Real-time Validation of Transcranial Doppler Criteria in Assessing Recanalization During Intra-arterial Procedures for Acute Ischemic Stroke An International, Multicenter Study

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Background and Purpose-The effect of tissue-type plasminogen activator on functional outcome decreases progressively over time. However, given the differential pattern of arterial occlusion, stroke severity, and speed of ischemic lesion growth among candidates for reperfusion, the time window should be adjusted accordingly. We aimed to identify the impact of time-to-treatment according to stroke severity on functional outcome in patients with acute ischemic stroke. Methods-We included 581 consecutive patients treated with alteplase according to the European Summary of Product Characteristics criteria. Patients were categorized according to National Institutes of Health Stroke Scale (NIHSS) severity in mild NIHSS (≤8), moderate NIHSS (9-15), and severe stroke NIHSS (≥16). We sequentially analyzed timeto-treatment to achieve favorable outcome (modified Rankin Scale ≤2 at 3 months

Section: Transcranial Doppler Ultrasound Protocolmentioning

confidence: 99%

“…Most of them were women (53.1%). The mean age was 74.08±12.15 years, and the median NIHSS score on admission was 20 [18][19][20][21]. The mean time-to-treatment was 164.74±74.84 minutes.…”

Section: Severe Strokementioning

confidence: 99%

Baseline National Institutes of Health Stroke Scale–Adjusted Time Window for Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke

Muchada

Rubiera

Rodríguez‐Luna

et al. 2014

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“…2 TCD criteria had been previously validated against CTA and digital subtraction angiography in real time. 13,14 TCD and CTA studies were reviewed and adjudicated locally by investigators. Recanalization was defined as an increase in thrombolysis in brain ischemia by ≥1 grade compared with baseline and an overall thrombolysis in brain ischemia ≥2.…”

Section: Vessel Imaging and Clinical Assessmentsmentioning

confidence: 99%

CLOTBUST-Hands Free

Barreto

Alexandrov

Shen

et al. 2013

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Background and Purpose— The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health–sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion. Methods— All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days. Results— Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows: 14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5–29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows: 8 of 20 (40%; 95% confidence interval, 19%–64%) complete and 2 of 20 (10%; 95% confidence interval, 1%–32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate: 8 of 14 (57%; 95% confidence interval, 29%–82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%–49) patients had a modified Rankin scale of 0 to 1. Conclusions— Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: CLOTBUST-HF NCT01240356.

“…However, it should be noted that a recent multicenter study has established the diagnostic accuracy (>80%) of ultrasound criteria for detection of recanalization during real-time TCD monitoring of intra-arterial reperfusion procedures in consecutive patients with AIS. 15 Second, the retrospective design of the present study as well as the lack of a prespecified sample size estimation require a cautious interpretation of the reported findings. Third, the authors did not include all potential confounders including residual flow at the site of intracranial occlusion, stroke subtype, length of thrombus, and degree of collateral circulation in the final multivariate logistic regression model evaluating the time dependency of tPA-induced recanalization.…”

mentioning

confidence: 88%

Does “Time Is Brain” Also Mean “Time Is Clot”?

Tsivgoulis

Alexandrov

2014

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P ooled analyses of major randomized controlled trials of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) [1][2][3] have established the clinical dictum of "Time is Brain" 4 because longer times from stroke symptom onset to the initiation of IVT are associated with a lower likelihood of good clinical outcomes at 3 months. Recanalization could be the main mechanism why this time dependency is seen, and the so-called recanalization hypothesis is supported by evidence from a meta-analysis of clinical studies that documented recanalization.5 However, no prospective study to date has demonstrated that indeed shorter onset-to-treatment times (OTTs) result in shorter time to recanalization of an intracranial occlusion, in turn proving it to be the key link to better long-term functional outcomes. Conversely, could this also mean that longer times to treatment produce less recanalization attributable to clot maturation and progression of ischemic injury to brain tissues? Could "Time is Brain" also mean "Time is Clot"? As time is lost, clot wins.In several pilot single-center studies of real-time monitoring of tissue-type plasminogen activator (tPA) infusion by transcranial Doppler (TCD), both the elapsed time from symptom onset to recanalization 6 and the speed of clot lysis 7 with IVT thrombolysis were associated with early clinical recovery from AIS as determined by serial National Institutes of Health Stroke Scale assessments. Nevertheless, the effect of the temporal profile of recanalization on 3-month functional outcome after adjusting for potential prognostic factors remains unknown. In this issue of Stroke, Muchada et al 8 provide a perspective on the "Time is Brain" dictum. They evaluated time dependency of tPA-induced recanalization in consecutive patients with AIS attributable to proximal or distal acute middle cerebral artery occlusions. The main findings of this retrospective analysis of prospectively collected data during a 12-year period in a single center indicate that the effect of IVT on early recanalization evaluated by TCD at 1 hour after the end of tPA infusion decreases over time. More specifically, treatment initiation after 270 minutes predicted the lack of recanalization especially in distal middle cerebral artery occlusions. Stemming from the way we diagnose some of these occlusions with TCD (dampened high-resistance flow pattern), 9 this finding points to either clot maturation or progression of ischemic injury with no reflow phenomenon, or both.The authors also observed a trend toward lower recanalization rates in patients with proximal intracranial occlusions treated after 90 minutes. This finding lends further support that patients with proximal occlusions and albeit more severe strokes should be treated as fast as possible with reperfusion therapies that yield the highest and fastest recanalization rates. These patients should be granted prompt access to comprehensive stroke centers.10 Hence, only OTT and pretreatment National Institutes of Health Stroke Scale score emerged as...