Background Nerinetide is a neuroprotective agent recently evaluated in the ESCAPE‐NEXT (Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis) trial (NCT04462536), which was terminated after failing to meet its Day 90 primary end point; however, by that time, Year 1 follow‐up outcomes were already available for 513 participants. Methods The primary end point at Year 1 was functional independence, defined as modified Rankin Scale score 0 to 2, analyzed by logistic regression adjusted for treatment and baseline covariates. In a post hoc analysis, the interaction between early (<3 hours) versus late (3–12 hours) enrollment window and treatment effect was also tested and the results reported separately by enrollment window. Results A total of 513 of 850 participants had documented Year 1 outcomes before study termination, of whom 442 reached their scheduled Year 1 visit. In the nerinetide group, 110 (48.0%) of 229 participants achieved functional independence at Year 1 compared with 102 (47.9%) of 213 in the placebo group (adjusted odds ratio [aOR], 1.12 [95% CI, 0.74–1.71]; P=0.593). There was treatment effect modification by enrollment window (early versus late; Pinteraction=0.044). Among early window participants (n=163), 51 (52.6%) in the nerinetide group and 30 (45.5%) in placebo achieved functional independence (aOR, 2.80 [95% CI, 1.18–6.66], P=0.019) at Year 1. Additionally, the nerinetide group exhibited improved survival (aOR, 2.61 [95% CI, 1.17–5.83], P=0.019). Conversely, no significant clinical benefit of nerinetide at Year 1 was observed among late window participants. Analyses on all 513 participants with documented Year 1 outcomes provided similar results. Conclusions Long‐term benefits of early administration of neuroprotection may emerge up to 1 year after stroke.
Abstract Background Spontaneous cervical artery dissection (sCeAD) is a rare vasculopathy whose pathophysiology remains incompletely understood. Impaired vascular extracellular matrix integrity, including elastic fibers, may contribute to its development. We investigated whether serum fibrillin-1 and soluble elastin fragments (sELF) differ between patients with sCeAD and controls during the acute and chronic stages. Methods Patients with acute sCeAD were prospectively enrolled at four German stroke centers. Blood samples were collected at baseline and after 6±1 months. Patients with a first acute ischemic stroke unrelated to sCeAD and healthy individuals served as controls. Serum fibrillin-1 and sELF concentrations were measured using enzyme-linked immunosorbent assays. Results 61 patients with sCeAD, 53 patients with first non-CeAD ischemic stroke, and 79 healthy controls were included. After sex-matching, serum fibrillin-1 concentrations were significantly lower in patients with acute sCeAD than in healthy controls (97 [60; 192] vs. 176 [113; 269] ng/mL; p=0.009). Fibrillin-1 concentrations were also lower in both male and female patients with sCeAD than in respective healthy controls. In patients with sCeAD, fibrillin-1 concentrations increased significantly after 6 months compared with baseline (171 [130; 270] vs. 104 [67; 205] ng/mL; p=0.021). Serum fibrillin-1 concentrations were higher in men than in women across all study groups. No significant differences in sELF concentrations were observed between groups or time points. Discussion Serum fibrillin-1 concentrations were lower during acute sCeAD and increased significantly during follow-up, whereas sELF concentrations remained unchanged. These findings support an association between circulating fibrillin-1 and acute sCeAD and warrant further investigation of its role in sCeAD pathophysiology. Pronounced sex-related differences in fibrillin-1 concentrations highlight the importance of sex-specific analyses in future.
BACKGROUND:Glenzocimab, a platelet glycoprotein VI antagonist, is a novel agent that inhibits platelet activation and aggregation. Its safety was demonstrated in the ACTIMIS trial (Acute Ischemic Stroke Interventional Study; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03803007) for patients with stroke receiving thrombolysis, with or without mechanical thrombectomy, and results suggested a reduction in intracranial hemorrhages and mortality. The ACTISAVE trial was designed as a confirmatory study to evaluate the efficacy and safety of glenzocimab in acute ischemic stroke.METHODS:ACTISAVE (Acute Ischemic Stroke Study Evaluating Glenzocimab Used as Add-On Therapy Versus Placebo) was an international, randomized, double-blind, placebo-controlled phase 2/3 study in patients with stroke, treated by thrombolysis within 4.5 hours of symptoms onset with or without mechanical thrombectomy. The study was conducted at 54 primary and comprehensive stroke centers located in 10 countries. Patients were randomized 1:1 to glenzocimab (1000 mg-IV) or placebo. The primary outcome was the modified Rankin Scale (mRS) score of 4 to 6 at day 90. Key secondary outcome was the mRS score of 0 to 2 at day 90. Mortality, mRS shift, National Institutes of Health Stroke Scale score, quality of life, and safety outcomes were assessed.RESULTS:Between September 2021 and October 2023, 438 patients were randomized, 421 treated, and included as randomized in the primary analysis set. Median age was 73 (63-80) years, and 43% were female. Thrombolysis was performed 2.3 hours (median) after symptom onset and followed by mechanical thrombectomy in 36% of patients. The assigned treatment began a median of 1.2 (interquartile range, 0.8-1.6) hours after thrombolysis initiation. Prethrombolysis National Institutes of Health Stroke Scale score median was 9 (6-15). At day 90, there was no statistically significant difference in the primary outcome between the treatment groups: the incidence of poor outcome (mRS score 4-6 versus 0-3) was 21.6% in the glenzocimab group compared with 15.3% placebo group (odds ratio, 1.51 [95% CI, 0.90-2.54]; P=0.120). No statistically significant difference in secondary outcomes was observed. There were no major safety signals with any intracerebral hemorrhage occurring respectively in 60 (28.6%) and 63 (29.9%) patients in glenzocimab and placebo arms.CONCLUSIONS:ACTISAVE failed to confirm a beneficial effect of glenzocimab on mRS in patients with acute ischemic stroke treated by thrombolysis.REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05070260.
BACKGROUND:Whether the large effect size of endovascular thrombectomy (EVT) for stroke due to large-vessel occlusion applies to stroke due to medium-vessel occlusion is unclear. METHODS:In a multicenter, prospective, randomized, open-label trial with blinded outcome evaluation, we assigned patients with acute ischemic stroke due to medium-vessel occlusion who presented within 12 hours from the time that they were last known to be well and who had favorable baseline noninvasive brain imaging to receive EVT plus usual care or usual care alone. The primary outcome was the modified Rankin scale score (range, 0 [no symptoms] to 6 [death]) at 90 days, reported as the percentage of patients with a score of 0 or 1. RESULTS:A total of 530 patients from five countries were enrolled between April 2022 and June 2024, with 255 patients assigned to the EVT group and 275 to the usual-care group. Most patients (84.7%) had primary occlusions in a middle-cerebral-artery branch. A modified Rankin scale score of 0 or 1 at 90 days occurred in 106 of 255 patients (41.6%) in the EVT group and in 118 of 274 (43.1%) in the usual-care group (adjusted rate ratio, 0.95; 95% confidence interval [CI], 0.79 to 1.15; P = 0.61). Mortality at 90 days was 13.3% in the EVT group and 8.4% in the usual-care group (adjusted hazard ratio, 1.82; 95% CI, 1.06 to 3.12). Symptomatic intracranial hemorrhage occurred in 14 of 257 patients (5.4%) in the EVT group and in 6 of 272 (2.2%) in the usual-care group. CONCLUSIONS:Endovascular treatment for acute ischemic stroke due to medium-vessel occlusion within 12 hours did not lead to better outcomes at 90 days than usual care. (Funded by the Canadian Institutes for Health Research and Medtronic; ESCAPE-MeVO ClinicalTrials.gov number, NCT05151172.).
Zusammenfassung: Die jüngsten Revisionen der Krankheitsklassifikationssysteme DSM-5 und ICD-11 stärken die Rolle der Neuropsychologie bei der Diagnose neurokognitiver Störungen. Zugleich ist eine gewisse Stagnation der neuropsychologischen Methodenentwicklung auf dem Gebiet der Demenzdiagnostik zu verzeichnen. Vor diesem Hintergrund wurde im Rahmen des computergestützten Wiener Testsystems (WTS) das portable Test-Set Cognitive Functions Dementia (CFD) entwickelt und anhand der hier berichteten multizentrischen Beobachtungsstudie im klinischen Einsatz evaluiert. Bei guter Akzeptanz zeigten sich keine besonderen Anwendungsprobleme. Die 14 Hauptvariablen und 6 Indizes des CFD unterscheiden Demenz-Erkrankte ( n = 131) deutlich von Gesunden ( n = 407) sowie Personen mit Depression (n = 145), leichter kognitiver Störung (n = 57) und Morbus Parkinson ( n = 52). Im Vergleich zum Mini-Mental Status Test (MMST) ist das CFD sensitiver für diskrete Beeinträchtigungen neurokognitiver Funktionen. Die Ergebnisse belegen die Eignung des Test-Sets für die Demenz-Früherkennung und Differenzialdiagnostik Demenz vs. Depression.
