Investigating Neurologic Improvement After IV Thrombolysis

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Investigating Neurologic Improvement After IV Thrombolysis : The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock. / Broocks, Gabriel; Meyer, Lukas; Bechstein, Matthias; Hanning, Uta; Kniep, Helge C; Schlemm, Eckhard; Kyselyova, Anna A; Winkelmeier, Laurens; Schön, Gerhard; Fiehler, Jens; Kemmling, Andre.

in: NEUROLOGY, Jahrgang 101, Nr. 17, 24.10.2023, S. e1678-e1686.

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@article{cd7822606df842ec9b8cb14a3dee9bfc,
title = "Investigating Neurologic Improvement After IV Thrombolysis: The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock",
abstract = "BACKGROUND AND OBJECTIVES: Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ({"}tissue clock{"}) using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time.METHODS: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90.RESULTS: Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT.DISCUSSION: CT-based measures of the {"}tissue clock{"} might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early {"}tissue clock{"} (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the {"}tissue clock{"} may be achieved.",
author = "Gabriel Broocks and Lukas Meyer and Matthias Bechstein and Uta Hanning and Kniep, {Helge C} and Eckhard Schlemm and Kyselyova, {Anna A} and Laurens Winkelmeier and Gerhard Sch{\"o}n and Jens Fiehler and Andre Kemmling",
note = "{\textcopyright} 2023 American Academy of Neurology.",
year = "2023",
month = oct,
day = "24",
doi = "10.1212/WNL.0000000000207714",
language = "English",
volume = "101",
pages = "e1678--e1686",
journal = "NEUROLOGY",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "17",

}

RIS

TY - JOUR

T1 - Investigating Neurologic Improvement After IV Thrombolysis

T2 - The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock

AU - Broocks, Gabriel

AU - Meyer, Lukas

AU - Bechstein, Matthias

AU - Hanning, Uta

AU - Kniep, Helge C

AU - Schlemm, Eckhard

AU - Kyselyova, Anna A

AU - Winkelmeier, Laurens

AU - Schön, Gerhard

AU - Fiehler, Jens

AU - Kemmling, Andre

N1 - © 2023 American Academy of Neurology.

PY - 2023/10/24

Y1 - 2023/10/24

N2 - BACKGROUND AND OBJECTIVES: Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time.METHODS: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90.RESULTS: Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT.DISCUSSION: CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.

AB - BACKGROUND AND OBJECTIVES: Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time.METHODS: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90.RESULTS: Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT.DISCUSSION: CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.

U2 - 10.1212/WNL.0000000000207714

DO - 10.1212/WNL.0000000000207714

M3 - SCORING: Journal article

C2 - 37657940

VL - 101

SP - e1678-e1686

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 17

ER -