Hashem Shaltoni

Is Intra-Arterial Thrombolysis Safe After Full-Dose Intravenous Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke?

Background and Purpose— The optimal approach for acute ischemic stroke patients who do not respond to intravenous recombinant tissue plasminogen activator (IV rt-PA) is uncertain. This study evaluated the safety and response to intra-arterial thrombolytics (IATs) in patients unresponsive to full-dose IV rt-PA. Methods— A case series from a prospectively collected database on consecutive acute ischemic stroke patients treated with IATs after 0.9 mg/kg IV rt-PA during a 7-year interval was collected. Primary outcome measures included symptomatic intracranial hemorrhage and mortality. As indicators of response, secondary outcome measures were recanalization and discharge disposition. Results— Sixty-nine patients (mean±SD age, 60±13 years; range, 26 to 85 years; 55% male) with a median pretreatment National Institutes of Health Stroke Scale score of 18 (range, 6 to 39) were included. IV rt-PA was started at 124±32 minutes (median, 120 minutes) and IAT, at 288±57 minutes (median, 285 minutes). IATs consisted of reteplase (n=56), alteplase (n=7), and urokinase (n=6), with an average total dosage of 2.8 U, 8.6 mg, and 700 000 U, respectively. Symptomatic intracranial hemorrhage occurred in 4 of 69 (5.8%) patients; 3 cases were fatal. Recanalization was achieved in 50 (72.5%) and a favorable outcome (home or inpatient rehabilitation) in 38 (55%). Conclusions— IAT therapy after full-dose IV rt-PA in patients with persisting occlusion and/or lack of clinical improvement appears safe compared with IV rt-PA alone or low-dose IV rt-PA followed by IAT. A high rate of recanalization and favorable outcome can be achieved.

Balloon Guide Catheter Improves Revascularization and Clinical Outcomes With the Solitaire Device Analysis of the North American Solitaire Acute Stroke Registry

Background and Purpose— Efficient and timely recanalization is an important goal in acute stroke endovascular therapy. Several studies demonstrated improved recanalization and clinical outcomes with the stent retriever devices compared with the Merci device. The goal of this study was to evaluate the role of the balloon guide catheter (BGC) and recanalization success in a substudy of the North American Solitaire Acute Stroke (NASA) registry. Methods— The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. BGC use was at the discretion of the treating physicians. Results— There were 354 patients included in the NASA registry. BGC data were reported in 338 of 354 patients in this subanalysis, of which 149 (44%) had placement of a BGC. Mean age was 67.3±15.2 years, and median National Institutes of Health Stroke Scale score was 18. Patients with BGC had more hypertension (82.4% versus 72.5%; P=0.05), atrial fibrillation (50.3% versus 32.8%; P=0.001), and were more commonly administered tissue plasminogen activator (51.6% versus 38.8%; P=0.02) compared with patients without BGC. Time from symptom onset to groin puncture and number of passes were similar between the 2 groups. Procedure time was shorter in patients with BGC (120±28.5 versus 161±35.6 minutes; P=0.02), and less adjunctive therapy was used in patients with BGC (20% versus 28.6%; P=0.05). Thrombolysis in cerebral infarction 3 reperfusion scores were higher in patients with BGC (53.7% versus 32.5%; P<0.001). Distal emboli and emboli in new territory were similar between the 2 groups. Discharge National Institutes of Health Stroke Scale score (mean, 12±14.5 versus 17.5±16; P=0.002) and good clinical outcome at 3 months were superior in patients with BGC compared with patients without (51.6% versus 35.8%; P=0.02). Multivariate analysis demonstrated that the use of BGC was an independent predictor of good clinical outcome (odds ratio, 2.5; 95% confidence interval, 1.2–4.9). Conclusions— Use of a BGC with the Solitaire Flow Restoration device resulted in superior revascularization results, faster procedure times, decreased need for adjunctive therapy, and improved clinical outcome.

Dual Antiplatelet Therapy Monitoring for Neurointerventional Procedures Using a Point-of-Care Platelet Function Test: A Single-Center Experience

BACKGROUND AND PURPOSE: Growing evidence of the relationship between poor antiplatelet response and occurrence of clinical events elicited the need of monitoring the response which has not been part of our daily practice. We present our initial experience with a new point-of-care antiplatelet-function test (VerifyNow assay) in neurointerventional procedures. MATERIALS AND METHODS: Among the 106 consecutive patients from July 2006 to April 2007, ninety-eight met the inclusion criteria. Our preferred antiplatelet regimen was aspirin (325 mg daily) and clopidogrel (300 mg of loading dose followed by 75 mg daily) starting 5–10 days before the procedure. The test results were reported as aspirin-reaction unit (ARU) for aspirin and P2Y12 reaction units (PRU), baseline (BASE), and percentage inhibition for the P2Y12 assay and were summarized as mean ± SD of the values. We analyzed the effects of several factors of poor clopidogrel response (<40% inhibition). The occurrence of thrombotic events was recorded. RESULTS: The mean ARU of aspirin assays was 438.3 ± 47.9 (range, 350–632), and the response was poor in 2 patients (2.1%). For clopidogrel, the mean of the BASE, PRU, and percentage inhibition was 356.8 ± 56.3 (range, 234–495), 198.9 ± 104.4 (range, 8–401), and 45.2 ± 27.1% (range, 0–98), respectively. Forty-two patients (42.9%) showed poor response. Multivariate analysis showed greater body weight (81.9 Kg ± 19.1 kg versus 69.9 ± 15 kg) in the poor-response group. All 3 cases of intraprocedural thrombosis (3.1%) were observed only in the poor-response group. CONCLUSION: We observed a high frequency of poor clopidogrel responses in the neurointerventional setting. Routine monitoring of the drug response would be helpful for the early identification of poor antiplatelet responders so that we may modify the regimen and/or treatment plan.

Yield and Accuracy of Urgent Combined Carotid/Transcranial Ultrasound Testing in Acute Cerebral Ischemia

Background and Purpose— We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). Methods— NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, ≥50% stenoses or thrombus in the symptomatic artery. Results— One hundred and fifty patients (70 women, mean age 66±15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS ≥10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. Conclusions— Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results

Background Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials. Methods The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage. Results 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. Clinical outcome: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2). Conclusions The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.

Thrombus Burden Is Associated With Clinical Outcome After Intra-Arterial Therapy for Acute Ischemic Stroke

Background and Purpose— Studies have established a relation between recanalization and improved clinical outcome in acute ischemic stroke patients; however, intra-arterial clot size has not been routinely assessed. The aim of the study was to determine the impact of intra-arterial thrombus burden on intra-arterial treatment (IAT) and clinical outcome. Methods— A retrospective review of our IAT stroke database included procedure time, recanalization, symptomatic intracranial hemorrhage, poor outcome (modified Rankin Scale score ≥4 at discharge), and mortality. The modified Thrombolysis in Myocardial Infarction thrombus grade was dichotomized into grades 0 to 3 (no clot or moderate thrombus, <2 vessel diameters) versus grade 4 (large thrombus, >2 vessel diameters). Results— Data were collected on 135 patients with thrombus grading. The baseline median National Institutes of Health Stroke Scale score was higher in patients of grade 4 compared with grades 0 to 3 (19 vs 17, P=0.012). Grade 4 thrombi required longer (median, range) times for IAT (113, 37 to 415 minutes vs 74, 22 to 215 minutes, respectively; P<0.001) and higher rates of mechanical clot disruption (wire, angioplasty, snare, stent, or Merci retriever) compared with grades 0 to 3 (76% vs 53%, P=0.005). There were no differences in rates of symptomatic intracranial hemorrhage (6.6% vs 4.1%, P=0.701) or recanalization (50% vs 61%, P=0.216) in grade 4 versus grades 0 to 3. Multivariate analysis adjusted for age, baseline National Institutes of Health Stroke Scale score, and artery of involvement showed that grade 4 thrombi were independently associated with poor outcome (odds ratio=2.4; 95% CI, 1.06 to 5.57; P=0.036) and mortality (odds ratio=4.0; 95% CI, 1.2 to 13.2; P=0.023). Conclusions— High thrombus grade as measured by the modified Thrombolysis in Myocardial Infarction criteria may be a risk factor that contributes to poor clinical outcome.

Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

BACKGROUND Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with tissue plasminogen activator (t-PA) in patients with acute stroke is safe and feasible. METHODS Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously [IV] x 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours [target temperature 33-35 degrees C] followed by 12 hours of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. RESULTS All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n = 8) or surface (n = 10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9 hours and 43 minutes. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2 hours and 30 minutes from induction and 6 hours and 21 minutes from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. DISCUSSION Combining caffeinol with hypothermia in patients with acute stroke given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia, or both.

Intravenous TPA for Very Old Stroke Patients

Background: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. Methods: We studied patients treated with intravenous TPA and divided them into younger (<80 years) and older (≧80 years) groups for comparison. Diagnostic transcranial Doppler was completed before bolus, and patients were consequently monitored for up to 2 h when feasible. Clinical data included NIH Stroke Scale score, symptomatic intracranial hemorrhage (ICH) and discharge disposition. Results: We studied 127 younger (mean 63 years, range 31–79) and 56 older patients (mean 84 years, range 80–93). Median baseline NIH Stroke Scale score was higher in the older group (18 vs. 14 points, NS). Occlusion locations, onset to needle time (median 130 vs. 120 min) as well as improvement at 24 h (median 5 vs. 4 points) were similar in both groups. Transcranial Doppler monitoring showed similar partial or complete recanalization rates (66 vs. 66%), onset to recanalization time (median 160 vs. 158 min) and reocclusion rates (26 vs. 25%). Symptomatic and fatal ICH was not higher in the older group (7.1 and 3.5% vs. 6.3 and 3.9%, NS). There was higher mortality among older patients (20 vs. 11%, NS). At discharge, 23% of older patients went home, 41% underwent rehabilitation and 16% were transferred to skilled nursing facilities, compared with 31, 43 and 15% respectively, in the younger group. Conclusion: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality.

North American SOLITAIRE Stent-Retriever Acute Stroke Registry: choice of anesthesia and outcomes.

Background and Purpose— Previous work that predated the availability of the safer stent-retriever devices has suggested that general anesthesia (GA) may have a negative impact on outcomes in patients with acute ischemic stroke undergoing endovascular therapy. Methods— We reviewed demographic, clinical, procedural (GA versus local anesthesia [LA], etc), and site-adjudicated angiographic and clinical outcomes data from consecutive patients treated with the Solitaire FR device in the investigator-initiated North American SOLITAIRE Stent-Retriever Acute Stroke (NASA) Registry. The primary outcomes were 90-day modified Rankin Scale, mortality, and symptomatic intracranial hemorrhage. Results— A total of 281 patients from 18 centers were enrolled. GA was used in 69.8% (196/281) of patients. Baseline demographic and procedural factors were comparable between the LA and GA groups, except the former demonstrated longer time-to-groin puncture (395.4±254 versus 337.4±208 min; P=0.04), lower National Institutes of Health Stroke Scale (NIHSS; 16.2±5.8 versus 18.8±6.9; P=0.002), lower balloon-guide catheter usage (22.4% versus 49.2%; P=0.0001), and longer fluoroscopy times (39.5±33 versus 28±22.8 min; P=0.008). Recanalization (thrombolysis in cerebral infarction ≥2b; 72.94% versus 73.6%; P=0.9) and rate of symptomatic intracranial hemorrhage (7.1% versus 11.2%; P=0.4) were similar but modified Rankin Scale ⩽2 was achieved in more LA patients, 52.6% versus 35.6% (odds ratio, 1.4 [1.1–1.8]; P=0.01). In multivariate analysis, hypertension, NIHSS, unsuccessful revascularization, and GA use (odds ratio, 3.3 [1.6–7.1]; P=0.001) were associated with death. When only anterior circulation and elective GA patients were included, there was a persistent difference in good outcomes in favor of LA patients (50.7% versus 35.5%; odds ratio, 1.3 [1.01–1.6]; P=0.04). Conclusions— The NASA Registry has demonstrated that clinical outcomes and survival are significantly better in patients treated with LA, without increased symptomatic intracranial hemorrhage risk. Future trials should prospectively evaluate the effect of GA on outcomes.

Predictors of poor outcome despite recanalization: a multiple regression analysis of the NASA registry

Background Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70–83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40–55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry. Methods Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0–2 (good outcome) vs 3–6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power. Results Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80). Conclusions Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization.