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Acute Stroke Management in the Era of Thrombectomy

Acute Stroke Management in the Era of Thrombectomy Edgar A. Samaniego David Hasan Editors 123
Edgar A. Samaniego David Hasan Editors
Edgar A. Samaniego
David Hasan
Editors
Acute Stroke Management in the Era of Thrombectomy Edgar A. Samaniego David Hasan Editors 123
Acute Stroke Management in the Era of Thrombectomy Edgar A. Samaniego David Hasan Editors 123
Acute Stroke Management in the Era of Thrombectomy Edgar A. Samaniego David Hasan Editors 123

123

Acute Stroke Management in the Era of Thrombectomy

Edgar A. Samaniego • David Hasan

Editors

Acute Stroke Management in the Era of Thrombectomy

Edgar A. Samaniego • David Hasan Editors Acute Stroke Management in the Era of Thrombectomy

Editors Edgar A. Samaniego Department of Neurology Neurosurgery and Radiology University of Iowa Hospitals and Clinics Iowa City, IA USA

David Hasan Department of Neurosurgery University of Iowa Hospitals and Clinics Iowa City, IA USA

ISBN 978-3-030-17534-4

© Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

ISBN 978-3-030-17535-1

(eBook)

This Springer imprint is published by the registered company Springer Nature Switzerland AG. The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

This book is dedicated to my parents, Edgar and Jenny, who taught me to love books and the value of hard work. Edgar A. Samaniego

Foreword

The Road Not Taken … Two roads diverged in a wood, and I took the one less traveled by, And that has made all the difference. Robert Lee Frost (San Francisco, March 26, 1874–Boston, January 29,

1963)

We are in the dawn of a new era for the treatment of cerebrovascular dis- eases. The beginning of this new road was the development of endovascular therapy. The endovascular era undoubtedly represents a revolutionary para- digm shift to treat cerebral circulation pathology by the inside of the vessel rather than by an open surgical approach. If the endovascular approach has been extremely successful for the treat- ment of cerebral aneurysms and vascular malformations, the road appeared more challenging for the treatment of acute ischemic stroke. In 1995, the NINDS IV tPA trial clearly showed that revascularization of the occluded artery was possible and, without a doubt, represented the way forward. Therefore, for large artery occlusions (LVO), endovascular recanalization was the most logical next step. Despite 3 initial negative trials in 2015, our prediction came true. In a year that we will never forget, we witnessed the publication of five multicenter randomized clinical trials showing superiority of the endovascular approach over medical management. These trials and other clinical trials published afterward showed overwhelming level 1A evidence that the endovascular approach is profoundly beneficial in patients with LVO. The reported number needed to treat to achieve a good functional outcome in acute stroke patients up to 24 hours after symptom onset is extremely low (between 3 and 4), which is also unprecedented in the history of stroke therapy. Since then, we have witnessed an explosion of new data, innovation, and new technology that propelled endovascular treatment of acute ischemic stroke as one of the most powerful, life- and disability-saving treatment we know today. With regard to the large volume of new data acquired so far, a recent MEDLINE search for mechanical thrombectomy yields over 3000 publications in peer-reviewed journals over the last few years. The current challenge is to harvest all current knowledge and present it in a format that is useful and valid both for its scientific complexity and for its technological aspect.

viii

Foreword

Acute Stroke Treatment in the Era of Thrombectomy, which is edited by Edgar A Samaniego and David Hasan, was created specifically for this pur- pose. The book represents a comprehensive “state-of-the art” approach in describing the treatment of patients with acute ischemic stroke from imaging to medical management, to anesthesia-related issues, and, of course, to the practical and scientific underpinning of mechanical thrombectomy. The for- mat and the content make this book the ideal companion for the practitioner, the training physician, the medical student, and the healthcare personnel involved in the care of acute stroke patients, and it should be present in their library. With this brief foreword, I also want to thank and congratulate the innova- tors, the forward thinkers, and the practitioners who, as authors, have given their time to harvest this large amount of knowledge and present it in Acute Stroke Treatment in the Era of Thrombectomy. The book elegantly also repre- sents their commitment in improving the care of stroke patients.

Italo Linfante, MD, FAHA Director, Interventional Neuroradiology Endovascular Neurosurgery Clinical Professor, Herbert Wertheim College of Medicine Florida International University President, Society of Vascular and Interventional Neurology (SVIN) Miami Cardiac and Vascular Institute, Baptist Hospital Miami, FL, USA

Preface

In the United States, approximately 800,000 people suffer a stroke every year, with a stroke occurring roughly every 40 seconds and accounting for about 1 in every 20 deaths [1]. It is estimated that the total direct and indirect cost of stroke in the United States in 2013 was $33.9 billion [2, 3]. Recent trials have shown the safety and effectiveness of mechanical thrombectomy (MT) in the treatment of strokes due to large vessel occlusions. The number of patients needed to be treated (NNT) for one patient to benefit in terms of preventing an adverse outcome in these landmark MT trials ranged from 3 (EXTEND IA) to 7.4 (MR CLEAN) [4, 5]. Moreover, the DAWN trial – MT up to 24 hours from symptom onset – revealed an NNT of 2 to prevent severe disability at 90 days from symptom onset [6]. Few interventions in medicine have such a strong effect in patient’s outcomes. A corollary to MT from a distinct field in medicine, such as cardiology, has shown that primary angio- plasty for ST elevation myocardial infarction compared to thrombolytics has a short-term mortality benefit with an NNT of 50 patients [7]. We are fortu- nate to witness and directly participate in the revolution of MT in stroke. This book is a compilation of this revolution and reflects the multidisciplinary care of stroke. Every piece has to function correctly and in a timely manner to beat the odds of nature and re-establish blood flow to the dying brain. The initial chapters summarize information about the best medical man- agement of acute ischemic stroke, imaging modalities, and patient selection for MT. The book then focuses on the nuances of MT, providing detailed information about the best approaches for anesthesia during MT, access, intra-arterial thrombolysis, recent devices and catheters, and technical pitfalls of MT. A specific chapter is dedicated to MT in the venous system. This is followed by a chapter about the most common complications of MT and post- procedural care of these patients. The last chapter covers different aspects of acute stroke care and MT in the developing world. The authors of this book comprise a multidisciplinary group of world experts in the field. The book is intended for all healthcare providers who care for patients with stroke, with special emphasis for the proceduralists who are interested in the technical tips to improve outcomes and minimize complica- tions. The authors were encouraged to include teaching cases to deliver a highly scientific book with a practical approach. The book includes approxi- mately 315 figures and 175 procedural and technical tips.

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Preface

References

1. Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin. 2008;26(4):871–95.

2. MEMBERS WG, et al. Heart disease and stroke statistics—2017 update:

a report from the American Heart Association. Circulation.

2017;135(10):e146.

3. Roger VL, et al. AHA statistical update. Heart disease and stroke statis- tics–2012 update. A report from the American Heart Association. Circulation. 2012;125:e2–e220.

4. Berkhemer OA, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20.

5. Campbell BC, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–18.

6. Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mis- match between deficit and infarct. N Engl J Med. 2018;378(1):11–21.

7. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361(9351):13–20.

Iowa City, IA, USA

Edgar A. Samaniego David Hasan

Contents

1

Best Medical Management for Acute Ischemic Stroke Amir Shaban and Enrique C. Leira

 

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Imaging of Acute Ischemic Girish Bathla, Bruno Policeni, and Colin P. Derdeyn

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3

Indications for Mechanical Thrombectomy Krishna Chaitanya Joshi and Michael Chen

25

4

Anesthesia During Endovascular Treatment of Acute Ischemic Stroke Waleed Brinjikji

39

5

Arterial Access and Intermediate Catheters:

 

Procedural and Technical Considerations Aldo Mendez Ruiz, Ali Sheharyar, and Santiago Ortega-Gutierrez

 

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Intra-arterial Thrombolytics for Treatment of Acute Ischemic Stroke Alicia C. Castonguay, Mouhammad A. Jumaa, and Syed F. Zaidi

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Mechanical Thrombectomy: Emerging Devices

 

. Waldo R. Guerrero, Sami Al Kasab, and Edgar A. Samaniego

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Mechanical Thrombectomy: Techniques and Hybrid Approaches for Recanalization Alhamza R. Al-Bayati, Raul G. Nogueira, Edgar A. Samaniego, and Diogo C. Haussen

 

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Acute Stenting During Acute Ischemic Stroke Lila Sheikhi and Gabor Toth

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Tandem Occlusion Causing Acute Ischemic James Rossen, Kaustubh Limaye, and David Hasan

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Mechanical Thrombectomy in Distal Vessels:

 

. Ahmad Sweid, Stavropoula Tjoumakaris, and Pascal Jabbour

M2s and Beyond

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12 Thrombectomy of the Posterior Circulation:

. Kasra Khatibi and Viktor Szeder

Tips and Tricks

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13 Thrombectomy in the Venous System:

 

Approaches and Jorge A. Roa, Maxim Mokin, and Edgar A. Samaniego

 

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14 Complications During Mechanical Thrombectomy:

 

. Rakesh Khatri, Alberto Maud, and Gustavo J. Rodriguez

Pitfalls and Bailouts

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15 Postoperative Care After Mechanical Thrombectomy Catherine Arnold Fiebelkorn and Alejandro Rabinstein

 

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16 Stroke Care and Mechanical Thrombectomy in Developing Countries Jorge A. Roa, Sheila C. Ouriques Martins, and Francisco Jose Mont’Alverne

 

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Contributors

Sami Al Kasab, MD Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Alhamza R. Al-Bayati, MD Department of Neurology, Grady Memorial Hospital, Emory University, School of Medicine, Atlanta, GA, USA

Girish Bathla, MBBS, FRCR, MMeD Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Waleed Brinjikji, MD Department of Radiology and Neurosurgery, Mayo Clinic, Rochester, MN, USA

Alicia C. Castonguay, PhD Department of Neurology, Research, University of Toledo, Toledo, OH, USA

Michael Chen, MD Department of Neurological Surgery, Rush University Medical Center, Chicago, IL, USA

Colin P. Derdeyn, MD, FACR Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Catherine Arnold Fiebelkorn, MD Department of Neurology, Mayo Clinic, Rochester, MN, USA

Waldo R. Guerrero, MD Aurora Neuroscience Innovation Institute, Milwaukee, WI, USA

David Hasan, MD Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Diogo C. Haussen, MD Department of Neurology, Grady Memorial Hospital, Emory University, School of Medicine, Atlanta, GA, USA

Pascal Jabbour, MD Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA

Krishna Chaitanya Joshi, MBBS, MS, MCh Department of Neurological Surgery, Rush University Medical Center, Chicago, IL, USA

Mouhammad A. Jumaa, MD Department of Neurology, Stroke Center, University of Toledo, Toledo, OH, USA

Kasra Khatibi, MD Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA

xiv

Contributors

Rakesh Khatri, MD Department of Neurology, Texas Tech University, Health Science Center El Paso, El Paso, TX, USA

Enrique C. Leira, MD, MS Department of Neurology and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA

Kaustubh Limaye, MD Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Alberto Maud, MD Department of Neurology, Texas Tech University, Health Science Center El Paso, El Paso, TX, USA

Maxim Mokin, MD, PhD Department of Neurology, Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA

Francisco Jose Mont’Alverne, MD, PhD Department of Interventional Neuroradiology, General Hospital of Fortaleza, Fortaleza, CE, Brazil

Raul G. Nogueira, MD Department of Neurology, Grady Memorial Hospital, Emory University, School of Medicine, Atlanta, GA, USA

Santiago Ortega-Gutierrez, MD, MSc Department of Neurology, Neurosurgery and Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Sheila C. Ouriques Martins, MD, MS, PhD Department of Neurology, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil

Bruno Policeni, MD, MBA Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Alejandro Rabinstein, MD Department of Neurology, Mayo Clinic, Rochester, MN, USA

Jorge A. Roa, MD Department of Neurology and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Gustavo J. Rodriguez, MD Department of Neurology, Texas Tech University, Health Science Center El Paso, El Paso, TX, USA

James Rossen, MD Department of Cardiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Aldo Mendez Ruiz, MD Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Edgar A. Samaniego, MD Department of Neurology, Neurosurgery and Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Amir Shaban, MD Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Ali Sheharyar, MD Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Contributors

xv

Lila Sheikhi, MD Cerebrovascular Center, Cleveland Clinic, Cleveland, OH, USA

Ahmad Sweid, MD Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA

Viktor Szeder, MD, PhD, MSc Department of Neurology and Interventional Neuroradiology, University of California, Los Angeles, Los Angeles, CA, USA

Stavropoula Tjoumakaris, MD Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA

Gabor Toth, MD Cerebrovascular Center, Cleveland Clinic, Cleveland, OH, USA

Syed F. Zaidi, MD Department of Neurology, Neurointerventional and Vascular Neurology Program, University of Toledo, Toledo, OH, USA

Best Medical Management for Acute Ischemic Stroke Amir Shaban and Enrique C. Leira Background Stroke

Best Medical Management for Acute Ischemic Stroke

Amir Shaban and Enrique C. Leira

Background

Stroke is the first cause of disability and fifth cause of death in the United States [1]. The overall preva- lence of stroke ranges between 2% and 15%, with higher prevalence in older patients. In the Western world, about 85% of all strokes are ischemic, and the rest are hemorrhagic, but brain hemorrhages are more common in other ethnicities such as Asians. Disparities in acute ischemic stroke (AIS) rates and outcomes based on gender, race, and geographic location have been identified. Women have higher life-time risk of AIS and poorer outcome. Black men have higher incidence of AIS, a disparity that is more obvious in young patients. Overall, mortal- ity related to AIS has been in constant decline; this may be related to the advancement in acute stroke care. In this chapter we discuss the principles of medical acute stroke care from arrival to the emer- gency department to the initiation of secondary prevention and rehabilitation (Fig. 1.1).

A. Shaban

Department of Neurology, Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

E. C. Leira (*)

Department of Neurology and Neurosurgery,

University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA e-mail: enrique-leira@uiowa.edu

Stabilization and Initial Evaluation

Acute ischemic stroke is a time-sensitive con- dition. On average, 1.9 million neurons die per minute in the hypo-perfused ischemic penum- bra that surrounds the core of the infarction. This sense of urgency should guide all the aspects of the patient evaluation and manage- ment. The first step, obviously, is to stabilize the patient. In patients with AIS, the most immediate threats are related to the airway and circulation. The airway is primarily assessed by inspection. While most patients with AIS are able to maintain their airway, that might not be the case for those presenting with a decreased level of consciousness (e.g., large hemispheric infarctions, top of the basilar artery syndrome, secondary seizures, large intracerebral hem- orrhages) or for those experiencing severe lower cranial nerve dysfunction and secre- tions (e.g., lower brainstem infarction, basilar artery occlusions). Oxygenation parameters (pulse oximeter or arterial blood gas) can be misleading and should not be used to endorse airway stability in AIS patients. Beside clinical features, operational factors (e.g., the need to transport to another facility or to obtain MRI) might influence the decision to intubate a patient. If the airway appears to be potentially compromised, a prophylactic endotracheal intubation might be necessary. In those cases, the provider should perform a quick neurologi-

© Springer Nature Switzerland AG 2019

E. A. Samaniego, D. Hasan (eds.), Acute Stroke Management in the Era of Thrombectomy,

https://doi.org/10.1007/978-3-030-17535-1_1

1

1

2

A. Shaban and E. C. Leira

AIS Symptoms

AIS Symptoms
Evaluate ABC: Airway Unstable BP Intubation Stable BP Control
Evaluate ABC:
Airway
Unstable
BP
Intubation
Stable
BP Control
Non-Contrast ICH or Mass? Head CT Consider Neurosurgery No ICH Consult 0-4.5 h Time Since
Non-Contrast
ICH or Mass?
Head CT
Consider
Neurosurgery
No ICH
Consult
0-4.5 h
Time Since Last
Known Normal?
4.5-24 h
rt PA eligi bl e
rt PA non-
eligible
History & Exam
Suggestive
LVO
IV rt PA 0.9 mg/Kg
(max 90 mg) 10%
bolus
History & Exam
NOT Suggestive
LVO
Advanced
Neuroimaging
LVO Status &
Penumbra
LVO Advanced Neuroimaging LVO Status & Penumbra MT Eligible Mechanical Thrombectomy Goal TICI 3 MT NOT
MT Eligible
MT Eligible
Mechanical Thrombectomy Goal TICI 3
Mechanical
Thrombectomy
Goal TICI 3
Penumbra MT Eligible Mechanical Thrombectomy Goal TICI 3 MT NOT Eligible Admit to a Dedicated Stroke
MT NOT Eligible
MT NOT
Eligible

Admit to a Dedicated Stroke Unit Monitor & Prevent Complications Investigate Stroke Subtype & Initiate Secindary Prevention

Fig. 1.1

Overview of acute stroke management

cal examination prior to intubation, since the neurological assessment will be clouded by the pharmacological sedation. The circulatory assessment should include blood pressure (BP) measurements and heart

rhythm assessment by a 12-lead EKG or telemetry. Most patients with AIS present with elevated BP values. Many of them are chronically hypertensive individuals, but even patients without a history of hypertension can have reactive elevated values on

1

Best Medical Management for Acute Ischemic Stroke

3

presentation. This acute hypertension can help perfuse a hemodynamically vulnerable ischemic penumbra. On the other hand, an excessive BP can increase the chances of reperfusion injury and hemorrhagic transformation, as well as systemic end-organ damage. In practice, AIS patients are more often harmed by aggressive BP lowering than by untreated hypertension. As a result, the American Stroke Association recommends per- missive hypertension of no more than 220/110 during the initial AIS evaluation, unless IV-tPA is being considered in which case 185/110 is recom- mended [2]. Often, just waiting for a few minutes without any intervention is enough to achieve more acceptable BP values. If treatment is needed, low-dose intravenous beta blocker such as labet- alol (10 mg) is preferred due to the moderate and predictable response. This treatment should be avoided in patients that consumed sympathetico- mimetic drugs as it could result in an unopposed alpha effect. If that is the case, or the patient has bradycardia, hydralazine (10 mg) is a reasonable alternative given its tendency to raise the heart rate. Less commonly, a continuous drip is required, and in those cases nicardipine is the first choice. In other parts of the world where these drugs may not be available or are too expensive, alternative agents such as nimodipine may be used to lower the BP.

Highlight

The American Stroke Association recom- mends permissive hypertension of no more than 220/110 during the initial AIS evalua- tion, unless IV-tPA is being considered in which case 185/110 is recommended.

The next step is establishing diagnosis, which is done clinically. The history should aim to detect any acute, focal, negative neurological symptoms that follow a vascular territory compatible with AIS. We should rapidly establish the last known normal (LKN) time. People tend to think events happen at the time they notice them, so rather than asking about the stroke onset, the evaluator should establish the most recent time when patients were at their usual baseline. Sometimes that can be

challenging, for example, in patients with lan- guage barriers or anosognosia who do not recog- nize their own symptoms. In these situations, the provider should seek collateral information from family or friends. For wake-up strokes, the time when patient went to bed the night before is usu- ally accepted as the LKN time. Despite all efforts, sometimes the LKN time remains unknown. In those cases, the neuroimaging findings might be used as a surrogate to establish the time of the infarction. A clear hypodensity on non-contrast CT scan, for instance, would be consistent with a subacute infarction that is several hours or days old. Similarly, a CT perfusion or perfusion MRI may help estimate the age of the infarction and the presence of viable penumbra. A quick review of patient’s past medical his- tory should be done in order to identify vascular risk factors such as previous strokes, hyperten- sion, atrial fibrillation, diabetes, smoking, and drug abuse. Identifying these risk factors may increase the likelihood that stroke is the correct diagnosis and may provide clues to the possible stroke mechanism. The most important informa- tion for treatment purposes is whether the patient is taking any anticoagulants or not. The optimal head position of the patient dur- ing the acute phase is controversial. Should the patient be kept flat to improve the collateral cere- bral blood flow in the ischemic penumbra, or should the bed be raised to prevent aspiration pneumonia/pneumonitis? The HeadPoST trial randomized patients with acute stroke (85% isch- emic) to flat vs. at least 30 degrees head eleva- tion. The functional outcomes and rates of pneumonia did not differ between the two groups [3]. The study had limitations, including the delay between the symptom onset and random- ization. We have to recognize that a small subset of AIS patients, often with a vessel occlusion or stenosis, is very sensitive to position changes in the hyperacute stage. We recommend flat for the first 24 hours unless there is a clinical concern for increased risk for aspiration, in which case the patient can be challenged with head elevation. For the initial neurological examination, one should use the National Institute of Health Stroke Scale (NIHSS) as a standardized scoring system

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A. Shaban and E. C. Leira

for patients with suspected stroke [4]. The base- line NIHSS score is a valuable tool as it predicts outcomes at 3 months, which is useful for provid- ers and families to decide about interventions [5]. The NIHSS has limitations, as it tends to under- estimate lesions in the non-dominant hemisphere and in the posterior circulation. The history and physical exam can help dif- ferentiate AIS from other mimics including brain hemorrhage. But this distinction is not good enough for making treatment decisions, so neuro- imaging is needed. A non-contrast CT is pre- ferred given the availability and speed of that technique. Because a CT will not typically detect a hyperacute AIS, the diagnosis remains largely clinical.

Decision Regarding Intravenous IV-tPA Treatment

Intravenous tissue plasminogen activator (IV-tPA) is effective and a standard of care treatment for adult patients with AIS. While the US Food and Drug Administration (FDA) has approved IV-tPA for use only within 3 hours of LKN, the American Heart Association in addition to other agencies around the world recommends its use up to 4.5 hours of LKN based on the ECASS-III trial [6]. IV-tPA therapy generally doubles the odds of having a favorable outcome (no symptoms, or non-disabling symptoms) at 3 months. Those odds vary depending how soon the treatment is administered [7]. Furthermore, patients treated within the first hour (golden hour) of LKN time had substantially higher odds of neurological recovery [8]. Treatment with IV-tPA is not rec- ommended if LKN time is >4.5 hours or unknown. IV-tPA therapy has known complications, which should be discussed with patient and family prior to treatment. Symptomatic intra- cerebral hemorrhage (sICH) is the most feared complication. About 6% of patients treated with IV-tPA had sICH (associated with worsening of at least 4 points on NIHSS) compared to 1–2% in patients who did not receive IV-tPA. The risk

for fatal hemorrhage is about 3% in patients treated with IV-tPA compared to less than 1% in controls [9]. Patients with severe stroke and higher NIHSS on presentation are more likely to have hemorrhagic transformation. However, it is important to recognize that, despite the increased ICH risk, IV-tPA increases the odds of a favorable outcome without an increase in mortality. Moreover, IV-tPA is considered stan- dard of care and most emergency rooms in the US have waived the need for informed consent before administering IV-tPA. Contraindications and cautions for IV-tPA therapy are reviewed in Table 1.1 [2, 10]. Please note that minor non-disabling strokes should be judged on a case-by-case basis. Observational studies have shown that one-third of patients who did not receive IV-tPA for minor or rapidly improving symptoms but were otherwise eligible were disabled at 3 months. On the other hand, a recent trial in mild non-disabled strokes did not show benefit of IV-tPA [11]. In clinical practice, the relative contraindications for IV-tPA have been widely questioned. In a recent review, Fugate et al. argue that 80 years of age should not be a contraindication [12]. To be eligible for IV-tPA, blood pressure must be below 185 mmHg systolic and 110 mmHg diastolic. Patients with higher blood pressure must be treated with intravenous blood pressure-lowering agents prior to the adminis- tration of IV-tPA. Blood can be drawn and sent to the laboratory, but the results are usually not needed to make the decision regarding IV-tPA unless the patient is taking warfarin, in which case the INR is needed. Hypoglycemia can closely mimic stroke symptoms and should be rapidly ruled out with an Accu-Check determination. The recommended dose of IV-tPA is 0.9 mg/ kg (maximum dose 90 mg) with 10% given as bolus over 1 minute and the rest given as infusion over 60 minutes. Patients should be closely moni- tored during the infusion for signs of hemor- rhagic transformation or angioedema. Patients with clinical suspicion for large ves- sel occlusion should be evaluated for mechani-

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Best Medical Management for Acute Ischemic Stroke

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Table 1.1

Contraindications for IV-tPA a

Absolute contraindications

Relative contraindications

Acute intracranial hemorrhage on brain imaging

Age > 80 year old

History of intracranial or subarachnoid hemorrhage

Taking warfarin and INR < 1.7 in 3–4.5 hours window

SBP >185 mmHg; DBP >110 mmHg

History of diabetes in 3–4.5 hours window

Stroke or severe head trauma within the past 3 months

Mild symptoms

Intracranial or intraspinal surgery during the last 3 months

NIHSS score 25, in 3–4.5 hours window

Patients presenting with symptoms of subarachnoid hemorrhage

Moderate to severe strokes that demonstrate early improvement but continue to have impairment

Gastrointestinal malignancy or gastrointestinal bleed within

Preexisting disability

21

days

Platelets <100,000/mm3, INR >1.7, aPTT >40 s, or PT >15 s. If heparin received within 48 hours, PTT should be normal for patient to be eligible

Seizure at the onset of stroke

Glucose levels of <50 mg/dL if symptoms resolved after glucose normalized

Menstruation

A treatment dose of low molecular weight heparin within the previous 24 hours

Intracranial dissection

Direct thrombin inhibitors or factor Xa inhibitors within

Unruptured intracranial aneurysm measuring <10 mm

48

hours

Infectious endocarditis

Patients with known AVM

Aortic arch dissection

Recent lumbar dural puncture

Intraaxial intracranial neoplasm is a contraindication for IV-tPA. Whereas, extra-axial intracranial neoplasm is not a contraindication

Presence cerebral microbleeds

Arterial puncture at non-compressible site in previous 7 days

Acute or recent myocardial infarction

 

Pregnancy

 

Major traumas not involving the head occurring within 14 days

 

For major surgeries occurring within 14 days

INR International Normalized Ratio, aPTT activated partial thromboplastin time, PT prothrombin time, NIHSS National Institutes of Health Stroke Scale, AVM arteriovenous malformation a Data from Demaerschalk et al. [10]

cal thrombectomy. Evaluation includes vessel imaging, preferably CT angiography, to identify the location of the clot. CT or MR perfusion is also commonly performed to calculate the size of the stroke core in comparison with the poten- tially salvageable penumbra. Current guidelines extend the window for mechanical thrombec- tomy treatment up to 24 hours in selected patients [13, 14]. As an effort to decrease time delay from symptoms onset to endovascular intervention, several scales have been developed for prehospi- tal stroke recognition, severity grading, and LVO identification. These scales are intended to pro- vide an easy and simple stroke prediction tool that can be scored by emergency and rescue per-

sonnel. Some of the most notable scales are briefly discussed in Table 1.2 [15].

Post-IV-tPA Care

Once IV-tPA has been initiated, blood pressure should be closely monitored and maintained below 180 mmHg for systolic and 105 mmHg for diastolic blood pressure for the first 24 hours. Frequent neurological examinations are necessary during the following IV-tPA infusion to readily diagnose any adverse effects. Angioedema is an acute complication that occurs in about 1% of the patients, with higher rates in patients taking angiotensin-converting enzyme

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A. Shaban and E. C. Leira

Table 1.2

Prehospital stroke scales a

Proposed scale

CPSS

LAMS

FAST-ED

PASS

G-FAST

RACE

ROSIER

sNIHSS-EMS

Item

               

Consciousness

   

 

       

Gaze

   

 

 

   

Hemineglect

           

   

Visual

     

 

 

 

 

Facial palsy

   

 

 

 

   

Motor arm

 

   

   

 

 

Motor leg

           

 

 

Grip strength

   

           

Sensory

     

         

Language

       

 

 

 

Dysarthria

             

 

History seizure

             

 

Cut-off value

2

4

4

2

3

5

4

6

Sensitivity

0.83

0.81

0.60

0.61

0.88

0.85

0.79

0.70

Specificity

0.40

0.89

0.89

0.83

0.39

0.68

0.76

0.81

PPV

0.40

 

0.72

0.66

0.31

0.42

0.61

0.70

NPV

0.88

 

0.82

0.80

0.92

0.94

0.88

0.81

CPSS Cincinnati Prehospital Stroke Severity Scale, FAST-ED Field Assessment Stroke Triage for Emergency Destination, G-FAST Gaze, Face, Arm and Speech Test scores, LAMS Los Angeles Motor Scale, PASS Prehospital Acute Stroke Severity scale, RACE Rapid Arterial Occlusion Evaluation scale, ROSIER Recognition Of Stroke In the Emergency Room score, sNIHSS-EMS shortened NIH Stroke Scale for emergency medical services, PPV positive pre- dictive value, NPV negative predictive value a Data from Vidale et al. [15]

inhibitors. It is typically asymmetric, worse on the side of the hemiparesis. Depending on the severity, the treatment may range from antihistamines or cor- ticosteroids for mild and moderate angioedema to intubation in extreme life-threatening cases.

Illustrative Cases

Case #1

A 55-year-old right-handed man with past medical

history of diabetes and hypertension taking aspirin and lisinopril presented with a mild right hemipare- sis and dysarthria that started 2 hours earlier and had an NIHSS score of 4. Head CT scan without contrast was unremarkable. Patient had no contra- indications for IV-tPA and treatment was started.

His deficit improved significantly in the first 30 min- utes. Close to the end of the infusion, he was noted

to have worsening dysarthria for labial and lingual

sounds only, not for guttural. Initially, there was concern for a hemorrhagic transformation, but he denied any headache and his blood pressure was

stable. His level of consciousness was intact and his hemiparesis had actually resolved. Physical exami- nation noted angioedema on his right lip and tongue. His airway was not compromised. Patient was given a dose of diphenhydramine and methyl- prednisolone and the angioedema rapidly improved. Hemorrhagic transformation following IV-tPA typically manifests with the combination of sud- den headache, acute blood pressure elevation, and worsening of the neurological exam and/or level of consciousness. If hemorrhagic transfor- mation is suspected based on the presence of those symptoms, the infusion should be discon- tinued immediately and an emergent head CT scan should be obtained after re-evaluating the need for airway protection. Labs including coag- ulation labs, platelet count, and fibrinogen should be obtained. A rapid reversal of IV-tPA is typi- cally achieved by administrating an initial dose of 10 units of cryoprecipitate. Fibrinogen levels should be rechecked following the reversal with a target goal of >150. Cryoprecipitate infusions should be repeated to achieve that goal. Platelets should be administered for counts lower than

1

Best Medical Management for Acute Ischemic Stroke

7

a
a
c
c

Fig. 1.2 Radiological classification of hemorrhagic transformation per ECASS I trial. (a) Hemorrhagic infarc- tion 1 (HI1): small petechia; (b) hemorrhagic infarction 2 (HI2): confluent petechia; (c) parenchymal hematoma

100,000. Neurosurgical consultation should be considered to evaluate the patient for a decom- pressive hemicraniectomy. Radiographically hemorrhagic transformation can be classified (based on the ECASS I trial) into hemorrhagic infarction 1 (HI1), hemorrhagic

b
b
d
d

1(PH1): 30% of the infarcted area with some mild space-occupying effect; (d) parenchymal hematoma 2 (PH2): >30% of the infarcted area with significant space- occupying effect, or clot remote from infarcted area

infarction 2 (HI2), parenchymal hematoma 1 (PH1), and parenchymal hematoma 2 (PH2) (Fig. 1.2). This classification is useful for predic- tion of outcomes, as only PH2 was associated with increased risk of early deterioration and 3-month mortality [16].

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A. Shaban and E. C. Leira

Case #2

A 74-year-old man with past medical history of coronary artery disease and diabetes developed sudden onset of right-sided weakness and aphasia 2 hours and 45 minutes earlier. On arrival he was fully alert but not able to respond to questions. He could follow simple commands. He was constantly repeating “I’m alright”. He scored 6 on the NIHSS. Head CT scan did not show any hemor- rhage and had an ASPECTS score of 8 for isch- emic changes seen in the M5 and M6 territories (Fig. 1.3). He had no contraindications for IV-tPA and treatment was started at 3:15 hours. A CT angiography did not reveal a large artery occlu- sion so thrombectomy was not indicated. Two hours later, he developed headache, nausea, vom- iting, and tachypnea and became drowsy and mute. His BP rose to 210/130 mm Hg. A repeated CT revealed hemorrhagic transformation with vasogenic edema and midline shift (Fig. 1.4). IV-tPA was reversed by administration of 10 units

1.4 ) . IV-tPA was reversed by administration of 10 units Fig. 1.3 Head CT scan

Fig. 1.3 Head CT scan without contrast showing no hemorrhage. Alberta Stroke Program Early CT Score (ASPECTS) of 8 for ischemic changes in M5 and M6 ter- ritories (arrows)

of cryoprecipitate. Fibrinogen levels were checked after administration and were 261 mg/dL and platelets levels were 256.000/mm 3 . His blood pres- sure was closely monitored with a systolic blood pressure goal of less than 160 mmHg. Later at night, neurological examination deteriorated fur- ther and repeated head CT showed expansion of the intraparenchymal hematoma. Decompressive hemicraniectomy was recommended. However, patient’s family declined the procedure and requested patient comfort care measures only. Patients with AIS should be admitted to a dedicated stroke unit, as that has been shown to improve mortality and decreased disability inde- pendently of any specific acute intervention [17]. The mechanism of how stroke units improve out- come is uncertain, but probably the result of bet- ter prevention and treatment of complications through organized nursing care. The American Heart Association, European, and UK guidelines all recommended early stroke unit admission and care.

all recommended early stroke unit admission and care. Fig. 1.4 A repeated head CT scan without

Fig. 1.4 A repeated head CT scan without contrast revealed hemorrhagic transformation (black arrow) with vasogenic edema, midline shift and compression of the lateral ventricle (white arrow)

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Best Medical Management for Acute Ischemic Stroke

9

Blood glucose levels should be closely moni- tored in AIS patients. Hyperglycemia is noted in 50% of AIS patients on presentation and could be related to the stress response. Hyperglycemia has been associated with poor outcomes. The GIST-UK trial showed no benefit for intravenous insulin treatment on outcomes in AIS, although it was probably underpowered [18]. Patient’s tem- perature should also be checked frequently. Hyperthermia is associated with worse outcomes in AIS patients, so normothermia should be maintained.

Management of Stroke Complications

Several complications can occur in the initial days to weeks, commonly during the initial hos- pitalization following the AIS. Neurological complications usually precede the medical, and both worsen patient outcomes, survival, and dis- ability and prolong length of hospital stay.

Neurological Complications

Intracranial Edema

Cerebral edema is an expected complication fol- lowing AIS, particularly in large MCA and posterior fossa strokes. It can cause injury by sev- eral mechanisms, including mass effect and decreased blood flow. Neurological deterioration resulting from cerebral edema typically peaks within 3–4 days from the onset of stroke in supra- tentorial strokes and 24–48 hours in the posterior fossa. The larger the stroke, the more worrisome its edema is going to be. Malignant MCA cerebral infarction (defined as infarct volume of >145 cc on MRI DWI or infarction of at least 50% of MCA territory on CT scan) is associated with increased risk of herniation and death. Medical management aimed to reduce cerebral edema with osmotic therapy is an option, either with hypertonic saline with goal serum sodium of around 150 mEq/L or mannitol therapy with goal serum osmolarity of 310 mOsm/L. However,

the evidence of efficacy is stronger for decom- pression. Several clinical trials (DESTINY, DECIMAL, HAMLET) investigated the benefit of early decompressive hemicraniectomy com- pared to conservative medical management in patients with large hemispheric strokes [2, 19]. Decompressive hemicraniectomy performed in the first 48 hours in patients <60 years old improved survival with number needed to treat (NNT) of 2 and improved survival with mRS 3 with NNT of 4 [2, 19]. That benefit still exists for patients older than 60 years old, but with lesser magnitude according to the DESTINY II trial [20]. It is important to note that hemicraniectomy improves survival and disability, but returning back to normal was not possible. As such, hemi- craniectomy should only be offered to patients willing to accept some degree of disability [20].

Highlight

Decompressive hemicraniectomy should be offered early—first 48 hours—in patients with a stroke volume > 145 cc or at least 50% of MCA territory.

Large posterior circulation strokes can also cause several complications including swelling, herniation, and hydrocephalus. These complica- tions can also lead to worsening outcome and death. Decompressive suboccipital craniectomy with dural expansion is recommended in large posterior fossa strokes with mass effect and neu- rological deterioration (Fig. 1.5) [2, 21, 22]. Ventriculostomy is the recommended treatment for obstructive hydrocephalus [2, 21, 22]. The risk of upward herniation associated with ven- triculostomy can be minimized by conservative fluid drainage or performing subsequent decom- pression [2, 21, 22].

Dysphagia

A swallowing evaluation is recommended for all stroke patients before initiating oral diet due to the high rate of dysphagia in the acute settings. Intravenous hydration should be started for

10

A. Shaban and E. C. Leira

a
a
b
b

Fig. 1.5 Sagittal (a) and axial (b) CT scans showings a decompressive suboccipital craniectomy (white arrows) performed in a patient with a large posterior circulation

stroke (black arrowheads) to prevent herniation and hydrocephalus secondary to cerebral edema. (Courtesy of Samaniego/Roa)

patients who fail swallowing evaluation. A naso- gastric tube should be placed early in patients with high risk for aspiration. Percutaneous endo- scopic gastrostomy (PEG) tube should be placed if more prolonged tube feeding is needed. Overall goals of care should be taken into con- sideration when making the decision for PEG tube placement. The FOOD trial compared these two modalities and found equipoise [23]. It is important to recognize that these devices decrease but do not eliminate the risk of aspiration.

Highlight

Every patient with a stroke should be NPO until a swallow evaluation is performed.

Seizures

Less than 10% of all AIS develop seizures. Hemorrhagic strokes or patient with AIS with hemorrhagic transformation have a higher risk for seizures. Routine prophylactic treatment with antiepileptic has shown no benefit. Once seizure is noted, then antiepileptic medication should be started.

Highlight

Routine administration of antiepileptics in patients with stroke—ischemic or hemor- rhagic—is not advised.

Sleep Apnea

Patient with stroke have higher prevalence of both obstructive and central sleep apneas. Routine screening with polysomnography is currently experimental and not recommended unless sleep apnea is suspected.

Non-Neurological Complications

Venous Thromboembolism

Stroke patients have increased risk for DVT/PE due to impaired mobility. In patients with restricted mobility, pharmacological prophylaxis is recommended. Pharmacological prophylaxis should be held for 24 hours if IV-tPA was administered. Low molecular weight heparin at 40 mg/day might be superior to unfractionated heparin with- out a significant difference in the incidence of intracranial hemorrhage [24]. Pneumatic com-

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Best Medical Management for Acute Ischemic Stroke

11

pression devices are effective for DVT preven- tion in immobilized patient with contraindications for heparin use. For patients with contraindica- tion to both heparin and pneumatic compression, aspirin can be used. Inferior vena cava filter is an option for high-risk patients with contraindica- tion to all pharmacological and mechanical means of prophylaxis.

Infections

Aspiration pneumonia and urinary tract infec- tions are the most common infections following AIS. Prophylactic treatment with antibiotics is not recommended [25]. Early mobilization and avoiding dwelling catheters are useful preventa- tive measures.

Depression

Poststroke depression is a common complication that delays recovery. It affects more than one- third of patients within the first year after stroke. Fluoxetine use in patients with motor deficit has shown to enhance motor recovery and decrease poststroke depression [26].

Etiology and Secondary Prevention

Antiplatelet therapy for secondary stroke preven- tion should be held during the first 24 hours after IV-tPA administration. Traditionally, a 24-hour head CT is used to rule out hemorrhagic conver- sion prior to initiating the antiplatelet therapy. Stroke etiology should be thoroughly investi- gated to determine the optimal secondary preven- tion strategy. Stroke etiologies are classified based on the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) as cardioembolic, large- artery atherosclerosis, small vessel, stroke of indeterminate etiology, and stroke of other deter- minate etiology [27]. The extent of investigations needed following an AIS varies case to case. Head and neck vessel imaging are usually obtained in the acute settings to evaluate for large vessel disease including extra and intracranial atherosclerosis. In patients with non-disabling AIS (mRS 0–2) in the carotid vascular territory, it is recommend to perform vessel imaging within

24 hours to look for a carotid disease. Early revascularization of carotid stenosis between day 2 and day 7 following non-disabling AIS is rec- ommended [28].

Highlight

Early revascularization—2–7 days—is rec- ommended in patients with low stroke bur- den and symptomatic carotid disease.

Carotid revascularization in patients with more severe AIS usually postponed until after the acute hospitalization. Regardless of the timing of the carotid revascularization, patients should be placed on an antiplatelet agent (specifically aspirin) and a lipid-lowering medication (spe- cifically atorvastatin) for additional protection. Patients who receive a carotid stent will need an addition of anti-platelet medication. There is currently no evidence for revascularization of incidentally found asymptomatic carotid disease [29]. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Study (CREST-2) is currently underway to com- pare carotid endarterectomy and carotid stenting to best medical management in asymptomatic patients. Aggressive medical management is cur- rently the standard of care for intracranial athero- sclerosis based on the SAMMPRIS trial results that showed better outcomes in patients who received aspirin, Plavix (90 days), and atorvas- tatin compared to those who underwent intracra- nial stenting [30]. Atrial fibrillation is the most common source of embolic strokes. All patients should be placed on cardiac monitoring for at least the first 24 hours. If atrial fibrillation was detected, anticoagulation is safe to be started 4–14 days following the AIS if patients had a small stroke [2]. Starting anticoagu- lation or antiplatelet therapy for patients with AIS with hemorrhagic conversion can be done cau- tiously and on a case-by-case basis. Prolonged car- diac monitoring beyond that period is of uncertain clinical benefit [2]. Several clinical trials have shown that prolonged cardiac monitoring increases the detection of occult atrial fibrillation; however,

12

A. Shaban and E. C. Leira

those trials did not provide evidence of any benefit of anticoagulation for atrial fibrillation found at a later time [31]. Transesophageal and transthoracic echocar- diograms have been used to investigate other car- diac sources of clot such as intracardiac thrombus or cardiac tumors. These cardiac causes are rare, which makes the routine use of echocardiogra- phy not cost-effective and only recommended when cardiac etiology is suspected [2]. Patent foramen ovale (PFO) is detected in about 20% of the population, but it is more commonly seen in cryptogenic strokes. The role of PFO closure to prevent stroke in patient with cryptogenic stroke has been extensively studied. A recent clinical trial has shown that PFO closure was associated to a decreased risk of recurrent events in patients with a higher risk lesion (atrial septal aneurysm or prominent right-to-left shunt) [32]. PFO clo- sure can be considered in young patients with a higher-risk lesion and no other alternative for stroke mechanism. Testing for hypercoagulable states is not rec- ommended routinely but should be considered in younger patients with cryptogenic stroke, when there is high clinical suspicion and no other etiol- ogy found. Other measures used for secondary stroke prevention include starting high-intensity statin therapy for all patients <75 years old with no contraindications for this therapy. Patients older than 75 years old should be considered on a case-by-case basis. Measurement of lipid profile is not needed prior to the initiation of statin ther- apy. Smoking cessation should be strongly rec- ommended [2].

Stroke Rehabilitation

Rehabilitation after AIS is known to improve functional outcomes and is strongly recom- mended. Even though rehabilitation should be initiated as soon as the patient can safely par- ticipate, very early rehabilitation (within the first 24 hours) is not recommended as it is asso- ciated with worse functional outcomes [33]. Therapy should be tailored to patient’s needs and tolerance.

Key Points

• Essential information to be obtained during history taking: LKN time, the acuity of symp- tom onset, vascular risk factors, and any pos- sible contraindications for IV-tPA.

• Blood pressure goals: for patients to be eligi- ble for IV-tPA <185/110, once IV-tPA initiated

180/105. For patients who are not eligible

for IV-tPA <220/110.

• IV-tPA dose is weight dependent (0.9 mg/kg, maximum dose 90 mg) with 10% given as bolus over 1 minute and the rest given as infu- sion over 60 minutes.

• Immediate complications following IV-tPA administration: angioedema and hemorrhagic transformation.

• Angioedema management: antihistamines, corticosteroids, and intubation if necessary.

• Hemorrhagic transformation management:

infusion discontinuation, emergent head CT scan, initial dose of 10 units of cryoprecipi- tate. If platelet count lower than 100,000, then platelets should be administrated. Recheck fibrinogen levels with goal of >150 mg/dL; cryoprecipitate should be repeated to achieve that goal.

References

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3. Anderson CS, et al. Cluster-randomized, crossover trial of head positioning in acute stroke. N Engl J Med.

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5. Adams HP Jr, et al. Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999;53(1):126–31.

6. Hacke W, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med.

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7. Wardlaw JM, et al. Thrombolysis for acute isch- aemic stroke. Cochrane Database Syst Rev.

2009;4:CD000213.

8. Tsivgoulis G, et al. Intravenous thrombolysis for isch- emic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry. J Neurol.

2017;264(5):912–20.

9. Whiteley WN, et al. Risk of intracerebral haemor- rhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta- analysis. Lancet Neurol. 2016;15(9):925–33.

10. Demaerschalk BM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke.

2016;47(2):581–641.

11. Yeatts SD, et al. Alteplase for the treatment of acute ischemic stroke in patients with low National Institutes of Health stroke scale and not clearly disabling deficits (potential of rtPA for ischemic strokes with mild symptoms PRISMS): rationale and design. Int J Stroke. 2018;13(6):654–61. https://doi.

12. Fugate JE, Rabinstein AA. Absolute and relative con- traindications to IV rt-PA for acute ischemic stroke. Neurohospitalist. 2015;5(3):110–21.

13. Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11–21.

14. Albers GW, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708–18.

15. Vidale S, Agostoni E. Prehospital stroke scales and large vessel occlusion: a systematic review. Acta Neurol Scand. 2018;138(1):24–31.

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2013;11(9):CD000197.

18. Gray CS, et al. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia:

the UK glucose insulin in stroke trial (GIST-UK). Lancet Neurol. 2007;6(5):397–406.

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pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6(3):215–22.

20. Juttler E, et al. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014;370(12):1091–100.

21. Mostofi K. Neurosurgical management of massive cerebellar infarct outcome in 53 patients. Surg Neurol Int. 2013;4:28.

22. Agarwalla PK, Stapleton CJ, Ogilvy CS. Craniectomy in acute ischemic stroke. Neurosurgery. 2014;74(Suppl

1):S151–62.

23. Dennis M, et al. FOOD: a multicentre randomised trial evaluating feeding policies in patients admitted to hospital with a recent stroke. Health Technol Assess. 2006;10(2): p. iii–iv, ix–x, 1–120.

24. Shorr AF, et al. Differences between low-molecular- weight and unfractionated heparin for venous throm- boembolism prevention following ischemic stroke: a metaanalysis. Chest. 2008;133(1):149–55.

25. Chamorro A, et al. The early systemic prophylaxis of infection after stroke study: a randomized clinical trial. Stroke. 2005;36(7):1495–500.

26. Chollet F, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a ran- domised placebo-controlled trial. Lancet Neurol.

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27. Adams HP Jr, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.

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2014;370(26):2467–77.

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33. AVERT Trial Collaboration group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet.

2015;386(9988):46–55.

Imaging of Acute Ischemic Stroke

Imaging of Acute Ischemic Stroke 2 Girish Bathla, Bruno Policeni, and Colin P. Derdeyn Background Brain

2

Girish Bathla, Bruno Policeni, and Colin P. Derdeyn

Background

Brain imaging has been required for stroke treatment decisions since the advent of IV-tPA [1]. The primary aim of imaging prior to fibrino- lytic therapy is not to diagnose acute ischemic stroke (AIS), but rather to exclude hemorrhage as the cause of the acute neurologic event, and by exclusion, support the diagnosis of AIS. Both computed tomography (CT) and magnetic reso- nance imaging (MRI) have been used for this purpose. Non-contrast head CT remains the most important initial imaging tool in the evalu- ation of stroke patients for consideration of IV-tPA. The advent of proven effective endovascular thrombectomy (ET) for selected patients with AIS was largely made possible by wide-spread adoption of CT angiography (CTA) to identify large vessel occlusion (LVO) [2, 3]. For exam- ple, the Interventional Management of Stroke (IMS) III trial failed to show a benefit for ET plus IV-tPA over tPA alone [4]. When the out- come analysis was restricted to patients selected by CTA, it demonstrated a benefit [5]. All the seven positive pivotal ET trials that were pub- lished from 2015 used CTA for patient selec- tion [2]. Within 6 hours of stroke onset,

G. Bathla · B. Policeni ( * ) · C. P. Derdeyn

Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA e-mail: bruno-policeni@uiowa.edu

guidelines advocate imaging selection based on non-contrast head CT and CTA alone [6].

Highlight

Non-contrast head CT and CTA are the only required imaging modalities for patient tri- age within 6 hours of symptom onset.

Finally, the last chapter on stroke imaging brings perfusion imaging into the picture for the after-6-hour patient population. Interest in perfu- sion imaging to identify viable but ischemic tis- sue, the penumbra, dates back to the 1990s, but it was not until the last year that a clinical trial has demonstrated a benefit of revascularization in a patient population identified with perfusion imaging. The DAWN and DEFUSE-III trials selected patients after 6 hours of symptom onset, with perfusion imaging used to identify small core infarction or large areas of tissue at risk, respectively [7, 8].

CT Versus MRI

The vast majority of image triage for stroke treat- ment is done using CT. CT is widely available, fast, and proven effective for patient selection for all indications and time-windows. Some institu-

© Springer Nature Switzerland AG 2019

E. A. Samaniego, D. Hasan (eds.), Acute Stroke Management in the Era of Thrombectomy,

https://doi.org/10.1007/978-3-030-17535-1_2

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G. Bathla et al.

tions use MRI for this purpose and are able to use it effectively. In addition, there are specific situa- tions where MRI is valuable. These include patients with suspected functional examinations, particularly those with repeated emergency room visits for suspected stroke. The primary advan- tage of MRI is the ability to positively identify ischemia, using diffusion weighted imaging (DWI). The bulk of this chapter will focus on CT, owing to its dominance.

Critical Need for Protocol-Driven Imaging

It is critically important that stroke centers, pri- mary and comprehensive, have well-designed imaging protocols for acute stroke patients that are automatically triggered either on arrival or upon notification of patient transport. Most high volume stroke centers take code stroke patients to the CT scanner directly from the ambulance, where a brief examination is performed prior to imaging [9]. This approach dramatically improves time to treat- ment. In our opinion, the imaging protocol should include a non-contrast CT, as well as CTA and CTP, regardless of time of symptom onset. As we will discuss below, the data supporting the use of CTA and CTP depends on time from symptom onset and eligibility for ET. However, a standard- ized approach that includes all three acquisitions adds little time, radiation, or contrast dose, and the benefits outweigh the risks. The rationale for this approach is to streamline imaging and eliminate variability. While there is no proven value in CTA or CTP for treatment decisions for patients that will be eligible for IV-tPA, many of these patients will also be eligible for ET, where CTA is neces- sary and CTP is often useful and sometimes required (more on this below). If MRI is being used instead of CT for routine stroke imaging, similar considerations are required.

Highlight

Every “stroke imaging” protocol should include a non-contrast CT, CTA, and CTP.

The University of Iowa Code Stroke CT Imaging Protocol

We work hard to ensure a large bore IV (18 gauge) has been placed prior to arrival. Code stroke patients are taken directly to the scanner, where we obtain a non-contrast head CT, followed by a low- dose CTP acquisition that allows reconstruction of a circle of Willis CTA (Table 2.1). Given the low dose of contrast used for CTA images which are post-processed from the CTP data at our institute, we do not routinely check serum creatinine in patients with suspected acute ischemic stroke. Other sites include a CTA of the neck, which has the advantage of screening for carotid artery stenosis and providing guidance for how ET might be approached. The disadvantage is more radiation, contrast, and time. Regardless of approach, it is important to make these protocols simple and standard. In addition, they should be monitored for keeping radiation doses as low as reasonably achievable.

Identification of Core Infarction

A key criterion for treatment decisions is the extent of early ischemic changes (Fig. 2.1). If the entire territory at risk is visibly infarcted by

Table 2.1 Technical parameters of the CTP study at our institute. The CTA images are post-processed from the CTP images

Parameter

Perfusion

Angiography

Mode

Cine

N/A a

imaging

Section thickness

10 mm b

1 mm

Kilovolt peak (kVp)

70

N/A a

Milliamperage second

200

N/A a

(mAs)

Contrast volume (mL)

40

N/A a

Contrast rate (mL/sec)

7

N/A a

Saline flush

50

N/A a

Delay (sec)

2

N/A a

Acquisition time (sec)

60

N/A a

Number of scan cycles

28

N/A a

Cycle time

1.5

N/A a

a CT angiography images are generated from the CT perfu- sion data. There is no rescanning or reinjection of contrast b The CTP images are acquired at 0.6 mm slice thickness

2

Imaging of Acute Ischemic Stroke

17

CT, there is no good reason to treat with IV-tPA or ET. The initial IV-tPA trials used greater than one third of the MCA territory as a sub- jective and relative exclusion criterion. Many of the pivotal 0–6-hour window ET trials used the ASPECTS in an attempt to make this exclu- sion more objective [6]. The ASPECTS identi- fies ten regions in the MCA territory [10].

Early ischemic changes (loss of gray-white junction) in any region subtract a point from the score. The bulk of the trials used ASPECTS of 6 or greater as an inclusion criterion. The challenge with ASPECTS is that this determi- nation is subtle. In addition, there is good evi- dence that patients with poor ASPECTS (less than 6) do better with treatment than without.

a
a
b
b
c
c
d
d

Fig. 2.1 Axial CT images (a, b) in a patient with acute stroke reveal obscuration of the left lentiform, internal capsule, and insula with CT ASPECTS score of 7. Reconstructed thick section maximal intensity projection (MIP) CTA images in axial and coronal plane (c, d) reveal

abrupt occlusion of the left proximal M1. CBF (e), CBV (f), and TTD (g) images of the CTP reveal a small region of infarct-like pattern in the left lentiform (low CBV and CBF) with a large penumbra involving the remainder of the left MCA vascular distribution

18

G. Bathla et al.

e f g
e
f
g

Fig. 2.1

(continued)

This is an area of great interest and future investigation – ET treatment of patients with larger cores. Careful windowing of the CT images is impor- tant to maximize the gray-white contrast. Standard window presets are generally too wide (~80) and sometimes set too high. Narrowing the window to around 40 and adjusting the level to find the best contrast between white and gray matter improve the visibility and detection of early ischemic changes [11].

Highlight

Precise windowing of non-contrast head CTs is key in determining the correct ASPECTS score.

The late-window ET trials (greater than 6 hours after symptom onset) used perfusion imaging to identify core infarction. It is impor- tant to note, and this will be covered in more

2

Imaging of Acute Ischemic Stroke

19

detail below, that the accuracy of perfusion parameters for the definition of core infarction is time-dependent, with greater accuracy at later time points. Using perfusion imaging over non- contrast head CT to exclude 0–6-hour patients from treatment is difficult to justify.

Highlight

Perfusion imaging is mainly used for triag- ing patients for ET after 6 hours from symptom onset.

Identification of Large Vessel Occlusion

All the pivotal ET trials used vascular imaging, the large majority CTA, to identify distal internal carotid or M1 occlusion [6]. Patients with basilar thrombosis were not included in these studies, nor were those with M2 occlusions, both of which are common targets for ET. CTA can be challenging to interpret in an urgent and time- critical situation. There are several ways to look at these images. The first is simple source images. These can be inspected on the scanner console and are often diagnostic. It can be difficult to trace out vessels that come in and out of the plane of section. The second common format for view- ing is thick slab maximum intensity projections, where several millimeters of scan data are col- lapsed together and the vessels become more elongated in the plane of the image (Fig. 2.1). These can be generated in coronal, axial, and sag- ittal planes. The latter are critical for M2 occlu- sions. Finally, three-dimensional reconstructions can be generated, but these often are time- consuming and not an option for AIS. One important caveat with both CTA and MRA is the ability to distinguish the length of occlusion when the thrombus occludes the distal ICA. When the distal ICA becomes occluded, there is often minimal flow into the internal carotid artery and the proximal ICA may appear occluded, when it is in fact patent (ICA pseudo-occlusion).

Perfusion Imaging

Most perfusion imaging in AIS by CT and MRI relies on a time-resolved measurement of an intravascular contrast agent as it passes from arteries to veins in the cerebral circulation. Both modalities use a bolus injection of contrast fol- lowed by rapid repeated scans of the brain to

track the passage of the bolus. Arterial spin label- ing is an alternative for MRI measurements of cerebral blood flow (CBF), but it is very sensitive to patient motion and is not generally used in AIS settings for this reason. From these sequential images, a time-contrast (or susceptibility for MRI) curve is generated on a pixel by pixel basis. This curve is the source of most of the perfusion imaging data. To calculate relative CBF, an input function is generated from a region of interest in

a normal artery, often contralateral to the occlu-

sion. A deconvolution algorithm is used to take this input data and convert it to an impulse func- tion that simulates instantaneous arrival of all contrast material. Maps of relative CBF are gen- erated from the slope of the arrival curve. An esti-

mate of first pass, not steady-state, cerebral blood volume (CBV) is generated from measurement of the area under the curve of the time-contrast curve. Mean transit time (MTT) is calculated as the ratio of volume over flow, on a pixel by pixel basis. It is consequently a noisy image, particu- larly in the ventricles where near zero or zero val- ues are divided by similar values. TMax is the time to peak contrast and is a relative parameter.

It is the least noisy as it is not a calculated value.

Time to drain (TTD) is a function of the washout curve and is also less noisy. As time from symptom onset gets longer, CT CBF becomes more strongly predictive of core infarction [12]. This was the parameter used in the DAWN and DEFUSE-III trials to identify core. Reduced CT CBV is also a good predictor of tissue infarction [13]. Areas of reduced CBF and maintained CBV may be viable. MTT, TMax, and TTD all track together as parameters that reflect autoregulatory vasodilation and reduced mean transit time (Figs. 2.1 and 2.2). In the absence of completed infarction, they are inter-

20

G. Bathla et al.

a
a
b
b
c
c
d
d

Fig. 2.2 Axial CT images (a, b) in another patient with acute stroke reveal hyperdense MCA in the right insular region with a CT ASPECTS score of 5. Reconstructed thick section maximal intensity projection (MIP) CTA

images in axial and coronal plane (c, d) reveal abrupt occlusion of the right M1 MCA. CBF (e), CBV (f), and TTD (g) images of the CTP reveal a large region of infarct- like pattern in the right MCA vascular distribution

2

Imaging of Acute Ischemic Stroke

21

e
e
g
g

Fig. 2.2

(continued)

f
f

22

G. Bathla et al.

preted as tissue at risk. Many clinicians refer to these areas of mismatch as the ischemic penum- bra; however, these perfusion patterns are not specific for this metabolic condition [14]. Some areas may be hypo perfused but not ischemic (benign oligemia) and others may already be dead or doomed to die (apoptosis) but not visible yet as infarct.

Early stroke window 0 to 6 Hours

Patients presenting in the first 6 hours need to be evaluated for eligibility for both IV-tPA and for ET. The clinical eligibility criteria are dis- cussed previously in this book. The key imag- ing findings for IV-tPA eligibility are the absence of hemorrhage and no evidence of a large completed stroke. This later criterion is a relative one and somewhat subjective. Most of the IV-tPA trials excluded patients with more than one third of the MCA already infarcted. The time-window for IV-tPA eligibility is 0–4.5 hours. At present, any and all patients that are eligible for IV-tPA should receive it, regard- less of whether they are also eligible for ET. There are ongoing trials to determine whether eligible patients would benefit by going straight to angio for ET bypassing IV-tPA. Clinically eligible patients for ET who present in the first 6 hours need a non-contrast head CT to exclude hemorrhage. A CTA to screen for LVO is also important, although many centers, including ours, routinely take some IV-tPA-treated patients in transfer from outside hospitals straight to angi- ography. These patients are generally ones with high NIHSS scores, outside non-contrast imag- ing showing no hemorrhage or extensive early ischemic changes, and time-windows that are approaching the 6-hour limit. These patients also have a clinical presentation compatible with a large vessel occlusion: neglect, gaze preference, and hemiplegia. This practice shortens the door to revascularization time by avoiding repeat imaging in the ED. The positive results from the 0 to 6-hour trials make it difficult to justify excluding patients from ET based on perfusion data within the first

6 hours. The MR CLEAN trial, the largest of the six, found a large absolute difference between treatment and control groups using non-contrast CT and CTA alone [15]. Similarly, the subset of IMS III patients selected by CTA for large vessel occlusion also showed a benefit in a post hoc analysis [5]. Selection of patients using perfusion imaging definitely defines a group likely to do very well, but likely excludes patients that would benefit from ET. In addition, the predictive ability for perfusion imaging to reliably identify either core infarction or potentially salvageable tissue (possible pen- umbra) appears to change over time. The perfu- sion thresholds for core infarction increase over time, and likely their predictive ability as well. This is consistent with experimental data in the first few hours of stroke that show that irrevers- ible infarction is largely related to both depth and duration of ischemia. Finally, there are many other factors that contribute to infarction that are not directly perfusion related, including spread- ing cortical depression, excitotoxicity, pH, increased temperature, and apoptosis. However, there is definite value for perfusion imaging in this time-window. The first is to stan- dardize imaging to reduce variability. Perfusion imaging is absolutely necessary in the after-6- hour population, and accurately parsing this out in an emergent situation increases the chance for error. The second reason is that perfusion imaging helps identify large vessel occlusions. Large M2 occlusions and even some M1 occlu- sions can be difficult to appreciate on CTA, and seeing a larger perfusion defect helps to find the occlusion.

After-6-Hour Patients

The recent DAWN and DEFUSE-III trials have firmly validated perfusion imaging as a key selec- tion criterion for the after-6-hour patients. In the DAWN trial, patients presenting 6–24 hours after symptom onset were selected based on several imaging criteria – ischemic changes in less than one-third of the MCA territory, occlusion of the terminal ICA or M1 segment of the MCA by

2

Imaging of Acute Ischemic Stroke

23

CTA or MRA, and a small core infarct volume as estimated by CT CBF (rCBF <30% reference normal (contralateral). Three groups were defined based on age, NIHSS score, and core volume. Group A were 80 years of age or older, had an NIHSS of 10 or higher, and had an infarct volume of less than 21 ml; Group B were younger than 80 years of age, had an NIHSS of 10 or higher, and had an infarct volume of less than 31 ml; and Group C were younger than 80 years of age, had an NIHSS of 20 or higher, and had an infarct vol- ume of 31 to less than 51 ml. This trial was essen- tially a study of patients with a mismatch of core infarction and a larger clinical ischemia – so- called clinical-core mismatch. The magnitude of the clinical deficit was used as a surrogate for an imaging definition of ischemic penumbra. The DEFUSE-III trial targeted patients from 6 to 16 hours after symptom onset or last seen well. Core volumes could be larger than DAWN (70 cc) and were also based on CT CBF. DEFUSE-III required an estimate of tissue at risk based on the volume of TMax >6 seconds. The tissue at risk (increased TMax and rCBF >30) had to be at least 15 cc and the ratio of TMax to CT CBF had to be 1.8 or greater.

Location of Imaging: Primary Versus Comprehensive Stroke Centers

Primary stroke centers must have 24/7 capability to perform a non-contrast CT to make IV-tPA deci- sions. With the advent of ET, however, there is a real need to develop protocols to rapidly identify and transfer patients that are eligible or are poten- tially eligible for it. Many primary stroke centers are not capable of performing CTA and CTP stud- ies 24/7, and interpretation is also an issue. Comprehensive stroke centers will need to work with their primary stroke center partners to develop reliable and rapid imaging protocols to allow quick identification and transfer. Some primary stroke centers may be able to obtain and evaluate CTA/ CTP and others may transfer based on NIHSS and CT findings. This is an area where we will see con- siderable change in the years to come.

Many institutions perform routine 24-hour imaging to surveil for hemorrhage or other com- plications of infarction such as mass effect. Both CT and MRI can be used for this purpose.

Future Directions

The past 3 years have seen dramatic changes in stroke treatment, largely driven by development of thrombectomy devices and advanced imaging tri- age. The future will see even more rapid change. In the near term, we will see a tremendous amount of work translating these new therapies to practice. This will involve implementation of advanced imaging at primary stroke centers and this may require automated image data analysis. Transfer and treatment decisions need to be made too quickly for standard teleradiology and image inter- pretation times. Faster methods of image transfer and review by treatment teams at ET centers may be another option. Mobile stroke units with CT and advanced imaging capabilities will have some impact in some urban and suburban environments. Other avenues of research involve diagnostic tools to exclude hemorrhage in the field, potentially allowing administration of IV-tPA in transport. Flat panel technology allows acquisition of CT and CTA data in the angiosuite, and some stroke cen- ters are taking patients with suspected LVO (NIHSS > 10) directly to angio to expedite ET. In terms of imaging selection itself, areas of future research will include expanding indica- tions for treatment – proving clinical efficacy for patients with larger cores, developing better defi- nition of ischemic thresholds over time, and vali- dating the use of perfusion imaging to identify important branch vessel occlusion.

Key Points

• Hospitals need to develop protocols to ensure rapid, reproducible image acquisition and analysis.

• Inclusion of vascular and perfusion imaging as part of the standard stroke imaging protocol improves efficiency and may be done without adding significantly more time or iodinated contrast.

24

G. Bathla et al.

• Perfusion imaging should not be used to exclude patients from endovascular treatment in the first 6 hours after symptom onset.

• Imaging strategies may be different for pri- mary, comprehensive, and critical access hos- pitals, and regional systems should work together to develop imaging protocols.

References

1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasmino- gen activator for acute ischemic stroke. N Engl J Med.

1995;333(24):1581–7.

2. An H, et al. Defining the ischemic penumbra using magnetic resonance oxygen metabolic index. Stroke.

2015;46(4):982–8.

3. Wintermark M, et al. Imaging recommendations for acute stroke and transient ischemic attack patients:

a joint statement by the American Society of

Neuroradiology, the American College of Radiology and the society of neurointerventional surgery. J Am Coll Radiol. 2013;10(11):828–32.

4. Broderick JP, et al. Endovascular therapy after intra- venous t-PA versus t-PA alone for stroke. N Engl J

Med. 2013;368(10):893–903.

5. Demchuk AM, et al. Recanalization and clinical out- come of occlusion sites at baseline CT angiography

in the interventional Management of Stroke III trial.

Radiology. 2014;273(1):202–10.

6. Powers WJ, et al. 2015 AHA/ASA focused update

of the 2013 guidelines for the early management

of patients with acute ischemic stroke regarding endovascular treatment: a guideline for health- care professionals from the American Heart Association/American Stroke Association. Stroke.

2015;46:3020–35.

7.

Albers GW, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708–18.

8.

Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11–21.

9.

Ford AL, et al. Reducing door-to-needle times using Toyota’s lean manufacturing principles and value stream analysis. Stroke. 2012;43(12):3395–8.

10.

Pexman JHW, et al. Use of the Alberta stroke program early CT score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol.

2001;22(8):1534–42.

11.

Lev MH, et al. Acute stroke: improved nonenhanced CT detection-benefits of soft-copy interpretation by using variable window width and center level settings. Radiology. 1999;213(1):150–5.

12.

d’Esterre CD, et al. Time-dependent computed tomo- graphic perfusion thresholds for patients with acute ischemic stroke. Stroke. 2015;46(12):3390–7.

13.

Eastwood JD, et al. Correlation of early dynamic CT perfusion imaging with whole-brain MR diffusion and perfusion imaging in acute hemispheric stroke. AJNR Am J Neuroradiol. 2003;24(9):1869–75.

14.

Goyal M, Menon BK, Derdeyn CP. Perfusion imag- ing in acute ischemic stroke: let us improve the sci- ence before changing clinical practice. Radiology.

2013;266(1):16–21.

15.

Berkhemer OA, et al. A randomized trial of intraar- terial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11–20.

Indications for Mechanical Thrombectomy

Indications for Mechanical Thrombectomy 3 Krishna Chaitanya Joshi and Michael Chen Current Status of ET for

3

Krishna Chaitanya Joshi and Michael Chen

Current Status of ET for AIS from LVO

Endovascular therapy for acute ischemic stroke (AIS) has undergone a paradigm shift in the last few years. After the publication of five random- ized clinical studies in 2015 showing positive results, endovascular thrombectomy (ET) has become standard of care for treatment of AIS [15]. Prior to 2015, the standard of care for emergency treatment of ischemic stroke was thrombolysis with intravenous tissue plasmino- gen activator (IV-tPA). The National Institute of Neurological Disorders and Stroke (NINDS)

group published results of the stroke study group which showed that patients who were given intra- venous thrombolysis (IVT) within 3 hours from symptom onset were 30% more likely to have minimal or no disability at 3 months [6]. The therapeutic window was further extended to

4.5 hours from symptom onset by the ECASS III,

which demonstrated similar benefits up to

4.5 hours in selected patients [7]. However, the

efficacy of IV-tPA in patients with large vessel occlusion (LVO) including the proximal M1 and carotid terminus was modest, with recanalization rates of only 4–30% [8]. To improve recanaliza- tion rates, newer endovascular methods were

K. C. Joshi · M. Chen (*)

Department of Neurological Surgery, Rush University Medical Center, Chicago, IL, USA

developed. The results of early trials in ET for AIS were disappointing. But with the evolution of modern endovascular devices, patient selec- tion, and shorter transfer times, ET has now become the standard of care for treatment of AIS. Despite clear-cut evidence showing benefit for ET, challenges remain in optimizing patient selection. Criteria that are too liberal may unnec- essarily expose patients to procedure risks and costs, while criteria that are too restrictive may miss opportunities for treatment. In this chapter, we review the evidence and current indications for ET in acute ischemic stroke.

Evolution of Selection Criteria:

A Brief Review of Current Literature

Acute ischemic stroke is an ensemble of patholo- gies leading to decreased cerebral blood flow and neuronal death associated with a myriad of clini- cal and radiological presentations. In the last decade, there has been a rapid evolution of selec- tion criteria for endovascular thrombectomy, guided by the lessons learnt from multiple clini- cal trials. One of the earliest trials to compare efficacy of IVT with ET to IVT alone was the IMS III trial. The trial, however, showed similar safety outcomes and no significant difference in functional independence with endovascular ther- apy after IVT, as compared with IVT alone [9]. This study was simultaneously published with

© Springer Nature Switzerland AG 2019

E. A. Samaniego, D. Hasan (eds.), Acute Stroke Management in the Era of Thrombectomy,

https://doi.org/10.1007/978-3-030-17535-1_3

25

26

K. C. Joshi and M. Chen

the results of the SYNTHESIS Expansion from Italy, which showed similar results [10]. The third study to come out in 2013 was the MR RESCUE [11], which compared the presence of substantial ischemic penumbral tissue and a small volume of predicted core infarct, as visual- ized on multimodal CT or MRI, to identify patients who were most likely to benefit from mechanical embolectomy for the treatment of acute ischemic stroke caused by a LVO up to 8 hours after symptom onset. The hypothesis was tested by analyzing whether the pretreatment penumbral pattern had a significant interaction with treatment assignment (embolectomy vs. standard medical care) as a determinant of func- tional outcome scores across all seven levels of the modified Rankin scale (mRS, shift in disabil- ity levels). However, the results failed to show that a favorable penumbral pattern on neuroimag- ing could identify patients who would differen- tially benefit from ET at the time. However, not only did these trials have several design limitations, but they also used a thrombec- tomy technique that was inferior to the use of stent retrievers. For example, only MR RESCUE routinely performed CT angiography (CTA) or MR angiography (MRA) to identify LVO prior to study enrollment. In IMS III, CTA was performed

in only 47% of patients, and approximately 20% of patients in the interventional arm neither had a LVO nor an inaccessible, distally located throm- bus. In the SYNTHESIS Expansion trial, approx- imately 10% of patients in the interventional arm did not have a LVO. In a 2014 post hoc subgroup analysis of patients with CTA-proven LVO, there was a statistical benefit from endovascular treat- ment within 90 minutes of IV-tPA [12]. Hence, many of these negative studies enrolled subjects that lacked the index disease that thrombectomy is designed to treat. Also, these trials were done using the older generation of thrombectomy devices like the MERCI device. Stent retrievers and/or contact aspiration were used in only 22%, 39%, and 19% of patients in the interventional arms of IMS III, MR RESCUE, and SYNTHESIS Expansion, respectively. This is widely regarded as respon- sible for the low rates of TICI 2b or 3 reperfusion. The rates of TICI 2b/3 recanalization were 40% in IMS III, 27% in MR RESCUE, and not reported in SYNTHESIS Expansion. In contrast to the negative trials, the five RCTs published in 2015 showed an overwhelmingly posi- tive treatment effect in the endovascular arm (Table 3.1). The earliest trial, MR CLEAN con- ducted by the Dutch heart foundation, compared ET

Table 3.1

The five most important published trials on endovascular therapy in stroke

 
 

MR CLEAN

ESCAPE

EXTEND IA

SWIFT PRIME

REVASCAT

Continent

Europe

North America, Europe, East Asia

Australia/New

North America and Europe

Europe

Zealand

Country

Netherlands

Multiple

Two

Multiple

Spain

Number of

502

316

70

196

206

Participants

Imaging

Non-contrast

Non-contrast CT/

Non-contrast CT/

Non-contrast CT/

Non-contrast CT/

modality

CT/CTA

CTA

CTA/CT perfusion

CTA/CT perfusion

CTA

Imaging

N/a

ASPECT 6-10,

CT perfusion

CT perfusion or DWI (1st 72 patients) thereafter CT or MRI ASPECTS 6–10

ASPECTS 6-10

criteria for

good collaterals

mismatch and

core

ischemic core

<70 ml

Clinical criteria

Age (years)

>18

>18

>18

18–80

18–80 (81–85 if ASPECTS >8)

Baseline

N/A

NIHSS > = 6

N/A

NIHSS 8–29

NIHSS > = 6

stroke severity

Cutoff time for ET(hours)

< = 6

< = 12

< = 6

< = 6

< = 8

Type of device

Any

Any

Solitaire

Solitaire

Solitaire

3

Indications for Mechanical Thrombectomy

27

to best medical management, with or without

IV-tPA, within 6 hours of stroke onset and showed a significant benefit from endovascular stroke therapy [1]. This was followed by publication of four other RCTs – ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA – done between December 2010 and December 2014. These trials showed consistent superiority of ET over standard medical manage- ment in patients with proximal anterior circulation occlusion, and all these trials were prematurely stopped due to efficacy and/or loss of clinical equi- poise. Uncertainties remain about the benefit of endovascular thrombectomy in patient groups under-represented in these individual trials, includ- ing those who presented late to treatment, the elderly, those with mild deficits, large core and those not eligible for IV-tPA [13]. A collaborative group, HERMES, performed a pooled analysis of these trials to further answer these questions [14]. They analyzed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653

assigned to control). ET led to significantly reduced disability at 90 days compared with control (95%

CI 1.76–3.53, p < 0.0001). The number needed to

treat (NNT) with ET to reduce disability by at least one level on mRS for one patient was 2.6. Effect sizes favoring ET over control were present in sev- eral strata of special interest, including in patients aged 80 years or older, those randomized more than 300 minutes after symptom onset, and those not eli- gible for IV-tPA. Mortality at 90 days and risk of parenchymal hematoma and symptomatic intracra- nial hemorrhage (sICH) did not differ between populations.

Highlight

The safety of current ET is such that the analysis by the HERMES group did not demonstrate a higher risk of hematoma and symptomatic intracranial hemorrhage in patients older than 80 years, those treated after 300 minutes from symptom onset, and those not eligible for IV-tPA. The number of patients needed to treat with ET to reduce disability by at least one level on mRS for one patient was 2.6.

Eligibility for Thrombectomy by Time

In the last few years, our understanding of stroke has evolved from a focus on “time is brain” to “collaterals is brain.” Many of the ear- lier positive thrombectomy trials had strict time windows up to 6 hours. However, more recent evidence supports a physiological rather than an exclusively time-based surrogate to deter- mine whether salvageable brain exists [15]. Using advanced imaging, two trials, DAWN [16] and DEFUSE-3 [17], published recently, showed benefit for ET up to 24 hours and 16 hours since last known well, respectively (Table 3.2). The DAWN trial [16] enrolled patients with occlusion of the intracranial inter- nal carotid artery (ICA) or proximal middle cerebral artery (MCA) who had last been known to be well 6–24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (in patients <80 years – core <51 cc and in 80 years – core <21 cc). Patients were randomly assigned to thrombectomy plus standard care (the throm- bectomy group) or to standard care alone (the control group). The results showed that the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group. The DEFUSE 3 trial [17] had less strict imaging criteria, including

Table 3.2 Comparison of selection criteria in DAWN and the DEFUSE 3 trials

   

DEFUSE

DAWN

3

Infarct Core

Group A: Age 80 years, Infarct <20 ml Group B: Age < 80 years, NIHSS 10, Infarct 30 ml Group C: Age < 80 years, NIHSS 20, Infarct >30 ml and < 50 ml

<70 ml

Mismatch

No cut off

>1.8

Penumbra

No cut off

>15 ml

(potentially

reversible

ischemia)

28

K. C. Joshi and M. Chen

patients with proximal ICA or MCA occlusion, an initial infarct size of <70 cc, and ratio of the volume of ischemic tissue on perfusion imag- ing to infarct volume of 1.8 or more were ran- domly assigned to ET plus standard medical care or standard medical therapy alone. ET plus standard medical therapy was associated with favorable shift in the distribution of functional outcomes on the mRS at 90 days. The 90-day mortality was 14% in the ET group and 26% in the medical therapy group. There was a 20% absolute reduction in death or severe disability, which represents the largest reduction in mor- tality/severe disability ever achieved in an acute stroke treatment trial.

Highlight

The DAWN and DEFUSE trials suggested a change in the treatment paradox of “time is brain” to “collaterals are brain.” Time is still a determinant of outcome, but some patients with collaterals are able to stand the test of time longer than others.

This was far higher than the HERMES results from their pooled analysis [14], which showed an increase in functional independence of 19.5% and a reduction in mortality and severe disability of 11%. What is the reason for this apparent par- adox? The answer lies within the differential rate of growth of ischemic core between different individuals, which in turn is caused by the pres- ence of collaterals in each patient. Essentially, the extended time window studies enrolled sub- jects who had better-than-average cerebral collaterals.

Highlight

In DEFUSE 3 trial, ET showed a 20% absolute reduction in death or severe dis- ability, which represents the largest reduc- tion in mortality/severe disability ever achieved in an acute stroke treatment trial.

Posterior Circulation Stroke

Less than 20–25% of strokes occur in posterior circulation territories [18]. They can have a myr- iad of clinical features and can be more difficult to diagnose compared to anterior circulation strokes. Specialist assessment and administration of IV-tPA are often delayed as a result. The com- monly used Face Arm Speech Test (FAST) score assesses whether a patient is likely to have an acute stroke and in particular to identify patients as potential candidates for thrombolysis but is positive in only 60.6% of patients of posterior circulation strokes as compared to 91.7% of patients with anterior circulation strokes [19]. The recent ET trials showing superiority of endo- vascular therapy excluded enrollment of poste- rior circulation strokes. Clinical and radiographic predictors of successful outcomes and optimal recanalization approaches in this specific group of patients have not been studied extensively. Preliminary results of the BEST trial demon- strated significant superiority of ET in treating basilar artery occlusion as compared to best med- ical therapy. In the ENDOSTROKE registry, which was a multinational stroke registry of patients undergo- ing ET, 148 patients were analyzed who under- went ET for basilar artery stroke and the most important patient-related factors determining clinical outcome were initial stroke severity and collateral status, the latter also determining recan- alization success [20]. In the ENDOSTROKE registry, the use of MRI was found to be associ- ated with better clinical outcomes than CT-based patient selection. The 2018 stroke guidelines state that although the benefits are uncertain, the use of mechanical thrombectomy with stent retriev- ers may be reasonable for carefully selected patients with AIS in whom treatment can be ini- tiated (groin puncture) within 6 hours of symp- tom onset and who have causative occlusion of the vertebral arteries, basilar artery, or posterior cerebral arteries [21]. Presently, no evidence- based recommendations for endovascular ther- apy of posterior circulation strokes exist beyond the 6-hour window. However, most centers with

3

Indications for Mechanical Thrombectomy

29

large volumes perform ET up to 24 hours from symptom onset on the posterior circulation. If there is any doubt of futile intervention, a brain MRI to determine the stroke volume can aid in the decision-making.

Highlight

Presently, no evidence-based recommenda- tions exist for ET in posterior circulation strokes beyond the 6-hour window. However, most large centers consider ET up to 24 hours from symptom onset. A brain MRI to determine the stroke burden may help the decision-making in patients who present beyond the 6-hour window.

A recent multicenter retrospective analysis of consecutive patients with posterior circulation strokes who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach), found that time to the start of procedure was an important predic- tor of clinical success. The rate of good clinical outcome was twice as high in patients whose thrombectomy was initiated within the first 6 hours than in patients treated beyond the 6-hour

window. Both stent retriever and aspiration thrombectomy as primary treatment approaches have been shown to be effective in achieving suc- cessful recanalization and favorable clinical out- comes [21, 22].

Tandem Occlusions

Tandem occlusions (TO) are occlusions or ste- nosis of cervical ICA with combined occlusion of either ICA terminus, MCA or ACA (Fig. 3.1). These lesions are not only difficult to manage but also lack consensus on how to approach them. TO have traditionally been known to have a worse prognosis, but this data is derived from trials which use IVT as the main modality of treatment [23]. Intuitively, this is under- standable because of the higher clot burden found in these cases [23, 24]. Currently, the main goal of treating acute TO is to address the cervical ICA lesion with balloon angioplasty either with or without stenting before or after intracranial thrombectomy. At times, the cervi- cal ICA is not critically stenosed and it may be possible to take the guide sheath across the ste- nosed segment to perform the thrombectomy. The thrombectomy first approach has the advantage of faster recanalization, whereas fix-

CBF<30% volume: 12 ml Tmax>6.0s volume: 202 ml Mismatch volume: 190 ml Mismatch ratio: 16.8
CBF<30% volume: 12 ml
Tmax>6.0s volume: 202 ml
Mismatch volume: 190 ml
Mismatch ratio: 16.8

30

K. C. Joshi and M. Chen

ing the cervical carotid first has the advantage of optimizing collaterals and anterograde flow just prior to the actual thrombectomy. In many cases though, cervical carotid angioplasty and stent placement can be done in less than 10 min- utes and may improve the odds for first pass complete recanalization. One of the main patient indication challenges for patients with tandem occlusions is whether a stent should be placed because of the need for

antiplatelet agents in addition to the intravenous thrombolytics that are oftentimes already infused. In a recently published meta-analysis of 237 patients from 11 studies conducted between 2010 and 2015 of patients undergoing ET in set- ting of tandem occlusions, 81% underwent stent placement followed by stent-retriever thrombec- tomy with recanalization rates reaching 81%. Pooled estimates showed favorable outcome in 44% of patients, with a 7% sICH rate, but the higher rate of ICH did not impact mortality [25]. In other meta-analysis, Maurer et al. [26] evalu- ated 43 patients and reported TICI grade 2b/3 recanalization in 76% of patients, 90 day mRS 2 in 32% of patients at discharge, and an aver- age time of 103 minutes from first angiographic run to recanalization. From the limited data available, stent placement during endovascular therapy of patients with tandem occlusion appears to have lower-than-expected rates of adverse events. The choice of antiplatelet agent may vary, but most centers use Abciximab (ReoPro) 0.25 mg/kg IV bolus over at least 1 minute, fol- lowed by 0.125 mcg/kg/min IV continuous infu- sion for 12 hours; not to exceed infusion rate of

10 mcg/min. Two hours before the end of the

infusion, oral Aspirin 325 mg and Clopidogrel

75 mg are given, either swallowed or through

nasogastric tube in case the patient does not pass the bedside swallow test. However, the recently published 2018 stroke guidelines sug- gest that tirofiban and eptifibatide may have bet- ter safety profile in patients with AIS [21]. Tirofiban and eptifibatide have a shorter half- life than abciximab and may be administered intravenous during the endovascular stenting, without a prior bolus.

Highlight

From the limited data available, stent place- ment during endovascular therapy of patients with tandem occlusion appears to have lower-than-expected rates of adverse events.

Role of NIHSS in Decision-Making

The National Institutes of Health Stroke Scale (NIHSS) was initially used for research pur- poses, and over time has become a clinical stroke assessment tool to evaluate and quantify the severity of neurologic deficits in stroke patients. The stroke scale is valid for predicting lesion size and can serve as a measure of stroke severity. The NIHSS has been shown to be a predictor of both short- and long-term outcome of stroke patients. In a large prospective study which was part of the Screening Technology and Outcomes Project in Stroke (STOPStroke), it was found that NIHSS score of greater than 10 had an 81% positive predictive value for LVO and also nearly 90% of patients without proxi- mal arterial occlusions presented with NIHSS scores 10, but so did 55% of all patients found to have occlusive lesions that may have been amenable for interventional therapy [27]. The 2018 stroke guidelines state that formal stroke scores or scales such as the NIHSS can be per- formed rapidly, have demonstrated utility and may be administered by a broad spectrum of healthcare providers with accuracy and reliabil- ity. Use of a standardized scale directly quanti- fies the degree of neurological deficit, facilitates communication, helps identify patients for thrombolytic or mechanical intervention, allows objective measurement of changing clinical sta- tus, and identifies those at higher risk for com- plications such as sICH. Although the guidelines do state that its benefits are uncertain, the use of ET with stent retrievers may be reasonable for patients with AIS in whom treatment can be ini- tiated (groin puncture) within 6 hours of symp- tom onset and who have a pre-stroke mRS

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Indications for Mechanical Thrombectomy

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score > 1, ASPECTS <6, or NIHSS score < 6 and causative occlusion of the internal carotid artery (ICA) or proximal MCA (M1). Additional RCT data are needed, and studies in the United States and Europe are underway to determine the safety and efficacy of ET in patients with LVO and low NIHSS (<6) [13]. The indications for ET in patients with low NIHSS are controversial. Most of the trials excluded patients with NIHSS <10 for ET. The fear of possibly causing more harm and the added expense are some of the reasons for the reluc- tance to perform ET in this subgroup of patients. However, recent studies have shown that the nat- ural history of LVO strokes associated with low NIHSS may not be benign. Nearly a quarter of patients primarily managed medically did not achieve independence at 90 days [28]. These patients may be heavily dependent on leptomen- ingeal collaterals, and good collaterals alone without recanalization might not prevent an unfa- vorable outcome.

Highlight

The natural history of LVO strokes associ- ated with low NIHSS may not be benign, as nearly a quarter of patients without recana- lization did not achieve independence at 90 days.

Vessel imaging might be very useful in select- ing patients in this subgroup for ET. CTA or MRA showing flow around a short ranged thrombus might predict a high feasibility of

recanalization [29]. In recent retrospective anal- ysis by Kaschner et al. of 1081 consecutive ante- rior circulation strokes, 30 patients with NIHSS scores 5 were analyzed [30]. At discharge, the median NIHSS score changed from 4 to 1

(p

< 0.001), median mRS decreased from 2 to 1

(p

< 0.001), and median Barthel Index improved

from 43 to 80 (p < 0.001). Although data from RCTs is still lacking, it seems prudent to con- sider early endovascular revascularization in this subset of patients.

Highlight

The use of ET may be reasonable for patients with AIS and LVO who have pre- stroke mRS score > 1, ASPECTS <6, or NIHSS score < 6.

Indications for ET in Special Populations: Low mRS and the Aged

Generally speaking, patients with pre-stroke mRS of 2 do poorly with ET. This continuum includes patients with cancer, those in advanced age, and patients with previous strokes. Ischemic stroke is common in patients with cancer, and approximately 10% of patients who develop AIS have cancer history [31]. Most of these patients have hypercoagulable state and have contraindication to IVT due to recent surger- ies. Successful recanalization does not always translate into good outcomes due to frailty, poor nutritional status, and slow rehabilitation in these patients. So it is often important to determine the baseline functional status before initiating stroke transfers, especially in patients with pre-morbid conditions or those who are already hospitalized. The other significant pro- portion of patients with poor functional status is the elderly or those 85 years. Most trials have shown poor outcome in these subgroups, and mostly it is because of their preexisting poor mRS. Nevertheless, it is still beneficial to consider ET in a selected group of octogenar- ians and nonagenarians who have good baseline functional status.

Highlight

Even though most trials have excluded/ shown poor outcome in older individuals

( 85 years), it is still beneficial to consider ET in a selected group of octogenarians and nonagenarians who have good baseline functional status.

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K. C. Joshi and M. Chen

Imaging Criteria

Conventionally, imaging in AIS is used to rule out patients who have ICH, which would allow for ET to recanalize the occluded artery. The plain head CT is the fast, widely available, and reliable way to assess for ICH. The Alberta Stroke Program Early CT Score (ASPECTS) is a widely used tool to guide acute stroke treatment. ASPECTS is calculated using a non-contrast CT of the head. In 1997, Von Kummer et al. showed that patients with early ischemic changes in over one-third of the MCA territory had a lower chance of good outcome after IV-tPA [32] and an ASPECTS <7 roughly corresponds with an infarct volume > one-third of the MCA territory. Most of the positive trials used ASPECTS to exclude patients. The limita- tions of ASPECTS is that it is limited to anterior circulation strokes only and gives unequal weightage to different regions. Another impor- tant limitation is the low sensitivity in early period after stroke. The HERMES meta-analysis performed a central reading of all pre-treatment scans from the five thrombectomy trials and found a clear benefit of thrombectomy in patients with ASPECTS >5. It is very difficult to lay down guidelines for inclusion-exclusion based solely on ASPECTS, but it might be pragmatic to con- sider additional imaging in select group of patients who have a low ASPECTS as candidates for ET. The other important feature of stroke imaging is the identification of the penumbra or the brain which would potentially be salvageable with revascularization. The penumbra is best indicated by the perfusion–diffusion mismatch. However, the visual assessment of PWI/DWI is insuffi- ciently reliable to be used in real-life situations because volumetric measurements need manual segmentation which can be time-consuming. The recently published DAWN and DEFUSE 3 trials showed excellent outcomes in patients presenting outside the previously defined 6–8- hour mark. The improved outcomes were achieved through the use of an automated soft- ware package called RAPID developed by iSch-

automated soft- ware package called RAPID developed by iSch- Fig. 3.2 MRA showing tandem occlusion of

Fig. 3.2 MRA showing tandem occlusion of left MCA (arrow) and left ICA

emaView (Fig. 3.2). RAPID is a fully automated image processing platform, developed to provide accurate and reliable perfusion and diffusion imaging processing that could be performed on any CT or MRI scanner. It requires images to be sent to the central server, and within minutes the images are processed, and the results sent back through email. The results include volume of core infarct, which is estimated from the volume of the tissue for which there was delayed arrival of an injected tracer (Tmax exceeding 6 sec- onds), the penumbra and the mismatch ratio. These values were used to provide cut-offs for DAWN and DEFUSE 3 trials (Table 3.2). RAPID was shown to identify patients who benefit from endovascular stroke therapy in the SWIFT- PRIME and EXTEND-IA trials in 2015. Patients treated in these trials had the highest rates of favorable clinical outcomes following ET ever achieved. With the success of RAPID, other auto- mated software for image analysis have surfaced. Applications of these software include M1 hyper- dense sign recognition, ASPECT calculation, quantification of penumbra/core, and volume quantification of ICH.

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Indications for Mechanical Thrombectomy

33

Highlight

CT- and MRI-based image processing platforms are reliable and quick tools that provide important information when selecting AIS patients for ET: volume of core infarct, penumbra, and mismatch ratio.

Role of IV-tPA

The 2018 stroke guidelines recommend IV-tPA in patients with diagnosis of AIS causing mea- surable neurological deficit, with onset of symptoms within 3–4.5 hours before beginning treatment, after weighing possible benefits ver- sus risks. It is not recommended for patients >80 years old, patients with severe stroke (NIHSS>25), patients taking an oral anticoagu- lant regardless of INR, or patients who had a recent surgery (in the last 14 days). Also, the administration of IV-tPA does not exclude eli- gible patients from receiving ET. The adminis- tration of IV-tPA at the site of diagnosis and then transfer to a comprehensive stroke center is called the “drip and ship” method. In recent times, there has been much speculation on role of IV-tPA in patients with LVO, as it is thought to be less effective in these patients due to higher clot burden. In a meta-analysis on out- come data reported in the literature of AIS patients undergoing mechanical thrombectomy with or without IV-tPA pre-treatment, it was found that ET plus IV-tPA patients had better functional outcomes (mRS 0–2), lower mortal- ity, and higher rate of successful recanalization without having increased odds of sICH when compared with ET without IV-tPA patients [33]. However, these results must also be inter- preted with important limitations. Patients who underwent mechanical thrombectomy in these studies were not randomized to receive intrave- nous thrombolysis or controlled. In view of the current evidence, it is advised to bridge patients with IV-tPA even if they are being considered for ET.

Highlight

Administration of IV-tPA does NOT exclude eligible patients from receiving ET. In fact, recent evidence suggests that patients treated with ET plus IV-tPA might have better func- tional outcomes, lower mortality, and higher rate of successful recanalization without having increased odds of sICH.

Illustrative Case

A 29-year-old male with a past medical history of tobacco use disorder is referred from an outside facility 5 hours after the acute onset of right-sided weakness and aphasia. A CT scan showed a subtle hyperintense signal at the left M3 vascular terri- tory (Fig. 3.3). His NIHSS was 2 and no IV-tPA was administered since he was outside the indi- cated time window (4.5 hours). However, since his speech was impaired, and after discussing with his family, it was decided to take him for a digital sub- traction angiography with possible intervention.

sub- traction angiography with possible intervention. Fig. 3.3 Axial CT showing a subtle hyperdense signal

Fig. 3.3 Axial CT showing a subtle hyperdense signal (arrowhead) in the left M3 vascular territory. (Courtesy of Samaniego/Roa)

34

K. C. Joshi and M. Chen

a b
a
b

Fig. 3.4 Lateral diagnostic DSA of the left ICA. (a) Suggested inadequate contrast transit in distal branches of the posterior MCA. A close-up of the affected area (b)

of the posterior MCA. A close-up of the affected area ( b ) Fig. 3.5 Superselective

Fig. 3.5 Superselective catheterization of the affected vessel with a microcatheter confirmed the presence of a clot (arrowhead) with decreased distal contrast opacifica- tion. (Courtesy of Samaniego/Roa)

Angiography demonstrated a clot in M3 pos- terior branch of the left MCA (Fig. 3.4). MT was performed after a Phenom 27 microcatheter (Medtronic) was inserted through the 6-French Envoy catheter (Codman) with the aid of a Synchro-2 soft microwire (Stryker). The microcath- eter was advanced distally to the M3 branch and

showing a clot occluding M3 posterior MCA branches (arrowhead). (Courtesy of Samaniego/Roa)

MCA branches (arrowhead). (Courtesy of Samaniego/Roa) Fig. 3.6 Deployment of Solitaire Platinum stentriever in

Fig. 3.6 Deployment of Solitaire Platinum stentriever in the affected vessel. (Courtesy of Samaniego/Roa)

then the Synchro-2 soft microwire was removed. Superselective catheterization at this level con- firmed the presence of a clot with decreased distal contrast opacification (Fig. 3.5). Then, a Solitaire Platinum 4x20 mm stentriever (Medtronic) was introduced in the microcatheter, unsheathed, and left in place for 5 minutes to ensure it embeds the clot (Fig. 3.6). While applying manual suction through the guide catheter with a 60-ml VacLok

3

Indications for Mechanical Thrombectomy

35

a b
a
b

Fig. 3.7

Fig. 3.4). (Courtesy of Samaniego/Roa)

Post-thrombectomy DSA (a, b) showing TICI 3 recanalization of M3 posterior MCA branches (compare to

3 recanalization of M3 posterior MCA branches (compare to Fig. 3.8 Follow-up axial DWI showing a

Fig. 3.8 Follow-up axial DWI showing a small wedge- shaped area of infarction in the area supplied by the posterior MCA branches. (Courtesy of Samaniego/Roa)

negative preparation syringe, the Solitaire was removed, and the clot was visualized attached to the stentriever. A post-thrombectomy angiogram showed complete recanalization the left MCA branches (TICI 3) (Fig. 3.7). A follow-up MRI showed a small area of infarction (Fig. 3.8); how-

Highlight

The safety of MT has pushed new boundar- ies in the treatment of patients with AIS. This case illustrates the benefit of MT in a patient with low NIHSS, but with involvement of a very eloquent area. The indications for MT are rapidly evolving as new evidence demonstrates its feasibility and effectiveness.

ever, the patient recovered completely with no evi- dence of aphasia.

Conclusion

The importance of patient selection for ET of AIS cannot be overemphasized. While controversy exists regarding the optimal imaging technique for patient selection, there are proven and readily available clinical indicators. Among the factors associated with poor functional recovery, age and NIHSS score are most relevant. Imaging plays a vital role in patient selection, and an assessment of collateral status is essential in patients who present after more than 6 hours of last known normal time. Though its role in patients undergo-

36

K. C. Joshi and M. Chen

ing thrombectomy is still not proven, for now IV-tPA should still be given in all patients who qualify for it.

Key Points

• All eligible patients who meet criteria for on- label use of IV tPA should receive it irrespec- tive of whether endovascular treatments are being considered.

• Endovascular thrombectomy should be con- sidered in all eligible patients with LVO within 6 hours, and select patients with significant penumbra and a small core on perfusion imag- ing from 6 to 24 hours.

• There seems to be a benefit of thrombectomy in patients with low NIHSS (<10) and a LVO, though superiority is yet to be clearly established.

• Based on current data, it seems beneficial to consider angioplasty and stenting of proximal carotid stenosis at the time of thrombectomy, but clinical utility is not yet established.

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4. Campbell BC, et al. Endovascular therapy for isch- emic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009–18.

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Anesthesia During Endovascular Treatment of Acute Ischemic Stroke Waleed Brinjikji Illustrative Case An 80-year-old male

Anesthesia During Endovascular Treatment of Acute Ischemic Stroke

Waleed Brinjikji

Illustrative Case

An 80-year-old male presents to the emergency department at 8 am after waking up with a dense left hemiparesis, left sided facial droop, and a left hemi-sensory loss. He is awake though moderately drowsy and able to follow basic commands. He was last seen normal at 3 am. The patient’s NIHSS is 17. Two days prior to admission, he presented to the emergency department with left sided amauro- sis fugax. CT angiography (CTA) at that time dem- onstrated a new occlusion of the right internal carotid artery (ICA) (Fig. 4.1). He was discharged after a 24-hour observation period with a new pre- scription for Enoxaparin. Past medical history is significant for coronary artery disease, congestive heart failure, atrial fibrillation, hypertension, hyperlipidemia, sleep apnea, and a remote history of non-aneurysmal subarachnoid hemorrhage. Non-contrast CT of the head demonstrates a hyperdense clot in the right middle cerebral artery (MCA) (Fig. 4.2a). CTA demonstrates an occlusive clot in the right M1 (Fig. 4.2b) as well as recanalization of the right ICA consistent with an artery-to-artery embolus (Fig. 4.2c). CT per- fusion demonstrates decreased cerebral blood volume in the right basal ganglia (Fig. 4.2d) and markedly diminished cerebral blood flow in the

W. Brinjikji (*) Department of Radiology and Neurosurgery, Mayo Clinic, Rochester, MN, USA e-mail: Brinjikji.waleed@mayo.edu

entirety of the right MCA territory consistent with a large ischemic penumbra (Fig. 4.2e, f). Patient is diagnosed with acute ischemic stroke (AIS) secondary to right MCA M1 occlu- sion. However, he is not an IV-tPA candidate due to time of onset, recent use of anticoagulation, and prior history of subarachnoid hemorrhage. Due to the large ischemic penumbra and small infarct core, he was considered a candidate of mechanical thrombectomy (MT). The patient was immediately transferred to the angio suite. Monitored anesthesia care (MAC) was given in the form of 25 mcg of fentanyl and 50 mg of mid- azolam. No airway support was necessary, and the patient was kept on his nasal cannula. Micropuncture set to access the right common femoral artery and an 8F sheath was placed in the right common femoral artery. 5F Simmons-2 glide catheter (Terumo) was then placed in the right com- mon carotid artery and the balloon guide catheter was advanced. Digital subtraction angiography (DSA) was performed. Angiogram demonstrated a patent right ICA and occlusion of the proximal right M1 (Fig. 4.3a, b). The microcatheter tip was advanced to an M2 branch of the right MCA. A 6 × 40 mm Solitaire stentriever (Medtronic) was deployed in the M1 segment. The microcatheter and stentriever were removed, but there was some per- sistent clot in the M1 segment (Fig. 4.3c). Because the patient was under monitored anesthesia care (MAC), we were able to exam- ine him during the procedure. He was able to

© Springer Nature Switzerland AG 2019 E. A. Samaniego, D. Hasan (eds.), Acute Stroke Management in the Era of Thrombectomy,

https://doi.org/10.1007/978-3-030-17535-1_4

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W. Brinjikji

Fig. 4.1 (a) Axial dual-energy CTA image demonstrates occlusion of the right internal carotid artery (arrow). (b) 3D reconstructed image demonstrates the occlusion of the right ICA (arrow)

a
a
b
b
a
a

Fig. 4.2 (a) Non-contrast head CT demonstrates a hyper- dense MCA (arrowhead). (b) CTA demonstrates a throm- bus in the right MCA (arrowhead). (c) Coronal reformatted CTA image demonstrates a patent right ICA. Two days prior the right ICA was occluded (Fig. 4.1), thus this is

b
b

consistent with an artery-to-artery embolus. (d) CT perfu- sion image CBV map demonstrates decreased CBV in the right basal ganglia (arrow). (e, f) CBF maps demonstrate decreased CBF in the entirety of the right MCA territory (arrows)

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Anesthesia During Endovascular Treatment of Acute Ischemic Stroke

41

c
c
d
d
e
e
f
f

Fig. 4.2

(continued)

42

W. Brinjikji

move his left arm. However, he suddenly re-lost function in his left upper extremity. A second run demonstrated reocclusion of the right MCA (Fig. 4.3d). Using coaxial technique, a 5F Sofia catheter (Microvention) was advanced to the site of the residual thrombus. Aspiration thrombec- tomy was then performed. Final control angio- gram demonstrated near total restoration of flow with TICI 2B flow (Fig. 4.3e, f).

a
a
c
c

Fig. 4.3 Right CCA injection in anteroposterior (a) and lateral (b) projections demonstrating an occlusion of the right M1 branch (arrow). (c) Post-stentriever deployment image demonstrates partial recanalization of the right M1 occlusion (arrow) with filling of MCA branch vessels. (d)

At 24 hours, the patient’s NIHSS was 8. The patient had some mental status changes 3 days post-recanalization. Non-contrast head CT dem- onstrated some increased mass effect and a small punctate hemorrhage in the right basal ganglia. The patient was discharged to a rehabilitation unit and 1-month following treatment was able to ambulate with a cane and had only trace weak- ness in his left upper and lower extremities.

b
b
d
d

Second run post-stentriever deployment demonstrates per- sistent thrombus in the right MCA (arrow). A 5 Max catheter was then advanced to the site of the thrombus and the clot was aspirated. Post-suction thrombectomy run (e, f) demon- strates recanalization of the right MCA with TICI 2B flow

4

Anesthesia During Endovascular Treatment of Acute Ischemic Stroke

43

e
e

Fig. 4.3

(continued)

Anesthesia Choices During Mechanical Thrombectomy

There are several challenges in the anesthetic management of patients receiving intra-arterial therapy for AIS. Similar to the patient in the previous vignette, stroke patients are generally elderly and suffer from multiple medical comorbidities such as hypertension, coronary artery disease, cardiac arrhythmias, sleep apnea, and congestive heart failure. Both the anesthesiologist and neurointerventionalist must consider a number of important factors in deciding how to manage these patients includ- ing choice of anesthetic method [general endo- tracheal anesthesia (GA) versus monitored anesthesia care (MAC, also known as “con- scious sedation”)], the ability of the patient to protect his or her airway, patient volume status and blood pressure management, and intraop- erative management of medical comorbidities such as hyperglycemia or dysrhythmias. Ultimately, decisions regarding the choice of anesthetic agents in patients receiving intra- arterial therapy for AIS should not be taken lightly [1].

f
f

Anesthetic choice for patients receiving endo- vascular recanalization procedures for treatment of AIS has historically been a topic of great con- troversy [24]. Many practitioners view GA as advantageous when compared to non-GA due to perceptions that GA eliminates intraoperative movement and thus improves procedural safety, intraoperative time, and efficacy [2]. Because stroke intervention requires navigation of micro- catheters and microguidewires in the cerebro- vasculature using road map images, accurate superimposition of the live fluoroscopic images on the road map image is essential in ensuring that devices are placed in the correct location. Any degree of patient movement following cre- ation of the road map can negatively affect the ability of the neurointerventionalist to properly navigate the microcatheter and microguidewire. In addition, patient movement could limit the ability of the neurointerventionalist to identify x-ray markers of catheters, mechanical devices, and wires. In the worst case scenario, this could lead to vessel perforation or dissection. It is because of perceptions of increased procedural efficiency, efficacy, and safety that general endo- tracheal anesthesia remains widely used in the intra-arterial treatment of AIS [5, 6].

44

W. Brinjikji

Highlight

Since endovascular intervention in AIS requires navigation of microcatheters and microguidewires in the cerebrovasculature using road map images, accurate superim- position of the live fluoroscopic images on the road map image is essential to ensure that devices are correctly placed and pre- vent vessel perforation/dissection.

Over the past several years, there have been many case series and post hoc analyses of ran- domized controlled trials (RCTs) which suggest that in many cases, the use of GA may be associ- ated with poorer clinical outcomes and lower recanalization rates when compared to MAC or local anesthesia. One meta-analysis of nearly 2000 patients demonstrated that patients receiv- ing GA had higher rates of death and respiratory complications, and lower odds of good neuro- logical outcome and recanalization [7]. A sub- group analysis of the HERMES study also found that the use of GA was associated with signifi- cantly lower rates of good functional outcome. To date, three RCTs comparing GA to non- GA have been reported [810]. In all these stud- ies, all important baseline variables were similar between groups (Table 4.1). Two of the three tri- als showed no difference in primary outcomes between groups, and two trials showed higher rates of good functional outcome at 90 days in the GA group compared to the non-GA group. However, there are some important limitations to

these trials. First, patients treated in these trials underwent procedural anesthetic management with a highly specialized anesthesia and neuro- critical care team with less than a 10-minute delay in puncture time and very low rates of procedural hypotension. This limits the generalizability of these results because many centers either do not have anesthesiologists readily available for stroke interventions or do not provide subspe- cialty anesthetic care for AIS. Furthermore, non- neurological specialists may not be attuned to the delicate blood pressure needs of stroke patients and the fast-paced atmosphere of a stroke inter- vention. Second, there was a high rate of con- version to GA in the non-GA groups in both SIESTA [8] and ANSTROKE [9] trials (14.2% and 15.6%, respectively). This is much higher than the 3% rate seen in previously discussed non-randomized studies. This could result in additional delays in care and complications from emergent endotracheal intubation. Lastly, these were all single-center RCTs, and there is a risk of bias given the potential that local practitioners may have been used to performing these proce- dures under GA before the start of the RCT.

Highlight

There is conflicting evidence regarding the ideal anesthesia management of patients with AIS, with several retrospective studies show- ing benefit of non-GA over GA, and three RCTs (SIESTA, ANSTROKE, GOLIATH) showing marginal benefit of GA over non-GA.

Table 4.1

Randomized controlled trials studying general anesthesia versus non-general anesthesia for mechanical

thrombectomy

 

SIESTA

ANSTROKE

GOLIATH

Setting

Single center

Single center

Single center

Number of patients (non-GA/GA)

150

90

128