ADVANCE PRAISE FOR EMERGENCY NEUROLOGY, SECOND EDITION
“Emergency Neurology provides practical guidance to approaching both common as well as newly described neurological syndromes. With illustrative cases, key points, and useful tables, each chapter addresses common diagnostic and therapeutic dilemmas in a brief, engaging, and high impact format. Emergency Neurology is a useful resource for clinicians at all levels of training and experience in neurology.”
John Probasco, MD, Vice Chair for Quality, Safety, and Service, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
“Now more than ever, hospital neurologists must be nimble and integrative in responding to complex consultations and urgent cases as their scope of practice continues to expand rapidly. In this Second Edition of Emergency Neurology, LaHue and Levin offer nuanced yet pragmatic approaches filled with clinical pearls relevant to trainees and seasoned clinicians alike. This book will get you into the mindset of a modern neurohospitalist and will surely improve your practice.”
Joshua P. Klein, MD, PhD, Vice Chair, Clinical Affairs, and Chief, Division of Hospital Neurology, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts
“This book makes it easy to grasp collection of critical issues pertinent to approaching a clinic, hospitalized patient, curbside consult, morning report, or clinic conference. The text is loaded with logical, stepwise approaches to differential diagnosis, gently guiding the reader on how to proceed in the golden hours of neurological emergencies. Ample updates sprinkled throughout the text span the breadth of topics with significant advances in recent years—comprehensive, easy on the eyes, and an essential guide for every clinician.”
Vineeta Singh, MD, Professor of Neurology, University of California, San Francisco
What Do I Do Now?
SERIES CO- EDITORS- IN- CHIEF
Lawrence C. Newman, MD
Director of the Headache Division
Professor of Neurology
New York University Langone
New York, New York
Morris Levin, MD
Director of the Headache Center
Professor of Neurology
University of California, San Francisco
San Francisco, California
OTHER VOLUMES IN THE SERIES
Headache and Facial Pain
Epilepsy
Pain
Emergency Neurology
Neuroinfections
Neurogenetics
Neurotology
Pediatric Neurology
Neurocritical Care
Stroke
Peripheral Nerve and Muscle Disease
Cerebrovascular Disease
Movement Disorders
Women’s Neurology
Neuroimmunology
Neuro-Ophthalmology
Concussion
SECOND EDITION
Sara C. LaHue, MD
Assistant Professor of Clinical Neurology
Department of Neurology
University of California
San Francisco, CA, USA
Morris Levin, MD Professor
Department of Neurology
University of California
San Francisco, CA, USA
1 Emergency Neurology
1
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Library of Congress Cataloging-in-Publication Data
Names: LaHue, Sara C., author. | Levin, Morris, 1955– author.
Title: Emergency neurology / Sara C. LaHue, Morris Levin.
Other titles: What do I do now?
Description: 2nd edition. | New York, NY : Oxford University Press, [2021] | Series: What do I do now | Morris Levin’s name appears first on previous edition. | Includes bibliographical references and index.
Identifiers: LCCN 2020020672 (print) | LCCN 2020020673 (ebook) | ISBN 9780190064303 (paperback) | ISBN 9780190064327 (epub) | ISBN 9780190064334 (online)
Subjects: MESH: Central Nervous System Diseases | Emergencies | Case Reports
LC record available at https://lccn.loc.gov/2020020672
LC ebook record available at https://lccn.loc.gov/2020020673
DOI: 10.1093/med/9780190064303.001.0001
This material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described in this material is highly dependent on the individual circumstances. And, while this material is designed to offer accurate information with respect to the subject matter covered and to be current as of the time it was written, research and knowledge about medical and health issues are constantly evolving and dose schedules for medications are being revised continually, with new side effects recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation. The publisher and the author make no representations or warranties to readers, express or implied, as to the accuracy or completeness of this material. Without limiting the foregoing, the publisher and the author make no representations or warranties as to the accuracy or efficacy of the drug dosages mentioned in the material. The author and the publisher do not accept, and expressly disclaim, any responsibility for any liability, loss, or risk that may be claimed or incurred as a consequence of the use and/or application of any of the contents of this material.
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SECTION 1 DIAGNOSTIC DILEMMAS
1 Neurological Deficits Following Carotid Endarterectomy 3
2 Prolonged Migraine Aura 7
3 Acute Generalized Weakness 13 4 Syncope 17
5 Monocular Visual Loss 23
SECTION 2 TREATMENT DILEMMAS
19 Cardioembolic Stroke with Contraindications to Anticoagulation 111
20 Recurring Transient Ischemic Attack 117
21 Acute Neuralgia 123
22 Intractable Migraine 129
23 Intracerebral Hemorrhage on Anticoagulation 135
24 First Seizure 141
25 Acute Stroke Up to 24 Hours 147
26 Acute Cervical Radiculopathy 153
27 Post-Cardiac Arrest Management 157
28 Myasthenic Crisis 163
29 Encephalopathy and Seizure After Transplant 169
30 Nonepileptic Spells 175
31 Migraine in a Pregnant Patient 179
SECTION 3 PEDIATRIC DILEMMAS
32 Acute Migraine in a Child 189
33 Febrile Seizure 193
34 Acute Ataxia in a Child 197
35 Concussion in an Adolescent 203
36 Acute Stroke in an Adolescent 209 Index 213
Preface
Some of the most exciting recent developments in neurology have occurred in the management of neurologic emergencies. This case-based second edition of Emergency Neurology features 13 new chapters as well as significant updates to chapters that appeared in the first edition and that provide practical approaches incorporating these clinical advances. The topics include acute stroke management and stroke prevention, status epilepticus, neurologic toxicities from cancer immunotherapy, newly appreciated autoimmune and paraneoplastic diseases, the prevention and management of delirium, and many others.
“Can I tell you about a new case?” is a common refrain among medical colleagues who strive to learn from each other and from our patients. Sharing cases serves as an internal check to our personal systematic approaches to the management of various diseases and are a delightfully interactive way to stay up to date in medicine. A number of clinical presentations that we see lead to diagnostic or therapeutic impasses (i.e., “What do I do now?”). We have tried to identify important examples and sort through them in a comprehensive but practical way. Our point of view is often that of an attendee at a morning rounds discussion, starting with key details of a relevant case, followed by a pragmatic discussion of the differential diagnosis, testing options, and management strategies.
This book is for clinicians at all levels of training and in all fields of medicine who treat patients with urgent or emergent neurological illnesses. This book can serve as a reference for common clinical questions or a focused primer to prepare the busy consultant for a number of eventualities on service. We hope that sharing our passion for caring for patients suffering from neurologic emergencies deepens your knowledge and clinical practice.
Sara C. LaHue,
MD
Morris Levin, MD San Francisco, CA, USA
Acknowledgments
As clinicians everywhere know, the management of each case is a team effort. It is no less true for texts like this one, and we have a number of people to thank for their assistance. First, we would like to express our sincere appreciation to our partners who put up with less support and time from us during the writing and editing of Emergency Neurology. There were also a number of colleagues at the University of California San Francisco (UCSF) who generously offered suggestions, answered questions, and supported this effort. We would like to express our gratitude to the UCSF Neurohospitalist Division faculty, who are each national leaders in the care of patients with complex and urgent neurological illnesses and are also exceptional teachers. UCSF is a very special medical institution, with seemingly an international expert in virtually every subject we wanted to be accurate about. We remain indebted to all of our colleagues here in the Neurology Department, and we could not think of more knowledgeable team to be part of. Any errors are ours, through misinterpretation or asking the wrong questions of them. Several editors at Oxford University Press helped on this project, including Jordan McAndrew and Craig Panner—many thanks to you all for being patient with us and alternately pushing us when that was needed. Finally, we would like to thank each other for the careful reading and editing of each other’s chapters before we sent them in to Oxford University Press. Thanks Mo, thanks Sara!
Sara C. LaHue Morris Levin
Emergency Neurology
SECTION 1
Diagnostic Dilemmas
1 Neurological Deficits Following Carotid Endarterectomy
A 68-year-old man who presented 6 days ago with transient language difficulty was found to have high-grade left internal carotid stenosis and then underwent left carotid endarterectomy (CAE) 3 days ago. Today he awoke with numbness in his right arm, which has persisted all morning. He also complains of a mild generalized headache. His wife called 911, and you are now seeing him the ER. Vital signs are normal, HEENT exams are normal, lungs are clear, and cardiac exam is normal. Neck is supple, and the endarterectomy incision is healing well. However, there is a bruit over this carotid. On neurological exam, his mental state, cranial nerves, strength, and coordination are all intact, but there does seem to be numbness over the entire right arm. CT scan without contrast is normal.
What do you do now?
Virtually every clinician treating adults knows that carotid endarterectomy (CEA) has been proven effective for treatment of symptomatic carotid stenosis. Fewer, however, have seen complications and feel comfortable dealing with them. It turns out that perioperative mortality can be as high as 3%, even at experienced centers. All of the usual potential postsurgical adverse consequences can occur in these patients. Wound dehiscence and infection are very rare. The most common adverse sequelae include myocardial infarction, transient ischemic attack (TIA)/stroke, hyperperfusion syndrome (HPS), neck region nerve injury, and parotitis. Stroke in the perioperative period can result from a number of contributing causes including platelet aggregation and thrombosis formation, plaque emboli, carotid dissection, and relatively low cerebral arterial perfusion pressure. The etiology of TIA or stroke must be assessed in order to choose the appropriate treatment.
After symptoms that could relate to carotid disease develop, the first step—and one which must be done quickly—is to rule out intracranial hemorrhage with head CT scan and then, if negative, to get a reliable visualization of the carotid artery over its cervical and intracranial course. This is best done via intraarterial angiography to detect flow-limiting dissection or thrombosis. CT angiography is often quicker and nearly as useful. If either is found, anti-coagulation had traditionally been the treatment of choice. High-quality duplex ultrasound evaluation can be helpful to confirm good flow through the proximal carotid and is used as a first step by some teams. Some surgeons favor surgical re-exploration if complications happen very early, with percutaneous carotid angioplasty with direct stenting. Many case reports document remission of neurological symptoms if stenting is done quickly, and several case series comparing stenting to surgical re-exploration attest to this.
Intraarterial thrombolytic therapy, in highly selected cases, may be another treatment option in patients with a postoperative thrombotic stroke suggested by arteriography. The rationale for the administration of tissue-type plasminogen activator (tPA) for these patients is based on its proven success in acute stroke, but there is no clear evidence to support its use here.
Myocardial infarction can occur after CEA, with incidence as high as 2%. Risk factors include older age, preexisting coronary artery disease, and peripheral arterial disease. Headaches are not uncommon after CEA and are often benign, but a severe headache should definitely prompt immediate medical attention. Contralateral stroke after CEA is rare but does occur, often for unclear reasons.
An important syndrome to exclude is HPS, which can produce three characteristic conditions: (1) persistent headache, (2) intracerebral hemorrhage, or (3) focal seizures. This last can involve significant post-seizure (“Todds”) paralysis which can be misleading. HPS tends to occur 3–10 days following endarterectomy. The etiology of the HPS is thought to be caused by some degree of cerebral autoregulation breakdown due to the large change in flow. HPS seems to be more likely with high-grade (>80%) preoperative carotid occlusion and in patients with recent stroke. It might be difficult to differentiate hyperperfusion consequences from peri- or postoperative stroke. Head CT and MRI with T2 or FLAIR sequences typically show cerebral edema with or without intracerebral hemorrhage. Transcranial Doppler testing can reveal cerebral hyperperfusion in some cases. Strict control of systemic hypertension (systolic pressure <150 mmHg) is the best way to treat HPS and may require intravenous antihypertensives. Generally, the lability in postoperative blood pressure (BP) tends to resolve in the first 24 hours.
Since cranial nerves can be damaged during the operative procedure, this cause of neurological deficits must also be excluded if cranial nerve symptoms and signs tend to predominate (unlike the presenting case). Nerves at risk include (1) vagus nerve, which, if damaged, can lead to vocal cord paralysis; (2) portions of the facial nerve, leading to an asymmetric smile; (3) glossopharyngeal nerve which can lead to carotid sinus dysfunction, and, finally, (4) the hypoglossal nerve, which may result in dysarthria, and tongue deviation to the side of injury on examination. Nerve damage is generally due to traction, but intraoperative transection is also possible. The most reliable predictor of cranial nerve injury during endarterectomy is surgery duration, with a very low likelihood of cranial nerve damage in patients for whom OR time was less than 2 hours.
KEY POINTS TO REMEMBER
• CAE is generally safe but postoperative complications include stroke and hyperperfusion syndrome.
• In patients who develop focal deficits in the perioperative period, immediate CT of the head is recommended to exclude hemorrhage.
• Vascular imaging is essential to determine the presence of thrombosis or dissection of the carotid artery.
• Assessment of intracranial arterial blood flow is important in determining the presence of the hyperperfusion syndrome.
• Management of arterial BP is crucial if hyperperfusion syndrome is suspected.
Further Reading
Adhiyaman V, Alexander S. Cerebral hyperperfusion syndrome following carotid endarterectomy. Q J Med. 2007;100:239–244.
Anzuini A, Briguori C, Roubin G, Rosanio S, et al. Emergency stenting to treat neurological complications occurring after carotid endarterectomy. J Am Coll Cardiol. 2001;37:2074–2079.
Farooq MU, Goshgarian C, Min J, Gorelick PB. Pathophysiology and management of reperfusion injury and hyperperfusion syndrome after carotid endarterectomy and carotid artery stenting. Exp Translational Stroke Med. 2016;8(1):7.
Flanigan DP, Flanigan ME, Dorne AL, et al. Long-term results of 442 consecutive, standardized carotid endarterectomy procedures in standard-risk and high-risk patients. J Vasc Surg. 2007;46:876.
Tu J, Wang S, Huo Z, Wu R, Yao C, Wang S. Repeated carotid endarterectomy versus carotid artery stenting for patients with carotid restenosis after carotid endarterectomy: Systematic review and meta-analysis. Surgery. 2015;57(6):1166–1173. doi:10.1016/j.surg.2015.02.005
2 Prolonged Migraine Aura
A 34-year-old woman, with a history of migraine attacks with aura, describes to the ER physician a typical migraine attack yesterday with scintillations and vision loss in the “left eye.” She states that the headache abated with oral sumatriptan but the visual symptoms have not. The longest her migraine aura has lasted in the past is approximately 60 minutes. She feels anxious and a bit confused, but mental status testing is normal. Funduscopy is normal, and the ophthalmology consultant has excluded ocular disease. There does seem to be a left visual field deficit involving both upper and lower visual quadrants, but it tends to fluctuate. Cranial nerve exam is otherwise normal. Motor exam is normal. Sensory exam is generally normal, but there may be some diminution to light touch and vibration in the left arm and trunk. Coordination is intact; gait seems limited by vision. Routine labs are normal. CT of the head with and without contrast is normal.
What do you do now?
This patient has relatively typical migraine aura symptoms (visual and sensory) but of atypical duration. The International Classification of Headache Disorders, 3rd edition (International Headache Society [ICHD] 2018) defines prolonged migraine aura as lasting more than 1 week without radiographic evidence of infarction. A second entity, migrainous stroke is defined as “one or more aura symptoms [which] persisting for >60 minutes” and where “Neuroimaging demonstrates ischaemic infarction in a relevant area” (see Boxes 2.1 and 2.2). Thus, our patient fits neither definition. An important deciding diagnostic test is MRI with diffusion-weighted imaging (DWI). If this is positive, it is very possible that a migrainous stroke has occurred. Migraine itself is a mild risk factor for stroke, particularly in certain populations, most notably young women. This increased stroke risk is primarily limited to patients who experience migraine auras, although migraine without aura carries an overall mild increased risk of stroke as well. An unanswered question is whether a longer than average duration of aura symptoms magnifies the risk. Also unanswered, and of great interest, is the question of stroke pathophysiology in migraine. Presumably this is related either to some migraine-induced circulatory compromise or hypermetabolic “exhaustion” of normal perfusion, leading to relative ischemia to one or more brain regions.
But if the MRI is negative, there are still two important imperatives: (1) to continue to investigate possible causes of ischemia or other possible causes of prolonged aura-like symptoms and (2) to attempt to curtail
BOX 2.1 International Classification of Headache Disorders, 3rd
Edition: Persistent aura without infarction. Aura symptoms persisting for 1 week or more without evidence of infarction on neuroimaging
Diagnostic criteria:
A. Aura fulfilling criterion B
B. Occurring in a patient with 1.2 Migraine with aura and typical of previous auras except that one or more aura symptoms persists for ≥1 week
C. Neuroimaging shows no evidence of infarction
D. Not better accounted for by another ICHD-3 diagnosis
BOX 2.2 International Classification of Headache Disorders, 3rd
Edition: Migrainous infarction. One or more migrainous aura symptoms associated with an ischemic brain lesion in appropriate territory demonstrated by neuroimaging
Diagnostic criteria:
A. A migraine attack fulfilling criteria B and C
B. Occurring in a patient with 1.2 Migraine with aura and typical of previous attacks except that one or more aura symptoms persists for >60 minutes
C. Neuroimaging demonstrates ischemic infarction in a relevant area
D. Not better accounted for by another ICHD-3 diagnosis
the aura. There are a number of conditions which may mimic prolonged auras including occipital lobe epilepsy, vertebrobasilar transient ischemic attacks, cerebral venous thrombosis, reversible cerebral vasoconstriction syndrome (RCVS), carotid or vertebral artery dissection, cerebral vasculitis, and hematological diseases causing “sludging.” Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are two other possibilities which MRI should exclude. CT angiography may be necessary in cases of prolonged aura to exclude vasculitis and RCVS. Imaging of the neck vessels with CT angiography (CTA) or MR angiography (MRA) may also be appropriate. EEG is very useful not only in excluding ongoing epileptic activity, but also to corroborate neurophysiological alterations in the cortex corresponding to the patient’s symptoms. In the presenting patient, one would suspect to see some altered electrophysiological activity in right posterior derivations.
Persistent aura symptoms are rare but well-documented. They are often bilateral and may actually last for months or years. The 1-week minimum required by the ICHD is based on the opinion of experts, and solid evidence supporting this timing has not really be presented. Similarly, there are no clear treatment guidelines for patients suffering from prolonged migraine auras. Historically, despite a lack of evidence of real benefit, inhalation
therapy with 10% carbon dioxide and 90% oxygen, amyl nitrate or isoproterenol, and sublingual nifedipine have been used based on the theory that migrainous auras were the result of prolonged vasoconstriction. And recent studies of patients with prolonged migraine aura have found areas of cortical hypoperfusion corresponding to the region of aura symptoms. However, it seems that this is the result of a decreased metabolic demand rather than an ischemic mechanism, so presumably there is ongoing cortical spreading depression in these patients which might respond to a different therapeutic approach. Hence, a number of agents have been tried including magnesium sulfate, prochlorperazine, divalproex, acetazolamide, verapamil, flunarizine, lamotrigine, gabapentin, and memantine. Intravenous magnesium sulfate is probably a good place to start due to its relative safety, followed by intravenous divalproex. Selected patients with persistent aura have responded to occipital nerve blocks.
So, in summary, with prolonged migraine aura it is imperative to look further for evidence of cerebral ischemia and other causes of focal neurological deficits, which can then be explored and managed. If there is no stroke on MRI DWI images, prolonged aura is the best diagnosis. There are several options for treating the aura in hopes of curtailing it but no clear guidelines. Unfortunately, little is known currently about the etiology, risk factors, prognosis, and best treatments in prolonged migraine aura. Clearly, this presentation is concerning to patients, so migraine preventive strategies should be optimized.
KEY POINTS TO REMEMBER
• Migraine auras typically develop over 5–20 minutes and resolve within 1 hour or less.
• When aura lasts beyond 1 hour, investigation into other possible causes of focal neurological deficits should be considered.
• MRI with DWI should be abnormal in migrainous infarction, and MR or CT imaging along with EEG can generally rule out other pathological causes.
• Treatments which have helped some patients to halt prolonged auras include magnesium sulfate, divalproex, oxygen, and verapimil.
Further Reading
Cuadrado ML, Aledo-Serrano Á, López-Ruiz P, Gutiérrez-Viedma Á, Fernández C, Orviz A, Arias JA. Greater occipital nerve block for the acute treatment of prolonged or persistent migraine aura. Cephalalgia. 2017; 37(8):812–818.
Headache Classification Committee of the International Headache Society. International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38:1–211.
Hu X, Zhou Y, Zhao H, Peng C. Migraine and the risk of stroke: an updated metaanalysis of prospective cohort studies. Neurological Sciences. 2017; 38(1):33–40.
Viana M, Sances G, Linde M, Nappi G, Khaliq F, Goadsby PJ, Tassorelli C. Prolonged migraine aura: new insights from a prospective diary-aided study. J Headache pain. 2018;19(1):77.
3 Acute Generalized Weakness
In the ED, a 28-year-old man complains of bilateral leg weakness for the past day and a half. He thinks it is due to a strenuous soccer match 2 days ago but feels that things seem to be worsening. He denies headache, visual problems, and any difficulty swallowing or breathing, but he also complains about some pain in his posterior thighs and back. He has had no bladder or bowel incontinence. He had a “cold” 2 weeks ago. He has been diagnosed with bipolar disorder and obsessive compulsive disorder and has been taking a combination of sodium divalproex and sertraline over the past 6 months. He also admits to frequent marijuana use and “some” alcohol use. An emergency medicine resident has examined this patient and found an entirely normal neurological exam. You repeat the exam and find that when asked to sit and stand, the patient has unexpected difficulty, and there is some impairment in gait. General exam is normal; there is no rash.
