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  • Thijs, Vincent  (5)
  • 2020-2024  (5)
  • 2022  (5)
  • 1
    Online Resource
    Online Resource
    Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 5 ( 2022-05), p. 1597-1605
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1597-1605
    Abstract: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24–72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. Methods: We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible ( 〈 1 mm), mild (≥1 to 〈 5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. Results: Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00–1.028), 1.03 (IQR, 1.01–1.077), and 1.15 (IQR, 1.08–1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days ( P 〈 0 .002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03–1.20], P =0.005; rHV β, 0.39 [95% CI, 0.24–0.55], P 〈 0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10–0.58], P =0.001; rHV β, −2.95 [95% CI, −4.61 to −11.29], P =0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14–0.98], P =0.045; rHV β, −2.59 [95% CI, −4.32 to −0.86], P =0.004). Conclusions: BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.121.036104
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 2
    Online Resource
    Online Resource
    Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 6 ( 2022-06), p. 1915-1923
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 6 ( 2022-06), p. 1915-1923
    Abstract: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. Methods: In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. Results: In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75–0.98]; P =0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. Conclusions: In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.121.036670
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
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  • 3
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    Online Resource
    Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion : A Pooled Analysis of the EXTEND-IA TNK Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology Vol. 98, No. 12 ( 2022-03-22), p. e1292-e1301
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 12 ( 2022-03-22), p. e1292-e1301
    Abstract: Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. Methods We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age ( 〉 80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results In patients 〉 80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. Discussion TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. Trial Registration Information NCT02388061, NCT03340493. Classification of Evidence This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients 〉 80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000013302
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Abstract 44: Safety Of Tenecteplase And Alteplase In Tandem Lesion Stroke: A Pooled Analysis Of The Extend-IA TNK Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. Suppl_1 ( 2022-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Introduction: The efficacy of tenecteplase (TNK) in patients with tandem lesions (TL) in the anterior circulation is unknown. The longer half-life of TNK could potentially lead to increased hemorrhage, especially in patients who require stenting of the extracranial internal carotid artery (eICA) and subsequent antiplatelet therapy. We assessed the efficacy and safety of TNK in a pooled analysis of the EXTEND-IA TNK trials. Methods: We compared the treatment effect of TNK (pooled analysis of 0.25 and 0.40mg/kg dosing) with alteplase (tPA), stratifying for TL presence. A TL was defined as a combination of eICA pathology (ipsilateral stenosis 〉 70% or occlusion) and intracranial LVO. Outcomes evaluated include 90-day mRS, intracranial reperfusion at initial angiographic assessment, mortality, ICH (symptomatic [sICH] and parenchymal hematoma [PH] ). Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: Of 483 patients with an anterior circulation occlusion, 71/483 (15%) patients had a TL and 43/71 (61%) patients required eICA stenting. In TL patients, reperfusion at initial angiographic assessment was observed in 11/56 (20%) of patients treated with TNK vs. 1/15 (7%) patients treated with tPA (aOR:3.71; 95% CI:0.42-32.75). sICH was observed in 4/71(6%) TL vs 7/412 (2%) nonTL patients (p=0.04). Among TL patients, sICH occurred in 4/56 (7%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.57); sICH occurred in 2/40 (5%) of the 0.25mg/kg TNK group and 2/16 (12.5%) of the 0.40mg/kg TNK group. PH was observed in 6/56 (11%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.33). 90-day mRS (TNK median 2 vs. tPA median 4, acOR:1.21; 95% CI:0.42-3.48), mortality (TNK: 5 [9%] vs. tPA: 3 [20%] , aOR:0.45; 95% CI:0.08-2.50), and eICA stenting (TNK: 35 [64%] vs. tPA: 8 [57%] , p=0.65) rates did not differ between the two treatment groups. Conclusions: Although patients with TL in the anterior circulation were at higher risk of hemorrhagic complications, these did not significantly differ between the TNK and tPA groups. A numeric increase in bleeding with TNK was not accompanied by an increase in mortality or worse functional outcome.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.53.suppl_1.44
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 5
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    Online Resource
    Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient‐Level Analysis from the EXTEND‐IA Trials, INSPIRE , and SELECT Studies
    Wiley ; 2022
    In:  Annals of Neurology Vol. 91, No. 5 ( 2022-05), p. 629-639
    Details
    In: Annals of Neurology, Wiley, Vol. 91, No. 5 ( 2022-05), p. 629-639
    Abstract: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. Methods In a pooled, patient‐level analysis of 3 randomized controlled trials (EXTEND‐IA, EXTEND‐and IA‐TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90‐day functional independence (modified Rankin Scale [mRS] = 0–2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. Results We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8–19) in EVT versus 10 (6–15) in MM, p   〈  0.001. Pretreatment ischemic core did not differ (EVT = 10 [0–24] ml vs MM = 9 [3–21] ml, p  = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI]  = 1.25–4.67, p  = 0.008, inverse probability of treatment weights [IPTW]‐OR = 1.75, 95% CI = 1.00–3.75, p  = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23–3.29, p  = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12–0.87, p  = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09–4.79, p  = 0.029, IPTW‐OR = 2.02, 1.08–3.78, p  = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p  = 0.17, IPTW‐OR: 0.71, 95% CI = 0.18–2.78, p  = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. Interpretation In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629–639
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v91.5
    DOI: 10.1002/ana.26331
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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