Socorro Piñeiro

Bridging Intravenous–Intra-Arterial Rescue Strategy Increases Recanalization and the Likelihood of a Good Outcome in Nonresponder Intravenous Tissue Plasminogen Activator-Treated Patients A Case–Control Study

Background and Purpose— Safety and efficacy of the “bridging therapy” (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV–IA thrombolysis using a case–control approach. Methods— Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV–IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Results— Forty-two IV–IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV–IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV–IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV–IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV–IA patients were functionally independent at 3 months and only 14.9% IV-NR (P=0.012). Conclusions— Bridging IV–IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.

Extending the time window for endovascular procedures according to collateral pial circulation.

Background and Purpose— Good collateral pial circulation (CPC) predicts a favorable outcome in patients undergoing intra-arterial procedures. We aimed to determine if CPC status may be used to decide about pursuing recanalization efforts. Methods— Pial collateral score (0–5) was determined on initial angiogram. We considered good CPC when pial collateral score <3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement >4-point decline in admission–discharge National Institutes of Health Stroke Scale. Results— We studied CPC in 61 patients (31 middle cerebral artery, 30 internal carotid artery). Good CPC patients (n=21 [34%]) had lower discharge National Institutes of Health Stroke Scale score (7 versus 21; P=0.02) and smaller infarcts (56 mL versus 238 mL; P<0.001). In poor CPC patients, a receiver operating characteristic curve defined a TTI cutoff point <300 minutes (sensitivity 67%, specificity 75%) that better predicted clinical improvement (TTI <300: 66.7% versus TTI >300: 25%; P=0.05). For good CPC patients, no temporal cutoff point could be defined. Although clinical improvement was similar for patients recanalizing within 300 minutes (poor CPC: 60% versus good CPC: 85.7%; P=0.35), the likelihood of clinical improvement was 3-fold higher after 300 minutes only in good CPC patients (23.1% versus 90.1%; P=0.01). Similarly, infarct volume was reduced 7-fold in good as compared with poor CPC patients only when TTI >300 minutes (TTI <300: poor CPC: 145 mL versus good CPC: 93 mL; P=0.56 and TTI >300: poor CPC: 217 mL versus good CPC: 33 mL; P<0.01). After adjusting for age and baseline National Institutes of Health Stroke Scale score, TTI <300 emerged as an independent predictor of clinical improvement in poor CPC patients (OR, 6.6; 95% CI, 1.01–44.3; P=0.05) but not in good CPC patients. In a logistic regression, good CPC independently predicted clinical improvement after adjusting for TTI, admission National Institutes of Health Stroke Scale score, and age (OR, 12.5; 95% CI, 1.6–74.8; P=0.016). Conclusions— Good CPC predicts better clinical response to intra-arterial treatment beyond 5 hours from onset. In patients with stroke receiving endovascular treatment, identification of good CPC may help physicians when considering pursuing recanalization efforts in late time windows.

Impact of blood pressure changes and course on hematoma growth in acute intracerebral hemorrhage

An association between high blood pressure (BP) in acute intracerebral hemorrhage (ICH) and hematoma growth (HG) has not been clearly demonstrated. Therefore, the impact of BP changes and course on HG and clinical outcome in patients with acute ICH was determined.

Serum Low-Density Lipoprotein Cholesterol Level Predicts Hematoma Growth and Clinical Outcome After Acute Intracerebral Hemorrhage

Background and Purpose— Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increased risk of death after intracerebral hemorrhage (ICH). Nevertheless, their link with hematoma growth (HG) is unknown. Therefore, we aimed to investigate the relationship between LDL-C levels, HG, and clinical outcome in patients with acute ICH. Methods— We prospectively studied 108 consecutive patients with primary supratentorial ICH presenting within 6 hours from symptoms onset. National Institutes of Health Stroke Scale score and ICH volume on computed tomography scan were recorded at baseline and at 24 hours. Lipid profile was obtained during the first 24 hours. Significant HG was defined as hematoma enlargement >33% or >6 mL at 24 hours. Early neurological deterioration as well as mortality and poor long-term outcome (modified Rankin Scale score >2) at 3 months were recorded. Results— Although LDL-C levels were not correlated with ICH volume (r=−0.18; P=0.078) or National Institutes of Health Stroke Scale score (r=−0.17; P=0.091) at baseline, lower LDL-C levels were associated with HG (98.1±33.7 mg/dL versus 117.3±25.8 mg/dL; P=0.003), early neurological deterioration (89.2±31.8 mg/dL versus 112.4±29.8 mg/dL; P=0.012), and 3-month mortality (94.9±37.4 mg/dL versus 112.5±28.5 mg/dL; P=0.029), but not with poor long-term outcome (109.5±31.3 mg/dL versus 108.3±30.5 mg/dL; P=0.875). Moreover, LDL-C levels were inversely related to the amount of hematoma enlargement at 24 hours (r=−0.31; P=0.004). In multivariate logistic regression analysis, LDL-C level <95 mg/dL emerged as an independent predictor of HG (OR, 4.24; 95% CI, 1.26–14.24; P=0.020), early neurological deterioration (OR, 8.27; 95% CI, 1.66–41.16; P=0.010), and 3-month mortality (OR, 6.34; 95% CI, 1.29–31.3; P=0.023). Conclusions— Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.

Predictors of Tissue-Type Plasminogen Activator Nonresponders According to Location of Vessel Occlusion

Background and Purpose— Information on the clinical and hemodynamic profile of intravenous tissue-type plasminogen activator nonresponders, at different locations of arterial occlusion, may improve the selection of candidates for rescue reperfusion therapies. Therefore, we aim to investigate predictors of failing intravenous tissue-type plasminogen activator therapy according to occluded vessel and location of the clot. Methods— We prospectively evaluated consecutive patients with an acute ischemic stroke admitted within the first 6 hours of onset. Five hundred forty-eight patients with documented intracranial occlusion were included. Patients were categorized according to site of vessel occlusion into 4 distinct groups: proximal middle cerebral artery occlusion (n=251), distal middle cerebral artery occlusion (n=194), internal carotid artery bifurcation occlusion (n=61), and basilar artery occlusion (n=42). Recanalization was assessed on transcranial Doppler at 1 hour of tissue-type plasminogen activator bolus. Results— Among patients with proximal middle cerebral artery occlusion, the presence of severe extracranial internal carotid artery stenosis or occlusion (OR, 2.36; 95% CI, 1.15–4.84; P=0.02) and age >74 years (OR, 1.84; 95% CI, 1.02–3.31; P=0.04) independently predicted no recanalization. No independent predictors of no recanalization were identified in patients with distal middle cerebral artery occlusion. In patients with internal carotid artery bifurcation occlusion, a previous diagnosis of hypertension (OR, 12.77; 95% CI, 2.12–76.88; P=0.05), and absence of atrial fibrillation (OR, 8.15; 95% CI, 1.40–47.44; P=0.02) emerged as independent predictors of no recanalization. Similarly, among patients with basilar artery occlusion, absence of atrial fibrillation was as an independent predictor of no recanalization (OR, 7.50; 95% CI, 1.40–40.35; P=0.02). Conclusions— The use of relevant predictors of no recanalization and a rapid neurovascular evaluation may improve the selection of patients for more aggressive rescue strategies.

Sonothrombolysis for the treatment of acute stroke: current concepts and future directions.

Achieving rapid reperfusion transcranial color-coded duplex is the critical issue in acute stroke treatment. Ultrasound (US) generates negative pressure waves that are associated with an increase in either intrinsic or intravenous tissue plasminogen activator (tPA)-induced fibrinolytic activity. Higher rates of tPA-induced arterial recanalization, associated with a trend towards better functional outcome, have been safely achieved by using high-frequency US. By contrast, the use of low-frequency US and transcranial color-coded duplex has been linked to significant hemorrhagic complications. US-accelerated thrombolysis has been safely enhanced by lowering the amount of energy needed for acoustic cavitation with the administration of microbubbles. Other applications of US are being studied, including its intra-arterial use. Operator-independent devices, which will spread the use of these US techniques further, are also being developed. This article reviews the present status of sonothrombolysis in acute stroke treatment, highlighting both experimental and clinical studies addressing this issue, and discusses its future regarding both efficacy and safety.

Preferential effect of premorbid statins on atherothrombotic strokes through collateral circulation enhancement.

Background/Aims: Endovascular recanalization therapies are an increasingly used strategy for acute cerebral ischemia with heterogeneous clinical outcomes. We aimed to determine the impact of previous medication on ischemic stroke following intra-arterial revascularization therapy. Methods: Consecutive patients receiving intra-arterial reperfusion therapy after an acute intracranial occlusion were analyzed. Premorbid use of antiplatelets, statins, oral antidiabetic drugs, antihypertensive drugs and oral anticoagulants were recorded. Collateral pial circulation (CPC) was scored on initial angiogram. Results: 118 patients were included (mean age 70.4 ± 11 years, 45% female). 66 patients (56%) were cardioembolic, 30 (25%) atherothrombotic, and 22 (19%) other/unknown etiologies. No significant impact of medication was detected in all the series or cardioembolic strokes. However, relevant differences were found among atherothrombotic strokes. The previous use of antiplatelets was associated with smaller infarct volume (64 vs. 170 ml; p = 0.043) whereas premorbid statin predicted reduced infarct volume (64 vs. 215 ml; p = 0.019), clinical improvement (79 vs. 29%; p = 0.016) and good CPC (100 vs. 20%; p = 0.04). Statins were the only medication independently predicting reduced infarct volume and clinical improvement and this effect depended on CPC. Conclusion: Previous use of statins may preferentially benefit patients with atherothrombotic strokes by favoring the development of CPC.

Selecting Endovascular Treatment Strategy according to the Location of Intracranial Occlusion in Acute Stroke

Background: Selection of endovascular approaches for acute stroke patients remains unclear. The efficacy of intra-arterial therapy (IAT) has been demonstrated in the past. However, in the last years, the use of mechanical thrombectomy by retrievers (RET) is increasing at the expense of IAT. We aimed to compare several clinical outcomes between patients treated with IAT or RET. Methods: In a 6-year period, acute stroke patients (<8 h) with confirmed internal carotid artery (ICA) occlusion or middle cerebral artery (MCA) occlusion undergoing endovascular therapy were prospectively included in our database. Patients who underwent intra-arterial tissue plasminogen activator (tPA) ± microguidewire mechanical clot disruption (IAT group) were compared with those who underwent thrombectomy with the Solitaire® or Trevo® retrievers (RET group). Recanalization (REC) was considered if at the end of the endovascular procedure thrombolysis in cerebral infarction score was 2a-3. Dramatic clinical improvement (DCI) was defined as a decrease of ≥10 NIHSSS points from baseline to discharge or 7 days. Results: One hundred and eighty patients were included, 100 (55.6%) patients in the IAT group and 80 patients (44.4%) in the RET group. There were no differences in baseline characteristics (age, gender, risk factors profile, previous treatment with i.v. tPA, baseline NIHSS, extracranial ICA angioplasty and time to REC). Rates of REC, DCI and symptomatic intracranial hemorrhage were also similar between groups. Among patients with ICA occlusions (41 IAT, 34 RET), REC was significantly higher with RET (83.9 vs. 61%; p = 0.04).There was a trend towards a higher DCI rate in the RET group (32.3%) compared with the IAT group (14.6%; p = 0.06). According to MCA occlusions, there were no major differences in the main outcome variables. The number needed to treat to achieve one additional DCI with RET compared with IAT was 12 for MCA occlusions, and only 5 for ICA occlusions. Conclusions: Among acute stroke patients undergoing endovascular therapies, the benefits of RET over IAT are greater in ICA occlusions. Retrievers may be considered as the first therapeutic option in these patients.

Arterial Blood Gas Analysis of Samples Directly Obtained Beyond Cerebral Arterial Occlusion During Endovascular Procedures Predicts Clinical Outcome

Real‐time intra‐procedure information about ischemic brain damage degree may help physicians in taking decisions about pursuing or not recanalization efforts.

Potential blood pressure thresholds and outcome in acute intracerebral hemorrhage.

Background: Little is known about the relationships between different systolic blood pressure (SBP) thresholds and their outcomes in acute intracerebral hemorrhage (ICH). We aimed to determine the associations of potential systolic blood pressure (SBP) thresholds with hematoma growth (HG) and clinical outcome in patients with acute ICH. Methods: 117 patients with acute (<6 h) spontaneous supratentorial ICH underwent blood pressure monitoring at 15 min interval over the first 24 h. SBP thresholds of 140, 150, 160, 170, 180, 190, and 200 mm Hg were assessed by means of the percentage of 24-hour values exceeding each threshold (SBP load). HG at 24 h, early neurological deterioration (END), 24-hour and 90-day mortality, and poor outcome were recorded. Results: SBP 170, 180, 190, and 200 loads were significantly correlated with the amount of both absolute and relative hematoma enlargement at 24 h. In multivariate analyses, SBP 170 load was related to HG and END, while SBP 160 load was associated with mortality at 24 h. No thresholds were independently related to outcomes at 90 days. Conclusion: In patients with acute ICH, SBP lowering to at least less than 160 mm Hg threshold may be needed to minimize the deleterious effect of high SBP on 24-hour outcomes.