Ischemic stroke is a major cause of morbidity and mortality for which the only approved treatment in the acute setting is intravenous thrombolysis. The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) have been firmly established within 3 h of symptom onset; however, few patients are eligible for treatment in this time window. Expanding the time for treatment has been challenging, but new evidence has demonstrated a modest statistical improvement in selected patients when rt-PA is administered within 4.5 h. This important finding hopefully will enable more patients to receive treatment and simultaneously provides an opportunity to reaffirm that the benefits of rt-PA diminish with time.

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is the most severe type of stroke. In 2012, the Joint Commission, in collaboration with the American Heart Association/American Stroke Association (AHA/ASA), launched the Advanced Certification for Comprehensive Stroke Centers (CSCs). This new level of certification was designed to promote higher standard of care for patients with complex stroke.

Objective

The goal of this study was to examine the treatment modality and quality benchmarks of aSAH at one of the first five certified CSCs in the United States.

Methods

Consecutive patients with aSAH at Cedars-Sinai Medical Center between April 1, 2012 and May 30, 2014 were included for this retrospective study. The ruptured aneurysm was treated with coiling or clipping within 24 h. All patients were managed per AHA guidelines. Discharge outcomes were assessed using modified Rankin Scale (mRS). The rate of aneurysm treatment, door-to-treatment time, rate of posttreatment rebleed, hospital length of stay (LOS), discharge outcome, and mortality rates were evaluated as quality indicators.

Results

The median age (interquartile range) of the 118 patients with aSAH was 55 (19). Among them, 84 (71.2%) were females, 94 (79.7%) were transfers from outside hospitals, and 74 (62.7%) had Hunt and Hess grades 1-3. Sixty patients (50.8%) were treated with coiling, 52 (44.1%) with clipping, and 6 (5.1%) untreated due to ictal cardiac arrest or severe comorbidities. The rate of aneurysm treatment was 95% (112/118) with median door-to-treatment time at 12.5 (8.5) h and 0.9% (1/112) posttreatment rebleed. The median ICU and hospital LOS were 12.5 (7) and 17.0 (14.5) days, respectively. Coiling was associated with significantly shorter LOS than clipping. There were 59 patients (50%) with favorable outcome and 19 deaths (16.1%) at hospital discharge. There was no significant difference in discharge outcome between coiling and clipping.

Conclusion

Care of aSAH at one of the early CSCs in the United States was associated with high rate of aneurysm treatment, fast door-to-treatment time, low posttreatment rebleed, excellent outcome, and low mortality rate. Coiling was associated with significant shorter LOS than clipping. There was no significant difference in discharge outcomes between treatment modalities.

Traumatic brain injury (TBI) is a common diagnosis requiring acute hospitalization. Long-term, TBI is a significant source of health and socioeconomic impact in the United States and globally. The goal of clinicians who manage TBI is to prevent secondary brain injury. In this population, post-traumatic cerebral infarction (PTCI) acutely after TBI is an important but under-recognized complication that is associated with negative functional outcomes. In this comprehensive review, we describe the incidence and pathophysiology of PTCI. We then discuss the diagnostic and treatment approaches for the most common etiologies of isolated PTCI, including brain herniation syndromes, cervical artery dissection, venous thrombosis, and post-traumatic vasospasm. In addition to these mechanisms, hypercoagulability and microcirculatory failure can also exacerbate ischemia. We aim to highlight the importance of this condition and future clinical research needs with the goal of improving patient outcomes after TBI.

Background and purpose

The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial.

Methods

The study drug, 3K3A-APC, is a pleiotropic cytoprotectant and may reduce thrombolysis-associated hemorrhage. The NeuroNEXT trial NN104 (RHAPSODY) is designed to establish a maximally tolerated dose of 3K3A-APC. Each trial site provided their IAT selection criteria. An expert panel reviewed site criteria and published evidence. Finally, the trial leadership designed IAT selection criteria.

Results

Derived selection criteria reflected consistency among the sites and comparability to published IAT trials. A protocol amendment allowing IAT (and relaxed age, National Institutes of Health Stroke Scale, and time limits) in the RHAPSODY trial was implemented on June 15, 2015. Recruitment before and after the amendment improved from 8 enrolled patients (601 screened, 1.3%) to 51 patients (821 screened, 6.2%; odds ratio [95% confidence limit] of 4.9 [2.3-10.4]; P<0.001). Gross recruitment was 0.11 patients per site month versus 0.43 patients per site per month, respectively, before and after the amendment.

Conclusions

It is feasible to include IAT in a neuroprotectant trial for acute ischemic stroke. Criteria are presented for including such patients in a manner that is consistent with published evidence for IAT while still preserving the ability to test the role of the putative neuroprotectant.

Clinical trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714.

Background

Vascular endothelial growth factor-A₁₆₅ (VEGF-A₁₆₅) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A₁₆₅a and antiangiogenic VEGF-A₁₆₅b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A₁₆₅ regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A₁₆₅ isoforms in ICAD and MMD.

Methods

Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A₁₆₅a and VEGF-A₁₆₅b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment.

Results

A significantly higher baseline VEGF-A₁₆₅a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A₁₆₅a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A₁₆₅a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A₁₆₅a/b ratio, P = .028).

Conclusions

Our study shows an increased VEGF-A₁₆₅a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A₁₆₅a/b ratio in ICAD patients.

Changes in neurovascular coupling are associated with both Alzheimer's disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18-85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p < 0.05), holding constant demographic and cerebrovascular risk. Increased alcohol use was associated with reduced overall cognitive function (Full Scale IQ 2.8 pts, p < 0.05), while cardiac disorders (Full Scale IQ 3.3 IQ pts; p < 0.05), high cholesterol (Full Scale IQ 3.9 pts; p < 0.05), and years of education (2 IQ pts/year; p < 0.001) were associated with higher general cognitive ability. Increased hemodynamic latency was associated with reduced executive functioning (p < 0.05) as well as reductions in verbal concept formation (p < 0.05) and the ability to synthesize and analyze abstract visual information (p < 0.01). Hemodynamic latency is associated with reduced cognitive ability across the lifespan, independently of other demographic and cerebrovascular risk factors. Vascular health may predict cognitive ability long before the onset of dementias.

OBJECTIVE: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC). METHODS: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution. RESULTS: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008). CONCLUSION: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019.

Background and purpose

The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke.

Summary of review

Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue.

Conclusions

Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

Background and purpose

The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers.

Methods

This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials.

Results

The imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers.

Conclusions

Recent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.