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 ◽  
...  

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.

2020 ◽  
Author(s):  
Feifeng Liu ◽  
Chen Chen ◽  
Lan Hong ◽  
Hao Shen ◽  
Wenjie Cao ◽  
...  

Abstract Purpose Endovascular therapy is widely used in acute large vessel occlusion. This study investigated whether imaging of lateral lenticulostriate arteries(LSAs) before thrombectomy would potentially be helpful for predicting prognosis of patients with acute M1 segment of middle cerebral artery occlusion(MCAO). Methods 59 consecutive patients with acute M1 segment of MCAO treated with mechanical thrombectomy at two comprehensive stroke center were analyzed. Patients were categorized into LSA+ (appearing of lateral LSAs) and LSA- (sparing of lateral LSAs) group according to preprocedural digital substraction angiography (DSA).Baseline data and clinical outcomes were compared. A good clinical outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The association between clinical and imaging parameters and functional outcome was evaluated with logistic regression analysis. Results LSA+ was shown in 36 patients (61%). LSA+ group had a significantly higher proportion of good outcome (72.2% vs. 8.7%, OR 27.3,95% CI 5.38-138.4, P <0.001), lower risk of symptomatic intracranial haemorrhages (sICH) (8.3% vs. 47.8%,OR 0.10,95% CI 0.02-0.42, P =0.001) and lower mortality in hospital (5.6% vs. 34.8%, OR 0.11,95% CI 0.02 -0.58, P <0.004) compared with LSA- group. Patients in LSA+ group had lower baseline NIHSS score( P <0.01) and NIHSS score at 14 days( P <0.01) and smaller infarct core volume( P =0.016) on computed tomography perfusion imaging (CTP) compared to the LSA- group. Multivariate logistic regression analysis showed that a small infarct core volume (OR 6.74,95% CI 1.148-39.569, P =0.035) and LSA+(OR 22.114,95% CI 3.339-146.470, P =0.001) were associated with a good clinical outcome. Conclusions Our data suggest that appearance of lateral LSAs before mechanical thrombectomy would be potentially helpful for predicting favorable prognosis of patients with acute M1 segment of MCAO.


2020 ◽  
Vol 11 ◽  
Author(s):  
Parisa Heidari ◽  
Sarah Blayney ◽  
Jarrhett Butler ◽  
Emi Hitomi ◽  
Marie Luby ◽  
...  

Background: Penumbral brain tissue identified with multimodal imaging can be salvaged with reperfusion in an extended time window. The risk of severe hemorrhagic complications after reperfusion therapy increases with worsening disruption of the blood-brain barrier (BBB). The relationship between penumbral tissue and BBB disruption has not been previously studied.Methods: Stroke patients presenting in an extended time window without a large vessel occlusion who underwent diffusion-perfusion MRI within 24 h of last-seen-normal were included. The volume of penumbral tissue was calculated using mismatch on MRI. Mean permeability derangement (MPD) of the BBB was measured within the ischemic lesion. A target profile (TP) for treatment was defined based on the EXTEND trial.Results: 222 patients were included with a median age of 73 and 55% women. The median NIHSS was 6, the mean core volume was 14 ml, the mean ischemic volume was 47 mL and the mean mismatch volume was 33 mL. Higher MPD was significantly associated with less mismatch volume (p = 0.001). A target profile was associated with lower MPD (OR 0.97; CI 0.96:0.99; p &lt; 0.001). Of the 105 patients who had a TP, 31 (30%) had a MPD &gt; 20% suggesting an increased risk of hemorrhage. Thus, 33% (74/222) of patients had a favorable profile for benefit and safety.Conclusions: Patients presenting in an extended time window with a favorable penumbral profile for treatment have less severe BBB disruption. Up to a third of patients who currently go untreated could be considered for enrollment in a clinical trial of thrombolysis in an extended time window.


2019 ◽  
pp. 174749301988452 ◽  
Author(s):  
Jawed Nawabi ◽  
Fabian Flottmann ◽  
Andre Kemmling ◽  
Helge Kniep ◽  
Hannes Leischner ◽  
...  

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.


Neurosurgery ◽  
2020 ◽  
Author(s):  
Gabriel Broocks ◽  
Sarah Elsayed ◽  
Helge Kniep ◽  
Andre Kemmling ◽  
Fabian Flottmann ◽  
...  

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.


2018 ◽  
Vol 5 (2) ◽  
pp. 643
Author(s):  
Abdulrahman Saleh Al-Mulhim

Background: Preoperative anemia is associated with adverse outcomes after surgery, but no evidence study demonstrates this risk after laparoscopic cholecystectomy. This study aimed to measure the prevalence of preoperative anemia, and to assess its effect on early clinical outcome in laparoscopic cholecystectomy patients.Methods: Data of 6342 consecutive laparoscopic cholecystectomy patients between Januarys 1995 to January 2015 were evaluated. Preoperative anemia was defined as a hemoglobin level of less than 120gm/l in female, and less than 130gm/l in male. Logistic regression used for analysis.Results: Preoperative anemia identified in 37.4% of laparoscopic cholecystectomy patients and it more prevalence in women. Analysis showed that patients with severe [odds ratio1.83 (95% Confidence interval 1.62-3.66)], moderate [odds ratio 1.21 (95% Confidence interval 1.11-1.38)], and mild [odds ratio 1.04 (95% Confidence interval 0.91-1.13)] anemia had higher morbidity than those with normal preoperative hemoglobin.Conclusions: Anemia is common among laparoscopic cholecystectomy patients, and it is associated with more complications.


Neurology ◽  
2019 ◽  
Vol 93 (9) ◽  
pp. e851-e863 ◽  
Author(s):  
Caty Carrera ◽  
Natalia Cullell ◽  
Nuria Torres-Águila ◽  
Elena Muiño ◽  
Alejandro Bustamante ◽  
...  

ObjectiveTo validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke.MethodsWe enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum.ResultsGenot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score (p = 2.02 × 10−6, p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C (p = 0.012, p = 0.034, p = 5.32 × 10−4). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%–15.7%, cohort B 1.5%–18.2%, cohort C 0%–100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46–18.08, p = 0.009).ConclusionThe Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012484
Author(s):  
Gabriel Broocks ◽  
Rosalie McDonough ◽  
Lukas Meyer ◽  
Matthias Bechstein ◽  
Helge Kniep Dipl.Ing ◽  
...  

Background and ObjectivesIn acute stroke, early ischemic lesion hypodensity in computed tomography (CT) is considered the imaging hallmark of brain infarction, representing a state of irreversible tissue damage with a continual increase of net water uptake. This dogma is however challenged by rare cases of apparently reversed early lesion hypodensity following complete reperfusion. The purpose of this study was to investigate the occurrence of reversible ischemic edema after endovascular treatment.Methods184 acute ischemic anterior circulation stroke patients were included after consecutive screening. Ischemic brain edema was determined using quantitative lesion net water uptake (NWU) in admission-CT and follow-up CT based on CT-densitometry and ΔNWU was calculated as the difference. The association of edema progression to imaging and clinical parameters was investigated. Clinical outcome was assessed using modified Ranking Scale (mRS) scores at day 90.Results27/184 patients (14.7%) showed edema arrest and 3 patients (1.6%) exhibited significant edema reversibility. Higher degree of recanalization (odds ratio (OR): 2.96, 95%CI: 1.46-6.01, p<0.01) and shorter time from imaging to recanalization (OR/hour: 0.32, 95%CI: 0.18-0.54, p<0.0001) were significantly associated with edema arrest or reversibility. Clinical outcome was significantly better in patients without edema progression (median mRS 2 versus mRS 5, p=0.004).DiscussionAlbeit rare, lesion hypodensity considered to be representative of early infarct in acute stroke CT may be reversible following complete recanalization. Arrest of edema progression of acute brain infarct lesions may occur after successful rapid vessel recanalization, resulting in improved functional outcome. Future research is needed to investigate conditions where early revascularization may halt or even reverse vasogenic edema of ischemic tissue.


Stroke ◽  
2022 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Nicole Blume ◽  
Omar Abu-Fares ◽  
Friedrich Götz ◽  
Johanna Ernst ◽  
...  

Background and Purpose: Cell-free DNA (cfDNA) and endogenous deoxyribonuclease activity are opposing mediators and might influence the inflammatory response following acute ischemic stroke. In this cohort study, we investigated the relation between these markers, circulating inflammatory mediators and clinical course including occurrence of stroke-associated infections (SAI) in patients with acute stroke. Methods: Ninety-two patients with stroke due to large vessel occlusion undergoing mechanical thrombectomy were prospectively recruited at Hannover Medical School from March 2018 to August 2019. Deoxyribonuclease activity, cfDNA, damage-associated molecular patterns, and circulating cytokines were measured in venous blood collected immediately before mechanical thrombectomy and 7 days later. Reperfusion status was categorized (sufficient/insufficient). Clinical outcome was evaluated using the modified Rankin Scale after 90 days, where a score of 3 to 6 was considered unfavorable. To validate findings regarding SAI, another stroke cohort (n=92) was considered with blood taken within 24 hours after stroke onset. Results: Patients with unfavorable clinical outcome had higher cfDNA concentrations. After adjustment for confounders (Essen Stroke Risk Score, National Institutes of Health Stroke Scale, and sex), 7-day cfDNA was independently associated with clinical outcome and especially mortality (adjusted odds ratio: 3.485 [95% CI, 1.001–12.134] and adjusted odds ratio: 9.585 [95% CI, 2.006–45.790]). No association was found between reperfusion status and cfDNA or deoxyribonuclease activity. While cfDNA concentrations correlated positively, deoxyribonuclease activity inversely correlated with distinct biomarkers. Baseline deoxyribonuclease activity was lower in patients who developed SAI compared with patients without SAI. This association was confirmed after adjustment for confounding factors (adjusted odds ratio: 0.447 [95% CI, 0.237–0.844]). In cohort 2, differences of deoxyribonuclease activity between patients with and without SAI tended to be higher with higher stroke severity. Conclusions: The interplay of endogenous deoxyribonuclease activity and cfDNA in acute stroke entails interesting novel diagnostic and potential therapeutic approaches. We confirm an independent association of cfDNA with a detrimental clinical course after stroke due to large vessel occlusion. This study provides first evidence for lower endogenous deoxyribonuclease activity as risk factor for SAI after severe stroke.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Yang-Ha Hwang ◽  
Dong-Hun Kang ◽  
Yong-Won Kim ◽  
Yong-Sun Kim

Background: Clinical outcome following reperfusion can be affected by the adequacy of baseline collaterals during endovascular therapy. We examined the relationship between onset-to-reperfusion time (ORT), collateral grade, and clinical outcome with the hypothesis that there is a narrow therapeutic time window for good clinical outcomes in patients having poor collaterals. Methods: Among 300 patients who underwent endovascular therapy for acute large vessel occlusion in the anterior circulation, we identified 220 patients having a final TICI score of 2 or more. Patients’ collateral grades, using the ASITN/SIR scale on baseline angiography, were dichotomized into poor (0-1) versus partial/complete (2-4). Favorable functional outcome was defined as a 3-month mRS of 0-2. Results: Angiographic data on collaterals were available for 207/220 patients, with 76 in the poor collateral group and 131 in the partial/complete group. The TICI 2b-3 reperfusion rates were similar between the two groups [51/76 (67%) vs. 89/131 (68%), p=0.902], though functional outcomes were significantly different [35/76 (46%) vs. 81/131 (63%), p=0.027]. In the poor collateral group, the odds of favorable outcome significantly dropped for patients reperfused beyond 6-hour from onset [28/53 (54%) vs. 7/24 (29%); odds ratio 0.35 (95% CI 0.13-0.99); p=0.045], whereas the probability of favorable outcome in partial/complete group was not as influenced by reperfusion beyond the 6-hour time window [56/85 (66%) vs. 25/46 (54%); odds ratio 0.62 (95% CI 0.30-1.29); p=0.195]. In subgroup analysis of the poor collateral group, each 30-minute increase in ORT was associated with a decreased chance of favorable outcome despite reperfusion after adjustment for age, baseline NIHSS score, and baseline ASPECTS score [odds ratio 0.77 (95% CI 0.64-0.93); p=0.006]. Conclusions: Onset-to-reperfusion time in patients with poor collaterals is an another important factor affecting favorable outcome, and future trials would benefit from a non-invasive imaging technique to detect poor collaterals along with a strategy for early reperfusion.


2021 ◽  
Vol 62 (7) ◽  
pp. 910-921
Author(s):  
Sang Il Cho ◽  
Young Myoung Park ◽  
Min Ahn ◽  
Nam Chun Cho ◽  
In Cheon You

Purpose: To describe the clinical manifestations, causative organisms, treatment, and prognostic factors of fungal keratitis based on analysis of patients over the past 20 years. Methods: A total of 177 patients (177 eyes) with fungal keratitis, who were diagnosed by smears and cultures, were reviewed retrospectively. Sex, age, predisposing factors, causative organisms, clinical manifestations, treatment, and prognosis were evaluated. The patients were divided into three groups: only potassium hydroxide (KOH)-positive, only culture-positive, and KOH- and culture-positive. Logistic regression was performed to identify the factors associated with a poor clinical outcome. Results: The mean age of the patients was 67.4 ± 11.3 years; 107 (60.5%) patients were men. The most common predisposing factor was ocular trauma (57.6%), especially by plants (29.4%). The most prevalent filamentous fungi were Fusarium species (31.6%, 49 isolates), and the most prevalent yeasts were Candida species (11.0%, 17 isolates). In cases of bacterial and fungal keratitis, filamentous fungus with Gram-positive bacterial infection (70.7%, 29/41) was the most common presentation. Visual improvement after treatment was common in the KOH-positive group (79.2%, 19/24), while visual deterioration after treatment was common in the culture-positive group (40.4%, 36/89). Previous ocular disease (odds ratio [OR]: 3.744, p = 0.010), hypopyon (OR: 2.941, p = 0.030), and surgical treatment (OR: 24.482, p < 0.001) were risk factors for a poor clinical outcome in the multivariate logistic regression model. Conclusions: Clinical prognosis was good in the KOH-positive only group, but poor in the culture-positive group. If fungal keratitis is suspected, diagnostic KOH staining and culture tests should be performed initially. Early intensive antifungal medical treatments are necessary for patients with risk factors for poor clinical outcomes.


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