Validation of FLAIR hyperintense lesions as imaging biomarkers to predict the outcome of acute stroke after intra-arterial thrombolysis following intravenous tissue plasminogen activator.

Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Chung JW ，Kim KJ ，Noh WY ，Jang MS ，Yang MH ，Han MK ，Kwon OK ，Jung C ，Kim JH ，Oh CW ，Lee JS ，Lee J ，Bae HJ ... -  《-》

Symptomatic intracranial hemorrhage following intravenous thrombolysis for acute ischemic stroke: a critical review of case definitions.

Symptomatic intracranial hemorrhage (SICH) is a devastating complication of intravenous thrombolysis treatment that is associated with high mortality. Clinical trials, stroke registries and cohort studies employ different case definitions to identify stroke patients with SICH following intravenous thrombolysis. We systematically reviewed the reported rates of SICH following intravenous thrombolysis and compared their consistency with mortality outcomes. Studies were identified from the PubMed and Embase databases from January 1994 to July 2011 by cross-referencing the following MeSH terms: 'thrombolysis', 'recombinant tissue plasminogen activator', 'rtPA', 'hemorrhagic stroke', 'cerebral hemorrhage', 'hematoma' and 'ischemic stroke'. Demographic information, baseline National Institute of Health Stroke Scale (NIHSS) scores, time from stroke onset to intravenous thrombolysis, SICH and mortality rates were derived from published data in 7 randomized controlled trials, 7 stroke registries and 10 cohort studies (4 multicenter and 6 single center) with more than 200 consecutively recruited patients. Mortality rates were considered as the percentage of patients treated with intravenous thrombolysis who died within 90 days after stroke. The mean age of patients included in this analysis was 68.8 years (standard deviation, SD 2.9, range 63-75), of whom 56.3% (SD 4.5, range 45-63) were men. They presented with a mean baseline NIHSS of 12.5 (SD 1.4, range 9-15) and received intravenous thrombolysis 175 min (SD 62, range 120-328) from stroke onset. The overall mean SICH and mortality rates of patients treated with intravenous thrombolysis were 5.6% (SD 2.3) and 14.7% (SD 4.8), respectively. A moderate correlation was observed between the incidence of SICH and mortality in patients treated with intravenous thrombolysis (r = 0.401, p = 0.050). The variation in SICH rates was highest across studies that reported SICH rates using the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria compared with the European Cooperative Acute Stroke Study and National Institute of Neurological Disorders and Stroke (NINDS) criteria. Studies that defined SICH as parenchymal hemorrhage with a neurological decline NIHSS ≥4 occurring within 36 h of intravenous thrombolysis reported a higher consistency between SICH and mortality rates (correlation coefficient 0.631). SICH rates vary considerably between studies and these differences may relate to the differences in the criteria used to define SICH. Until a case definition with high interrater agreement and good correlation with stroke outcomes becomes available, detailed information on the type of bleeding, the extent of NIHSS deterioration, neuroimaging features and the time from thrombolysis to diagnosis of hemorrhage should be reported to permit a correct interpretation of SICH rates.

Seet RC ，Rabinstein AA 《-》

Safety and efficacy of MRI-based thrombolysis in unclear-onset stroke. A preliminary report.

Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0-1, 37.5 vs. 35.0%; mRS 0-2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset.

Cho AH ，Sohn SI ，Han MK ，Lee DH ，Kim JS ，Choi CG ，Sohn CH ，Kwon SU ，Suh DC ，Kim SJ ，Bae HJ ，Kang DW ... -  《-》

Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.

Higashida RT ，Furlan AJ ，Roberts H ，Tomsick T ，Connors B ，Barr J ，Dillon W ，Warach S ，Broderick J ，Tilley B ，Sacks D ，Technology Assessment Committee of the American Society of Interventional and Therapeutic Neuroradiology ，Technology Assessment Committee of the Society of Interventional Radiology ... -  《-》

Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke patients after early non-responsive intravenous tissue plasminogen activator therapy.

Kim DJ ，Kim DI ，Kim SH ，Lee KY ，Heo JH ，Han SW ... -  《NEURORADIOLOGY》