Is intracerebral hemorrhage a time-dependent phenomenon after successful combined intravenous and intra-arterial therapy?

BACKGROUND AND PURPOSE: Onset-to-reperfusion time (ORT) has recently emerged as an essential prognostic factor in acute ischemic stroke therapy. Although favorable outcome is associated with reduced ORT, it remains unclear whether intracranial bleeding depends on ORT. We therefore sought to determine whether ORT influenced the risk and volume of intracerebral hemorrhage (ICH) after combined intravenous and intra-arterial therapy. METHODS: Based on our prospective registry, we included 157 consecutive acute ischemic stroke patients successfully recanalized with combined intravenous and intra-arterial therapy between April 2007 and October 2011. Primary outcome was any ICH within 24 hours posttreatment. Secondary outcomes included occurrence of symptomatic ICH (sICH) and ICH volume measured with the ABC/2. RESULTS: Any ICH occurred in 26% of the study sample (n=33). sICH occurred in 5.5% (n=7). Median ICH volume was 0.8 mL. ORT was increased in patients with ICH (median=260 minutes; interquartile range=230-306) compared with patients without ICH (median=226 minutes; interquartile range=200-281; P=0.008). In the setting of sICH, ORT reached a median of 300 minutes (interquartile range=276-401; P=0.004). The difference remained significant after adjustment for potential confounding factors (adjusted P=0.045 for ICH; adjusted P=0.002 for sICH). There was no correlation between ICH volume and ORT (r=0.16; P=0.33). CONCLUSIONS: ORT influences the rate but not the volume of ICH and appears to be a critical predictor of symptomatic hemorrhage after successful combined intravenous and intra-arterial therapy. To minimize the risk of bleeding, revascularization should be achieved within 4.5 hours of stroke onset

Elevated Hypoperfusion Intensity Ratio (HIR) observed in patients with a large vessel occlusion (LVO) presenting in the evening.

Circadian variability has been implicated in timing of stroke onset, yet the full impact of underlying biological rhythms on acute stroke perfusion patterns is not known. We aimed to describe the relationship between time of stroke onset and perfusion profiles in patients with large vessel occlusion (LVO). A retrospective observational study was conducted using prospective registries of four stroke centers across North America and Europe with systematic use of perfusion imaging in clinical care. Included patients had stroke due to ICA, M1 or M2 occlusion and baseline perfusion imaging performed within 24h from last-seen-well (LSW). Stroke onset was divided into eight hour intervals: (1) Night: 23:00-6:59, (2) Day: 7:00-14:59, (3) Evening: 15:00-22:59. Core volume was estimated on CT perfusion (rCBF <30%) or DWI-MRI (ADC <620) and the collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR = [Tmax>10s]/[Tmax>6s]). Non-parametric testing was conducted using SPSS to account for the non-normalized dependent variables. A total of 1506 cases were included (median age 74.9 years, IQR 63.0-84.0). Median NIHSS, core volumes, and HIR were 14.0 (IQR 8.0-20.0), 13.0mL (IQR 0.0-42.0), and 0.4 (IQR 0.2-0.6) respectively. Most strokes occurred during the Day (n = 666, 44.2%), compared to Night (n = 360, 23.9%), and Evening (n = 480, 31.9%). HIR was highest, indicating worse collaterals, in the Evening compared to the other timepoints (p = 0.006). Controlling for age and time to imaging, Evening strokes had significantly higher HIR compared to Day (p = 0.013). Our retrospective analysis suggests that HIR is significantly higher in the evening, indicating poorer collateral activation which may lead to larger core volumes in these patients

Outcomes after thrombolysis in AIS according to prior statin use: a registry and review.

The impact of prior statin use on outcomes after thrombolysis is unclear. We evaluated outcomes of patients treated by IV, intra-arterial (IA) thrombolysis, or combined therapy, according to prior statin use. We analyzed data from a patient registry (606 patients) and conducted a systematic review. We identified 11 previous studies (6,438 patients) that evaluated the effect of statin use on outcomes after IV thrombolysis (8 studies), IA thrombolysis (2 studies), or a single/combined approach (1 study). In our registry and in most of the retrieved studies, statin users had more risk factors and concomitant antiplatelet treatment than nonstatin users. Regardless of treatment strategy, prior statin use was not associated with favorable outcome (adjusted odds ratio [OR] 1.36; 95 confidence interval [CI] 0.86-2.16), symptomatic intracranial hemorrhage (sICH) (OR 0.57; 95% CI 0.22-1.49), or recanalization (OR 1.87; 95% CI 0.69-5.03). In meta-analysis, prior statin use was not associated with favorable outcome (crude OR 0.99; 95% CI 0.88-1.12), but was associated with an increased risk of sICH (crude OR 1.55; 95% CI 1.23-1.95). However, when the available multivariable associations were combined (5 studies), the effect of prior statin use on risk of sICH was not significant (OR 1.31; 95% CI 0.97-1.76). These results suggest no beneficial or detrimental effect of prior statin use in acute stroke patients treated by IV thrombolysis, IA thrombolysis, or combined therapy, although the numbers of patients treated by IA thrombolysis or combined therapy are too small to exclude an effect

Atherogenic Dyslipidemia in Patients With Transient Ischemic Attack

Background and Purpose-There is mounting evidence that atherogenic dyslipidemia (ie, low high-density lipoprotein cholesterol combined with high triglyceride concentrations) is an independent predictor of high cardiovascular risk and possibly of stroke. Methods-All patients included in the SOS-TIA cohort underwent an initial standardized evaluation, including medical history, physical examination, routine blood biochemistry, and diagnostic testing, and were followed for 1 year. Lipid profile was evaluated under fasting conditions. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol blood concentration = 150 mg/dL. Results-Among 1471 consecutive patients with transient ischemic attack (TIA) or minor stroke, overall prevalence of atherogenic dyslipidemia was 5.8%, but varied from 4.6% to 11.1%, depending on final diagnosis (possible TIA or TIA with a cerebral ischemic lesion, respectively). Prevalence of atherogenic dyslipidemia was independently associated with male sex, diabetes, and body mass index, but not with ABCD2 score. Atherogenic dyslipidemia also strongly associated with symptomatic intracranial stenosis >= 50% (adjusted odds ratio, 2.77; 95% CI, 1.38-5.55), but not with symptomatic extracranial stenosis >= 50% (adjusted odds ratio, 1.20; 95% CI, 0.64-2.26). Despite appropriate secondary prevention treatment, 90-day stroke risk was greater in patients with versus without atherogenic dyslipidemia (4.8% versus 1.7%; P=0.04). Conclusions-The atherogenic dyslipidemia phenotype in patients with TIA may be associated with intracranial artery stenosis and higher risk of early recurrent stroke. Additional data are needed to confirm these findings and to assess the best way to reduce important residual risk in such patients. (Stroke. 2011;42:2131-2137.

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment

Background and Purpose-Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. Methods-We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. Results-In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37 CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3 CI, 0.8-2.24 P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). Conclusions-In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required. © 2013 American Heart Association, Inc

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment

10.1161/STROKEAHA.113.001576Stroke44102814-2820SJCC

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion.

The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities. Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) >6 second with Tmax >10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients. Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p < 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p < 0.001 and p = 0.030, respectively). The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers

Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: A multicenter study

OBJECTIVES: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria. METHODS: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. RESULTS: A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up. CONCLUSIONS: Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds