Speed of tPA-Induced Clot Lysis Predicts DWI Lesion Evolution in Acute Stroke (original) (raw)
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Can clot density predict recanalization in acute ischemic stroke treated with intravenous tPA?
Clinical and Translational Neuroscience
Stroke has become an absolute emergency that is treated by additional endovascular means or by replacing pharmacological options. Modern neuroradiological techniques such as computed tomography (CT) allow us to examine multiple parameters of the diseased brain. These focused on the parenchyma and hemodynamics for pretherapeutic decisions. However, it has become evident that the clot is the current target for interventional measures. Clot length is established as a marker for recanalization. The dense artery sign is known as an acute CT sign of stroke that is readily visible on acute nonenhanced CT. The rationale behind our study was to study if clot density might represent clot vulnerability or resistance to treatment. We conducted a prospective study of all consecutive stroke patients admitted to our hospital over 1 year, who presented with signs of acute middle cerebral artery stroke within the therapeutic window, and who underwent either intravenous or combined intravenous and in...
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.)
2010
Background-The duration of cerebral blood flow impairment correlates with irreversibility of brain damage in animal models of cerebral ischemia. Our aim was to correlate clinical recovery from stroke with the timing of arterial recanalization after therapy with intravenous tissue plasminogen activator (tPA). Methods-Patients with symptoms of cerebral ischemia were treated with 0.9 mg/kg tPA IV within 3 hours after stroke onset (standard protocol) or with 0.6 mg/kg at 3 to 6 hours (an experimental institutional review board-approved protocol). National Institutes of Health Stroke Scale (NIHSS) scores were obtained before treatment, at the end of tPA infusion, and at 24 hours; Rankin Scores were obtained at long-term follow-up. Transcranial Doppler (TCD) was used to locate arterial occlusion before tPA and to monitor recanalization (Marc head frame, Spencer Technologies; Multigon 500M, DWL MultiDop-T). Recanalization on TCD was determined according to previously developed criteria. Results-Forty patients were studied (age 70Ϯ16 years, baseline NIHSS score 18.6Ϯ6.2). A tPA bolus was administered at 132Ϯ54 minutes from symptom onset. Recanalization on TCD was found at the mean time of 251Ϯ171 minutes after stroke onset: complete recanalization occurred in 12 (30%) patients and partial recanalization occurred in 16 (40%) patients (maximum observation time 360 minutes). Recanalization occurred within 60 minutes of tPA bolus in 75% of patients who recanalized. The timing of recanalization inversely correlated with early improvement in the NIHSS scores within the next hour (polynomial curve, third order r 2 ϭ0.429, PϽ0.01) as well as at 24 hours. Complete recanalization was common in patients who had follow-up Rankin Scores if 0 to 1 (Pϭ0.006). No patients had early complete recovery if an occlusion persisted for Ͼ300 minutes. Conclusions-The timing of arterial recanalization after tPA therapy as determined with TCD correlates with clinical recovery from stroke and demonstrates a 300-minute window to achieve early complete recovery. These data parallel findings in animal models of cerebral ischemia and confirm the relevance of these models in the prediction of response to reperfusion therapy. (Stroke. 2000;31:1812-1816.)
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.)
Apparent Diffusion Coefficient Thresholds Do Not Predict the Response to Acute Stroke Thrombolysis
Stroke, 2005
Background and Purpose-Apparent diffusion coefficient (ADC) thresholds for tissue infarction have been identified in acute stroke. IV tissue plasminogen activator (tPA) is associated with tissue salvage. We hypothesized that tPA would lower the ADC threshold for infarction. Methods-ADC and mean transit time (MTT) maps were generated for 26 patients imaged within 6 hours of stroke onset (12 tPA and 14 conservatively managed controls). MTT maps and day-90 T2-weighted images were coregistered to ADC maps. Relative ADC (rADC) values were calculated for initial diffusion-weighted imaging (DWI) lesions, infarct growth regions (final infarct volumeϪthe acute DWI lesion volume), and hypoperfused salvaged regions (HS; MTT map abnormalityϪthe final infarct volume). When relevant, the DWI lesion was subdivided into DWI reversal and DWI infarct regions. Results-Mean DWI lesion rADC was 0.79 in tPA and 0.74 in untreated patients (Pϭ0.097). Mean rADC in HS and infarct growth regions were similar in tPA patients (0.950 and 0.946) and untreated patients (0.957, Pϭ0.76; 0.970, Pϭ0.08, respectively). The rADC in HS tissue was directly correlated with the time to treatment with tPA (rϭ0.685; Pϭ0.029). DWI reversal was seen in 67% of tPA-treated patients and in 36% of those conservatively managed (Fisher exact test; Pϭ0.238). In the 13 patients with DWI reversal, the mean rADC in these regions (0.81Ϯ0.07) was significantly higher than in the acute DWI region that infarcted (0.74Ϯ0.07; Pϭ0.02), although no absolute thresholds could be identified. Conclusions-The peri-DWI lesion region contains tissue with intermediate ADC values. The fate of this tissue is variable and cannot be predicted based on the ADC alone. DWI expansion occurs in bioenergetically normal tissue, and this is attenuated by tPA in a time-dependent fashion. (Stroke. 2005;36:2626-2631.)
Stroke, 2003
Background and Purpose-We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA). Methods-Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion-(DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion. Results-Twenty-nine patients (16 men and 13 women; meanϮSD age, 65Ϯ14 years) underwent MRI; the mean time from symptom onset to treatment was 255Ϯ62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7Ϯ5.4 if recanalization had occurred and 14Ϯ2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved (rϭϪ0.68, Pϭ0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume: rϭ0.51, Pϭ0.006, TTP: rϭ0.35, Pϭ0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score (rϭ0.58, Pϭ0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 (Pϭ0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score (Pϭ0.03). Conclusions-Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke. (Stroke. 2003;34:458-463.
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%).