James Charles Grotta

Background and ObjectivesHematoma expansion (HE), an increase in bleeding into the brain, is a modifiable cause of disability and death after intracerebral hemorrhage (ICH). Some specialized hemost...

Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are the keystones of current treatment for acute ischemic stroke. Most IVT candidates harbor medium or distal arterial occlusions,...

BACKGROUND: Cerebral edema is a life-threatening complication of ischemic stroke that disproportionally affects patients with large established infarction. We assessed whether endovascular thrombectomy (EVT) reduces or exacerbates edema development, and the association between edema with short-term and long-term outcomes in this high-risk population. METHODS: In this prespecified secondary analysis of the SELECT2 randomized clinical trial (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), which tested the efficacy and safety of EVT versus medical management in adult patients with acute anterior circulation large vessel occlusion presenting with large ischemic core (defined as Alberta Stroke Program Early Computed Tomography Score of 3–5 or core volume ≥50 mL on computed tomography perfusion or diffusion magnetic resonance imaging), we assessed maximum midline shift (MLS) within 7 days of randomization between treatment groups using a probabilistic index model. RESULTS: After exclusion of 10 patients who underwent hemicraniectomy before follow-up imaging, 342 patients were analyzed. The median MLS on follow-up magnetic resonance imaging or computed tomography was 6.39 mm (interquartile range, 0–12.0) in the EVT and 4.18 mm (interquartile range, 0–9.66) in medical management patients ( P =0.021). EVT was independently associated with greater MLS (adjusted odds ratio, 1.63 [95% CI, 1.25–2.12]; P =0.0027) after adjusting for age and core volume. There was no interaction between EVT and core volume at presentation on the association with MLS ( P >0.79). MLS was associated with the development of early neurological worsening (adjusted odds ratio, 1.15 [95% CI, 1.07–1.23]; P P =0.0029). On mediation analysis, cerebral edema reduced the effect of EVT on functional outcome by 10.6%. CONCLUSIONS: Despite overall clinical benefit, EVT in patients presenting with a large ischemic core was associated with increased cerebral edema, which, in turn, was associated with early neurological worsening and worse functional outcome at 90 days. Early recognition and individualized treatment to prevent secondary injury from cerebral edema in this population are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03876457.

The concept of vascular neurology-specific education was launched nearly 50 years ago in response to a growing understanding of the pathophysiology of stroke. The vascular neurology field, and the training required to support its growth and evolution, has been heavily influenced by a simultaneously increasing breadth of knowledge in approaches to clinical management of stroke. There are increasing numbers of vascular neurology fellows each academic year, yet we continue to experience shortages in clinical coverage for patients with vascular neurological conditions. Here, we review the origins of vascular neurology training and current challenges in sustaining educational programs. We then propose action items to help shape the future of vascular neurology education.

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: Recent years have seen improvements in stroke-care pathways, including mobile stroke units (MSUs), and this may have affected the rate, predictors, and outcomes of patients with acute ischemic stroke who qualify for but do not receive treatment with intravenous thrombolysis (IVT). METHODS: This was a secondary observational cohort analysis of the prospective, multicenter BEST-MSU trial (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared With Standard Management by Emergency Medical Services), conducted in 7 US cities from 2014 to 2020, comparing MSU management versus standard emergency department management for patients with suspected acute ischemic stroke. The analytical cohort comprised enrolled patients with confirmed acute ischemic stroke and no guideline contraindications to IVT. The outcome was a potential missed IVT opportunity, defined as patients not treated with IVT despite lacking contraindications. We used multivariable logistic regression to evaluate whether demographics, prestroke modified Rankin Scale, study site, comorbidities, National Institutes of Health Stroke Scale, blood pressure, international normalized ratio, glucose, antithrombotic use, and thrombectomy were associated with this outcome. RESULTS: Of 1515 enrolled patients, 927 met criteria for this analysis. Fifty-one participants (5.5%) had a potential missed IVT opportunity, including 4 of 555 (0.7%) in the MSU group versus 47 of 372 (12.6%) in the emergency department group (odds ratio, 0.05 [95% CI, 0.02–0.12]). In multivariable analysis, omitting study group, lower National Institutes of Health Stroke Scale (odds ratio, 0.95 [95% CI, 0.90–0.99]) and longer last known well-to-door time (odds ratio per 10 minutes, 1.08 [95% CI, 1.03–1.13]) were independently associated with a potential missed IVT opportunity. The leading reasons documented for withholding IVT were resolving symptoms (43%), time window concerns (18%), and minor deficits (10%). Among participants with a potential missed IVT opportunity and a recorded 3-month modified Rankin Scale (n=49), 19 (39%) had a score of 3 to 6. CONCLUSIONS: In the BEST-MSU trial, potential missed IVT opportunities occurred in 1-in-8 patients in the emergency department, and rarely on the MSU. Although often due to early improvement or minor deficits, more than one-third of these patients had poor functional status at 3 months. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02190500.

Background: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi‐arm Optimization of Stroke Thrombolysis) trial. Methods: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The primary outcome of interest was the utility weighted modified Rankin Scale (mRS) score at 90 days after stroke. The secondary outcomes were mRS score ≤1, ≤2 at 90 days, 90‐day mRS score, thrombolysis in cerebral infarction 2B or better, 24‐hour National Institutes of Health Stroke Scale score, 24‐hour change in National Institutes of Health Stroke Scale score, and 90‐day mortality. Results: A total of 219 patients underwent mechanical thrombectomy with 101 patients receiving GA and 118 patients receiving CS. Our analysis showed that GA was associated with a lower average utility weighted mRS score at 90 days compared with CS ( P ≤0.02). Similarly, GA was associated with higher odds of worse outcomes on 90‐day mRS 0 to 2 ( P P P P <0.001). A sensitivity analysis of patients with anterior stroke alone also favored better neurologic outcomes in the CS group compared with the GA group. Conclusions: In patients undergoing endovascular thrombectomy in the MOST trial, GA was associated with poorer functional outcomes compared with CS.