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Tick Tock Goes the Collateral Clock

Houman Khosravani, MD, PhD

Vagal A, Aviv R, Sucharew H, Reddy M, Hou Q, Michel P, et al. Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes. Stroke. 2018

“We hold these truths to be self-evident” is stated in the Declaration of Independence, and some say that with the passage of time, all becomes self-evident. Thus, what is the impact of time, and what is the truth behind the function and abundance of collateral circulation? These answers are critical to the late-window management of acute stroke. The topic will be one that keeps on giving, and an important contribution to this topic comes from a recent paper by Vagal et al.

In both early and extended time-windows brought about by DAWN and DEFUSE 3, the presence and functional capacity of robust collaterals has become uniquely important. The ischemic penumbra can persist for prolonged periods of time (up to 48 hrs), and its survival rests in part with the collateral circulation. The ability to assess this important aspect of tissue health is key in the evolution of thinking that is taking place: a move from time-window to tissue-health window. At the forefront of this assessment is perfusion imaging — in the case of this research, using CT perfusion. Understanding how time affects the natural history of the penumbra stands to inform assessment and decision-making in the era of EVT for patients within 24 hrs of symptom onset. Vagal et al. explore time from stroke onset and infarct growth in untreated acute ischemic stroke patients within this time window with the purpose of understanding how collaterals affect this evolution. However, it is important to note that data in this study were collected in the era of TPA first up to 3 hrs, then up to 4.5 hrs, and IA-TPA up to six hours (spanning 2003-2011) — thus, prior to the current EVT era. Nonetheless, patients who met inclusion criteria did not receive any therapy allowing for assessment of the penumbra’s natural history.

Carotid Endarterectomy is Safe After Intravenous Thrombolysis

Mohammad Anadani, MD

Ijäs P, Aro E, Eriksson H, Vikatmaa P, Soinne L, Venermo M. Prior Intravenous Stroke Thrombolysis Does Not Increase Complications of Carotid Endarterectomy. Stroke. 2018

The benefit of carotid endarterectomy (CEA) for symptomatic carotid stenosis is well established; however, the optimal timing of procedure after stroke is still a matter of debate. Although few studies showed an increased risk of periprocedural stroke and death with early CEA (within 48 hours), others did not. In patients who receive intravenous thrombolysis (IVT), CEA is often delayed due to a concern of increased risk of intracerebral hemorrhage (ICH). However, this delay may result in a theoretical increase in risk of recurrent stroke while waiting for CEA.

In this study, Ijäs and colleagues underwent a retrospective registry study to investigate the safety and optimal timing of CEA after IV thrombolysis (IVT).

Cortical Cerebral Microinfarcts as a Novel Neuroimaging Marker of Cerebral Amyloid Angiopathy

Victor J. Del Brutto, MD

Xiong L, van Veluw SJ, Bounemia N, Charidimou A, Pasi M, Boulouis G, et al. Cerebral Cortical Microinfarcts on Magnetic Resonance Imaging and Their Association With Cognition in Cerebral Amyloid Angiopathy. Stroke. 2018

Cerebral Amyloid Angiopathy (CAA) results from the deposition of amyloid β-protein in the media and adventitia of small vessels in the leptomeninges and cerebral cortex. CAA is tightly associated with aging and is known to be a major cause of intracranial hemorrhage (ICH) and cognitive decline in the elderly. On pathological examination, vessels affected by CAA show degeneration of the smooth muscle cells, splitting of the vessel wall, microaneursymal dilation and perivascular hemorrhages. These pathological changes lead to the development of hemorrhagic lesions including lobar ICH, cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS), as well as ischemic changes such as cortical infracts and white matter disease. All of them contribute to neuronal loss and development of global brain atrophy.

By |October 10th, 2018|clinical|0 Comments

Combining CT Biomarkers for Prediction of Hematoma Expansion

Lina Palaiodimou, MD

Morotti A, Boulouis G, Charidimou A, Schwab K, Kourkoulis C, Anderson C, et al. Integration of Computed Tomographic Angiography Spot Sign and Noncontrast Computed Tomographic Hypodensities to Predict Hematoma Expansion. Stroke. 2018

Recently, there is increasing interest regarding available therapeutic options that can restrict hematoma expansion after spontaneous intracerebral hemorrhage (ICH) and may contribute to improved functional outcomes. Despite the initial enthusiasm in different therapeutic strategies (tranexamic acid, blood pressure lowering medication, etc.), the efficacy of such an approach has not been validated in the context of a randomized controlled clinical trial.

The question arises, whether these disappointing results would be different, if inclusion criteria were stricter (narrower time window) or based on patient selection using specific biomarkers. One proposed radiological biomarker is the presence of intrahematoma hypodensities (HD), which are defined as any hypodense region inside the hematoma, as seen in a non-contrast computed tomography (NCCT), having any morphology and size, disconnected from surrounding brain parenchyma. Another biomarker is the spot-sign (SS), which can be seen in a CT angiography (CTA) and is defined as presence of at least one focus of contrast, pooling within the hemorrhage and lack of connection with normal or abnormal vessels surrounding the hemorrhage. Both of these biomarkers have been shown to independently predict hematoma expansion in ICH and can be obtained by readily available imaging techniques.

Article Commentary: “Long-Term Exposure to Particulate Matter Air Pollution Is a Risk Factor for Stroke”

Burton J. Tabaac, MD

Scheers H, Jacobs L, Casas L, Nemery B, Nawrot TS. Long-Term Exposure to Particulate Matter Air Pollution Is a Risk Factor for Stroke: Meta-Analytical Evidence. Stroke. 2018

A study in 2010, published in INTERSTROKE, detailed the risk factors for stroke in 22 countries. It was shown that 90% of all ischemic and hemorrhagic strokes can be attributed to 10 major risk factors, hypertension and current smoking being the most prominent.1 This current meta-analytical article, written by Scheers et al, analyzed the Pubmed citation database to quantify the pooled association between stroke incidence and mortality with long-term exposure to particulate matter. This meta-analysis suggests a statistically significant effect of recent particulate matter exposure and the risk of stroke.

The article incorporates 20 publications, including more than 10 million people, and more than 200,000 stroke events to reveal that the association between long-term particulate matter exposure and stroke event was positive in North America and Europe (but not statistically significant for the latter) and null in Asia. The authors are keen to differentiate recent and long-term exposure to particulate matter, as they are different pathophysiological concepts. The study focus regarding short-term exposure asks when strokes are most likely to occur, whereas the consideration pertaining to long-term exposure focuses on where people are at risk.

Ischemic Penumbra and the Race Against Time. Or Is It?

Kara Jo Swafford, MD

Vagal A, Aviv R, Sucharew H, Reddy M, Hou Q, Michel P, et al. Collateral Clock Is More Important Than Time Clock for Tissue Fate: A Natural History Study of Acute Ischemic Strokes. Stroke. 2018

The ischemic penumbra represents hypo-perfused tissue at risk of infarction if cerebral blood flow is not restored and may persist for hours after onset of ischemia. Progression from penumbra to infarction may be delayed due to the presence of collateral circulation. The 2018 American Heart Association acute ischemic stroke guidelines, in part based on the results of the DAWN and DEFUSE 3 trials, support the use of perfusion imaging for identifying patients with potentially salvageable tissue to help in selecting appropriate candidates for mechanical thrombectomy. Limited data exists on penumbra characteristics in patients with untreated acute ischemic stroke compared to those receiving reperfusion therapy within a delayed time window (i.e., up to 24 hours after stroke onset). Vagal et al designed a multicenter retrospective cross-sectional study to investigate how time from stroke onset may affect penumbral salvage and infarct growth in untreated acute ischemic stroke patients within the first 24 hours, including the role of collaterals.

Predicting Outcomes on the Stroke Checkerboard

Kevin S. Attenhofer, MD

Le Bouc R, Clarençon F, Meseguer E, Lapergue B, Consoli A, Turc G, et al. Efficacy of Endovascular Therapy in Acute Ischemic Stroke Depends on Age and Clinical Severity. Stroke. 2018

Today, we are seeing a more and more expanded role of endovascular therapy (EVT) in acute ischemic stroke. Despite the ever-growing body of research describing indications for EVT, we continually see patients in practice who do not “fit the mold” of the various trials’ inclusion criteria. Weighing heavily on many stroke practitioners is how to best approach and manage the patient with an apparent large vessel occlusion with a mild corresponding clinical syndrome. How can we predict if these patients will incur more benefit or risk from EVT? While some clinical trials are pending, this observational study describes a prediction score based on age and stroke severity which they called the Stroke Checkerboard (SC) score.

By |September 28th, 2018|clinical|0 Comments

Emerging Significance of Non-Focal TIA Symptoms

Richard Jackson, MD

Ishihara T, Sato S, Uehara T, Ohara T, Hayakawa M, Kimura K, et al. Significance of Nonfocal Symptoms in Patients With Transient Ischemic Attack: The PROMISE-TIA Study. Stroke. 2018

Anyone who takes calls or sees patients in the emergency room is all too familiar with acute symptoms in patients with vascular risk factors for stroke, but which are non-localizing, anatomically unlikely to be vascular, or classically associated with non-vascular problems. This paper is a valuable step in the identification of patients who would benefit from treatment and risk-stratification but who present with atypical symptoms by building on previous observational studies using modern-day MRI imaging to assess the localization and prognosis of this symptoms.  The main limitation is that the study population is limited to people of Asian ancestry, which limits generalizability.

Historical review of the beginnings of the analysis of non-focal symptoms starts in the article with Dutch TIA Trial (DTT) in 1992, where it was found that non-focal TIA symptoms alongside focal symptoms were associated with a higher risk of cardiac death but not stroke. There have been two significant retrospective analyses since that trial continuing to investigate non-focal symptoms.  A retrospective analysis in 2005 by Compter found no difference in outcomes between focal and non-focal symptoms, but non-focal symptoms in isolation were not included in the study and the imaging modality used was CT. The Rotterdam study by Bos J et al in 2007 was a retrospective analysis from 1990 to 2005, which found that patients with both focal and non-focal symptoms of TIA each had an increased risk of stroke and the imaging modality was MRI.

By |September 26th, 2018|clinical|0 Comments

Investigation of Iron Overloaded Mice Administered Tissue Plasminogen Activator for Acute Ischemic Stroke

Kara Jo Swafford, MD

García-Yébenes I, García-Culebras A, Peña-Martínez C, Fernández-López D, Díaz-Guzmán J, Negredo P, et al. Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice. Stroke. 2018

Oxidative stress, activation of proteases and infiltration of circulating white cells are involved in short-term blood brain barrier (BBB) damage and hemorrhagic transformation (HT) after acute ischemic stroke. Iron can generate toxic reactive oxygen species associated with injury to the BBB after cerebral ischemia that may also increase HT. Some clinical studies found an increased risk of HT in the setting of iron overload. García-Yébenes, et al investigated whether iron overload increases the risk of HT with tPA in a murine model of ischemic stroke and sought to elucidate the mechanisms involved.

By |September 24th, 2018|basic sciences|0 Comments

Tandem Occlusion: If You See It, Stent It

Mohammad Anadani, MD

Papanagiotou, P, Haussen, DC, Turjman F, Labreuche  J, Piotin M, Kastrup A, RG et al. Carotid stenting with antithrombotic agents and intracranial thrombectomy leads to the highest recanalization rate in patients with acute stroke with tandem lesions. JACC: Cardiovascular Interventions. 2018

Tandem occlusion, which includes cervical Internal Carotid Artery (ICA) severe stenosis/occlusion and intracranial occlusion, has been a challenge for decades. IV tPA, which was the only available acute stroke treatment before the thrombectomy era, achieves recanalization in as low as 4% of patients. After the publications of 5 randomized trials and subsequent meta-analysis (HERMES) showing the benefit of thrombectomy in large vessel occlusion including tandem occlusion, thrombectomy has become the standard of care for tandem occlusion. However, the best approach to the ICA stenosis/occlusion remained unclear.  In tandem occlusion, there are generally three treatment options: thrombectomy alone, thrombectomy with ICA stenting, and thrombectomy with ICA angioplasty.

In this entry, I will discuss a recent publication by Panagiotis Papanagiotou and his colleagues regarding the best treatment approach for patients with tandem occlusion.

By |September 21st, 2018|clinical|0 Comments