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Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease

Alexis N. Simpkins, MD, PhD

Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, et al. Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease. Stroke. 2017

Cerebral small vessel disease (sCVD) is an important cause of both vascular dementia and lacunar infarction. Accumulation of white matter lesions and lacunar infarcts from sCVD is associated with cognitive dysfunction, increased risk of stroke, and worsened neurologic outcome after stroke. Here the authors test the hypothesis that remote ischemic conditioning (RIC) can improve cognitive outcomes in patients with mild cognitive impairment and cSVD as a follow up to the pilot study in which they showed that cSVD can reduce white matter disease and increase mean velocity of the middle cerebral arteries.

This study was a 1-year, single-center, prospective, double-blinded, randomized, placebo controlled study of consented patients of Han Chinese decent between 45 and 80 years of age with mild cognitive impairment defined by a pre-treatment MMSE and MOCA score, sCVD as defined by the Standards for Reporting Vascular Changes on Neuroimaging criteria on pre-treatment brain MRI and automated measurements of white matter disease of MRI-fluid-attenuated inversion recovery sequences. Patients were excluded if they did not complete > 80 % of the therapy, had significant cardiac disease, medical illness, medical contraindication to having RIC performed, intracerebral hemorrhage, stroke within the past 6 months, or an alternate etiology of small vessel disease such as vasculitis, genetic disorder, > 50% stenosis of intracranial vessel, or atrial fibrillation. The difference between the RIC and placebo group was the pressure of the cuff inflation from the automated device (200 mmHg in RIC cycling for 5 cycles of inflation and deflating for 5 minutes vs. 50mmHg in control).

Is It Possible to Predict the Occurrence of Cerebral Edema After Intravenous Thrombolysis? An Exploratory Analysis From the SITS-ISTR Registry

Aristeidis H. Katsanos, MD, PhD

Thorén M, Azevedo E, Dawson J, Egido JA, Falcou A, Ford GA, et al. Predictors for Cerebral Edema in Acute Ischemic Stroke Treated With Intravenous Thrombolysis. Stroke. 2017

Even though cerebral edema (CED) is one of the most severe complications of acute ischemic stroke (AIS) and the cause of mortality in 5% of all AIS patients, there are scarce data on risk factors predicting the development of CED following AIS — including the subgroup of AIS patients treated with intravenous thrombolysis (IVT).

Thorén and colleagues aimed to determine potential baseline clinical and radiological predictors of CED after IVT by analyzing data from 42,187 AIS patients recorded in the Safe Implementation of Treatments in Stroke International Register (SITS-ISTR) during a 10-year period. After performing an image-based classification on the severity of post-IVT CED, they found that increased baseline stroke severity, high blood glucose, decreased level of consciousness, the presence of hyperdense artery sign and signs of infract on baseline neuroimaging were the most important baseline predictors for early CED. As expected, patients with CED had worse 3-month functional outcomes and increased mortality rates —proportionally to the severity of edema — compared to patients without CED. Moreover, the authors found increased risk of symptomatic intracerebral hemorrhage in patients with severe CED, providing further support to the hypothesis of a blood-brain disruption induced common pathway leading to both cerebral edema and hemorrhage in the acute phase of cerebral ischemia.

Ticagrelor Versus Aspirin — A Closer Look at ESUS in SOCRATES

Kevin S. Attenhofer, MD

Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, et al. Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source. Stroke. 2017

Embolic stroke of undetermined source is a sub-classification of cryptogenic stroke which describes non-lacunar stroke without an identified cardio embolic source or occlusive atherosclerosis. While multiple pathologies may be at the heart of ESUS, it is thought that the undiagnosed embolic phenomenon driving the ischemia could be treated with anticoagulation. Multiple ongoing and recent trials seek to determine the optimal secondary stroke prevention in patients with ESUS by comparing aspirin to various direct oral anticoagulants (RESPECT-ESUS, NAVIGATE-ESUS, ARCADIA, ATTICUS). Considering the possibility that these studies may be neutral or negative, Amarenco et al. examined the use of antiplatelet agents for ESUS. The authors used data from the Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial to retrospectively compare ticagrelor and aspirin for ESUS. Their hypothesis was that all or some patients with ESUS would show greater benefit from ticagrelor than aspirin.

Importance of Intravenous Thrombolysis for Large Vessel Anterior Circulation Stroke in the Era of Endovascular Therapy

Tapan Mehta, MBBS, MPH

Mistry EA, Mistry AM, Nakawah MO, Chitale RV, James RF, Volpi JJ, et al. Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients. Stroke. 2017

Mechanical thrombectomy (MT) has been proven to be superior to intravenous thrombolysis (IVT) in proximal large vessel anterior circulation strokes (LVO); however, the standard of care is still to provide IVT to eligible patients before MT. Rigorous data is lacking, however; the need for IVT in the patients with LVO who are eligible for MT is being questioned.

The article by Mistry et al is an important meta-analysis of 13 studies that explored the differences in clinical outcomes (mortality, morbidity with mRS (Modified Rankin Scale; 0-2 defined as good outcome), symptomatic intracranial hemorrhagic (sICH), and successful recanalization rates for patients receiving MT+IVT versus only MT (MT – IVT)). This meta-analysis included studies from 2006 to 2016. Separate sub-group analyses were performed for randomized clinical trials (RCT) and non-randomized studies each. Sub-group analysis for the RCT group demonstrated higher, but nonsignificant, Odds Ratio (OR) for good functional outcomes (OR, 1.28 [95% confidence interval (CI), 0.93–1.75], P=0.12) and a significantly lower OR for mortality (OR, 0.56 [95% CI, 0.36–0.86], P=0.007) in MT+IVT compared with MT−IVT patients. The sub-group analysis of patients in nonrandomized studies demonstrated a strong trend with quantitatively similar OR of 1.31 (95% CI, 0.99–1.73, p=0.06) for good functional outcomes and OR 0.76 (95% CI, 0.56–1.03, p=0.08) in MT+IVT compared to MT−IVT patients.

Taking Patients Directly to Comprehensive Stroke Centers May Be Feasible for Patients and Hospitals

Neal S. Parikh, MD 
@NealSParikhMD

Katz BS, Adeoye O, Sucharew H, Broderick JP, McMullan J, Khatri P, et al. Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers. An Urban Population-Based Study. Stroke. 2017

Whether all acute stroke patients should be taken to a comprehensive stroke center (CSC) remains unclear. However, there is mounting computer modeling and clinical data that support transporting acute stroke patients directly to CSCs, especially when the additional travel time is not excessive. The American Heart Association recommends transporting patients directly to CSCs if additional travel time does not exceed 15–20 minutes.

Brian Katz and colleagues performed an analysis to examine real-world EMS transport practices in the Greater Cincinnati/Northern Kentucky (GCNK) region. They performed computer modeling to evaluate the implications of adhering more closely to AHA recommendations. The authors identified patients with acute stroke from the GCNK Study who were transported by EMS in 2010. The GCNK region has 1 CSC and a total of 14 primary stroke centers (PSC) and acute stroke ready hospitals (ASRH). Patients’ addresses were geocoded, and software was used to estimate travel distances to each patient’s initial presenting hospital and also to the CSC.

Statins and Carotid Artery Stenting

Tapan Mehta, MBBS, MPH

Hong JH, Sohn SI, Kwak J, Yoo J, Chang HW, Kwon OK, et al. Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting. Stroke. 2017

In this entry, I discuss a recent publication by Dr. Jeong-Ho Hong and colleagues regarding effectiveness of statin pretreatment on preventing the periprocedural complications of carotid artery stenting (CAS).

CAS as a procedure has evolved significantly in the past two decades. Previous studies have shown increased periprocedural complication risk with CAS compared to carotid endarterectomy (CEA). Invention of new endovascular devices, distal embolization protection systems and antiplatelet medications, along with increasing operator experience, have contributed in reduction of periprocedural complications. Recently published CREST trial data can be considered an important example of this. As there is already data available on statin pretreatment reducing periprocedural complication risk for CEA and percutaneous coronary intervention, this study importantly extends the possibility of benefit with pre-procedural statin use for patients undergoing CAS.

Carotid Stenting vs. Endarterectomy: Vascular Anatomy Predicts Stroke Risk

Hatim Attar, MD

Müller MD, Ahlhelm FJ, von Hessling A, Doig D, Nederkoorn PJ, Macdonald S, et al. Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy. Stroke. 2017

There has been a longstanding debate on management of patients with carotid disease. In the ICSS study, patients were randomly assigned to Carotid Artery Stent (CAS) vs. Carotid Endarterectomy (CEA). CAS was related to higher peri-procedural stroke risk, but both therapies were equally effective in long-term stroke prevention. This study is a post-hoc analysis on a sub group of the ICSS study, providing the first randomized trial on vascular anatomy as an independent procedural risk factor for stroke during CAS and CEA. Studies have been completed assessing vascular anatomy for procedural risks with CAS, but none have compared the risk between CAS and CEA, making this study unique and its results invaluable.

In the ICSS MRI subgroup, brain MRI was performed before and 1-3 days after CAS or CEA; primary outcome was new diffusion restricted lesions. Patients in this study underwent Contrast Enhanced Magnetic Resonance Angiography (CE- MRA) or Computed Tomographic Angiography (CTA) to define vascular anatomy. Vascular anatomy was objectified with measurable criteria. Aortic arches were divided into three types based on origins of supra aortic arteries, and angles between all large vessels were defined, as shown below in the images.

 The authors validated the inter-rater reliability on reading these anatomic parameters. Associations were made between the laterality, stenosis length and degree, plaque ulcerations and vasculature angles.

There were 184 patients with vessel imaging; 97 were assigned to CAS, 87 to CEA. Procedural cerebral ischemia was found in 49 of the CAS group (51%), with only 14 after CEA (16%). After correcting for age, only two factors were found to be statistically significant in the CAS group—aortic arch configuration type 2 and 3, and larger ICA angulation (≥ 60 degrees). 

Author Interview: Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

A conversation with Alexandros Rentzos, MD, Diagnostic and Interventional Neuroradiology, Sahlgrenska University Hospital, and Pia Löwhagen Hendén, MD, PhD, Anesthesiology and Intensive Care department, Sahlgrenska University Hospital, about the role of anesthesia and conscious sedation for patients undergoing embolectomy for stroke.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper, “General Anesthesia Versus Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The AnStroke Trial (Anesthesia During Stroke),” published in the June 2017 issue of Stroke.

Dr. Merino: Could you please summarize the key findings of your study and put them in context of what was known on the topic?

Drs. Rentzos and Löwhagen: Since a number of retrospective studies showed that general anesthesia during endovascular stroke treatment was associated with poor neurological outcome, conscious sedation became the main method in most neurointerventional centers after 2010. However, the retrospective studies were limited by important selection bias, such as inclusion of posterior strokes (in some of the series) and, importantly, more severe stroke in patients treated under GA. Furthermore, most retrospective studies on anesthesia technique did not describe the anesthesia technique, nor the anesthetic management!

At our institute, we have used mainly general anesthesia since 1991 when we started with endovascular stroke treatment, and, in our experience, patients treated with GA did not have worse neurological outcome. That is why we started the randomized trial AnStroke in 2013. The results were presented in ESOC 2017 in Prague on May 18. In our trial, general anesthesia did not lead to worse neurological outcome compared to conscious sedation.

Higher Admission Heart Rate Associated with Death and Poor Functional Outcome in ICH

Alexander E. Merkler, MD

Qiu M, Sato S, Zheng D, Wang X, Carcel C, Hirakawa Y, et al. Admission Heart Rate Predicts Poor Outcomes in Acute Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies. Stroke. 2016

Intracerebral hemorrhage is a devastating disease with a one-month mortality of 40%. Larger ICH volume, older age, and hematoma expansion are some of the factors associated with both poor functional outcome and death. Admission heart rate (HR) has previously been shown to predict higher mortality in coronary artery disease and ischemic stroke, but its impact on patients with ICH is unknown. 


In this study, Drs. Qiu et al perform a post-hoc analysis on data from the INTERACT trials to evaluate the effect of admission heart rate on outcome in ICH. Clinical outcomes included mortality and functional outcome (mRS) at 90 days. Imaging outcome was hematoma growth on 24 hour CT. HR was divided into quartiles (<65, 65-74, 75-84, ≥85) and Cox logistic regression was used to account for possible confounders in the relationship between admission HR and the outcomes of interest.

Of 3185 patients with ICH, patients with higher admission HR had higher BP, more frequent intraventricular extension of hematoma, and were less likely enrolled in China; patients with lower admission HR were more likely older, more often were taking a beta-blocker or antithrombotic, and had larger hematomas that were less likely to be in a lobar location.  Overall, higher admission HR was associated with higher mortality (adjusted hazard ratio for HR ≥85 vs. <65: 1.5; CI, 1.07-2.11). In addition, higher admission HR was associated with worse functional outcome at 90 days (adjusted odds ratio 1.33; CI 1.08-1.63). There was no significant association between admission HR and hematoma expansion on 24 hour CT.

Similar to coronary artery disease and ischemic stroke, admission HR appears to be associated with increased mortality and poor functional outcomes in patients with ICH. As the authors suggest, perhaps higher admission HR is a marker of poor general health, dehydration, anemia, or a marker of cardiac disease, all of which are predictors of poor outcome after stroke. One major limitation is the lack of adjustment for heart rate variability, which has also been shown to be associated with poor outcomes after stroke.  

In conclusion, admission HR is associated with increased mortality and poor functional outcome in patients with ICH. 

Residual Arterial Stenosis after Endovascular Thrombectomy: a Relationship with in Situ Thrombo-occlusion and Reocclusion Rates

Mark R. Etherton, MD, PhD
The advent of efficacious endovascular thrombectomy (EVT) for ischemic stroke secondary to acute occlusion of proximal anterior circulation vessels has allowed for the characterization of occlusive lesions. Understanding the underlying pathology of these occlusive lesions could be informative for predicting the success of the endovascular intervention as well as prognostication of clinical outcomes.

In the present study, Hwang et al. characterized residual stenosis post EVT at the site of the arterial occlusive lesion in an Asian population with acute ischemic stroke secondary to middle cerebral artery M1 occlusion. In this population with a high prevalence of intracranial atherosclerotic disease (ICAD), the authors’ hypothesis was that residual stenosis, as defined by the Arterial Occlusive Lesion (AOL) scale, would be sequelae of in situ thrombo-occlusion (IST) with underlying ICAD. Angiographic imaging during EVT and follow up imaging (MR or CT angiography) 5 to 7 days post-procedure was performed to assess stenosis.
Out of 163 patients enrolled in the study, 74 patients (45.5%) had partial recanalization (AOL 2) on post-procedural angiography. Rates of favorable clinical outcomes at 3 months (defined as mRS of 2 or less) did not differ between the group with partial (AOL 2) versus complete recanalization (AOL 3). Forty patients (24.5%) in the study were determined to have IST as their stroke etiology, and all of these patients had residual stenosis present on the post-procedural angiogram (AOL 2). 27% of patients with partial recanalization compared to only 1.1% of patients with complete recanalization developed instant reocclusion during EVT. In addition, those patients with partial recanalization during EVT were more likely to have worse stenosis or occlusion (10.8% vs 1.1%) on follow-up imaging. On multivariable regression analysis, delayed reocclusion in patients with partial recanalization was predicted by excellent baseline collateral-flow (OR 8.477; 95%CI 1.169-61.464) and neurological worsening post-procedure (OR 10.388; 95%CI 1.287-83.876).

It is important to note that the authors used a radiologic-based approach to identify IST that was based on the presence and severity (>50%) of residual stenosis and the presence of ICAD. The majority of patients with IST determined using these criteria were classified as partial recanalization with residual stenosis exceeding 50% on follow-up angiography. This study suggests that IST is a common cause of large vessel occlusion in an Asian population and that residual stenosis is associated with increased risk of reocclusion and early neurologic deterioration. Going forward, work should include controlling for endovascular approach utilized and characterizing the pathologic correlates for radiographic-determined IST.