Background-Matrix metalloproteinase (MMP) expression is related to blood brain barrier disruption after cerebral ischemia. Moreover, MMP inhibitors reduce hemorrhagic transformation (HT) after embolic ischemia in tissue plasminogen activator (t-PA)-treated animals. We aimed to correlate plasmatic MMP levels with the appearance of intracranial bleeding complications in stroke patients treated with t-PA. Methods and Results-Serial MMP-2 and MMP-9 determinations were performed (ELISA, ng/mL) in 41 strokes involving the middle cerebral artery territory in patients who received t-PA within 3 hours of stroke onset. Blood samples were obtained at baseline (pretreatment) and at 12 and 24 hours after symptom onset.

Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short- and long-term outcome.

Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

Background and Purpose-In animal models of cerebral ischemia, matrix metalloproteinase (MMP) expression was significantly increased and related to blood-brain barrier disruption, edema formation, and hemorrhagic transformation (HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasminogen activator-treated animals. We aimed to determine the relationship between MMPs and HT after human ischemic stroke. Methods-Serial MMP-2 and MMP-9 determinations were performed by means of ELISA in 39 cardioembolic strokes in the middle cerebral artery territory. Hemorrhagic events were classified according to clinical and CT criteria (hemorrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated on CT at 48 hours (early HT) and again between day 5 and 7 (late HT). Results-HT was present in 41% of the patients (43.75% early HI, 25% early PH and 31.25% late HI). MMP-2 values were within normal range and were unrelated to HT. Increased expression of MMP-9 (normal range Ͻ97 ng/mL) was found among patients with and without HT (159.3Ϯ82 versus 143.9Ϯ112.6 ng/mL; Pϭ0.64). According to HT subtypes, the highest baseline MMP-9 levels corresponded to patients with late HI (240.4Ϯ111.2 versus 102.5Ϯ76.7 ng/mL for all other patients, Pϭ0.002). Baseline MMP-9 was the only variable associated with late HI in the multiple logistic regression model (OR 9; CI 1.46, 55.24; Pϭ0.010). Peak of MMP-9 at the 24-hour time point (250.6 ng/mL) was found before appearance of PH. Conclusions-MMPs are involved in some subtypes of HT after human cardioembolic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak precedes early PH. Key Words: cerebral ischemia Ⅲ embolism, cerebral Ⅲ hematoma, parenchymal Ⅲ hemorrhagic stroke Ⅲ matrix metalloproteinase H emorrhagic transformation (HT) is a feared event that may follow ischemic stroke. Thrombolytic therapy has been shown to be beneficial for acute stroke, although this therapy increases risk of HT. 1 Therefore, identification of the underlying mechanisms of this complication is critical to improvement of the safety profile of thrombolytic agents for stroke treatment.Matrix metalloproteinases (MMPs) belong to a family of zinc-binding proteolytic enzymes that normally remodel the extracellular matrix. 2 MMP-2 and MMP-9 specifically attack type IV collagen, laminin, and fibronectin, the major components of the basal lamina around cerebral blood vessels. 3 In animal models of cerebral ischemia, MMP expression was increased significantly and related to blood-brain barrier disruption, edema formation, and HT. 4,5 However, whether HT in humans also is related to MMP action remains unknown.We hypothesize that after MMPs degrade ECM components of the basal lamina, blood elements may extravasate, which leads to HT. In the present exploratory study, we aimed to correlate the expression of MMPs after human cardioembolic stroke with the appearance of different subtypes of HT. Subjects and Methods Study PopulationFrom June 1999 through March 2000, we studied prospectively consecut...