Background and Purpose-Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. Methods-This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. Results-Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (Pϭ0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (nϭ42 of 256) in the EPO and 9.0% (nϭ24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; Pϭ0.01) without any particular mechanism of death unexpected after stroke. Conclusions-Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis. (Stroke. 2009;40:e647-e656.)

Background— Carotid angioplasty and stenting (CAS) is increasingly being used for treatment of symptomatic and asymptomatic carotid artery disease (CAD). To evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during CAS, we conducted a systematic review of studies reporting on the incidence of minor stroke, major stroke, or death within 30 days after CAS. Summary of Review— We searched for studies published between January 1990 and June 2002 by means of a PubMed search and a cumulative review of reference lists of all relevant publications. In 2357 patients a total of 2537 CAS procedures had been performed without protection devices, and in 839 patients 896 CAS procedures had been performed with protection devices. Both groups were similar with respect to age, sex distribution, cerebrovascular risk factors, and indications for CAS. In many studies the periprocedural complication rates had not been presented separately for patients with symptomatic and asymptomatic CAD. The combined stroke and death rate within 30 days in both symptomatic and asymptomatic patients was 1.8% in patients treated with cerebral protection devices compared with 5.5% in patients treated without cerebral protection devices (χ 2 =19.7, P <0.001). This effect was mainly due to a decrease in the occurrence of minor strokes (3.7% without cerebral protection versus 0.5% with cerebral protection; χ 2 =22.4, P <0.001) and major strokes (1.1% without cerebral protection versus 0.3% with cerebral protection; χ 2 =4.3, P <0.05), whereas death rates were almost identical (≈0.8%; χ 2 =0.3, P =0.6). Conclusions— On the basis of this early analysis of single-center studies, the use of cerebral protection devices appears to reduce thromboembolic complications during CAS. These technical aspects should be taken into account before the initiation of further randomized trials comparing CAS with carotid endarterectomy.

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.

New DWI lesions occur more frequently after CAS than after CEA. However, technical advances mainly in the field of endovascular therapy potentially reduce the incidence of these adverse ischemic events. In this scenario, DWI appears to be an ideal tool to compare and further improve both techniques.

Noise properties, the signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and signal responses were compared during functional activation of the human brain at 1.5 and 3.0 T. At the higher field spiral gradient-echo (GRE) brain images revealed an average gain in SNR of 1.7 in fully relaxed and 2.2 in images with a repetition time (TR) of 1.5 sec. The tempered gain at longer TRs reflects the fact that the physiological noise depends on the signal strength and becomes a larger fraction of the total noise at 3.0 T. Activation of the primary motor and visual cortex resulted in a 36% and 44% increase of "activated pixels" at 3.0 T, which reflects a greater sensitivity for the detection of activated gray matter at the higher field. The gain in the CNR exhibited a dependency on the underlying tissue, i.e., an increase of 1.8؋ in regions of particular high activation-induced signal changes (presumably venous vessels) and of 2.2؋ in the average activated areas. These results demonstrate that 3.0 T provides a clear advantage over MRI modalities are often limited by the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). Both SNR and CNR have been shown to increase with magnetic field strength B 0 (1,2). Consequently, the "optimal field strength" and the field dependency in blood oxygenation level dependent (BOLD) MRI have been the subject of various investigations (1,3-6). For many MRI applications a magnetic field strength of 1.5 Tesla (T) seems to represent a good compromise. Functional MRI (fMRI), however, is particularly dependent on good SNR and CNR properties, since typically observed BOLD signal changes at 1.5 T are on the order of a few percent and often exceed the intrinsic noise only slightly. Several biophysical models of activation-induced changes of the oxygenation-sensitive MRI signals have proposed that the changes in the relaxation rate ⌬R* 2 and subsequently the BOLD effect are proportional to B 0 for large vessels and proportional to B 0 2 for small vessels and capillaries (7,8). Thus, higher fields may provide an important improvement in fMRI. Indeed, recent investigations have demonstrated a superlinear increase in the BOLD CNR with the field strength (1,4,5), suggesting that high field fMRI methods may be able to resolve oxygenation changes in small vessels and capillaries, which are spatially localized near the origin of the neuronal activity.In the present study, various BOLD-relevant properties were compared at 1.5 T and 3.0 T. In order to establish identical BOLD-sensitivities, we investigated the T* 2 relaxation times for gray matter at each field strength and scaled the corresponding echo time (TE), and the excitation angle at 3.0 T. We compared intrinsic noise contributions and the SNR in gradient-echo (GRE) images and examined activation-induced BOLD responses during visual and motor activation at both fields in terms of spatial extent, the mean z-score, and the CNR of "activated voxels." T* 2 -maps from various brain sections were calculated to investigate spatial aspect...