Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

Posterior reversible encephalopathy syndrome (PRES) associated with COVID-19.

The novel human coronavirus disease (COVID-19) has been associated with vascular and thrombotic complications, some of which may result from endothelial dysfunction, including the posterior reversible encephalopathy syndrome (PRES). We report a case series of 8 patients with COVID-19 and PRES diagnosed at two academic medical centers between March and July of 2020. The clinical, laboratory and radiographic data, treatment, and short-term outcomes were retrospectively analyzed. The mean age was 57.9 ± 12 years, and 50% were women. Four patients had previous vascular comorbidities. All the patients suffered from severe pneumonia, requiring intensive care unit admission. Five patients were not hypertensive at presentation (all SBP < 127 mmHg). Neurologic symptoms included seizures in 7 patients; impaired consciousness in 5 patients; focal neurological signs in 3 patients; and visual disturbances in 1 patient. All patients underwent brain magnetic resonance imaging which indicated asymmetric T2 prolongation or diffusion changes (50%), extensive fronto-parieto-occipital involvement (25%), vascular irregularities (12.5%) and intracranial hemorrhage (25%). Four patients were treated with tocilizumab. Three patients were discharged without neurologic disability, 2 patients had persistent focal neurologic deficits and 2 expired. One patient's prognosis remains guarded. Together, these data support the relationship between PRES and endothelial dysfunction associated with severe COVID-19. In patients with severe COVID-19, PRES can be triggered by uncontrolled hypertension, or occur independently in the setting of systemic illness and certain medications. Like other infectious processes, critically ill patients with COVID-19 may be at greater risk of PRES because of impaired vasoreactivity or the use of novel agents like Tocilizumab.

COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center.

BACKGROUND: An increased rate of thrombotic events has been associated to Coronavirus Disease 19 (COVID-19) with a variable rate of acute stroke. Our aim is to uncover the rate of acute stroke in COVID-19 patients and identify those cases in which a possible causative relationship could exist. METHODS: We performed a single-center analysis of a prospective mandatory database. We studied all patients with confirmed COVID-19 and stroke diagnoses from March 2nd to April 30th. Demographic, clinical, and imaging data were prospectively collected. Final diagnosis was determined after full diagnostic work-up unless impossible due to death. RESULTS: Of 2050 patients with confirmed SARS-CoV-2 infection, 21 (1.02%) presented an acute ischemic stroke 21 and 4 (0.2%) suffered an intracranial hemorrhage. After the diagnostic work-up, in 60.0% ischemic and all hemorrhagic strokes patients an etiology non-related with COVID-19 was identified. Only in 6 patients the stroke cause was considered possibly related to COVID-19, all of them required mechanical ventilation before stroke onset. Ten patients underwent endovascular treatment; compared with patients who underwent EVT in the same period, COVID-19 was an independent predictor of in-hospital mortality (50% versus 15%; Odds Ratio, 6.67; 95% CI, 1.1-40.4; p 0.04). CONCLUSIONS: The presence of acute stroke in patients with COVID-19 was below 2% and most of them previously presented established stroke risk factors. Without other potential cause, stroke was an uncommon complication and exclusive of patients with a severe pulmonary injury. The presence of COVID-19 in patients who underwent EVT was an independent predictor of in-hospital mortality.