Thrombolysis-Related Hemorrhagic Infarction: A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion (original) (raw)
Related papers
Stroke, 2004
Background and Purpose-We aimed to evaluate the timing, speed, and degree of tissue plasminogen activator (tPA)-induced recanalization in patients with proximal middle cerebral artery (MCA) occlusion of different stroke subtypes. Methods-We evaluated 72 patients with acute stroke caused by proximal MCA occlusion treated with intravenous tPA in Ͻ3 hours. Transcranial Doppler monitoring of recanalization was conducted during tPA infusion and at 6 hours. Strokes were categorized as large-vessel disease strokes, cardioembolic strokes, or strokes of undetermined origin according to Trial of Org 10172 in Acute Stroke Treatment criteria. Results-During 1-hour tPA infusion, recanalization occurred in 34 patients (47%); 32% showed a sudden, 50% showed a stepwise, and 18% showed a slow pattern of recanalization. One-hour recanalization was more frequent in patients with cardioembolic stroke (59%) compared with large-vessel disease (8%) and undetermined origin (50%) strokes. A cardiac source of emboli was identified in 81% of patients who showed a sudden clot breakup during tPA infusion. Rate of complete recanalization at 6 hours was higher (Pϭ0.006) in patients with cardioembolic stroke (50%) compared with other stroke subtypes (27%). Sudden recanalization was associated (Pϭ0.002) with a higher degree of neurological improvement at 24 hours compared with stepwise, slow, and no recanalization. A graded response in long-term outcome was observed in relation to the speed of clot lysis during tPA administration. Conclusions-We demonstrate that the pattern of tPA-induced MCA recanalization differs among stroke subtypes. Early recanalization was more frequent, faster, and more complete in patients with cardioembolic stroke compared with other stroke subtypes. (Stroke. 2004;35:486-490.)
Stroke, 2001
Background and Purpose-The relationship between arterial recanalization, infarct size, and outcome in patients treated with intravenous thrombolytics remains unclear. Therefore, we aimed to determine the time course of recombinant tissue plasminogen activator (rtPA)-induced recanalization in patients with cardioembolic stroke treated Ͻ3 hours from symptom onset and to investigate the relationship between arterial recanalization, infarct volume, and outcome. Methods-We prospectively studied 72 patients with an acute cardioembolic stroke in the middle cerebral artery territory: 24 treated with rtPA at Ͻ3 hours and 48 matched controls. Serial transcranial Doppler examinations were performed on admission and at 6,12, 24, and 48 hours. Infarct volume was measured by use of CT at day 5 to 7. Modified Rankin Scale score was used to assess outcome at 3 months. Results-Rate of 6-hour recanalization was higher (PϽ0.001) in the rtPA group (66%) than in the control group (15%).
The Tokai Journal of Experimental and Clinical Medicine, 2013
We examined the predictive value of clinical and radiological findings, including cerebral microbleeds (CMBs) seen in gradient-echo T2*-weighted magnetic resonance images, for hemorrhagic transformation (HT) following ischemic stroke, in ischemic stroke patients treated with recombinant tissue plasminogen activator (rt-PA). The subjects were 71 patients with acute ischemic stroke treated with rt-PA (50 males, 21 females; mean age±standard deviation 73±10 years; 53 cardiogenic stroke, 18 atherothrombotic). HT on computed tomography (CT)(mean: 24 hours after onset) was seen in 26 (37%) subjects. The mean Alberta stroke programme early CT score on diffusion-weighted images (ASPECTS-DWI) score was significantly lower in the group with HT than that in the group without HT (6.5±2.3 vs 8.4±1.6, P<0.001). Prevalence of CMBs was not significantly different between the groups with and without HT. Relative risk of various factors for appearance of HT was evaluated by logistic regression ana...
Stroke, 2014
See related article, p 2555. S ince 1994, thrombolysis treatment with alteplase (tissue-type plasminogen activator [tPA]) before 3 hours in acute stroke has been the only therapy approved for this disease, and it is associated with improved functional outcome in acute ischemic stroke. 1-4 Initially, studies such as National Institute of Neurological Disorder and Stroke (NINDS) and European Cooperative Acute Stroke Study (ECASS) I and II have demonstrated the safety of intravenous thrombolysis during the first 3 hours since stroke symptoms onset. 5-7 Afterward, studies such as ECASS III and Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SIST-ISTR) have demonstrated that safety and functional outcomes are less favorable after 3 hours, but the wider time window till 4.5 hours also offers an opportunity for some patients. 8,9 Early artery reopening has been recognized as a surrogate marker of good outcome after tPA therapy. 10,11 However, recanalization is achieved in only 30% to 40% of patients, and <50% of them become independent at long term. 12,13 There is evidence that recanalization after intravenous tPA is influenced by several factors, including size and location of arterial occlusion, atrial fibrillation, and diabetes mellitus. 14-16 Although the efficacy on functional outcome of thrombolytic treatment depends on time, it is not clear whether the effect of intravenous tPA on recanalization is also time dependent. Therefore, we aimed to identify the impact of time to treatment on tPA-related recanalization in patients with acute ischemic stroke. Background and Purpose-Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. Methods-Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. Results-Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1-0.933) and time to treatment ≤270 minutes (OR, 0.995; 95% CI, 0.99-0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952-0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855-0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195-0.887). None recanalized >270 minutes. Conclusions-The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.
Stroke, 2010
Background and Purpose— Acute rates of recanalization after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in proximal vessel occlusion have been estimated sparingly, typically using transcranial Doppler (TCD). We aimed to study acute recanalization rates of IV rt-PA in CT angiogram-proven proximal (internal carotid artery [ICA], M1 middle cerebral artery [MCA], M2-MCA, and basilar artery) occlusions and their effects on outcome. Materials and Methods— The CT angiogram database of the Calgary stroke program was reviewed for the period 2002 to 2009. All patients with proximal vessel occlusions receiving IV rt-PA who were assessed for recanalization by TCD or angiogram (for acute endovascular treatment) were included for analysis. Rates of acute recanalization as observed on TCD/first run of angiogram and postendovascular therapy recanalization rates were noted. Modified Rankin Scale score ≤2 at 3 months was used as a good outcome. Results— Among 1341 patients in th...
Thrombolysis-Related Hemorrhagic Infarction
Stroke, 2002
Background and Purpose — The role of early and delayed recanalization after thrombolysis in the development of hemorrhagic transformation (HT) subtypes remains uncertain. We sought to explore the association between the timing of recanalization and HT risk in patients with proximal middle cerebral artery (MCA) occlusion treated with intravenous recombinant tissue plasminogen activator (rtPA) <3 hours of stroke onset and to investigate the relationship between HT subtypes, infarct volume, and outcome. Methods — Thirty-two patients with acute stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom onset were prospectively studied. Serial transcranial Doppler examinations were performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess outcome at 3 months. Results — Early and delayed recanalization was identified in 17 patients (53.1%) and 8 patients (25%), res...
Stroke, 2005
Background and Purpose-We aimed to determine clinical and hemodynamic predictors of early reocclusion (RO) in stroke patients treated with intravenous tissue plasminogen activator (tPA). Methods-We studied 142 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. All patients underwent carotid ultrasound and transcranial Doppler (TCD) examination before tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were performed at baseline and serially for Ͻ24 hours. TCD monitoring of MCA recanalization (RE) and RO was performed during the first 2 hours after tPA bolus and repeated when clinical deterioration occurred Ͻ24 hours after documented RE in absence of intracranial hemorrhage. Results-After 1 hour of tPA administration, RE occurred in 84 (61%) patients (53 partial, 31 complete). Of these, 21 (25%) patients worsened after an initial improvement and 17 (12%) of them showed RO on TCD. RO was identified at a mean time of 65Ϯ55 minutes after documented RE. RO was associated (Pϭ0.034) with a lower degree of 24-hour NIHSS score improvement than sustained RE, and a higher modified Rankin scale score at 3 months (Pϭ0.002). Age older than 75 years (Pϭ0.012), previous antiplatelet treatment (Pϭ0.048), baseline NIHSS score Ͼ16 points (Pϭ0.009), higher leukocytes count (Pϭ0.042), beginning of RE Ͻ60 minutes after tPA bolus (Pϭ0.039), and ipsilateral severe carotid stenosis/occlusion (Pϭ0.001) were significantly associated with RO. In a logistic regression model, NIHSS score Ͼ16 at baseline (odds ratio [OR], 7.1; 95% CI, 1.3 to 32) and severe ipsilateral carotid disease (OR, 13.3; 95% CI, 3.2 to 54) remained as independent predictors of RO. Conclusions-Stroke severity and ipsilateral severe carotid artery disease independently predict RO after tPA-induced MCA RE. (Stroke. 2005;36:1452-1456.)
Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke
Annals of Neurology, 1992
An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator(rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebal hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assesed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation, Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 ± 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occured in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occured significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.