No abstract

Background and Purpose-Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods-We randomized patients with acute stroke (Ͻ12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (nϭ9) or room air (controls, nϭ7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results-Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (ϮSD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8Ϯ22% versus 149.1Ϯ41%; Pϭ0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (Pϭ0.6). Conclusions-High-flow

Intense immunosuppression followed by AHSCT is significantly superior to MTX in reducing MRI activity in severe cases of MS. These results strongly support further phase III studies with primary clinical endpoints. The study was registered as EUDRACT No. 2007-000064-24.