Thrombolysis In Brain Ischemia Grade Research Articles

Transcranial Doppler After Successful Endovascular Revascularization and Hospitalization Outcomes

Background Almost half of large‐vessel occlusion strokes have unfavorable outcomes despite successful endovascular therapy. We aim to investigate whether postrevascularization cerebral hemodynamics, determined by transcranial Doppler (TCD), associate with hospitalization outcomes in this population. Methods The current observational cohort study analyzed 155 patients with successfully revascularized anterior circulation large‐vessel occlusion stroke (mean age, 68.3±15.4 years; 55% women) who had TCD within 48 hours from endovascular therapy. TCD parameters (mean flow velocity, peak systolic velocity, and pulsatility index) were recorded at the ipsilateral middle cerebral artery, and blood flow signals were categorized using the Thrombolysis in Brain Ischemia grades into normal (grade 5), stenotic (grade 4), or dampened (grade ≤3). Hospitalization outcomes comprised favorable discharge modified Rankin Scale score (0–2), favorable discharge destination (home or acute inpatient rehabilitation), and in‐hospital mortality. Logistic regression models adjusted for age, initial National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT [Computed Tomography] Score were fit to determine TCD findings in association with study outcomes. Results Abnormal TCD‐derived blood flow was found in 54 (35%) cases, including 35 (23%) with Thrombolysis in Brain Ischemia grade 4 and 19 (12%) with Thrombolysis in Brain Ischemia grade ≤3. Overall, 31% had favorable discharge modified Rankin Scale score, 65% had favorable destination, and 14% died. Thrombolysis in Brain Ischemia grade ≤3 was associated with lower likelihood of both favorable discharge modified Rankin Scale score (adjusted odds ratio [OR], 0.09 [95% CI, 0.01–0.81]) and favorable destination (adjusted OR, 0.22 [95% CI, 0.07–0.71]). Mean flow velocity and peak systolic velocity were not associated with study outcomes. Conversely, increased pulsatility index was inversely associated with favorable destination (adjusted OR, 0.34 [95% CI, 0.13–0.87]). Conclusions TCD after successful endovascular therapy identified abnormal blood flow in one‐third of cases. Dampened flow and markers of increased microvascular resistance were associated with unfavorable hospitalization outcomes. TCD could provide valuable prognostic information in this population and identify potential therapeutic targets.

Abnormal Blood Flow on Transcranial Duplex Sonography Predicts Poor Outcome After Stroke Thrombectomy.

Background and Purpose- Hemodynamic changes following mechanical thrombectomy for large vessel occlusion stroke could be associated with complications and might affect prognosis. We investigated postinterventional middle cerebral artery blood flow on transcranial duplex sonography (TCD) and its prognostic value for anterior large vessel occlusion stroke patients. Methods- We identified all ischemic stroke patients who had undergone mechanical thrombectomy for anterior circulation large vessel occlusion from 2010 onwards. Postinterventional middle cerebral artery flow was graded according to the sonographic Thrombolysis in Brain Ischemia score and related to patient outcome stratified by the angiographic Thrombolysis in Cerebral Infarction reperfusion status. Results- Of 215 large vessel occlusion stroke patients, 193 patients (90%) showed successful angiographic recanalization (Thrombolysis in Cerebral Infarction grade 2b-3). Of those, 69 (36%) patients had abnormal sonographic middle cerebral artery blood flow (Thrombolysis in Brain Ischemia grade 0-4) within 72 hours after mechanical thrombectomy, which was an independent predictor for poor 90-day outcome. Conclusions- TCD indicates abnormal middle cerebral artery hemodynamics in a substantial proportion of patients with angiographically defined successful mechanical thrombectomy of the anterior cerebral circulation. Such changes are associated with poor short-term outcome.

Normal Findings on Pretreatment Transcranial Ultrasound in Patients Treated with Sonothrombolysis

In populations with a high (≥14) median National Institute of Health Stroke Score (NIHSS), a normal finding of Thrombolysis in Brain Ischemia grade 5 (TIBI 5) in the artery of interest has been reported to be an unusual finding when transcranial ultrasound is performed during thrombolysis. In such instances, a stroke mimic can be suspected, but there are alternative pathophysiological explanations. In this case series, the median NIHSS was relatively low (5), and 33% (6/18) of the patients treated with thrombolysis had TIBI 5 in the artery of interest at the time of treatment initiation. These 6 patients had normal findings on the computerized tomography angiography. Only 33% (2/6) of these patients were stroke mimics, the remaining had either lacunar (n = 2) or cortical strokes (n = 2). These cortical stroke patients probably had a pretreatment recanalization marked by partial symptom regression before treatment onset. Compared to patients with TIBI <5 at baseline, the patients with TIBI 5 at baseline tended to be younger (p = 0.19, Mann-Whitney test) and more often have lacunar syndrome (p = 0.18, g² test). Thus, among patients treated with thrombolysis and with a low median NIHSS, a finding of TIBI 5 is not unusual. This does not mean that the patient has a stroke mimic per se, and it tends to be more common among patients with lacunar syndrome than among patients with cortical syndromes. i 2014 S. Karger AG, Basel

Abstract W MP24: Modified Tibi (Thrombolysis in Brain Ischemia) Grading System for Assessment of Abnormal Residual Flow at Site of Intracranial Occlusion in Acute Ischemic Stroke

Background and purpose: The intracranial blood flow at the site of arterial occlusion in acute ischemic stroke can be measured with Transracial Doppler (TCD) using the Thrombolysis in Brain Ischemia (TIBI) grading system. The TIBI ranges from 0 to 5, where 0 no flow and 5 normal flow. Our study’s aim is to modify the TIBI grading system in order to make it simple to implement in an acute stroke setting. METHODS: We classified Modified TIBI grading as: Grade 0- no flow, Grade 1- Bad flow: there is systolic flow but no diastolic flow or systolic flow with delayed acceleration and diastolic flow, Grade 2-Good flow: normal upstroke systolic flow and diastolic flow with decreased mean flow velocity compared to contralateral vessel by 30 %. We used the clotbust database to evaluate the modified TIBI scoring system. Poor long-term outcome was defined as modified rankin scale (MRS) score &gt; 2. RESULTS: Total of 369 patients with acute ischemic stroke and intracranial arterial occlusion received IV r TPA. Median age was 71 years (IQ range: 58.7-79), Sex: women: 170(46.1%). Median NIHSS was 16 (IQ range: 12.7-2), 17/98 (17.3%) patients with modified TIBI 0, 73/205(35.6%) with modified TIBI 1 and 31/66( 47%) with modified TIBI 2 had achieved complete recanalization ( p value=0001). The multiple logistic regression model revealed Baseline higher NIHSS, systolic BP, glucose and modified TIBI grade 0 were independent negative predictor of complete recanalization. Patients with modified TIBI 3 had high probability of complete recanalization compared to TIBI 0(OR 3.14, CI 95%: 1.4-6.8, P=0.004).Poor outcome at 3 months (MRS&gt;2) was found in 46/75(61.3%) patients with modified TIBI 0, 94/170(55.3%) with modified TIBI 1 and 19/38(33.3%) with modified TIBI 2(P value &lt;0.004). On logistic model age, baseline NIHSS, glucose and TIBI 0 were independent negative predictors of good outcome.Although statistically insignificant but patients with modified TIBI 3 had a trend towards high probability of good functional outcome (OR: 1.73, CI 95%:0.73-4.12, p=0.20). CONCLUSION: Modified TIBI grading system is simplified version of TIBI grading and is easy to understand and apply clinically. It also predicts reliably the recanalization and functional outcome.

Comparative study of transcranial Doppler ultrasonography and magnetic resonance angiography on recanalization of intravenous thrombolysis with alteplase in acute ischemic stroke patients

Objective To evaluate the accuracy and clinical diagnostic values of thrombolysis in brain ischemia (TIBI) grade system of transcranial Doppler ultrasomography (TCD) in assessing the situation of recanalization after thrombolytic therapy with modified thrombolysis in cerebral infarction (m-TICI) grade system of MRA as reference. Methods Select 61 acute ischemic stroke patients with middle cerebral artery (MCA), basilar artery (BA) stenosis or occlusion receiving thrombolytic therapy with alteplase. The patients underwent MRA and TCD examination before and after 24 h thrombolysis. Use m-TICI and TIBI grade system to evaluate the rate of occlusion and recanalization of target artery and test the consistency of two systems on recanalization evaluation. Results Before thrombolytic therapy, m-TICI grade showed artery occlusion in 49 cases (80.33% ) and TIBI grade displayed artery occlusion in 45 cases (73.77% ), indicating high consistency statistically (κ = 0.816, P = 0.000). Twenty-four hours after thrombolytic therapy, m-TICI and TIBI grade showed complete recanalization in 9 cases (14.75%) and 11 cases (18.03%), partial recanalization in 18 cases (29.51% ) and 17 cases (27.87% ) respectively, showing high statistical consistency. The comprehensive evaluation of m-TICI and TIBI grade system revealed total recanalization in 27 cases (44.26%) and 28 cases (45.90%), showing high statistical consistency (κ = 0.917, P = 0.000). Conclusion The TIBI grade system of TCD has high consistency in diagnosing artery stenosis or occlusion and evaluating vascular recanalization in acute ischemic stroke patients with thrombolytic therapy compared with m-TICI grade system of MRA examination. TCD examination is flexible, convenient, economical, repeatable and can give bedside long monitoring, so it is worthy of further in-depth research, in order to promote its application in thrombolytic treatment process. doi：10.3969/j.issn.1672-6731.2013.12.010

Post-intervention TCD examination may be useful to predict outcome in acute ischemic stroke patients with successful intra-arterial intervention

Background and purposeSome acute stoke patients have a poor outcome despite successful arterial recanalization. We hypothesized that transcranial Doppler (TCD) findings from the rescued artery might predict poor outcome in patients with recanalization. MethodsAcute stroke patients treated with internal carotid artery or middle cerebral artery (MCA) occlusions with follow-up TCD examination after intra-arterial (IA) intervention were retrospectively analyzed. Only patients with at least a Thrombolysis In Myocardial Infarction (TIMI) flow grade ≥2 in the MCA territory were included. Mean flow velocity (MFV) and pulsatility index (PI) of the rescued MCA were obtained by TCD. Poor clinical outcome was defined as in-hospital death or decompressive craniectomy. ResultsAmong 50 patients, there were 8 (16%) in the Poor Outcome group and 42 (84%) in the Non-poor Outcome group. TCD was conducted at a median of 1day (interquartile range, 1–1) after IA therapy. Although MCA MFV was not different between the two groups, MCA PI was significantly higher in the Poor Outcome group than in the Non-poor Outcome group (1.3 [1.1–1.7] vs. 0.8 [0.7–1.1], p=0.002). After adjusting for the National Institutes of Health Stroke Scale score on admission, the Alberta Stroke Programme Early Computed Tomography score, a past history of coronary artery disease and the Thrombolysis In Brain Ischemia grade, MCA PI was an independent predictor of poor outcome (odds ratio: 1.71, 95% confidence interval: 1.10–2.66, p=0.017). ConclusionFollow-up TCD examination after IA intervention in acute stroke patients may predict poor outcome beyond angiographic residual TIMI flow.

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

We sought to evaluate the diagnostic accuracy of ultrasound criteria for recanalization during real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures in acute ischemic stroke patients in an international, multicenter study. Consecutive acute ischemic stroke patients with proximal intracranial occlusions underwent intra-arterial reperfusion procedures with simultaneous real-time transcranial Doppler monitoring at 3 tertiary-care stroke centers. Residual flow signals at the site of angiographically confirmed occlusions were monitored at a constant transtemporal insonation angle using a standard head-frame. Recanalization was assessed simultaneously by digital subtraction angiography and ultrasound using thrombolysis in myocardial infarction and thrombolysis in brain ischemia (TIBI) criteria, respectively. Independent readers blinded to digital subtraction angiography performed validation of TIBI flow grades. The interrater reliability for assessment of TIBI grades was investigated. We evaluated time-linked real-time digital subtraction angiography transcranial Doppler images from 96 diagnostic digital subtraction angiography runs during intra-arterial reperfusion procedures in 62 acute ischemic stroke patients (mean age, 59 ± 17 years; 58% men; median baseline National Institutes of Health Stroke Scale score, 18 [interquartile range 12-21]; median time from symptom onset to intra-arterial procedure initiation, 240 minutes [interquartile range 163-308]). The interrater reliability for evaluation of TIBI grades and assessment of recanalization was good (Cohen κ: 0.838 and 0.874, respectively; P<0.001). Compared with angiography, transcranial Doppler had the following accuracy parameters for detection of complete recanalization (TIBI 4 and 5 versus thrombolysis in myocardial infarction 3, flow grades): sensitivity, 88% (95% confidence interval, 72%-96%); specificity, 89% (79%-95%); positive predictive value, 81% (65%-91%); negative predictive value, 93% (84%-98%); and overall accuracy 89% (80%-94%). At laboratories with high-interrater reliability, TIBI criteria can accurately predict brain recanalization in real time as compared with thrombolysis in myocardial infarction angiographic scores.

Bilateral atherosclerotic internal carotid artery occlusion causing acute bihemispheric infarctions

Multiple acute brain infarctions in both cerebral hemispheres involving the anterior circulation are uncommon (affecting less 1.0–6.0 % of acute stroke patients) and usually suggest an embolic mechanism, particularly one of aortic or cardiac origin [1–4]. Unilateral internal carotid artery (ICA) atherosclerotic lesions may rarely cause acute bihemispheric infarctions through crossflow in the anterior communicating artery with the contralateral anterior cerebral artery (ACA) territory being invariably involved in all described cases [4]. To the best of our knowledge there has been no report of bilateral extracranial atherothrombotic ICA occlusion causing acute bihemispheric infarctions involving both middle cerebral artery territories. A 73-year-old man with a history of hypertension, hypercholesterolemia and smoking presented with an acute right upper arm weakness that he noticed on awakening. Admission brain CT and electrocardiogram were normal. Neurological examination disclosed a mild left hemipareris and left-side visual neglect with an NIH Stroke Scale score (NIHSS-score) of 5 points. The patient underwent emergent carotid duplex evaluation showing multiple hyperechoic plaques in both common carotid arteries (CCA) and acute bilateral ICA occlusion (Fig. 1a, b). Transcranial Doppler examination showed (1) acute bilateral middle cerebral artery (MCA) occlusion with minimal flow (thrombolysis in brain ischemia grade I) in right and blunted flow (thrombolysis in brain ischemia grade II) in left MCA, (2) present collateral flow through reversed ophthalmic artery (OA) bilaterally and (3) absent collateral flow through posterior communicating arteries. The patient also underwent 30-min bilateral transcranial doppler monitoring that documented the presence of microembolic signals in both MCAs (Fig. 2). Acute reperfusion therapies including intravenous or intra-arterial thrombolysis as well as mechanical thrombectomy were withheld because of unknown time of stroke onset. Emergent echocardiography excluded the presence of cardiac thrombus and other source of cardiogenic embolism (including aortic arch dissection). He was treated with aspirin (325 mg) and enoxeparin (40 mg). Fourteen hours later, he became quadriplegic and lethargic (NIHSS-score 26 points). Repeat brain CT (performed after 12 h from the baseline CT) showed bilateral cortical infarctions (Fig. 1c, d) in both MCA territories (arrowheads). The patient expired the following day. Simultaneous occurrence of multiple infarcts in different arterial territories is a characteristic feature of cardioembolic stroke according to the findings of recent studies G. Tsivgoulis (&) I. Heliopoulos K. Vadikolias M. Flamouridou S. Tsakaldimi C. Piperidou Department of Neurology, University Hospital of Alexandroupolis, Democritus University of Thrace, Kapodistriou 3, Nea Xili, Alexandroupolis 68100, Greece e-mail: tsivgoulisgiorg@yahoo.gr

Abstract 60: Outcomes Following Sonothrombolysis in Severe Acute Ischemic Stroke

Background&amp;Purpose: A recent meta-analysis showed that sonothrombolysis is safe and can double the rate of early recanalization in acute ischemic stroke (AIS). We sought to explore whether patients with severe strokes could clinically benefit from ultrasound amplification of tPA-induced recanalization. Subjects&amp;Methods: We compared functional outcomes at 3 months among randomized AIS patients with pre-treatment NIHSS scores &gt;=10 in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and pilot randomized clinical safety study of sonothrombolysis with microspheres (Definity study). Patients had proximal arterial occlusions identified by baseline TCD and received intravenous (IV) tPA or IV tPA plus continuous 2-hour TCD ultrasound monitoring (=sonothrombolysis). Favorable outcome was defined as modified Rankin Scale (mRS) 0-1 at 3 months. Sustained complete recanalization was defined as Thrombolysis in Brain Ischemia (TIBI) flow grades 4-5 assessed by TCD at 2 hours after tPA bolus. Symptomatic intracranial hemorrhage (sICH) was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS &gt;=4) within 72 hours from stroke onset. Results: A total of 139 AIS patients with severe stroke due to proximal arterial occlusions (mean age 69±13years, 56% men, median NIHSS 17, interquartile range 14-21, range 10-34) were randomized in CLOTBUST (n=105), TUCSON (n=21) and Definity (n=13). A total of 60 (43%) and 79 (57%) patients were randomized to IV tPA and sonothrombolysis, respectively. Patients treated with IV tPA and sonothrombolysis did not differ in terms of age, baseline stroke severity, baseline TIBI grades and onset-to-treatment time. Symptomatic ICH rates were similar in patients treated with IV tPA and sonothrombolysis (5.0% vs. 5.1%; p=0.987). More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA group (38.0% vs. 18.3%; p=0.012). Favorable outcome (mRS 0-1) tended to be more prevalent in the sonothrombolysis than in the IV tPA group (36.6% vs. 23.2%; p=0.104). Conclusions: Our data point to a signal-of-efficacy and provide basis to determine the sample size of a phase 3 randomized trial of sonothrombolysis in patients with severe strokes ( NCT01098981 ).

Stroke severity and residual flow determined by transcranial colour-coded ultrasound (TCCD) predict recanalization and clinical outcome during thrombolysis

ObjectiveTo determine clinical, neuroradiological or ultrasonographic parameters associated with early recanalization and clinical outcome in patients treated with intravenous (IVT) or combined intravenous–intra-arterial (IVT–IAT) thrombolysis. MethodsFrom 2004 to 2007, all consecutive ischemic stroke patients admitted within a 3-hour window and who underwent thrombolytic therapy were reviewed. Degree of occlusion and recanalization during IVT was assessed by transcranial color-coded ultrasound (TCCD) using Thrombolysis In Brain Ischemia (TIBI) classification. According to our protocol, in case of recanalization (modification of TIBI grade≥1) after 30min of IVT, the procedure was maintained over 1h. When TIBI grade failed to improve after 30min, IVT was discontinued and IAT performed using the remaining tPA dose. The study endpoints were early recanalization defined as achievement of TIBI≥3 grade at 30min (for this endpoint all patients presenting a TIBI grade 3 at admission were excluded from the model) and clinical outcome at 3months assessed by the modified Rankin scale. ResultsSeventy-one patients underwent either IVT (n=41) or IVT-IAT (n=30). Among all the variables, NIHSS and TIBI grades assessed at baseline were the only independent factors associated with early recanalization and clinical outcome. Furthermore, the combination of these two parameters was superior in predicting early recanalization and outcome to either one of them taken separately. An inverse correlation between NIHSS, TIBI grades and early recanalization was found: the lower the TIBI grade, the lower the probability to recanalize for any given NIHSS. ConclusionBaseline NIHSS and TIBI grades were the only independent factors associated with early recanalization and clinical outcome. The combination of these two parameters was superior to each single variable in predicting the study endpoints and could therefore be used to improve the selection of patients for IVT or more aggressive therapies.

End-Diastolic Velocity Increase Predicts Recanalization and Neurological Improvement in Patients With Ischemic Stroke With Proximal Arterial Occlusions Receiving Reperfusion Therapies

It is unknown how little flow velocity improvement is necessary to achieve recanalization and clinical recovery. We sought to investigate which flow velocity parameter was associated with complete recanalization/reperfusion and neurological improvement in patients receiving reperfusion therapies. Patients with proximal intracranial occlusions were treated with systemic or intra-arterial tissue plasminogen activator within 6 hours from symptom onset. Consecutive peak systolic and end-diastolic (EDV) velocities were measured during continuous transcranial Doppler monitoring. Recanalization was graded with Thrombolysis in Brain Ischemia grades. Neurological and functional outcomes were assessed by the National Institutes of Health Stroke Scale and modified Rankin Scale scores. Of 36 patients (mean age 57 + or - 19 years, median National Institutes of Health Stroke Scale 15 points, interquartile range 9), 13 (36%) achieved complete recanalization and those had greater EDV increase during transcranial Doppler monitoring (15 + or - 11 cm/s versus 6 + or - 10 cm/s; P=0.001). Peak systolic velocity increase with complete recanalization was 25 + or - 11 cm/s (versus 20 + or - 25 cm/s with partial recanalization/persisting occlusion; P=0.123). Neurological improvement at 24 hours positively correlated to EDV increase (Spearman r=0.337, P=0.044) but not to peak systolic velocity (r=0.197, P=0.250). EDV increase at the end of monitoring was higher in patients with favorable functional outcome at 3 months (13 + or - 13 cm/s versus 4 + or - 8 cm/s; P=0.021). After adjustment for potential confounders, including age, stroke risk factors, and baseline stroke severity, a 10-cm/s increase in EDV was independently associated with a 3-point decline in the National Institutes of Health Stroke Scale score at 24 hours from baseline (95% CI: 0 to 5; P=0.045). A modest increase in the EDV as opposed to peak systolic velocity is associated with complete recanalization/reperfusion, early neurological improvement, and favorable functional outcome. Diastolic flow augmentation may represent a novel target for development of reperfusion therapies.

Evaluation of perfusion CT and TIBI grade in acute stroke for predicting thrombolysis benefit and clinical outcome

To evaluate the prognostic accuracy of combining perfusion CT (PCT) and thrombolysis in brain ischemia (TIBI) ultrasonographic grade in the triage of stroke patients who will benefit from thrombolysis and in predicting the clinical outcome. We conducted a prospective study of all consecutive stroke patients admitted to our hospital from March 2003 to July 2007, presenting with signs of acute stroke within the therapeutic window, who had undergone either intravenous or combined intravenous and intra-arterial thrombolysis. All patients were evaluated by a complete stroke CT protocol, transcranial color-coded duplex sonographic monitoring, follow-up imaging (CT or MRI) and clinical outcome at 3 months, as assessed by the modified Rankin scale (mRS). A total of 34 patients were included with a mean NIHSS on admission of 14.2. This study revealed that PCT had 95% sensitivity and 71% specificity in the evaluation of therapy benefit as well as 75% sensitivity and 39% specificity in predicting clinical outcome. The extent of ischemic tissue according to PCT and TIBI grade were significantly correlated (p<0.05). Using the MTT-TTP approach was an alternative to the classical MTT-CBV approach for determining tissue at risk. The clinical outcome assessed by the mRS was considered favorable (mRS 0-2) in 16 patients and unfavorable (mRS>2) in 18 patients. PCT was the most accurate predictor of both thrombolytic therapy benefit and clinical outcome. The TIBI score was useful for determining whether or not to perform intravenous therapy alone or as a combined therapy.

Residual Flow at the Site of Intracranial Occlusion on Transcranial Doppler Predicts Response to Intravenous Thrombolysis: A Multi-Center Study

Background: We examined if transcranial Doppler (TCD) flow findings at the site of intracranial occlusions predict outcomes of stroke patients receiving intravenous rt-PA treatment. Subjects and Methods: TCD detected residual flow with the Thrombolysis in Brain Ischemia (TIBI) grading system before intravenous rt-PA bolus in patients with acute arterial intracranial occlusion. Timing and completion of early recanalization were measured for occlusive TIBI flow grades using TCD monitoring. Poor responders were defined as modified Rankin scores (mRS) >2 at 3 months. Results: A total of 361 patients with proximal arterial occlusion received intravenous rt-PA at 137.4 ± 36 min (median NIHSS 16). Mean age 69 ± 13, women: 168 (46.5%). Seventeen of 96 (17.7%) patients with TIBI 0, 41/124 (33.1%) with TIBI 1, 29/76 (38.2%) with TIBI 2 and 31/65 (47.7%) with TIBI 3 had achieved complete recanalization (p < 0.001). Higher NIHSS, SBP, glucose and lower TIBI grades were independent negative predictors of complete recanalization in the final logistic model. Patients with TIBI 0 had less probability of complete recanalization than patients with residual flow (TIBI 1–3) (OR_adj 0.4, CI 95% 0.22–0.8, p = 0.008). Median time to recanalization in patients with TIBI 0 was longer (155 min, interquartile range 104–190 min) than with TIBI ≥1 (120 min, range 60–170 min, p = 0.01, Mann-Whitney U test). In the stepwise multiple linear regression models adjusting for baseline characteristics, the only 2 factors that independently associated with time to recanalization were: time to rt-PA treatment and the absent flow (TIBI 0) on baseline TCD. Absent flow (TIBI 0) was associated with a longer time of recanalization of 35.2 min (95% CI 0.3–70.1 min, p = 0.048). Poor outcomes at 3 months were found in 61.3% of patients with no residual flow (TIBI 0), 56.9% with minimal (TIBI 1), 51.5% with blunted (TIBI 2), and 33.9% with dampened (TIBI 3) flows (p = 0.012). Patients with TIBI 0 have a higher likelihood of poor outcome (OR 3.1, 95% CI 1.5–6.4, p = 0.002). Patients who achieved complete recanalization have OR_adj 5.2 for good outcome (95% CI 2.8–9.8, p < 0.001). Conclusions: The pretreatment residual flow at intracranial occlusion predicts the likelihood of complete recanalization, time of recanalization and long-term outcome. No detectable residual flow indicates the least chance to achieve recanalization and recovery with systemic thrombolysis and may support an early decision for combined endovascular rescue.

Sonothrombolysis With Transcranial Color-Coded Sonography and Recombinant Tissue-Type Plasminogen Activator in Acute Middle Cerebral Artery Main Stem Occlusion

Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented. Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control group. All underwent standard thrombolysis with intravenous recombinant tissue-type plasminogen activator. Thirty-seven subjects were included; 19 subjects were treated in the target (US) group and 18 in the control (no-US) group, all with no residual flow in the middle cerebral artery main stem occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with the no-US group, the US group showed greater improvement in National Institutes of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator initiation. Recanalization (complete or partial) after 1 hour occurred in 57.9% of the US group and 22.2% of the no-US group (P=0.045). After 90 days, 4 subjects from the US group had a modified Rankin Score <or=1 (none from the no-US group) and 8 had a Barthel Index >or=95 (none from the no US group; P=0.106 and P=0.003, respectively). Three subjects from the US group (15.8%) developed a symptomatic intracranial hemorrhage as did one (5.6%) in the no-US group (P=0.60). This small randomized study indicates a beneficial impact of transcranial ultrasound on recanalization and short-term outcome in subjects with middle cerebral artery main stem occlusion and recombinant tissue-type plasminogen activator treatment.

Association of Pretreatment ASPECTS Scores with tPA‐Induced Arterial Recanalization in Acute Middle Cerebral Artery Occlusion

The Alberta Stroke Program Early CT-Score (ASPECTS) assesses early ischemic changes within the middle cerebral artery (MCA) and predicts poor outcome and increased risk for thrombolysis-related symptomatic ICH. We evaluated the potential relationship between pretreatment ASPECTS and tPA-induced recanalization in patients with MCA occlusions. Consecutive patients with acute ischemic stroke due to MCA occlusion were treated with standard IV-tPA and assessed with transcranial Doppler (TCD) for arterial recanalization. Early recanalization was determined with previously validated Thrombolysis in Brain Ischemia (TIBI) flow-grading system at 120 minutes after tPA-bolus. All pretreatment CT-scans were prospectively scored by trained investigators blinded to TCD findings. Functional outcome at 3 months was evaluated using the modified Rankin Scale (mRS). IV-tPA was administered in 192 patients (mean age 68 +/- 14 years, median NIHSS-score 17). Patients with complete recanalization (n= 51) had higher median pretreatment ASPECTS (10, interquartile range 2) than patients with incomplete or absent recanalization (n= 141; median ASPECTS 9, interquartile range 3, P= .034 Mann-Whitney U-test). An ASPECTS < or =6 was documented in 4% and 17% of patients with present and absent recanalization, respectively (P= .019). Pretreatment ASPECTS was associated with complete recanalization (OR per 1-point increase: 1.54; 95% CI 1.06-2.22, P= .023) after adjustment for baseline characteristics, risk factors, NIHSS-score, pretreatment TIBI grades and site of arterial occlusion on baseline TCD. Complete recanalization (OR: 33.97, 95% CI 5.95-185.99, P < .001) and higher ASPECTS (OR per 1-point increase: 1.91; 95% CI 1.17-3.14, P= .010) were independent predictors of good functional outcome (mRS 0-2). Higher pretreatment ASPECT-scores are associated with a greater chance of complete recanalization and favorable long-term outcome in tPA-treated patients with acute MCA occlusion.

Association of Pretreatment Blood Pressure With Tissue Plasminogen Activator-Induced Arterial Recanalization in Acute Ischemic Stroke

Elevated systolic blood pressure (SBP) and lack of early vessel recanalization are predictors of poor outcome among patients with stroke treated with systemic tissue plasminogen activator (tPA). We aimed to evaluate the potential relationship between pretreatment SBP and tPA-induced recanalization. Consecutive patients with acute ischemic stroke resulting from intracranial artery occlusion were treated with standard intravenous tPA and assessed with 2-MHz transcranial Doppler for arterial recanalization. Early arterial recanalization was determined with previously validated Thrombolysis in Brain Ischemia flow grading system at 120 minutes after tPA bolus. Functional outcome at 3 months was evaluated using the modified Rankin Scale. A total of 351 patients received intravenous tPA (mean age: 68.7+/-13.4 years, median National Institutes of Health Stroke Scale score 16.5). Patients with complete recanalization (n=94) had lower mean pretreatment SBP values (152+/-23 mm Hg) than patients with incomplete or absent recanalization (n=257, 160+/-22 mm Hg, P=0.010). Pretreatment SBP levels were inversely associated with complete recanalization (OR per 10-mm Hg increase: 0.85; 95% CI: 0.74 to 0.98, P=0.022) after adjustment for demographics, risk factors, stroke severity, pretreatment Thrombolysis in Brain Ischemia grades, and continuous versus intermittent exposure to transcranial Doppler. Although patients with poor functional 3-month outcomes (modified Rankin Scale >2) had higher pretreatment SBP values (160+/-25 mm Hg) than functionally independent patients (154+/-20 mm Hg, P=0.027), pretreatment SBP levels were not independently associated with functional outcome on multivariable analysis. Age, complete recanalization, baseline National Institutes of Health Stroke Scale score, and time from symptom onset to tPA bolus were independent (P<0.05) predictors of 3-month outcome. Higher pretreatment SBP levels are associated with poor recanalization in patients with acute stroke treated with intravenous tPA.

Residual Flow Signals Predict Complete Recanalization in Stroke Patients Treated With TPA

Residual blood flow around thrombus prior to treatment predicts success of coronary thrombolysis. The authors aimed to correlate the presence of residual flow signals in the middle cerebral artery (MCA) with completeness of recanalization after intravenous tissue plasminogen activator (TPA). The authors studied consecutive patients treated with intravenous TPA therapy who had a proximal MCA occlusion on pretreatment transcranial Doppler (TCD). Patients were continuously monitored for 2 hours after TPA bolus. Absent residual flow signals correspond to the thrombolysis in brain ischemia (TIBI) 0 grade, and the presence of residual flow signals was determined as TIBI 1-3 flow grades. Complete recanalization was defined as flow improvement to TIBI grades 4-5. Seventy-five patients with a proximal MCA occlusion had median pre-bolus NIHSS 16 (85% with > or = 10 points). TPA bolus was given at 141 +/- 56 minutes (median 120 minutes). Complete recanalization was observed in 25 (33%), partial in 23 (31%), and no early recanalization was seen in 27 (36%) patients within 2 hours after TPA bolus. Only 19% with absent residual flow signals (TIBI grade 0, n = 26) on pretreatment TCD had complete early recanalization. If pretreatment TCD showed the presence of any residual flow (TIBI 1-3, n = 49), 41% had complete recanalization within 2 hours of TPA bolus (P = .03). Patients with detectable residual flow signals before IV TPA bolus are twice as likely to have early complete recanalization. Those with no detectable residual flow signals have less than 20% chance for complete early recanalization with intravenous TPA and may be candidates for intra-arterial therapies.