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

Abstract

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...

Mechanical thrombeсtomy and trombaspiration in stroke. Problem claims

“…Термін «час-мозок», запропонований J.L. Saver у 2005 р., також означає «частромб», адже з часом у тромбі відбуваються структурні зміни, які призводять до його ущільнення, що разом з його протяжністю знижує ефективність ендоваскулярного втручання [22,23] [24]. Ця проблема за межами 4,5-годинного терапевтичного вікна для тромболізису не вирішена і потребує подальшого вивчення.…”

“Time lost is clot resolution lost”: the neglected perspective of the therapeutic time window for ischemic stroke

“…Treatment initiation after 270 min was an independent predictor of lack of recanalization in distal MCA occlusion, whereas there was a trend toward lower recanalization in proximal MCA occlusion treated after 90 min. In the related editorial comment, Tsivgoulis and Alexandros ( 11 ) proposed the motto “time is clot” for thrombolytic therapy. After 1 year, Kim et al ( 12 ) reported a linear inverse relationship between time from symptom onset to treatment and the degree of thrombus resolution after rtPA administration, assessed by a thin section non-contrast computed tomography scan performed at 1 h after IVT.…”