Renal Dysfunction Associated with Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis.

Renal dysfunction (RD) is prevalent in patients with acute ischemic stroke requiring intravenous thrombolysis. The relationship between renal function and thrombolysis related intracranial hemorrhagic (ICH) complications is contradictory according to previous studies. The current study is to clarify whether RD could increase the risk of symptomatic intracranial hemorrhage (SICH) after recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke patients. In this observational study, acute ischemic stroke patients who received IV rtPA within 4.5 hours of symptom onset were retrospectively analyzed. Creatinine levels on admission served to calculate glomerular filtration rate (GFR) to estimate RD. SICH was defined with National Institute of Neurological Disorder and Stroke (NINDS, SICHNINDS) or European Cooperative Acute Stroke Study II (ECASS II, SICHECASSII) criteria. Association of RD with SICH was assessed using continuous GFR or binary GFR (RD defined as GFR < 90 ml/minute/1.73 m2). Of 312 patients included, the incidence of SICHNINDS was 7.69%, of SICHECASSII was 5.45%. Patients with RD had higher prevalence of SICHNINDS (12.80% versus 2.03%, P < .001) and SICHECASS II (9.15% versus 1.35%, P = .002). GFR as a continuous variable was associated with SICHNINDS (ORadjust = .97, P = .003), but not with SICHECASS II. GFR less than 90 ml/minute/1.73 m2 remained independently associated with SICHNINDS (ORadjust = 4.79, P = .016), and SICHECASS II (ORadjust = 2.99, P = .032) in multiple logistic regression analysis. Renal function is independently associated with SICH after IV rtPA thrombolysis. RD is an independent predictor for both SICHNINDS and SICHECASS II. RD should be considered when evaluating the risk of intravenous thrombolysis with IV rtPA.

Zhu J ，Shen X ，Han C ，Mei C ，Zhou Y ，Wang H ，Kong Y ，Jiang Y ，Fang Q ，Cai X ... -  《-》

Symptomatic Intracerebral Hemorrhage after Intravenous Thrombolysis: Predictive Factors and Validation of Prediction Models.

Thrombolytic therapy with intravenous alteplase (IV-rtPA) has a known risk of symptomatic intracerebral hemorrhage (sICH). We aim to identify factors with a significant association with the development of sICH post-IV-rtPA. We also aim to perform an external validation of sICH predicting scores in our patient population. We performed a retrospective chart review of patients who received IV-rtPA at our tertiary care hospital. We excluded patients who underwent mechanical thrombectomy. We analyzed various factors recorded at presentation such as presenting mean arterial pressure (MAP), blood glucose, National Institutes of Health Stroke Scale (NIHSS) score, verify Aspirin, verify Plavix, age, sex, platelet count, international normalized ratio, prothrombin time, partial thromboplastin time, hemoglobin A1c, low-density lipoprotein, onset to treatment time, weight, sex, and early infarct signs on computed tomography (CT) head and compared them between sICH and non-sICH groups. For validation of sICH scores, we used documented variables to calculate the following scores for each patient: stroke prognostication using age and NIH stroke scale-100 (SPAN-100), DRAGON, CUCCHIARA, hemorrhage after thrombolysis (HAT), SEDAN, totaled health risks in vascular events, and safe implementation of thrombolysis in stroke-symptomatic intracerebral hemorrhage. sICH rate in our cohort of 89 patients was 5.62% according to the European-Australasian Cooperative Acute Stroke Study-II (ECASS-II) criteria and 7.86% according to the National Institute of Neurological Disorders and Stroke (NINDS) criteria. In the multivariate regression analysis, MAP (95% CI, .001-.01; P .002), blood glucose greater than or equal to 185 mg/dL (95% CI, .12-.45; P .001) and presence of early infarct signs (95% CI, .06-.25; P .002) had a significant association with the development of sICH with the ECASS-II definition of sICH post-IV-rtPA, whereas, only MAP (95% CI, 1.01-1.18; P .025) and verify Aspirin less than 500 (95% CI, .01-.80; P .032) had a significant association with the development of sICH with the NINDS definition of sICH post-IV-rtPA. Our study found that HAT (95% CI, .58-.96; P .044) and DRAGON (95% CI, .61-.96; P .012) scores had the highest area under the curve (AUC) with respect to ECASS-II and NINDS criteria of sICH, respectively. We found that presenting MAP, presence of early infarct signs on CT Head and blood glucose greater than or equal to 185 mg/dL upon a patient's presentation have a significant association with sICH post-IV-rtPA when the ECASS-II definition was used, while presenting MAP and verify Aspirin less than 500 upon a patient's presentation have a significant association with sICH post-IV-rtPA when the NINDS definition was used. Our study found that HAT and DRAGON scores had the highest AUC, and they were the most valid in predicting the development of sICH in our independent cohort. Patients with these risk factors should receive more intensive neurological monitoring.

Nisar T ，Hanumanthu R ，Khandelwal P 《-》

Renal impairment reduces the efficacy of thrombolytic therapy in acute ischemic stroke.

Renal impairment is a potent risk factor for stroke, which remains a leading cause of death and disability. Thrombolysis for acute ischemic stroke has transformed patient outcomes, although the safety and efficacy of this approach remain poorly characterized in patients with renal dysfunction, who manifest a higher risk of bleeding due to uremia. We therefore examined the impact of renal impairment on clinical outcomes with thrombolysis within the current 4.5-hour therapeutic window. This retrospective multicenter cohort study (2009-2011) examined 229 stroke patients receiving thrombolysis with alteplase (0.9 mg/kg; mean age 70 ± 13 years; 59% male, 24% diabetic). Sixty-five patients had an estimated glomerular filtration rate (eGFR) <60 ml/min. The primary outcome was the improvement in National Institutes of Health Stroke Scale (NIHSS) score at 24 h. Secondary outcomes included the NIHSS score at 7 days, the incidence of symptomatic and asymptomatic intracranial hemorrhage (ICH), extracranial bleeding and death during the index hospitalization. Univariate and multivariate regression analyses were performed to determine the association between demographic characteristics and comorbid factors of interest and outcomes. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. There was no significant difference in mean time to thrombolysis between the groups (221 ± 66 vs. 220 ± 70 min from symptom onset; p = 0.9). An eGFR <60 ml/min was independently associated with a statistically significant reduction of the therapeutic effect of alteplase at 24 h on multivariate regression [coefficient -2.3, 95% confidence interval (CI) -3.7 to -0.9; p = 0.002], and this persisted at 7 days (coefficient -3.5, 95% CI -5.3 to -1.7; p < 0.001). On modeling eGFR as a continuous variable, every 10 ml/min decline in eGFR was associated with a 0.40 diminution in NIHSS score improvement with alteplase (95% CI 0.07-0.74; p = 0.02). Older age and a higher presenting NIHSS score were associated with a greater therapeutic effect (p = 0.04 and p < 0.001, respectively). In-patient mortality was 5%, with no significant differences between groups. Renal impairment was not associated with a higher rate of ICH (6.2 vs. 6.7%; p = 0.9). Greater NIHSS score at presentation was the only factor associated with a greater risk of death (odds ratio 1.24, 95% CI 1.10-1.40; p < 0.001) and ICH (odds ratio 1.12, 95% CI 1.03-1.23; p = 0.004). Our results suggest that renal impairment is associated with reduced efficacy of thrombolysis in acute ischemic stroke without any excess hemorrhagic complications. This may relate to diminished fibrinolysis in the uremic milieu or differences in infarct anatomy. Longer-term prospective studies are required to characterize and improve functional outcomes following stroke in a manifestly high-risk group.

Power A ，Epstein D ，Cohen D ，Bathula R ，Devine J ，Kar A ，Taube D ，Duncan N ，Ames D ... -  《-》

Severe renal impairment is associated with symptomatic intracerebral hemorrhage after thrombolysis for ischemic stroke.

Tütüncü S ，Ziegler AM ，Scheitz JF ，Slowinski T ，Rocco A ，Endres M ，Nolte CH ... -  《-》

Prior Asymptomatic Parenchymal Hemorrhage Does Not Increase the Risk for Intracranial Hemorrhage after Intravenous Thrombolysis.

The NINDS trial demonstrated the efficacy of intravenous (IV) recombinant tissue plasminogen activator (rtPA) in improving the neurologic outcome in patients presenting with acute ischemic strokes. Patients who had a prior history of intracranial hemorrhage (ICH) were excluded from this trial, possibly due to a hypothetical increase in the subsequent bleeding risk. Thus, there is little data available, whether against or in favor of, the use of IV rtPA in patients with prior ICH. We aim to aid in determining the safety of IV rtPA in such patients through a retrospective hospital-based single center study. We reviewed the brain imaging of all patients who received IV rtPA at our comprehensive stroke center from January 2006 to April 2014 for evidence of prior ICH at the time of IV rtPA administration. Their outcomes were determined in terms of subsequent development of symptomatic ICH as defined by the NINDS trial. Brain imaging for 640 patients was reviewed. A total of 27 patients showed evidence of prior ICH at the time of IV thrombolysis, all intra-parenchymal. Only 1 patient (3.7%) developed subsequent symptomatic ICH after the administration of IV rtPA. Of the remaining 613 patients who received IV rtPA, 25 patients (4.1%) developed symptomatic ICH. This retrospective study provides Level C evidence that patients with imaging evidence of prior asymptomatic intra-parenchymal hemorrhage presenting with an acute ischemic stroke do not show an increased risk of developing symptomatic ICH after IV thrombolysis.

AbdelRazek MA ，Mowla A ，Hojnacki D ，Zimmer W ，Elsadek R ，Abdelhamid N ，Elsadek L ，Farooq S ，Kamal H ，Crumlish A ，Shirani P ，Ching M ，Sawyer R ... -  《-》