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BACKGROUND AND PURPOSE Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy. METHODS All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively. RESULTS A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046). CONCLUSIONS Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.

A 76-year-old man with a history of arterial hypertension, obstructive sleep apnea, dyslipidemia, family history of cardiovascular events, prestroke and overweight presented 90 minutes after acute onset of right-sided sensorimotor hemiparesis, hemiataxia and dysarthria (National Institutes of Health Stroke Scale (NIHSS) 9/42). Magnetic resonance imaging (MRI) revealed a pontine ischemia and MR angiography showed a thrombus in the middle to distal portion of the basilar artery. Owing to the location, an occlusion of one lumen of a fenestrated basilar artery was suspected. Fearing the risk of peripheral dislocation, intravenous thrombolysis was withheld after an interdisciplinary discussion and direct endovascular thrombectomy (Solitaire stent retriever) was successfully performed by passing the stent retriever specifically through the affected lumen and between the thrombus and the vascular wall, which would normally be avoided. Angiography after complete reperfusion (Thrombolysis in Cerebral Infarction grade 3) confirmed a fenestration in the middle to distal portion of the basilar artery where the thrombus was initially located (blue and green arrow). Follow-up MRI after 24 hours showed only minimal ischemic damage in the left pontine area, and the patient was discharged home with ambulatory physiotherapy for residual minimal gait disturbance (NIHSS 0).

Background and Purpose— Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. Methods— We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. Results— From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia ( P =0.019), coronary heart disease ( P =0.039), and shorter intervals from symptom onset to endovascular intervention ( P =0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ ( P >0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage ( P =0.023) and lower mortality ( P =0.007) in the direct MT group. Conclusions— In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.

N-Glycosylation is normally a co-translational process that occurs as soon as a nascent and unfolded polypeptide chain has emerged ~12 residues into the lumen of the endoplasmic reticulum (ER). Here, we describe the efficient utilization of an N-glycosylation site engineered within the luminal extreme C-terminal residues of distinct integral membrane glycoproteins, a native ER resident protein and an engineered secreted protein. This N-glycan addition required that the acceptor asparagine within an Asn-Trp-Ser sequon be located at least four residues away from the C-terminus of the polypeptide and, in the case of membrane proteins, at least 13 residues away from the lumenal side of the transmembrane segment. Pulse-chase assays revealed that the natural N-glycans of the proteins studied were attached co-translationally, whereas C-terminal N-glycosylation occurred post-translocationally within a time frame of hours in Xenopus laevis oocytes and minutes in human embryonic kidney 293 (HEK293) cells. In oocyte and HEK cell expression systems, affinity tag-driven C-terminal N-glycosylation may facilitate the determination of orientation of the C-terminal tail of membrane proteins relative to the membrane.