Jorge Pagola

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.

Ultraearly hematoma growth predicts poor outcome after acute intracerebral hemorrhage

Objective: To investigate the impact of the adjustment of initial intracerebral hemorrhage (ICH) volume by onset-to-imaging time (ultraearly hematoma growth [uHG]) on further hematoma enlargement and outcome in patients with acute ICH. Methods: We studied 133 patients with acute (<6 hours) supratentorial ICH. Patients underwent baseline and 24-hour CT scans for ICH volume measurement, and a CT angiography (CTA) for the detection of the spot sign. We defined uHG as the relation between baseline ICH volume/onset-to-imaging time, hematoma growth (HG) as hematoma enlargement >33% or >6 mL at 24 hours, early neurologic deterioration (END) as increase ≥4 points in the NIH Stroke Scale score or death at 24 hours, and poor long-term outcome as modified Rankin Scale score >2 at 3 months. Results: The uHG was significantly faster in spot sign patients (p < 0.001), as well as in patients who experienced HG (p = 0.021), END (p < 0.001), 3-month mortality (p < 0.001), and poor long-term outcome (p < 0.001). The uHG improved the accuracy of baseline ICH volume in the prediction of END (sensitivity 93.1% vs 82.8%, specificity 85.3% vs 82.4%) and 3-month mortality (sensitivity 77.5% vs 70%, specificity 87.9% vs 84.6%). A uHG >10.2 mL/hour emerged as the most powerful predictor of HG (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.39–9.07, p = 0.008), END (OR 70.22, 95% CI 14.63–337.03, p < 0.001), 3-month mortality (OR 16.96, 95% CI 5.32–54.03, p < 0.001), and poor long-term outcome (OR 6.19, 95% CI 1.32–28.98, p = 0.021). Conclusions: The uHG represents a powerful and easy-to-use tool for improving the prediction of HG and outcome in patients with acute ICH.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

Background and Purpose— We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. Methods— We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ⩽ or >80 years; onset-to-groin puncture ⩽ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ⩽2) and mortality at 3 months by multivariate modeling. Results— We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ⩽6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. Conclusions— This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke.

Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Matrix metalloproteinases (MMPs) have been implicated in blood–brain barrier disruption and ICH pathogenesis. In this study, we determined the levels MMP‐2 and MMP‐9 in plasma and their brain expression in CAA‐associated hemorrhagic stroke. Although MMP‐2 and MMP‐9 plasma levels did not differ among patients and controls, their brain expression was increased in perihematoma areas of CAA‐related hemorrhagic strokes compared with contralateral areas and nonhemorrhagic brains. In addition, MMP‐2 reactivity was found in β‐amyloid (Aβ)‐damaged vessels located far from the acute ICH and in chronic microbleeds. MMP‐2 expression was associated to endothelial cells, histiocytes and reactive astrocytes, whereas MMP‐9 expression was restricted to inflammatory cells. In summary, MMP‐2 expression within and around Aβ‐compromised vessels might contribute to the vasculature fatal fate, triggering an eventual bleeding.

Association Between Time to Reperfusion and Outcome Is Primarily Driven by the Time From Imaging to Reperfusion

Background and Purpose— A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear. Methods— We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0–2) was described via adjusted odds ratios (ORs) for every 30-minute delay. Results— Median admission National Institutes of Health Stroke Scale was 17.0 (14.0–20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59–0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67–1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54–0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35–0.9) but not in ASPECTS≥8 (OR, 0.99; 95% CI, 0.68–1.44). Conclusions— Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Difficult catheter access to the occluded vessel during endovascular treatment of acute ischemic stroke is associated with worse clinical outcome

Background and aim During endovascular procedures for acute ischemic stroke, catheter access to the occluded vessel may be technically difficult or impossible. The aim of this study was to access the impact of difficult catheter access to target the carotid artery on clinical outcome. Methods Anterior circulation stroke patients undergoing transfemoral endovascular procedures where studied. Patients were divided into four groups according to time from groin puncture to target carotid catheterization quartiles. Patients in quartile 4 (Q4) were considered difficult carotid access. We defined several outcome measures: recanalisation (final Thrombolysis in Cerebral Infarction score ≥2a), time from groin puncture to recanalisation and favorable long term outcome (modified Rankin Scale score <3 at 3 months). Results Of 130 patients studied, carotid catheterization was impossible in seven patients (5.1%). These patients had significantly lower rates of recanalization (14.3% vs 80.5%; p<0.01) and favorable outcome (0% vs 36%; p=0.038). Among patients with an accessible carotid artery(n=123), median time from groin puncture to carotid catheterization was 20 min (IQR 10). A negative correlation between time to carotid access and recanalization was observed (r=−0.31; p<0.01). Patients in Q4 (>30 min) had lower rates of recanalization (60.7% vs 82.4%; p=0.02) and a lower favorable outcome (13.6% vs 41.3%; p=0.04). A logistic regression adjusted by age showed that baseline National Institutes of Health Stroke Scale score (OR 0.8; 95% CI: 0.72 to 0.92 p<0.01) and having difficult access (OR 1.3; 95% CI 1.3 to 20.1 p=0.018) independently predicted worse long term outcome. Conclusions Difficult catheter access to target the carotid is common during acute endovascular treatment of stroke patients and is associated with a worse clinical outcome. If transfemoral access appears difficult, alternative access such as direct carotid puncture could be explored.

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.

Trevo versus solitaire a head-to-head comparison between two heavy weights of clot retrieval.

Recent reports have indicated that mechanical thrombectomy may have potential to treat acute ischemic stroke. However, few comparative studies of neurothrombectomy devices are reported. This study aims to compare the safety and effectiveness of two retrievable stent systems in acute ischemic stroke patients.