Poor Collateral Circulation Assessed by Multiphase Computed Tomographic Angiography Predicts Malignant Middle Cerebral Artery Evolution After Reperfusion Therapies.

BACKGROUND AND PURPOSE: Collateral circulation (CC) has been associated with recanalization, infarct volume, and clinical outcome in patients undergoing acute reperfusion therapies. However, its relationship with the development to malignant middle cerebral artery infarction (mMCAi) has not been evaluated. Our aim was to determine the impact of CC using multiphase computed tomographic angiography (during the acute stroke phase in the prediction of mMCAi. METHODS: Patients with consecutive acute stroke with <4.5 hours who were evaluated for reperfusion therapies and presented with an M1-MCA or terminal internal carotid artery occlusion by CTA were included. CC was evaluated on 6 grades by multiphase CTA according to the University of Calgary CC Scale; CC status was defined as poor (grades, 0-3) or good (grades, 4-5). The mMCAi was defined according to clinical and radiological criteria. Recanalization was assessed with transcranial Doppler at 24 hours and final Thrombolysis in Brain Ischemia score≥2b in patients undergoing endovascular reperfusion treatment. RESULTS: Eighty-two patients were included. Mean age was 65.1±13.83 years, median baseline National Institutes of Health Stroke Scale score was 18 (interquartile range, 13-20), and 67.9% M1 and 32.1% terminal internal carotid artery occlusions. Fifty-three patients received endovascular reperfusion treatment. Fifteen patients developed mMCAi. In the univariate analysis, patients with mMCAi had lower CC scores (2.29 versus 3.71; P=0.001). Endovascular reperfusion treatment was associated with lower rate of mMCAi development than only intravenous reperfusion treatment (9.4% versus 29.6%; P=0.028). Patients with poor CC had higher risk of developing mMCAi (13% versus 2%; P=0.001). On the multivariate analysis adjusted by age, vessel occlusion, baseline National Institutes of Health Stroke Scale, and recanalization, the presence of poor CC by multiphase CTA was the only independent predictor of mMCAi (P=0.048; odds ratio, 9.72; 95% confidence interval, 1.387-92.53). CONCLUSIONS: CC assessment by multiphase CTA independently predicts malignant MCA infarction progression. In patients with persistent occlusion after reperfusion therapies, the presence of poor CC may improve the early mMCAi detection and management.

Baseline National Institutes of Health stroke scale-adjusted time window for intravenous tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND AND PURPOSE: The effect of tissue-type plasminogen activator on functional outcome decreases progressively over time. However, given the differential pattern of arterial occlusion, stroke severity, and speed of ischemic lesion growth among candidates for reperfusion, the time window should be adjusted accordingly. We aimed to identify the impact of time-to-treatment according to stroke severity on functional outcome in patients with acute ischemic stroke. METHODS: We included 581 consecutive patients treated with alteplase according to the European Summary of Product Characteristics criteria. Patients were categorized according to National Institutes of Health Stroke Scale (NIHSS) severity in mild NIHSS (≤8), moderate NIHSS (9-15), and severe stroke NIHSS (≥16). We sequentially analyzed time-to-treatment to achieve favorable outcome (modified Rankin Scale ≤2 at 3 months). RESULTS: Overall, 19.8% had mild, 30.3% had moderate, and 49.9% had severe stroke. Favorable outcome occurred in 79.1%, 60.8%, and 26.2%, respectively. In patients with mild stroke, younger age (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.8-0.95), no previous history of stroke (OR, 0.16; 95% CI [0.039-0.65]), and no proximal occlusion (OR, 0.183; 95% CI [0.038-0.89]) independently predicted favorable outcome. In patients with moderate stroke, age (OR, 0.95; 95% CI [0.92-0.98]), no proximal occlusion (OR, 0.362; 95% CI [0.17-0.75]), and time-to-treatment before 120 minutes (OR, 2.70; 95% CI [1.14-6.38]) emerged as independent predictors of favorable outcome. In patients with severe stroke, younger age (OR, 0.96; 95% CI [0.94-0.99]), lower previous modified Rankin Scale (OR, 0.42; 95% CI [0.21-0.82]), and absence of proximal occlusion (OR, 0.48; 95% CI [0.25-0.94]) appeared as independent predictors. CONCLUSIONS: The impact of time-to-treatment on favorable outcome varies widely depending on baseline stroke severity. The window for favorable outcome was ≤120 min for moderate strokes. However, time-to-treatment seemed unrelated to functional outcome in mild and severe stroke.

Impact of time to treatment on tissue-type plasminogen activator-induced recanalization in acute ischemic stroke.

BACKGROUND AND PURPOSE: Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. METHODS: Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. RESULTS: Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1-0.933) and time to treatment ≤270 minutes (OR, 0.995; 95% CI, 0.99-0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952-0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855-0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195-0.887). None recanalized >270 minutes. CONCLUSIONS: The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.

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.

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.

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.

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.

Monitoring of cortical activity postreperfusion. A powerful tool for predicting clinical response immediately after recanalization.

BACKGROUND: In acute ischemic stroke, although early recanalization predicts rapid neurological recovery, in some cases early reperfusion does not immediately correlate to clinical improvement as "stunned brain" patients. The cortical activity monitoring in stroke patients is usually performed to evaluate epileptic activity through electroencephalogram. Bispectral index (BIS) monitor the cortical activity by fronto-temporal electrodes and is currently used for monitoring level of conscious on sedo-analgesia patients. Some studies have shown certain sensibility to detect cerebrovascular events during carotid revascularization. We aimed to evaluate the impact of BIS monitoring before and shortly after reperfusion on early and delayed clinical improvement on stroke patients. METHODS: Consecutive patients with acute anterior circulation ischemic stroke who received reperfusion therapies were monitored with bicortical BIS during the first 6 hours of admission. We registered initial and final BIS value on the affected and contralateral side and determined asymmetry and changes in relation to recanalization and other clinical variables as sedation and perprocedure complications. We defined major clinical improvement decrease ≥ 8 points at discharge or 5 day at admission. Infarct volume was measure on 24-hour CT scan. Modified Rankin score at 3 months was evaluated. RESULTS: A total of 53 patients were monitored with BIS. Median age was 73 years, median baseline National Institutes of Health Stroke Scale (NIHSS) 16. We observed an inverse correlation between final BIS score and NIHSS at discharge (P < .001; r = -.538) and infarct volume at 24 hours (P = .031; r = -.430). A receiver-operator characteristic curve identified a final BIS score of >81 as the value that better predicted further clinical improvement. After adjusting for recanalization, posttreatment NIHSS and age, final BIS emerged as the only independent predictor of clinical improvement(OR 1.21; CI 95%:1.01-1.28; P = .024). Among patients without improvement at 24 hours, after adjusting for recanalization, posttreatment NIHSS and age, final BIS value >81 emerged as the only independent predictor of clinical improvement(OR 11.6; CI 95%:1.112-122.3; P = .04). CONCLUSION: BIS value is associated with clinical and radiological variables in acute stroke patients. The final BIS value is a powerful independent predictor of further clinical improvement. Larger studies are needed to assess the value of post reperfusion cortical activity measured by BIS.

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.