Carotid Endarterectomy vs. Carotid Stenting: Fairly Comparable or Unfairly Compared?

A commentary on Stenting versus endarterectomy for treatment of carotid-artery stenosis. by Thomas G. Brott et al. (2010). CREST Trial. N. Engl. J. Med. May 26. (10.1056/ NEJMoa0912321) Carotid revascularization with carotid endarterectomy (CEA) has been shown to be superior to medical therapy for stroke prevention in symptomatic and asymptomatic patients with moderate to severe stenosis who meet well defined medical and surgical selection criteria. The benefit of CEA is significantly higher in symptomatic compared to asymptomati

Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion

Background and Purpose A progressive decline in the odds of favorable outcome as time to reperfusion increases is well known. However, the impact of specific workflow intervals is not clear.; Methods We studied the mechanical thrombectomy group (n=103) of the prospective, randomized REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset) trial. We defined 3 workflow metrics: time from symptom onset to reperfusion (OTR), time from symptom onset to computed tomography, and time from computed tomography (CT) to reperfusion. Clinical characteristics, core laboratory-evaluated Alberta Stroke Program Early CT Scores (ASPECTS) and 90-day outcome data were analyzed. The effect of time on favorable outcome (modified Rankin scale, 0-2) was described via adjusted odds ratios (ORs) for every 30-minute delay.; Results Median admission National Institutes of Health Stroke Scale was 17.0 (14.0-20.0), reperfusion rate was 66%, and rate of favorable outcome was 43.7%. Mean (SD) workflow times were as follows: OTR: 342 (107) minute, onset to CT: 204 (93) minute, and CT to reperfusion: 138 (56) minute. Longer OTR time was associated with a reduced likelihood of good outcome (OR for 30-minute delay, 0.74; 95% confidence interval [CI], 0.59-0.93). The onset to CT time did not show a significant association with clinical outcome (OR, 0.87; 95% CI, 0.67-1.12), whereas the CT to reperfusion interval showed a negative association with favorable outcome (OR, 0.72; 95% CI, 0.54-0.95). A similar subgroup analysis according to admission ASPECTS showed this relationship for OTR time in ASPECTS<8 patients (OR, 0.56; 95% CI, 0.35-0.9) but not in ASPECTS8 (OR, 0.99; 95% CI, 0.68-1.44).; Conclusions Time to reperfusion is negatively associated with favorable outcome, being CT to reperfusion, as opposed to onset to CT, the main determinant of this association. In addition, OTR was strongly associated to outcome in patients with low ASPECTS scores but not in patients with high ASPECTS scores.; Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.Peer ReviewedPostprint (author's final draft

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease

ImportanceWhile the understanding of inflammation in the pathogenesis of many neurological diseases is now accepted, this special commentary addresses the need to study chronic inflammation in the propagation of cognitive Fog, Asthenia, and Depression Related to Inflammation which we name Brain FADE syndrome. Patients with Brain FADE syndrome fall in the void between neurology and psychiatry because the depression, fatigue, and fog seen in these patients are not idiopathic, but instead due to organic, inflammation involved in neurological disease initiation.ObservationsA review of randomized clinical trials in stroke, multiple sclerosis, Parkinson’s disease, COVID, traumatic brain injury, and Alzheimer’s disease reveal a paucity of studies with any component of Brain FADE syndrome as a primary endpoint. Furthermore, despite the relatively well-accepted notion that inflammation is a critical driving factor in these disease pathologies, none have connected chronic inflammation to depression, fatigue, or fog despite over half of the patients suffering from them.Conclusions and relevanceBrain FADE Syndrome is important and prevalent in the neurological diseases we examined. Classical “psychiatric medications” are insufficient to address Brain FADE Syndrome and a novel approach that utilizes sequential targeting of innate and adaptive immune responses should be studied

Intra-Arterial Treatment Methods in Acute Stroke Therapy

Acute revascularization is associated with improved outcomes in ischemic stroke patients. It is unclear which method of intra-arterial intervention, if any, is ideal. Promising approaches in acute stroke treatment are likely a combination of intravenous and endovascular revascularization efforts, combining early treatment initiation with direct clot manipulation and/or PTA/stenting. In this review, we will discuss available thrombolytic therapies and endovascular recanalization techniques, beginning with chemical thrombolytic agents, followed by mechanical devices, and a review of ongoing trials. Further randomized studies comparing medical therapy, intravenous and endovascular treatments are essential, and their implementation will require the wide support and enthusiasm from the neurologic, neuroradiologic, and neurosurgical stroke communities

APRIL: a double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo).Peer ReviewedPostprint (published version

Endovascular treatment improves cognition after stroke. A secondary analysis of REVASCAT trial

Objective: To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial. Methods: REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded. Results: From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51-6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60-8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life. Conclusions: Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery. Classification of evidence: This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time &lt;24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730

Rapid alteplase administration improves functional outcomes in patients with stroke due to large vessel occlusions

Background and Purpose: We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods: Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital. The primary outcome was disability defined on the modified Rankin Scale at 3 months. Results: Among 601 patients, mean age was 66.0 years (SD, 13.9), 50% were women, and median National Institutes of Health Stroke Scale score was 17. Onset-to-treatment time was median 125 minutes (interquartile range, 90–170). Door-to-treatment time was median 38 minutes (interquartile range, 26–55). Each 60-minute onset-to-treatment time delay was associated with greater disability at 90 days; the odds of functional independence (modified Rankin Scale, 0–2) at 90 days was 0.82 (95% CI, 0.66–1.03). With each 60-minute delay in door-to-needle time; the odds of functional independence was 0.55 (95% CI, 0.37–0.81) at 90 days. The absolute decline in the rate of excellent outcome (modified Rankin Scale, 0–1 at 90 days) was 20.3 per 1000 patients treated per 15-minute delay in door-to-needle time. The adjusted absolute risk difference for a door-to-needle time &lt;30 minutes versus 30 to 60 minutes was 19.3% for independent outcome (number-needed-to-treat ≈5 to gain 1 additional good outcome). Symptomatic intracranial hemorrhage occurred in 3.4% of patients, without a significant time dependency: odds ratio, 0.74 (95% CI, 0.43–1.28). Conclusions: Faster intravenous thrombolysis delivery is associated with less disability at 3 months among patients with large vessel occlusion

Transfer to the Local Stroke Center vs Direct Transfer to Endovascular Center of Acute Stroke Patients with Suspected Large Vessel Occlusion in the Catalan Territory (RACECAT): study protocol of a cluster randomized within a cohort trial

Rationale: Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion (LVO) have not been assessed in randomized trials. Aim: To establish whether stroke subjects with RACE scale based suspicion of LVO evaluated by Emergency Medical Services in the field, have higher rates of favorable outcome when transferred directly to an Endovascular Center (EVT-SC), as compared to the standard transfer to the closest Local Stroke Center (Local-SC).Design: Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment. Procedure: Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial LVO based on a pre-hospital RACE scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 hours from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with 3 strata: day/night, distance to the EVT-SC and week/week-end day. Study outcome: The primary endpoint is the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome is mortality at 90 days. Analysis: The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores (mRS) at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The trial is sponsored by the nonprofit foundation Fundació Privada Ictus Malaltia Vascular, beneficiary of an unrestricted grant by Medtronic. Trial sponsor: Fundació Privada Ictus Malaltia Vascular. Elisabeth Ortínez ([email protected]). Study sponsor and funders do not participate in the study design, collection, management, analysis and interpretation of data, writing of the report or the decision to submit results for publication