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Opinion statement Symptomatic carotid artery disease is a significant cause of ischemic stroke, and these patients are at high risk for recurrent vascular events. Patients with symptoms of stroke or transient ischemic attack attributable to a significantly stenotic vessel (70–99% luminal narrowing) should be treated with intensive medical therapy. Intensive medical therapy is a combination of pharmacologic and lifestyle interventions consistent with best-known practices as follows: initiation of antiplatelet agent or anticoagulation if medically indicated, high potency statin medication, blood pressure control with goal blood pressure of greater than 140/90, Mediterranean-style diet, exercise, and smoking cessation. Further, patients who have extracranial culprit lesions should be considered for revascularization with either carotid endarterectomy or carotid angioplasty and stenting depending on several factors including the patient’s anatomy, age, gender, and procedural risk. Based on current evidence, patients with symptomatic intracranial stenosis should be managed with intensive medical therapy, including the use of dual antiplatelet therapy with aspirin and clopidogrel for the first 90 days following the ischemic event. While the literature has shown a stronger benefit of revascularization of extracranial symptomatic disease among certain subgroups of patients with greater than 70% stenosis, there is less benefit from revascularization with endarterectomy in patients with moderate stenosis of 50–69% if the surgeon’s risk of perioperative stroke or death rate is greater than 6%.

Purpose of Review To review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS. Recent Findings There have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS. In patients with AIS due to large vessel occlusion, one randomized controlled trial demonstrated superiority of TNK for vessel recanalization rates and long-term functional outcomes when compared to alteplase. A meta-analysis of all phase two and three trials evaluating TNK in AIS concluded that TNK has a comparable safety and efficacy profile to alteplase. The results of these trials prompted new recommendations in the Acute Stroke Guideline published by the AHA suggesting it may be reasonable to use as an alternative to alteplase. Furthermore, recent real-world data has also reported decreased door-to-needle time with TNK utilization. Summary In patients with AIS, use of a thrombolytic agent is standard of care and has been shown to reduce neurological disability and improve functional outcome. Randomized controlled trials have demonstrated that TNK is non-inferior to alteplase from a clinical outcome and safety standpoint. The existing data evaluating the efficacy of TNK compared to alteplase in acute AIS within 4.5 h from symptom onset showed no significant difference between these two agents with regard to functional outcome at 90 days but improved median time to treatment and large vessel recanalization in TNK-treated patients. The results from ongoing TNK trials in larger patient cohorts and in wake-up stroke populations will be instrumental to the wide-scale utilization of TNK in acute AIS management.

Opinion statement Ischemic stroke accounts for approximately 85% of all strokes. Although severe strokes constitute a minority of cases, they are associated with a majority of the subsequent disability and death. Reperfusion therapy with intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy is a mainstay of acute stroke management. Intensive care management of stroke is focused on reducing complications of reperfusion, such as hemorrhagic transformation, and minimizing secondary brain injury, including brain edema and progressive stroke. Additionally, severe stroke patients frequently need ventilatory or hemodynamic support provided in an intensive care unit (ICU) setting. Here, we discuss the current medical and surgical ICU management aspects of acute ischemic stroke and identify areas where ongoing studies may reveal new treatments to improve neurological recovery.

Purpose of review Cryptogenic stroke describes a subset of ischemic stroke for which no cause can be found despite a structured investigation. There are a number of putative mechanisms of cryptogenic ischemic stroke including a covert structural cardiac lesion, paroxysmal atrial fibrillation, hypercoagulable state or undiagnosed malignancy. Because many of these proposed mechanisms are embolic – and based on studies of thrombus history showing commonalities between thrombus composition between cardioembolic and cryptogenic strokes – the concept of embolic stroke of undetermined source (ESUS) (Hart et al. Lancet Neurol. 13(4):429–38, 2014 ; Stroke. 48(4):867–72, 2017 ) has been proposed to describe cryptogenic strokes that may warrant systemic anticoagulation. In this review, we discuss the phenomena of cryptogenic stroke, ESUS and a proposed management pathway. Recent findings 1. The concept of ESUS was proposed in 2014 as a potentially useful therapeutic entity. Two recent trials – NAVIGATE-ESUS (Hart et al. N Engl J Med. 378(23):2191–201, 2018 ) and RESPECT-ESUS (Diener 2018 ) were proposed based on this concept. They were negative for their primary endpoint and for the secondary endpoint of ischemic stroke recurrence. Post-hoc analysis of the WARSS trial (Longstreth et al. Stroke. 44(3):714–9, 2013 ) suggested that people with elevated pro-BNP benefited from systemic anticoagulation whereas those with a normal pro-BNP did not. This led to the hypothesis that a subgroup of patients at higher risk for embolism from the left atrium would benefit from anticoagulation, even if the WARSS trial was negative for the primary endpoint. Thus, the ARCADIA trial (Kamel et al. Int J Stroke. 14(2):207–14, 2019 ) was proposed – a randomized, active-control, multi-center trial comparing apixaban with aspirin for secondary stroke prevention in patients with ESUS and biomarkers of left atrial cardiopathy. This trial is actively recruiting. 2. Carotid web – an intimal form of fibromuscular dysplasia – has come to increased prominence in the literature as a cause of embolic stroke. It is a non-stenosis, non-atherosclerotic lesion in the posterior wall of the internal carotid artery that leads to pooling with stasis of blood distal to the lesion and, as a consequence, embolic stroke. It is not usually detected by a standard stroke workup as it masquerades as non-calcified atherosclerosis and does not cause hemodynamically significant stenosis. There have been two major recent papers – a meta-analysis in Stroke (Zhang et al. Stroke. 49(12):2872–6, 2018 ) and narrative review in JAMA Neurology (Kim et al. JAMA Neurol. 2018 ) – that addressed this topic. Summary Cryptogenic stroke describes a stroke for which no cause has been found. ESUS is a more precisely-defined entity that mandates a specific workup and implicates remote embolism as a cause of stroke. In ESUS, the options for further investigation include long-term cardiac monitoring, transesophageal echocardiography, investigation for occult malignancy or arterial hypercoagulability. Options for management include anti-platelet therapy (the current standard of care), empiric anticoagulation or enrollment in to a clinical trial examining the use of NOACs compared with aspirin for secondary prevention (such as ARCADIA or ATTICUS). In a person less than 60 years old with ESUS and a patent foramen ovale the risk of a recurrent stroke is low but recent trials have suggested that percutaneous device closure reduces this risk further with an acceptable complication rate.

Opinion statement Cerebral small vessel disease (SVD) is characterised by damage to deep grey and white matter structures of the brain and is responsible for a diverse range of clinical problems that include stroke and dementia. In this review, we describe advances in neuroimaging published since January 2015, mainly with magnetic resonance imaging (MRI), that, in general, are improving quantification, observation and investigation of SVD focussing on three areas: quantifying the total SVD burden, imaging brain microstructural integrity and imaging vascular malfunction. Methods to capture ‘whole brain SVD burden’ across the spectrum of SVD imaging changes will be useful for patient stratification in clinical trials, an approach that we are already testing. More sophisticated imaging measures of SVD microstructural damage are allowing the disease to be studied at earlier stages, will help identify specific factors that are important in development of overt SVD imaging features and in understanding why specific clinical consequences may occur. Imaging vascular function will help establish the precise blood vessel and blood flow alterations at early disease stages and, together with microstructural integrity measures, may provide important surrogate endpoints in clinical trials testing new interventions. Better knowledge of SVD pathophysiology will help identify new treatment targets, improve patient stratification and may in future increase efficiency of clinical trials through smaller sample sizes or shorter follow-up periods. However, most of these methods are not yet sufficiently mature to use with confidence in clinical trials, although rapid advances in the field suggest that reliable quantification of SVD lesion burden, tissue microstructural integrity and vascular dysfunction are imminent.

Purpose of the review Intracranial atherosclerotic disease is a complex stroke etiology with numerous challenges in its management. We present an update on the latest therapeutic research on this disease and the potential role of surgical interventions. Recent findings Despite improvements in medical therapy, intracranial atherosclerosis presents one of the highest stroke recurrences even with the best contemporary medical management. Interventions such as direct bypass, angioplasty, and stenting have failed to demonstrate superiority to medical management in well-conducted randomized clinical trials. New avenues of research are focusing on alternative interventions such as submaximal angioplasty and indirect bypass. Summary Patients with intracranial atherosclerosis should undergo intensive medical management. Angioplasty and stenting should be avoided in this population outside of well-designed clinical trials. Surgical strategies are promising but have not been tested in pivotal studies. There is an urgent need for randomized controlled clinical trials to evaluate surgical interventions like indirect bypass in patients with intracranial atherosclerosis. There is a need for early and intermediate development clinical trials for other interventions such as angioplasty without stenting or new stenting techniques.

Purpose of review High-resolution magnetic resonance vessel wall imaging (VWI) permits direct visualization of intracranial arterial wall pathology, providing diagnostic and prognostic information that is complementary to conventional imaging techniques. We highlight the most recent studies that have advanced the clinical application of VWI. Recent findings VWI aids in distinguishing and diagnosing intracranial atherosclerotic disease (ICAD), intracranial dissections, central nervous system vasculitis, reversible cerebral vasoconstriction syndrome, and moyamoya disease. VWI may help predict recurrent stroke in ICAD, treatment effects in vasculitis, and disease progression in moyamoya. VWI also identifies ruptured intracranial aneurysms and may predict stability of unruptured aneurysms. Summary Implementing VWI as an adjunctive imaging technique may permit earlier and noninvasive discrimination of rare vasculopathies. However the prognostic utility of VWI for more common cerebrovascular pathologies requires further validation.

Purpose of Review The goal of this review is to provide the reader with an overview of symptomatic carotid stenosis and the approach to medical management of patients undergoing surgical intervention with both carotid endarterectomy (CEA) and carotid artery stenting (CAS). Recent Findings CEA is recommended for patients with moderate to severe symptomatic carotid stenosis and transient ischemic attack (TIA) or non-disabling stroke. More recently CAS has also been shown to be a beneficial, less invasive option for patients with symptomatic carotid stenosis. All patients need urgent medical therapy to reduce the risk of stroke before, during, and after surgical intervention. These therapies have traditionally included single anti-platelet and/or anticoagulation therapy. More recent studies have demonstrated the benefit of dual antiplatelet therapy (DAPT) and lipid-lowering medications, specifically statins. Summary Patients with symptomatic carotid stenosis who are undergoing CEA or CAS must also be placed on the appropriate medical therapy during this time. General guidelines exist regarding the approach to medical management; however, largely due to the lack of modern randomized clinical trials, the specific management approach likely varies between institutions.

Purpose of review Endovascular thrombectomy (ET), the standard of treatment for emergent large vessel occlusion (ELVO) strokes, has been subject to rigorous efforts to further improve its usage and delivery for optimised patient outcomes. This review aims to provide an outline and discussion about the recently established and emerging recommendations regarding endovascular treatment of stroke. Recent findings The indications for ET have expanded continually, with perfusion imaging now enabling selection of patients presenting 6–24 h after last-known-well, and improved device and operator proficiency allowing treatment of M2-MCA occlusions and tandem occlusions. Further inclusion of paediatric patients and patients with larger infarct core or milder stroke symptoms for ET has been proposed; however, this remains unproven. This growing applicability is supported by more efficient systems of care, employing modern techniques such as telemedicine, mobile stroke units and helicopter medical services. Ongoing debate exists regarding thrombolytic agent, thrombectomy technique, anaesthesia method and the role of advanced neuroimaging, with upcoming RCTs expected to provide clarification. Summary The journey to further improving the efficacy of ET has advanced and diversified rapidly over recent years, involving improved patient selection, increased utility of advanced neuroimaging and ongoing device redevelopment, within the setting of more efficient, streamlined systems of care. This dynamic and ongoing influx of evidence-based refinements is key to further optimising outcomes for ELVO patients.