This article reviews recent breakthroughs in the treatment of acute ischemic stroke, mainly focusing on the evolution of endovascular thrombectomy, its impact on guidelines, and the need for and ...implications of next-generation randomized controlled trials.
Endovascular thrombectomy is a powerful tool to treat large vessel occlusion strokes and multiple trials over the past 5 years have established its safety and efficacy in the treatment of anterior circulation large vessel occlusion strokes up to 24 hours from stroke onset.
In 2015, multiple landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, and EXTEND IA) established the superiority of endovascular thrombectomy over medical management for the treatment of anterior circulation large vessel occlusion strokes. Endovascular thrombectomy has a strong treatment effect with a number needed to treat ranging from 3 to 10. These trials selected patients based on occlusion location (proximal anterior occlusion: internal carotid or middle cerebral artery), time from stroke onset (early window: up to 6-12 hours), and acceptable infarct burden (Alberta Stroke Program Early CT Score ASPECTS ≥6 or infarct volume <50 mL). In 2017, the DAWN and DEFUSE-3 trials successfully extended the time window up to 24 hours in appropriately selected patients. Societal and national thrombectomy guidelines have incorporated these findings and offer Class 1A recommendation to a subset of well-selected patients. Thrombectomy ineligible stroke subpopulations are being studied in ongoing randomized controlled trials. These trials, built on encouraging data from pooled analysis of early trials (HERMES collaboration) and emerging retrospective data, are studying large vessel occlusion strokes with mild deficits (National Institutes of Health Stroke Scale <6) and large infarct burden (core volume >70 mL).
Summary Background Present mechanical devices are unable to achieve recanalisation in up to 20–40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new ...stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever. Methods In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18–85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8–29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69–85 years) and NIHSS scores (≤18 vs 19–29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01270867. Findings Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92–9·69; psuperiority <0·0001). Incidence of the primary safety endpoint did not differ between groups (13 15% patients in the Trevo group vs 21 23% in the Merci group; p=0·1826). Interpretation Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever. Funding Stryker Neurovascular.
Stable and efficient locomotion requires the precise coordination of movement across the limbs and body. Learned changes in interlimb coordination can be induced by exposure to a split-belt treadmill ...that imposes different speeds under each side of the body. Here, we demonstrate locomotor learning on a split-belt treadmill in mice. Mouse locomotor adaptation is specific to measures of interlimb coordination, has spatial and temporal components that adapt at different rates, and is context specific. The many similarities between human and mouse locomotor adaptation suggest that this form of locomotor learning is highly conserved across vertebrates. Using a variety of approaches, we demonstrate that split-belt adaptation in mice specifically depends on the intermediate cerebellum but is insensitive to large lesions of the cerebral cortex. Finally, cell-type-specific chemogenetics combined with quantitative behavioral analysis reveals that spatial and temporal components of locomotor adaptation are dissociable on the circuit level.
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•Locomotor learning on a split-belt treadmill is highly conserved across vertebrates•Mice regain gait symmetry by calibrating interlimb coordination in space and time•Locomotor adaptation requires intermediate cerebellum but not cerebral cortex•Circuit mechanisms for spatial and temporal components of learning are dissociable
Darmohray et al. describe a rapid form of cerebellum-dependent locomotor learning in mice that appears to be highly conserved across vertebrates. Cell-type-specific chemogenetics combined with quantitative behavioral analysis reveals that mechanisms for spatial and temporal components of learning are dissociable on the circuit level.
Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined ...the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.
The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.
Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).
The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.
Endovascular therapy is increasingly used in acute ischemic stroke treatment and is now considered the gold standard approach for selected patient populations. Prior studies have demonstrated that ...eventual patient outcomes depend on both patient-specific factors and procedural considerations. However, these factors remain unclear for acute basilar artery occlusion stroke. We sought to determine prognostic factors of good outcome in acute posterior circulation large vessel occlusion strokes treated with endovascular therapy.
We reviewed our prospectively collected endovascular databases at 2 US tertiary care academic institutions for patients with acute posterior circulation strokes from September 2005 to September 2015 who had 3-month modified Rankin Scale documented. Baseline characteristics, procedural data, and outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. The association between clinical and procedural parameters and functional outcome was assessed.
A total of 214 patients qualified for the study. Smoking status, creatinine levels, baseline National Institutes of Health Stroke Scale score, anesthesia modality (conscious sedation versus general anesthesia), procedural length, and reperfusion status were significantly associated with good outcomes in the univariate analysis. Multivariate logistic regression indicated that only smoking (odds ratio=2.61; 95% confidence interval, 1.23-5.56;
=0.013), low baseline National Institutes of Health Stroke Scale score (odds ratio=1.09; 95% confidence interval, 1.04-1.13;
<0.0001), and successful reperfusion status (odds ratio=10.80; 95% confidence interval, 1.36-85.96;
=0.025) were associated with good outcome.
In our retrospective case series, only smoking, low baseline National Institutes of Health Stroke Scale score, and successful reperfusion status were associated with good outcome in patients with posterior circulation stroke treated with endovascular therapy.
Xenon CT cerebral blood flow in acute stroke Gupta, Rishi; Jovin, Tudor G; Yonas, Howard
Neuroimaging clinics of North America,
08/2005, Letnik:
15, Številka:
3
Journal Article
Recenzirano
Acute stroke therapy is evolving rapidly as research moves toward extending the time window for treatment so that more patients can benefit. As physiology-based imaging increasingly is used in ...patient selection, it is becoming evident that rigid time windows are not applicable to individual patients. Xenon CT has an important role in acute stroke therapeutic intervention as a quantitative, reproducible, rapid, and safe modality, which can provide valuable physiologic data that can optimize patient triage and aid in management.
Summary Background Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether ...MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. Methods In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0–1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data. Findings 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7–29·0) in the target mismatch group and 0·2 (0·0–1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3–12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2–18·7). Interpretation Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted. Funding National Institute for Neurological Disorders and Stroke.
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