Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial.

PURPOSE: This randomized, placebo-controlled, double-blind, dose-escalation acute ischemic stroke trial was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous dodecafluoropentane emulsion (DDFPe) was used as neuroprotection. METHODS: Acute ischemic stroke patients (n = 24) with National Institutes of Health Stroke Scale (NIHSS) score of 2-20 were randomized to either 3 doses of intravenous DDFPe or placebo, 1 every 90 minutes, starting within 12 hours of symptom onset. Doses were given without affecting standard stroke care. Each of the 3 dose cohorts included 8 patients, with 2 receiving placebo and 6 receiving DDFPe. Primary outcomes were serious adverse events (SAEs), AEs, NIHSS score, and modified Rankin Score (mRS). RESULTS: No dose-limiting toxicities were encountered, and no maximum tolerated dose was defined. One unrelated delayed death occurred in a DDFPe patient, and another occurred in the placebo group. Group SAEs and AEs were similar in incidence and severity. Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = .03). Thirty- and 90-day mRS after high-dose therapy suggested clinical improvement (P = .01 and P = .03, respectively). However, the significance of differences in clinical outcomes was limited by small patient numbers and differences in stroke severity between cohorts. CONCLUSIONS: Intravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.

SEIMLESS: Simultaneous Extracranial, Intracranial Management of (tandem) LESsions in Stroke.

BACKGROUND: Pooled individual data from the landmark stroke trials of 2015 conclude that the benefit of endovascular thrombectomy for patients with intracranial arterial occlusion also extends to patients with concomitant (so-called 'tandem') occlusions of proximal vessels. However, there is heterogeneity and debate in the management of these patients, without a clear standard of care. In particular, there is contention regarding whether the proximal or distal lesion should be treated first. We present a case control study and describe the Simultaneous Extracranial, Intracranial Management of (tandem) LESsions in Stroke (SEIMLESS) technique, an efficient approach to the acute ischemic stroke (AIS) patient who presents with tandem lesions (TLs). METHODS: We describe 5 patients, presenting with AIS and TLs between 2015 and 2017, who we treated with SEIMLESS. Cases were reviewed for clinical data, including arterial puncture to intracranial reperfusion, total fluoroscopy time, amount of contrast, age, and gender. Our series was matched to 5 patients treated with the standard 'sequential' approach (angioplasty followed by thrombectomy) in the same time period by the same operator. RESULTS: Arterial access to intracranial recanalization time was significantly shorter in patients treated with SEIMLESS versus those who had angioplasty followed by thrombectomy (39.6±5.9 min vs 85.2±20.6 min; P=0.014). Patients treated 'seimlessly' also received significantly less iodinated contrast (117±13.5 mL vs 213±48.9 mL; P=0.005) and significantly less fluoroscopy time (21.1±5.2 min vs 55.9±17.8 min; P=0.003). There was no difference in the post-procedural Thrombolysis in Cerebral Infarction score for patients treated with SEIMLESS versus the sequential method (p=0.658). CONCLUSION: SEIMLESS is an efficient procedural method that simultaneously treats a distal intracranial occlusion and a more proximal one. Our small case controlled study finds that this technique is feasible and can lead to faster intracranial recanalization compared with the standard 'sequential' method, utilizing less contrast and radiation in the process. Larger studies are needed to verify our findings.