Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial

Davis, Stephen M.; Donnan, Geoffrey A.; Parsons, Mark; Levi, Christopher; Butcher, Ken; Peeters, André; Barber, P. Alan; Bladin, Christopher; Silva, Deidre Anne De; Byrnes, Graham; Chalk, Jonathan B.; Fink, John; Kimber, Thomas; Schultz, David; Hand, Peter J.; Frayne, Judith; Hankey, Graeme J.; Muir, Keith W.; Gerraty, Richard; Tress, Brian M.; Desmond, Patricia

doi:10.1016/s1474-4422(08)70044-9

Cited by 981 publications

(913 citation statements)

References 34 publications

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“…Moreover, there is ambiguity about the optimal perfusion threshold that can distinguish benign oligemia from 'penumbral' tissue (Dani et al, 2011). Clinical trials using 'mismatch' as a selection criteria for thrombolysis have shown variable success (Davis et al, 2008;Hacke et al, 2005Hacke et al, , 2009). An imaging marker of stunned but potentially salvageable tissue may help to overcome shortcomings of DWI and PWI.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Functional Cerebral Blood Volume Responses to Normobaric Hyperoxia in Acute Ischemic Stroke

Mandeville

et al. 2012

J Cereb Blood Flow Metab

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Studies suggest that neuroprotective effects of normobaric oxygen (NBO) therapy in acute stroke are partly mediated by hemodynamic alterations. We investigated cerebral hemodynamic effects of repeated NBO exposures. Serial magnetic resonance imaging (MRI) was performed in Wistar rats subjected to focal ischemic stroke. Normobaric oxygen-induced functional cerebral blood volume (fCBV) responses were analyzed. All rats had diffusion-weighted MRI (DWI) lesions within larger perfusion deficits, with DWI lesion expansion after 3 hours. Functional cerebral blood volume responses to NBO were spatially and temporally heterogeneous. Contralateral healthy tissue responded consistently with vasoconstriction that increased with time. No significant responses were evident in the acute DWI lesion. In hypoperfused regions surrounding the acute DWI lesion, tissue that remained viable until the end of the experiment showed relative preservation of mean fCBV at early time points, with some rats showing increased fCBV (vasodilation); however, these regions later exhibited significantly decreased fCBV (vasoconstriction). Tissue that became DWI abnormal by study-end initially showed marginal fCBV changes that later became moderate fCBV reductions. Our results suggest that a reverse-steal hemodynamic effect may occur in peripheral ischemic zones during NBO treatment of focal stroke. In addition, CBV responses to NBO challenge may have potential as an imaging marker to distinguish ischemic core from salvageable tissues.

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Section: Discussionmentioning

confidence: 99%

Dynamic Functional Cerebral Blood Volume Responses to Normobaric Hyperoxia in Acute Ischemic Stroke

Mandeville

et al. 2012

J Cereb Blood Flow Metab

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“…Growth of the core region can be variable (continuous or dashed arrows) depending on the defined DWI and CBF thresholds, reperfusion, and individual tissue resistance. mismatch might respond better to thrombolytic therapy, the DIAS-2 study did not show any benefit in patients selected for thrombolysis based on the existence of a mismatch (Albers et al, 2006;Davis et al, 2008;Donnan et al, 2009;Hacke et al, 2009). Of note, the mismatch in DIAS-2 was defined as a PWI lesion volume > 20% of the DWI lesion volume by visual inspection at each participating stroke center.…”

Section: The Mismatch Conceptmentioning

confidence: 99%

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

Farr

Wegener

2010

J Cereb Blood Flow Metab

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Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

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“…The duration of ischemia is a leading predictor of neurological outcome, but with modern penumbral imaging it may be that time alone may not be a necessary arbiter of who qualifies for IAT [16][17][18]. The author (Abou-Chebl [19]) and his colleagues have treated highly-selected patients well beyond these time limits with excellent success, but such treatment is not the standard of care, and it is controversial and considered experimental [20].…”

Section: Indicationsmentioning

confidence: 99%

“…Patients must also have a clinical deficit severe enough to warrant intervention both to avoid the risk of the procedure and to ensure that an intervention is likely to be of benefit, because patients with mild strokes (National Institutes of Health Stroke Score [NIHSS]<4) are unlikely to have a visible arterial occlusion and are likely to have a good outcome without therapy [21]. In contrast, patients with the most severe strokes (NIHSS>20) are less likely to benefit from treatment although penumbral imaging to identify patients with small ischemic cores and large perfusion deficits may help select who may benefit from treatment [16][17][18]. It is important to note that such approaches remain unproven.…”

Section: Indicationsmentioning

confidence: 99%

“…A total of 177 patients were enrolled in the Multi MERCI trial, but the device was deployed in only 164 patients, with a mean age of 68.1± 16.0 years. The median NIHSS score was 19 (range, [15][16][17][18][19][20][21][22][23], and the median procedural duration was 1.6 h (1.2-2.3 h). As in the MERCI trial, the patients had a high thrombus burden with ICA terminus occlusion (32%), M1 or M2 segments of the MCA branch occlusion (60%), and posterior circulation occlusion (8%).…”

Section: Mechanical Clot Disruption and Extractionmentioning

confidence: 99%

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Intra-arterial Therapy for Acute Ischemic Stroke

Aböu-Chebl

2011

Neurotherapeutics

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Intra-arterial therapy (IAT) for acute ischemic stroke refers to endovascular catheter-based approaches to achieve recanalization using mechanical clot disruption, locally injected thrombolytic agents or both. IAT may be used in addition to intravenous tissue plasminogen activator (tPA) or in patients who do not qualify for tPA, usually because they are outside the approved 3-h timeframe window or have contraindications, such as elevated international normalized ratio or partial thromboplastin time. Recanalization rates correlate with clinical improvement, and with the newest catheters it is possible to achieve recanalization in roughly 80% of patients treated. However, while the catheters are approved by the Food and Drug Administration, there are still no randomized trial data demonstrating the role of current IAT therapy vs either tPA or standard management. IAT is reserved for patients with large artery occlusions in the basilar, distal carotid, or proximal middle cerebral arteries. Imaging the penumbra using magnetic resonance imaging or computed tomographic perfusion is currently the most frequently used way to identify patients who might benefit. However, the imaging and clinical criteria for identifying which patients benefit, and perhaps more importantly those who will do poorly despite IAT, remain unclear.

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Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial

Cited by 981 publications

References 34 publications

Dynamic Functional Cerebral Blood Volume Responses to Normobaric Hyperoxia in Acute Ischemic Stroke

Dynamic Functional Cerebral Blood Volume Responses to Normobaric Hyperoxia in Acute Ischemic Stroke

Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

Intra-arterial Therapy for Acute Ischemic Stroke

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