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How Antitrust Failed Workers 1st Edition Eric A. Posner
FOR PLUM AND POSNER’S DIAGNOSIS AND TREATMENT OF STUPOR AND COMA
“Facing patients with impaired consciousness or coma is among the most urgent and difficult medical emergencies. The 1966 first edition of the ‘Diagnosis of Stupor and Coma’ by Plum and Posner illuminated medical science with an orderly approach in dealing with the comatose patient. In this fifth edition, Saper and colleagues provide a concise state of the art update of this topic necessary for patient care and is a must read for all health care providers who wish to acquire or hone their knowledge to care for these patients.”
—David A. Hafler, MD, William S. and Lois Stiles Edgerly Professor of Neurology and Immunobiology, Chairman, Department of Neurology, Yale School of Medicine, Neurologist-inChief, Yale New Haven Hospital, CT
“Plum and Posner’s Diagnosis and Treatment of Stupor and Coma has long provided the best description of both the pathophysiology and the diagnostic approach to disorders of consciousness. Remarkably, this edition was able to integrate the many new diagnostic and therapeutic tools that have become available while still maintaining the clarity and logic that made the book so useful. Every neurologist should read it!”
—John Kessler, MD, Davee Professor, Davee Department of Neurology, Northwestern University, Chicago, IL
“This new 5th Edition of the seminal Plum and Posner’s ‘Stupor and Coma’ contributed by a brilliant, and partly renewed, band associating Posner, Saper, Schiff, and Claassen is not a ‘USA dormant cop’ (anagram of the title), but a worldwide must-read for all those interested by the neurology, physiology and anatomy of consciousness, and by its disorders. Keeping with the very insightful and hitherto unseen tone of the 1972 first edition, this new opus covers almost exhaustively the rich and fast-growing relevant literature, and it can be read at different levels of expertise ranging from fresh college students to emeritus professors, including active neurologists, intensivists, and medical practitioners.”
—Prof. Lionel Naccache, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
“As both the authoritative text on the subject, and compulsory reading for all neurologists, neurosurgeons, intensivists and ER physicians, the 5th edition of Plum and Posner’s Diagnosis and Treatment of Stupor and Coma is as indelible a contribution as its four prior editions. Continuing in the tradition of the first edition’s 1966 grounding in brain structure-function relationships as they apply to disorders of consciousness, this edition is a welcome update to 2007’s 4th edition capturing important advances in knowledge in the field. It is a comprehensive, yet succinct, well referenced, scholarly summary of our present day understanding of the molecular basis of consciousness as much as it is a practical clinician’s guide to evaluation, treatment, and prognosis. A triumph—indeed! A wonderful and necessary addition to the bookshelf of a wide audience whose interests include the brain’s role in modulating normal and disturbed states of consciousness.”
—David B. Rye, MD, PhD, Professor of Neurology, Emory University School of Medicine, Atlanta, GA
“This new edition provides a comprehensive update of a classic and essential text. It preserves the best elements of the original—the succinct formulation of the pathophysiology of coma, the approach to examining a comatose patient—but brings the book solidly into the 21st Century with inclusion of modern technologies and methods. The expanded discussion of the treatment of comatose patients is most welcome, delivering a wealth of information in a concise format. This remains a remarkable book: at once both comprehensive and accessible, equally suitable for extended study and as a quick bedside reference. It deserves a place in the library of every practicing neurologist.”
—David G. Standaert, MD, PhD, John N. Whitaker Professor and Chair, Department of Neurology, The University of Alabama at Birmingham, AL
SERIES EDITOR
Eva Feldman, MD, PhD, FAAN, FANA
Russell N. DeJong Professor of Neurology
University of Michigan
Contemporary Neurology Series
PRINCIPLES OF DRUG THERAPY IN NEUROLOGY
Second Edition
Michael V. Johnston, MD, and Robert A. Gross, MD, PhD, Editors
NEUROLOGIC COMPLICATIONS OF CANCER
Second Edition
Lisa M. DeAngelis, MD, and Jerome B. Posner, MD
NEUROLOGIC COMPLICATIONS OF CRITICAL ILLNESS
Third Edition
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PARANEOPLASTIC SYNDROMES
Robert B. Darnell, MD, PhD, and Jerome B. Posner, MD
JASPER’S BASIC MECHANISMS OF THE EPILEPSIES
Jeffrey L. Noebels, MD, PhD, Massimo Avoli, MD, PhD, Michael A. Rogawski, MD, PhD, Richard W. Olsen, PhD, and Antonio V. Delgado-Escueta, MD
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Jerome Engel, Jr., MD, PhD
MULTIPLE SCLEROSIS
Moses Rodriguez, MD, Orhun H. Kantarci, MD, and Istvan Pirko, MD FRONTOTEMPORAL DEMENTIA
Bruce L. Miller, MD
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HYPERKINETIC MOVEMENT DISORDERS
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THE NEUROLOGY OF EYE MOVEMENTS
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Third Edition
David W. Dodick, MD, and Stephen D. Silberstein, MD, FACP, FAHS, FAAN CLINICAL NEUROPHYSIOLOGY
Fourth Edition
Devon Rubin and Jasper Daube, Editors
PLUM AND POSNER’S DIAGNOSIS AND TREATMENT OF STUPOR AND COMA
Fifth Edition
Jerome B. Posner
George C. Cotzias Chair of Neuro-oncology Emeritus
Evelyn Few American Cancer Society Clinical Research Professor Emeritus
Memorial-Sloan Kettering Cancer Center
Weill Cornell Medical College
New York, NY
Clifford B. Saper
James Jackson Putnam Professor of Neurology and Neuroscience
Chairman, Department of Neurology
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, MA
Nicholas D. Schiff
Jerold B. Katz Professor of Neurology and Neuroscience
Brain Mind Research Institute
Weill Cornell Medical College
New York, NY
Jan Claassen
Associate Professor of Neurology
Department of Neurology
New York Presbyterian Hospital
Columbia University School of Medicine
New York, NY
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Library of Congress Cataloging-in-Publication
Data
Names: Posner, Jerome B., 1932– editor. | Saper, C. B. (Clifford B.), editor. | Schiff, Nicholas D., editor. | Claassen, Jan, editor
Title: Plum and Posner’s diagnosis and treatment of stupor and coma / edited by Jerome B. Posner, Clifford B. Saper, Nicholas D. Schiff, and Jan Claassen. Other titles: Diagnosis and treatment of stupor and coma | Contemporary neurology series ; 93. 0069-9446
Description: Fifth edition. | Oxford ; New York : Oxford University Press, [2019] | Series: Contemporary neurology series ; #93 | Includes bibliographical references and index.
Identifiers: LCCN 2019006311 | ISBN 9780190208875 (hardback : alk. paper) | ISBN 9780190208882 (updf) | ISBN 9780190208899 (epub) | ISBN 9780190208905 (on-line)
Classification: LCC RB150.C6 | NLM WB 182 | DDC 616.8/49—dc23 LC record available at https://lccn.loc.gov/2019006311
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CONTENTS
Preface to the Fifth Edition
1. PATHOPHYSIOLOGY OF SIGNS AND SYMPTOMS OF COMA
ALTERED STATES OF CONSCIOUSNESS
DEFINITIONS
Consciousness • Acutely Altered States of Consciousness
• Subacute or Chronic Alterations of Consciousness
APPROACH TO THE DIAGNOSIS OF THE COMATOSE PATIENT
PHYSIOLOGY AND PATHOPHYSIOLOGY OF CONSCIOUSNESS AND COMA
The Ascending Arousal System • Behavioral State Switching • Relationship of Coma to Sleep • The Cerebral Hemispheres and Conscious Behavior • Structural Lesions that Cause Altered Consciousness in Humans
2. EXAMINATION OF THE COMATOSE PATIENT
OVERVIEW
HISTORY
GENERAL PHYSICAL EXAMINATION
LEVEL OF CONSCIOUSNESS
ABC: AIRWAY, BREATHING, CIRCULATION
Circulation • Respiration
PUPILLARY RESPONSES
Examine the Pupils and Their Responses • Pathophysiology of Pupillary Responses: Peripheral Anatomy of the Pupillomotor System • Pharmacology of the Peripheral Pupillomotor System • Localizing Value of Abnormal Pupillary Responses in Patients in Coma • Metabolic and Pharmacologic Causes of Abnormal Pupillary Response
OCULOMOTOR RESPONSES
Functional Anatomy of the Peripheral Oculomotor System • Functional Anatomy of the Central Oculomotor System • The Ocular Motor Examination • Interpretation of Abnormal Ocular Movements
MOTOR RESPONSES
Motor Tone • Motor Reflexes • Motor Responses
FALSE LOCALIZING SIGNS IN PATIENTS WITH METABOLIC COMA
Respiratory Responses • Pupillary Responses • Ocular Motor Responses • Motor Responses
MAJOR LABORATORY DIAGNOSTIC AIDS
Blood and Urine Testing • Computed Tomography Imaging and Angiography • Magnetic Resonance Imaging and Angiography • Magnetic Resonance Spectroscopy • Neurosonography • Lumbar Puncture • Electroencephalography and Evoked Potentials
3. STRUCTURAL CAUSES OF STUPOR AND COMA
COMPRESSIVE LESIONS AS A CAUSE OF COMA
COMPRESSIVE LESIONS MAY DIRECTLY DISTORT THE AROUSAL SYSTEM
Compression at Different Levels of the Central Nervous System Presents in Distinct Ways • The Role of Increased Intracranial Pressure in Coma • The Role of Vascular Factors and Cerebral Edema in Mass Lesions
HERNIATION SYNDROMES: INTRACRANIAL SHIFTS IN THE PATHOGENESIS OF COMA
Anatomy of the Intracranial Compartments • Patterns of Brain Shifts that Contribute to Coma • Clinical Findings in Uncal Herniation Syndrome • Clinical Findings in Central Herniation Syndrome • Clinical Findings in Dorsal Midbrain Syndrome • Safety of Lumbar Puncture in Comatose Patients • False Localizing Signs in the Diagnosis of Structural Coma
DESTRUCTIVE LESIONS AS A CAUSE OF COMA
Diffuse, Bilateral Cortical Destruction • Destructive Disease of the Diencephalon • Destructive Lesions of the Brainstem
5. METABOLIC AND DIFFUSE ENCEPHALOPATHIES: DISRUPTION OF THE INTERNAL MILIEU
PART 1: DISTINGUISHING METABOLIC FROM STRUCTURAL COMA
Key Features of the Neurological Examination in Metabolic Encephalopathies
PART 2: THE INTERNAL MILIEU: AN OVERVIEW OF CEREBRAL METABOLISM AND THE ENVIRONMENT NECESSARY TO MAINTAIN NORMAL NEURONAL FUNCTION
Cerebral Blood Flow, Oxygen, and Glucose Utilization • Ionic Environment in the Brain and Cortical Spreading Depolarization • Synaptic Environment in the Brain and Seizures
PART 3: DISORDERS OF THE INTERNAL MILIEU: LACK OF SUBSTRATE
Sedative/Hypnotic Drugs and Anesthetics (GABAA Receptor Enhancers) • Intoxication with “Endogenously Produced” Benzodiazepines • Ethanol Intoxication and Ethanol Withdrawal • Ketamine, Phencyclidine (NMDA Receptor Antagonist Drugs) • Antidepressants • Neuroleptics
• Opiates • Intoxication with Antipyretic/Analgesic Medications • Intoxication with Drugs of Abuse • Intoxication with Drugs Causing Metabolic Acidosis
6. PSYCHOGENIC UNRESPONSIVENESS
CONVERSION REACTIONS
CATATONIA
PSYCHOGENIC SEIZURES
CEREBELLAR COGNITIVE AFFECTIVE SYNDROME
“AMYTAL INTERVIEW”
7. INITIAL MANAGEMENT OF PATIENTS WITH STUPOR AND COMA
A CLINICAL REGIMEN FOR DIAGNOSIS AND MANAGEMENT
ALGORITHM AND PRINCIPLES OF EMERGENCY MANAGEMENT
Support Vital Signs: Airway, Breathing, and Circulation • Ensure Oxygenation, Airway, and Ventilation • Maintain the Circulation
HISTORY, EXAM, AND BASIC DIAGNOSTICS
Emergency Neurological Examination of the Comatose or Stuporous Patient • Verbal Responses • Respiratory Pattern • Eye Opening • Pupillary Reactions • Eye Position at Rest • Spontaneous Eye Movement • Oculocephalic Responses • Caloric Vestibulo-Ocular Responses • Corneal Responses • Motor Responses • Tendon Reflexes • Skeletal Muscle Tone
EMERGENT TREATMENT FOR ALL PATIENTS WITH STUPOR OR COMA
Hypoglycemia or Hyperglycemia • Thiamine • Antidotes • Infections • Intracranial Pressure • Seizures • Hypo- and Hyperthermia • Acid–Base Abnormalities • Control Agitation • Protect the Eyes
MORE DEFINITIVE DIAGNOSIS AND TREATMENT OF SPECIFIC ETIOLOGIES OF STUPOR AND COMA
8. MANAGEMENT OF FREQUENTLY ENCOUNTERED CAUSES OF UNCONSCIOUSNESS
STRUCTURAL LESIONS: SUPRATENTORIAL OR INFRATENTORIAL COMPRESSIVE/DESTRUCTIVE ETIOLOGIES
NONSTRUCTURAL LESIONS: METABOLIC, DIFFUSE, OR MULTIFOCAL COMA
Central Nervous System Infections • Acute Disseminated Encephalomyelitis • Hypoxic Brain Injury/Cardiac Arrest • Metabolic Coma
GENERAL MANAGEMENT CONSIDERATIONS APPLYING TO ALL OR MOST BRAININJURED PATIENTS
GOALS OF CARE
A FINAL WORD
9. PROGNOSIS IN COMA AND RELATED DISORDERS OF CONSCIOUSNESS AND MECHANISMS UNDERLYING OUTCOMES
INTRODUCTION
PROGNOSIS IN COMA
PROGNOSIS BY DISEASE STATE
Traumatic Brain Injury • Nontraumatic Coma • Vascular Disease • Central Nervous System Infection • Autoimmune Encephalitis and Encephalomyelitis • Hepatic Coma • Prolonged Hypoglycemia • Depressant Drug Poisoning
PROGNOSIS IN DISORDERS OF CONSCIOUSNESS
Vegetative State • Minimally Conscious State • Locked-In State
MECHANISMS UNDERLYING OUTCOMES OF COMA: INVESTIGATIONAL STUDIES OF DISORDERS OF CONSCIOUSNESS
Functional Imaging of the Vegetative State • Atypical Behavioral Features in PVS • Isolated Neuroimaging of Cortical Responses in PVS Patients • Functional Neuroimaging of Minimally Conscious State • Conceptualizing Patterns of Restoration of Cerebral Network Activity in Disorders of Consciousness Following Coma • Functional Imaging of Recovery of Consciousness: Linked Roles of the Anterior Forebrain Mesocircuit and Default Mode Network/Posterior Medial Complex • Cognitive Motor Dissociation
ASSESSMENTS OF PATIENTS WITH CHRONIC DISORDERS OF CONSCIOUSNESS: AN EMPIRICAL GUIDE TO TIME-LIMITED PHARMACOLOGIC TRIALS
10. BRAIN DEATH
DETERMINATION OF BRAIN DEATH
CLINICAL SIGNS OF BRAIN DEATH
Brainstem Function • Confirmatory Laboratory Tests and Diagnosis • Diagnosis of Brain Death in Profound Anesthesia or Coma of Undetermined Etiology • Pitfalls in the Diagnosis of Brain Death • Brain Death Versus Prolonged Coma • Management of the Brain Dead Patient
11.
DISORDERS OF CONSCIOUSNESS IN CLINICAL PRACTICE:
ETHICAL, LEGAL AND POLICY
CONSIDERATIONS
Joseph J. Fins
PROFESSIONAL OBLIGATIONS AND CLINICAL DISCERNMENT
AN EMERGING NOSOLOGY AND ETHIC OF CARE
BRAIN STATES
Coma • Brain Death • Vegetative State • Unresponsive Wakefulness Syndrome • The Minimally Conscious State
NEUROETHICS OF COVERT CONSCIOUSNESS
Normative Significance of Covert Consciousness • Ancillary Care Obligations • Translating Research to Practice
CAPACITY, COMPETENCE, AND SURROGATE DECISION-MAKING
Intensive Care • Discharge Planning • Rehabilitation and Long-Term Care
NEUROPALLIATIVE CARE
Pain and Suffering • Withholding and Withdrawing Life-Sustaining Therapy • Family Burden and Bereavement
RIGHTS COME TO MIND
Index
PREFACE TO THE FIFTH EDITION
The first three editions of The Diagnosis of Stupor and Coma were prepared by Fred Plum and Jerry Posner, based on their experiences in diagnosis of patients with disorders of consciousness, first at King County Hospital in Seattle, and then at New York Hospital. During those three editions, medicine in general and neurology in particular underwent a revolution with the introduction of computerized tomography. Nevertheless, the principles of applying the clinical neurological exam to the comatose patient for the purpose of rapid diagnosis and treatment did not change. The fourth edition of this book was published in 2007, and it incorporated the many advances made in the previous two decades, including the use of magnetic resonance imaging in the diagnosis of comatose patients. The need for the neurological examination to determine the best course for workup of the comatose patient, however, remained paramount. Drs. Clifford Saper and Nicholas Schiff, two former residents of Drs. Plum and Posner, were added to update the basic science of consciousness and the outcomes of patients with disorders of consciousness. Although Fred Plum could not participate in the final text of the fourth edition, we tried to the greatest extent possible to preserve his approach and his voice in the text. Out of respect for the original authors and to recognize their indelible contribution to the concept and structure of the text, Drs. Plum and Posner’s names were formally added to the title of the book: Plum and Posner’s Diagnosis and Treatment of Stupor and Coma. With this fifth edition, both the book and the field have evolved further. Dr. Plum has passed on, and Dr. Posner participated in overseeing but not writing the revision. We have added Dr. Jan Claassen, Director of the Neurological Intensive Care Unit at Columbia University, as an additional author. His expertise has greatly expanded our section on the treatment of comatose patients so that we have again changed the title to reflect that refocusing of the book to Plum and Posner’s Diagnosis and Treatment of
Stupor and Coma. We once again had the honor to have a final chapter contributed by Dr. Joseph J. Fins on the ethical, legal and policy considerations of managing patients with disorders of consciousness. This chapter has been greatly updated and expanded from the portion of a chapter that he prepared for the fourth edition.
The primary text of Chapters 1–4 and 6 were prepared by Dr. Saper, that of Chapter 5 by Drs. Saper and Claassen, Chapters 7 and 8 by Dr. Claassen, Chapters 9 and 10 by Dr. Schiff, and Chapter 11 by Dr. Fins. However, all chapters were read and edited by Drs. Saper, Claassen, and Schiff who now bear the responsibility for the text and for any errors it may contain.
We owe a great debt of gratitude to Dr. Eva Feldman, who has taken over editing the Contemporary Neurology Series and who worked with the authors to keep us on time. However, it was the tireless work of Craig Panner and Emily Samulski at Oxford University Press who drew together the disparate schedules of the authors, herded us through the preparation of the chapters, and now provide the final oversight of the editing and production of the book.
Finally, we would like to thank our families for putting up with our extended reveries and writing time in order to finish this volume. A work like this always takes more time than anyone can expect, but it once again has been a labor of love. We have learned a great deal from preparing it, and we hope you will find it equally informative and thought-provoking as a companion to the management of patients with disorders of consciousness.
Jerome B. Posner, MD
Jan Claassen, MD, PhD
Clifford B. Saper, MD, PhD
Nicholas D. Schiff, MD November 29, 2018
Chapter 1
Pathophysiology of Signs and Symptoms of Coma
ALTERED STATES OF CONSCIOUSNESS
DEFINITIONS
Consciousness
Acutely Altered States of Consciousness
Subacute or Chronic Alterations of Consciousness
APPROACH TO THE DIAGNOSIS OF THE COMATOSE PATIENT
PHYSIOLOGY AND PATHOPHYSIOLOGY OF CONSCIOUSNESS AND COMA
The Ascending Arousal System
Behavioral State Switching
Relationship of Coma to Sleep
The Cerebral Hemispheres and Conscious Behavior
Structural Lesions that Cause Altered Consciousness in Humans
ALTERED STATES OF CONSCIOUSNESS
And men should know that from nothing else but from the brain came joys, delights, laughter and jests, and sorrows, griefs, despondency and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear and know what are foul, and what are fair, what sweet and what unsavory . . .
—The Hippocratic Writings
Impaired consciousness is among the most difficult and dramatic of clinical problems. The ancient Greeks knew that normal consciousness depends on an intact brain and that impaired consciousness signifies brain failure. The brain tolerates only limited physical or metabolic injury, so that impaired consciousness is often a sign of impending irreparable damage to the brain. Stupor and coma imply advanced brain failure just as, for example, uremia means renal failure, and the longer such brain failure lasts, the narrower the margin between recovery and the development of permanent neurologic injury. The limited time for action and the multiplicity of potential causes of
brain failure challenge the physician and frighten both the physician and the family; only the patient escapes anxiety.
Many conditions cause coma. Table 1.1 lists some of the common and often perplexing causes of unconsciousness that the physician may encounter in the emergency department or intensive care unit of a general hospital. The purpose of this monograph is to describe a systematic approach to the diagnosis of the patient with reduced consciousness, stupor, or coma based on anatomic and physiologic principles. Accordingly, this book divides the causes of unconsciousness into two major categories: structural and metabolic. This chapter provides background information on the pathophysiology of impaired consciousness, as well as on the signs and symptoms that accompany it. In Chapter 2, this information is used to define a brief but informative neurologic examination that is necessary to determine if the reduced consciousness has a structural cause (and therefore may require immediate imaging and perhaps surgical treatment) or a metabolic cause (in which case the diagnostic approach can be more lengthy and extensive). Chapters 3 and 4 discuss pathophysiology and specific causes of structural injury to the brain that result in defects of consciousness. Chapter 5 examines the broad range of metabolic causes of unconsciousness and the specific treatments they require. Chapter 6 explores psychiatric causes of unresponsiveness, which must be differentiated from organic causes of stupor and coma. Chapters 7 and 8 provide a systematic discussion of the treatment of both structural and nonstructural coma. Chapter 9 reviews the determination of brain death and the examination necessary for making that diagnosis. Chapter 10 explores the outcomes of coma of different causes, including the prognosis for useful recovery and the states of long-term impairment of consciousness. Chapter 11 reviews some ethical problems encountered in treating unconscious individuals.
a Represents only patients for whom a neurologist was consulted because the initial diagnosis was uncertain and in whom a final diagnosis was established. Thus, obvious diagnoses such as known poisonings, meningitis, and closed head injuries and cases of mixed metabolic encephalopathies in which a specific etiologic diagnosis was never established are underrepresented.
DEFINITIONS
Consciousness
Consciousness is the state of full awareness of the self and one’s relationship to the environment. Clinically, the level of consciousness of a
patient is defined operationally at the bedside by the responses of the patient to the examiner. It is clear from this definition that it is possible for a patient to be conscious yet not responsive to the examiner, for example, if the patient lacks sensory inputs, is paralyzed (see locked-in syndrome, page 6), or for psychologic reasons decides not to respond. Thus, the determination of the state of consciousness can be a technically challenging exercise. In the definitions that follow, we assume that the patient is not unresponsive due to sensory or motor impairment or psychiatric disease.
Consciousness has two major dimensions: content and arousal. The content of consciousness represents the sum of all functions mediated at a cerebral cortical level, including both cognitive and affective responses. These functions are subserved by unique networks of cortical neurons, and it is possible for a lesion that is strategically placed to disrupt one of the networks, causing a fractional loss of consciousness.1 Such patients may have preserved awareness of most stimuli, but, having suffered the loss of a critical population of neurons (e.g., for recognizing language symbol content, differences between colors or faces, or the presence of the left side of space), the patient literally becomes unconscious of that class of stimuli. Patients with these deficits are often characterized as “confused” by inexperienced examiners because they do not respond as expected to behavioral stimuli. More experienced clinicians recognize the focal cognitive deficits and that the alteration of consciousness is confined to one class of stimuli. Occasionally, patients with right parietotemporal lesions may be sufficiently inattentive as to appear to be globally confused, but they are not sleepy and, in fact, are usually agitated.2
Thus, unless the damage to cortical networks is diffuse or very widespread, the level of consciousness is not reduced. For example, patients with advanced Alzheimer’s disease may lose memory and other cognitive functions but remain awake and alert until the damage is so extensive and severe that response to stimuli is reduced as well (see vegetative state, page 7). Hence, a reduced level of consciousness is not due to focal impairments of cognitive function, but rather to a global reduction in the level of behavioral responsiveness. In addition to being caused by widespread cortical impairment, a reduced level of consciousness can result from injury to a specific set of brainstem and diencephalic pathways that regulate the overall level of cortical function and hence consciousness.
Of course, the content and level of consciousness interact. The arousal system receives extensive inputs from medial prefrontal cognitive areas, which can drive arousal even under adverse conditions if the behavioral situation demands it (e.g., a doctor who is taking care of a very sick patient in the emergency department late at night).3,4 Conversely, a very sleepy patient may not be able to participate meaningfully in cognitive testing.
Sleep is a recurrent, physiologic form of reduced consciousness in which the responsiveness of brain systems responsible for cognitive function is globally reduced so that the brain does not respond readily to environmental stimuli. Pathologic alteration of the relationships between the brain systems that are responsible for wakefulness and sleep can impair consciousness. The systems subserving normal sleep and wakefulness are reviewed later in this chapter. A key difference between sleep and coma is that sleep is intrinsically reversible: sufficient stimulation will return the individual to a normal waking state. In contrast, if patients with pathologic alterations of consciousness can be awakened at all, they rapidly fall back into a sleeplike state when stimulation ceases.
Patients who have a sleep-like appearance and remain behaviorally unresponsive to all external stimuli are unconscious clinically. However, continuous sleep-like coma as a result of brain injury rarely lasts more than 2–4 weeks. Like the emergence of spasticity from the initial flaccid state after spinal cord transection (spinal shock), the “forebrain shock” due to damage to the intrinsic arousal systems gives way to reorganization of that circuitry, and there is gradual emergence of wake–sleep cycles over a period of weeks after the injury. But, like spinal spasticity, which supplies tone but not complex functions, those wake–sleep cycles may be useless for performing daily tasks if there is extensive damage also to cognitive networks. Wakefulness in the absence of such content is called a vegetative state or unresponsive wakefulness syndrome (UWS). Recent studies using functional imaging have found that some UWS patients may retain contextually relevant cortical activation yet lack an external response (see Chapter 9). However, similar studies have not been done in acutely comatose patients.
Acutely Altered States of Consciousness
The terms used to describe altered states of consciousness break down into two groups: those that indicate depressed level of consciousness and those
that describe a mixture of drowsiness with hyperexcitability. Within these categories, there are relatively mild states and those with more profound behavioral disruption (see Table 1.2).
Table 1.2 Terms Used to Describe Disorders of Consciousness
Acute
Clouding
Delirium
Obtundation
Stupor
Coma
Locked-in (must be distinguished from coma)
Subacute or chronic
Dementia
Hypersomnia
Abulia
Akinetic mutism
Minimally conscious state
Vegetative or unresponsive wake state
Brain death
Clouding of consciousness, for example, is a term applied to minimally reduced wakefulness or awareness, which may include hyperexcitability and irritability alternating with drowsiness. A key distinction must be made in such patients between those who are confused (i.e., do not respond appropriately to their environment) because of a focal deficit of cognitive function versus those who have more global impairment. The beclouded patient is usually incompletely oriented to time and sometimes to place. Such patients are inattentive and perform poorly on repeating numbers backward (the normal range is at least four or five) and remembering details or even the meaning of stories. Drowsiness is often prominent during the day, but agitation may predominate at night.
The pathophysiology of brain function in such patients has rarely been studied, but there is evidence that the clouding of consciousness is associated with reduced cerebral blood flow and oxygen consumption in a wide range of pathologies, from hepatic encephalopathy to Wernicke’s encephalopathy.5,6 The pathogenesis of clouding of consciousness and delirium is discussed in more detail in Chapter 5.
Delirium, from the Latin “to go out of the furrow,” is a more floridly abnormal mental state characterized by misperception of sensory stimuli and, often, vivid hallucinations. Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)7 as follows: “A. Disturbance of attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment).
B. The disturbance develops over a short period of time (usually hours to a few days), representing an acute change from baseline attention and awareness, and tends to fluctuate in severity during the course of the day. C. An additional disturbance in cognition (e.g., deficit in memory, orientation, language, visuospatial ability, or perception). D. The condition is not better explained by a pre-existing, established, or evolving neurocognitive disorder. E. The condition is a direct physiological consequence of another medical condition.”
Delirious patients are disoriented, first to time, next to place, and then to persons in their environment. Rarely are patients unaware of who they are, although sometimes married women will revert to their maiden name. Patients are often fearful or irritable and may overreact or misinterpret the normal activities of physicians and nurses. Delusions or hallucinations may place the patient completely out of contact with the environment and the examiner. Full-blown delirious states tend to come on rapidly and rarely last more than 4–7 days. However, fragments of misperceptions may persist for several weeks, especially among alcoholics and patients with cerebral involvement from collagen vascular diseases.
Delirium is often seen in hospitalized patients, particularly the elderly. The occurrence of delirium in an elderly patient is both a risk factor for developing dementia and often a turning point, one at which the decline in cognitive function accelerates.8 In recent years, there has been a tendency to equate delirium with acute confusional states, and the most common way of assessing delirium has been the Confusion Assessment Method (CAM).9,10 The CAM and other methods of assessing delirium rely predominantly on testing attention, which is largely a right parietal lobe function. However, neurologists also see many patients with right parietal lobe lesions who are inattentive and confused but not delirious. Delirium also includes an element of sensory misperception that suggests a more widespread degradation of cortical sensory processing. In fact, most delirious patients are suffering from a toxic-metabolic state, such as an anticholinergic or sedative drug, hepatic or renal failure, or a systemic infection (see Chapter 5). One of the few exceptions to this rule is the rare group of patients with focal lesions of the right parieto-occipitotemporal cortex.2,11 Lesions in this area can produce a florid state of multimodal sensory hallucination that transcends the confusional states seen in patients with purely right parietal attentional disorders.
Obtundation, by contrast, denotes a relatively mild state of reduced arousal. From the Latin “to beat against or blunt,” it literally means mental blunting or torpidity. In a medical setting, such patients have a mild to moderate reduction in alertness accompanied by a lesser interest in the environment. Obtunded patients have slower psychologic responses to stimulation. They may have an increased number of hours of sleep and may be drowsy between sleep bouts, but they still are responsive and can maintain a waking state.
Stupor, from the Latin “to be stunned,” is a condition of deep sleep or similar behavioral unresponsiveness from which the subject can be aroused only with vigorous and continuous stimulation. Even when maximally aroused, the level of cognitive function may be impaired. Such patients can be differentiated from those with psychiatric impairment, such as catatonia or severe depression, because they can be aroused by vigorous stimulation to respond to simple stimuli.
Coma, from the Greek “deep sleep or trance,” is a state of unresponsiveness in which the patient lies with eyes closed and cannot be aroused to respond appropriately to stimuli even with vigorous stimulation. The patient may grimace in response to painful stimuli and limbs may demonstrate stereotyped withdrawal responses, but the patient does not make localizing responses or discrete defensive movements. As coma deepens, the responsiveness of the patient, even to painful stimuli, may diminish or disappear. However, it is difficult to equate the lack of motor responses to the depth of the coma because the neural structures that regulate motor responses differ from those that regulate consciousness, and they may be differentially impaired by specific brain disorders.
The locked-in syndrome describes a state in which the patient is deefferented, resulting in paralysis of all four limbs and the lower cranial nerves. This condition has been recognized at least as far back as the nineteenth century, but its distinctive name was applied in the first edition of this monograph (1966), reflecting the implications of this condition for the diagnosis of coma and for the specialized care such patients require. Although not unconscious, locked-in patients are unable to respond to most stimuli. A high level of clinical suspicion is required on the part of the examiner to distinguish a locked-in patient from one who is comatose. The most common cause is a lesion of the base and tegmentum of the midpons that interrupts descending cortical control of motor functions. Such patients
usually retain control of vertical eye movements and eyelid opening, which can be used to verify their responsiveness. They may be taught to respond to the examiner by using eye blinks as a code. Rare patients with subacute motor neuropathy, such as Guillain-Barré syndrome, also may become completely de-efferented, but there is a history of progressive, subacute paralysis. In both instances, electroencephalographic (EEG) examination discloses a reactive posterior alpha rhythm12 (see EEG section, page 87).
It is important to identify locked-in patients so that they may be treated appropriately by the medical and nursing staff. At the bedside, discussion should be with the patient, not, as with an unconscious individual, about the patient. Patients with lower pontine lesions that cause a locked-in state often are awake most of the time, with greatly diminished sleep on physiologic recordings.13 They may suffer greatly if they are treated by hospital staff as if they are nonresponsive. For this reason, and because some patients even with extensive brain injury may retain some cognitive ability on functional MRI (fMRI) scanning (see Chapter 9), many clinicians treat all patients in an unresponsive state as if they could potentially be sentient but unable to respond.
As the preceding definitions imply, each of these conditions includes a fairly wide range of behavioral responsiveness, and there may be some overlap among them. Therefore, it is generally best to describe a patient by indicating what stimuli do or do not result in responses and the kinds of responses that are seen, rather than using less precise terms.
Subacute or Chronic Alterations of Consciousness
Dementia defines an enduring and often progressive decline in mental processes owing to an organic disorder not usually accompanied by a reduction in arousal. Conventionally, the term implies a diffuse or disseminated reduction in cognitive functions rather than the impairment of a single cognitive modality such as language. DSM-5 avoids the term “dementia,” which it considered to be stigmatizing, and instead divides such individuals into minor and major neurocognitive disorders. Both involve chronic and usually progressive decline in cognitive function in one or more domains, with the difference being that the declines in minor neurocognitive disorder do not interfere with independent living and are typically within 1 or 2 standard deviations of normal (a range that neurologists and gerontologists usually call minor cognitive impairment or
MCI), whereas the major neurocognitive disorder does interfere with independent living and typically includes deficits of 2 or more standard deviations below the norm. This definition is difficult to apply to individuals whose function begins several standard deviations above the norm, and who thus may have substantial decline without meeting the definition.
The term “dementia” as applied by neurologists refers to the effects of primary disorders of the cerebral hemispheres, such as degenerative conditions, traumatic injuries, and neoplasms. Occasionally, dementia can be at least partially reversible, such as when it accompanies thyroid or vitamin B12 deficiency or results from a reversible communicating hydrocephalus14; more often, however, the term applies to chronic conditions carrying limited hopes for improvement.
Patients with dementia are usually awake and alert but, as the dementia worsens, may become less responsive and eventually evolve into a vegetative state (see later discussion). Patients with dementia are at significantly increased risk of developing delirium when they become medically ill or develop comorbid brain disease.15
Hypersomnia refers to a state characterized by excessive but normalappearing sleep from which the subject readily, even if briefly, awakens when stimulated. Many patients with either acute or chronic alterations of consciousness sleep excessively. However, when awakened, consciousness is clearly clouded. In the truly hypersomniac patient, sleep appears normal and cognitive functions are normal when patients are awakened. Hypersomnia due to a brain injury typically results from posterior hypothalamic or midbrain dysfunction, as indicated later in this chapter.16,17
Abulia (from the Greek for “lack of will”) is an apathetic state in which the patient responds slowly if at all to verbal stimuli and generally does not initiate conversation or activity. When sufficiently stimulated, however, cognitive functions may be normal. Unlike hypersomnia, the patient usually appears fully awake. Abulia is usually associated with bilateral frontal lobe disease and, when severe, may evolve into akinetic mutism.
Akinetic mutism describes a condition of silent, alert-appearing immobility that characterizes certain subacute or chronic states of altered consciousness in which sleep–wake cycles have returned, but externally obtainable evidence for mental activity remains almost entirely absent and
spontaneous motor activity is lacking. Such patients generally have lesions including the hypothalamus and adjacent basal ganglia.
The term minimally conscious state (MCS) was developed by the Aspen Workgroup, a consortium of neurologists, neurosurgeons, neuropsychologists, and rehabilitation specialists.18 MCS identifies a condition of severely impaired consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated. Like the vegetative state, MCS often exists as a transitional state arising during recovery from coma or worsening of progressive neurologic disease. In some patients, however, it may be an essentially permanent condition. Preserved pockets of cognitive function seen on fMRI scans in some MCS patients have prompted the suggestion to rename MCS “cortically mediated state.”19 However, because virtually all states of consciousness are mediated by the cerebral cortex, we prefer the term MCS for this distinct group of patient. For a detailed discussion of the clinical criteria for the diagnosis of the MCS, see Chapter 9.
The vegetative state (VS; now often called the unresponsive wakefulness syndrome,20 UWS) denotes the recovery of crude cycling of arousal states heralded by the appearance of “eyes-open” periods in an unresponsive patient. Very few surviving patients with severe forebrain damage remain in eyes-closed coma for more than 2–4 weeks. In most patients, vegetative behavior usually replaces coma by that time. Patients in the vegetative state, like comatose patients, show no evidence of awareness of self or their environment. Unlike brain death, in which the cerebral hemispheres and the brainstem both undergo overwhelming functional impairment, patients in vegetative states retain brainstem regulation of cardiopulmonary function and visceral autonomic regulation. Although the original term persistent vegetative state (PVS) was not associated with a specific timeframe, the use of PVS is now commonly reserved for patients remaining in a vegetative state for at least 30 days. The American Neurological Association advises that PVS be applied only to patients in the state for 1 month, although some patients recover from PVS even after that interval.21 On the other hand, most patients who have recovered consciousness after months or years have been in a MCS, not PVS or UWS (see Chapter 9). Other terms in the older literature designating the vegetative state include coma vigil and the apallic state.
