. 12.1%; p < 0.001) with similar time from symptom onset to imaging (2.6 h vs. 2.4 h; p = 0.7). Based on receiver operating curve analysis, NWU above 10% identified patients with very poor outcome with high discriminative power (AUC 0.85), followed by Alberta Stroke Program Early CT Score (ASPECTS) (AUC: 0.72) and National Institutes of Health Stroke Scale (NIHSS) (AUC: 0.72). Conclusions Quantitative NWU may serve as an indicator of “tissue clock” and pronounced early brain edema with elevated NWU might suggest a desynchronized “tissue clock” with real “time clock” and therefore predict futile recanalization with poor clinical outcome.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke

2015 ◽  
Vol 40 (5-6) ◽  
pp. 258-269 ◽  
Author(s):  
Tom van Seeters ◽  
Geert Jan Biessels ◽  
L. Jaap Kappelle ◽  
Irene C. van der Schaaf ◽  
Jan Willem Dankbaar ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Acute Ischemic Stroke ◽  
Ct Angiography ◽  
Predictive Value ◽  
Prognostic Value ◽  
Ct Perfusion ◽  
Patient Characteristics ◽  
Poor Clinical Outcome ◽  
Poor Outcome

Background: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). Methods: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. Results: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. Conclusions: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

scholarly journals LncRNA RHPN1-AS1 promotes cholangiocarcinoma progression and predicts poor clinical outcome through miR-345-5p/YAP1 axis

2020 ◽  
Author(s):  
Lifeng Ma ◽  
Tao Li ◽  
Guochao Liu ◽  
Jianlong Wang ◽  
Zhaoqiang Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Clinical Practice ◽  
Clinical Outcome ◽  
Carcinoma Cell ◽  
Poor Clinical Outcome ◽  
Xenograft Growth ◽  
Poor Outcome ◽  
New Strategies

Abstract Background LncRNAs have proven to be involved in the initiation and progression of cholangiocarcinoma (CCA), although the mechanism by which this occurs remains unknown. Methods The current study reveals that RHPN1-AS1 was overexpressed in CCA patient samples, which predicted poor outcome of CCA patients. RHPN1-AS1 increased in vitro pancreatic carcinoma cell proliferation as well as promoted xenograft growth in vivo. Mechanistically, DANCR upregulated expression of YAP1 by competitively binding to miR-345-5p. Importantly, RHPN1-AS1 level was positively correlated with YAP1 expression level in CCA tissues. Moreover, YAP1 overexpression could predicted a poor outcome of CCA patients. Results Taken together, our results suggested that RHPN1-AS1 might be a remarkable biomarker to evaluate prognosis in CCA. Conclusion The RHPN1-AS1/YAP1 axis may provide new strategies for CCA clinical practice.

Early Prediction of Malignant Cerebellar Edema in Posterior Circulation Stroke Using Quantitative Lesion Water Uptake

Neurosurgery ◽  
2020 ◽  
Author(s):  
Gabriel Broocks ◽  
Sarah Elsayed ◽  
Helge Kniep ◽  
Andre Kemmling ◽  
Fabian Flottmann ◽  
...  
Keyword(s):  
Water Uptake ◽  
Roc Analysis ◽  
Early Stage ◽  
Area Under The Curve ◽  
Posterior Circulation ◽  
Receiver Operating Curve ◽  
Imaging Biomarker ◽  
Anterior Circulation ◽  
Ischemic Lesion ◽  
Posterior Circulation Stroke

Abstract BACKGROUND Malignant cerebellar edema (MCE) is a life-threatening complication of ischemic posterior circulation stroke that requires timely diagnosis and management. Yet, there is no established imaging biomarker that may serve as predictor of MCE. Early edematous water uptake can be determined using quantitative lesion water uptake, but this biomarker has only been applied in anterior circulation strokes. OBJECTIVE To test the hypothesis that lesion water uptake in early posterior circulation stroke predicts MCE. METHODS A total 179 patients with posterior circulation stroke and multimodal admission CT were included. A total of 35 (19.5%) patients developed MCE defined by using an established 10-point scale in follow-up CT, of which ≥4 points are considered malignant. Posterior circulation net water uptake (pcNWU) was quantified in admission CT based on CT densitometry and compared with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) as predictor of MCE using receiver operating curve (ROC) analysis and logistic regression analysis. RESULTS Acute pcNWU within the early ischemic lesion was 24.6% (±8.4) for malignant and 7.2% (±7.4) for nonmalignant infarctions, respectively (P &lt; .0001). Based on ROC analysis, pcNWU above 14.9% identified MCE with high discriminative power (area under the curve: 0.94; 95% CI: 0.89-0.97). Early pcNWU (odds ratio [OR]: 1.28; 95% CI: 1.15-1.42, P &lt; .0001) and pc-ASPECTS (OR: 0.71, 95% CI: 0.53-0.95, P = .02) were associated with MCE, adjusted for age and recanalization status. CONCLUSION Quantitative pcNWU in early posterior circulation stroke is an important marker for MCE. Besides pc-ASPECTS, lesion water uptake measurements may further support identifying patients at risk for MCE at an early stage indicating stricter monitoring and consideration for further therapeutic measures.

Quantitative Lesion Water Uptake as Stroke Imaging Biomarker: A Tool for Treatment Selection in the Extended Time Window?

Stroke ◽  
2021 ◽  
Author(s):  
Gabriel Broocks ◽  
Andre Kemmling ◽  
Svenja Teßarek ◽  
Rosalie McDonough ◽  
Lukas Meyer ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Clinical Outcome ◽  
Water Uptake ◽  
Odds Ratio ◽  
Mechanical Thrombectomy ◽  
Time Window ◽  
Imaging Biomarker ◽  
Extended Time ◽  
Ischemic Lesion ◽  
Clinical Prognosis

Background and Purpose: Patients presenting in the extended time window may benefit from mechanical thrombectomy. However, selection for mechanical thrombectomy in this patient group has only been performed using specialized image processing platforms, which are not widely available. We hypothesized that quantitative lesion water uptake calculated in acute stroke computed tomography (CT) may serve as imaging biomarker to estimate ischemic lesion progression and predict clinical outcome in patients undergoing mechanical thrombectomy in the extended time window. Methods: All patients with ischemic anterior circulation stroke presenting within 4.5 to 24 hours after symptom onset who received initial multimodal CT between August 2014 and March 2020 and underwent mechanical thrombectomy were analyzed. Quantitative lesion net water uptake was calculated from the admission CT. Prediction of clinical outcome was assessed using univariable receiver operating characteristic curve analysis and logistic regression analyses. Results: One hundred two patients met the inclusion criteria. In the multivariable logistic regression analysis, net water uptake (odds ratio, 0.78 [95% CI, 0.64–0.95], P =0.01), age (odds ratio, 0.94 [95% CI, 0.88–0.99]; P =0.02), and National Institutes of Health Stroke Scale (odds ratio, 0.88 [95% CI, 0.79–0.99], P =0.03) were significantly and independently associated with favorable outcome (modified Rankin Scale score ≤1), adjusted for degree of recanalization and Alberta Stroke Program Early CT Score. A multivariable predictive model including the above parameters yielded the highest diagnostic ability in the classification of functional outcome, with an area under the curve of 0.88 (sensitivity 92.3%, specificity 82.9%). Conclusions: The implementation of quantitative lesion water uptake as imaging biomarker in the diagnosis of patients with ischemic stroke presenting in the extended time window might improve clinical prognosis. Future studies could test this biomarker as complementary or even alternative tool to CT perfusion.

Serum S-100 Protein, Relationship to Clinical Outcome in Acute Stroke

1997 ◽  
Vol 34 (5) ◽  
pp. 546-550 ◽  
Author(s):  
Hagosa D Abraha ◽  
Richard J Butterworth ◽  
Philip M W Bath ◽  
Wassif S Wassif ◽  
John Garthwaite ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Barthel Index ◽  
Protein Concentration ◽  
Protein A ◽  
Haemorrhagic Stroke ◽  
Poor Clinical Outcome ◽  
Anterior Circulation ◽  
S 100

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0·27 (0·09)μg/L, n = 68] and haemorrhagic stroke [0·43 (0·23)μg/L, n=13] compared to controls [0·11 (0·03)μg/L, n = 51, P<0·0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0·40 (0·22) μg/L], and small vessel (‘lacunar’) infarcts concentrations having the lowest [0·20 (0·06)μg/L, P<0·0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales ( n = 81): modified Barthel index ( rs=–0·285, P = 0·01), modified Rankin score ( rs = 0·313, P = 0·004) and Lindley score ( rs = 0·262, P = 0·018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0·63 (0·29)μg/L and 0·37 (0·13)μg/L, respectively] compared to those who were discharged home [0·26 (0·11)μg/L, P = 0·13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated. Indexing terms: acute stroke/serum S-100/Barthel index/Rankin scale.

scholarly journals Predicting the combined occurrence of poor clinical and radiographic outcomes following cervical deformity corrective surgery

2020 ◽  
Vol 32 (2) ◽  
pp. 182-190 ◽  
Author(s):  
Samantha R. Horn ◽  
Peter G. Passias ◽  
Cheongeun Oh ◽  
Virginie Lafage ◽  
Renaud Lafage ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cobb Angle ◽  
Thoracic Kyphosis ◽  
Pelvic Tilt ◽  
Major Complication ◽  
Neurological Status ◽  
Radiographic Outcome ◽  
Poor Clinical Outcome ◽  
Poor Outcome ◽  
Poor Outcomes

OBJECTIVECervical deformity (CD) correction is clinically challenging. There is a high risk of developing complications with these highly complex procedures. The aim of this study was to use baseline demographic, clinical, and surgical factors to predict a poor outcome following CD surgery.METHODSThe authors performed a retrospective review of a multicenter prospective CD database. CD was defined as at least one of the following: cervical kyphosis (C2–7 Cobb angle > 10°), cervical scoliosis (coronal Cobb angle > 10°), C2–7 sagittal vertical axis (cSVA) > 4 cm, or chin-brow vertical angle (CBVA) > 25°. Patients were categorized based on having an overall poor outcome or not. Health-related quality of life measures consisted of Neck Disability Index (NDI), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scale scores. A poor outcome was defined as having all 3 of the following categories met: 1) radiographic poor outcome: deterioration or severe radiographic malalignment 1 year postoperatively for cSVA or T1 slope–cervical lordosis mismatch (TS-CL); 2) clinical poor outcome: failing to meet the minimum clinically important difference (MCID) for NDI or having a severe mJOA Ames modifier; and 3) complications/reoperation poor outcome: major complication, death, or reoperation for a complication other than infection. Univariate logistic regression followed by multivariate regression models was performed, and internal validation was performed by calculating the area under the curve (AUC).RESULTSIn total, 89 patients with CD were included (mean age 61.9 years, female sex 65.2%, BMI 29.2 kg/m2). By 1 year postoperatively, 18 (20.2%) patients were characterized as having an overall poor outcome. For radiographic poor outcomes, patients’ conditions either deteriorated or remained severe for TS-CL (73% of patients), cSVA (8%), horizontal gaze (34%), and global SVA (28%). For clinical poor outcomes, 80% and 60% of patients did not reach MCID for EQ-5D and NDI, respectively, and 24% of patients had severe symptoms (mJOA score 0–11). For the complications/reoperation poor outcome, 28 patients experienced a major complication, 11 underwent a reoperation, and 1 had a complication-related death. Of patients with a poor clinical outcome, 75% had a poor radiographic outcome; 35% of poor radiographic and 37% of poor clinical outcome patients had a major complication. A poor outcome was predicted by the following combination of factors: osteoporosis, baseline neurological status, use of a transition rod, number of posterior decompressions, baseline pelvic tilt, T2–12 kyphosis, TS-CL, C2–T3 SVA, C2–T1 pelvic angle (C2 slope), global SVA, and number of levels in maximum thoracic kyphosis. The final model predicting a poor outcome (AUC 86%) included the following: osteoporosis (OR 5.9, 95% CI 0.9–39), worse baseline neurological status (OR 11.4, 95% CI 1.8–70.8), baseline pelvic tilt > 20° (OR 0.92, 95% CI 0.85–0.98), > 9 levels in maximum thoracic kyphosis (OR 2.01, 95% CI 1.1–4.1), preoperative C2–T3 SVA > 5.4 cm (OR 1.01, 95% CI 0.9–1.1), and global SVA > 4 cm (OR 3.2, 95% CI 0.09–10.3).CONCLUSIONSOf all CD patients in this study, 20.2% had a poor overall outcome, defined by deterioration in radiographic and clinical outcomes, and a major complication. Additionally, 75% of patients with a poor clinical outcome also had a poor radiographic outcome. A poor overall outcome was most strongly predicted by severe baseline neurological deficit, global SVA > 4 cm, and including more of the thoracic maximal kyphosis in the construct.

scholarly journals Serum S-100 Protein, Relationship to Clinical Outcome in Acute Stroke

1997 ◽  
Vol 34 (4) ◽  
pp. 366-370 ◽  
Author(s):  
Hagosa D Abraha ◽  
Richard J Butterworth ◽  
Philip M W Bath ◽  
Wassif S Wassif ◽  
John Garthwaite ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Barthel Index ◽  
Protein Concentration ◽  
Protein A ◽  
Haemorrhagic Stroke ◽  
Poor Clinical Outcome ◽  
Anterior Circulation ◽  
S 100

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0·27 (0·09) μg/L, n = 68] and haemorrhagic stroke [0·43 (0·23) μg/L, n = 13] compared to controls [0·11 (0·03) μg/L, n = 51, P<0·0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0·40 (0·22) μg/L], and small vessel (‘lacunar’) infarcts concentrations having the lowest [0·20 (0·06) μg/L, P<0·0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales ( n = 81): modified Barthel index ( rs=–0·285, P = 0·01), modified Rankin score ( rs = 0·313, P = 0·004) and Lindley score ( rs = 0·262, P = 0·018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0·63 (0·29) μg/L and 0·37 (0·13) μg/L, respectively] compared to those who were discharged home [0·26 (0·11) μg/L, P = 0·13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated. Indexing terms: acute stroke/serum S-100/Barthel index/Rankin scale.

scholarly journals Favorable revascularization therapy in patients with ASPECTS ≤ 5 on DWI in anterior circulation stroke

2017 ◽  
Vol 10 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Isabelle Mourand ◽  
Eitan Abergel ◽  
Daniel Mantilla ◽  
Xavier Ayrignac ◽  
Tzvika Sacagiu ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Acute Stroke ◽  
Intravenous Thrombolysis ◽  
Reperfusion Therapy ◽  
Control Group ◽  
Anterior Circulation ◽  
Malignant Infarction ◽  
Baseline Characteristics ◽  
Revascularization Therapy ◽  
Favorable Clinical Outcome

BackgroundA low baseline Alberta Stroke Programme Early CT Score (ASPECTS) is strongly associated with low rates of favorable outcome in patients with acute stroke.ObjectiveTo evaluate the efficacy and safety of revascularization therapy in patient with ASPECTS ≤5 in anterior circulation infarct.MethodsWe retrospectively analyzed 108 consecutive patients presenting low ASPECTS on diffusion-weighted imaging. Sixty patients were treated by mechanical thrombectomy, including 34 patients who received simultaneously intravenous thrombolysis. A control group of 48 patients not eligible for reperfusion therapy gave us a perspective on the natural history. Clinical outcome was evaluated at 90 days using the modified Rankin Scale (mRS) score. Hemicraniectomy after malignant infarction, mortality, and symptomatic intracranial haemorrhage (sICH) were also reported.ResultsThrombolysis in Cerebral Infarction 2b–3 was assessed in 75% of treated patients. Reperfusion therapy led to significantly reduced disability (mRS score 0–2) at 90 days compared with the control group (30% vs 2.1%, p<0.001), hemicraniectomy (3.3% vs 22.9%, p=0.002), and death at 90 days (25% vs 47.9%, p=0.01). The sICH level was similar in treated patients and in the control group (p=0.78). Patients aged ≤70 years in the thrombectomy group had a significantly better clinical outcome than older patients (37.5% vs 10%, p=0.02), regardless of baseline characteristics or recanalization rate.ConclusionsIn patients with acute stroke in the anterior circulation and ASPECTS ≤5 revascularization therapy contributes to a favorable clinical outcome at 90 days, especially in patients younger than 70 years.

scholarly journals Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction

Stroke ◽  
2018 ◽  
Vol 49 (8) ◽  
pp. 1906-1912 ◽  
Author(s):  
Gabriel Broocks ◽  
Fabian Flottmann ◽  
Alexandra Scheibel ◽  
Annette Aigner ◽  
Tobias D. Faizy ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Acute Stroke ◽  
Water Uptake ◽  
Malignant Infarction
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