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3rd Edition

HARRISONS
TM

NEUROLOGY
IN CLINICAL
MEDICINE
Derived from Harrisons Principles of Internal Medicine, 18th Edition

Editors
DAN L. LONGO, MD ANTHONY S. FAUCI, MD
Professor of Medicine, Harvard Medical School; Chief, Laboratory of Immunoregulation;
Senior Physician, Brigham and Womens Hospital; Director, National Institute of Allergy and Infectious Diseases,
Deputy Editor, New England Journal of Medicine, National Institutes of Health,
Boston, Massachusetts Bethesda, Maryland

DENNIS L. KASPER, MD STEPHEN L. HAUSER, MD


William Ellery Channing Professor of Medicine, Robert A. Fishman Distinguished Professor and Chairman,
Professor of Microbiology and Molecular Genetics, Department of Neurology,
Harvard Medical School; Director, Channing Laboratory, University of California, San Francisco,
Department of Medicine, Brigham and Womens Hospital, San Francisco, California
Boston, Massachusetts

J. LARRY JAMESON, MD, PhD JOSEPH LOSCALZO, MD, PhD


Robert G. Dunlop Professor of Medicine; Hersey Professor of the Theory and Practice of Medicine,
Dean, University of Pennsylvania School of Medicine; Harvard Medical School; Chairman, Department of Medicine;
Executive Vice-President of the University of Pennsylvania Physician-in-Chief, Brigham and Womens Hospital,
for the Health System, Philadelphia, Pennsylvania Boston, Massachusetts
3rd Edition

HARRISONS
TM

NEUROLOGY
IN CLINICAL
MEDICINE

EDITOR
Stephen L. Hauser, MD
Robert A. Fishman Distinguished
Professor and Chairman, Department of Neurology,
University of California, San Francisco, San Francisco, California

ASSOCIATE EDITOR
S. Andrew Josephson, MD
Associate Professor of Clinical Neurology
C. Castro-Franceschi and G. Mitchell Endowed Neurohospitalist Chair
Vice-Chairman, Parnassus Programs
University of California, San Francisco, San Francisco, California

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CONTENTS

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 13 Gait and Balance Disorders. . . . . . . . . . . . . . . . 110


Lewis Sudarsky
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
14 Video Library of Gait Disorders . . . . . . . . . . . . 116
Gail Kang, Nicholas B. Galianakis, Michael
SECTION I Geschwind
INTRODUCTION TO NEUROLOGY 15 Numbness, Tingling, and Sensory Loss . . . . . . . 117
1 Approach to the Patient with Neurologic Michael J. Aminoff, Arthur K. Asbury
Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 16 Confusion and Delirium . . . . . . . . . . . . . . . . . 125
Daniel H. Lowenstein, Joseph B. Martin, Stephen L. S. Andrew Josephson, Bruce L. Miller
Hauser
17 Coma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
2 The Neurologic Screening Exam . . . . . . . . . . . . 11 Allan H. Ropper
Daniel H. Lowenstein
18 Aphasia, Memory Loss, and Other Focal
3 Video Atlas of the Detailed Neurologic Cerebral Disorders . . . . . . . . . . . . . . . . . . . . . . 142
Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 M.-Marsel Mesulam
Martin A. Samuels
19 Video Atlas: Primary Progressive Aphasia,
4 Neuroimaging in Neurologic Disorders . . . . . . . 13 Memory Loss, and Other Focal Cerebral
William P. Dillon Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Maria Luisa Gorno-Tempini, Jennifer Ogar,
5 Electrodiagnostic Studies of Nervous System
Joel Kramer, Bruce L. Miller, Gil Rabinovici,
Disorders: EEG, Evoked Potentials,
Maria Carmela Tartaglia
and EMG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Michael J. Aminoff 20 Sleep Disorders . . . . . . . . . . . . . . . . . . . . . . . . 158
Charles A. Czeisler, John W. Winkelman, Gary S.
6 Technique of Lumbar Puncture . . . . . . . . . . . . . 35
Richardson
Elizabeth Robbins, Stephen L. Hauser
21 Disorders of Vision . . . . . . . . . . . . . . . . . . . . . 174
Jonathan C. Horton
SECTION II
CLINICAL MANIFESTATIONS OF 22 Video Library of Neuro-Ophthalmology . . . . . 198
NEUROLOGIC DISEASE Shirley H. Wray

7 Pain: Pathophysiology and Management . . . . . . . 40 23 Disorders of Smell and Taste . . . . . . . . . . . . . . 199


James P. Rathmell, Howard L. Fields Richard L. Doty, Steven M. Bromley

8 Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 24 Disorders of Hearing . . . . . . . . . . . . . . . . . . . . 207


Peter J. Goadsby, Neil H. Raskin Anil K. Lalwani

9 Back and Neck Pain . . . . . . . . . . . . . . . . . . . . . 71


SECTION III
John W. Engstrom, Richard A. Deyo
DISEASES OF THE NERVOUS SYSTEM
10 Syncope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
25 Mechanisms of Neurologic Diseases . . . . . . . . . 218
Roy Freeman
Stephen L. Hauser, M. Flint Beal
11 Dizziness and Vertigo . . . . . . . . . . . . . . . . . . . . 98
26 Seizures and Epilepsy . . . . . . . . . . . . . . . . . . . . 231
Mark F. Walker, Robert B. Daroff
Daniel H. Lowenstein
12 Weakness and Paralysis. . . . . . . . . . . . . . . . . . . 103 27 Cerebrovascular Diseases . . . . . . . . . . . . . . . . . 256
Michael J. Aminoff Wade S. Smith, Joey D. English, S. Claiborne Johnston
v
vi Contents

28 Neurologic Critical Care, Including 44 Paraneoplastic Neurologic Syndromes. . . . . . . . 558


Hypoxic-Ischemic Encephalopathy, Josep Dalmau, Myrna R. Rosenfeld
and Subarachnoid Hemorrhage . . . . . . . . . . . . 294
J. Claude Hemphill, III, Wade S. Smith, 45 Peripheral Neuropathy. . . . . . . . . . . . . . . . . . . 566
Daryl R. Gress Anthony A. Amato, Richard J. Barohn

29 Alzheimers Disease and Other Dementias . . . . 310 46 Guillain-Barr Syndrome and Other
William W. Seeley, Bruce L. Miller Immune-Mediated Neuropathies . . . . . . . . . . . 599
Stephen L. Hauser, Anthony A. Amato
30 Parkinsons Disease and Other Extrapyramidal
Movement Disorders . . . . . . . . . . . . . . . . . . . . 333 47 Myasthenia Gravis and Other Diseases of
C. Warren Olanow, Anthony H. V. Schapira the Neuromuscular Junction . . . . . . . . . . . . . . 609
Daniel B. Drachman
31 Ataxic Disorders . . . . . . . . . . . . . . . . . . . . . . . 357
Roger N. Rosenberg 48 Muscular Dystrophies and Other
Muscle Diseases . . . . . . . . . . . . . . . . . . . . . . . . 618
32 Amyotrophic Lateral Sclerosis and Other Motor Anthony A. Amato, Robert H. Brown, Jr.
Neuron Diseases . . . . . . . . . . . . . . . . . . . . . . . 370
Robert H. Brown, Jr. 49 Polymyositis, Dermatomyositis, and Inclusion
Body Myositis . . . . . . . . . . . . . . . . . . . . . . . . . 648
33 Disorders of the Autonomic Nervous System . . . . 380 Marinos C. Dalakas
Phillip A. Low, John W. Engstrom
50 Special Issues in Inpatient Neurologic
34 Trigeminal Neuralgia, Bells Palsy, and Consultation . . . . . . . . . . . . . . . . . . . . . . . . . . 660
Other Cranial Nerve Disorders . . . . . . . . . . . . 392 S. Andrew Josephson, Martin A. Samuels
M. Flint Beal, Stephen L. Hauser
51 Atlas of Neuroimaging . . . . . . . . . . . . . . . . . . . 668
35 Diseases of the Spinal Cord . . . . . . . . . . . . . . . 400 Andre Furtado, William P. Dillon
Stephen L. Hauser, Allan H. Ropper
SECTION IV
36 Concussion and Other Head Injuries . . . . . . . . 415
CHRONIC FATIGUE SYNDROME
Allan H. Ropper
52 Chronic Fatigue Syndrome . . . . . . . . . . . . . . . 704
37 Primary and Metastatic Tumors of the Nervous
Gijs Bleijenberg, Jos W. M. van der Meer
System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Lisa M. DeAngelis, Patrick Y. Wen
SECTION V
38 Neurologic Disorders of the Pituitary and PSYCHIATRIC DISORDERS
Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . 439
Shlomo Melmed, J. Larry Jameson 53 Biology of Psychiatric Disorders . . . . . . . . . . . . 710
Robert O. Messing, John H. Rubenstein, Eric J. Nestler
39 Multiple Sclerosis and Other Demyelinating
Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474 54 Mental Disorders . . . . . . . . . . . . . . . . . . . . . . . 720
Stephen L. Hauser, Douglas S. Goodin Victor I. Reus

40 Meningitis, Encephalitis, Brain Abscess, 55 Neuropsychiatric Illnesses in War Veterans . . . . 742


and Empyema . . . . . . . . . . . . . . . . . . . . . . . . . 493 Charles W. Hoge
Karen L. Roos, Kenneth L. Tyler
41 Chronic and Recurrent Meningitis . . . . . . . . . . 527 SECTION VI
Walter J. Koroshetz, Morton N. Swartz ALCOHOLISM AND DRUG DEPENDENCY
42 HIV Neurology. . . . . . . . . . . . . . . . . . . . . . . . 536 56 Alcohol and Alcoholism . . . . . . . . . . . . . . . . . . 752
Anthony S. Fauci, H. Clifford Lane Marc A. Schuckit
43 Prion Diseases . . . . . . . . . . . . . . . . . . . . . . . . . 549 57 Opioid Drug Abuse and Dependence . . . . . . . . 761
Stanley B. Prusiner, Bruce L. Miller Thomas R. Kosten
Contents vii

58 Cocaine and Other Commonly Review and Self-Assessment . . . . . . . . . . . . . . . 801


Abused Drugs . . . . . . . . . . . . . . . . . . . . . . . . . 767 Charles Wiener,Cynthia D. Brown,
Nancy K. Mello, Jack H. Mendelson Anna R. Hemnes
Appendix
Laboratory Values of Clinical Importance . . . . . . . 775
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851
Alexander Kratz, Michael A. Pesce, Robert C. Basner,
Andrew J. Einstein
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CONTRIBUTORS

Numbers in brackets refer to the chapter(s) written or cowritten by the contributor.


Anthony A. Amato, MD Richard A. Deyo, MD, MPH
Professor of Neurology, Harvard Medical School; Department of Kaiser Permanente Professor of Evidence-Based Family Medi-
Neurology, Brigham and Womens Hospital, Boston, Massachusetts cine, Department of Family Medicine, Department of Medicine,
[45, 46, 48] Department of Public Health and Preventive Medicine, Center for
Research in Occupational and Environmental Toxicology, Oregon
Michael J. Aminoff, MD, DSc
Health and Science University; Clinical Investigator, Kaiser Perman-
Professor of Neurology, University of California, San Francisco
ente Center for Health Research, Portland, Oregon [9]
School of Medicine, San Francisco, California [5, 12, 15]
Richard J. Barohn, MD William P. Dillon, MD
Chairman, Department of Neurology; Gertrude and Dewey Ziegler Elizabeth Guillaumin Professor of Radiology, Neurology and
Professor of Neurology, University of Kansas Medical Center, Neurosurgery; Executive Vice-Chair, Department of Radiology and
Kansas City, Kansas [45] Biomedical Imaging, University of California, San Francisco, San
Francisco, California [4, 51]
Robert C. Basner, MD
Professor of Clinical Medicine, Division of Pulmonary, Allergy, and Richard L. Doty, PhD
Critical Care Medicine, Columbia University College of Physicians Professor, Department of Otorhinolaryngology: Head and Neck
and Surgeons, New York, New York [Appendix] Surgery; Director, Smell and Taste Center, University of
M. Flint Beal, MD Pennsylvania School of Medicine, Philadelphia, Pennsylvania [23]
Chairman of Neurology and Neuroscience; Neurologist-in-Chief,
Daniel B. Drachman, MD
New York Presbyterian Hospital; Weill Cornell Medical College,
Professor of Neurology and Neuroscience, W. W. Smith Charitable
New York, New York [25, 34]
Trust Professor of Neuroimmunology, Department of Neurology,
Gijs Bleijenberg, PhD Johns Hopkins School of Medicine, Baltimore, Maryland [47]
Professor; Head, Expert Centre for Chronic Fatigue, Radboud
University Nijmegen Medical Centre, Nijmegen, Netherlands [52] Andrew J. Einstein, MD, PhD
Assistant Professor of Clinical Medicine, Columbia University
Steven M. Bromley, MD
College of Physicians and Surgeons; Department of Medicine, Divi-
Clinical Assistant Professor of Neurology, Department of Medicine,
sion of Cardiology, Department of Radiology, Columbia University
New Jersey School of Medicine and DentistryRobert Wood
Medical Center and New York-Presbyterian Hospital, New York,
Johnson Medical School, Camden, New Jersey [23]
New York [Appendix]
Cynthia D. Brown, MD
Assistant Professor of Medicine, Division of Pulmonary and Critical Joey D. English, MD
Care Medicine, University of Virginia, Charlottesville, Virginia Assistant Clinical Professor, Department of Neurology, Univeristy of
[Review and Self-Assessment] California, San Francisco, San Francisco, California [27]
Robert H. Brown, Jr., MD, PhD John W. Engstrom, MD
Chairman, Department of Neurology, University of Massachusetts Betty Anker Fife Distinguished Professor of Neurology; Neurology
Medical School, Worchester, Massachusetts [32, 48] Residency Program Director; Clinical Chief of Service, University
Charles A. Czeisler, MD, PhD, FRCP of California, San Francisco, San Francisco, California [9, 33]
Baldino Professor of Sleep Medicine; Director, Division of Sleep
Medicine, Harvard Medical School; Chief, Division of Sleep Medi- Anthony S. Fauci, MD, DSc (Hon), DM&S (Hon), DHL
cine, Department of Medicine, Brigham and Womens Hospital, (Hon), DPS (Hon), DLM (Hon), DMS (Hon)
Boston, Massachusetts [20] Chief, Laboratory of Immunoregulation; Director, National Institute
of Allergy and Infectious Diseases, National Institutes of Health,
Marinos C. Dalakas, MD, FAAN Bethesda, Maryland [42]
Professor of Neurology, Department of Pathophysiology, National
University of Athens Medical School, Athens, Greece [49] Howard L. Fields, MD, PhD
Professor of Neurology, University of California, San Francisco, San
Josep Dalmau, MD, PhD
Francisco, California [7]
ICREA Research Professor, Institute for Biomedical Investiga-
tions, August Pi i Sunyer (IDIBAPS)/Hospital Clinic, Department Roy Freeman, MBCHB
of Neurology, University of Barcelona, Barcelona, Spain; Adjunct Professor of Neurology, Harvard Medical School, Boston,
Professor of Neurology University of Pennsylvania, Philadelphia, Massachusetts [10]
Pennsylvania [44]
Robert B. Daroff, MD Andre Furtado, MD
Professor and Chair Emeritus, Department of Neurology, Case Associate Specialist at the Department of Radiology,
Western Reserve University School of Medicine; University Neuroradiology Section, University of California, San Francisco,
HospitalsCase Medical Center, Cleveland, Ohio [11] San Francisco, California [51]

Lisa M. DeAngelis, MD Nicholas B. Galianakis, MD, MPH


Professor of Neurology, Weill Cornell Medical College; Chair, Assistant Clinical Professor, Surgical Movement Disorders Center,
Department of Neurology, Memorial Sloan-Kettering Cancer Department of Neurology, University of California, San Francisco,
Center, New York, New York [37] San Francisco, California [14]
ix
x Contributors

Michael Geschwind, MD, PhD Thomas R. Kosten, MD


Associate Professor of Neurology, Memory and Aging Center, Baylor College of Medicine; Veterans Administration Medical
University of California, San Francisco, School of Medicine, San Center, Houston, Texas [57]
Francisco, California [14]
Joel Kramer, PsyD
Peter J. Goadsby, MD, PhD, DSc, FRACP FRCP Clinical Professor of Neuropsychology in Neurology; Director of
Professor of Neurology, University of California, San Francisco, Neuropsychology, Memory and Aging Center, University of
California; Honorary Consultant Neurologist, Hospital for Sick California, San Francisco, San Francisco, California [19]
Children, London, United Kingdom [8]
Alexander Kratz, MD, PhD, MPH
Douglas S. Goodin, MD Associate Professor of Pathology and Cell Biology, Columbia
Professor of Neurology, University of California, San Francisco University College of Physicians and Surgeons; Director, Core
School of Medicine, San Francisco, California [39] Laboratory, Columbia University Medical Center, New York, New
Maria Luisa Gorno-Tempini, MD, PhD York [Appendix]
Associate Professor of Neurology, Memory and Aging Center, Uni-
versity of California, San Francisco, San Francisco, California [19] Anil K. Lalwani, MD
Professor, Departments of Otolaryngology, Pediatrics, and Physiol-
Daryl R. Gress, MD, FAAN, FCCM ogy and Neuroscience, New York University School of Medicine,
Associate Professor of Neurology New York, New York [24]
University of Virginia, Charlottesville, Virginia [28]
H. Clifford Lane, MD
Stephen L. Hauser, MD Clinical Director; Director, Division of Clinical Research; Deputy
Robert A. Fishman Distinguished Professor and Chairman, Depart- Director, Clinical Research and Special Projects; Chief, Clinical and
ment of Neurology, University of California, San Francisco, San Molecular Retrovirology Section, Laboratory of Immunoregula-
Francisco, California [1, 6, 25, 34, 35, 39, 46] tion, National Institute of Allergy and Infectious Diseases, National
Anna R. Hemnes, MD Institutes of Health, Bethesda, Maryland [42]
Assistant Professor, Division of Allergy, Pulmonary, and Critical Phillip A. Low, MD
Care Medicine, Vanderbilt University Medical Center, Nashville, Robert D. and Patricia E. Kern Professor of Neurology, Mayo
Tennessee [Review and Self-Assessment] Clinic College of Medicine, Rochester, Minnesota [33]
J. Claude Hemphill, III, MD, MAS
Professor of Clinical Neurology and Neurological Surgery, De- Daniel H. Lowenstein, MD
partment of Neurology, University of California, San Francisco; Dr. Robert B. and Mrs. Ellinor Aird Professor of Neurology; Direc-
Director of Neurocritical Care, San Francisco General Hospital, San tor, Epilepsy Center, University of California, San Francisco, San
Francisco, California [28] Francisco, California [1, 2, 26]

Charles W. Hoge, MD Joseph B. Martin, MD, PhD


Senior Scientist and Staff Psychiatrist, Center for Psychiatry and Edward R. and Anne G. Leer Professor, Department of Neurobi-
Neuroscience, Walter Reed Army Institute of Research and Water ology, Harvard Medical School, Boston, Massachusetts [1]
Reed Army Medical Center, Silver Spring, Maryland [55]
Nancy K. Mello, PhD
Jonathan C. Horton, MD, PhD Professor of Psychology (Neuroscience), Harvard Medical School,
William F. Hoyt Professor of Neuro-ophthalmology, Profes- Boston, Massachusetts; Director, Alcohol and Drug Abuse Research
sor of Ophthalmology, Neurology and Physiology, University Center, McLean Hospital, Belmont, Massachusetts [58]
of California, San Francisco School of Medicine, San Francisco,
California [21] Shlomo Melmed, MD
Senior Vice President and Dean of the Medical Faculty, Cedars-
J. Larry Jameson, MD, PhD
Sinai Medical Center, Los Angeles, California [38]
Robert G. Dunlop Professor of Medicine; Dean, University of
Pennsylvania School of Medicine; Executive Vice President of the Jack H. Mendelson,a MD
University of Pennsylvania for the Health System, Philadelphia, Professor of Psychiatry (Neuroscience), Harvard Medical School,
Pennsylvania [38] Belmont, Massachusetts [58]
S. Claiborne Johnston, MD, PhD
Robert O. Messing, MD
Professor of Neurology and Epidemiology, University of California,
Professor, Department of Neurology; Senior Associate Director,
San Francisco School of Medicine, San Francisco, California [27]
Ernest Gallo Clinic and Research Center, University of California,
S. Andrew Josephson, MD San Francisco, San Francisco, California [53]
Associate Professor, Department of Neurology; Director, Neuro-
hospitalist Program, University of California, San Francisco, San M.-Marsel Mesulam, MD
Francisco, California [16, 50] Professor of Neurology, Psychiatry and Psychology, Cognitive Neu-
rology and Alzheimers Disease Center, Northwestern University
Gail Kang, MD Feinberg School of Medicine, Chicago, Illinois [18]
Assistant Clinical Professor of Neurology, Memory and Aging
Center, University of California, San Francisco, San Francisco, Bruce L. Miller, MD
California [14] AW and Mary Margaret Clausen Distinguished Professor of
Neurology, University of California, San Francisco School of
Walter J. Koroshetz, MD Medicine, San Francisco, California [16, 19, 29, 43]
National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, Maryland [41] a
Deceased
Contributors xi

Eric J. Nestler, MD, PhD Martin A. Samuels, MD, DSc(hon), FAAN, MACP, FRCP
Nash Family Professor and Chair, Department of Neuroscience; Di- Professor of Neurology, Harvard Medical School; Chairman, De-
rector, Friedman Brain Institute, Mount Sinai School of Medicine, partment of Neurology, Brigham and Womens Hospital, Boston,
New York, New York [53] Massachusetts [3, 50]
Jennifer Ogar, MS Anthony H. V. Schapira, DSc, MD, FRCP, FMedSci
Speech Pathologist, Memory and Aging Center, University of University Department of Clinical Neurosciences, University
California, San Francisco, San Francisco, California; Acting Chief of College London; National Hospital for Neurology and Neurosur-
Speech Pathology at the Department of Veterans Affairs, Martinez, gery, Queens Square, London, United Kingdom [30]
California [19]
Marc A. Schuckit, MD
C. Warren Olanow, MD, FRCPC Distinguished Professor of Psychiatry, University of California, San
Department of Neurology and Neuroscience, Mount Sinai School Diego School of Medicine, La Jolla, California [56]
of Medicine, New York, New York [30]
William W. Seeley, MD
Michael A. Pesce, PhD Associate Professor of Neurology, Memory and Aging Center,
Professor Emeritus of Pathology and Cell Biology, Columbia Uni- University of California, San Francisco, San Francisco, California [29]
versity College of Physicians and Surgeons; Columbia University
Medical Center, New York, New York [Appendix] Wade S. Smith, MD, PhD
Professor of Neurology, Daryl R. Gress Endowed Chair of Neu-
Stanley B. Prusiner, MD rocritical Care and Stroke; Director, University of California, San
Director, Institute for Neurodegenerative Diseases; Professor, De- Francisco Neurovascular Service, San Francisco, San Francisco,
partment of Neurology, University of California, San Francisco, San California [27, 28]
Francisco, California [43]
Lewis Sudarsky, MD
Gil Rabinovici, MD
Associate Professor of Neurology, Harvard Medical School; Director
Attending Neurologist, Memory and Aging Center, University of
of Movement Disorders, Brigham and Womens Hospital, Boston,
California, San Francisco, San Francisco, California [19]
Massachusetts [13]
Neil H. Raskin, MD Morton N. Swartz, MD
Department of Neurology, University of California, San Francisco, Professor of Medicine, Harvard Medical School; Chief, Jackson
San Francisco, San Francisco, California [8] Firm Medical Service and Infectious Disease Unit, Massachusetts
James P. Rathmell, MD General Hospital, Boston, Massachusetts [41]
Associate Professor of Anesthesia, Harvard Medical School; Chief, Maria Carmela Tartaglia, MD, FRCPC
Division of Pain Medicine, Massachusetts General Hospital, Boston, Clinical Instructor of Neurology, Memory and Aging Center, Uni-
Massachusetts [7] versity of California, San Francisco, San Francisco, California [19]
Victor I. Reus, MD, DFAPA, FACP Kenneth L. Tyler, MD
Department of Psychiatry, University of California, San Francisco Reuler-Lewin Family Professor and Chair, Department of Neurol-
School of Medicine; Langley Porter Neuropsychiatric Institute, San ogy; Professor of Medicine and Microbiology, University of Colo-
Francisco, San Francisco, California [54] rado School of Medicine, Denver, Colorado; Chief of Neurology,
Gary S. Richardson, MD University of Colorado Hospital, Aurora, Colorado [40]
Senior Research Scientist and Staff Physician, Henry Ford Hospital, Jos W. M. van der Meer, MD, PhD
Detroit, Michigan [20] Professor of Medicine; Head, Department of General Internal Medi-
cine, Radboud University, Nijmegen Medical Centre, Nijmegen,
Elizabeth Robbins, MD
Netherlands [52]
Clinical Professor of Pediatrics, University of California,
San Francisco, San Francisco, California [6] Mark F. Walker, MD
Associate Professor, Department of Neurology, Case Western
Karen L. Roos, MD Reserve University School of Medicine; Daroff-Dell Osso Ocular
John and Nancy Nelson Professor of Neurology and Professor of Motility Laboratory, Louis Stokes Cleveland Department of Veter-
Neurological Surgery, Indiana University School of Medicine, ans Affairs Medical Center, Cleveland, Ohio [11]
Indianapolis, Indiana [40]
Patrick Y. Wen, MD
Allan H. Ropper, MD Professor of Neurology, Harvard Medical School; Dana-Farber Can-
Professor of Neurology, Harvard Medical School; Executive Vice cer Institute, Boston, Massachusetts [37]
Chair of Neurology, Raymond D. Adams Distinguished Clinician,
Brigham and Womens Hospital, Boston, Massachusetts [17, 35, 36] Charles M. Wiener, MD
Dean/CEO Perdana University Graduate School of Medicine,
Roger N. Rosenberg, MD Selangor, Malaysia; Professor of Medicine and Physiology,
Zale Distinguished Chair and Professor of Neurology, Department Johns Hopkins University School of Medicine, Baltimore, Maryland
of Neurology, University of Texas Southwestern Medical Center, [Review and Self-Assessment]
Dallas, Texas [31]
John W. Winkelman, MD, PhD
Myrna R. Rosenfeld, MD, PhD Associate Professor of Psychiatry, Harvard Medical School; Medical
Professor of Neurology and Chief, Division of Neuro-oncology, Director, Sleep Health Centers, Brigham and Womens Hospital,
University of Pennsylvania, Philadelphia, Pennsylvania [44] Boston, Massachusetts [20]
John H. Rubenstein, MD, PhD Shirley H. Wray, MB, ChB, PhD, FRCP
Nina Ireland Distinguished Professor in Child Psychiatry, Center for Professor of Neurology, Harvard Medical School; Department of
Neurobiology and Psychiatry, Department of Psychiatry, University Neurology, Massachusetts General Hospital, Boston, Massachusetts
of California, San Francisco, San Francisco, California [53] [22]
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PREFACE

The rst two editions of Harrisons Neurology in Clinical development of independent neurology services, depart-
Medicine were unqualied successes. Readers responded ments, and training programs at many medical centers,
enthusiastically to the convenient, attractive, expanded, reducing the exposure of trainees in internal medicine to
and updated stand-alone volume, which was based neurologic problems. All of these forces, acting within
upon the neurology and psychiatry sections from Harri- the fast paced environment of modern medical practice,
sons Principles of Internal Medicine. Our original goal was can lead to an overreliance on unfocused neuroimaging
to provide, in an easy-to-use format, full coverage of tests, suboptimal patient care, and unfortunate outcomes.
the most authoritative information available anywhere Because neurologists represent less than 1% of all physi-
of clinically important topics in neurology and psychia- cians, the vast majority of neurologic care must be de-
try, while retaining the focus on pathophysiology and livered by nonspecialists who are often generalists and
therapy that has always been characteristic of Harrisons. usually internists.
This new third edition of Harrisons Neurology in Clinical The old adage that neurologists know everything but
Medicine has been extensively updated to highlight recent do nothing has been rendered obsolete by advances in
advances in the understanding, diagnosis, treatment, and molecular medicine, imaging, bioengineering, and clinical
prevention of neurologic and psychiatric diseases. New research. Examples of new therapies include: thrombolytic
chapters discuss the pathogenesis and treatment of syn- therapy for acute ischemic stroke; endovascular recanaliza-
cope, dizziness and vertigo, smell and taste disorders, Par- tion for cerebrovascular disorders; intensive monitoring of
kinsons disease, tumors of the nervous system, peripheral brain pressure and cerebral blood ow for brain injury;
neuropathy, and neuropsychiatric problems among war effective therapies for immune-mediated neurologic dis-
veterans, among other topics. Extensively updated cover- orders; new designer drugs for migraine; the rst genera-
age of the dementias highlights new ndings from genet- tion of rational therapies for neurodegenerative diseases;
ics, molecular imaging, cell biology, and clinical research neural stimulators for Parkinsons disease; drugs for narco-
that are transforming our understanding of these common lepsy and other sleep disorders; and control of epilepsy by
problems. Neuroimmunology is another dynamic and surgical resection of small seizure foci precisely localized
rapidly changing eld of neurology, and the new edition by functional imaging and electrophysiology. The pipeline
of Harrisons provides extensive coverage of progress in continues to grow, stimulated by a quickening tempo of
this area, including a practical guide to navigating the large discoveries generating opportunities for rational design of
number of treatment options now available for multiple new diagnostics, interventions, and drugs.
sclerosis. Another new chapter reviews advances in deci- The founding editors of Harrisons Principles of Inter-
phering the pathogenesis of common psychiatric disorders nal Medicine acknowledged the importance of neurology
and discusses challenges to the development of more ef- but were uncertain as to its proper role in a textbook of
fective treatments. Many illustrative neuroimaging gures internal medicine. An initial plan to exclude neurology
appear throughout the section, and an updated and ex- from the rst edition (1950) was reversed at the eleventh
panded atlas of neuroimaging ndings is also included. We hour, and a neurology section was hastily prepared by
are extremely pleased that readers of the new edition of Houston Merritt. By the second edition, the section was
Harrisons will for the rst time be able to access a remark- considerably enlarged by Raymond D. Adams, whose
able series of high-denition video presentations including inuence on the textbook was profound. The third
wonderful guides to screening and detailed neurological neurology editor, Joseph B. Martin, brilliantly led the
examinations, as well as video libraries illustrating gait dis- book during the 1980s and 1990s as neurology was trans-
orders, focal cerebral disorders, and neuro-ophthalmologic formed from a largely descriptive discipline to one of the
disturbances. most dynamic and rapidly evolving areas of medicine.
For many physicians, neurologic diseases represent With these changes, the growth of neurology coverage
particularly challenging problems. Acquisition of the req- in Harrisons became so pronounced that Harrison sug-
uisite clinical skills is often viewed as time-consuming, gested the book be retitled, The Details of Neurology and
difcult to master, and requiring a working knowledge Some Principles of Internal Medicine. His humorous com-
of obscure anatomic facts and laundry lists of diagnostic ment, now legendary, underscores the depth of coverage
possibilities. The patients themselves may be difcult, as of neurologic medicine in Harrisons betting its critical
neurologic disorders often alter an individuals capacity role in the practice of internal medicine.
to recount the history of an illness or to even recognize The Editors are indebted to our authors, a group
that something is wrong. An additional obstacle is the of internationally recognized authorities who have
xiii
xiv Preface

magnicently distilled a daunting body of information the Internet to nd facts, but that he reads Harrisons
into the essential principles required to understand and to learn medicine. Our aim has always been to pro-
manage commonly encountered neurologic problems. vide the reader with an integrated, organic summary
Thanks also to Dr. Elizabeth Robbins who has served for of the science and the practice of medicine rather than
more than 15 years as managing editor of the neurology a mere compendium of chapters, and we are delighted
section of Harrisons; she has overseen the complex logis- and humbled by the continuing and quite remarkable
tics required to produce a multiauthored textbook, and growth in popularity of Harrisons at a time when many
has promoted exceptional standards for clarity, language, classics in medicine seem less relevant than in years
and style. Finally, we wish to acknowledge and express past. We are of course cognizant of the exibility in in-
our great appreciation to our colleagues at McGraw-Hill. formation delivery that todays readers seek, and so we
This new volume was championed by James Shanahan have also made the third edition of Harrisons Neurology
and impeccably managed by Kim Davis. in Clinical Medicine available in a number of eBook for-
We live in an electronic, wireless age. Information mats for all major devices, including the iPad (available
is downloaded rather than pulled from the shelf. Some via the iBookstore).
have questioned the value of traditional books in this It is our sincere hope that you will enjoy using Har-
new era. We believe that as the volume of information, risons Neurology in Clinical Medicine, Third Edition, as an
and the ways to access this information, continues to authoritative source for the most up-to-date information
grow, the need to grasp the essential concepts of medi- in clinical neurology.
cal practice becomes even more challenging. One of
our young colleagues recently remarked that he uses Stephen L. Hauser, MD
NOTICE
Medicine is an ever-changing science. As new research and clinical experi-
ence broaden our knowledge, changes in treatment and drug therapy are re-
quired. The authors and the publisher of this work have checked with sources
believed to be reliable in their efforts to provide information that is complete
and generally in accord with the standards accepted at the time of publication.
However, in view of the possibility of human error or changes in medical sci-
ences, neither the authors nor the publisher nor any other party who has been
involved in the preparation or publication of this work warrants that the in-
formation contained herein is in every respect accurate or complete, and they
disclaim all responsibility for any errors or omissions or for the results obtained
from use of the information contained in this work. Readers are encouraged
to conrm the information contained herein with other sources. For example
and in particular, readers are advised to check the product information sheet
included in the package of each drug they plan to administer to be certain that
the information contained in this work is accurate and that changes have not
been made in the recommended dose or in the contraindications for adminis-
tration. This recommendation is of particular importance in connection with
new or infrequently used drugs.

Review and self-assessment questions and answers were taken from Wiener CM,
Brown CD, Hemnes AR (eds). Harrisons Self-Assessment and Board Review, 18th ed.
New York, McGraw-Hill, 2012, ISBN 978-0-07-177195-5.

The global icons call greater attention to key epidemiologic and clinical differences in the practice of medicine
throughout the world.

The genetic icons identify a clinical issue with an explicit genetic relationship.
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SECTION I

INTRODUCTION TO
NEUROLOGY
CHAPTER 1

APPROACH TO THE PATIENT WITH


NEUROLOGIC DISEASE

Daniel H. Lowenstein Joseph B. Martin Stephen L. Hauser

Neurologic diseases are common and costly. According


to recent estimates by the World Health Organization,
THE NEUROLOGIC METHOD
neurologic disorders affect over 1 billion people world- LOCATE THE LESION(S)
wide (Table 1-1), constitute 6.3% of the global burden
of disease, and cause 12% of global deaths. Most patients The rst priority is to identify the region of the nervous
with neurologic symptoms seek care from internists system that is likely to be responsible for the symptoms.
and other generalists rather than from neurologists. Can the disorder be mapped to one specic location,
Because therapies now exist for many neurologic disor- is it multifocal, or is a diffuse process present? Are the
ders, a skillful approach to diagnosis is essential. Errors symptoms restricted to the nervous system, or do they
commonly result from an overreliance on costly neuro- arise in the context of a systemic illness? Is the prob-
imaging procedures and laboratory tests, which, while lem in the central nervous system (CNS), the peripheral
useful, do not substitute for an adequate history and nervous system (PNS), or both? If in the CNS, is the
examination. The proper approach to the patient with cerebral cortex, basal ganglia, brainstem, cerebellum, or
a neurologic illness begins with the patient and focuses spinal cord responsible? Are the pain-sensitive meninges
the clinical problem rst in anatomic and then in patho- involved? If in the PNS, could the disorder be located
physiologic terms; only then should a specic diagnosis in peripheral nerves and, if so, are motor or sensory
be entertained. This method ensures that technology is nerves primarily affected, or is a lesion in the neuromus-
judiciously applied, a correct diagnosis is established in cular junction or muscle more likely?
an efcient manner, and treatment is promptly initiated. The rst clues to dening the anatomic area of
involvement appear in the history, and the examination
is then directed to conrm or rule out these impressions
TABLE 1-1 and to clarify uncertainties. A more detailed examina-
PREVALENCE OF NEUROLOGIC AND PSYCHIATRIC tion of a particular region of the CNS or PNS is often
DISEASES WORLDWIDE indicated. For example, the examination of a patient
who presents with a history of ascending paresthesias and
DISORDER PATIENTS, MILLIONS
weakness should be directed toward deciding, among
Nutritional disorders and 352 other things, if the location of the lesion is in the spi-
neuropathies nal cord or peripheral nerves. Focal back pain, a spinal
Migraine 326 cord sensory level, and incontinence suggest a spinal
Trauma 170 cord origin, whereas a stocking-glove pattern of sensory
Cerebrovascular diseases 61
loss suggests peripheral nerve disease; areexia usually
indicates peripheral neuropathy but may also be present
Epilepsy 50
with spinal shock in acute spinal cord disorders.
Dementia 24 Deciding where the lesion is accomplishes the task
Neurologic infections 18 of limiting the possible etiologies to a manageable, nite
number. In addition, this strategy safeguards against
Source: World Health Organization estimates, 20022005. making serious errors. Symptoms of recurrent vertigo,

2
diplopia, and nystagmus should not trigger multiple features? Does the patient have difculty with brushing 3
sclerosis as an answer (etiology) but brainstem or hair or reaching upward (proximal) or buttoning but-
pons (location); then a diagnosis of brainstem arte- tons or opening a twist-top bottle (distal)? Negative

CHAPTER 1
riovenous malformation will not be missed for lack of associations may also be crucial. A patient with a right
consideration. Similarly, the combination of optic neu- hemiparesis without a language decit likely has a lesion
ritis and spastic ataxic paraparesis should initially suggest (internal capsule, brainstem, or spinal cord) different
optic nerve and spinal cord disease; multiple sclerosis from that of a patient with a right hemiparesis and apha-
(MS), CNS syphilis, and vitamin B12 deciency are treat- sia (left hemisphere). Other pertinent features of the
able disorders that can produce this syndrome. Once the history include the following:

Approach to the Patient with Neurologic Disease


question, Where is the lesion? is answered, then the
question, What is the lesion? can be addressed. 1. Temporal course of the illness. It is important to
determine the precise time of appearance and rate
of progression of the symptoms experienced by the
DEFINE THE PATHOPHYSIOLOGY patient. The rapid onset of a neurologic complaint,
Clues to the pathophysiology of the disease process occurring within seconds or minutes, usually indi-
may also be present in the history. Primary neuronal cates a vascular event, a seizure, or migraine. The
(gray matter) disorders may present as early cogni- onset of sensory symptoms located in one extremity
tive disturbances, movement disorders, or seizures, that spread over a few seconds to adjacent portions
whereas white matter involvement produces predomi- of that extremity and then to the other regions of
nantly long tract disorders of motor, sensory, visual, the body suggests a seizure. A more gradual onset
and cerebellar pathways. Progressive and symmetric and less well-localized symptoms point to the
symptoms often have a metabolic or degenerative ori- possibility of a transient ischemic attack (TIA). A
gin; in such cases lesions are usually not sharply cir- similar but slower temporal march of symptoms
cumscribed. Thus, a patient with paraparesis and a clear accompanied by headache, nausea, or visual dis-
spinal cord sensory level is unlikely to have vitamin turbance suggests migraine. The presence of posi-
B12 deciency as the explanation. A Lhermitte symptom tive sensory symptoms (e.g., tingling or sensations
(electric shocklike sensations evoked by neck exion) that are difcult to describe) or involuntary motor
is due to ectopic impulse generation in white matter movements suggests a seizure; in contrast, tran-
pathways and occurs with demyelination in the cervi- sient loss of function (negative symptoms) suggests
cal spinal cord; among many possible causes, this symp- a TIA. A stuttering onset where symptoms appear,
tom may indicate MS in a young adult or compressive stabilize, and then progress over hours or days also
cervical spondylosis in an older person. Symptoms that suggests cerebrovascular disease; an additional history
worsen after exposure to heat or exercise may indicate of transient remission or regression indicates that the
conduction block in demyelinated axons, as occurs in process is more likely due to ischemia rather than
MS. A patient with recurrent episodes of diplopia and hemorrhage. A gradual evolution of symptoms over
dysarthria associated with exercise or fatigue may have hours or days suggests a toxic, metabolic, infectious,
a disorder of neuromuscular transmission such as myas- or inammatory process. Progressing symptoms
thenia gravis. Slowly advancing visual scotoma with associated with the systemic manifestations of fever,
luminous edges, termed fortication spectra, indicates stiff neck, and altered level of consciousness imply
spreading cortical depression, typically with migraine. an infectious process. Relapsing and remitting symp-
toms involving different levels of the nervous system
suggest MS or other inammatory processes. Slowly
THE NEUROLOGIC HISTORY progressive symptoms without remissions are char-
acteristic of neurodegenerative disorders, chronic
Attention to the description of the symptoms experienced infections, gradual intoxications, and neoplasms.
by the patient and substantiated by family members 2. Patients descriptions of the complaint. The same words
and others often permits an accurate localization and often mean different things to different patients.
determination of the probable cause of the complaints, Dizziness may imply impending syncope, a
even before the neurologic examination is performed. sense of disequilibrium, or true spinning vertigo.
The history also helps to bring a focus to the neuro- Numbness may mean a complete loss of feeling, a
logic examination that follows. Each complaint should positive sensation such as tingling, or even weakness.
be pursued as far as possible to elucidate the location of Blurred vision may be used to describe unilat-
the lesion, the likely underlying pathophysiology, and eral visual loss, as in transient monocular blindness,
potential etiologies. For example, a patient complains or diplopia. The interpretation of the true meaning
of weakness of the right arm. What are the associated of the words used by patients to describe symptoms
4 obviously becomes even more complex when there patients with disorders of neuromuscular transmission,
are differences in primary languages and cultures. such as myasthenia gravis, and may cause dizziness
3. Corroboration of the history by others. It is almost always secondary to ototoxicity. Vincristine and other anti-
SECTION I

helpful to obtain additional information from family, neoplastic drugs can cause peripheral neuropathy, and
friends, or other observers to corroborate or expand immunosuppressive agents such as cyclosporine can
the patients description. Memory loss, aphasia, loss produce encephalopathy. Excessive vitamin inges-
of insight, intoxication, and other factors may impair tion can lead to disease; for example vitamin A and
the patients capacity to communicate normally with pseudotumor cerebri, or pyridoxine and peripheral
the examiner or prevent openness about factors that neuropathy. Many patients are unaware that over-
Introduction to Neurology

have contributed to the illness. Episodes of loss of the-counter sleeping pills, cold preparations, and
consciousness necessitate that details be sought from diet pills are actually drugs. Alcohol, the most prev-
observers to ascertain precisely what has happened alent neurotoxin, is often not recognized as such by
during the event. patients, and other drugs of abuse such as cocaine
4. Family history. Many neurologic disorders have an and heroin can cause a wide range of neurologic
underlying genetic component. The presence of a abnormalities. A history of environmental or industrial
Mendelian disorder, such as Huntingtons disease or exposure to neurotoxins may provide an essential
Charcot-Marie-Tooth neuropathy, is often obvious clue; consultation with the patients coworkers or
if family data are available. More detailed questions employer may be required.
about family history are often necessary in polygenic 7. Formulating an impression of the patient. Use the
disorders such as MS, migraine, and many types of opportunity while taking the history to form an
epilepsy. It is important to elicit family history about impression of the patient. Is the information forth-
all illnesses, in addition to neurologic and psychiatric coming, or does it take a circuitous course? Is there
disorders. A familial propensity to hypertension or evidence of anxiety, depression, or hypochondriasis?
heart disease is relevant in a patient who presents Are there any clues to defects in language, memory,
with a stroke. There are numerous inherited neu- insight, or inappropriate behavior? The neurologic
rologic diseases that are associated with multisystem assessment begins as soon as the patient comes into
manifestations that may provide clues to the correct the room and the rst introduction is made.
diagnosis (e.g., neurobromatosis, Wilsons disease,
neuro-ophthalmic syndromes).
5. Medical illnesses. Many neurologic diseases occur in
the context of systemic disorders. Diabetes mellitus, THE NEUROLOGIC EXAMINATION
hypertension, and abnormalities of blood lipids pre-
dispose to cerebrovascular disease. A solitary mass The neurologic examination is challenging and complex;
lesion in the brain may be an abscess in a patient it has many components and includes a number of skills
with valvular heart disease, a primary hemorrhage in that can be mastered only through repeated use of the
a patient with a coagulopathy, a lymphoma or toxo- same techniques on a large number of individuals with
plasmosis in a patient with AIDS, or a metastasis in a and without neurologic disease. Mastery of the com-
patient with underlying cancer. Patients with malig- plete neurologic examination is usually important only
nancy may also present with a neurologic paraneo- for physicians in neurology and associated specialties.
plastic syndrome (Chap. 44) or complications from However, knowledge of the basics of the examina-
chemotherapy or radiotherapy. Marfans syndrome tion, especially those components that are effective in
and related collagen disorders predispose to dissection screening for neurologic dysfunction, is essential for all
of the cranial arteries and aneurysmal subarachnoid clinicians, especially generalists.
hemorrhage; the latter may also occur with polycystic There is no single, universally accepted sequence of
kidney disease. Various neurologic disorders occur the examination that must be followed, but most clini-
with dysthyroid states or other endocrinopathies. It is cians begin with assessment of mental status followed by
especially important to look for the presence of sys- the cranial nerves, motor system, sensory system, coor-
temic diseases in patients with peripheral neuropathy. dination, and gait. Whether the examination is basic or
Most patients with coma in a hospital setting have a comprehensive, it is essential that it be performed in
metabolic, toxic, or infectious cause. an orderly and systematic fashion to avoid errors and
6. Drug use and abuse and toxin exposure. It is essential to serious omissions. Thus, the best way to learn and gain
inquire about the history of drug use, both prescribed expertise in the examination is to choose ones own
and illicit. Sedatives, antidepressants, and other psy- approach and practice it frequently and do it in the
choactive medications are frequently associated with same exact sequence each time.
acute confusional states in the elderly. Aminoglycoside The detailed description of the neurologic examina-
antibiotics may exacerbate symptoms of weakness in tion that follows describes the more commonly used
parts of the examination, with a particular emphasis on values for dening normal performance, the test is 5
the components that are considered most helpful for 85% sensitive and 85% specic for making the diag-
the assessment of common neurologic problems. Each nosis of dementia that is moderate or severe, espe-

CHAPTER 1
section also includes a brief description of the minimal cially in educated patients. When there is sufcient
examination necessary for adequate screening for abnor- time available, the MMSE is one of the best meth-
malities in a patient who has no symptoms suggesting ods for documenting the current mental status of the
neurologic dysfunction. A screening examination done patient, and this is especially useful as a baseline assess-
in this way can be completed in 35 min. ment to which future scores of the MMSE can be
Several additional points about the examination are compared.

Approach to the Patient with Neurologic Disease


worth noting. First, in recording observations, it is Individual elements of the mental status examina-
important to describe what is found rather than to apply tion can be subdivided into level of consciousness,
a poorly dened medical term (e.g., patient groans to orientation, speech and language, memory, fund of
sternal rub rather than obtunded). Second, subtle information, insight and judgment, abstract thought,
CNS abnormalities are best detected by carefully com- and calculations.
paring a patients performance on tasks that require Level of consciousness is the patients relative state of
simultaneous activation of both cerebral hemispheres awareness of the self and the environment, and ranges
(e.g., eliciting a pronator drift of an outstretched arm from fully awake to comatose. When the patient is
with the eyes closed; extinction on one side of bilater- not fully awake, the examiner should describe the
ally applied light touch, also with eyes closed; or decreased responses to the minimum stimulus necessary to elicit
arm swing or a slight asymmetry when walking). Third, if a reaction, ranging from verbal commands to a brief,
the patients complaint is brought on by some activity, painful stimulus such as a squeeze of the trapezius
reproduce the activity in the ofce. If the complaint is muscle. Responses that are directed toward the stimu-
of dizziness when the head is turned in one direction, lus and signify some degree of intact cerebral function
have the patient do this and also look for associated (e.g., opening the eyes and looking at the examiner
signs on examination (e.g., nystagmus or dysmetria). If or reaching to push away a painful stimulus) must be
pain occurs after walking two blocks, have the patient distinguished from reex responses of a spinal origin
leave the ofce and walk this distance and immediately (e.g., triple exion responseexion at the ankle,
return, and repeat the relevant parts of the examination. knee, and hip in response to a painful stimulus to
Finally, the use of tests that are individually tailored the foot).
to the patients problem can be of value in assessing Orientation is tested by asking the person to state his
changes over time. Tests of walking a 7.5-m (25-ft) or her name, location, and time (day of the week and
distance (normal, 56 s; note assistance, if any), repeti- date); time is usually the rst to be affected in a variety
tive nger or toe tapping (normal, 2025 taps in 5 s), or of conditions.
handwriting are examples. Speech is assessed by observing articulation, rate,
rhythm, and prosody (i.e., the changes in pitch and
accentuation of syllable and words).
MENTAL STATUS EXAMINATION Language is assessed by observing the content of
the patients verbal and written output, response to
The bare minimum: During the interview, look for
spoken commands, and ability to read. A typical test-
difculties with communication and determine whether the
ing sequence is to ask the patient to name successively
patient has recall and insight into recent and past events.
more detailed components of clothing, a watch, or a
The mental status examination is underway as soon pen; repeat the phrase No ifs, ands, or buts; follow a
as the physician begins observing and talking with the three-step, verbal command; write a sentence; and read
patient. If the history raises any concern for abnormali- and respond to a written command.
ties of higher cortical function or if cognitive problems Memory should be analyzed according to three main
are observed during the interview, then detailed testing time scales: (1) immediate memory is assessed by say-
of the mental status is indicated. The patients ability to ing a list of three items and having the patient repeat
understand the language used for the examination, cul- the list immediately, (2) short-term memory is tested by
tural background, educational experience, sensory or asking the patient to recall the same three items 5 and
motor problems, or comorbid conditions need to be 15 min later, and (3) long-term memory is evaluated
factored into the applicability of the tests and interpreta- by determining how well the patient is able to provide
tion of results. a coherent chronologic history of his or her illness or
The Folstein mini-mental status examination (MMSE) personal events.
(Table 29-5) is a standardized screening examination of Fund of information is assessed by asking questions
cognitive function that is extremely easy to adminis- about major historic or current events, with special
ter and takes <10 min to complete. Using age-adjusted attention to educational level and life experiences.
6 Abnormalities of insight and judgment are usually sufcient for a normal response. Focal perimetry and
detected during the patient interview; a more detailed tangent screen examinations should be used to map out
assessment can be elicited by asking the patient to visual eld defects fully or to search for subtle abnor-
SECTION I

describe how he or she would respond to situations malities. Optic fundi should be examined with an oph-
having a variety of potential outcomes (e.g., What thalmoscope, and the color, size, and degree of swelling
would you do if you found a wallet on the sidewalk?). or elevation of the optic disc noted, as well as the color
Abstract thought can be tested by asking the patient and texture of the retina. The retinal vessels should be
to describe similarities between various objects or con- checked for size, regularity, arterial-venous nicking at
cepts (e.g., apple and orange, desk and chair, poetry crossing points, hemorrhage, exudates, etc.
Introduction to Neurology

and sculpture) or to list items having the same attributes


(e.g., a list of four-legged animals). CN III, IV, VI (oculomotor, trochlear, abducens)
Calculation ability is assessed by having the patient
carry out a computation that is appropriate to the Describe the size and shape of pupils and reaction to
patients age and education (e.g., serial subtraction of light and accommodation (i.e., as the eyes converge
7 from 100 or 3 from 20; or word problems involving while following your nger as it moves toward the
simple arithmetic). bridge of the nose). To check extraocular movements,
ask the patient to keep his or her head still while track-
ing the movement of the tip of your nger. Move
CRANIAL NERVE EXAMINATION the target slowly in the horizontal and vertical planes;
observe any paresis, nystagmus, or abnormalities of
The bare minimum: Check the fundi, visual elds, pupil smooth pursuit (saccades, oculomotor ataxia, etc.).
size and reactivity, extraocular movements, and facial If necessary, the relative position of the two eyes, both
movements. in primary and multidirectional gaze, can be assessed
The cranial nerves (CN) are best examined in by comparing the reections of a bright light off both
numerical order, except for grouping together CN III, pupils. However, in practice it is typically more use-
IV, and VI because of their similar function. ful to determine whether the patient describes diplopia
in any direction of gaze; true diplopia should almost
CN I (olfactory) always resolve with one eye closed. Horizontal nystag-
mus is best assessed at 45 and not at extreme lateral
Testing is usually omitted unless there is suspicion for gaze (which is uncomfortable for the patient); the target
inferior frontal lobe disease (e.g., meningioma). With must often be held at the lateral position for at least a
eyes closed, ask the patient to sniff a mild stimulus such few seconds to detect an abnormality.
as toothpaste or coffee and identify the odorant.
CN V (trigeminal)
CN II (optic)
Examine sensation within the three territories of the
Check visual acuity (with eyeglasses or contact lens cor- branches of the trigeminal nerve (ophthalmic, maxillary,
rection) using a Snellen chart or similar tool. Test the and mandibular) on each side of the face. As with other
visual elds by confrontation, i.e., by comparing the parts of the sensory examination, testing of two sensory
patients visual elds to your own. As a screening test, modalities derived from different anatomic pathways
it is usually sufcient to examine the visual elds of (e.g., light touch and temperature) is sufcient for a
both eyes simultaneously; individual eye elds should screening examination. Testing of other modalities, the
be tested if there is any reason to suspect a problem of corneal reex, and the motor component of CN V (jaw
vision by the history or other elements of the examina- clenchmasseter muscle) is indicated when suggested
tion, or if the screening test reveals an abnormality. Face by the history.
the patient at a distance of approximately 0.61.0 m
(23 ft) and place your hands at the periphery of your
CN VII (facial)
visual elds in the plane that is equidistant between you
and the patient. Instruct the patient to look directly at Look for facial asymmetry at rest and with spontaneous
the center of your face and to indicate when and where movements. Test eyebrow elevation, forehead wrin-
he or she sees one of your ngers moving. Beginning kling, eye closure, smiling, and cheek puff. Look in par-
with the two inferior quadrants and then the two supe- ticular for differences in the lower versus upper facial
rior quadrants, move your index nger of the right muscles; weakness of the lower two-thirds of the face
hand, left hand, or both hands simultaneously and with preservation of the upper third suggests an upper
observe whether the patient detects the movements. motor neuron lesion, whereas weakness of an entire
A single small-amplitude movement of the nger is side suggests a lower motor neuron lesion.
CN VIII (vestibulocochlear) or with voluntary movements (intention tremor of cere- 7
bellar disease or familial tremor).
Check the patients ability to hear a nger rub or whis-
pered voice with each ear. Further testing for air versus

CHAPTER 1
mastoid bone conduction (Rinne) and lateralization of a Tone
512-Hz tuning fork placed at the center of the forehead Muscle tone is tested by measuring the resistance to
(Weber) should be done if an abnormality is detected by passive movement of a relaxed limb. Patients often
history or examination. Any suspected problem should have difculty relaxing during this procedure, so it is
be followed up with formal audiometry. For further dis- useful to distract the patient to minimize active move-
cussion of assessing vestibular nerve function in the set- ments. In the upper limbs, tone is assessed by rapid

Approach to the Patient with Neurologic Disease


ting of dizziness, coma, or hearing loss, see Chaps. 11, pronation and supination of the forearm and exion
17, and 24, respectively. and extension at the wrist. In the lower limbs, while
the patient is supine the examiners hands are placed
behind the knees and rapidly raised; with normal tone
CN IX, X (glossopharyngeal, vagus) the ankles drag along the table surface for a variable
Observe the position and symmetry of the palate and distance before rising, whereas increased tone results in
uvula at rest and with phonation (aah). The pha- an immediate lift of the heel off the surface. Decreased
ryngeal (gag) reex is evaluated by stimulating the tone is most commonly due to lower motor neuron or
posterior pharyngeal wall on each side with a sterile, peripheral nerve disorders. Increased tone may be evi-
blunt object (e.g., tongue blade), but the reex is often dent as spasticity (resistance determined by the angle
absent in normal individuals. and velocity of motion; corticospinal tract disease),
rigidity (similar resistance in all angles of motion; extra-
pyramidal disease), or paratonia (uctuating changes
CN XI (spinal accessory) in resistance; frontal lobe pathways or normal dif-
Check shoulder shrug (trapezius muscle) and head rota- culty in relaxing). Cogwheel rigidity, in which passive
tion to each side (sternocleidomastoid) against resistance. motion elicits jerky interruptions in resistance, is seen
in parkinsonism.

CN XII (hypoglossal)
Inspect the tongue for atrophy or fasciculations, position Strength
with protrusion, and strength when extended against Testing for pronator drift is an extremely useful method
the inner surface of the cheeks on each side. for screening upper limb weakness. The patient is asked
to hold both arms fully extended and parallel to the
ground with eyes closed. This position should be main-
MOTOR EXAMINATION tained for 10 s; any exion at the elbow or ngers or
The bare minimum: Look for muscle atrophy and check pronation of the forearm, especially if asymmetric, is a
extremity tone. Assess upper extremity strength by check- sign of potential weakness. Muscle strength is further
ing for pronator drift and strength of wrist or nger exten- assessed by having the patient exert maximal effort for
sors. Tap the biceps, patellar, and Achilles reexes. Test the particular muscle or muscle group being tested. It
for lower extremity strength by having the patient walk is important to isolate the muscles as much as possible,
normally and on heels and toes. i.e., hold the limb so that only the muscles of interest
are active. It is also helpful to palpate accessible muscles
The motor examination includes observations of mus- as they contract. Grading muscle strength and evaluat-
cle appearance, tone, strength, and reexes. Although gait ing the patients effort is an art that takes time and prac-
is in part a test of motor function, it is usually evaluated tice. Muscle strength is traditionally graded using the
separately at the end of the examination. following scale:
0 = no movement
1 = icker or trace of contraction but no associated
Appearance
movement at a joint
Inspect and palpate muscle groups under good light and 2 = movement with gravity eliminated
with the patient in a comfortable and symmetric position. 3 = movement against gravity but not against resistance
Check for muscle fasciculations, tenderness, and atrophy 4 = movement against a mild degree of resistance
or hypertrophy. Involuntary movements may be present at 4 = movement against moderate resistance
rest (e.g., tics, myoclonus, choreoathetosis), during main- 4+ = movement against strong resistance
tained posture (pill-rolling tremor of Parkinsons disease), 5 = full power
8 However, in many cases it is more practical to use coordination. Supercial abdominal reexes are elicited
the following terms: by gently stroking the abdominal surface near the umbi-
licus in a diagonal fashion with a sharp object (e.g., the
Paralysis = no movement
SECTION I

wooden end of a cotton-tipped swab) and observing the


Severe weakness = movement with gravity eliminated
movement of the umbilicus. Normally, the umbilicus
Moderate weakness = movement against gravity but not
will pull toward the stimulated quadrant. With upper
against mild resistance
motor neuron lesions, these reexes are absent. They
Mild weakness = movement against moderate
are most helpful when there is preservation of the upper
resistance
(spinal cord level T9) but not lower (T12) abdomi-
Full strength
Introduction to Neurology

nal reexes, indicating a spinal lesion between T9 and


Noting the pattern of weakness is as important as T12, or when the response is asymmetric. Other use-
assessing the magnitude of weakness. Unilateral or bilat- ful cutaneous reexes include the cremasteric (ipsilateral
eral weakness of the upper limb extensors and lower elevation of the testicle following stroking of the medial
limb exors (pyramidal weakness) suggests a lesion of thigh; mediated by L1 and L2) and anal (contraction of
the pyramidal tract, bilateral proximal weakness suggests the anal sphincter when the perianal skin is scratched;
myopathy, and bilateral distal weakness suggests periph- mediated by S2, S3, S4) reexes. It is particularly
eral neuropathy. important to test for these reexes in any patient with
suspected injury to the spinal cord or lumbosacral roots.
Reexes Primitive reexes
Muscle stretch reexes With disease of the frontal lobe pathways, several
Those that are typically assessed include the biceps (C5, primitive reexes not normally present in the adult
C6), brachioradialis (C5, C6), and triceps (C7, C8) may appear. The suck response is elicited by lightly
reexes in the upper limbs and the patellar or quadri- touching the center of the lips, and the root response
ceps (L3, L4) and Achilles (S1, S2) reexes in the lower the corner of the lips, with a tongue blade; the patient
limbs. The patient should be relaxed and the muscle will move the lips to suck or root in the direction of
positioned midway between full contraction and exten- the stimulus. The grasp reex is elicited by touching
sion. Reexes may be enhanced by asking the patient the palm between the thumb and index nger with the
to voluntarily contract other, distant muscle groups examiners ngers; a positive response is a forced grasp
(Jendrassik maneuver). For example, upper limb reexes of the examiners hand. In many instances stroking the
may be reinforced by voluntary teeth-clenching, and back of the hand will lead to its release. The palmo-
the Achilles reex by hooking the exed ngers of the mental response is contraction of the mentalis muscle
two hands together and attempting to pull them apart. (chin) ipsilateral to a scratch stimulus diagonally applied
For each reex tested, the two sides should be tested to the palm.
sequentially, and it is important to determine the small-
est stimulus required to elicit a reex rather than the Sensory examination
maximum response. Reexes are graded according to
the following scale: The bare minimum: Ask whether the patient can feel light
touch and the temperature of a cool object in each distal
0 = absent 3 = exaggerated extremity. Check double simultaneous stimulation using
1 = present but diminished 4 = clonus light touch on the hands.
2 = normoactive
Evaluating sensation is usually the most unreliable
Cutaneous reexes part of the examination, because it is subjective and is
The plantar reex is elicited by stroking, with a nox- difcult to quantify. In the compliant and discerning
ious stimulus such as a tongue blade, the lateral sur- patient, the sensory examination can be extremely help-
face of the sole of the foot beginning near the heel and ful for the precise localization of a lesion. With patients
moving across the ball of the foot to the great toe. The who are uncooperative or lack an understanding of
normal reex consists of plantar exion of the toes. the tests, it may be useless. The examination should be
With upper motor neuron lesions above the S1 level focused on the suspected lesion. For example, in spinal
of the spinal cord, a paradoxical extension of the toe is cord, spinal root, or peripheral nerve abnormalities, all
observed, associated with fanning and extension of the major sensory modalities should be tested while looking
other toes (termed an extensor plantar response, or Babinski for a pattern consistent with a spinal level and derma-
sign). However, despite its popularity, the reliability tomal or nerve distribution. In patients with lesions at
and validity of the Babinski sign for identifying upper or above the brainstem, screening the primary sensory
motor neuron weakness is limitedit is far more use- modalities in the distal extremities along with tests of
ful to rely on tests of tone, strength, stretch reexes, and cortical sensation is usually sufcient.
The ve primary sensory modalitieslight touch, Rapid alternating movements in the upper limbs are 9
pain, temperature, vibration, and joint positionare tested separately on each side by having the patient make
tested in each limb. Light touch is assessed by stimu- a st, partially extend the index nger, and then tap

CHAPTER 1
lating the skin with single, very gentle touches of the the index nger on the distal thumb as quickly as pos-
examiners nger or a wisp of cotton. Pain is tested sible. In the lower limb, the patient rapidly taps the foot
using a new pin, and temperature is assessed using a against the oor or the examiners hand. Finger-to-nose
metal object (e.g., tuning fork) that has been immersed testing is primarily a test of cerebellar function; the
in cold and warm water. Vibration is tested using a patient is asked to touch his or her index nger repeti-
128-Hz tuning fork applied to the distal phalanx of the tively to the nose and then to the examiners out-

Approach to the Patient with Neurologic Disease


great toe or index nger just below the nail bed. By stretched nger, which moves with each repetition.
placing a nger on the opposite side of the joint being A similar test in the lower extremity is to have the
tested, the examiner compares the patients threshold patient raise the leg and touch the examiners nger with
of vibration perception with his or her own. For joint the great toe. Another cerebellar test in the lower limbs
position testing, the examiner grasps the digit or limb is the heel-knee-shin maneuver; in the supine position
laterally and distal to the joint being assessed; small 1- to the patient is asked to slide the heel of each foot from
2-mm excursions can usually be sensed. The Romberg the knee down the shin of the other leg. For all these
maneuver is primarily a test of proprioception. movements, the accuracy, speed, and rhythm are noted.
The patient is asked to stand with the feet as close
together as necessary to maintain balance while the eyes
are open, and the eyes are then closed. A loss of balance GAIT EXAMINATION
with the eyes closed is an abnormal response. The bare minimum: Observe the patient while walking
Cortical sensation is mediated by the parietal normally, on the heels and toes, and along a straight line.
lobes and represents an integration of the primary
sensory modalities; testing cortical sensation is only Watching the patient walk is the most important part
meaningful when primary sensation is intact. Double of the neurologic examination. Normal gait requires
simultaneous stimulation is especially useful as a that multiple systemsincluding strength, sensation, and
screening test for cortical function; with the patients coordinationfunction in a highly integrated fashion.
eyes closed, the examiner lightly touches one or both Unexpected abnormalities may be detected that prompt
hands and asks the patient to identify the stimuli. With the examiner to return in more detail to other aspects of
a parietal lobe lesion, the patient may be unable to the examination. The patient should be observed while
identify the stimulus on the contralateral side when walking and turning normally, walking on the heels,
both hands are touched. Other modalities relying walking on the toes, and walking heel-to-toe along a
on the parietal cortex include the discrimination of straight line. The examination may reveal decreased arm
two closely placed stimuli as separate (two-point dis- swing on one side (corticospinal tract disease), a stooped
crimination), identication of an object by touch and posture and short-stepped gait (parkinsonism), a broad-
manipulation alone (stereognosis), and the identica- based unstable gait (ataxia), scissoring (spasticity), or a
tion of numbers or letters written on the skin surface high-stepped, slapping gait (posterior column or periph-
(graphesthesia). eral nerve disease), or the patient may appear to be stuck
in place (apraxia with frontal lobe disease).

COORDINATION EXAMINATION
The bare minimum: Test rapid alternating movements of the NEUROLOGIC DIAGNOSIS
hands and the nger-to-nose and heel-knee-shin maneuvers.
The clinical data obtained from the history and exami-
Coordination refers to the orchestration and uid- nation are interpreted to arrive at an anatomic localiza-
ity of movements. Even simple acts require coopera- tion that best explains the clinical ndings (Table 1-2),
tion of agonist and antagonist muscles, maintenance of to narrow the list of diagnostic possibilities, and to select
posture, and complex servomechanisms to control the the laboratory tests most likely to be informative. The
rate and range of movements. Part of this integration laboratory assessment may include (1) serum electrolytes;
relies on normal function of the cerebellar and basal complete blood count; and renal, hepatic, endocrine,
ganglia systems. However, coordination also requires and immune studies; (2) cerebrospinal uid examination;
intact muscle strength and kinesthetic and proprio- (3) focused neuroimaging studies (Chap. 4); or (4) elec-
ceptive information. Thus, if the examination has dis- trophysiologic studies (Chap. 5). The anatomic localiza-
closed abnormalities of the motor or sensory systems, tion, mode of onset and course of illness, other medical
the patients coordination should be assessed with these data, and laboratory ndings are then integrated to estab-
limitations in mind. lish an etiologic diagnosis.
10 TABLE 1-2 The neurologic examination may be normal even in
FINDINGS HELPFUL FOR LOCALIZATION WITHIN THE patients with a serious neurologic disease, such as sei-
NERVOUS SYSTEM zures, chronic meningitis, or a TIA. A comatose patient
SECTION I

SIGNS
may arrive with no available history, and in such cases
the approach is as described in Chap. 17. In other
Cerebrum Abnormal mental status or cognitive
patients, an inadequate history may be overcome by a
impairment
Seizures
succession of examinations from which the course of
Unilateral weaknessa and sensory the illness can be inferred. In perplexing cases it is useful
abnormalities including head and limbs to remember that uncommon presentations of com-
Introduction to Neurology

Visual eld abnormalities mon diseases are more likely than rare etiologies. Thus,
Movement abnormalities (e.g., diffuse even in tertiary care settings, multiple strokes are usu-
incoordination, tremor, chorea) ally due to emboli and not vasculitis, and dementia with
Brainstem Isolated cranial nerve abnormalities myoclonus is usually Alzheimers disease and not due to
(single or multiple) a prion disorder or a paraneoplastic cause. Finally, the
Crossed weaknessa and sensory most important task of a primary care physician faced
abnormalities of head and limbs, e.g.,
with a patient who has a new neurologic complaint is
weakness of right face and left arm
and leg
to assess the urgency of referral to a specialist. Here, the
imperative is to rapidly identify patients likely to have
Spinal cord Back pain or tenderness
nervous system infections, acute strokes, and spinal cord
Weaknessa and sensory abnormalities
sparing the head
compression or other treatable mass lesions and arrange
Mixed upper and lower motor neuron for immediate care.
ndings
Sensory level
Sphincter dysfunction
Spinal roots Radiating limb pain
Weaknessb or sensory abnormalities fol-
lowing root distribution (see Figs. 15-2
and 15-3)
Loss of reexes
Peripheral nerve Mid or distal limb pain
Weaknessb or sensory abnormalities
following nerve distribution (see
Figs. 15-2 and 15-3)
Stocking or glove distribution of
sensory loss
Loss of reexes
Neuromuscular Bilateral weakness including face
junction (ptosis, diplopia, dysphagia) and
proximal limbs
Increasing weakness with exertion
Sparing of sensation
Muscle Bilateral proximal or distal weakness
Sparing of sensation

a
Weakness along with other abnormalities having an upper motor
neuron pattern, i.e., spasticity, weakness of extensors > exors in
the upper extremity and exors > extensors in the lower extremity,
hyperreexia.
b
Weakness along with other abnormalities having a lower motor
neuron pattern, i.e., accidity and hyporeexia.
CHAPTER 2

THE NEUROLOGIC SCREENING EXAM

Daniel H. Lowenstein

Knowledge of the basic neurologic examination is appear daunting at rst, skills usually improve rapidly
an essential clinical skill. A simple neurologic screen- with repetition and practice. In this video, the tech-
ing examinationassessment of mental status, cranial nique of performing a simple and efcient screen-
nerves, motor system, sensory system, coordination, ing examination is presented. Videos for this chapter
and gaitcan be reliably performed in 35 min. can be accessed at the following link: http://www
Although the components of the examination may .mhprofessional.com/mediacenter/.

11
CHAPTER 3

VIDEO ATLAS OF THE DETAILED NEUROLOGIC


EXAMINATION

Martin A. Samuels

The comprehensive neurologic examination is an irreplace- also becomes a thing of beautythe pinnacle of the art of
able tool for the efcient diagnosis of neurologic disorders. medicine. In this video, the most commonly used compo-
Mastery of its details requires knowledge of normal nervous nents of the examination are presented in detail, with a par-
system anatomy and physiology combined with personal ticular emphasis on those elements that are most helpful for
experience performing orderly and systematic examinations assessment of common neurologic problems. Videos for this
on large numbers of patients and healthy individuals. In chapter can be accessed at the following link: http://www
the hands of a great clinician, the neurologic examination .mhprofessional.com/mediacenter/.

12
CHAPTER 4

NEUROIMAGING IN NEUROLOGIC DISORDERS

William P. Dillon

The clinician caring for patients with neurologic symptoms diagnostic information regarding bone marrow inltra-
is faced with myriad imaging options, including com- tive processes that are difcult to detect on CT.
puted tomography (CT), CT angiography (CTA), per-
fusion CT (pCT), magnetic resonance imaging (MRI),
MR angiography (MRA), functional MRI (fMRI), COMPUTED TOMOGRAPHY
MR spectroscopy (MRS), MR neurography (MRN),
TECHNIQUE
diffusion and diffusion track imaging (DTI), susceptibil-
ity weighted MR imaging (SWI), and perfusion MRI The CT image is a cross-sectional representation of
(pMRI). In addition, an increasing number of interven- anatomy created by a computer-generated analysis of
tional neuroradiologic techniques are available, includ- the attenuation of x-ray beams passed through a sec-
ing angiography catheter embolization, coiling, and tion of the body. As the x-ray beam, collimated to the
stenting of vascular structures; and spine diagnostic and desired slice width, rotates around the patient, it passes
interventional techniques such as diskography, transfo- through selected regions in the body. X-rays that are
raminal and translaminar epidural and nerve root injec- not attenuated by body structures are detected by sensi-
tions and blood patches. Recent developments such tive x-ray detectors aligned 180 from the x-ray tube.
as multidetector CTA (MDCTA) and gadolinium- A computer calculates a back projection image from
enhanced MRA, have narrowed the indications for the 360 x-ray attenuation prole. Greater x-ray attenu-
conventional angiography, which is now reserved for ation (e.g., as caused by bone) results in areas of high
patients in whom small-vessel detail is essential for diag- density, while soft tissue structures that have poor
nosis or for whom concurrent interventional therapy is attenuation of x-rays such as organs and air-lled cavi-
planned (Table 4-1). ties are lower in density. The resolution of an image
In general, MRI is more sensitive than CT for the depends on the radiation dose, the detector size, colli-
detection of lesions affecting the central nervous sys- mation (slice thickness), the eld of view, and the matrix
tem (CNS), particularly those of the spinal cord, size of the display. A modern CT scanner is capable of
cranial nerves, and posterior fossa structures. Diffusion obtaining sections as thin as 0.51 mm with submillime-
MR, a sequence sensitive to the microscopic motion ter resolution at a speed of 0.31 s per rotation; complete
of water, is the most sensitive technique for detect- studies of the brain can be completed in 210 s.
ing acute ischemic stroke of the brain or spinal cord, Multidetector CT (MDCT) is now standard in most
and it is also useful in the detection of encephalitis, radiology departments. Single or multiple (from 4 to
abscesses, and prion diseases. CT, however, is quickly 256) detectors positioned 180 to the x-ray source result
acquired and is widely available, making it a pragmatic in multiple slices per revolution of the beam around
choice for the initial evaluation of patients with acute the patient. The table moves continuously through the
changes in mental status, suspected acute stroke, hem- rotating x-ray beam, generating a continuous helix of
orrhage, and intracranial or spinal trauma. CT is also information that can be reformatted into various slice
more sensitive than MRI for visualizing ne osseous thicknesses and planes. Advantages of MDCT include
detail and is indicated in the initial evaluation of con- shorter scan times, reduced patient and organ motion,
ductive hearing loss as well as lesions affecting the skull and the ability to acquire images dynamically during
base and calvarium. MR may, however, add important the infusion of intravenous contrast that can be used to

13
14 TABLE 4-1 construct CT angiograms of vascular structures and CT
GUIDELINES FOR THE USE OF CT, ULTRASOUND, perfusion images (Fig. 4-1B and C). CTA images are
AND MRI postprocessed for display in three dimensions to yield
SECTION I

RECOMMENDED
angiogram-like images (Fig. 4-1C, 4-2 E and F, and
CONDITION TECHNIQUE see Fig. 27-4). CTA has proved useful in assessing the
cervical and intracranial arterial and venous anatomy.
Hemorrhage
Acute parenchymal CT, MR
Intravenous iodinated contrast is often administered
Subacute/chronic MRI
prior to or during a CT study to identify vascular struc-
Subarachnoid CT, CTA, lumbar puncture tures and to detect defects in the blood-brain barrier
Introduction to Neurology

hemorrhage angiography (BBB) that are associated with disorders such as tumors,
Aneurysm Angiography > CTA, MRA infarcts, and infections. In the normal CNS, only vessels
Ischemic infarction and structures lacking a BBB (e.g., the pituitary gland,
Hemorrhagic infarction CT or MRI choroid plexus, and dura) enhance after contrast admin-
Bland infarction MRI > CT, CTA, angiography istration. The use of iodinated contrast agents car-
Carotid or vertebral MRI/MRA ries a small risk of allergic reaction and adds additional
dissection
expense. While helpful in characterizing mass lesions as
Vertebral basilar CTA, MRI/MRA
insufciency well as essential for the acquisition of CTA studies, the
Carotid stenosis CTA > Doppler ultrasound, decision to use contrast material should always be con-
MRA sidered carefully.
Suspected mass lesion
Neoplasm, primary or MRI + contrast
metastatic INDICATIONS
Infection/abscess MRI + contrast
Immunosuppressed with MRI + contrast CT is the primary study of choice in the evaluation
focal ndings of an acute change in mental status, focal neurologic
Vascular malformation MRI angiography ndings, acute trauma to the brain and spine, sus-
White matter disorders MRI
pected subarachnoid hemorrhage, and conductive hear-
Demyelinating disease MRI contrast
Dementia MRI > CT
ing loss (Table 4-1). CT is complementary to MR in
Trauma the evaluation of the skull base, orbit, and osseous
Acute trauma CT (noncontrast) structures of the spine. In the spine, CT is useful in
Shear injury/chronic MRI + gradient echo imaging evaluating patients with osseous spinal stenosis and
hemorrhage spondylosis, but MRI is often preferred in those with
Headache/migraine CT (noncontrast)/MRI neurologic decits. CT can also be obtained following
Seizure intrathecal contrast injection to evaluate the intracra-
First time, no focal ?CT as screen contrast
nial cisterns (CT cisternography) for cerebrospinal uid
neurologic decits
Partial complex/refrac- MRI with coronal T2W imag-
(CSF) stula, as well as the spinal subarachnoid space
tory ing (CT myelography).
Cranial neuropathy MRI with contrast
Meningeal disease MRI with contrast
Spine COMPLICATIONS
Low back pain CT is safe, fast, and reliable. Radiation exposure
No neurologic decits MRI or CT after 4 weeks depends on the dose used but is normally between
With focal decits MRI > CT 2 and 5 mSv (millisievert) for a routine brain CT study.
Spinal stenosis MRI or CT Care must be taken to reduce exposure when imaging
Cervical spondylosis MRI or CT myelography children. With the advent of MDCT, CTA, and CT
Infection MRI + contrast, CT
perfusion, care must be taken to appropriately mini-
Myelopathy MRI + contrast
mize radiation dose whenever possible. Advanced soft-
Arteriovenous malforma- MRI, angiography
tion
ware that permits noise reduction may permit lower
radiation doses. The most frequent complications are
Abbreviations: CT, computed tomography; CTA, CT angiography;
associated with use of intravenous contrast agents. Two
MRA, MR angiography; MRI, magnetic resonance imaging; T2W,
T2-weighted. broad categories of contrast media, ionic and non-
ionic, are in use. Although ionic agents are relatively
safe and inexpensive, they are associated with a higher
incidence of reactions and side effects. As a result, ionic
agents have been largely replaced by safer nonionic
compounds.
Contrast nephropathy may result from hemodynamic 15
changes, renal tubular obstruction and cell damage,
or immunologic reactions to contrast agents. A rise in

CHAPTER 4
serum creatinine of at least 85 mol/L (1 mg/dL) within
48 h of contrast administration is often used as a de-
nition of contrast nephropathy, although other causes
of acute renal failure must be excluded. The prognosis
is usually favorable, with serum creatinine levels return-
ing to baseline within 12 weeks. Risk factors for

Neuroimaging in Neurologic Disorders


contrast nephropathy include advanced age (>80 years),
preexisting renal disease (serum creatinine exceeding
2 mg/dL), solitary kidney, diabetes mellitus, dehydration,
paraproteinemia, concurrent use of nephrotoxic medica-
tion or chemotherapeutic agents, and high contrast dose.
Patients with diabetes and those with mild renal failure
should be well hydrated prior to the administration of
contrast agents, although careful consideration should
be given to alternative imaging techniques such as MR
imaging or noncontrast CT or ultrasound (US) exami-
nations. Nonionic, low-osmolar media produce fewer
abnormalities in renal blood ow and less endothelial
cell damage but should still be used carefully in patients
at risk for allergic reaction. Estimated glomerular ltra-
tion rate (eGFR) is a more reliable indicator of renal
function compared to creatinine alone as it takes into
account age, race, and sex. In one study, 15% of outpa-
tients with a normal serum creatinine had an estimated
creatinine clearance of 50 mL/min/1.73 m2 or less (nor-
mal is 90 mL/min/1.73 m2 or more). The exact eGFR
threshold, below which withholding intravenous con-
trast should be considered, is controversial. The risk of
contrast nephropathy increases in patients with an eGFR
<60 mL/min/1.732; however the majority of these
patients will only have a temporary rise in creatinine.
The risk of dialysis after receiving contrast signicantly
increases in patients with eGFR <30 mL/min/1.732.
Thus, an eGFR threshold between 60 and 30 mL/
min/1.732 is appropriate; however the exact number is
somewhat arbitrary. A creatinine of 1.6 in a 70-year-old,
non-African-American male corresponds to an eGFR of
approximately 45 mL/min/1.732. The American College
of Radiology suggests using an eGFR of 45 as a thresh-
old below which iodinated contrast should not be given
without serious consideration of the potential for con-
FIGURE 4-1
trast nephropathy. If contrast must be administered to a
CT angiography (CTA) of ruptured anterior cerebral artery
patient with an eGRF below 45, the patient should be
aneurysm in a patient presenting with acute headache. well hydrated, and a reduction in the dose of contrast
A. Noncontrast CT demonstrates subarachnoid hemorrhage should be considered. Use of other agents such as bicar-
and mild obstructive hydrocephalus. B. Axial maximum-intensity bonate and acetylcysteine may reduce the incidence of
projection from CT angiography demonstrates enlargement contrast nephropathy. Other side effects of CT scanning
of the anterior cerebral artery (arrow). C. 3D surface recon- are rare but include a sensation of warmth throughout
struction using a workstation conrms the anterior cerebral the body and a metallic taste during intravenous adminis-
aneurysm and demonstrates its orientation and relationship to tration of iodinated contrast media. The most serious side
nearby vessels (arrow). CTA image is produced by 0.51-mm effects are anaphylactic reactions, which range from mild
helical CT scans performed during a rapid bolus infusion of hives to bronchospasm, acute anaphylaxis, and death.
intravenous contrast medium. The pathogenesis of these allergic reactions is not fully
16
SECTION I
Introduction to Neurology

FIGURE 4-2
Acute left hemiparesis due to middle cerebral artery abrupt occlusion of the proximal right middle cerebral artery
occlusion. A. Axial noncontrast CT scan demonstrates high (arrow). E. Sagittal reformation through the right internal
density within the right middle cerebral artery (arrow) asso- carotid artery demonstrates a low-density lipid-laden plaque
ciated with subtle low density involving the right putamen (arrowheads) narrowing the lumen (black arrow) F. 3D surface-
(arrowheads). B. Mean transit time CT perfusion paramet- rendered CTA image demonstrates calcication and narrowing
ric map indicating prolonged mean transit time involving the of the right internal carotid artery (arrow), consistent with ath-
right middle cerebral territory (arrows). C. Cerebral blood erosclerotic disease. G. Coronal maximum-intensity projection
volume map shows reduced CBV involving an area within from MRA shows right middle cerebral artery (MCA) occlusion
the defect shown in B, indicating a high likelihood of infarc- (arrow). H and I. Axial diffusion-weighted image (H) and appar-
tion (arrows). D. Axial maximum-intensity projection from ent diffusion coefcient image (I) document the presence of a
a CTA study through the circle of Willis demonstrates an right middle cerebral artery infarction.
TABLE 4-2 of Rf energy (the echo), which is detected by the coils 17
GUIDELINES FOR PREMEDICATION OF PATIENTS that delivered the Rf pulses. The echo is transformed
WITH PRIOR CONTRAST ALLERGY by Fourier analysis into the information used to form

CHAPTER 4
12 h prior to examination:
an MR image. The MR image thus consists of a map of
Prednisone, 50 mg PO or methylprednisolone, 32 mg PO the distribution of hydrogen protons, with signal inten-
sity imparted by both density of hydrogen protons as
2 h prior to examination:
Prednisone, 50 mg PO or methylprednisolone, 32 mg PO
well as differences in the relaxation times (see below) of
and Cimetidine, 300 mg PO or ranitidine, 150 mg PO hydrogen protons on different molecules. While clini-
cal MRI currently makes use of the ubiquitous hydro-
Immediately prior to examination:

Neuroimaging in Neurologic Disorders


Benadryl, 50 mg IV (alternatively, can be given PO 2 h prior gen proton, research into sodium and carbon imaging
to exam) appears promising.

T1 and T2 relaxation times

understood but is thought to include the release of medi- The rate of return to equilibrium of perturbed protons is
ators such as histamine, antibody-antigen reactions, and called the relaxation rate. The relaxation rate varies among
complement activation. Severe allergic reactions occur normal and pathologic tissues. The relaxation rate of a
in 0.04% of patients receiving nonionic media, sixfold hydrogen proton in a tissue is inuenced by local inter-
lower than with ionic media. Risk factors include a his- actions with surrounding molecules and atomic neigh-
tory of prior contrast reaction, food allergies to shellsh, bors. Two relaxation rates, T1 and T2, inuence the
and atopy (asthma and hay fever). In such patients, a signal intensity of the image. The T1 relaxation time
noncontrast CT or MRI procedure should be considered is the time, measured in milliseconds, for 63% of the
as an alternative to contrast administration. If iodinated hydrogen protons to return to their normal equilib-
contrast is absolutely required, a nonionic agent should rium state, while the T2 relaxation is the time for 63%
be used in conjunction with pretreatment with gluco- of the protons to become dephased owing to interac-
corticoids and antihistamines (Table 4-2). Patients with tions among nearby protons. The intensity of the signal
allergic reactions to iodinated contrast material do not within various tissues and image contrast can be mod-
usually react to gadolinium-based MR contrast material, ulated by altering acquisition parameters such as the
although such reactions can occur. It would be wise to interval between Rf pulses (TR) and the time between
pretreat patients with a prior allergic history to MR con- the Rf pulse and the signal reception (TE). So-called
trast administration in a similar fashion. T1-weighted (T1W) images are produced by keeping
the TR and TE relatively short. T2-weighted (T2W)
images are produced by using longer TR and TE times.
Fat and subacute hemorrhage have relatively shorter
MAGNETIC RESONANCE IMAGING T1 relaxation rates and thus higher signal intensity than
TECHNIQUE brain on T1W images. Structures containing more water
such as CSF and edema, have long T1 and T2 relax-
MRI is a complex interaction between hydrogen pro- ation rates, resulting in relatively lower signal intensity
tons in biologic tissues, a static magnetic eld (the on T1W images and a higher signal intensity on T2W
magnet), and energy in the form of radiofrequency (Rf) images (Table 4-3). Gray matter contains 1015%
waves of a specic frequency introduced by coils placed
next to the body part of interest. Images are made by
computerized processing of resonance information TABLE 4-3
received from protons in the body. Field strength of the
SOME COMMON INTENSITIES ON T1- AND
magnet is directly related to signal-to-noise ratio. While T2-WEIGHTED MRI SEQUENCES
1.5-Telsa magnets have become the standard high-
eld MRI units, 3T8T magnets are now available and SIGNAL INTENSITY
have distinct advantages in the brain and musculoskel- IMAGE TR TE CSF FAT BRAIN EDEMA
etal systems. Spatial localization is achieved by magnetic T1W Short Short Low High Low Low
gradients surrounding the main magnet, which impart T2W Long Long High Low High High
slight changes in magnetic eld throughout the imaging
FLAIR Long Long Low Medium High High
volume. Rf pulses transiently excite the energy state of
(T2)
the hydrogen protons in the body. Rf is administered
at a frequency specic for the eld strength of the mag- Abbreviations: CSF, cerebrospinal uid; TE, interval between Rf
net. The subsequent return to equilibrium energy state pulse and signal reception; TR, interval between radiofrequency (Rf)
(relaxation) of the hydrogen protons results in a release pulses; T1W and T2W, T1- and T2-weighted.
18 more water than white matter, which accounts for MR contrast material
much of the intrinsic contrast between the two on MRI
(Fig. 4-6B). T2W images are more sensitive than T1W The heavy-metal element gadolinium forms the
basis of all currently approved intravenous MR con-
SECTION I

images to edema, demyelination, infarction, and chronic


hemorrhage, while T1W imaging is more sensitive to trast agents. Gadolinium is a paramagnetic substance,
subacute hemorrhage and fat-containing structures. which means that it reduces the T1 and T2 relaxation
Many different MR pulse sequences exist, and each times of nearby water protons, resulting in a high sig-
can be obtained in various planes (Figs. 4-2, 4-3, 4-4). nal on T1W images and a low signal on T2W images
The selection of a proper protocol that will best (the latter requires a sufcient local concentration,
usually in the form of an intravenous bolus). Unlike
Introduction to Neurology

answer a clinical question depends on an accurate


clinical history and indication for the examination. iodinated contrast agents, the effect of MR contrast
Fluid-attenuated inversion recovery (FLAIR) is a use- agents depends on the presence of local hydrogen
ful pulse sequence that produces T2W images in which protons on which it must act to achieve the desired
the normally high signal intensity of CSF is suppressed effect. Gadolinium is chelated to DTPA (diethylene-
(Fig. 4-6B). FLAIR images are more than sensitive triaminepentaacetic acid), which allows safe renal
standard spin echo images for any water-containing excretion. Approximately 0.2 mL/kg body weight
lesions or edema. Susceptibility weighted imaging, such is administered intravenously; the cost is $60 per
as gradient echo imaging, is most sensitive to magnetic dose. Gadolinium-DTPA does not normally cross
susceptibility generated by blood, calcium, and air and is the intact BBB immediately but will enhance lesions
indicated in patients suspected of pathology that might lacking a BBB (Fig. 4-3A) and areas of the brain that
result in microhemorrhages (Fig. 4-5C). MR images normally are devoid of the BBB (pituitary, choroid
can be generated in any plane without changing the plexus). However, gadolinium contrast has been noted
patients position. Each sequence, however, must be to slowly cross an intact BBB if given over time and
obtained separately and takes 110 min on average to especially in the setting of reduced renal clearance.
complete. Three-dimensional volumetric imaging is also The agents are generally well tolerated; severe aller-
possible with MRI, resulting in a 3D volume of data gic reactions are rare but have been reported. The
that can be reformatted in any orientation to highlight adverse reaction rate in patients with a prior history
certain disease processes. of atopy or asthma is 3.7%; however, the reaction rate

FIGURE 4-3
Cerebral abscess in a patient with fever and a right B. Axial diffusion-weighted image demonstrates restricted
hemiparesis. A. Coronal postcontrast T1-weighted image diffusion (high signal intensity) within the lesion, which in this
demonstrates a ring enhancing mass in the left frontal lobe. setting is highly suggestive of cerebral abscess.
19

CHAPTER 4
Neuroimaging in Neurologic Disorders
A B

FIGURE 4-4 indicating restricted diffusion involving the right medial


Herpes simplex encephalitis in a patient presenting with temporal lobe and hippocampus (arrows) as well as subtle
altered mental status and fever. A and B. Coronal (A) and involvement of the left inferior temporal lobe (arrowhead).
axial (B) T2-weighted FLAIR images demonstrate expan- This is most consistent with neuronal death and can be seen
sion and high signal intensity involving the right medial in acute infarction as well as encephalitis and other inam-
temporal lobe and insular cortex (arrows). C. Coronal dif- matory conditions. The suspected diagnosis of herpes sim-
fusion-weighted image demonstrates high signal intensity plex encephalitis was conrmed by CSF PCR analysis.

increases to 6.3% in those patients with a prior history contrast agents. The onset of NSF has been reported
of unspecied allergic reaction to iodinated contrast between 5 and 75 days following exposure; histologic
agents. Gadolinium contrast material can be adminis- features include thickened collagen bundles with sur-
tered safely to children as well as adults, although these rounding clefts, mucin deposition, and increased num-
agents are generally avoided in those under 6 months bers of brocytes and elastic bers in skin. In addition
of age. Renal failure does not occur. to dermatologic symptoms, other manifestations include
A rare complication, nephrogenic systemic brosis widespread brosis of the skeletal muscle, bone, lungs,
(NSF), has recently been reported in patients with renal pleura, pericardium, myocardium, kidney, muscle,
insufciency who have been exposed to gadolinium bone, testes, and dura. For this reason, the American
20
SECTION I
Introduction to Neurology

A B

FIGURE 4-5
Susceptibility weighted imaging in a patient with familial lesions (arrows). C. Susceptibility weighted image shows
cavernous malformations. A. Noncontrast CT scan shows numerous low-intensity lesions consistent with hemosiderin-
one hyperdense lesion in the right hemisphere (arrow). B. laden cavernous malformations (arrow).
T2-weighted fast spin echo image shows subtle low-intensity

College of Radiology recommends that prior to elec- 5. History of severe hepatic disease/liver transplant/
tive gadolinium-based MR contrast agent (GBMCA) pending liver transplant: for these patients it is rec-
administration, a recent (e.g., past 6 weeks) glomerular ommended that the patients GFR assessment be
ltration rate (GFR) assessment be obtained in patients nearly contemporaneous with the MR examination.
with a history of:
The incidence of NSF in patients with severe renal
1. Renal disease (including solitary kidney, renal trans- dysfunction (GFR <30) varies from 0.19 to 4%. A
plant, renal tumor) recent meta-analysis reported an odds ratio of 26.7 (95%
2. Age >60 years CI = 10.369.4) for development of NSF after gado-
3. History of hypertension linium administration in patients with impaired renal
4. History of diabetes function (GFR <30 mL/min/1.72 m). Thus, it is not
21

CHAPTER 4
Neuroimaging in Neurologic Disorders
A B

FIGURE 4-6
Diffusion tractography in cerebral glioma. A. An axial high signal glioma in left temporal lobe. C. Axial diffusion
postcontrast T1-weighted image shows a nonenhancing gli- fractional anisotropy image shows the position of the deep
oma (T) of the left temporal lobe cortex lateral to the bers of white matter bers (arrow) relative to the enhancing tumor (T).
the internal capsule. B. Coronal T2 FLAIR image demonstrates

recommended to administer gadolinium to any patient that is moved into a long, narrow gap within the mag-
with a GFR below 30. Caution is advised for patients net. Approximately 5% of the population experiences
with a GFR below 45. severe claustrophobia in the MR environment. This can
be reduced by mild sedation but remains a problem for
some. Unlike CT, movement of the patient during an
COMPLICATIONS AND CONTRAINDICATIONS
MR sequence distorts all the images; therefore, unco-
From the patients perspective, an MRI examination operative patients should either be sedated for the MR
can be intimidating, and a higher level of cooperation study or scanned with CT. Generally, children under
is required than with CT. The patient lies on a table the age of 10 years usually require conscious sedation
22 TABLE 4-4 spin echo MR images. Slower-owing blood, as occurs
COMMON CONTRAINDICATIONS TO MR IMAGING in veins or distal to arterial stenosis, may appear high in
Cardiac pacemaker or permanent pacemaker leads signal. However, using special pulse sequences called
SECTION I

Internal debrillatory device gradient echo sequences, it is possible to increase the signal
Cochlear prostheses intensity of moving protons in contrast to the low sig-
Bone growth stimulators nal background intensity of stationary tissue. This cre-
Spinal cord stimulators ates angiography-like images, which can be manipulated
Electronic infusion devices in three dimensions to highlight vascular anatomy and
Intracranial aneurysm clips (some but not all)
relationships.
Ocular implants (some) or ocular metallic foreign body
Introduction to Neurology

McGee stapedectomy piston prosthesis Time-of-ight (TOF) imaging, currently the tech-
Duraphase penile implant nique used most frequently, relies on the suppression
Swan-Ganz catheter of nonmoving tissue to provide a low-intensity back-
Magnetic stoma plugs ground for the high signal intensity of owing blood
Magnetic dental implants entering the section; arterial or venous structures may
Magnetic sphincters be highlighted. A typical TOF angiography sequence
Ferromagnetic IVC lters, coils, stentssafe 6 weeks after
results in a series of contiguous, thin MR sections
implantation
Tattooed eyeliner (contains ferromagnetic material and
(0.60.9 mm thick), which can be viewed as a stack
may irritate eyes) and manipulated to create an angiographic image data
set that can be reformatted and viewed in various planes
Note: See also http://www.mrisafety.com. and angles, much like that seen with conventional
angiography (Fig. 4-2G).
Phase-contrast MRA has a longer acquisition time
than TOF MRA, but in addition to providing anatomic
in order to complete the MR examination without information similar to that of TOF imaging, it can be
motion degradation. used to reveal the velocity and direction of blood ow
MRI is considered safe for patients, even at very high in a given vessel. Through the selection of different
eld strengths (>34 T). Serious injuries have been imaging parameters, differing blood velocities can be
caused, however, by attraction of ferromagnetic objects highlighted; selective venous and arterial MRA images
into the magnet, which act as missiles if brought too can thus be obtained. One advantage of phase-contrast
close to the magnet. Likewise, ferromagnetic implants MRA is the excellent suppression of high-signal-
such as aneurysm clips, may torque within the mag- intensity background structures.
net, causing damage to vessels and even death. Metallic MRA can also be acquired during infusion of
foreign bodies in the eye have moved and caused intra- contrast material. Advantages include faster imaging
ocular hemorrhage; screening for ocular metallic frag- times (12 min vs. 10 min), fewer ow-related arti-
ments is indicated in those with a history of metal work facts, and higher-resolution images. Recently, con-
or ocular metallic foreign bodies. Implanted cardiac trast-enhanced MRA has become the standard for
pacemakers are generally a contraindication to MRI extracranial vascular MRA. This technique entails
owing to the risk of induced arrhythmias; however, rapid imaging using coronal three-dimensional TOF
some newer pacemakers have been shown to be safe. sequences during a bolus infusion of 1520 mL of
All health care personnel and patients must be screened gadolinium-DTPA. Proper technique and timing
and educated thoroughly to prevent such disasters as the of acquisition relative to bolus arrival are critical for
magnet is always on. Table 4-4 lists common contra- success.
indications for MRI. MRA has lower spatial resolution compared with
conventional lm-based angiography, and therefore the
detection of small-vessel abnormalities, such as vasculitis
MAGNETIC RESONANCE ANGIOGRAPHY and distal vasospasm, is problematic. MRA is also less
sensitive to slowly owing blood and thus may not reli-
MR angiography is a general term describing several MR ably differentiate complete from near-complete occlu-
techniques that result in vascular-weighted images. sions. Motion, either by the patient or by anatomic
These provide a vascular ow map rather than the ana- structures, may distort the MRA images, creating arti-
tomic map shown by conventional angiography. On facts. These limitations notwithstanding, MRA has
routine spin echo MR sequences, moving protons proved useful in evaluation of the extracranial carotid
(e.g., owing blood, CSF) exhibit complex MR sig- and vertebral circulation as well as of larger-caliber
nals that range from high- to low-signal intensity rela- intracranial arteries and dural sinuses. It has also proved
tive to background stationary tissue. Fast-owing blood useful in the noninvasive detection of intracranial aneu-
returns no signal (ow void) on routine T1W or T2W rysms and vascular malformations.
ECHO-PLANAR MR IMAGING
task activation. Neuronal activity elicits a slight increase 23
in the delivery of oxygenated blood ow to a specic
Recent improvements in gradients, software, and region of activated brain. This results in an alteration in

CHAPTER 4
high-speed computer processors now permit extremely the balance of oxyhemoglobin and deoxyhemoglobin,
rapid MRI of the brain. With echo-planar MRI (EPI), which yields a 23% increase in signal intensity within
fast gradients are switched on and off at high speeds to veins and local capillaries. Further studies will determine
create the information used to form an image. In rou- whether these techniques are cost-effective or clinically
tine spin echo imaging, images of the brain can be useful, but currently preoperative somatosensory and
obtained in 510 min. With EPI, all of the informa- auditory cortex localization is possible. This technique

Neuroimaging in Neurologic Disorders


tion required for processing an image is accumulated in has proved useful to neuroscientists interested in inter-
50150 ms, and the information for the entire brain is rogating the localization of certain brain functions.
obtained in 12 min, depending on the degree of reso-
lution required or desired. Fast MRI reduces patient and
organ motion, permitting diffusion imaging and tractog- MAGNETIC RESONANCE
raphy (Figs. 4-2H, 4-3, 4-4C, 4-6; and see Fig. 27-16), NEUROGRAPHY
perfusion imaging during contrast infusion, fMRI, and
kinematic motion studies. MRN is a T2-weighted MR technique that shows prom-
Perfusion and diffusion imaging are EPI techniques ise in detecting increased signal in irritated, inamed, or
that are useful in early detection of ischemic injury of inltrated peripheral nerves. Images are obtained with
the brain and may be useful together to demonstrate fat-suppressed fast spin echo imaging or short inversion
infarcted tissue as well as ischemic but potentially viable recovery sequences. Irritated or inltrated nerves will
tissue at risk of infarction (e.g., the ischemic penumbra). demonstrate high signal on T2W imaging. This is indi-
Diffusion-weighted imaging (DWI) assesses microscopic cated in patients with radiculopathy whose conventional
motion of water; restriction of motion appears as rela- MR studies of the spine are normal, or in those suspected
tive high-signal intensity on diffusion-weighted images. of peripheral nerve entrapment or trauma.
Infarcted tissue reduces the water motion within cells
and in the interstitial tissues, resulting in high signal on
DWI. DWI is the most sensitive technique for detec- POSITRON EMISSION TOMOGRAPHY
tion of acute cerebral infarction of <7 days duration (PET)
(Fig. 4-2H) and is also sensitive to encephalitis and abscess
formation, which have reduced diffusion and result in PET relies on the detection of positrons emitted during
high signal on diffusion-weighted images (Fig. 4-3B). the decay of a radionuclide that has been injected into
Perfusion MRI involves the acquisition of EPI a patient. The most frequently used moiety is 2-[18F]
images during a rapid intravenous bolus of gadolin- uoro-2-deoxy-D-glucose (FDG), which is an analogue
ium contrast material. Relative perfusion abnormali- of glucose and is taken up by cells competitively with
ties can be identied on images of the relative cerebral 2-deoxyglucose. Multiple images of glucose uptake
blood volume, mean transit time, and cerebral blood activity are formed after 4560 min. Images reveal
ow. Delay in mean transit time and reduction in cere- differences in regional glucose activity among nor-
bral blood volume and cerebral blood ow are typi- mal and pathologic brain structures. A lower activity
cal of infarction. In the setting of reduced blood ow, of FDG in the parietal lobes has been associated with
a prolonged mean transit time of contrast but normal Alzheimers disease. FDG PET is used primarily for the
or elevated cerebral blood volume may indicate tissue detection of extracranial metastatic disease. Combina-
supplied by collateral ow that is at risk of infarction. tion PET-CT scanners, in which both CT and PET are
Perfusion MRI imaging can also be used in the assess- obtained at one sitting, are replacing PET scans alone
ment of brain tumors to differentiate intraaxial primary for most clinical indications. Functional images super-
tumors from extraaxial tumors or metastasis. imposed on high-resolution CT scans result in more
Diffusion tensor imaging (DTI) is a diffusion MRI precise anatomic diagnoses.
technique that assesses the direction of microscopic
motion of water along white matter tracts. This technique
has great potential in the assessment of brain maturation
as well as disease entities that undermine the integrity of MYELOGRAPHY
the white matter architecture. It has proven valuable in
TECHNIQUE
preoperative assessment of subcortical white matter tract
anatomy prior to brain tumor surgery (Fig. 4-6). Myelography involves the intrathecal instillation of
Functional MRI of the brain is an EPI technique specially formulated water-soluble iodinated contrast
that localizes regions of activity in the brain following medium into the lumbar or cervical subarachnoid space.
24 CT scanning is usually performed after myelography Management of postlumbar puncture headache is
(CT myelography) to better demonstrate the spinal cord discussed in Chap. 8.
and roots, which appear as lling defects in the opaci- If signicant headache persists for longer than 48 h,
SECTION I

ed subarachnoid space. Low-dose CT myelography, in placement of an epidural blood patch should be con-
which CT is performed after the subarachnoid injec- sidered. Hearing loss is a rare complication of myelog-
tion of a small amount of relatively dilute contrast mate- raphy. It may result from a direct toxic effect of the
rial, has replaced conventional myelography for many contrast medium or from an alteration of the pressure
indications, thereby reducing exposure to radiation equilibrium between CSF and perilymph in the inner
and contrast media. Newer multidetector scanners now ear. Puncture of the spinal cord is a rare but serious
Introduction to Neurology

obtain CT studies quickly so that reformations in sagit- complication of cervical (C12) or high lumbar punc-
tal and coronal planes, equivalent to traditional myelog- ture. The risk of cord puncture is greatest in patients
raphy projections, are now routine. with spinal stenosis, Chiari malformations, or conditions
that reduce CSF volume. In these settings, a low-dose
lumbar injection followed by thin-section CT or MRI
INDICATIONS is a safer alternative to cervical puncture. Intrathecal
Myelography has been largely replaced by CT myelog- contrast reactions are rare, but aseptic meningitis and
raphy and MRI for diagnosis of diseases of the spinal encephalopathy may occur. The latter is usually dose
canal and cord (Table 4-1). Remaining indications for related and associated with contrast entering the intra-
conventional plain-lm myelography include the evalu- cranial subarachnoid space. Seizures occur follow-
ation of suspected meningeal or arachnoid cysts and the ing myelography in 0.10.3% of patients. Risk factors
localization of spinal dural arteriovenous or CSF stulas. include a preexisting seizure disorder and the use of a
Conventional myelography and CT myelography pro- total iodine dose of >4500 mg. Other reported compli-
vide the most precise information in patients with prior cations include hyperthermia, hallucinations, depression,
spinal fusion and spinal xation hardware. and anxiety states. These side effects have been reduced
by the development of nonionic, water-soluble contrast
agents as well as by head elevation and generous hydra-
CONTRAINDICATIONS tion following myelography.
Myelography is relatively safe; however, it should be
performed with caution in any patient with elevated
intracranial pressure, evidence of a spinal block, or a SPINE INTERVENTIONS
history of allergic reaction to intrathecal contrast media.
In patients with a suspected spinal block, MR is the DISKOGRAPHY
preferred technique. If myelography is necessary, only The evaluation of back pain and radiculopathy may
a small amount of contrast medium should be instilled require diagnostic procedures that attempt either to
below the lesion in order to minimize the risk of neu- reproduce the patients pain or relieve it, indicating
rologic deterioration. Lumbar puncture is to be avoided its correct source prior to lumbar fusion. Diskography
in patients with bleeding disorders, including patients is performed by uoroscopic placement of a 22- to
receiving anticoagulant therapy, as well as in those with 25-gauge needle into the intervertebral disk and sub-
infections of the overlying soft tissues. sequent injection of 13 mL of contrast media. The
intradiskal pressure is recorded, as is an assessment of the
patients response to the injection of contrast material.
COMPLICATIONS Typically little or no pain is felt during injection of a
Headache, nausea, and vomiting are the most fre- normal disk, which does not accept much more than
quent complications of myelography and are reported 1 mL of contrast material, even at pressures as high as
to occur in up to 38% of patients. These symptoms 415690 kPa (60100 lb/in2). CT and plain lms are
result from either neurotoxic effects of the contrast obtained following the procedure. Concerns have been
agent, persistent leakage of CSF at the puncture site, raised that diskography may contribute to an accelerated
or psychological reactions to the procedure. Vasova- rate of disk degeneration.
gal syncope may occur during lumbar puncture; it is
accentuated by the upright position used during lum-
SELECTIVE NERVE ROOT AND EPIDURAL
bar myelography. Adequate hydration before and
SPINAL INJECTIONS
after myelography will reduce the incidence of this
complication. Postural headache (postlumbar punc- Percutaneous selective nerve root and epidural blocks
ture headache) is generally due to leakage of CSF with glucocorticoid and anesthetic mixtures may be
from the puncture site, resulting in CSF hypotension. both therapeutic as well as diagnostic, especially if
a patients pain is relieved. Typically, 12 mL of an either by an underlying disease or by the injection of 25
equal mixture of a long-acting glucocorticoid such as hyperosmolar contrast agent. Ionic contrast media
betamethasone and a long-acting anesthetic such as are less well tolerated than nonionic media, probably

CHAPTER 4
bupivacaine 0.75% is instilled under CT or uoroscopic because they can induce changes in cell membrane
guidance in the intraspinal epidural space or adjacent to electrical potentials. Patients with dolichoectasia of the
an existing nerve root. basilar artery can suffer reversible brainstem dysfunction
and acute short-term memory loss during angiography,
owing to the slow percolation of the contrast material
and the consequent prolonged exposure of the brain.
ANGIOGRAPHY

Neuroimaging in Neurologic Disorders


Rarely, an intracranial aneurysm ruptures during an
Catheter angiography is indicated for evaluating intra- angiographic contrast injection, causing subarachnoid
cranial small-vessel pathology (such as vasculitis), for hemorrhage, perhaps as a result of injection under high
assessing vascular malformations and aneurysms, and pressure.
in endovascular therapeutic procedures (Table 4-1).
Angiography has been replaced for many indications by
SPINAL ANGIOGRAPHY
CT/CTA or MRI/MRA.
Angiography carries the greatest risk of morbidity of Spinal angiography may be indicated to evaluate vascu-
all diagnostic imaging procedures, owing to the neces- lar malformations and tumors and to identify the artery of
sity of inserting a catheter into a blood vessel, direct- Adamkiewicz (Chap. 35) prior to aortic aneurysm repair.
ing the catheter to the required location, injecting The procedure is lengthy and requires the use of relatively
contrast material to visualize the vessel, and removing large volumes of contrast; the incidence of serious com-
the catheter while maintaining hemostasis. Therapeu- plications, including paraparesis, subjective visual blurring,
tic transcatheter procedures (see below) have become and altered speech, is 2%. Gadolinium-enhanced MRA
important options for the treatment of some cerebro- has been used successfully in this setting, as has iodinated
vascular diseases. The decision to undertake a diag- contrast CTA, which has promise for replacing diagnostic
nostic or therapeutic angiographic procedure requires spinal angiography for some indications.
careful assessment of the goals of the investigation and
its attendant risks.
To improve tolerance to contrast agents, patients
undergoing angiography should be well hydrated before INTERVENTIONAL NEURORADIOLOGY
and after the procedure. Since the femoral route is used
most commonly, the femoral artery must be compressed This rapidly developing eld is providing new
after the procedure to prevent a hematoma from devel- therapeutic options for patients with challenging neuro-
oping. The puncture site and distal pulses should be vascular problems. Available procedures include detach-
evaluated carefully after the procedure; complications able coil therapy for aneurysms, particulate or liquid
can include thigh hematoma or lower extremity emboli. adhesive embolization of arteriovenous malformations,
balloon angioplasty and stenting of arterial stenosis or
vasospasm, transarterial or transvenous embolization
of dural arteriovenous stulas, balloon occlusion of
COMPLICATIONS
carotid-cavernous and vertebral stulas, endovascular
A common femoral arterial puncture provides retrograde treatment of vein-of-Galen malformations, preoperative
access via the aorta to the aortic arch and great vessels. embolization of tumors, and thrombolysis of acute arte-
The most feared complication of cerebral angiography is rial or venous thrombosis. Many of these disorders place
stroke. Thrombus can form on or inside the tip of the the patient at high risk of cerebral hemorrhage, stroke,
catheter, and atherosclerotic thrombus or plaque can be or death.
dislodged by the catheter or guidewire or by the force The highest complication rates are found with the
of injection and can embolize distally in the cerebral cir- therapies designed to treat the highest-risk diseases. The
culation. Risk factors for ischemic complications include advent of electrolytically detachable coils has ushered
limited experience on the part of the angiographer, ath- in a new era in the treatment of cerebral aneurysms.
erosclerosis, vasospasm, low cardiac output, decreased One randomized trial found a 28% reduction of mor-
oxygen-carrying capacity, advanced age, and prior his- bidity and mortality at 1 year among those treated for
tory of migraine. The risk of a neurologic complica- anterior circulation aneurysm with detachable coils
tion varies but is 4% for transient ischemic attack and compared with neurosurgical clipping. It remains to be
stroke, 1% for permanent decit, and <0.1% for death. determined what the role of coils will be relative to sur-
Ionic contrast material injected into the cerebral gical options, but in many centers, coiling has become
vasculature can be neurotoxic if the BBB is breached, standard therapy for many aneurysms.
CHAPTER 5

ELECTRODIAGNOSTIC STUDIES OF NERVOUS


SYSTEM DISORDERS: EEG, E VOKED POTENTIALS,
AND EMG

Michael J. Aminoff

ELECTROENCEPHALOGRAPHY THE EEG AND EPILEPSY


The EEG is most useful in evaluating patients with sus-
The electrical activity of the brain (the electroen- pected epilepsy. The presence of electrographic seizure
cephalogram [EEG]) is easily recorded from electrodes activityi.e., of abnormal, repetitive, rhythmic activity
placed on the scalp. The potential difference between having an abrupt onset and termination and a charac-
pairs of electrodes on the scalp (bipolar derivation) or teristic evolutionclearly establishes the diagnosis. The
between individual scalp electrodes and a relatively absence of such electrocerebral accompaniment does
inactive common reference point (referential deriva- not exclude a seizure disorder, however, because there
tion) is amplied and displayed on a computer moni- may be no change in the scalp-recorded EEG during
tor, oscilloscope, or paper. The characteristics of the certain focal seizures. With generalized tonic-clonic sei-
normal EEG depend on the patients age and level of zures, the EEG is always abnormal during the episode.
arousal. The rhythmic activity normally recorded rep- It is often not possible to obtain an EEG during clinical
resents the postsynaptic potentials of vertically oriented events that may represent seizures, especially when such
pyramidal cells of the cerebral cortex and is character- events occur unpredictably or infrequently. Continuous
ized by its frequency. In normal awake adults lying monitoring for prolonged periods in video-EEG telem-
quietly with the eyes closed, an 8- to 13-Hz alpha etry units has made it easier to capture the electrocere-
rhythm is seen posteriorly in the EEG, intermixed with bral accompaniments of such clinical episodes. Monitor-
a variable amount of generalized faster (beta) activ- ing by these means is sometimes helpful in conrming
ity (>13 Hz); the alpha rhythm is attenuated when the that seizures are occurring, characterizing the nature of
eyes are opened (Fig. 5-1). During drowsiness, the clinically equivocal episodes, and determining the fre-
alpha rhythm is also attenuated; with light sleep, slower quency of epileptic events.
activity in the theta (47 Hz) and delta (<4 Hz) ranges The EEG ndings may also be helpful in the inter-
becomes more conspicuous. ictal period by showing certain abnormalities that are
Digital systems are now widely used for recording strongly supportive of a diagnosis of epilepsy. Such epi-
the EEG. They allow the EEG to be reconstructed and leptiform activity consists of bursts of abnormal discharges
displayed with any desired format and manipulated for containing spikes or sharp waves. The presence of epi-
more detailed analysis, and also permit computerized leptiform activity is not specic for epilepsy, but it has
techniques to be used to detect certain abnormalities. a much greater prevalence in epileptic patients than in
Activating procedures are generally undertaken while normal individuals. However, even in an individual
the EEG is recorded in an attempt to provoke abnor- who is known to have epilepsy, the initial routine inter-
malities. Such procedures commonly include hyperven- ictal EEG may be normal up to 60% of the time. Thus,
tilation (for 3 or 4 min), photic stimulation, sleep, and the EEG cannot establish the diagnosis of epilepsy in
sleep deprivation on the night prior to the recording. many cases.
Electroencephalography is relatively inexpensive and The EEG ndings have been used in classifying sei-
may aid clinical management in several different contexts. zure disorders and selecting appropriate anticonvulsant
26
Eyes open 27
Fp1-F3 F3-C3
F3-C3 C3-P3

CHAPTER 5
C3-P3 P3-O1
P3-O1 F4-C4
Fp2-F4 C4-P4
F4-C4 P4-O2
C4-P4 T3-CZ
P4-O2 CZ-T4

Electrodiagnostic Studies of Nervous System Disorders: EEG, E voked Potentials, and EMG
A B

F3-A1
Fp1-F3
C3-A1 F3-C3
P3-A1 C3-P3
O1-A1 P3-O1
Fp2-F4
F4-A2
F4-C4
C4-A2
C4-P4
P4-A2 P4-O2
O2-A2
C D

FIGURE 5-1
A. Normal EEG showing a posteriorly situated 9-Hz alpha in other panels. (From MJ Aminoff, ed: Electrodiagnosis in Clini-
rhythm that attenuates with eye opening. B. Abnormal EEG cal Neurology, 5th ed. New York, Churchill Livingstone, 2005.) In
showing irregular diffuse slow activity in an obtunded patient this and the following gure, electrode placements are indicated
with encephalitis. C. Irregular slow activity in the right cen- at the left of each panel and accord with the international 10:20
tral region, on a diffusely slowed background, in a patient with system. A, earlobe; C, central; F, frontal; Fp, frontal polar; P, pari-
a right parietal glioma. D. Periodic complexes occurring once etal; T, temporal; O, occipital. Right-sided placements are indi-
every second in a patient with Creutzfeldt-Jakob disease. Hori- cated by even numbers, left-sided placements by odd numbers,
zontal calibration: 1 s; vertical calibration: 200 V in A, 300 V and midline placements by Z.

medication for individual patients (Fig. 5-2). The epi- to develop seizures, because in such circumstances epi-
sodic generalized spike-wave activity that occurs during leptiform activity is commonly encountered regardless
and between seizures in patients with typical absence of whether seizures occur. The EEG ndings are some-
epilepsy contrasts with focal interictal epileptiform dis- times used to determine whether anticonvulsant medi-
charges or ictal patterns found in patients with focal cation can be discontinued in epileptic patients who
seizures. These latter seizures may have no correlates have been seizure-free for several years, but the nd-
in the scalp-recorded EEG or may be associated with ings provide only a general guide to prognosis. Further
abnormal rhythmic activity of variable frequency, a seizures may occur after withdrawal of anticonvulsant
localized or generalized distribution, and a stereotyped medication despite a normal EEG or, conversely, may
pattern that varies with the patient. Focal or lateral- not occur despite a continuing EEG abnormality. The
ized epileptogenic lesions are important to recognize, decision to discontinue anticonvulsant medication is
especially if surgical treatment is contemplated. Inten- made on clinical grounds, and the EEG does not have a
sive long-term monitoring of clinical behavior and the useful role in this context except for providing guidance
EEG is required for operative candidates, however, and when there is clinical ambiguity or the patient requires
this generally also involves recording from intracranially reassurance about a particular course of action.
placed electrodes (which may be subdural, extradural, The EEG has no role in the management of tonic-
or intracerebral in location). clonic status epilepticus except when there is clinical
The ndings in the routine scalp-recorded EEG may uncertainty whether seizures are continuing in a coma-
indicate the prognosis of seizure disorders: In general, tose patient. In patients treated by pentobarbital-induced
a normal EEG implies a better prognosis than other- coma for refractory status epilepticus, the EEG nd-
wise, whereas an abnormal background or profuse epi- ings are useful in indicating the level of anesthesia and
leptiform activity suggests a poor outlook. The EEG whether seizures are occurring. During status epilepticus,
ndings are not helpful in determining which patients the EEG shows repeated electrographic seizures or con-
with head injuries, stroke, or brain tumors will go on tinuous spike-wave discharges. In nonconvulsive status
28 A THE EEG AND COMA
F3-C3
C3-P3
In patients with an altered mental state or some degree
of obtundation, the EEG tends to become slower as
SECTION I

P3-O1
consciousness is depressed, regardless of the underlying
F4-C4 cause (Fig. 5-1). Other ndings may also be present and
C4-P4 may suggest diagnostic possibilities, as when electro-
P4-O2 graphic seizures are found or there is a focal abnormality
T3-CZ indicating a structural lesion. The EEG generally slows
CZ-T4 in metabolic encephalopathies, and triphasic waves may
Introduction to Neurology

be present. The ndings do not permit differentiation


of the underlying metabolic disturbance but help to
B
exclude other encephalopathic processes by indicating
Fp1-F7
the diffuse extent of cerebral dysfunction. The response
F7-T3 of the EEG to external stimulation is helpful prognos-
T3-T5 tically because electrocerebral responsiveness implies
a lighter level of coma than a nonreactive EEG. Serial
T5-O1
records provide a better guide to prognosis than a sin-
Fp2-F8 gle record and supplement the clinical examination in
F8-T4 following the course of events. As the depth of coma
T4-T6 increases, the EEG becomes nonreactive and may show
a burst-suppression pattern, with bursts of mixed-fre-
T6-O2
quency activity separated by intervals of relative cere-
bral inactivity. In other instances there is a reduction in
C amplitude of the EEG until eventually activity cannot
Fp1-A1 be detected. Such electrocerebral silence does not nec-
F7-A1 essarily reect irreversible brain damage, because it may
T3-A1 occur in hypothermic patients or with drug overdose.
T5-A1
The prognosis of electrocerebral silence, when recorded
using an adequate technique, depends upon the clini-
Fp2-A2 cal context in which it is found. In patients with severe
F8-A2 cerebral anoxia, for example, electrocerebral silence in a
T4-A2 technically satisfactory record implies that useful cogni-
T6-A2
tive recovery will not occur.
In patients with clinically suspected brain death, an
EEG, when recorded using appropriate technical stan-
dards, may be conrmatory by showing electrocerebral
silence. However, complicating disorders that may
FIGURE 5-2
produce a similar but reversible EEG appearance (e.g.,
Electrographic seizures. A. Onset of a tonic seizure show-
hypothermia or drug intoxication) must be excluded.
ing generalized repetitive sharp activity with synchronous
onset over both hemispheres. B. Burst of repetitive spikes
The presence of residual EEG activity in suspected brain
occurring with sudden onset in the right temporal region dur-
death fails to conrm the diagnosis but does not exclude
ing a clinical spell characterized by transient impairment of it. The EEG is usually normal in patients with locked-in
external awareness. C. Generalized 3-Hz spike-wave activ- syndrome and helps in distinguishing this disorder from
ity occurring synchronously over both hemispheres during an the comatose state with which it is sometimes confused
absence (petit mal) attack. Horizontal calibration: 1 s; verti- clinically.
cal calibration: 400 mV in A, 200 mV in B, and 750 mV in C.
(From MJ Aminoff, ed: Electrodiagnosis in Clinical Neurology,
5th ed. New York, Churchill Livingstone, 2005.)
THE EEG IN OTHER NEUROLOGIC
DISORDERS
In the developed countries, CT scanning and MRI
epilepticus, a disorder that may not be recognized unless have taken the place of EEG as a noninvasive means
an EEG is performed, the EEG may also show continu- of screening for focal structural abnormalities of the
ous spike-wave activity (spike-wave stupor) or, less brain, such as tumors, infarcts, or hematomas (Fig. 5-1).
commonly, repetitive electrographic seizures (focal status Nonetheless, the EEG is still used for this purpose
epilepticus). in many parts of the world, although infratentorial or
slowly expanding lesions may fail to cause any abnor- epilepsy, MEG is useful in localizing epileptogenic foci 29
malities. Focal slow-wave disturbances, a localized loss for surgery and for guiding the placement of intracranial
of electrocerebral activity, or more generalized electro- electrodes for electrophysiologic monitoring. MEG has

CHAPTER 5
cerebral disturbances are common ndings but provide also been used for mapping brain tumors, identifying
no reliable indication about the nature of the underly- the central ssure preoperatively, and localizing func-
ing pathology. tionally eloquent cortical areas such as those concerned
In patients with an acute encephalopathy, focal or with language.
lateralized periodic slow-wave complexes, sometimes
with a sharpened outline, suggest a diagnosis of her-

Electrodiagnostic Studies of Nervous System Disorders: EEG, E voked Potentials, and EMG
pes simplex encephalitis, and periodic lateralizing epi-
leptiform discharges (PLEDs) are commonly found EVOKED POTENTIALS
with acute hemispheric pathology such as a hematoma, SENSORY EVOKED POTENTIALS
abscess, or rapidly expanding tumor. The EEG ndings
in dementia are usually nonspecic and do not distin- The noninvasive recording of spinal or cerebral poten-
guish between the different causes of cognitive decline tials elicited by stimulation of specic afferent pathways
except in rare instances when, for example, the pres- is an important means of monitoring the functional
ence of complexes occurring with a regular repetition integrity of these pathways but does not indicate the
rate (so-called periodic complexes) supports a diagnosis pathologic basis of lesions involving them. Such evoked
of Creutzfeldt-Jakob disease (Fig. 5-1) or subacute scle- potentials (EPs) are so small compared to the back-
rosing panencephalitis. In most patients with demen- ground EEG activity that the responses to a number of
tias, the EEG is normal or diffusely slowed, and the stimuli have to be recorded and averaged with a com-
EEG ndings alone cannot indicate whether a patient puter in order to permit their recognition and deni-
is demented or distinguish between dementia and tion. The background EEG activity, which has no xed
pseudodementia. temporal relationship to the stimulus, is averaged out by
this procedure.
Visual evoked potentials (VEPs) are elicited by mon-
CONTINUOUS EEG MONITORING ocular stimulation with a reversing checkerboard pat-
The brief EEG obtained routinely in the laboratory tern and are recorded from the occipital region in the
often fails to reveal abnormalities that are transient and midline and on either side of the scalp. The compo-
infrequent. Continuous monitoring over 12 or 24 h nent of major clinical importance is the so-called P100
or longer may detect abnormalities or capture clini- response, a positive peak having a latency of approxi-
cal events that would otherwise be missed. The EEG is mately 100 ms. Its presence, latency, and symmetry
often recorded continuously in critically ill patients to over the two sides of the scalp are noted. Amplitude
detect early changes in neurologic status, which is par- may also be measured, but changes in size are much
ticularly useful when the clinical examination is limited. less helpful for the recognition of pathology. VEPs are
Continuous EEG recording in this context has been most useful in detecting dysfunction of the visual path-
used to detect acute events such as nonconvulsive sei- ways anterior to the optic chiasm. In patients with
zures or developing cerebral ischemia, to monitor cere- acute severe optic neuritis, the P100 is frequently lost
bral function in patients with metabolic disorders such or grossly attenuated; as clinical recovery occurs and
as liver failure, and to manage the level of anesthesia in visual acuity improves, the P100 is restored but with
pharmacologically induced coma. an increased latency that generally remains abnormally
prolonged indenitely. The VEP ndings are therefore
helpful in indicating previous or subclinical optic neuri-
tis. They may also be abnormal with ocular abnormali-
MAGNETOENCEPHALOGRAPHY AND ties and with other causes of optic nerve disease, such
MAGNETIC SOURCE IMAGING as ischemia or compression by a tumor. Normal VEPs
may be elicited by ash stimuli in patients with cortical
Recording the magnetic eld of the electrical activity of blindness. Routine VEPs record a mass response over
the brain (magnetoencephalography [MEG]) provides a a relatively large cortical area and thus may be insen-
means of examining cerebral activity that is less subject sitive to localized waveform abnormalities. A newer
to distortion by other biologic tissues than the EEG. technique, multifocal VEP, measures responses from 120
MEG is used in only a few specialized centers because individual sectors within each affected eye, and thus is
of the complexity and expense of the necessary equip- likely to be more sensitive than routine VEP.
ment. It permits the source of activity to be localized Brainstem auditory evoked potentials (BAEPs) are elic-
and coregistered with the MRI in a technique that is ited by monaural stimulation with repetitive clicks and
known as magnetic source imaging. In patients with focal are recorded between the vertex of the scalp and the
30 mastoid process or earlobe. A series of potentials, desig- SSEPs have been used to indicate the completeness of
nated by roman numerals, occurs in the rst 10 ms after the lesion. The presence or early return of a cortically
the stimulus and represents in part the sequential acti- generated response to stimulation of a nerve below
SECTION I

vation of different structures in the pathway between the injured segment of the cord indicates an incom-
the auditory nerve (wave I) and the inferior colliculus plete lesion and thus a better prognosis for functional
(wave V) in the midbrain. The presence, latency, and recovery than otherwise. In surgery, intraoperative EP
interpeak latency of the rst ve positive potentials monitoring of neural structures placed at risk by the
recorded at the vertex are evaluated. The ndings are procedure may permit the early recognition of dys-
helpful in screening for acoustic neuromas, detecting function and thereby permit a neurologic complication
Introduction to Neurology

brainstem pathology, and evaluating comatose patients. to be averted or minimized.


The BAEPs are normal in coma due to metabolic/toxic Visual and auditory acuity may be determined using
disorders or bihemispheric disease but abnormal in the EP techniques in patients whose age or mental state
presence of brainstem pathology. precludes traditional ophthalmologic or audiologic
Somatosensory evoked potentials (SSEPs) are recorded examinations.
over the scalp and spine in response to electrical stimu-
lation of a peripheral (mixed or cutaneous) nerve. The
conguration, polarity, and latency of the responses COGNITIVE EVOKED POTENTIALS
depend on the nerve that is stimulated and on the Certain EP components depend on the mental atten-
recording arrangements. SSEPs are used to evaluate tion of the subject and the setting in which the stimulus
proximal (otherwise inaccessible) portions of the occurs, rather than simply on the physical characteristics
peripheral nervous system and the integrity of the cen- of the stimulus. Such event-related potentials (ERPs)
tral somatosensory pathways. or endogenous potentials are related in some manner
to the cognitive aspects of distinguishing an infrequently
Clinical utility of EPs occurring target stimulus from other stimuli occur-
EP studies may detect and localize lesions in afferent ring more frequently. For clinical purposes, attention
pathways in the central nervous system (CNS). They has been directed particularly at the so-called P3 com-
have been used particularly to investigate patients ponent of the ERP, which is also designated the P300
with suspected multiple sclerosis (MS), the diagnosis component because of its positive polarity and latency
of which requires the recognition of lesions involving of approximately 300400 ms after onset of an audi-
several different regions of the central white matter. tory target stimulus. The P3 component is prolonged
In patients with clinical evidence of only one lesion, in latency in many patients with dementia, whereas
the electrophysiologic recognition of abnormalities in it is generally normal in patients with depression or
other sites helps to suggest or support the diagnosis but other psychiatric disorders that might be mistaken for
does not establish it unequivocally. Multimodality EP dementia. ERPs are, therefore, sometimes helpful in
abnormalities are not specic for MS; they may occur making this distinction when there is clinical uncer-
in AIDS, Lyme disease, systemic lupus erythematosus, tainty, although a response of normal latency does not
neurosyphilis, spinocerebellar degenerations, famil- exclude dementia.
ial spastic paraplegia, and deciency of vitamin E or
B12, among other disorders. The diagnostic utility of
the electrophysiologic ndings therefore depends on MOTOR EVOKED POTENTIALS
the circumstances in which they are found. Abnor- The electrical potentials recorded from muscle or the
malities may aid in the localization of lesions to broad spinal cord following stimulation of the motor cor-
areas of the CNS, but attempts at precise localization tex or central motor pathways are referred to as motor
on electrophysiologic grounds are misleading because evoked potentials. For clinical purposes such responses are
the generators of many components of the EP are recorded most often as the compound muscle action
unknown. potentials elicited by transcutaneous magnetic stimula-
The EP ndings are sometimes of prognostic rel- tion of the motor cortex. A strong but brief magnetic
evance. Bilateral loss of SSEP components that are eld is produced by passing a current through a coil,
generated in the cerebral cortex implies that cognition and this induces stimulating currents in the subjacent
may not be regained in posttraumatic or postanoxic neural tissue. The procedure is painless and apparently
coma, and EP studies may also be useful in evaluating safe. Abnormalities have been described in several neu-
patients with suspected brain death. In patients who rologic disorders with clinical or subclinical involve-
are comatose for uncertain reasons, preserved BAEPs ment of central motor pathways, including MS and
suggest either a metabolic-toxic etiology or bihemi- motor neuron disease. In addition to a possible role in
spheric disease. In patients with spinal cord injuries, the diagnosis of neurologic disorders or in evaluating
the extent of pathologic involvement, the technique 31
provides information of prognostic relevance (e.g., in A 100 V
suggesting the likelihood of recovery of motor func- 10 ms

CHAPTER 5
tion after stroke) and provides a means of monitoring
intraoperatively the functional integrity of central motor B 100 V
tracts. Nevertheless, it is not used widely for clinical
purposes. 100 ms

100 V

Electrodiagnostic Studies of Nervous System Disorders: EEG, E voked Potentials, and EMG
C D E
ELECTROPHYSIOLOGIC STUDIES OF
MUSCLE AND NERVE
10 ms
The motor unit is the basic element subserving motor
function. It is dened as an anterior horn cell, its axon FIGURE 5-3
and neuromuscular junctions, and all the muscle bers Activity recorded during EMG. A. Spontaneous brillation
innervated by the axon. The number of motor units in potentials and positive sharp waves. B. Complex repetitive
a muscle ranges from approximately 10 in the extraocu- discharges recorded in partially denervated muscle at rest.
lar muscles to several thousand in the large muscles of C. Normal triphasic motor unit action potential. D. Small,
the legs. There is considerable variation in the average short-duration, polyphasic motor unit action potential such
number of muscle bers within the motor units of an as is commonly encountered in myopathic disorders. E.
individual muscle, i.e., in the innervation ratio of dif- Long-duration polyphasic motor unit action potential such as
ferent muscles. Thus the innervation ratio is <25 in the may be seen in neuropathic disorders.
human external rectus or platysma muscle and between
1600 and 1700 in the medial head of the gastrocnemius the spontaneous activity of individual motor units) are
muscle. The muscle bers of individual motor units are characteristic of slowly progressive neuropathic disor-
divided into two general types by distinctive contrac- ders, especially those with degeneration of anterior horn
tile properties, histochemical stains, and characteristic cells (such as amyotrophic lateral sclerosis). Myotonic
responses to fatigue. Within each motor unit, all of the dischargeshigh-frequency discharges of potentials
muscle bers are of the same type. derived from single muscle bers that wax and wane
in amplitude and frequencyare the signature of myo-
tonic disorders such as myotonic dystrophy or myoto-
ELECTROMYOGRAPHY
nia congenita but occur occasionally in polymyositis or
The pattern of electrical activity in muscle (i.e., the other, rarer, disorders.
electromyogram [EMG]), both at rest and during activ- Slight voluntary contraction of a muscle leads to acti-
ity, may be recorded from a needle electrode inserted vation of a small number of motor units. The potentials
into the muscle. The nature and pattern of abnormali- generated by any muscle bers of these units that are
ties relate to disorders at different levels of the motor within the pickup range of the needle electrode will be
unit. recorded (Fig. 5-3). The parameters of normal motor
Relaxed muscle normally is electrically silent except unit action potentials depend on the muscle under study
in the end plate region, but abnormal spontaneous and age of the patient, but their duration is normally
activity (Fig. 5-3) occurs in various neuromuscular dis- between 5 and 15 ms, amplitude is between 200 V
orders, especially those associated with denervation or and 2 mV, and most are bi- or triphasic. The number
inammatory changes in affected muscle. Fibrillation of units activated depends on the degree of voluntary
potentials and positive sharp waves (which reect mus- activity. An increase in muscle contraction is associated
cle ber irritability) and complex repetitive discharges with an increase in the number of motor units that are
are most oftenbut not alwaysfound in denervated activated (recruited) and in the frequency with which
muscle and may also occur after muscle injury and in they discharge. With a full contraction, so many motor
certain myopathic disorders, especially inammatory units are normally activated that individual motor unit
disorders such as polymyositis. After an acute neuro- action potentials can no longer be distinguished, and
pathic lesion, they are found earlier in proximal rather a complete interference pattern is said to have been
than distal muscles and sometimes do not develop dis- produced.
tally in the extremities for 46 weeks; once present, The incidence of small, short-duration, polyphasic
they may persist indenitely unless reinnervation occurs motor unit action potentials (i.e., having more than four
or the muscle degenerates so completely that no viable phases) is usually increased in myopathic muscle, and an
tissue remains. Fasciculation potentials (which reect excessive number of units is activated for a specied degree
32 of voluntary activity. By contrast, the loss of motor units Recording
electrodes
that occurs in neuropathic disorders leads to a reduction
in number of units activated during a maximal contrac- Reference Ground
SECTION I

tion and an increase in their ring rate, i.e., there is an Active


incomplete or reduced interference pattern. The congu- Cathode
ration and dimensions of the potentials may also be abnor- Anode
mal, depending on the duration of the neuropathic process
and on whether reinnervation has occurred. The surviv- Stimulating Stimulating
ing motor units are initially normal in conguration but, as electrodes electrodes
Introduction to Neurology

reinnervation occurs, they increase in amplitude and dura-


Stimulation
tion and become polyphasic (Fig. 5-3). site
Action potentials from the same motor unit some-
Wrist
times re with a consistent temporal relationship to
each other, so that double, triple, or multiple discharges
are recorded, especially in tetany, hemifacial spasm, or
myokymia. Below
Electrical silence characterizes the involuntary, sus- elbow

tained muscle contraction that occurs in phosphorylase


deciency, which is designated a contracture.
EMG enables disorders of the motor units to be Above
detected and characterized as either neurogenic or myo- elbow
pathic. In neurogenic disorders, the pattern of affected
muscles may localize the lesion to the anterior horn
cells or to a specic site as the axons traverse a nerve Axilla 5 mV
root, limb plexus, and peripheral nerve to their termi- 10 ms
nal arborizations. The ndings do not enable a specic
FIGURE 5-4
etiologic diagnosis to be made, however, except in con-
Arrangement for motor conduction studies of the ulnar
junction with the clinical ndings and results of other nerve. Responses are recorded with a surface electrode
laboratory studies. from the abductor digiti minimi muscle to supramaximal
The ndings may provide a guide to the severity of stimulation of the nerve at different sites, and are shown in
an acute disorder of a peripheral or cranial nerve (by the lower panel. (From Aminoff MJ: Electromyography in
indicating whether denervation has occurred and the Clinical Practice: Electrodiagnostic Aspects of Neuromuscular
completeness of the lesion) and whether the pathologic Disease, 3rd ed. New York, Churchill Livingstone, 1998.)
process is active or progressive in chronic or degenera-
tive disorders such as amyotrophic lateral sclerosis. Such
information is important for prognostic purposes. velocity to be determined in the fastest-conducting
Various quantitative EMG approaches have been motor bers between the points of stimulation. The
developed. The most common is to determine the latency and amplitude of the electrical response of
mean duration and amplitude of 20 motor unit action muscle (i.e., of the compound muscle action poten-
potentials using a standardized technique. The tech- tial) to stimulation of its motor nerve at a distal site
nique of macro-EMG provides information about the are also compared with values dened in normal sub-
number and size of muscle bers in a larger volume of jects. Sensory nerve conduction studies are performed
the motor unit territory and has also been used to esti- by determining the conduction velocity and ampli-
mate the number of motor units in a muscle. Scanning tude of action potentials in sensory bers when these
EMG is a computer-based technique that has been used bers are stimulated at one point and the responses
to study the topography of motor unit action potentials are recorded at another point along the course of the
and, in particular, the spatial and temporal distribution nerve. In adults, conduction velocity in the arms is
of activity in individual units. The technique of single- normally between 50 and 70 m/s, and in the legs is
ber EMG is discussed separately below. between 40 and 60 m/s.
Nerve conduction studies complement the EMG
examination, enabling the presence and extent of periph-
eral nerve pathology to be determined. They are particu-
NERVE CONDUCTION STUDIES larly helpful in determining whether sensory symptoms are
Recording of the electrical response of a muscle arising from pathology proximal or distal to the dorsal root
to stimulation of its motor nerve at two or more ganglia (in the former instance, peripheral sensory conduc-
points along its course (Fig. 5-4) permits conduction tion studies will be normal) and whether neuromuscular
dysfunction relates to peripheral nerve disease. In patients F-WAVE STUDIES 33
with a mononeuropathy, they are invaluable as a means
of localizing a focal lesion, determining the extent and Stimulation of a motor nerve causes impulses to travel
antidromically (i.e., toward the spinal cord) as well as

CHAPTER 5
severity of the underlying pathology, providing a guide
to prognosis, and detecting subclinical involvement of orthodromically (to the nerve terminals). Such anti-
other peripheral nerves. They enable a polyneuropathy dromic impulses cause a few of the anterior horn cells
to be distinguished from a mononeuropathy multiplex to discharge, producing a small motor response that
when this is not possible clinically, an important distinc- occurs considerably later than the direct response elic-
tion because of the etiologic implications. Nerve conduc- ited by nerve stimulation. The F wave so elicited is
sometimes abnormal (absent or delayed) with proximal

Electrodiagnostic Studies of Nervous System Disorders: EEG, E voked Potentials, and EMG
tion studies provide a means of following the progression
and therapeutic response of peripheral nerve disorders pathology of the peripheral nervous system, such as a
and are being used increasingly for this purpose in clinical radiculopathy, and may therefore be helpful in detect-
trials. They may suggest the underlying pathologic basis ing abnormalities when conventional nerve conduc-
in individual cases. Conduction velocity is often mark- tion studies are normal. In general, however, the clinical
edly slowed, terminal motor latencies are prolonged, utility of F-wave studies has been disappointing, except
and compound motor and sensory nerve action poten- perhaps in Guillain-Barr syndrome, where they are
tials may be dispersed in the demyelinative neuropathies often absent or delayed.
(such as in Guillain-Barr syndrome, chronic inamma-
tory polyneuropathy, metachromatic leukodystrophy,
or certain hereditary neuropathies); conduction block H-REFLEX STUDIES
is frequent in acquired varieties of these neuropathies. The H reex is easily recorded only from the soleus
By contrast, conduction velocity is normal or slowed muscle (S1) in normal adults. It is elicited by low-
only mildly, sensory nerve action potentials are small or intensity stimulation of the tibial nerve and represents a
absent, and there is EMG evidence of denervation in monosynaptic reex in which spindle (Ia) afferent bers
axonal neuropathies such as occur in association with constitute the afferent arc and alpha motor axons the
metabolic or toxic disorders. efferent pathway. The H reexes are often absent bilat-
The utility and complementary role of EMG and erally in elderly patients or with polyneuropathies and
nerve conduction studies are best illustrated by refer- may be lost unilaterally in S1 radiculopathies.
ence to a common clinical problem. Numbness and
paresthesias of the little nger and associated wasting
of the intrinsic muscles of the hand may result from
MUSCLE RESPONSE TO REPETITIVE
a spinal cord lesion, C8/T1 radiculopathy, brachial
NERVE STIMULATION
plexopathy (lower trunk or medial cord), or a lesion
of the ulnar nerve. If sensory nerve action poten- The size of the electrical response of a muscle to supra-
tials can be recorded normally at the wrist following maximal electrical stimulation of its motor nerve relates
stimulation of the digital bers in the affected n- to the number of muscle bers that are activated. Neu-
ger, the pathology is probably proximal to the dor- romuscular transmission can be tested by several dif-
sal root ganglia (i.e., there is a radiculopathy or more ferent protocols, but the most helpful is to record with
central lesion); absence of the sensory potentials, by surface electrodes the electrical response of a muscle to
contrast, suggests distal pathology. EMG examination supramaximal stimulation of its motor nerve by repeti-
will indicate whether the pattern of affected muscles tive (23 Hz) shocks delivered before and at selected
conforms to radicular or ulnar nerve territory, or is intervals after a maximal voluntary contraction.
more extensive (thereby favoring a plexopathy). There is normally little or no change in size of the
Ulnar motor conduction studies will generally also compound muscle action potential following repetitive
distinguish between a radiculopathy (normal ndings) stimulation of a motor nerve at 23 Hz with stimuli
and ulnar neuropathy (abnormal ndings) and will delivered at intervals after voluntary contraction of the
often identify the site of an ulnar nerve lesion. The muscle for about 2030 s, even though preceding activ-
nerve is stimulated at several points along its course ity in the junctional region inuences the release of ace-
to determine whether the compound action potential tylcholine and thus the size of the end-plate potentials
recorded from a distal muscle that it supplies shows a elicited by a test stimulus. This is because more acetyl-
marked alteration in size or area or a disproportion- choline is normally released than is required to bring the
ate change in latency, with stimulation at a particu- motor end-plate potentials to the threshold for generat-
lar site. The electrophysiologic ndings thus permit ing muscle ber action potentials. In disorders of neu-
a denitive diagnosis to be made and specic treat- romuscular transmission this safety factor is reduced.
ment instituted in circumstances where there is clini- Thus in myasthenia gravis, repetitive stimulation, par-
cal ambiguity. ticularly at a rate of between 2 and 5 Hz, may lead to a
34 depression of neuromuscular transmission, with a dec- record action potentials from two muscle bers belong-
rement in size of the response recorded from affected ing to the same motor unit. The time interval between
muscles. Similarly, immediately after a period of maxi- the two potentials will vary in consecutive discharges;
SECTION I

mal voluntary activity, single or repetitive stimuli of this is called the neuromuscular jitter. The jitter can be
the motor nerve may elicit larger muscle responses than quantied as the mean difference between consecutive
before, indicating that more muscle bers are respond- interpotential intervals and is normally between 10 and
ing. This postactivation facilitation of neuromuscu- 50 s. This value is increased when neuromuscular
lar transmission is followed by a longer-lasting period transmission is disturbed for any reason, and in some
of depression, maximal between 2 and 4 min after the instances impulses in individual muscle bers may fail
Introduction to Neurology

conditioning period and lasting for as long as 10 min or to occur because of impulse blocking at the neuromus-
so, during which responses are reduced in size. cular junction. Single-ber EMG is more sensitive than
Decrementing responses to repetitive stimulation repetitive nerve stimulation or determination of acetyl-
at 25 Hz are common in myasthenia gravis but may choline receptor antibody levels in diagnosing myasthe-
also occur in the congenital myasthenic syndromes. In nia gravis.
Lambert-Eaton myasthenic syndrome, in which there is Single-ber EMG can also be used to determine the
defective release of acetylcholine at the neuromuscular mean ber density of motor units (i.e., mean number of
junction, the compound muscle action potential elicited muscle bers per motor unit within the recording area)
by a single stimulus is generally very small. With repeti- and to estimate the number of motor units in a muscle,
tive stimulation at rates of up to 10 Hz, the rst few but this is of less immediate clinical relevance.
responses may decline in size, but subsequent responses
increase. If faster rates of stimulation are used (2050
Hz), the increment may be dramatic so that the ampli-
tude of compound muscle action potentials eventually BLINK REFLEXES
reaches a size that is several times larger than the ini- Electrical or mechanical stimulation of the supraorbital
tial response. In patients with botulism, the response to nerve on one side leads to two separate reex responses
repetitive stimulation is similar to that in Lambert-Eaton of the orbicularis oculian ipsilateral R1 response hav-
myasthenic syndrome, although the ndings are some- ing a latency of approximately 10 ms and a bilateral
what more variable and not all muscles are affected. R2 response with a latency in the order of 30 ms. The
trigeminal and facial nerves constitute the afferent and
efferent arcs of the reex, respectively. Abnormalities of
SINGLE-FIBER ELECTROMYOGRAPHY either nerve or intrinsic lesions of the medulla or pons
This technique is particularly helpful in detecting dis- may lead to uni- or bilateral loss of the response, and
orders of neuromuscular transmission. A special needle the ndings may therefore be helpful in identifying or
electrode is placed within a muscle and positioned to localizing such pathology.
CHAPTER 6

TECHNIQUE OF LUMBAR PUNCTURE

Elizabeth Robbins Stephen L. Hauser

In experienced hands, lumbar puncture (LP) is usually low-molecular-weight heparin are at increased risk of
a safe procedure. Major complications are extremely post-LP spinal or epidural hematoma, and doses should
uncommon but can include cerebral herniation, injury be held for 24 h before the procedure.
to the spinal cord or nerve roots, hemorrhage, or infec- LP should not be performed through infected skin
tion. Minor complications occur with greater frequency as organisms can be introduced into the subarachnoid
and can include backache, post-LP headache, and radic- space (SAS).
ular pain or numbness.

ANALGESIA
IMAGING AND LABORATORY STUDIES
Anxiety and pain can be minimized prior to begin-
PRIOR TO LP
ning the procedure. Anxiety can be allayed by the use
Patients with an altered level of consciousness, a focal of lorazepam, 12 mg given PO 30 min prior to the
neurologic decit, new-onset seizure, papilledema, or procedure or IV 5 min prior to the procedure. Topi-
an immunocompromised state are at increased risk for cal anesthesia can be achieved by the application of a
potentially fatal cerebellar or tentorial herniation fol- lidocaine-based cream. Lidocaine 4% is effective when
lowing LP. Neuroimaging should be obtained in these applied 30 min prior to the procedure; lidocaine/pri-
patients prior to LP to exclude a focal mass lesion or locaine requires 60120 min. The cream should be
diffuse swelling. Imaging studies should include the applied in a thick layer so that it completely covers the
spine in patients with symptoms suggesting spinal cord skin; an occlusive dressing is used to keep the cream in
compression, such as back pain, leg weakness, urinary place.
retention, or incontinence. In patients with suspected
meningitis who require neuroimaging prior to diag-
nostic LP, administration of antibiotics, preferably fol- POSITIONING
lowing blood culture, should precede the neuroimaging
study. Proper positioning of the patient is essential. The pro-
Patients receiving therapeutic anticoagulation or cedure should be performed on a rm surface; if the
those with coagulation defects including thrombocy- procedure is to be performed at the bedside, the patient
topenia are at increased risk of post-LP spinal subdural should be positioned at the edge of the bed and not
or epidural hematomas, either of which can produce in the middle. The patient is asked to lie on his or
permanent nerve injury and/or paralysis. If a bleeding her side, facing away from the examiner, and to roll
disorder is suspected, the platelet count, international up into a ball. The neck is gently ante-exed and the
normalized ratio (INR), and partial thromboplastin time thighs pulled up toward the abdomen; the shoulders and
should be checked prior to lumbar puncture. There are pelvis should be vertically aligned without forward or
no data available to assess the safety of LP in patients backward tilt (Fig. 6-1). The spinal cord terminates
with low platelet counts; a count of <20,000/L is con- at approximately the L1 vertebral level in 94% of indi-
sidered to be a contraindication to LP. Bleeding com- viduals. In the remaining 6%, the conus extends to the
plications rarely occur in patients with platelet counts L2-L3 interspace. LP is therefore performed at or below
50,000/L and an INR 1.5. Patients receiving the L3-L4 interspace. A useful anatomic guide is a line
35
36 Level of the iliac crests 510 mini-boluses are injected, using a total of 5 mL
of lidocaine.
L3L4 interspace If possible, the LP should be delayed for 1015 min
SECTION I

following the completion of the injection of anesthetic;


this signicantly decreases and can even eliminate pain
from the procedure. Even a delay of 5 min will help to
reduce pain.
FIGURE 6-1 The LP needle (typically 20- to 22-gauge) is inserted
Proper positioning of a patient in the lateral decubitus in the midline, midway between two spinous processes,
Introduction to Neurology

position. Note that the shoulders and hips are in a vertical and slowly advanced. The bevel of the needle should be
plane; the torso is perpendicular to the bed. (From RP Simon maintained in a horizontal position, parallel to the direc-
et al [eds]: Clinical Neurology, 7th ed. New York, McGraw- tion of the dural bers and with the at portion of the
Hill, 2009.) bevel pointed upward; this minimizes injury to the bers
as the dura is penetrated. When lumbar puncture is per-
drawn between the posterior superior iliac crests, which formed in patients who are sitting, the bevel should be
corresponds closely to the level of the L3-L4 interspace. maintained in the vertical position. In most adults, the
The interspace is chosen following gentle palpation to needle is advanced 45 cm (12 in.) before the SAS is
identify the spinous processes at each lumbar level. reached; the examiner usually recognizes entry as a sud-
An alternative to the lateral recumbent position is the den release of resistance, a pop. If no uid appears
seated position. The patient sits at the side of the bed, despite apparently correct needle placement, then the
with feet supported on a chair. The patient is instructed needle may be rotated 90180. If there is still no uid,
to curl forward, trying to touch the nose to the umbi- the stylet is reinserted and the needle is advanced slightly.
licus. It is important that the patient not simply lean Some examiners halt needle advancement periodically
forward onto a bedside tabletop, as this is not an opti- to remove the stylet and check for ow of cerebrospinal
mal position for opening up the spinous processes. LP uid (CSF). If the needle cannot be advanced because it
is sometimes more easily performed in obese patients if hits bone, if the patient experiences sharp radiating pain
they are sitting. A disadvantage of the seated position is down one leg, or if no uid appears (dry tap), the
that measurement of opening pressure may not be accu- needle is partially withdrawn and reinserted at a differ-
rate. In situations in which LP is difcult using palpable ent angle. If on the second attempt the needle still hits
spinal landmarks, bedside ultrasound to guide needle bone (indicating lack of success in introducing it between
placement may be employed. the spinous processes), then the needle should be com-
pletely withdrawn and the patient should be repositioned.
The second attempt is sometimes more successful if the
TECHNIQUE patient straightens the spine completely prior to reposi-
tioning. The needle can then be reinserted at the same
Once the desired target for needle insertion has been level or at an adjacent one.
identied, the examiner should put on sterile gloves. Once the SAS is reached, a manometer is attached
After cleansing the skin with povidone-iodine or simi- to the needle and the opening pressure measured. The
lar disinfectant, the area is draped with a sterile cloth; examiner should look for normal oscillations in CSF
the needle insertion site is blotted dry using a sterile pressure associated with pulse and respirations. The
gauze pad. Proper local disinfection reduces the risk of upper limit of normal opening pressure with the patient
introducing skin bacteria into the SAS or other sites. supine is 180 mmH2O in adults but may be as high as
Local anesthetic, typically 1% lidocaine, 35 mL total, is 200250 mmH2O in obese adults.
injected into the subcutaneous tissue; in nonemergency CSF is allowed to drip into collection tubes; it should
situations a topical anesthetic cream can be applied (see not be withdrawn with a syringe. Depending on the
above). When time permits, pain associated with the clinical indication, uid is then obtained for studies
injection of lidocaine can be minimized by slow, serial including: (1) cell count with differential; (2) protein
injections, each one progressively deeper than the last, and glucose concentrations; (3) culture (bacterial, fun-
over a period of 5 min. Approximately 0.51 mL of gal, mycobacterial, viral); (4) smears (e.g., Grams and
lidocaine is injected at a time; the needle is not usu- acid-fast stained smears); (5) antigen tests (e.g., latex
ally withdrawn between injections. A pause of 15 s agglutination); (6) polymerase chain reaction (PCR)
between injections helps to minimize the pain of the amplication of DNA or RNA of microorganisms (e.g.,
subsequent injection. The goal is to inject each mini- herpes simplex virus, enteroviruses); (7) antibody lev-
bolus of anesthetic into an area of skin that has become els against microorganisms; (8) immunoelectrophoresis
numb from the preceding injection. Approximately for determination of -globulin level and oligoclonal
banding; and (9) cytology. Although 15 mL of CSF is when a patient is upright there is probably dilation and 37
sufcient to obtain all of the listed studies, the yield of tension placed on the brains anchoring structures, the
fungal and mycobacterial cultures and cytology increases pain-sensitive dural sinuses, resulting in pain. Although

CHAPTER 6
when larger volumes are sampled. In general 2030 mL intracranial hypotension is the usual explanation for
may be safely removed from adults. severe LP headache, the syndrome can occur in patients
A bloody tap due to penetration of a meningeal ves- with normal CSF pressure.
sel (a traumatic tap) may result in confusion with Because post-LP headache usually resolves without
subarachnoid hemorrhage (SAH). In these situations specic treatment, care is largely supportive with oral
a specimen of CSF should be centrifuged immediately analgesics (acetaminophen, nonsteroidal anti-inamma-

Technique of Lumbar Puncture


after it is obtained; clear supernatant following CSF tory drugs, opioids [Chap. 7]) and antiemetics. Patients
centrifugation supports the diagnosis of a bloody tap, may obtain relief by lying in a comfortable (especially a
whereas xanthochromic supernatant suggests SAH. In recumbent or head-down Trendelenburg) position. For
general, bloody CSF due to the penetration of a men- some patients, beverages with caffeine can provide tem-
ingeal vessel clears gradually in successive tubes, whereas porary pain relief.
blood due to SAH does not. In addition to SAH, xan- For patients with persistent pain, treatment with IV
thochromic CSF may also be present in patients with caffeine (500 mg in 500 mL saline administered over
liver disease and when the CSF protein concentration is 2 h) may be effective; atrial brillation is a rare side effect.
markedly elevated (>1.52 g/L [150200 mg/dL]). Alternatively, an epidural blood patch accomplished by
Prior to removing the LP needle, the stylet is rein- injection of 15 mL of autologous whole blood is usu-
serted to avoid the possibility of entrapment of a nerve ally effective. This procedure is most often performed by
root in the dura as the needle is being withdrawn; a pain specialist or anesthesiologist. The blood patch has
entrapment could result in a dural CSF leak, causing an immediate effect, making it unlikely that sealing off a
headache. Some practitioners question the safety of this dural hole with blood clot is its sole mechanism of action.
maneuver, with its potential risk of causing a needle- The acute benet may be due to compression of the CSF
stick injury to the examiner. Injury is unlikely, how- space by the clot, increasing CSF pressure. Some clini-
ever, given the exibility of the small-diameter stylet, cians reserve epidural blood patch for patients who do not
which tends to bend, rather than penetrate, on contact. respond to caffeine, while others prefer to use blood patch
Following LP, the patient is customarily positioned in a as initial management for unremitting post-LP symptoms.
comfortable, recumbent position for 1 h before rising, Strategies to decrease the incidence of post-LP head-
although this may be unnecessary as it does not appear ache are listed in Table 6-1. Use of a smaller caliber
to affect the development of headache (see below). needle is associated with a lower risk: In one study, the
risk of headache following use of a 24- to 27-gauge
standard (Quincke) needle was 512%, compared
POST-LP HEADACHE to 2040% when a 20- or 22-gauge needle was used.
The smallest gauge needles usually require the use of
The principal complication of LP is headache, occur- an introducer needle and are associated with a slower
ring in 1030% of patients. Younger age and female CSF ow rate. Use of an atraumatic (Sprotte, pen-
gender are associated with an increased risk of post-LP cil point, or noncutting) needle also reduces the
headache. Headache usually begins within 48 h but incidence of moderate to severe headache compared
may be delayed for up to 12 days. Head pain is dramati-
cally positional; it begins when the patient sits or stands
upright; there is relief upon reclining or with abdomi- TABLE 6-1
nal compression. The longer the patient is upright, the REDUCING THE INCIDENCE OF POST-LP HEADACHE
longer the latency before head pain subsides. The pain
Effective Strategies
is usually a dull ache but may be throbbing; its location
is occipitofrontal. Nausea and stiff neck often accom- Use of small-diameter needle (22-gauge or smaller)
pany headache, and occasionally, patients report blurred Use of atraumatic needle (Sprotte and others)
Replacement of stylet prior to removal of needle
vision, photophobia, tinnitus, and vertigo. In more than
Insertion of needle with bevel oriented in a cephalad to
three-quarters of patients, symptoms completely resolve caudad direction (when using standard needle)
within a week, but in a minority they can persist for
Ineffective Strategies
weeks or even months.
Post-LP headache is caused by a drop in CSF pres- Bed rest (up to 4 h) following LP
sure related to persistent leakage of CSF at the site where Supplemental uids
the needle entered the subarachnoid space. Loss of CSF Minimizing the volume of spinal uid removed
Immediate mobilization following LP
volume decreases the brains supportive cushion, so that
38 TABLE 6-2
CEREBROSPINAL FLUIDa
SECTION I

CONVENTIONAL
CONSTITUENT SI UNITS UNITS
Glucose 2.223.89 mmol/L 4070 mg/dL

FIGURE 6-2 Lactate 12 mmol/L 1020 mg/dL


Comparison of the standard (traumatic or Quincke) LP Total protein
needle with the atraumatic (Sprotte). The atraumatic Lumbar 0.150.5 g/L 1550 mg/dL
Introduction to Neurology

needle has its opening on the top surface of the needle, a


Cisternal 0.150.25 g/L 1525 mg/dL
design intended to reduce the chance of cutting dural bers
that, by protruding through the dura, could be responsible Ventricular 0.060.15 g/L 615 mg/dL
for subsequent CSF uid leak and post-LP headache. (From Albumin 0.0660.442 g/L 6.644.2 mg/dL
SR Thomas et al: BMJ 321:986, 2000.) IgG 0.0090.057 g/L 0.95.7 mg/dL
b
with standard LP (Quincke, or traumatic) needles IgG index 0.290.59
(Fig. 6-2). However, because atraumatic needles are Oligoclonal bands <2 bands not
more difcult to use, more attempts may be required (OGB) present in
to perform the LP, particularly in overweight patients. matched serum
It may also be necessary to use an introducer with the sample
atraumatic needle, which does not have the customary Ammonia 1547 mol/L 2580 g/dL
cutting, beveled tip. There is a low risk of needle dam- CSF pressure 50180 mmH2O
age, e.g., breakage, with the Sprotte atraumatic needle. CSF volume (adult) 150 mL
Another strategy to decrease the incidence of headache
Red blood cells 0 0
is to replace the stylet before removing the LP needle.
Patients are often advised to remain in a recumbent Leukocytes
position for up to an hour following lumbar puncture. Total 05 mononuclear
However, studies comparing mobilization immediately cells per mm3
following LP with bed rest for periods up to 4 h show Differential
no signicant differences in the incidence of headache, Lymphocytes 6070%
suggesting that the customary practice of remaining in a
Monocytes 3050%
recumbent position post-LP may be unnecessary.
Neutrophils None

a
Because cerebrospinal uid concentrations are equilibrium values,
NORMAL VALUES measurements of the same parameters in blood plasma obtained
at the same time are recommended. However, there is a time lag in
(See Table 6-2) In uninfected CSF, the normal white attainment of equilibrium, and cerebrospinal levels of plasma con-
stituents that can uctuate rapidly (such as plasma glucose) may not
blood cell count is fewer than ve mononuclear cells
achieve stable values until after a signicant lag phase.
(lymphocytes and monocytes) per L. Polymorpho- b
IgG index = CSF IgG (mg/dL) serum albumin (g/dL)/serum IgG (g/
nuclear leukocytes (PMNs) are not found in normal dL) CSF albumin (mg/dL).
unconcentrated CSF; however, rare PMNs can be
found in centrifuged or concentrated CSF specimens
such as those utilized for cytologic examination. Red
blood cells (RBCs) are not normally present in CSF;
if RBCs are present from a traumatic tap, their num-
ber decreases as additional CSF is collected. CSF glu-
cose concentrations <2.2 mmol/L (<40 mg/dL) are
abnormal.
SECTION II

CLINICAL
MANIFESTATIONS OF
NEUROLOGIC DISEASE
CHAPTER 7

PAIN: PATHOPHYSIOLOGY AND MANAGEMENT

James P. Rathmell Howard L. Fields

The task of medicine is to preserve and restore health neurons, and sympathetic postganglionic neurons
and to relieve suffering. Understanding pain is essen- (Fig. 7-1). The cell bodies of primary sensory afferents
tial to both of these goals. Because pain is universally are located in the dorsal root ganglia in the vertebral
understood as a signal of disease, it is the most com- foramina. The primary afferent axon has two branches:
mon symptom that brings a patient to a physicians one projects centrally into the spinal cord and the other
attention. The function of the pain sensory system is projects peripherally to innervate tissues. Primary affer-
to protect the body and maintain homeostasis. It does ents are classied by their diameter, degree of myelina-
this by detecting, localizing, and identifying potential or tion, and conduction velocity. The largest-diameter
actual tissue-damaging processes. Because different dis- afferent bers, A-beta (A), respond maximally to light
eases produce characteristic patterns of tissue damage, touch and/or moving stimuli; they are present primarily
the quality, time course, and location of a patients pain in nerves that innervate the skin. In normal individuals,
complaint provide important diagnostic clues. It is the the activity of these bers does not produce pain. There
physicians responsibility to provide rapid and effective are two other classes of primary afferents: the small-
pain relief. diameter myelinated A-delta (A) and the unmyelin-
ated (C ber) axons (Fig. 7-1). These bers are present
in nerves to the skin and to deep somatic and visceral
structures. Some tissues, such as the cornea, are inner-
THE PAIN SENSORY SYSTEM
vated only by A and C ber afferents. Most A and C
Pain is an unpleasant sensation localized to a part of the ber afferents respond maximally only to intense (pain-
body. It is often described in terms of a penetrating or ful) stimuli and produce the subjective experience of
tissue-destructive process (e.g., stabbing, burning, twist- pain when they are electrically stimulated; this denes
ing, tearing, squeezing) and/or of a bodily or emotional them as primary afferent nociceptors (pain receptors). The
reaction (e.g., terrifying, nauseating, sickening). Further- ability to detect painful stimuli is completely abolished
more, any pain of moderate or higher intensity is accom- when conduction in A and C ber axons is blocked.
panied by anxiety and the urge to escape or terminate the Individual primary afferent nociceptors can respond
feeling. These properties illustrate the duality of pain: it to several different types of noxious stimuli. For exam-
is both sensation and emotion. When it is acute, pain is ple, most nociceptors respond to heat; intense cold;
characteristically associated with behavioral arousal and intense mechanical stimuli, such as a pinch; changes in
a stress response consisting of increased blood pressure, pH, particularly an acidic environment; and application
heart rate, pupil diameter, and plasma cortisol levels. In of chemical irritants including adenosine triphosphate
addition, local muscle contraction (e.g., limb exion, (ATP), serotonin, bradykinin, and histamine.
abdominal wall rigidity) is often present.
Sensitization
PERIPHERAL MECHANISMS When intense, repeated, or prolonged stimuli are
applied to damaged or inamed tissues, the threshold
The primary afferent nociceptor
for activating primary afferent nociceptors is lowered,
A peripheral nerve consists of the axons of three differ- and the frequency of ring is higher for all stimulus
ent types of neurons: primary sensory afferents, motor intensities. Inammatory mediators such as bradykinin,

40
Dorsal root 41
ganglion

Peripheral nerve
Spinal
cord

CHAPTER 7
A
C
Sympathetic
Sympathetic preganglionic
postganglionic

Pain: Pathophysiology and Management


FIGURE 7-1
Components of a typical cutaneous nerve. There are two ganglion. Primary afferents include those with large-diameter
distinct functional categories of axons: primary afferents myelinated (A), small-diameter myelinated (A), and unmy-
with cell bodies in the dorsal root ganglion, and sympathetic elinated (C) axons. All sympathetic postganglionic bers are
postganglionic bers with cell bodies in the sympathetic unmyelinated.

nerve-growth factor, some prostaglandins, and leukotri- A large proportion of A and C ber afferents inner-
enes contribute to this process, which is called sensitiza- vating viscera are completely insensitive in normal non-
tion. Sensitization occurs at the level of the peripheral injured, noninamed tissue. That is, they cannot be
nerve terminal (peripheral sensitization) as well as at the activated by known mechanical or thermal stimuli and
level of the dorsal horn of the spinal cord (central sensi- are not spontaneously active. However, in the presence
tization). Peripheral sensitization occurs in damaged or of inammatory mediators, these afferents become sen-
inamed tissues, when inammatory mediators activate sitive to mechanical stimuli. Such afferents have been
intracellular signal transduction in nociceptors, prompt- termed silent nociceptors, and their characteristic proper-
ing an increase in the production, transport, and mem- ties may explain how, under pathologic conditions, the
brane insertion of chemically gated and voltage-gated relatively insensitive deep structures can become the
ion channels. These changes increase the excitability of source of severe and debilitating pain and tenderness.
nociceptor terminals and lower their threshold for acti- Low pH, prostaglandins, leukotrienes, and other inam-
vation by mechanical, thermal, and chemical stimuli. matory mediators such as bradykinin play a signicant
Central sensitization occurs when activity, generated by role in sensitization.
nociceptors during inammation, enhances the excit-
ability of nerve cells in the dorsal horn of the spinal
cord. Following injury and resultant sensitization, nor-
Nociceptor-induced inammation
mally innocuous stimuli can produce pain. Sensitiza-
tion is a clinically important process that contributes to Primary afferent nociceptors also have a neuroeffec-
tenderness, soreness, and hyperalgesia (increased pain tor function. Most nociceptors contain polypeptide
intensity in response to the same noxious stimulus; e.g., mediators that are released from their peripheral termi-
moderate pressure causes severe pain). A striking exam- nals when they are activated (Fig. 7-2). An example
ple of sensitization is sunburned skin, in which severe is substance P, an 11-amino-acid peptide. Substance P
pain can be produced by a gentle slap on the back or a is released from primary afferent nociceptors and has
warm shower. multiple biologic activities. It is a potent vasodilator,
Sensitization is of particular importance for pain and degranulates mast cells, is a chemoattractant for leu-
tenderness in deep tissues. Viscera are normally relatively kocytes, and increases the production and release of
insensitive to noxious mechanical and thermal stimuli, inammatory mediators. Interestingly, depletion of sub-
although hollow viscera do generate signicant discomfort stance P from joints reduces the severity of experimen-
when distended. In contrast, when affected by a disease tal arthritis. Primary afferent nociceptors are not simply
process with an inammatory component, deep structures passive messengers of threats to tissue injury but also
such as joints or hollow viscera characteristically become play an active role in tissue protection through these
exquisitely sensitive to mechanical stimulation. neuroeffector functions.
42 A Primary activation Skin

K+

PG
BK
H+
SECTION II

Viscus Anterolateral
tract axon

FIGURE 7-3
The convergence-projection hypothesis of referred pain.
Clinical Manifestations of Neurologic Disease

According to this hypothesis, visceral afferent nociceptors


B Secondary activation converge on the same pain-projection neurons as the affer-
ents from the somatic structures in which the pain is per-
ceived. The brain has no way of knowing the actual source of
input and mistakenly projects the sensation to the somatic
structure.

Mast cell
terminals of primary afferent axons contact spinal neu-
SP H
SP rons that transmit the pain signal to brain sites involved
in pain perception. When primary afferents are acti-
vated by noxious stimuli, they release neurotransmit-
5HT BK ters from their terminals that excite the spinal cord
Platelet neurons. The major neurotransmitter released is gluta-
mate, which rapidly excites dorsal horn neurons. Pri-
mary afferent nociceptor terminals also release peptides,
including substance P and calcitonin gene-related pep-
FIGURE 7-2 tide, which produce a slower and longer-lasting excita-
Events leading to activation, sensitization, and spread tion of the dorsal horn neurons. The axon of each pri-
of sensitization of primary afferent nociceptor terminals. mary afferent contacts many spinal neurons, and each
A. Direct activation by intense pressure and consequent cell spinal neuron receives convergent inputs from many
damage. Cell damage induces lower pH (H+) and leads to primary afferents.
release of potassium (K+) and to synthesis of prostaglandins The convergence of sensory inputs to a single spinal
(PG) and bradykinin (BK). Prostaglandins increase the sensi- pain-transmission neuron is of great importance because
tivity of the terminal to bradykinin and other pain-producing it underlies the phenomenon of referred pain. All spi-
substances. B. Secondary activation. Impulses generated in
nal neurons that receive input from the viscera and deep
the stimulated terminal propagate not only to the spinal cord
musculoskeletal structures also receive input from the
but also into other terminal branches where they induce the
skin. The convergence patterns are determined by the
release of peptides, including substance P (SP). Substance
spinal segment of the dorsal root ganglion that supplies
P causes vasodilation and neurogenic edema with further
accumulation of bradykinin (BK). Substance P also causes
the afferent innervation of a structure. For example, the
the release of histamine (H) from mast cells and serotonin
afferents that supply the central diaphragm are derived
(5HT) from platelets. from the third and fourth cervical dorsal root ganglia.
Primary afferents with cell bodies in these same ganglia
supply the skin of the shoulder and lower neck. Thus,
CENTRAL MECHANISMS sensory inputs from both the shoulder skin and the cen-
tral diaphragm converge on pain-transmission neurons
The spinal cord and referred pain
in the third and fourth cervical spinal segments. Because
The axons of primary afferent nociceptors enter the of this convergence and the fact that the spinal neurons are most
spinal cord via the dorsal root. They terminate in the often activated by inputs from the skin, activity evoked in spi-
dorsal horn of the spinal gray matter (Fig. 7-3). The nal neurons by input from deep structures is mislocalized by
the patient to a place that roughly corresponds with the region 43
of skin innervated by the same spinal segment. Thus, inam- A F B
mation near the central diaphragm is usually reported as C
shoulder discomfort. This spatial displacement of pain
sensation from the site of the injury that produces it is SS
known as referred pain.
Thalamus
Hypothalamus
Ascending pathways for pain

CHAPTER 7
A majority of spinal neurons contacted by primary affer-
ent nociceptors send their axons to the contralateral Midbrain
thalamus. These axons form the contralateral spinotha- Spinothalamic
lamic tract, which lies in the anterolateral white matter tract
of the spinal cord, the lateral edge of the medulla, and Medulla
the lateral pons and midbrain. The spinothalamic path-
way is crucial for pain sensation in humans. Interruption Injury

Pain: Pathophysiology and Management


of this pathway produces permanent decits in pain and
temperature discrimination.
Spinothalamic tract axons ascend to several regions
of the thalamus. There is tremendous divergence of the
pain signal from these thalamic sites to broad areas of Spinal
cord
the cerebral cortex that subserve different aspects of the
pain experience (Fig. 7-4). One of the thalamic pro- FIGURE 7-4
jections is to the somatosensory cortex. This projec- Pain transmission and modulatory pathways. A. Trans-
tion mediates the purely sensory aspects of pain, i.e., its mission system for nociceptive messages. Noxious stimuli
location, intensity, and quality. Other thalamic neurons activate the sensitive peripheral ending of the primary afferent
project to cortical regions that are linked to emotional nociceptor by the process of transduction. The message
responses, such as the cingulate gyrus and other areas is then transmitted over the peripheral nerve to the spi-
of the frontal lobes, including the insular cortex. These nal cord, where it synapses with cells of origin of the major
pathways to the frontal cortex subserve the affective or ascending pain pathway, the spinothalamic tract. The mes-
unpleasant emotional dimension of pain. This affective sage is relayed in the thalamus to the anterior cingulate (C),
dimension of pain produces suffering and exerts potent frontal insular (F), and somatosensory cortex (SS). B. Pain-
control of behavior. Because of this dimension, fear is a modulation network. Inputs from frontal cortex and hypothal-
constant companion of pain. As a consequence, injury amus activate cells in the midbrain that control spinal pain-
or surgical lesions to areas of the frontal cortex activated transmission cells via cells in the medulla.
by painful stimuli diminish the emotional impact of pain
while largely preserving the individuals ability to rec-
ognize noxious stimuli as painful. administration of an inert substance can increase its per-
ceived intensity (the nocebo effect).
The powerful effect of expectation and other psy-
chological variables on the perceived intensity of pain
PAIN MODULATION
is explained by brain circuits that modulate the activity
The pain produced by injuries of similar magnitude is of the pain-transmission pathways. One of these circuits
remarkably variable in different situations and in differ- has links to the hypothalamus, midbrain, and medulla,
ent individuals. For example, athletes have been known and it selectively controls spinal pain-transmission neu-
to sustain serious fractures with only minor pain, and rons through a descending pathway (Fig. 7-4).
Beechers classic World War II survey revealed that Human brainimaging studies have implicated this
many soldiers in battle were unbothered by injuries pain-modulating circuit in the pain-relieving effect of
that would have produced agonizing pain in civilian attention, suggestion, and opioid analgesic medica-
patients. Furthermore, even the suggestion that a treat- tions (Fig. 7-5). Furthermore, each of the component
ment will relieve pain can have a signicant analgesic structures of the pathway contains opioid receptors and
effect (the placebo effect). On the other hand, many is sensitive to the direct application of opioid drugs.
patients nd even minor injuries (such as venipunc- In animals, lesions of this descending modulatory sys-
ture) frightening and unbearable, and the expectation tem reduce the analgesic effect of systemically adminis-
of pain can induce pain even without a noxious stim- tered opioids such as morphine. Along with the opioid
ulus. The suggestion that pain will worsen following receptor, the component nuclei of this pain-modulating
44 Pain-modulating circuits can enhance as well as sup-
press pain. Both pain-inhibiting and pain-facilitating neu-
rons in the medulla project to and control spinal pain-
transmission neurons. Because pain-transmission neurons
can be activated by modulatory neurons, it is theoretically
possible to generate a pain signal with no peripheral nox-
ious stimulus. In fact, human functional imaging studies
have demonstrated increased activity in this circuit during
migraine headaches. A central circuit that facilitates pain
SECTION II

could account for the nding that pain can be induced


by suggestion or enhanced by expectation and provides
a framework for understanding how psychological factors
can contribute to chronic pain.
Clinical Manifestations of Neurologic Disease

NEUROPATHIC PAIN
Lesions of the peripheral or central nociceptive path-
ways typically result in a loss or impairment of pain sen-
sation. Paradoxically, damage to or dysfunction of these
pathways can also produce pain. For example, damage
to peripheral nerves, as occurs in diabetic neuropathy,
or to primary afferents, as in herpes zoster, can result
in pain that is referred to the body region innervated
by the damaged nerves. Pain may also be produced by
damage to the central nervous system (CNS), for exam-
ple, in some patients following trauma or cerebrovas-
cular injury to spinal cord, brainstem, or thalamic areas
that contain central nociceptive pathways. Such neuro-
pathic pains are often severe and are typically resistant to
standard treatments for pain.
Neuropathic pain typically has an unusual burning,
tingling, or electric shocklike quality and may be trig-
FIGURE 7-5
gered by very light touch. These features are rare in
Functional magnetic resonance imaging (fMRI) dem-
other types of pain. On examination, a sensory decit
onstrates placebo-enhanced brain activity in anatomic
is characteristically present in the area of the patients
regions correlating with the opioidergic descending
pain. Hyperpathia, a greatly exaggerated pain sensation
pain control system. Top panel, Frontal fMRI image shows
placebo-enhanced brain activity in the dorsal lateral prefron-
to innocuous or mild nociceptive stimuli, is also char-
tal cortex (DLPFC). Bottom panel, Sagittal fMRI images show
acteristic of neuropathic pain; patients often complain
placebo-enhanced responses in the rostral anterior cingu- that the very lightest moving stimulus evokes exquisite
late cortex (rACC), the rostral ventral medullae (RVM), the pain (allodynia). In this regard, it is of clinical interest
periaqueductal gray (PAG) area, and the hypothalamus. The that a topical preparation of 5% lidocaine in patch form
placebo-enhanced activity in all areas was reduced by nalox- is effective for patients with postherpetic neuralgia who
one, demonstrating the link between the descending opioi- have prominent allodynia.
dergic system and the placebo analgesic response. (Adapted A variety of mechanisms contribute to neuropathic
with permission from F Eippert et al: Neuron 63:533, 2009.) pain. As with sensitized primary afferent nociceptors, dam-
aged primary afferents, including nociceptors, become
circuit contain endogenous opioid peptides such as the highly sensitive to mechanical stimulation and may gen-
enkephalins and -endorphin. erate impulses in the absence of stimulation. Increased
The most reliable way to activate this endogenous sensitivity and spontaneous activity are due, in part, to an
opioid-mediated modulating system is by suggestion of increased concentration of sodium channels. Damaged pri-
pain relief or by intense emotion directed away from mary afferents may also develop sensitivity to norepineph-
the pain-causing injury (e.g., during severe threat or rine. Interestingly, spinal cord pain-transmission neurons
an athletic competition). In fact, pain-relieving endog- cut off from their normal input may also become sponta-
enous opioids are released following surgical procedures neously active. Thus, both CNS and peripheral nervous
and in patients given a placebo for pain relief. system hyperactivity contribute to neuropathic pain.
Sympathetically maintained pain these compounds inhibit cyclooxygenase (COX), and, 45
Patients with peripheral nerve injury occasionally develop except for acetaminophen, all have anti-inflammatory
spontaneous pain in the region innervated by the nerve. actions, especially at higher dosages. They are particu-
This pain is often described as having a burning quality. larly effective for mild to moderate headache and for
The pain typically begins after a delay of hours to days pain of musculoskeletal origin.
or even weeks and is accompanied by swelling of the Because they are effective for these common types
extremity, periarticular bone loss, and arthritic changes of pain and are available without prescription, COX
in the distal joints. The pain may be relieved by a local inhibitors are by far the most commonly used analge-
anesthetic block of the sympathetic innervation to the sics. They are absorbed well from the gastrointestinal

CHAPTER 7
affected extremity. Damaged primary afferent nocicep- tract and, with occasional use, have only minimal side
tors acquire adrenergic sensitivity and can be activated effects. With chronic use, gastric irritation is a common
by stimulation of the sympathetic outow. This con- side effect of aspirin and NSAIDs and is the problem
stellation of spontaneous pain and signs of sympathetic that most frequently limits the dose that can be given.
dysfunction following injury has been termed complex Gastric irritation is most severe with aspirin, which may
regional pain syndrome (CRPS). When this occurs after an cause erosion and ulceration of the gastric mucosa lead-

Pain: Pathophysiology and Management


identiable nerve injury, it is termed CRPS type II (also ing to bleeding or perforation. Because aspirin irrevers-
known as posttraumatic neuralgia or, if severe, causalgia). ibly acetylates platelet cyclooxygenase and thereby
When a similar clinical picture appears without obvi- interferes with coagulation of the blood, gastrointesti-
ous nerve injury, it is termed CRPS type I (also known nal bleeding is a particular risk. Older age and history of
as reex sympathetic dystrophy). CRPS can be produced gastrointestinal disease increase the risks of aspirin and
by a variety of injuries, including fractures of bone, NSAIDs. In addition to the well-known gastrointestinal
soft tissue trauma, myocardial infarction, and stroke toxicity of NSAIDs, nephrotoxicity is a significant prob-
(Chap. 33). CRPS type I typically resolves with symp- lem for patients using these drugs on a chronic basis.
tomatic treatment; however, when it persists, detailed Patients at risk for renal insufficiency, particularly those
examination often reveals evidence of peripheral nerve with significant contraction of their intravascular vol-
injury. Although the pathophysiology of CRPS is ume as occurs with chronic diuretic use or acute hypo-
poorly understood, the pain and the signs of inam- volemia, should be monitored closely. NSAIDs can also
mation, when acute, can be rapidly relieved by block- increase blood pressure in some individuals. Long-term
ing the sympathetic nervous system. This implies that treatment with NSAIDs requires regular blood pressure
sympathetic activity can activate undamaged nocicep- monitoring and treatment if necessary. Although toxic
tors when inammation is present. Signs of sympathetic to the liver when taken in high doses, acetaminophen
hyperactivity should be sought in patients with post- rarely produces gastric irritation and does not interfere
traumatic pain and inammation and no other obvious with platelet function.
explanation. The introduction of a parenteral form of NSAID,
ketorolac, extends the usefulness of this class of com-
pounds in the management of acute severe pain. Ketor-
olac is sufficiently potent and rapid in onset to supplant
TREATMENT Acute Pain opioids for many patients with acute severe headache
and musculoskeletal pain.
The ideal treatment for any pain is to remove the cause;
There are two major classes of COX: COX-1 is consti-
thus, while treatment can be initiated immediately,
tutively expressed, and COX-2 is induced in the inflam-
efforts to establish the underlying etiology should
matory state. COX-2selective drugs have similar anal-
always proceed as treatment begins. Sometimes, treat-
gesic potency and produce less gastric irritation than
ing the underlying condition does not immediately
the nonselective COX inhibitors. The use of COX-2
relieve pain. Furthermore, some conditions are so pain-
selective drugs does not appear to lower the risk of
ful that rapid and effective analgesia is essential (e.g.,
nephrotoxicity compared to nonselective NSAIDs. On
the postoperative state, burns, trauma, cancer, or sickle
the other hand, COX-2selective drugs offer a signifi-
cell crisis). Analgesic medications are a first line of treat-
cant benefit in the management of acute postopera-
ment in these cases, and all practitioners should be
tive pain because they do not affect blood coagulation.
familiar with their use.
Nonselective COX inhibitors are usually contraindicated
ASPIRIN, ACETAMINOPHEN, AND NON- postoperatively because they impair platelet-mediated
STEROIDAL ANTI-INFLAMMATORY AGENTS blood clotting and are thus associated with increased
(NSAIDS) These drugs are considered together bleeding at the operative site. COX-2 inhibitors, includ-
because they are used for similar problems and may ing celecoxib (Celebrex), are associated with increased
have a similar mechanism of action (Table 7-1). All cardiovascular risk. It is possible that this is a class effect
46 TABLE 7-1
DRUGS FOR RELIEF OF PAIN
GENERIC NAME DOSE, mg INTERVAL COMMENTS
Nonnarcotic Analgesics: Usual Doses and Intervals
Acetylsalicylic acid 650 PO q4h Enteric-coated preparations available
Acetaminophen 650 PO q4h Side effects uncommon
Ibuprofen 400 PO q 46 h Available without prescription
Naproxen 250500 PO q 12 h Delayed effects may be due to long half-life
SECTION II

Fenoprofen 200 PO q 46 h Contraindicated in renal disease


Indomethacin 2550 PO q8h Gastrointestinal side effects common
Ketorolac 1560 IM/IV q 46 h Available for parenteral use
Celecoxib 100200 PO q 1224 h Useful for arthritis
Valdecoxib 1020 PO q1224 h Removed from U.S. market in 2005
GENERIC NAME PARENTERAL DOSE, mg PO DOSE, mg COMMENTS
Clinical Manifestations of Neurologic Disease

Narcotic Analgesics: Usual Doses and Intervals


Codeine 3060 q 4 h 3060 q 4 h Nausea common
Oxycodone 510 q 46 h Usually available with acetaminophen or aspirin
Morphine 5q4h 30 q 4 h
Morphine sustained 1560 bid to tid Oral slow-release preparation
release
Hydromorphone 12 q 4 h 24 q 4 h Shorter acting than morphine sulfate
Levorphanol 2 q 68 h 4 q 68 h Longer acting than morphine sulfate; absorbed
well PO
Methadone 510 q 68 h 520 q 68 h Delayed sedation due to long half-life;
therapy should not be initiated with greater
than 40 mg/day and dose escalation should
be made no more frequently than every 3
days
Meperidine 50100 q 34 h 300 q 4 h Poorly absorbed PO; normeperidine a toxic
metabolite; routine use of this agent is not
recommended
Butorphanol 12 q 4 h Intranasal spray
Fentanyl 25100 g/h 72-h transdermal patch
Tramadol 50100 q 46 h Mixed opioid/adrenergic action
UPTAKE BLOCKADE AVE.
SEDATIVE ANTICHOLINERGIC ORTHOSTATIC CARDIAC DOSE, RANGE,
GENERIC NAME 5-HT NE POTENCY POTENCY HYPOTENSION ARRHYTHMIA mg/d mg/d
Antidepressantsa
Doxepin ++ + High Moderate Moderate Less 200 75400
Amitriptyline ++++ ++ High Highest Moderate Yes 150 25300
Imipramine ++++ ++ Moderate Moderate High Yes 200 75400
Nortriptyline +++ ++ Moderate Moderate Low Yes 100 40150
Desipramine +++ ++++ Low Low Low Yes 150 50300
Venlafaxine +++ ++ Low None None No 150 75400
Duloxetine +++ +++ Low None None No 40 3060

GENERIC NAME PO DOSE, mg INTERVAL GENERIC NAME PO DOSE, mg INTERVAL


a
Anticonvulsants and Antiarrhythmics
Phenytoin 300 daily/qhs Clonazepam 1 q6h
Carbamazepine 200300 q6h Gabapentinb 6001200 q8h
Oxcarbazepine 300 bid Pregabalin 150600 bid

a
Antidepressants, anticonvulsants, and antiarrhythmics have not been approved by the U.S. Food and Drug Administration (FDA) for the
treatment of pain.
b
Gabapentin in doses up to 1800 mg/d is FDA approved for postherpetic neuralgia.
Note: 5-HT, serotonin; NE, norepinephrine.
of NSAIDs, excluding aspirin. These drugs are contraindi- determining whether the drug has adequately relieved 47
cated in patients in the immediate period after coronary the pain and frequent reassessment to determine the
artery bypass surgery and should be used with caution optimal interval for dosing. The most common error made
in patients with a history of or significant risk factors for by physicians in managing severe pain with opioids is to pre-
cardiovascular disease. scribe an inadequate dose. Because many patients are reluc-
tant to complain, this practice leads to needless suffering.
OPIOID ANALGESICS Opioids are the most potent In the absence of sedation at the expected time of peak
pain-relieving drugs currently available. Of all analgesics, effect, a physician should not hesitate to repeat the initial
they have the broadest range of efficacy and provide the dose to achieve satisfactory pain relief.

CHAPTER 7
most reliable and effective method for rapid pain relief. An innovative approach to the problem of achiev-
Although side effects are common, most are reversible: ing adequate pain relief is the use of patient-controlled
nausea, vomiting, pruritus, and constipation are the most analgesia (PCA). PCA uses a microprocessor-controlled
frequent and bothersome side effects. Respiratory depres- infusion device that can deliver a baseline continuous
sion is uncommon at standard analgesic doses, but can dose of an opioid drug as well as preprogrammed addi-
be life-threatening. Opioid-related side effects can be tional doses whenever the patient pushes a button. The

Pain: Pathophysiology and Management


reversed rapidly with the narcotic antagonist naloxone. patient can then titrate the dose to the optimal level.
The physician should not hesitate to use opioid analgesics This approach is used most extensively for the manage-
in patients with acute severe pain. Table 7-1 lists the most ment of postoperative pain, but there is no reason why
commonly used opioid analgesics. it should not be used for any hospitalized patient with
Opioids produce analgesia by actions in the CNS. persistent severe pain. PCA is also used for short-term
They activate pain-inhibitory neurons and directly home care of patients with intractable pain, such as that
inhibit pain-transmission neurons. Most of the commer- caused by metastatic cancer.
cially available opioid analgesics act at the same opi- It is important to understand that the PCA device
oid receptor (-receptor), differing mainly in potency, delivers small, repeated doses to maintain pain relief; in
speed of onset, duration of action, and optimal route patients with severe pain, the pain must first be brought
of administration. Some side effects are due to accu- under control with a loading dose before transitioning
mulation of nonopioid metabolites that are unique to to the PCA device. The bolus dose of the drug (typically 1
individual drugs. One striking example of this is norme- mg morphine, 0.2 mg hydromorphone, or 10 g fentanyl)
peridine, a metabolite of meperidine. Normeperidine can then be delivered repeatedly as needed. To prevent
produces hyperexcitability and seizures that are not overdosing, PCA devices are programmed with a lockout
reversible with naloxone. Normeperidine accumulation period after each demand dose is delivered (510 min) and
is increased in patients with renal failure. a limit on the total dose delivered per hour. While some
The most rapid relief with opioids is obtained by have advocated the use of a simultaneous continuous or
intravenous administration; relief with oral administra- basal infusion of the PCA drug, this increases the risk of
tion is significantly slower. Common side effects include respiratory depression and has not been shown to increase
nausea, vomiting, constipation, and sedation. The most the overall efficacy of the technique.
serious side effect is respiratory depression. Patients Many physicians, nurses, and patients have a certain
with any form of respiratory compromise must be kept trepidation about using opioids that is based on an
under close observation following opioid administration; exaggerated fear of addiction. In fact, there is a vanish-
an oxygen-saturation monitor may be useful. Opioid- ingly small chance of patients becoming addicted to
induced respiratory depression is typically accompa- narcotics as a result of their appropriate medical use.
nied by significant sedation and a reduction in respira- The availability of new routes of administration has
tory rate. A fall in oxygen saturation represents a critical extended the usefulness of opioid analgesics. Most
level of respiratory depression and the need for immedi- important is the availability of spinal administration.
ate intervention to prevent life-threatening hypoxemia. Opioids can be infused through a spinal catheter placed
Ventilatory assistance should be maintained until the either intrathecally or epidurally. By applying opioids
opioid-induced respiratory depression has resolved. The directly to the spinal or epidural space adjacent to the
opioid antagonist naloxone should be readily available spinal cord, regional analgesia can be obtained using
whenever opioids are used at high doses or in patients relatively low total doses. Indeed, the dose required to
with compromised pulmonary function. Opioid effects produce effective localized analgesia when using mor-
are dose-related, and there is great variability among phine intrathecally (0.10.3 mg) is a fraction of that
patients in the doses that relieve pain and produce side required to produce similar analgesia when adminis-
effects. Because of this, initiation of therapy requires titra- tered intravenously (510 mg). In this way, side effects
tion to optimal dose and interval. The most important such as sedation, nausea, and respiratory depression can
principle is to provide adequate pain relief. This requires be minimized. This approach has been used extensively
48 in obstetric procedures and for postoperative pain relief CHRONIC PAIN
following surgical procedures on the lower extremities.
Continuous intrathecal delivery via implanted spinal drug- Managing patients with chronic pain is intellectually
delivery systems is now commonly used, particularly for and emotionally challenging. The patients problem is
the treatment of cancer-related pain that would require often difcult or impossible to diagnose with certainty;
sedating doses for adequate pain control if given systemi- such patients are demanding of the physicians time and
cally. Opioids can also be given intranasally (butorpha- often appear emotionally distraught. The traditional
nol), rectally, and transdermally (fentanyl), thus avoiding medical approach of seeking an obscure organic pathol-
the discomfort of frequent injections in patients who ogy is usually unhelpful. On the other hand, psycholog-
SECTION II

cannot be given oral medication. The fentanyl transder- ical evaluation and behaviorally based treatment para-
mal patch has the advantage of providing fairly steady digms are frequently helpful, particularly in the setting
plasma levels, which maximizes patient comfort. of a multidisciplinary pain-management center. Unfor-
Recent additions to the armamentarium for treating tunately, this approach, while effective, remains largely
opioid-induced side effects are the peripherally acting underused in current medical practice.
opioid antagonists alvimopan (Entereg) and methyl- There are several factors that can cause, perpetuate,
Clinical Manifestations of Neurologic Disease

naltrexone (Rellistor). Alvimopan is available as an orally or exacerbate chronic pain. First, of course, the patient
administered agent that is restricted to the intestinal may simply have a disease that is characteristically pain-
lumen by limited absorption; methylnaltrexone is avail- ful for which there is presently no cure. Arthritis, can-
able in a subcutaneously administered form that has vir- cer, chronic daily headaches, bromyalgia, and diabetic
tually no penetration into the CNS. Both agents act by neuropathy are examples of this. Second, there may be
binding to peripheral -receptors, thereby inhibiting or secondary perpetuating factors that are initiated by dis-
reversing the effects of opioids at these peripheral sites. ease and persist after that disease has resolved. Examples
The action of both agents is restricted to receptor sites include damaged sensory nerves, sympathetic efferent
outside of the CNS; thus, these drugs can reverse the activity, and painful reex muscle contraction. Finally,
adverse effects of opioid analgesics that are mediated a variety of psychological conditions can exacerbate or
through their peripheral receptors without reversing even cause pain.
their analgesic effects. Both agents are effective for per- There are certain areas to which special attention
sistent ileus following abdominal surgery to the extent should be paid in a patients medical history. Because
that opioid analgesics used for postoperative pain control depression is the most common emotional disturbance
contribute to this serious problem. Likewise, both agents in patients with chronic pain, patients should be ques-
have been tested for their effectiveness in treating opi- tioned about their mood, appetite, sleep patterns, and
oid-induced bowel dysfunction (constipation) in patients daily activity. A simple standardized questionnaire,
taking opioid analgesics on a chronic basis. Although such as the Beck Depression Inventory, can be a use-
contradictory, the weight of evidence indicates that alvi- ful screening device. It is important to remember that
mopan can reduce the incidence and duration of ileus major depression is a common, treatable, and potentially
following major abdominal surgery and methylnaltrex- fatal illness.
one can produce rapid reversal of constipation in many Other clues that a signicant emotional disturbance
patients receiving opioids on a chronic basis. is contributing to a patients chronic pain complaint
include pain that occurs in multiple, unrelated sites; a
Opioid and COX Inhibitor Combinations
pattern of recurrent, but separate, pain problems begin-
When used in combination, opioids and COX inhibitors ning in childhood or adolescence; pain beginning at a
have additive effects. Because a lower dose of each can be time of emotional trauma, such as the loss of a parent or
used to achieve the same degree of pain relief and their spouse; a history of physical or sexual abuse; and past or
side effects are nonadditive, such combinations are used present substance abuse.
to lower the severity of dose-related side effects. However, On examination, special attention should be paid
fixed-ratio combinations of an opioid with acetaminophen to whether the patient guards the painful area and
carry a special risk. Dose escalation as a result of increased whether certain movements or postures are avoided
severity of pain or decreased opioid effect as a result of tol- because of pain. Discovering a mechanical component
erance may lead to levels of acetaminophen that are toxic to the pain can be useful both diagnostically and ther-
to the liver. Although acetaminophen-related hepatotoxicity apeutically. Painful areas should be examined for deep
is uncommon, it remains a leading cause for liver failure. tenderness, noting whether this is localized to muscle,
Thus, many practitioners have moved away from the use ligamentous structures, or joints. Chronic myofascial
of opioid-acetaminophen combination analgesics to avoid pain is very common, and, in these patients, deep pal-
the risk of excessive acetaminophen exposure as the dose pation may reveal highly localized trigger points that
of the analgesic is escalated. are rm bands or knots in muscle. Relief of the pain
following injection of local anesthetic into these trigger TABLE 7-2 49
points supports the diagnosis. A neuropathic component PAINFUL CONDITIONS THAT RESPOND TO
to the pain is indicated by evidence of nerve damage, TRICYCLIC ANTIDEPRESSANTS
such as sensory impairment, exquisitely sensitive skin, Postherpetic neuralgiaa
weakness, and muscle atrophy, or loss of deep tendon Diabetic neuropathya
reexes. Evidence suggesting sympathetic nervous sys- Tension headachea
tem involvement includes the presence of diffuse swell- Migraine headachea
ing, changes in skin color and temperature, and hyper- Rheumatoid arthritisa,b
sensitive skin and joint tenderness compared with the Chronic low back painb

CHAPTER 7
normal side. Relief of the pain with a sympathetic block Cancer
Central post-stroke pain
is diagnostic.
A guiding principle in evaluating patients with a
Controlled trials demonstrate analgesia.
b
chronic pain is to assess both emotional and organic fac- Controlled studies indicate benet but not analgesia.
tors before initiating therapy. Addressing these issues
together, rather than waiting to address emotional
issues after organic causes of pain have been ruled out,

Pain: Pathophysiology and Management


clearly not necessary for all chronic pain patients. For
improves compliance in part because it assures patients some, pharmacologic management alone can provide
that a psychological evaluation does not mean that the adequate relief.
physician is questioning the validity of their complaint.
Even when an organic cause for a patients pain can ANTIDEPRESSANT MEDICATIONS The tricy-
be found, it is still wise to look for other factors. For clic antidepressants (TCAs), particularly nortriptyline
example, a cancer patient with painful bony metastases and desipramine (Table 7-1), are useful for the man-
may have additional pain due to nerve damage and may agement of chronic pain. Although developed for the
also be depressed. Optimal therapy requires that each of treatment of depression, the TCAs have a spectrum of
these factors be looked for and treated. dose-related biologic activities that include analgesia
in a variety of chronic clinical conditions. Although the
mechanism is unknown, the analgesic effect of TCAs
TREATMENT Chronic Pain has a more rapid onset and occurs at a lower dose
than is typically required for the treatment of depres-
Once the evaluation process has been completed and sion. Furthermore, patients with chronic pain who are
the likely causative and exacerbating factors identi- not depressed obtain pain relief with antidepressants.
fied, an explicit treatment plan should be developed. There is evidence that TCAs potentiate opioid analge-
An important part of this process is to identify specific sia, so they may be useful adjuncts for the treatment of
and realistic functional goals for therapy, such as get- severe persistent pain such as occurs with malignant
ting a good nights sleep, being able to go shopping, tumors. Table 7-2 lists some of the painful conditions
or returning to work. A multidisciplinary approach that that respond to TCAs. TCAs are of particular value in the
uses medications, counseling, physical therapy, nerve management of neuropathic pain such as occurs in dia-
blocks, and even surgery may be required to improve betic neuropathy and postherpetic neuralgia, for which
the patients quality of life. There are also some newer, there are few other therapeutic options.
relatively invasive procedures that can be helpful for The TCAs that have been shown to relieve pain have
some patients with intractable pain. These include significant side effects (Table 7-1; Chap. 53). Some of
image-guided interventions such as epidural injec- these side effects, such as orthostatic hypotension,
tion of glucocorticoids for acute radicular pain, radio- drowsiness, cardiac-conduction delay, memory impair-
frequency treatment of the facet joints for chronic ment, constipation, and urinary retention, are particu-
facet-related pain, percutaneous intradiscal treatments larly problematic in elderly patients, and several are
for both axial and radicular pain, and placement of additive to the side effects of opioid analgesics. The
implanted intraspinal electrodes and implantation of selective serotonin reuptake inhibitors such as fluox-
intrathecal drug-delivery systems for severe and per- etine (Prozac) have fewer and less serious side effects
sistent pain that is unresponsive to more conservative than TCAs, but they are much less effective for relieving
treatments. There are no set criteria for predicting which pain. It is of interest that venlafaxine (Effexor) and dulox-
patients will respond to these procedures. They are gen- etine (Cymbalta), which are nontricyclic antidepressants
erally reserved for patients who have not responded to that block both serotonin and norepinephrine reup-
conventional pharmacologic approaches. Referral to a take, appear to retain most of the pain-relieving effect
multidisciplinary pain clinic for a full evaluation should of TCAs with a side-effect profile more like that of the
precede any invasive procedures. Such referrals are selective serotonin reuptake inhibitors. These drugs may
50 be particularly useful in patients who cannot tolerate of methylnaltrexone, a peripherally acting mu opioid
the side effects of TCAs. antagonist that blocks the constipation and itching
associated with chronic opioid use without interfering with
ANTICONVULSANTS AND ANTIARRHYTH-
analgesia; the usual dose is 0.15 mg/kg of body weight
MICS These drugs are useful primarily for patients
given subcutaneously no more often than once daily.
with neuropathic pain. Phenytoin (Dilantin) and carbam-
azepine (Tegretol) were first shown to relieve the pain of
TREATMENT OF NEUROPATHIC PAIN It is
trigeminal neuralgia. This pain has a characteristic brief,
important to individualize treatment for patients with
shooting, electric shocklike quality. In fact, anticonvul-
neuropathic pain. Several general principles should
sants seem to be particularly helpful for pains that have
SECTION II

guide therapy: the first is to move quickly to provide


such a lancinating quality. Newer anticonvulsants, gaba-
relief, and the second is to minimize drug side effects.
pentin (Neurontin) and pregabalin (Lyrica), are effective
For example, in patients with postherpetic neuralgia
for a broad range of neuropathic pains. Furthermore,
and significant cutaneous hypersensitivity, topical lido-
because of their favorable side-effect profile, these newer
caine (Lidoderm patches) can provide immediate relief
anticonvulsants are often used as first-line agents.
without side effects. Anticonvulsants (gabapentin or
Clinical Manifestations of Neurologic Disease

CHRONIC OPIOID MEDICATION The long- pregabalin, see above) or antidepressants (nortripty-
term use of opioids is accepted for patients with pain line, desipramine, duloxetine, or venlafaxine) can be
due to malignant disease. Although opioid use for used as first-line drugs for patients with neuropathic
chronic pain of nonmalignant origin is controversial, pain. Systemically administered antiarrhythmic drugs
it is clear that for many such patients, opioid analge- such as lidocaine and mexiletene are less likely to be
sics are the best available option. This is understand- effective; although intravenous infusion of lidocaine
able because opioids are the most potent and have predictably provides analgesia in those with many
the broadest range of efficacy of any analgesic medica- forms of neuropathic pain, the relief is usually tran-
tions. Although addiction is rare in patients who first sient, typically lasting just hours after the cessation of
use opioids for pain relief, some degree of tolerance the infusion. The oral lidocaine congener mexiletene is
and physical dependence is likely with long-term use. poorly tolerated, producing frequent gastrointestinal
Therefore, before embarking on opioid therapy, other adverse effects. There is no consensus on which class
options should be explored, and the limitations and of drug should be used as a first-line treatment for any
risks of opioids should be explained to the patient. It is chronically painful condition. However, because rela-
also important to point out that some opioid analgesic tively high doses of anticonvulsants are required for
medications have mixed agonist-antagonist properties pain relief, sedation is very common. Sedation is also a
(e.g., pentazocine and butorphanol). From a practical problem with TCAs but is much less of a problem with
standpoint, this means that they may worsen pain by serotonin/norepinephrine reuptake inhibitors (SNRIs,
inducing an abstinence syndrome in patients who are e.g., venlafaxine and duloxetine). Thus, in the elderly
physically dependent on other opioid analgesics. or in those patients whose daily activities require high-
With long-term outpatient use of orally administered level mental activity, these drugs should be considered
opioids, it is desirable to use long-acting compounds the first line. In contrast, opioid medications should
such as levorphanol, methadone, or sustained-release be used as a second- or third-line drug class. While
morphine (Table 7-1). Transdermal fentanyl is another highly effective for many painful conditions, opioids
excellent option. The pharmacokinetic profile of these are sedating, and their effect tends to lessen over time,
drug preparations enables prolonged pain relief, mini- leading to dose escalation and, occasionally, a worsen-
mizes side effects such as sedation that are associated ing of pain due to physical dependence. Drugs of dif-
with high peak plasma levels, and reduces the likelihood ferent classes can be used in combination to optimize
of rebound pain associated with a rapid fall in plasma pain control.
opioid concentration. While long-acting opioid prepara- It is worth emphasizing that many patients, espe-
tions may provide superior pain relief in patients with a cially those with chronic pain, seek medical attention
continuous pattern of ongoing pain, others suffer from primarily because they are suffering and because only
intermittent severe episodic pain and experience supe- physicians can provide the medications required for
rior pain control and fewer side effects with the periodic pain relief. A primary responsibility of all physicians is to
use of short-acting opioid analgesics. Constipation is a minimize the physical and emotional discomfort of their
virtually universal side effect of opioid use and should patients. Familiarity with pain mechanisms and analgesic
be treated expectantly. A recent advance for patients medications is an important step toward accomplishing
with chronic debilitating conditions is the development this aim.
CHAPTER 8

HEADACHE

Peter J. Goadsby Neil H. Raskin

Headache is among the most common reasons patients ANATOMY AND PHYSIOLOGY
seek medical attention. Diagnosis and management are OF HEADACHE
based on a careful clinical approach augmented by an
understanding of the anatomy, physiology, and pharma- Pain usually occurs when peripheral nociceptors are
cology of the nervous system pathways that mediate the stimulated in response to tissue injury, visceral disten-
various headache syndromes. sion, or other factors (Chap. 7). In such situations, pain
perception is a normal physiologic response mediated
by a healthy nervous system. Pain can also result when
pain-producing pathways of the peripheral or central
GENERAL PRINCIPLES nervous system (CNS) are damaged or activated inap-
propriately. Headache may originate from either or
A classication system developed by the International
both mechanisms. Relatively few cranial structures are
Headache Society characterizes headache as primary
pain-producing; these include the scalp, middle menin-
or secondary (Table 8-1). Primary headaches are those
geal artery, dural sinuses, falx cerebri, and proximal seg-
in which headache and its associated features are the
ments of the large pial arteries. The ventricular epen-
disorder in itself, whereas secondary headaches are those
dyma, choroid plexus, pial veins, and much of the brain
caused by exogenous disorders. Primary headache often
parenchyma are not pain-producing.
results in considerable disability and a decrease in the
The key structures involved in primary headache
patients quality of life. Mild secondary headache, such
appear to be
as that seen in association with upper respiratory tract
infections, is common but rarely worrisome. Life- the large intracranial vessels and dura mater and the
threatening headache is relatively uncommon, but vigi- peripheral terminals of the trigeminal nerve that
lance is required in order to recognize and appropriately innervate these structures
treat such patients. the caudal portion of the trigeminal nucleus, which
extends into the dorsal horns of the upper cervical
spinal cord and receives input from the rst and sec-
TABLE 8-1
ond cervical nerve roots (the trigeminocervical com-
COMMON CAUSES OF HEADACHE plex)
PRIMARY HEADACHE SECONDARY HEADACHE rostral pain-processing regions, such as the ventro-
posteromedial thalamus and the cortex
TYPE % TYPE %
the pain-modulatory systems in the brain that modu-
Tension-type 69 Systemic infection 63 late input from trigeminal nociceptors at all levels of
Migraine 16 Head injury 4 the pain-processing pathways
Idiopathic stabbing 2 Vascular disorders 1 The innervation of the large intracranial vessels and
Exertional 1 Subarachnoid hemorrhage <1 dura mater by the trigeminal nerve is known as the
Cluster 0.1 Brain tumor 0.1 trigeminovascular system. Cranial autonomic symptoms,
such as lacrimation and nasal congestion, are prominent
Source: After J Olesen et al: The Headaches. Philadelphia, Lippin- in the trigeminal autonomic cephalalgias, including
cott, Williams & Wilkins, 2005. cluster headache and paroxysmal hemicrania, and may

51
52 also be seen in migraine. These autonomic symptoms puncture (LP) is also required, unless a benign etiology
reect activation of cranial parasympathetic pathways, can be otherwise established. A general evaluation of
and functional imaging studies indicate that vascu- acute headache might include the investigation of car-
lar changes in migraine and cluster headache, when diovascular and renal status by blood pressure monitor-
present, are similarly driven by these cranial auto- ing and urine examination; eyes by funduscopy, intra-
nomic systems. Migraine and other primary headache ocular pressure measurement, and refraction; cranial
types are not vascular headaches; these disorders arteries by palpation; and cervical spine by the effect of
do not reliably manifest vascular changes, and treat- passive movement of the head and by imaging.
ment outcomes cannot be predicted by vascular effects. The psychological state of the patient should also be
SECTION II

Migraine is a brain disorder, and best understood and evaluated since a relationship exists between head pain
managed as such. and depression. Many patients in chronic daily pain
cycles become depressed, although depression itself is
rarely a cause of headache. Drugs with antidepressant
CLINICAL EVALUATION OF ACUTE, NEW- actions are also effective in the prophylactic treatment
ONSET HEADACHE of both tension-type headache and migraine.
Underlying recurrent headache disorders may be
Clinical Manifestations of Neurologic Disease

The patient who presents with a new, severe headache activated by pain that follows otologic or endodontic
has a differential diagnosis that is quite different from the surgical procedures. Thus, pain about the head as the
patient with recurrent headaches over many years. In result of diseased tissue or trauma may reawaken an oth-
new-onset and severe headache, the probability of nd- erwise quiescent migrainous syndrome. Treatment of
ing a potentially serious cause is considerably greater than the headache is largely ineffective until the cause of the
in recurrent headache. Patients with recent onset of pain primary problem is addressed.
require prompt evaluation and appropriate treatment. Serious underlying conditions that are associated with
Serious causes to be considered include meningitis, sub- headache are described next. Brain tumor is a rare cause
arachnoid hemorrhage, epidural or subdural hematoma, of headache and even less commonly a cause of severe
glaucoma, tumor, and purulent sinusitis. When worri- pain. The vast majority of patients presenting with
some symptoms and signs are present (Table 8-2), rapid severe headache have a benign cause.
diagnosis and management are critical.
A complete neurologic examination is an essen-
tial rst step in the evaluation. In most cases, patients
with an abnormal examination or a history of recent- SECONDARY HEADACHE
onset headache should be evaluated by a CT or MRI
study. As an initial screening procedure for intracranial The management of secondary headache focuses on
pathology in this setting, CT and MRI methods appear diagnosis and treatment of the underlying condition.
to be equally sensitive. In some circumstances, a lumbar

MENINGITIS
TABLE 8-2 Acute, severe headache with stiff neck and fever sug-
HEADACHE SYMPTOMS THAT SUGGEST A SERIOUS gests meningitis. Lumbar puncture is mandatory. Often
UNDERLYING DISORDER there is striking accentuation of pain with eye move-
Worst headache ever ment. Meningitis can be easily mistaken for migraine
First severe headache in that the cardinal symptoms of pounding headache,
Subacute worsening over days or weeks
photophobia, nausea, and vomiting are frequently pres-
ent, perhaps reecting the underlying biology of some
Abnormal neurologic examination
of the patients.
Fever or unexplained systemic signs Meningitis is discussed in Chaps. 40 and 41.
Vomiting that precedes headache
Pain induced by bending, lifting, cough
Pain that disturbs sleep or presents immediately upon INTRACRANIAL HEMORRHAGE
awakening
Acute, severe headache with stiff neck but without
Known systemic illness fever suggests subarachnoid hemorrhage. A ruptured
Onset after age 55 aneurysm, arteriovenous malformation, or intraparen-
Pain associated with local tenderness, e.g., region of tem- chymal hemorrhage may also present with headache
poral artery alone. Rarely, if the hemorrhage is small or below the
foramen magnum, the head CT scan can be normal.
Therefore, lumbar puncture may be required to diag- appear in migraine. Most patients can recognize that 53
nose denitively subarachnoid hemorrhage. the origin of their head pain is supercial, external to
Intracranial hemorrhage is discussed in Chap. 28. the skull, rather than originating deep within the cra-
nium (the pain site for migraineurs). Scalp tenderness is
present, often to a marked degree; brushing the hair or
BRAIN TUMOR resting the head on a pillow may be impossible because
Approximately 30% of patients with brain tumors con- of pain. Headache is usually worse at night and often
sider headache to be their chief complaint. The head aggravated by exposure to cold. Additional ndings may
pain is usually nondescriptan intermittent deep, dull include reddened, tender nodules or red streaking of the

CHAPTER 8
aching of moderate intensity, which may worsen with skin overlying the temporal arteries, and tenderness of
exertion or change in position and may be associated the temporal or, less commonly, the occipital arteries.
with nausea and vomiting. This pattern of symptoms The erythrocyte sedimentation rate (ESR) is often,
results from migraine far more often than from brain though not always, elevated; a normal ESR does not
tumor. The headache of brain tumor disturbs sleep in exclude giant cell arteritis. A temporal artery biopsy fol-
about 10% of patients. Vomiting that precedes the lowed by immediate treatment with prednisone 80 mg
daily for the rst 46 weeks should be initiated when clini-

Headache
appearance of headache by weeks is highly characteristic
of posterior fossa brain tumors. A history of amenorrhea cal suspicion is high. The prevalence of migraine among
or galactorrhea should lead one to question whether a the elderly is substantial, considerably higher than that of
prolactin-secreting pituitary adenoma (or the polycystic giant cell arteritis. Migraineurs often report amelioration
ovary syndrome) is the source of headache. Headache of their headaches with prednisone; thus, caution must be
arising de novo in a patient with known malignancy used when interpreting the therapeutic response.
suggests either cerebral metastases or carcinomatous
meningitis, or both. Head pain appearing abruptly after GLAUCOMA
bending, lifting, or coughing can be due to a posterior
fossa mass, a Chiari malformation, or low CSF volume. Glaucoma may present with a prostrating headache
Brain tumors are discussed in Chap. 37. associated with nausea and vomiting. The headache
often starts with severe eye pain. On physical exami-
nation, the eye is often red with a xed, moderately
TEMPORAL ARTERITIS dilated pupil.
Glaucoma is discussed in Chap. 21.
(See also Chap. 21) Temporal (giant cell) arteritis is
an inammatory disorder of arteries that frequently
involves the extracranial carotid circulation. It is a com-
mon disorder of the elderly; its annual incidence is 77 PRIMARY HEADACHE SYNDROMES
per 100,000 individuals age 50 and older. The average
age of onset is 70 years, and women account for 65% Primary headaches are disorders in which headache
of cases. About half of patients with untreated tempo- and associated features occur in the absence of any
ral arteritis develop blindness due to involvement of the exogenous cause (Table 8-1). The most common are
ophthalmic artery and its branches; indeed, the isch- migraine, tension-type headache, and cluster headache.
emic optic neuropathy induced by giant cell arteritis is
the major cause of rapidly developing bilateral blindness
MIGRAINE
in patients >60 years. Because treatment with gluco-
corticoids is effective in preventing this complication, Migraine, the second most common cause of head-
prompt recognition of the disorder is important. ache, aficts approximately 15% of women and 6% of
Typical presenting symptoms include headache, men over a 1-year period. It is usually an episodic head-
polymyalgia rheumatica, jaw claudication, fever, and ache associated with certain features such as sensitiv-
weight loss. Headache is the dominant symptom and ity to light, sound, or movement; nausea and vomiting
often appears in association with malaise and muscle often accompany the headache. A useful description of
aches. Head pain may be unilateral or bilateral and is migraine is a benign and recurring syndrome of head-
located temporally in 50% of patients but may involve ache associated with other symptoms of neurologic dys-
any and all aspects of the cranium. Pain usually appears function in varying admixtures (Table 8-3). Migraine
gradually over a few hours before peak intensity is can often be recognized by its activators, referred to as
reached; occasionally, it is explosive in onset. The qual- triggers.
ity of pain is only seldom throbbing; it is almost invari- The brain of the migraineur is particularly sensi-
ably described as dull and boring, with superimposed tive to environmental and sensory stimuli; migraine-
episodic stabbing pains similar to the sharp pains that prone patients do not habituate easily to sensory stimuli.
54 TABLE 8-3 effects. Other brainstem regions likely to be involved in
SYMPTOMS ACCOMPANYING SEVERE MIGRAINE descending modulation of trigeminal pain include the
ATTACKS IN 500 PATIENTS nucleus locus coeruleus in the pons and the rostroven-
SYMPTOM PATIENTS AFFECTED, %
tromedial medulla.
Pharmacologic and other data point to the involve-
Nausea 87 ment of the neurotransmitter 5-hydroxytryptamine
Photophobia 82 (5-HT; also known as serotonin) in migraine. Approxi-
Lightheadedness 72 mately 60 years ago, methysergide was found to antago-
Scalp tenderness 65
nize certain peripheral actions of 5-HT and was intro-
SECTION II

duced as the rst drug capable of preventing migraine


Vomiting 56
attacks. The triptans are designed to selectively stimulate
Visual disturbances 36 subpopulations of 5-HT receptors; at least 14 different
Paresthesias 33 5-HT receptors exist in humans. The triptans are potent
Vertigo 33 agonists of 5-HT1B, 5-HT1D, and 5-HT1F receptors and
are less potent at the 5-HT1A receptor. A growing body
Photopsia 26
of data indicates that the antimigraine efcacy of the
Clinical Manifestations of Neurologic Disease

Alteration of consciousness 18 triptans relates to their ability to stimulate 5-HT1B/1D


Diarrhea 16 receptors, which are located on both blood vessels and
Fortication spectra 10 nerve terminals. Separately, it has now been shown that
Syncope 10 selective 5-HT1F receptor activation, which has a purely
neural effect, can terminate acute migraine.
Seizure 4
Data also support a role for dopamine in the patho-
Confusional state 4 physiology of migraine. Most migraine symptoms
can be induced by dopaminergic stimulation. More-
Source: From NH Raskin, Headache, 2nd ed. New York, Churchill
over, there is dopamine receptor hypersensitivity in
Livingston, 1988; with permission.
migraineurs, as demonstrated by the induction of yawn-
ing, nausea, vomiting, hypotension, and other symp-
This sensitivity is amplied in females during the men- toms of a migraine attack by dopaminergic agonists at
strual cycle. Headache can be initiated or amplied by doses that do not affect nonmigraineurs. Dopamine
various triggers, including glare, bright lights, sounds, or receptor antagonists are effective therapeutic agents in
other afferent stimulation; hunger; excess stress; physi- migraine, especially when given parenterally or concur-
cal exertion; stormy weather or barometric pressure rently with other antimigraine agents.
changes; hormonal uctuations during menses; lack of Migraine genes identied by studying families with
or excess sleep; and alcohol or other chemical stimula- familial hemiplegic migraine (FHM) reveal involvement
tion. Knowledge of a patients susceptibility to specic of ion channels, suggesting that alterations in mem-
triggers can be useful in management strategies involv- brane excitability can predispose to migraine. Mutations
ing lifestyle adjustments. involving the Cav2.1 (P/Q)type voltage-gated calcium
channel CACNA1A gene are now known to cause
Pathogenesis FHM 1; this mutation is responsible for about 50% of
FHM. Mutations in the Na+-K+ATPase ATP1A2 gene,
The sensory sensitivity that is characteristic of migraine designated FHM 2, are responsible for about 20% of
is probably due to dysfunction of monoaminergic sen- FHM. Mutations in the neuronal voltage-gated sodium
sory control systems located in the brainstem and thala- channel SCN1A cause FHM 3. Functional neuroim-
mus (Fig. 8-1). aging has suggested that brainstem regions in migraine
Activation of cells in the trigeminal nucleus results (Fig. 8-2) and the posterior hypothalamic gray mat-
in the release of vasoactive neuropeptides, particularly ter region close to the human circadian pacemaker
calcitonin generelated peptide (CGRP), at vascular cells of the suprachiasmatic nucleus in cluster headache
terminations of the trigeminal nerve and within the tri- (Fig. 8-3) are good candidates for specic involvement
geminal nucleus. CGRP receptor antagonists have now in primary headache.
been shown to be effective in the acute treatment of
migraine. Centrally, the second-order trigeminal neu-
Diagnosis and clinical features
rons cross the midline and project to ventrobasal and
posterior nuclei of the thalamus for further process- Diagnostic criteria for migraine headache are listed in
ing. Additionally, there are projections to the periaq- Table 8-4. A high index of suspicion is required to
ueductal gray and hypothalamus, from which recipro- diagnose migraine: the migraine aura, consisting of
cal descending systems have established antinociceptive visual disturbances with ashing lights or zigzag lines
55
Cortex
Thalamus
Quintothalamic
tract
Hypothalamus Dorsal raphe
nucleus

Locus

CHAPTER 8
Dura coeruleus

Superior
salivatory nucleus

Magnus raphe
nucleus

Headache
TCC

Trigeminal
ganglion

Pterygopalatine
ganglion

FIGURE 8-1
Brainstem pathways that modulate sensory input. The turn project in the quintothalamic tract and, after decussat-
key pathway for pain in migraine is the trigeminovascular ing in the brainstem, synapse on neurons in the thalamus.
input from the meningeal vessels, which passes through the Important modulation of the trigeminovascular nociceptive
trigeminal ganglion and synapses on second-order neurons input comes from the dorsal raphe nucleus, locus coeruleus,
in the trigeminocervical complex (TCC). These neurons in and nucleus raphe magnus.

FIGURE 8-2
Positron emission tomography (PET) activation in lateralization of changes in this region of the brainstem cor-
migraine. In spontaneous attacks of episodic migraine there relates with lateralization of the head pain in hemicranial
is activation of the region of the dorsolateral pons; an iden- migraine; the scans shown in panels A and B are of patients
tical pattern is found in chronic migraine (not shown). This with acute migraine headache on the right and left side,
area, which includes the noradrenergic locus coeruleus, respectively. (From S Afridi et al: Brain 128:932, 2005.)
is fundamental to the expression of migraine. Moreover,
56
SECTION II

A B
Clinical Manifestations of Neurologic Disease

FIGURE 8-3
Posterior hypothalamic gray matter activation on positron morphometry demonstrates increased gray matter activity,
emission tomography (PET) in a patient with acute clus- lateralized to the side of pain in a patient with cluster head-
ter headache (A). (From A May et al: Lancet 352:275, 1998.) ache (B). (From A May et al: Nat Med 5:836, 1999.)
High-resolution T1-weighted MRI obtained using voxel-based

moving across the visual eld or of other neurologic but with little or no headache. Vertigo can be promi-
symptoms, is reported in only 2025% of patients. A nent; it has been estimated that one-third of patients
headache diary can often be helpful in making the diag- referred for vertigo or dizziness have a primary diagnosis
nosis; this is also helpful in assessing disability and the of migraine.
frequency of treatment for acute attacks. Patients with
episodes of migraine that occur daily or near-daily are
considered to have chronic migraine (see Chronic
TREATMENT Migraine Headaches
Daily Headache, later in this chapter). Migraine must
be differentiated from tension-type headache (discussed Once a diagnosis of migraine has been established, it
later), the most common primary headache syndrome is important to assess the extent of a patients disease
seen in clinical practice. Migraine at its most basic level is and disability. The Migraine Disability Assessment Score
headache with associated features, and tension-type headache is (MIDAS) is a well-validated, easy-to-use tool (Fig. 8-4).
headache that is featureless. Most patients with disabling head- Patient education is an important aspect of migraine
ache probably have migraine. management. Information for patients is available at
Patients with acephalgic migraine experience recurrent www.achenet.org, the website of the American Council
neurologic symptoms, often with nausea or vomiting, for Headache Education (ACHE). It is helpful for patients
to understand that migraine is an inherited tendency to
TABLE 8-4 headache; that migraine can be modified and controlled
SIMPLIFIED DIAGNOSTIC CRITERIA FOR MIGRAINE by lifestyle adjustments and medications, but it cannot
Repeated attacks of headache lasting 472 h in patients with a
be eradicated; and that, except in some occasions in
normal physical examination, no other reasonable cause for the women on oral estrogens or contraceptives, migraine is
headache, and: not associated with serious or life-threatening illnesses.
AT LEAST 2 OF THE PLUS AT LEAST 1 OF THE
FOLLOWING FEATURES: FOLLOWING FEATURES: NONPHARMACOLOGIC MANAGEMENT Mi-
graine can often be managed to some degree by a vari-
Unilateral pain Nausea/vomiting
ety of nonpharmacologic approaches. Most patients
Throbbing pain Photophobia and phonophobia benefit by the identification and avoidance of spe-
Aggravation by movement cific headache triggers. A regulated lifestyle is helpful,
Moderate or severe including a healthful diet, regular exercise, regular sleep
intensity patterns, avoidance of excess caffeine and alcohol, and
avoidance of acute changes in stress levels.
Source: Adapted from the International Headache Society Clas- The measures that benefit a given individual
sication (Headache Classication Committee of the International should be used routinely since they provide a simple,
Headache Society, 2004).
*MIDAS Questionnaire 57
INSTRUCTIONS: Please answer the following questions about ALL headaches you have had
over the last 3 months. Write zero if you did not do the activity in the last 3 months.

1. On how many days in the last 3 months did you miss work or school because
of your headaches? ............................................................................................... days
2. How many days in the last 3 months was your productivity at work or school
reduced by half or more because of your headaches (do not include days
you counted in question 1 where you missed work or school)? ............................ days
3. On how many days in the last 3 months did you not do household work

CHAPTER 8
because of your headaches? ................................................................................ days
4. How many days in the last 3 months was your productivity in household work
reduced by half or more because of your headaches (do not include days
you counted in question 3 where you did not do household work)? ..................... days
5. On how many days in the last 3 months did you miss family, social, or leisure
activities because of your headaches? ................................................................. days

Headache
A. On how many days in the last 3 months did you have a headache? (If a
headache lasted more than one day, count each day.) ......................................... days
B. On a scale of 010, on average how painful were these headaches? (Where
0 = no pain at all, and 10 = pain as bad as it can be.) ..........................................
*Migraine Disability Assessment Score
(Questions 15 are used to calculate the MIDAS score.)
Grade IMinimal or Infrequent Disability: 05
Grade IIMild or Infrequent Disability: 610
Grade IIIModerate Disability: 1120
Grade IVSevere Disability: > 20
Innovative Medical Research 1997
FIGURE 8-4
MIDAS Questionnaire.

cost-effective approach to migraine management. anti-inflammatory agents, 5-HT1B/1D receptor agonists,


Patients with migraine do not encounter more stress and dopamine receptor antagonists.
than headache-free individuals; overresponsiveness In general, an adequate dose of whichever agent
to stress appears to be the issue. Since the stresses of is chosen should be used as soon as possible after the
everyday living cannot be eliminated, lessening ones onset of an attack. If additional medication is required
response to stress by various techniques is helpful for within 60 min because symptoms return or have not
many patients. These may include yoga, transcenden- abated, the initial dose should be increased for subse-
tal meditation, hypnosis, and conditioning techniques quent attacks. Migraine therapy must be individualized;
such as biofeedback. For most patients, this approach a standard approach for all patients is not possible. A
is, at best, an adjunct to pharmacotherapy. Nonphar- therapeutic regimen may need to be constantly refined
macologic measures are unlikely to prevent all migraine until one is identified that provides the patient with
attacks. If these measures fail to prevent an attack, rapid, complete, and consistent relief with minimal side
pharmacologic approaches are then needed to abort effects (Table 8-6).
an attack.
NONSTEROIDAL ANTI-INFLAMMATORY DR-
ACUTE ATTACK THERAPIES FOR MIGRAINE UGS (NSAIDs) Both the severity and duration of
The mainstay of pharmacologic therapy is the judicious a migraine attack can be reduced significantly by non-
use of one or more of the many drugs that are effective steroidal anti-inflammatory agents (Table 8-5). Indeed,
in migraine (Table 8-5). The selection of the optimal many undiagnosed migraineurs are self-treated with
regimen for a given patient depends on a number of nonprescription NSAIDs. A general consensus is that
factors, the most important of which is the severity of NSAIDs are most effective when taken early in the
the attack. Mild migraine attacks can usually be man- migraine attack. However, the effectiveness of anti-
aged by oral agents; the average efficacy rate is 5070%. inflammatory agents in migraine is usually less than
Severe migraine attacks may require parenteral therapy. optimal in moderate or severe migraine attacks. The
Most drugs effective in the treatment of migraine are combination of acetaminophen, aspirin, and caffeine
members of one of three major pharmacologic classes: has been approved for use by the U.S. Food and Drug
58 TABLE 8-5
TREATMENT OF ACUTE MIGRAINE
DRUG TRADE NAME DOSAGE

Simple Analgesics
Acetaminophen, aspirin, caffeine Excedrin Two tablets or caplets q6h (max 8 per day)
Migraine
NSAIDs
Naproxen Aleve, Anaprox, generic 220550 mg PO bid
SECTION II

Ibuprofen Advil, Motrin, Nuprin, generic 400 mg PO q34h


Tolfenamic acid Clotam Rapid 200 mg PO. May repeat 1 after 12 h
5-HT1 Agonists
Oral
Ergotamine Ergomar One 2 mg sublingual tablet at onset and q1/2h (max 3 per day, 5 per week)
Ergotamine 1 mg, Ercaf, Wigraine One or two tablets at onset, then one tablet q1/2h (max 6 per day, 10 per week)
Clinical Manifestations of Neurologic Disease

caffeine 100 mg
Naratriptan Amerge 2.5 mg tablet at onset; may repeat once after 4 h
Rizatriptan Maxalt 510 mg tablet at onset; may repeat after 2 h (max 30 mg/d)
Maxalt-MLT
Sumatriptan Imitrex 50100 mg tablet at onset; may repeat after 2 h (max 200 mg/d)
Frovatriptan Frova 2.5 mg tablet at onset, may repeat after 2 h (max 5 mg/d)
Almotriptan Axert 12.5 mg tablet at onset, may repeat after 2 h (max 25 mg/d)
Eletriptan Relpax 40 or 80 mg
Zolmitriptan Zomig 2.5 mg tablet at onset; may repeat after 2 h (max 10 mg/d)
Zomig Rapimelt
Nasal
Dihydroergotamine Migranal Nasal Spray Prior to nasal spray, the pump must be primed 4 times; 1 spray (0.5 mg) is
administered, followed in 15 min by a second spray
Sumatriptan Imitrex Nasal Spray 520 mg intranasal spray as 4 sprays of 5 mg or a single 20 mg spray
(may repeat once after 2 h, not to exceed a dose of 40 mg/d)
Zolmitriptan Zomig 5 mg intranasal spray as one spray (may repeat once after 2 h, not to
exceed a dose of 10 mg/d)
Parenteral
Dihydroergotamine DHE-45 1 mg IV, IM, or SC at onset and q1h (max 3 mg/d, 6 mg per week)
Sumatriptan Imitrex Injection 6 mg SC at onset (may repeat once after 1 h for max of 2 doses in 24 h)
Dopamine Antagonists
Oral
Metoclopramide Reglan,a generica 510 mg/d
Prochlorperazine Compazine,a generica 125 mg/d
Parenteral
Chlorpromazine Generica 0.1 mg/kg IV at 2 mg/min; max 35 mg/d
Metoclopramide Reglan,a generic 10 mg IV
Prochlorperazine Compazine,a generica 10 mg IV
Other
Oral
Acetaminophen, 325 mg, plus Midrin, Duradrin, generic Two capsules at onset followed by 1 capsule q1h (max 5 capsules)
dichloralphenazone, 100 mg,
plus isometheptene, 65 mg
Nasal
Butorphanol Stadola 1 mg (1 spray in 1 nostril), may repeat if necessary in 12 h
Parenteral
Narcotics Generica Multiple preparations and dosages; see Table 7-1

a
Not all drugs are specically indicated by the FDA for migraine. Local regulations and guidelines should be consulted.
Note: Antiemetics (e.g., domperidone 10 mg or ondansetron 4 or 8 mg) or prokinetics (e.g., metoclopramide 10 mg) are sometimes useful adjuncts.
Abbreviations: NSAIDs, nonsteroidal anti-inammatory drugs; 5-HT, 5-hydroxytryptamine.
TABLE 8-6
tans are selective 5-HT1B/1D receptor agonists. A variety 59
CLINICAL STRATIFICATION OF ACUTE SPECIFIC of triptans, 5-HT1B/1D receptor agonistsnaratriptan,
MIGRAINE TREATMENTS
rizatriptan, eletriptan, sumatriptan, zolmitriptan, almo-
CLINICAL SITUATION TREATMENT OPTIONS triptan, and frovatriptanare now available for the
Failed NSAIDs/anal- First tier treatment of migraine.
gesics Sumatriptan 50 mg or 100 mg PO Each drug in the triptan class has similar pharmaco-
Almotriptan 12.5 mg PO logic properties but varies slightly in terms of clinical
Rizatriptan 10 mg PO efficacy. Rizatriptan and eletriptan are the most effica-
cious of the triptans currently available in the United

CHAPTER 8
Eletriptan 40 mg PO
Zolmitriptan 2.5 mg PO States. Sumatriptan and zolmitriptan have similar rates
Slower effect/better tolerability
of efficacy as well as time to onset, with an advantage
Naratriptan 2.5 mg PO of having multiple formulations, whereas almotriptan,
Frovatriptan 2.5 mg PO frovatriptan, and naratriptan are somewhat slower in
Infrequent headache onset and are better tolerated. Clinical efficacy appears
Ergotamine 12 mg PO to be related more to the tmax (time to peak plasma

Headache
Dihydroergotamine nasal level) than to the potency, half-life, or bioavailability.
spray 2 mg This observation is consistent with a large body of data
Early nausea or dif- Zolmitriptan 5 mg nasal spray indicating that faster-acting analgesics are more effec-
culties taking tablets Sumatriptan 20 mg nasal spray tive than slower-acting agents.
Unfortunately, monotherapy with a selective oral
Rizatriptan 10 mg MLT wafer 5-HT1B/1D agonist does not result in rapid, consistent,
Headache recurrence Ergotamine 2 mg (most effective and complete relief of migraine in all patients. Triptans
PR/usually with caffeine) are not effective in migraine with aura unless given
Naratriptan 2.5 mg PO after the aura is completed and the headache initiated.
Almotriptan 12.5 mg PO Side effects are common though often mild and tran-
sient. Moreover, 5-HT1B/1D agonists are contraindicated
Eletriptan 40 mg
in individuals with a history of cardiovascular and cere-
Tolerating acute treat- Naratriptan 2.5 mg brovascular disease. Recurrence of headache is another
ments poorly
Almotriptan 12.5 mg important limitation of triptan use and occurs at least
Early vomiting Zolmitriptan 5 mg nasal spray occasionally in most patients. Evidence from random-
ized controlled trials show that coadministration of a
Sumatriptan 25 mg PR
longer-acting NSAID, naproxen 500 mg, with sumatrip-
Sumatriptan 6 mg SC
tan will augment the initial effect of sumatriptan and,
Menses-related Prevention importantly, reduce rates of headache recurrence.
headache Ergotamine PO at night Ergotamine preparations offer a nonselective means
Estrogen patches of stimulating 5-HT1 receptors. A nonnauseating dose
Treatment of ergotamine should be sought since a dose that pro-
Triptans vokes nausea is too high and may intensify head pain.
Dihydroergotamine nasal spray Except for a sublingual formulation of ergotamine, oral
formulations of ergotamine also contain 100 mg caf-
Very rapidly develop- Zolmitriptan 5 mg nasal spray
ing symptoms feine (theoretically to enhance ergotamine absorption
Sumatriptan 6 mg SC
and possibly to add additional analgesic activity). The
Dihydroergotamine 1 mg IM average oral ergotamine dose for a migraine attack is
2 mg. Since the clinical studies demonstrating the effi-
cacy of ergotamine in migraine predated the clinical
Administration (FDA) for the treatment of mild to mod- trial methodologies used with the triptans, it is difficult
erate migraine. The combination of aspirin and metoclo- to assess the clinical efficacy of ergotamine versus the
pramide has been shown to be comparable to a single triptans. In general, ergotamine appears to have a much
dose of sumatriptan. Important side effects of NSAIDs higher incidence of nausea than triptans, but less head-
include dyspepsia and gastrointestinal irritation. ache recurrence.
5-HT1 RECEPTOR AGONISTS
Nasal The fastest-acting nonparenteral antimigraine
Oral Stimulation of 5-HT1B/1D receptors can stop an therapies that can be self-administered include nasal
acute migraine attack. Ergotamine and dihydroergota- formulations of dihydroergotamine (Migranal), zolmi-
mine are nonselective receptor agonists, while the trip- triptan (Zomig nasal), or sumatriptan. The nasal sprays
60 result in substantial blood levels within 3060 min. Parenteral Narcotics are effective in the acute treat-
Although in theory nasal sprays might provide faster ment of migraine. For example, IV meperidine (50100
and more effective relief of a migraine attack than oral mg) is given frequently in the emergency room. This
formulations, their reported efficacy is only approxi- regimen works in the sense that the pain of migraine is
mately 5060%. Studies with an inhalational formula- eliminated. However, this regimen is clearly suboptimal
tion of dihydroergotamine indicate that its absorption for patients with recurrent headache. Narcotics do not
problems can be overcome to produce rapid onset of treat the underlying headache mechanism; rather, they
action with good tolerability. act to alter the pain sensation. Moreover, in patients tak-
ing oral narcotics such as oxycodone or hydrocodone,
SECTION II

Parenteral Parenteral administration of drugs such


narcotic addiction can greatly confuse the treatment
as dihydroergotamine and sumatriptan is approved by
of migraine. Narcotic craving and/or withdrawal can
the FDA for the rapid relief of a migraine attack. Peak
aggravate and accentuate migraine. Therefore, it is rec-
plasma levels of dihydroergotamine are achieved 3 min
ommended that narcotic use in migraine be limited to
after IV dosing, 30 min after IM dosing, and 45 min after
patients with severe, but infrequent, headaches that are
SC dosing. If an attack has not already peaked, SC or
unresponsive to other pharmacologic approaches.
IM administration of 1 mg dihydroergotamine suffices
Clinical Manifestations of Neurologic Disease

for about 8090% of patients. Sumatriptan, 6 mg SC, is MEDICATION-OVERUSE HEADACHE Acute


effective in 7080% of patients. attack medications, particularly codeine or barbiturate-
containing compound analgesics, have a propensity
DOPAMINE ANTAGONISTS to aggravate headache frequency and induce a state
Oral Oral dopamine antagonists should be consid- of refractory daily or near-daily headache called med-
ered as adjunctive therapy in migraine. Drug absorption ication-overuse headache. This condition is likely not a
is impaired during migraine because of reduced gas- separate headache entity but a reaction of the migraine
trointestinal motility. Delayed absorption occurs even patient to a particular medicine. Migraine patients who
in the absence of nausea and is related to the sever- have two or more headache days a week should be cau-
ity of the attack and not its duration. Therefore, when tioned about frequent analgesic use (see Chronic Daily
oral NSAIDs and/or triptan agents fail, the addition of a Headache, later in this chapter).
dopamine antagonist such as metoclopramide 10 mg PREVENTIVE TREATMENTS FOR MIGRAINE
should be considered to enhance gastric absorption. In Patients with an increasing frequency of migraine attacks,
addition, dopamine antagonists decrease nausea/vom- or with attacks that are either unresponsive or poorly
iting and restore normal gastric motility. responsive to abortive treatments, are good candidates
Parenteral Parenteral dopamine antagonists (e.g.,
for preventive agents. In general, a preventive medica-
chlorpromazine, prochlorperazine, metoclopramide) tion should be considered in the subset of patients with
can also provide significant acute relief of migraine; they five or more attacks a month. Significant side effects are
can be used in combination with parenteral 5-HT1B/1D associated with the use of many of these agents; further-
agonists. A common IV protocol used for the treatment more, determination of dose can be difficult since the
of severe migraine is the administration over 2 min of a recommended doses have been derived for conditions
mixture of 5 mg of prochlorperazine and 0.5 mg of dihy- other than migraine. The mechanism of action of these
droergotamine. drugs is unclear; it seems likely that the brain sensitivity
that underlies migraine is modified. Patients are usually
OTHER MEDICATIONS FOR started on a low dose of a chosen treatment; the dose is
ACUTE MIGRAINE then gradually increased, up to a reasonable maximum to
achieve clinical benefit.
Oral The combination of acetaminophen, dichloral-
Drugs that have the capacity to stabilize migraine are
phenazone, and isometheptene, one to two capsules,
listed in Table 8-7. Drugs must be taken daily, and there
has been classified by the FDA as possibly effective in
is usually a lag of at least 212 weeks before an effect is
the treatment of migraine. Since the clinical studies dem-
seen. The drugs that have been approved by the FDA for
onstrating the efficacy of this combination analgesic in
the prophylactic treatment of migraine include propran-
migraine predated the clinical trial methodologies used
olol, timolol, sodium valproate, topiramate, and methy-
with the triptans, it is difficult to compare the efficacy of
sergide (not available in the United States). In addition,
this sympathomimetic compound to other agents.
a number of other drugs appear to display prophylactic
Nasal A nasal preparation of butorphanol is available efficacy. This group includes amitriptyline, nortripty-
for the treatment of acute pain. As with all narcotics, the line, flunarizine, phenelzine, gabapentin, and cypro-
use of nasal butorphanol should be limited to a select heptadine. Placebo-controlled trials of onabotulinum
group of migraineurs, as described next. toxin type A in episodic migraine were negative, while,
TABLE 8-7 61
a
PREVENTIVE TREATMENTS IN MIGRAINE
DRUG DOSE SELECTED SIDE EFFECTS
b
Pizotifen 0.52 mg qd Weight gain
Drowsiness
Beta blocker
Propranolol 40120 mg bid Reduced energy
Tiredness

CHAPTER 8
Postural symptoms
Contraindicated in asthma
Tricyclics
Amitriptyline 1075 mg at night Drowsiness
Dothiepin 2575 mg at night

Headache
Nortriptyline 2575 mg at night Note: Some patients may only need a total dose of 10 mg,
although generally 11.5 mg/kg body weight is required
Anticonvulsants
Topiramate 25200 mg/d Paresthesias
Cognitive symptoms
Weight loss
Glaucoma
Caution with nephrolithiasis
Valproate 400600 mg bid Drowsiness
Weight gain
Tremor
Hair loss
Fetal abnormalities
Hematologic or liver abnormalities
Gabapentin 9003600 mg qd Dizziness
Sedation
Serotonergic drugs
Methysergide 14 mg qd Drowsiness
Leg cramps
Hair loss
Retroperitoneal brosis (1-month drug holiday is required
every 6 months)
Flunarizineb 515 mg qd Drowsiness
Weight gain
Depression
Parkinsonism
No convincing evidence from controlled trials
Verapamil
Controlled trials demonstrate no effect
Nimodipine
Clonidine
SSRIs: uoxetine
a
Commonly used preventives are listed with typical doses and common side effects. Not all listed medicines are approved by the FDA; local
regulations and guidelines should be consulted.
b
Not available in the United States.
62 overall, placebo-controlled trials in chronic migraine Pathophysiology
were positive. Phenelzine and methysergide are usually The pathophysiology of TTH is incompletely under-
reserved for recalcitrant cases because of their serious stood. It seems likely that TTH is due to a primary dis-
potential side effects. Phenelzine is a monoamine oxi- order of CNS pain modulation alone, unlike migraine,
dase inhibitor (MAOI); therefore, tyramine-containing which involves a more generalized disturbance of sen-
foods, decongestants, and meperidine are contraindi- sory modulation. Data suggest a genetic contribution
cated. Methysergide may cause retroperitoneal or car- to TTH, but this may not be a valid nding: given
diac valvular fibrosis when it is used for >6 months, and the current diagnostic criteria, the studies undoubtedly
thus monitoring is required for patients using this drug; included many migraine patients. The name tension-type
SECTION II

the risk of fibrosis is about 1:1500 and is likely to reverse headache implies that pain is a product of nervous tension,
after the drug is stopped. but there is no clear evidence for tension as an etiology.
The probability of success with any one of the anti- Muscle contraction has been considered to be a feature
migraine drugs is 5075%. Many patients are managed that distinguishes TTH from migraine, but there appear
adequately with low-dose amitriptyline, propranolol, to be no differences in contraction between the two
topiramate, gabapentin, or valproate. If these agents fail headache types.
Clinical Manifestations of Neurologic Disease

or lead to unacceptable side effects, second-line agents


such as methysergide or phenelzine can be used. Once
effective stabilization is achieved, the drug is continued TREATMENT Tension-Type Headache
for 6 months and then slowly tapered to assess the
continued need. Many patients are able to discontinue The pain of TTH can generally be managed with simple
medication and experience fewer and milder attacks for analgesics such as acetaminophen, aspirin, or NSAIDs.
long periods, suggesting that these drugs may alter the Behavioral approaches including relaxation can also be
natural history of migraine. effective. Clinical studies have demonstrated that trip-
tans in pure TTH are not helpful, although triptans are
effective in TTH when the patient also has migraine.
TENSION-TYPE HEADACHE For chronic TTH, amitriptyline is the only proven treat-
ment (Table 8-7); other tricyclics, selective serotonin
Clinical features reuptake inhibitors, and the benzodiazepines have not
The term tension-type headache (TTH) is commonly used been shown to be effective. There is no evidence for
to describe a chronic head-pain syndrome characterized the efficacy of acupuncture. Placebo-controlled trials
by bilateral tight, bandlike discomfort. The pain typically of onabotulinum toxin type A in chronic TTH have not
builds slowly, uctuates in severity, and may persist more shown benefit.
or less continuously for many days. The headache may
be episodic or chronic (present >15 days per month).
A useful clinical approach is to diagnose TTH in TRIGEMINAL AUTONOMIC CEPHALALGIAS,
patients whose headaches are completely without INCLUDING CLUSTER HEADACHE
accompanying features such as nausea, vomiting, pho- The trigeminal autonomic cephalalgias (TACs) describe
tophobia, phonophobia, osmophobia, throbbing, and a grouping of primary headaches including cluster head-
aggravation with movement. Such an approach neatly ache, paroxysmal hemicrania, and SUNCT (short-
separates migraine, which has one or more of these fea- lasting unilateral neuralgiform headache attacks with
tures and is the main differential diagnosis, from TTH. conjunctival injection and tearing)/SUNA (short-lasting
The International Headache Societys main denition unilateral neuralgiform headache attacks with cranial
of TTH allows an admixture of nausea, photophobia, autonomic symptoms). TACs are characterized by rela-
or phonophobia in various combinations, although the tively short-lasting attacks of head pain associated with
appendix denition does not; this illustrates the dif- cranial autonomic symptoms, such as lacrimation, con-
culty in distinguishing these two clinical entities. In junctival injection, or nasal congestion (Table 8-8).
clinical practice, dichotomizing patients on the basis of Pain is usually severe and may occur more than once a
the presence of associated features (migraine) and the day. Because of the associated nasal congestion or rhi-
absence of associated features (TTH) is highly recom- norrhea, patients are often misdiagnosed with sinus
mended. Indeed patients whose headaches t the TTH headache and treated with decongestants, which are
phenotype and who have migraine at other times, along ineffective.
with a family history of migraine, migrainous illnesses of TACs must be differentiated from short-lasting head-
childhood, or typical migraine triggers to their migraine aches that do not have prominent cranial autonomic
attacks, may be biologically different from those who syndromes, notably trigeminal neuralgia, primary stab-
have TTH headache with none of the features. bing headache, and hypnic headache. The cycling
TABLE 8-8 63
CLINICAL FEATURES OF THE TRIGEMINAL AUTONOMIC CEPHALALGIAS
CLUSTER HEADACHE PAROXYSMAL HEMICRANIA SUNCT

Gender M>F F=M FM


Pain
Type Stabbing, boring Throbbing, boring, stabbing Burning, stabbing, sharp
Severity Excruciating Excruciating Severe to excruciating
Site Orbit, temple Orbit, temple Periorbital

CHAPTER 8
Attack frequency 1/alternate day8/d 140/d (>5/d for more than 3200/d
half the time)
Duration of attack 15180 min 230 min 5240 s
Autonomic features Yes Yes Yes (prominent conjunctival
injection and lacrimation)a

Headache
Migrainous featuresb Yes Yes Yes
Alcohol trigger Yes No No
Cutaneous triggers No No Yes
Indomethacin effect Yesc
Abortive treatment Sumatriptan injection No effective treatment Lidocaine (IV)
or nasal spray
Oxygen
Prophylactic treatment Verapamil Indomethacin Lamotrigine
Methysergide Topiramate
Lithium Gabapentin

a
If conjunctival injection and tearing not present, consider SUNA.
b
Nausea, photophobia, or phonophobia; photophobia and phonophobia are typically unilateral on the side of the pain.
c
Indicates complete response to indomethacin.
Abbreviation: SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing.

pattern and length, frequency, and timing of attacks are Onset is nocturnal in about 50% of patients, and men
useful in classifying patients. Patients with TACs should are affected three times more often than women.
undergo pituitary imaging and pituitary function tests as Patients with cluster headache tend to move about dur-
there is an excess of TAC presentations in patients with ing attacks, pacing, rocking, or rubbing their head for
pituitary tumorrelated headache. relief; some may even become aggressive during attacks.
This is in sharp contrast to patients with migraine, who
prefer to remain motionless during attacks.
Cluster headache
Cluster headache is associated with ipsilateral symp-
Cluster headache is a rare form of primary headache toms of cranial parasympathetic autonomic activa-
with a population frequency of approximately 0.1%. tion: conjunctival injection or lacrimation, rhinorrhea
The pain is deep, usually retroorbital, often excruciat- or nasal congestion, or cranial sympathetic dysfunc-
ing in intensity, nonuctuating, and explosive in qual- tion such as ptosis. The sympathetic decit is periph-
ity. A core feature of cluster headache is periodicity. At eral and likely to be due to parasympathetic activation
least one of the daily attacks of pain recurs at about the with injury to ascending sympathetic bers surrounding
same hour each day for the duration of a cluster bout. a dilated carotid artery as it passes into the cranial cavity.
The typical cluster headache patient has daily bouts of When present, photophobia and phonophobia are far
one to two attacks of relatively short-duration unilateral more likely to be unilateral and on the same side of the
pain for 8 to 10 weeks a year; this is usually followed pain, rather than bilateral, as is seen in migraine. This
by a pain-free interval that averages a little less than 1 phenomenon of unilateral photophobia/phonophobia is
year. Cluster headache is characterized as chronic when characteristic of TACs. Cluster headache is likely to be
there is no signicant period of sustained remission. a disorder involving central pacemaker neurons in the
Patients are generally perfectly well between episodes. region of the posterior hypothalamus (Fig. 8-3).
64 regarding the early symptoms of ergotism, which may
TREATMENT Cluster Headache
include vomiting, numbness, tingling, pain, and cyanosis
The most satisfactory treatment is the administration of of the limbs; a weekly limit of 14 mg should be adhered to.
drugs to prevent cluster attacks until the bout is over. Lithium (600900 mg qd) appears to be particularly useful
However, treatment of acute attacks is required for all for the chronic form of the disorder.
cluster headache patients at some time. Many experts favor verapamil as the first-line pre-
ventive treatment for patients with chronic cluster
ACUTE ATTACK TREATMENT Cluster head-
headache or prolonged bouts. While verapamil com-
ache attacks peak rapidly, and thus a treatment with
pares favorably with lithium in practice, some patients
SECTION II

quick onset is required. Many patients with acute clus-


require verapamil doses far in excess of those admin-
ter headache respond very well to oxygen inhalation.
istered for cardiac disorders. The initial dose range is
This should be given as 100% oxygen at 1012 L/min for
4080 mg twice daily; effective doses may be as high
1520 min. It appears that high flow and high oxygen
as 960 mg/d. Side effects such as constipation and leg
content are important. Sumatriptan 6 mg SC is rapid in
swelling can be problematic. Of paramount concern,
onset and will usually shorten an attack to 1015 min;
however, is the cardiovascular safety of verapamil,
Clinical Manifestations of Neurologic Disease

there is no evidence of tachyphylaxis. Sumatriptan (20


particularly at high doses. Verapamil can cause heart
mg) and zolmitriptan (5 mg) nasal sprays are both effec-
block by slowing conduction in the atrioventricular
tive in acute cluster headache, offering a useful option
node, a condition that can be monitored by following
for patients who may not wish to self-inject daily. Oral
the PR interval on a standard ECG. Approximately 20%
sumatriptan is not effective for prevention or for acute
of patients treated with verapamil develop ECG abnor-
treatment of cluster headache.
malities, which can be observed with doses as low as
PREVENTIVE TREATMENTS (Table 8-9) The 240 mg/d; these abnormalities can worsen over time
choice of a preventive treatment in cluster headache in patients on stable doses. A baseline ECG is recom-
depends in part on the length of the bout. Patients with mended for all patients. The ECG is repeated 10 days
long bouts or those with chronic cluster headache require after a dose change in those patients whose dose is
medicines that are safe when taken for long periods. For being increased above 240 mg daily. Dose increases
patients with relatively short bouts, limited courses of are usually made in 80-mg increments. For patients on
oral glucocorticoids or methysergide (not available in the long-term verapamil, ECG monitoring every 6 months
United States) can be very useful. A 10-day course of pred- is advised.
nisone, beginning at 60 mg daily for 7 days and followed
NEUROSTIMULATION THERAPY When medical
by a rapid taper, may interrupt the pain bout for many
therapies fail in chronic cluster headache, neurostimula-
patients. When ergotamine (12 mg) is used, it is most
tion strategies can be employed. Deep-brain stimulation of
effective when given 12 h before an expected attack.
the region of the posterior hypothalamic gray matter has
Patients who use ergotamine daily must be educated
proven successful in a substantial proportion of patients.
Favorable results have also been reported with the less-
TABLE 8-9 invasive approach of occipital nerve stimulation.
PREVENTIVE MANAGEMENT OF CLUSTER
HEADACHE
SHORT-TERM PREVENTION LONG-TERM PREVENTION PAROXYSMAL HEMICRANIA
EPISODIC CLUSTER Paroxysmal hemicrania (PH) is characterized by fre-
HEADACHE & PROLONGED quent unilateral, severe, short-lasting episodes of head-
EPISODIC CLUSTER CHRONIC CLUSTER
HEADACHE HEADACHE
ache. Like cluster headache, the pain tends to be ret-
roorbital but may be experienced all over the head and
Prednisone 1 mg/kg up to Verapamil 160960 mg/d is associated with autonomic phenomena such as lacri-
60 mg qd, tapering over
mation and nasal congestion. Patients with remissions
21 days
Lithium 400800 mg/d
are said to have episodic PH, whereas those with the
nonremitting form are said to have chronic PH. The
Methysergide 312 mg/d Methysergide 312 mg/d
essential features of PH are unilateral, very severe pain;
Verapamil 160960 mg/d Topiramatea 100400 mg/d short-lasting attacks (245 min); very frequent attacks
Greater occipital nerve Gabapentina 12003600 mg/d (usually more than ve a day); marked autonomic fea-
injection tures ipsilateral to the pain; rapid course (<72 h); and
Melatonina 912 mg/d excellent response to indomethacin. In contrast to clus-
ter headache, which predominantly affects males, the
a
Unproven but of potential benet. male:female ratio in PH is close to 1:1.
Indomethacin (2575 mg tid), which can completely Secondary (Symptomatic) SUNCT 65
suppress attacks of PH, is the treatment of choice. SUNCT can be seen with posterior fossa or pituitary
Although therapy may be complicated by indometh- lesions. All patients with SUNCT/SUNA should be
acin-induced gastrointestinal side effects, currently evaluated with pituitary function tests and a brain MRI
there are no consistently effective alternatives. Topira- with pituitary views.
mate is helpful in some cases. Piroxicam has been used,
although it is not as effective as indomethacin. Vera-
pamil, an effective treatment for cluster headache, does TREATMENT SUNCT/SUNA
not appear to be useful for PH. In occasional patients,

CHAPTER 8
PH can coexist with trigeminal neuralgia (PH-tic syn-
ABORTIVE THERAPY Therapy of acute attacks is
drome); similar to cluster-tic syndrome, each compo-
nent may require separate treatment. not a useful concept in SUNCT/SUNA since the attacks are
Secondary PH has been reported with lesions in the of such short duration. However, IV lidocaine, which arrests
region of the sella turcica, including arteriovenous mal- the symptoms, can be used in hospitalized patients.
formation, cavernous sinus meningioma, and epider- PREVENTIVE THERAPY Long-term prevention
moid tumors. Secondary PH is more likely if the patient

Headache
to minimize disability and hospitalization is the goal of
requires high doses (>200 mg/d) of indomethacin. In treatment. The most effective treatment for prevention is
patients with apparent bilateral PH, raised CSF pressure lamotrigine, 200400 mg/d. Topiramate and gabapentin
should be suspected. It is important to note that indo- may also be effective. Carbamazepine, 400500 mg/d,
methacin reduces CSF pressure. When a diagnosis of has been reported by patients to offer modest benefit.
PH is considered, MRI is indicated to exclude a pitu- Surgical approaches such as microvascular decom-
itary lesion. pression or destructive trigeminal procedures are sel-
dom useful and often produce long-term complications.
Greater occipital nerve injection has produced limited
SUNCT/SUNA
benefit in some patients. Occipital nerve stimulation
SUNCT (short-lasting unilateral neuralgiform headache is probably helpful in an important subgroup of these
attacks with conjunctival injection and tearing) is a rare patients. Complete control with deep-brain stimulation
primary headache syndrome characterized by severe, uni- of the posterior hypothalamic region was reported in a
lateral orbital or temporal pain that is stabbing or throb- single patient. For intractable cases, short-term preven-
bing in quality. Diagnosis requires at least 20 attacks, tion with IV lidocaine can be effective, as can occipital
lasting for 5240 s; ipsilateral conjunctival injection and nerve stimulation.
lacrimation should be present. In some patients conjunc-
tival injection or lacrimation is missing, and the diagnosis
of SUNA (short-lasting unilateral neuralgiform headache CHRONIC DAILY HEADACHE
attacks with cranial autonomic symptoms) can be made. The broad diagnosis of chronic daily headache (CDH)
can be applied when a patient experiences headache
Diagnosis
on 15 days or more per month. CDH is not a single
The pain of SUNCT/SUNA is unilateral and may be
entity; it encompasses a number of different headache
located anywhere in the head. Three basic patterns
syndromes, including chronic TTH as well as headache
can be seen: single stabs, which are usually short-lived;
secondary to trauma, inammation, infection, medica-
groups of stabs; or a longer attack comprising many
tion overuse, and other causes (Table 8-10). Popula-
stabs between which the pain does not completely
tion-based estimates suggest that about 4% of adults
resolve, thus giving a saw-tooth phenomenon with
have daily or near-daily headache. Daily headache may
attacks lasting many minutes. Each pattern may be seen
be primary or secondary, an important consideration in
in the context of an underlying continuous head pain.
guiding management of this complaint.
Characteristics that lead to a suspected diagnosis of
SUNCT are the cutaneous (or other) triggerability of
attacks, a lack of refractory period to triggering between APPROACH TO THE
attacks, and the lack of a response to indomethacin. PATIENT Chronic Daily Headache
Apart from trigeminal sensory disturbance, the neuro-
The first step in the management of patients with CDH
logic examination is normal in primary SUNCT.
is to diagnose any underlying condition (Table 810).
The diagnosis of SUNCT is often confused with tri-
For patients with primary headaches, diagnosis of the
geminal neuralgia (TN) particularly in rst-division TN
headache type will guide therapy. Preventive treat-
(Chap. 34). Minimal or no cranial autonomic symptoms
ments such as tricyclics, either amitriptyline or nortrip-
and a clear refractory period to triggering indicate a
tyline at doses up to 1 mg/kg, are very useful in patients
diagnosis of TN.
66 TABLE 8-10
Management of Medication Overuse: Out-
CLASSIFICATION OF CHRONIC DAILY HEADACHE patients For patients who overuse medications, it is
PRIMARY essential that analgesic use be reduced and eliminated.
One approach is to reduce the medication dose by 10%
>4 h DAILY <4 h DAILY SECONDARY
every 12 weeks. Immediate cessation of analgesic use
a
Chronic migraine Chronic cluster Posttraumatic is possible for some patients, provided there is no con-
headacheb Head injury traindication. Both approaches are facilitated by the use
Iatrogenic of a medication diary maintained during the month or
Postinfectious two before cessation; this helps to identify the scope of
SECTION II

Chronic tension- Chronic Inammatory, such as the problem. A small dose of an NSAID such as naproxen,
type headachea paroxysmal Giant cell arteritis 500 mg bid, if tolerated, will help relieve residual pain as
hemicrania Sarcoidosis analgesic use is reduced. NSAID overuse is not usually a
Behets syndrome problem for patients with daily headache when the dose
Hemicrania SUNCT/SUNA Chronic CNS is taken once or twice daily; however, overuse problems
continuaa infection may develop with more frequent dosing schedules. Once
Clinical Manifestations of Neurologic Disease

New daily persis- Hypnic Medication-overuse the patient has substantially reduced analgesic use, a
tent headachea headache headachea preventive medication should be introduced. It must be
emphasized that preventives generally do not work in the
a
May be complicated by analgesic overuse. presence of analgesic overuse. The most common cause
b
Some patients may have headache >4 h/d.
of unresponsiveness to treatment is the use of a preven-
Abbreviations: SUNA, short-lasting unilateral neuralgiform head-
ache attacks with cranial autonomic symptoms; SUNCT, short- tive when analgesics continue to be used regularly. For
lasting unilateral neuralgiform headache attacks with conjunctival some patients, discontinuing analgesics is very difficult;
injection and tearing. often the best approach is to directly inform the patient
that some degree of pain is inevitable during this initial
period.
with CDH arising from migraine or tension-type head-
ache. Tricyclics are started in low doses (1025 mg) Management of Medication Overuse: Inpa-
daily and may be given 12 h before the expected time tients Some patients will require hospitalization for
of awakening in order to avoid excess morning sleepi- detoxification. Such patients have typically failed efforts
ness. Anticonvulsants, such as topiramate, valproate, at outpatient withdrawal or have a significant medical
and gabapentin, are also useful in migraineurs. Flunari- condition, such as diabetes mellitus, which would com-
zine can also be very effective for some patients, as can plicate withdrawal as an outpatient. Following admission
methysergide or phenelzine. to the hospital, acute medications are withdrawn com-
pletely on the first day, in the absence of a contraindica-
MANAGEMENT OF MEDICALLY INTRAC- tion. Antiemetics and fluids are administered as required;
TABLE DISABLING CHRONIC DAILY HEAD- clonidine is used for opiate withdrawal symptoms. For
ACHE The management of medically intractable acute intolerable pain during the waking hours aspirin,
headache is difficult. At this time, the only promising 1 g IV (not approved in United States), is useful. IM chlor-
approach is occipital nerve stimulation, which appears promazine can be helpful at night; patients must be ade-
to modulate thalamic processing in migraine and quately hydrated. Three to five days into the admission
has also shown promise in chronic cluster headache, as the effect of the withdrawn substance settles a course
SUNCT/SUNA, and hemicrania continua (see next). of IV dihydroergotamine (DHE) can be employed. DHE,
MEDICATION-OVERUSE HEADACHE Over- administered every 8 h for 5 consecutive days, can induce
useof analgesic medication for headache can aggravate a significant remission that allows a preventive treatment
headache frequency and induce a state of refractory to be established. 5-HT3 antagonists, such as ondansetron
daily or near-daily headache called medication-overuse or granisetron, are often required with DHE to prevent
headache. A proportion of patients who stop taking significant nausea, and domperidone (not approved in
analgesics will experience substantial improvement in the United States) orally or by suppository can be very
the severity and frequency of their headache. However, helpful.
even after cessation of analgesic use, many patients NEW DAILY PERSISTENT HEADACHE New
continue to have headache, although they may feel clin- daily persistent headache (NDPH) is a clinically distinct
ically improved in some way, especially if they have been syndrome; its causes are listed in Table 8-11.
using codeine or barbiturates regularly. The residual
symptoms probably represent the underlying headache CLINICAL PRESENTATION The patient with
disorder. NDPH presents with headache on most if not all days
TABLE 8-11
toms appear to result from low volume rather than low 67
DIFFERENTIAL DIAGNOSIS OF NEW DAILY pressure: although low CSF pressures, typically 050
PERSISTENT HEADACHE
mmH2O, are usually identified, a pressure as high as 140
PRIMARY SECONDARY mmH2O has been noted with a documented leak.
Migrainous-type Subarachnoid hemorrhage Postural orthostatic tachycardia syndrome (POTS
[Chap. 33]) can present with orthostatic headache simi-
Featureless (tension-type) Low CSF volume headache
lar to low CSF volume headache and is a diagnosis that
Raised CSF pressure headache needs consideration here.
Posttraumatic headachea When imaging is indicated to identify the source of

CHAPTER 8
Chronic meningitis a presumed leak, an MRI with gadolinium is the initial
study of choice (Fig. 8-5). A striking pattern of diffuse
a
Includes postinfectious forms. meningeal enhancement is so typical that in the appro-
priate clinical context the diagnosis is established. Chiari
malformations may sometimes be noted on MRI; in such
and the patient can clearly, and often vividly, recall cases, surgery to decompress the posterior fossa usu-

Headache
the moment of onset. The headache usually begins ally worsens the headache. Spinal MRI with T2 weight-
abruptly, but onset may be more gradual; evolution ing may reveal a leak and spinal MRI may demonstrate
over 3 days has been proposed as the upper limit for spinal meningeal cysts whose role in these syndromes
this syndrome. Patients typically recall the exact day is yet to be elucidated. The source of CSF leakage may
and circumstances of the onset of headache; the new, be identified by spinal MRI, by CT, or increasingly with
persistent head pain does not remit. The first priority MR myelography, or with 111In-DTPA CSF studies; in the
is to distinguish between a primary and a secondary absence of a directly identified site of leakage, early
cause of this syndrome. Subarachnoid hemorrhage is emptying of 111In-DTPA tracer into the bladder or slow
the most serious of the secondary causes and must be progress of tracer across the brain suggests a CSF leak.
excluded either by history or appropriate investigation Initial treatment for low CSF volume headache is
(Chap. 28). bed rest. For patients with persistent pain, IV caffeine
Secondary NDPH (500 mg in 500 mL saline administered over 2 h) can be
very effective. An ECG to screen for arrhythmia should
Low CSF Volume Headache In these syn- be performed before administration. It is reasonable
dromes, head pain is positional: it begins when the to administer at least two infusions of caffeine before
patient sits or stands upright and resolves upon reclin- embarking on additional tests to identify the source of
ing. The pain, which is occipitofrontal, is usually a dull the CSF leak. Since IV caffeine is safe and can be curative,
ache but may be throbbing. Patients with chronic low
CSF volume headache typically present with a history of
headache from one day to the next that is generally not
present on waking but worsens during the day. Recum-
bency usually improves the headache within minutes,
but it takes only minutes to an hour for the pain to
return when the patient resumes an upright position.
The most common cause of headache due to per-
sistent low CSF volume is CSF leak following lumbar
puncture (LP). Post-LP headache usually begins within
48 h but may be delayed for up to 12 days. Its inci-
dence is between 10 and 30%. Beverages with caffeine
may provide temporary relief. Besides LP, index events
may include epidural injection or a vigorous Valsalva
maneuver, such as from lifting, straining, coughing,
clearing the eustachian tubes in an airplane, or multiple
orgasms. Spontaneous CSF leaks are well recognized,
and the diagnosis should be considered whenever the
headache history is typical, even when there is no obvi-
ous index event. As time passes from the index event,
the postural nature may become less apparent; cases FIGURE 8-5
Magnetic resonance image showing diffuse meningeal
in which the index event occurred several years before
enhancement after gadolinium administration in a patient
the eventual diagnosis have been recognized. Symp-
with low CSF volume headache.
68 it spares many patients the need for further investiga- infectious episode, typically viral meningitis, a flulike ill-
tions. If unsuccessful, an abdominal binder may be help- ness, or a parasitic infection. Complaints of dizziness,
ful. If a leak can be identified, an autologous blood patch vertigo, and impaired memory can accompany the head-
is usually curative. A blood patch is also effective for ache. Symptoms may remit after several weeks or persist
post-LP headache; in this setting, the location is empiri- for months and even years after the injury. Typically the
cally determined to be the site of the LP. In patients with neurologic examination is normal and CT or MRI stud-
intractable pain, oral theophylline is a useful alternative; ies are unrevealing. Chronic subdural hematoma may on
however, its effect is less rapid than caffeine. occasion mimic this disorder. In one series, one-third of
patients with NDPH reported headache beginning after
SECTION II

Raised CSF Pressure Headache Raised CSF a transient flulike illness characterized by fever, neck
pressure is well recognized as a cause of headache. stiffness, photophobia, and marked malaise. Evaluation
Brain imaging can often reveal the cause, such as a reveals no apparent cause for the headache. There is no
space-occupying lesion. NDPH due to raised CSF pres- convincing evidence that persistent Epstein-Barr infec-
sure can be the presenting symptom for patients with tion plays a role in this syndrome. A complicating factor
idiopathic intracranial hypertension (pseudotumor is that many patients undergo LP during the acute ill-
Clinical Manifestations of Neurologic Disease

cerebri) without visual problems, particularly when the ness; iatrogenic low CSF volume headache must be con-
fundi are normal. Persistently raised intracranial pres- sidered in these cases. Posttraumatic headache may also
sure can trigger chronic migraine. These patients typi- be seen after carotid dissection and subarachnoid hem-
cally present with a history of generalized headache orrhage, and following intracranial surgery. The underly-
that is present on waking and improves as the day ing theme appears to be that a traumatic event involving
goes on. It is generally worse with recumbency. Visual the pain-producing meninges can trigger a headache
obscurations are frequent. The diagnosis is relatively process that lasts for many years.
straightforward when papilledema is present, but the Treatment is largely empirical. Tricyclic antidepres-
possibility must be considered even in patients without sants, notably amitriptyline, and anticonvulsants such as
funduscopic changes. Formal visual field testing should topiramate, valproate, and gabapentin, have been used
be performed even in the absence of overt ophthal- with reported benefit. The MAOI phenelzine may also be
mic involvement. Headache on rising in the morning or useful in carefully selected patients. The headache usually
nocturnal headache is also characteristic of obstructive resolves within 35 years, but it can be quite disabling.
sleep apnea or poorly controlled hypertension.
Primary NDPH Primary NDPH occurs in both males
Evaluation of patients suspected to have raised CSF
and females. It can be of the migrainous type, with fea-
pressure requires brain imaging. It is most efficient to
tures of migraine, or it can be featureless, appearing as
obtain an MRI, including an MR venogram, as the initial
new-onset TTH (Table 8-11). Migrainous features are
study. If there are no contraindications, the CSF pres-
common and include unilateral headache and throb-
sure should be measured by LP; this should be done
bing pain; each feature is present in about one-third of
when the patient is symptomatic so that both the pres-
patients. Nausea, photophobia, and/or phonophobia
sure and the response to removal of 2030 mL of CSF
occur in about half of patients. Some patients have a
can be determined. An elevated opening pressure and
previous history of migraine; however, the proportion of
improvement in headache following removal of CSF is
NDPH sufferers with preexisting migraine is no greater
diagnostic.
than the frequency of migraine in the general population.
Initial treatment is with acetazolamide (250500 mg
At 24 months, 86% of patients are headache-free. Treat-
bid); the headache may improve within weeks. If inef-
ment of migrainous-type primary NDPH consists of using
fective, topiramate is the next treatment of choice; it
the preventive therapies effective in migraine (Table 8-7).
has many actions that may be useful in this setting,
Featureless NDPH is one of the primary headache forms
including carbonic anhydrase inhibition, weight loss,
most refractory to treatment. Standard preventive thera-
and neuronal membrane stabilization, likely mediated
pies can be offered but are often ineffective.
via effects on phosphorylation pathways. Severely dis-
abled patients who do not respond to medical treat-
ment require intracranial pressure monitoring and may
require shunting. OTHER PRIMARY HEADACHES
Hemicrania continua
Posttraumatic Headache A traumatic event
can trigger a headache process that lasts for many The essential features of hemicrania continua are moder-
months or years after the event. The term trauma is used ate and continuous unilateral pain associated with uc-
in a very broad sense: headache can develop following tuations of severe pain; complete resolution of pain with
an injury to the head, but it can also develop after an indomethacin; and exacerbations that may be associated
with autonomic features, including conjunctival injec- lesion causing obstruction of CSF pathways or displac- 69
tion, lacrimation, and photophobia on the affected side. ing cerebral structures can be the cause of the head pain.
The age of onset ranges from 11 to 58 years; women are Other conditions that can present with cough or exer-
affected twice as often as men. The cause is unknown. tional headache as the initial symptom include cerebral
aneurysm, carotid stenosis, and vertebrobasilar disease.
Benign cough headache can resemble benign exertional
TREATMENT Hemicrania Continua headache (discussed next), but patients with the former
condition are typically older.
Treatment consists of indomethacin; other NSAIDs

CHAPTER 8
appear to be of little or no benefit. The IM injection of 100
mg indomethacin has been proposed as a diagnostic tool TREATMENT Primary Cough Headache
and administration with a placebo injection in a blinded
fashion can be very useful diagnostically. Alternatively, a Indomethacin 2550 mg two to three times daily is the
trial of oral indomethacin, starting with 25 mg tid, then treatment of choice. Some patients with cough head-
50 mg tid, and then 75 mg tid, can be given. Up to two ache obtain pain relief with LP; this is a simple option
when compared to prolonged use of indomethacin, and

Headache
weeks at the maximal dose may be necessary to assess
whether a dose has a useful effect. Topiramate can be it is effective in about one-third of patients. The mecha-
helpful in some patients. Occipital nerve stimulation may nism of this response is unclear.
have a role in patients with hemicrania continua who are
unable to tolerate indomethacin. Primary exertional headache
Primary exertional headache has features resembling
Primary stabbing headache both cough headache and migraine. It may be pre-
The essential features of primary stabbing headache are cipitated by any form of exercise; it often has the pul-
stabbing pain conned to the head or, rarely, the face, satile quality of migraine. The pain, which can last
lasting from 1 to many seconds or minutes and occur- from 5 min to 24 h, is bilateral and throbbing at onset;
ring as a single stab or a series of stabs; absence of asso- migrainous features may develop in patients susceptible
ciated cranial autonomic features; absence of cutane- to migraine. Primary exertional headache can be pre-
ous triggering of attacks; and a pattern of recurrence at vented by avoiding excessive exertion, particularly in
irregular intervals (hours to days). The pains have been hot weather or at high altitude.
variously described as ice-pick pains or jabs and The mechanism of primary exertional headache is
jolts. They are more common in patients with other unclear. Acute venous distension likely explains one
primary headaches, such as migraine, the TACs, and syndrome, the acute onset of headache with strain-
hemicrania continua. ing and breath holding, as in weightlifters headache.
As exertion can result in headache in a number of seri-
ous underlying conditions, these must be considered
in patients with exertional headache. Pain from angina
TREATMENT Primary Stabbing Headache
may be referred to the head, probably by central con-
The response of primary stabbing headache to indo- nections of vagal afferents, and may present as exertional
methacin (2550 mg two to three times daily) is usu- headache (cardiac cephalgia). The link to exercise is the
ally excellent. As a general rule, the symptoms wax and main clinical clue that headache is of cardiac origin.
wane, and after a period of control on indomethacin, it Pheochromocytoma may occasionally cause exertional
is appropriate to withdraw treatment and observe the headache. Intracranial lesions and stenosis of the carotid
outcome. arteries are other possible etiologies.

Primary cough headache TREATMENT Primary Exertional Headache

Primary cough headache is a generalized headache that Exercise regimens should begin modestly and progress
begins suddenly, lasts for several minutes, and is precipi- gradually to higher levels of intensity. Indomethacin at
tated by coughing; it is preventable by avoiding cough- daily doses from 25 to 150 mg is generally effective in
ing or other precipitating events, which can include benign exertional headache. Indomethacin (50 mg),
sneezing, straining, laughing, or stooping. In all patients ergotamine (1 mg orally), dihydroergotamine (2 mg
with this syndrome, serious etiologies must be excluded by nasal spray), or methysergide (12 mg orally given
before a diagnosis of benign primary cough head- 3045 min before exercise) are useful prophylactic mea-
ache can be established. A Chiari malformation or any sures.
70 Primary Sex Headache aneurysm is uncertain. When neuroimaging studies and
LP exclude subarachnoid hemorrhage, patients with
Sex headache is precipitated by sexual excitement. The thunderclap headache usually do very well over the
pain usually begins as a dull bilateral headache that sud- long term. In one study of patients whose CT scans and
denly becomes intense at orgasm. The headache can CSF ndings were negative, 15% had recurrent epi-
be prevented or eased by ceasing sexual activity before sodes of thunderclap headache, and nearly half subse-
orgasm. Three types of sex headache are reported: a quently developed migraine or tension-type headache.
dull ache in the head and neck that intensies as sex- The rst presentation of any sudden-onset severe
ual excitement increases; a sudden, severe, explosive headache should be vigorously investigated with neuro-
headache occurring at orgasm; and a postural head-
SECTION II

imaging (CT or, when possible, MRI with MR angi-


ache developing after coitus that resembles the head- ography) and CSF examination. Formal cerebral angi-
ache of low CSF pressure. The latter arises from vigor- ography should be reserved for those cases in which no
ous sexual activity and is a form of low CSF pressure primary diagnosis is forthcoming and for clinical situa-
headache. Headaches developing at the time of orgasm tions that are particularly suggestive of intracranial aneu-
are not always benign; 512% of cases of subarachnoid rysm. Reversible segmental cerebral vasoconstriction
hemorrhage are precipitated by sexual intercourse. Sex may be seen in primary thunderclap headache without
Clinical Manifestations of Neurologic Disease

headache is reported by men more often than women an intracranial aneurysm. In the presence of posterior
and may occur at any time during the years of sexual leukoencephalopathy, the differential diagnosis includes
activity. It may develop on several occasions in succes- cerebral angiitis, drug toxicity (cyclosporine, intrathecal
sion and then not trouble the patient again, even with- methotrexate/cytarabine, pseudoephedrine, or cocaine),
out an obvious change in sexual activity. In patients posttransfusion effects, and postpartum angiopathy.
who stop sexual activity when headache is rst noticed, Treatment with nimodipine may be helpful, although
the pain may subside within a period of 5 min to 2 h. In by denition the vasoconstriction of primary thunder-
about half of patients, sex headache will subside within clap headache resolves spontaneously.
6 months. About half of patients with sex headache
have a history of exertional headaches, but there is no
excess of cough headache. Migraine is probably more Hypnic headache
common in patients with sex headache. This headache syndrome typically begins a few hours
after sleep onset. The headaches last from 15 to 30
min and are typically moderately severe and general-
TREATMENT Primary Sex Headache ized, although they may be unilateral and can be throb-
bing. Patients may report falling back to sleep only to
Benign sex headaches recur irregularly and infrequently. be awakened by a further attack a few hours later; up
Management can often be limited to reassurance and to three repetitions of this pattern occur through the
advice about ceasing sexual activity if a mild, warning night. Daytime naps can also precipitate head pain.
headache develops. Propranolol can be used to prevent Most patients are female, and the onset is usually after
headache that recurs regularly or frequently, but the age 60 years. Headaches are bilateral in most, but may
dosage required varies from 40 to 200 mg/d. An alter- be unilateral. Photophobia or phonophobia and nausea
native is the calcium channelblocking agent diltiazem, are usually absent. The major secondary consideration
60 mg tid. Ergotamine (1 mg) or indomethacin (2550 in this headache type is poorly controlled hypertension;
mg) taken about 3045 min prior to sexual activity can 24-h blood pressure monitoring is recommended to
also be helpful. detect this treatable condition.

Primary thunderclap headache


Sudden onset of severe headache may occur in the TREATMENT Hypnic Headache
absence of any known provocation. The differential
Patients with hypnic headache generally respond to
diagnosis includes the sentinel bleed of an intracra-
a bedtime dose of lithium carbonate (200600 mg).
nial aneurysm, cervicocephalic arterial dissection, and
For those intolerant of lithium, verapamil (160 mg) or
cerebral venous thrombosis. Headaches of explosive
methysergide (14 mg at bedtime) may be alternative
onset may also be caused by the ingestion of sympa-
strategies. One to two cups of coffee or caffeine, 60 mg
thomimetic drugs or of tyramine-containing foods in a
orally, at bedtime may be effective in approximately
patient who is taking MAOIs, or they may be a symp-
one-third of patients. Case reports suggest that flunari-
tom of pheochromocytoma. Whether thunderclap head-
zine, 5 mg nightly, can be effective.
ache can be the presentation of an unruptured cerebral
CHAPTER 9

BACK AND NECK PAIN

John W. Engstrom Richard A. Deyo

The importance of back and neck pain in our society The apposition of a superior and inferior facet consti-
is underscored by the following: (1) the cost of back tutes a facet joint. The functions of the posterior spine
pain in the United States exceeds $100 billion annually; are to protect the spinal cord and nerves within the spi-
approximately one-third of these costs are direct health nal canal and to provide an anchor for the attachment
care expenses, and two-thirds are indirect costs resulting of muscles and ligaments. The contraction of muscles
from loss of wages and productivity; (2) back symptoms attached to the spinous and transverse processes and
are the most common cause of disability in those <45 laminae works like a system of pulleys and levers that
years; (3) low back pain is the second most common results in exion, extension, and lateral bending move-
reason for visiting a physician in the United States; and ments of the spine.
(4) 1% of the U.S. population is chronically disabled Nerve root injury (radiculopathy) is a common cause
because of back pain. of neck, arm, low back, buttock, and leg pain (Figs.
15-2 and 15-3). The nerve roots exit at a level above
their respective vertebral bodies in the cervical region
ANATOMY OF THE SPINE (e.g., the C7 nerve root exits at the C6-C7 level) and
below their respective vertebral bodies in the thoracic
The anterior portion of the spine consists of cylindri- and lumbar regions (e.g., the T1 nerve root exits at the
cal vertebral bodies separated by intervertebral disks and T1-T2 level). The cervical nerve roots follow a short
held together by the anterior and posterior longitudi- intraspinal course before exiting. By contrast, because
nal ligaments. The intervertebral disks are composed of the spinal cord ends at the vertebral L1 or L2 level, the
a central gelatinous nucleus pulposus surrounded by a lumbar nerve roots follow a long intraspinal course and
tough cartilaginous ring, the annulus brosis. Disks are can be injured anywhere from the upper lumbar spine
responsible for 25% of spinal column length and allow to their exit at the intervertebral foramen. For example,
the bony vertebrae to move easily upon each other disk herniation at the L4-L5 level can produce not only
(Figs. 9-1 and 9-2). Desiccation of the nucleus pulp- L5 root compression, but also compression of the tra-
osus and degeneration of the annulus brosus increase versing S1 nerve root (Fig. 9-3).
with age and results in loss of height. The disks are larg- Pain-sensitive structures of the spine include the
est in the cervical and lumbar regions where move- periosteum of the vertebrae, dura, facet joints, annulus
ments of the spine are greatest. The functions of the brosus of the intervertebral disk, epidural veins and
anterior spine are to absorb the shock of body move- arteries, and the posterior longitudinal ligament. Disease
ments such as walking and running, and to protect the of these diverse structures may explain many cases of
contents of the spinal canal. back pain without nerve root compression. The nucleus
The posterior portion of the spine consists of the ver- pulposus of the intervertebral disk is not pain-sensitive
tebral arches and processes. Each arch consists of paired under normal circumstances. Pain sensation from within
cylindrical pedicles anteriorly and paired laminae poste- the spinal canal is conveyed partially by the sinuverte-
riorly. The vertebral arch also gives rise to two trans- bral nerve that arises from the spinal nerve at each spine
verse processes laterally, one spinous process posteri- segment and reenters the spinal canal through the inter-
orly, plus two superior and two inferior articular facets. vertebral foramen at the same level.

71
72 Posterior Posterior Anterior

Spinous process Superior articular Superior vertebral


process notch
Superior Intervertebral
articular Lamina Transverse foramen
process process

Spinous
process Intervertebral
SECTION II

disk
Pedicle
Transverse
process
Body

Spinal canal Body


Inferior articular Inferior vertebral
Clinical Manifestations of Neurologic Disease

process (facet) notch

A Anterior B
FIGURE 9-1
Vertebral anatomy. (From A Gauthier Cornuelle, DH Gronefeld: Radiographic Anatomy Posi-
tioning. New York, McGraw-Hill, 1998; with permission.)

1
2
Attention is also focused on identification of risk factors
3 Cervical for serious underlying diseases; the majority of these
4
Cervical (7) curvature are due to radiculopathy, fracture, tumor, infection, or
5
6
7
referred pain from visceral structures (Table 9-1).
1 Local pain is caused by injury to pain-sensitive struc-
2
3
tures that compress or irritate sensory nerve endings.
4 The site of the pain is near the affected part of the back.
5
Thoracic Pain referred to the back may arise from abdominal or
6
curvature pelvic viscera. The pain is usually described as primarily
7
Thoracic (12) 8 abdominal or pelvic but is accompanied by back pain
9
and usually unaffected by posture. The patient may
10
11
occasionally complain of back pain only.
12 Pain of spine origin may be located in the back or
1 referred to the buttocks or legs. Diseases affecting the
2
upper lumbar spine tend to refer pain to the lumbar
region, groin, or anterior thighs. Diseases affecting the
Lumbar
Lumbar (5)
3
curvature lower lumbar spine tend to produce pain referred to the
4 buttocks, posterior thighs, or rarely the calves or feet.
5 Referred or sclerotomal pain may explain instances
where the pain crosses multiple dermatomes without
Sacrum Sacral evidence of nerve root compression.
curvature Radicular back pain is typically sharp and radiates
Coccyx from the low back to a leg within the territory of a nerve
Anterior view Right lateral view root (see Lumbar Disk Disease, later in this chapter).
FIGURE 9-2
Coughing, sneezing, or voluntary contraction of abdomi-
Spinal column. (From A Gauthier Cornuelle, DH Gronefeld: nal muscles (lifting heavy objects or straining at stool)
Radiographic Anatomy Positioning. New York, McGraw-Hill, may elicit the radiating pain. The pain may increase in
1998; with permission.) postures that stretch the nerves and nerve roots. Sitting
with the leg outstretched places traction on the sciatic
APPROACH TO THE nerve and L5 and S1 roots because the nerve passes pos-
PATIENT Back Pain
terior to the hip. The femoral nerve (L2, L3, and L4 roots)
passes anterior to the hip and is not stretched by sitting.
TYPES OF BACK PAIN Understanding the types The description of the pain alone often fails to distin-
of pain reported by patients is the essential first step. guish between sclerotomal pain and radiculopathy.
73

4th Lumbar
pedicle 4th Lumbar
vertebral body
L4 root

CHAPTER 9
Protruded
L4-L5 disk
5th Lumbar
vertebral body

L5 Root

Back and Neck Pain


Protruded
L5-S1 disk

S1 Root

S2 Root

FIGURE 9-3
Compression of L5 and S1 roots by herniated disks. (From Adams and Victors
Principles of Neurology, 9th ed. New York, McGraw-Hill, 2009; with permission.)

Pain associated with muscle spasm, although of


TABLE 9-1 obscure origin, is commonly associated with many spine
ACUTE LOW BACK PAIN: RISK FACTORS FOR AN disorders. The spasms are accompanied by abnormal
IMPORTANT STRUCTURAL CAUSE posture, tense paraspinal muscles, and dull or achy pain
History in the paraspinal region.
Pain worse at rest or at night Knowledge of the circumstances associated with the
Prior history of cancer onset of back pain is important when weighing possible
serious underlying causes for the pain. Some patients
History of chronic infection (esp. lung, urinary tract, skin)
involved in accidents or work-related injuries may exag-
History of trauma gerate their pain for the purpose of compensation or for
Incontinence psychological reasons.
Age >70 years EXAMINATION OF THE BACK A physical exam-
Intravenous drug use ination that includes the abdomen and rectum is advis-
Glucocorticoid use able. Back pain referred from visceral organs may be
History of a rapidly progressive neurologic decit
reproduced during palpation of the abdomen (pancre-
atitis, abdominal aortic aneurysm [AAA]) or percussion
Examination
over the costovertebral angles (pyelonephritis).
Unexplained fever The normal spine has a cervical and lumbar lordosis,
Unexplained weight loss and a thoracic kyphosis. Exaggeration of these normal
Percussion tenderness over the spine alignments may result in hyperkyphosis of the thoracic
spine or hyperlordosis of the lumbar spine. Inspection
Abdominal, rectal, or pelvic mass
may reveal a lateral curvature of the spine (scoliosis)
Patricks sign or heel percussion sign
or an asymmetry in the prominence of the paraspi-
Straight leg or reverse straight legraising signs nal muscles, suggesting muscle spasm. Back pain of
Progressive focal neurologic decit bony spine origin is often reproduced by palpation or
74 percussion over the spinous process of the affected but the key feature is reproduction of the patients usual
vertebrae. pain. The crossed SLR sign is positive when flexion of one
Forward bending is often limited by paraspinal mus- leg reproduces the usual pain in the opposite leg or but-
cle spasm; the latter may flatten the usual lumbar lordo- tocks. The crossed SLR sign is less sensitive but more
sis. Flexion at the hips is normal in patients with lumbar specific for disk herniation than the SLR sign. The nerve
spine disease, but flexion of the lumbar spine is limited or nerve root lesion is always on the side of the pain. The
and sometimes painful. Lateral bending to the side reverse SLR sign is elicited by standing the patient next
opposite the injured spinal element may stretch the to the examination table and passively extending each
damaged tissues, worsen pain, and limit motion. Hyper- leg with the knee fully extended. This maneuver, which
SECTION II

extension of the spine (with the patient prone or stand- stretches the L2-L4 nerve roots, lumbosacral plexus,
ing) is limited when nerve root compression, facet joint and femoral nerve, is considered positive if the patients
pathology, or other bony spine disease is present. usual back or limb pain is reproduced.
Pain from hip disease may mimic the pain of lumbar The neurologic examination includes a search for
spine disease. Hip pain can be reproduced by internal and focal weakness or muscle atrophy, focal reflex changes,
external rotation at the hip with the knee and hip in flexion diminished sensation in the legs, or signs of spinal cord
Clinical Manifestations of Neurologic Disease

(Patricks sign) and by tapping the heel with the examiners injury. The examiner should be alert to the possibility of
palm while the leg is extended (heel percussion sign). breakaway weakness, defined as fluctuating strength
With the patient supine, passive flexion of the during muscle testing. Breakaway weakness may be due
extended leg at the hip stretches the L5 and S1 nerve to pain or a combination of pain and underlying true
roots and the sciatic nerve (straight legraising maneu- weakness. Breakaway weakness without pain is almost
ver). Passive dorsiflexion of the foot during the maneu- always due to a lack of effort. In uncertain cases, elec-
ver adds to the stretch. While flexion to at least 80 is tromyography (EMG) can determine whether or not true
normally possible without causing pain, many patients weakness due to nerve tissue injury is present. Findings
normally report a tight, stretching sensation in the ham- with specific nerve lumbosacral nerve root lesions are
string muscles unrelated to back pain. The straight leg shown in Table 9-2 and are discussed next.
raising (SLR) test is positive if the maneuver reproduces
the patients usual back or limb pain. Eliciting the SLR LABORATORY, IMAGING, AND EMG STUD-
sign in the sitting position can help determine if the IES Routine laboratory studies are rarely needed for
finding is reproducible. The patient may describe pain the initial evaluation of nonspecific acute (<3 months
in the low back, buttocks, posterior thigh, or lower leg, duration) low back pain (ALBP). If risk factors for a serious

TABLE 9-2
LUMBOSACRAL RADICULOPATHYNEUROLOGIC FEATURES
EXAMINATION FINDINGS
LUMBOSACRAL
NERVE ROOTS REFLEX SENSORY MOTOR PAIN DISTRIBUTION
a
L2 Upper anterior thigh Psoas (hip exion) Anterior thigh
a
L3 Lower anterior thigh Psoas (hip exion) Anterior thigh, knee
Anterior knee Quadriceps (knee extension)
Thigh adduction
L4a Quadriceps (knee) Medial calf Quadriceps (knee extension)b Knee, medial calf
Thigh adduction Anterolateral thigh
Tibialis anterior (foot dorsiexion)
L5c Dorsal surfacefoot Peroneii (foot eversion)b Lateral calf, dorsal foot,
Lateral calf Tibialis anterior (foot dorsiexion) posterolateral thigh, but-
Gluteus medius (hip abduction) tocks
Toe dorsiexors
S1c Gastrocnemius/ Plantar surfacefoot Gastrocnemius/soleus (foot plan- Bottom foot, posterior calf,
soleus (ankle) Lateral aspectfoot tar exion)b posterior thigh, buttocks
Abductor hallucis (toe exors)b
Gluteus maximus (hip extension)

a
Reverse straight legraising sign presentsee Examination of the Back.
b
These muscles receive the majority of innervation from this root.
c
Straight legraising sign presentsee Examination of the Back.
underlying cause are present (Table 9-1), then laboratory TABLE 9-3 75
studies (complete blood count [CBC], erythrocyte sedi- CAUSES OF BACK OR NECK PAIN
mentation rate [ESR], urinalysis) are indicated. Congenital/Developmental
CT scanning is superior to routine x-rays for the Spondylolysis and spondylolisthesis
detection of fractures involving posterior spine struc-
Kyphoscoliosis
tures, craniocervical and craniothoracic junctions, C1
and C2 vertebrae, bone fragments within the spinal Spina bida occulta
canal, or misalignment; CT scans are increasingly used Tethered spinal cord
as a primary screening modality for moderate to severe

CHAPTER 9
Minor Trauma
trauma. In the absence of risk factors, these imaging
studies are rarely helpful in nonspecific ALBP. MRI and Strain or sprain
CT-myelography are the radiologic tests of choice for Whiplash injury
evaluation of most serious diseases involving the spine.
Fractures
MRI is superior for the definition of soft tissue structures,
whereas CT-myelography provides optimal imaging of Traumafalls, motor vehicle accidents

Back and Neck Pain


the lateral recess of the spinal canal, and is better toler- Atraumatic fracturesosteoporosis, neoplastic inltration,
ated by claustrophobic patients. While the added diag- exogenous steroids, osteomyelitis
nostic value of modern neuroimaging is significant, Intervertebral Disk Herniation
there is concern that these studies may be overutilized
Degenerative
in patients with benign ALBP.
Electrodiagnostic studies can be used to assess the Intervertebral foraminal narrowing
functional integrity of the peripheral nervous system Disk-osteophyte complex
(Chap. 5). Sensory nerve conduction studies are normal Internal disk disruption
when focal sensory loss is due to nerve root damage
LSS with neurogenic claudication
because the nerve roots are proximal to the nerve cell
bodies in the dorsal root ganglia. Injury to nerve tissue Uncovertebral joint disease
distal to the dorsal root ganglion (e.g., plexus or periph- Atlantoaxial joint disease (e.g., rheumatoid arthritis)
eral nerve) results in reduced sensory nerve signals. Arthritis
Needle EMG complements nerve conduction studies Spondylosis
by detecting denervation or reinnervation changes in
Facet or sacroiliac arthropathy
a myotomal (segmental) distribution. Multiple muscles
supplied by different nerve roots and nerves are sam- Neoplasmsmetastatic, hematologic, primary bone
tumors
pled; the pattern of muscle involvement indicates the
nerve root(s) responsible for the injury. Needle EMG Infection/Inammation
provides objective information about motor nerve fiber Vertebral osteomyelitis
injury when clinical evaluation of weakness is limited by Spinal epidural abscess
pain or poor effort. EMG and nerve conduction studies
Septic disk (diskitis)
will be normal when sensory nerve root injury or irrita-
Meningitis
tion is the source of the pain.
Lumbar arachnoiditis
Autoimmune (e.g., ankylosing spondylitis, reactive arthri-
tis [formerly known as Reiters syndrome])
CAUSES OF BACK PAIN
Metabolic
(Table 9-3) Osteoporosishyperparathyroidism, immobility
Osteosclerosis (e.g., Pagets disease)
CONGENITAL ANOMALIES OF THE LUMBAR Vascular
SPINE Abdominal aortic aneurysm
Spondylolysis is a bony defect in the vertebral pars inter- Vertebral artery dissection
articularis (a segment near the junction of the pedicle Other
with the lamina); the cause is usually a stress microfrac- Referred pain from visceral disease
ture in a congenitally abnormal segment. It occurs in Postural
up to 6% of adolescents. The defect (usually bilateral)
Psychiatric, malingering, chronic pain syndromes
is best visualized on plain x-rays, CT scan, or bone scan
and is frequently asymptomatic. Symptoms may occur
76 in the setting of a single injury, repeated minor injuries, deceleration such as in an automobile accident. These
or growth. Spondylolysis is the most common cause of terms are used loosely and do not clearly describe a spe-
persistent low back pain in adolescents and is often asso- cic anatomic lesion. The pain is usually conned to
ciated with sports-related activities. the lower back, and there is no radiation to the buttocks
Spondylolisthesis is the anterior slippage of the vertebral or legs. Patients with paraspinal muscle spasm often
body, pedicles, and superior articular facets, leaving the assume unusual postures.
posterior elements behind. Spondylolisthesis can be associ-
ated with spondylolysis, congenital anomalies, degenerative Traumatic vertebral fractures
spine disease, or other causes of mechanical weakness of
Most traumatic fractures of the lumbar vertebral bod-
SECTION II

the pars (e.g., infection, osteoporosis, tumor, trauma, prior


surgery). The slippage may be asymptomatic or may cause ies result from injuries producing anterior wedging or
low back pain and hamstring tightness, nerve root injury compression. With severe trauma, the patient may sus-
(the L5 root most frequently), symptomatic spinal stenosis, tain a fracture-dislocation or a burst fracture involv-
or cauda equina syndrome (CES) in severe cases. Tender- ing the vertebral body and posterior elements. Trau-
ness may be elicited near the segment that has slipped matic vertebral fractures are caused by falls from a
forward (most often L4 on L5 or occasionally L5 on S1). height (a pars interarticularis fracture of the L5 vertebra
Clinical Manifestations of Neurologic Disease

A step may be present on deep palpation of the poste- is common), sudden deceleration in an automobile acci-
rior elements of the segment above the spondylolisthetic dent, or direct injury. Neurologic impairment is com-
joint. The trunk may be shortened and the abdomen pro- mon, and early surgical treatment is indicated. In vic-
tuberant as a result. Anterolisthesis or retrolisthesis can also tims of blunt trauma, CT scans of the chest, abdomen,
occur at other cervical or lumbar levels in adults and be or pelvis can be reformatted to detect associated verte-
the source of neck or low back pain. Plain x-rays with the bral fractures.
neck or low back in exion and extension will reveal the
movement at the abnormal spinal segment. Surgery is con-
sidered for pain symptoms that do not respond to conser- LUMBAR DISK DISEASE
vative measures (e.g., rest, physical therapy), and in cases This is a common cause of chronic or recurrent low
with progressive neurologic decit, postural deformity, back and leg pain (Figs. 9-3 and 9-4). Disk disease is
slippage >50%, or scoliosis. most likely to occur at the L4-L5 or L5-S1 levels, but
Spina bida occulta is a failure of closure of one or sev- upper lumbar levels are involved occasionally. The
eral vertebral arches posteriorly; the meninges and spinal cause is often unknown; the risk is increased in over-
cord are normal. A dimple or small lipoma may overlie weight individuals. Disk herniation is unusual prior
the defect. Most cases are asymptomatic and discovered to age 20 years and is rare in the brotic disks of the
incidentally during an evaluation for back pain. elderly. Genetic factors may play a role in predisposing
Tethered cord syndrome usually presents as a progressive some patients to disk disease. The pain may be located
cauda equina disorder (see later), although myelopa- in the low back only or referred to a leg, buttock, or
thy may also be the initial manifestation. The patient is hip. A sneeze, cough, or trivial movement may cause
often a young adult who complains of perineal or peri- the nucleus pulposus to prolapse, pushing the frayed and
anal pain, sometimes following minor trauma. MRI weakened annulus posteriorly. With severe disk disease,
studies reveal a low-lying conus (below L1-L2) and a the nucleus may protrude through the annulus (hernia-
short and thickened lum terminale. tion) or become extruded to lie as a free fragment in the
spinal canal.
The mechanism by which intervertebral disk injury
TRAUMA causes back pain is controversial. The inner annulus
A patient complaining of back pain and an inability to brosus and nucleus pulposus are normally devoid of
move the legs may have a spinal fracture or dislocation, innervation. Inammation and production of proin-
and, with fractures above L1, spinal cord compression. ammatory cytokines within the protruding or ruptured
Care must be taken to avoid further damage to the spi- disk may trigger or perpetuate back pain. Ingrowth of
nal cord or nerve roots by immobilizing the back pend- nociceptive (pain) nerve bers into inner portions of
ing the results of radiologic studies. a diseased disk may be responsible for chronic disk-
ogenic pain. Nerve root injury (radiculopathy) from
disk herniation may be due to compression, inamma-
Sprains and strains
tion, or both; pathologically, demyelination and axonal
The terms low back sprain, strain, and mechanically induced loss are usually present.
muscle spasm refer to minor, self-limited injuries asso- A ruptured disk may be asymptomatic or cause back
ciated with lifting a heavy object, a fall, or a sudden pain, abnormal posture, limitation of spine motion
77

Herniated L4 disc

Herniated L4 disc

Compressed
Compressed

CHAPTER 9
L5 root
Thecal Sac

A B

Back and Neck Pain


FIGURE 9-4
Left L5 radiculopathy. A. Sagittal T2-weighted image on displacement of the thecal sac medially and the left L5 nerve
the left reveals disk herniation at the L4-L5 level. B. Axial root posteriorly in the left lateral recess.
T1-weighted image shows paracentral disk herniation with

(particularly exion), a focal neurologic decit, or intervertebral foramen are optimally visualized by CT-
radicular pain. A dermatomal pattern of sensory loss or myelography. The correlation of neuroradiologic ndings
a reduced or absent deep tendon reex is more sugges- to symptoms, particularly pain, is not simple. Contrast-
tive of a specic root lesion than is the pattern of pain. enhancing tears in the annulus brosus or disk protru-
Motor ndings (focal weakness, muscle atrophy, or fas- sions are widely accepted as common sources of back
ciculations) occur less frequently than focal sensory or pain; however, studies have found that many asymp-
reex changes. Symptoms and signs are usually unilat- tomatic adults have similar ndings. Asymptomatic disk
eral, but bilateral involvement does occur with large protrusions are also common and may enhance with
central disk herniations that compress multiple roots contrast. Furthermore, in patients with known disk herniation
or cause inammation of nerve roots within the spi- treated either medically or surgically, persistence of the hernia-
nal canal. Clinical manifestations of specic nerve root tion 10 years later had no relationship to the clinical outcome.
lesions are summarized in Table 9-2. There is suggestive In summary, MRI ndings of disk protrusion, tears in the
evidence that lumbar disk herniation with a nonprogres- annulus brosus, or contrast enhancement are common
sive nerve root decit can be managed nonsurgically. incidental ndings that, by themselves, should not dictate
The differential diagnosis covers a variety of seri- management decisions for patients with back pain.
ous and treatable conditions, including epidural abscess, The diagnosis of nerve root injury is most secure
hematoma, fracture, or tumor. Fever, constant pain when the history, examination, results of imaging
uninuenced by position, sphincter abnormalities, or studies, and the EMG are concordant. The correla-
signs of spinal cord disease suggest an etiology other tion between CT and EMG for localization of nerve
than lumbar disk disease. Absence of ankle reexes can root injury is between 65 and 73%. Up to one-third
be a normal nding in persons older than age 60 years of asymptomatic adults have a lumbar disk protrusion
or a sign of bilateral S1 radiculopathy. An absent deep detected by CT or MRI scans.
tendon reex or focal sensory loss may indicate injury Management of lumbar disk disease is discussed later
to a nerve root, but other sites of injury along the nerve in the chapter.
must also be considered. For example, an absent knee Cauda equina syndrome (CES) signies an injury
reex may be due to a femoral neuropathy or an L4 of multiple lumbosacral nerve roots within the spi-
nerve root injury. A loss of sensation over the foot and nal canal distal to the termination of the spinal cord
lateral lower calf may result from a peroneal or lateral at L1-2. Low back pain, weakness and areexia in
sciatic neuropathy or an L5 nerve root injury. Focal the legs, saddle anesthesia, or loss of bladder func-
muscle atrophy may reect a nerve root, peripheral tion may occur. The problem must be distinguished-
nerve, anterior horn cell disease, or disuse. from disorders of the lower spinal cord (conus medul-
A lumbar spine MRI scan or CT-myelogram is neces- laris syndrome), acute transverse myelitis (Chap. 35),
sary to establish the location and type of pathology. Spine and Guillain-Barr syndrome (Chap. 46). Combi-
MRIs yield exquisite views of intraspinal and adjacent ned involvement of the conus medullaris and cauda
soft tissue anatomy. Bony lesions of the lateral recess or equina can occur. CES is commonly due to a ruptured
78 lumbosacral intervertebral disk, lumbosacral spine frac- stenosis. Acquired factors that contribute to spinal ste-
ture, hematoma within the spinal canal (e.g., follow- nosis include degenerative diseases (spondylosis, spondy-
ing lumbar puncture in patients with coagulopathy), lolisthesis, scoliosis), trauma, spine surgery, metabolic or
compressive tumor, or other mass lesion. Treatment endocrine disorders (epidural lipomatosis, osteoporosis,
options include surgical decompression, sometimes acromegaly, renal osteodystrophy, hypoparathyroidism),
urgently, in an attempt to restore or preserve motor and Pagets disease. MRI provides the best denition of
or sphincter function, or radiotherapy for metastatic the abnormal anatomy (Fig. 9-5).
tumors (Chap. 37). Conservative treatment of symptomatic LSS includes
nonsteroidal anti-inammatory drugs (NSAIDs), acet-
SECTION II

aminophen, exercise programs, and symptomatic treat-


DEGENERATIVE CONDITIONS ment of acute pain episodes. There is insufcient evi-
Lumbar spinal stenosis (LSS) describes a narrowed lum- dence to support the use of epidural glucocorticoid
bar spinal canal and is frequently asymptomatic. Neuro- injections. Surgical therapy is considered when medical
genic claudication is the usual symptom, consisting of back therapy does not relieve symptoms sufciently to allow
and buttock or leg pain induced by walking or standing for activities of daily living or when signicant focal
neurologic signs are present. Most patients with neu-
Clinical Manifestations of Neurologic Disease

and relieved by sitting. Symptoms in the legs are usu-


ally bilateral. Lumbar stenosis, by itself, is frequently rogenic claudication treated surgically experience sig-
asymptomatic, and the correlation between the severity nicant relief of back and leg pain within 6 weeks post-
of symptoms and degree of stenosis of the spinal canal is operation, and pain relief persists for at least 2 years.
poor. Unlike vascular claudication, symptoms are often Patients treated nonoperatively improve uncommonly.
provoked by standing without walking. Unlike lum- Up to one-quarter develop recurrent stenosis at the
bar disk disease, symptoms are usually relieved by sit- same spinal level or an adjacent level 710 years after
ting. Patients with neurogenic claudication can often the initial surgery; recurrent symptoms usually respond
walk much farther when leaning over a shopping cart to a second surgical decompression.
and can pedal a stationary bike while sitting with ease. Neural foraminal narrowing with radiculopathy is a com-
These exed positions increase the anteroposterior spi- mon degenerative disorder most often caused by the
nal canal diameter and reduce intraspinal venous hyper- same processes that cause lumbar spinal stenosis (Figs.
tension, resulting in pain relief. Focal weakness, sensory 9-1 and 9-6), including osteophytes, lateral disk protru-
loss, or reex changes may occur when spinal stenosis is sion, calcied disk-osteophytes, facet joint hypertrophy,
associated with neural foraminal narrowing and radicu- uncovertebral joint hypertrophy (cervical spine), congen-
lopathy. Severe neurologic decits, including paralysis itally shortened pedicles, or, frequently, a combination
and urinary incontinence, occur only rarely. of these processes. Neoplasms (primary or metastatic),
LSS can be acquired (75%), congenital, or due to a fractures, infections (epidural abscess), or hematomas are
combination of these factors. Congenital forms (achon- other considerations. These conditions can produce uni-
droplasia, idiopathic) are characterized by short, thick lateral nerve root symptoms or signs due to bony com-
pedicles that produce both spinal canal and lateral recess pression at the intervertebral foramen or lateral recess;

Compressed Thecal sac

Normal
Thecal sac Normal
Nerve roots
Facet joints

A B

FIGURE 9-5
Axial T2-weighted images of the lumbar spine. A. The image in the posterior thecal sac with the patient supine. B. The thecal
shows a normal thecal sac within the lumbar spinal canal. The sac is not well visualized due to severe lumbar spinal canal ste-
thecal sac is bright. The lumbar roots are dark punctuate dots nosis, partially the result of hypertrophic facet joints.
Ankylosing spondylitis 79
Uncinate hypertophy
This distinctive arthritic spine disease typically pres-
ents with the insidious onset of low back and buttock
pain. Patients are often males below age 40. Associ-
ated features include morning back stiffness, nocturnal
pain, pain unrelieved by rest, an elevated ESR, and
Compressed C7 root the histocompatibility antigen HLA-B27. Onset at a
young age and back pain improving with exercise are
B characteristic. Loss of the normal lumbar lordosis and

CHAPTER 9
exaggeration of thoracic kyphosis develop as the dis-
ease progresses. Inammation and erosion of the outer
bers of the annulus brosus at the point of contact
with the vertebral body are followed by ossication
C6-C7 disc bulge and bony growth that bridges adjacent vertebral bodies
and reduces spine mobility in all planes. MRI has been

Back and Neck Pain


used to assess the presence of inammation in joints as
A Sagittal T2 cervical spine well as response to treatment and is more sensitive than
FIGURE 9-6 plain x-rays. In later stages, plain x-rays reveal bridg-
Right C7 radiculopathy. A. Sagittal T2-weighted image ing of vertebral bodies to produce the fused bamboo
shows mild disk bulging at C6-C7 and a mildly narrowed spine.
spinal canal, but no visible nerve root compression. B. Axial Stress fractures after minimal or no trauma can occur
T2-weighted image. The combination of uncinate hypertro- through the spontaneously ankylosed posterior bony
phy and facet hypertrophy (ovoid dark space just lateral to elements of the rigid, osteoporotic spine and can pro-
the C7 root) narrows the right C6-C7 intervertebral foramen duce focal pain, spinal instability, spinal cord compres-
resulting in right C7 nerve root compression. sion, or CES. Atlantoaxial subluxation with spinal cord
compression can occur in up to 20% of patients over
time. Ankylosis of the ribs to the spine and a decrease
symptoms are indistinguishable from disk-related radicu- in the height of the thoracic spine may compromise
lopathy, but treatment may differ depending upon the respiratory function. Therapy with antitumor necrosis
specic etiology. The history and neurologic examina- factor agents is effective in reducing disease activity and
tion alone cannot distinguish between these possibili- improving function. Similar to ankylosing spondylitis,
ties, and a spinal neuroimaging (CT or MRI) procedure restricted movements may accompany reactive arthritis
is required to identify the underlying cause. Neurologic (formerly known as Reiters syndrome), psoriatic arthri-
ndings from the examination and EMG can help direct tis, and chronic inammatory bowel disease.
the attention of the radiologist to specic nerve or root
structures that are best visualized on axial images. For facet
joint hypertrophy, surgical foraminotomy produces long- NEOPLASMS
term relief of leg and back pain in 8090% of patients. Back pain is the most common neurologic symptom
The usefulness of therapeutic facet joint blocks for pain in patients with systemic cancer and is the present-
has not been rigorously studied. ing symptom in 20%. The cause is usually vertebral
body metastasis but can also result from spread of can-
cer through the intervertebral foramen (especially with
ARTHRITIS
lymphoma) or from carcinomatous meningitis. Cancer-
Spondylosis, or osteoarthritic spine disease, typically related back pain tends to be constant, dull, unrelieved
occurs in later life and primarily involves the cervi- by rest, and worse at night. By contrast, mechanical low
cal and lumbosacral spine. Patients often complain of back pain usually improves with rest. MRI, CT, and
back pain that increases with movement and is associ- CT-myelography are the studies of choice when spi-
ated with stiffness. The relationship between clinical nal metastasis is suspected. Once a metastasis is found,
symptoms and radiologic ndings is usually not straight- imaging of the entire spine reveals additional tumor
forward. Pain may be prominent when x-ray, CT, or deposits in one-third of patients. MRI is preferred for
MRI ndings are minimal, and prominent degenera- soft tissue denition, but the most rapidly available
tive spine disease can be seen in asymptomatic patients. imaging modality is best because the patients condi-
Osteophytes or combined disk-osteophytes may cause tion may worsen quickly without intervention. Fewer
or contribute to central spinal canal stenosis, lateral than 5% of patients who are nonambulatory at the time
recess stenosis, or neural foraminal narrowing. of diagnosis ever regain the ability to walk; thus, early
80 diagnosis is crucial. The management of spinal metasta- metastatic carcinoma, or glucocorticoid use may accel-
sis is discussed in detail in Chap. 37. erate osteoporosis and weaken the vertebral body, lead-
ing to compression fractures and pain. Up to two-thirds
of compression fractures seen on radiologic imaging are
INFECTIONS/INFLAMMATION asymptomatic. The most common nontraumatic verte-
Vertebral osteomyelitis is often caused by staphylococci, bral body fractures are due to postmenopausal or senile
but other bacteria or tuberculosis (Potts disease) may osteoporosis. The risk of an additional vertebral fracture
be responsible. The primary source of infection is usu- at 1 year following a rst vertebral fracture is 20%. The
ally the urinary tract, skin, or lungs. Intravenous drug presence of fever, weight loss, fracture at a level above
SECTION II

use is a well-recognized risk factor. Whenever pyogenic T4, or other conditions described above should increase
osteomyelitis is found, the possibility of bacterial endo- the suspicion for a cause other than senile osteoporosis.
carditis should be considered. Back pain unrelieved by If tumor is suspected, a bone biopsy or diagnostic search
rest, spine tenderness over the involved spine segment, for a primary tumor is indicated. The sole manifestation
and an elevated ESR are the most common ndings of a compression fracture may be localized back pain
in vertebral osteomyelitis. Fever or an elevated white or radicular pain exacerbated by movement and often
reproduced by palpation over the spinous process of the
Clinical Manifestations of Neurologic Disease

blood cell count is found in a minority of patients. MRI


and CT are sensitive and specic for early detection affected vertebra. The clinical context, neurologic signs,
of osteomyelitis; CT may be more readily available in and radiologic appearance of the spine establish the
emergency settings and better tolerated by some patients diagnosis.
with severe back pain. The intervertebral disk can also Relief of acute pain can often be achieved with
be affected by infection (diskitis), and very rarely by acetaminophen or a combination of opioids and acet-
tumor. aminophen. The role of NSAIDs is controversial.
Spinal epidural abscess (Chap. 35) presents with back Both pain and disability are improved with bracing.
pain (aggravated by movement or palpation), fever, Antiresorptive drugs, especially bisphosphonates (e.g.,
radiculopathy, or signs of spinal cord compression. The alendronate), have been shown to reduce the risk of
subacute development of two or more of these ndings osteoporotic fractures and are the preferred treatment
should increase the index of suspicion for spinal epidu- to prevent additional fractures. Less than one-third
ral abscess. The abscess may track over multiple spinal of patients with prior compression fractures are ade-
levels and is best delineated by spine MRI. quately treated for osteoporosis despite the increased
Lumbar adhesive arachnoiditis with radiculopathy is risk for future fractures; even fewer at-risk patients
due to brosis following inammation within the sub- without a history of fracture are adequately treated.
arachnoid space. The brosis results in nerve root adhe- Interventions (percutaneous vertebroplasty [PVP],
sions, and presents as back and leg pain associated with kyphoplasty) exist for osteoporotic compression frac-
motor, sensory, or reex changes. Causes of arach- tures associated with debilitating pain. Controlled stud-
noiditis include multiple lumbar operations, chronic ies suggest a benet for pain reduction acutely, but not
spinal infections (especially tuberculosis in the develop- at 2 months, when compared with conservative care.
ing world), spinal cord injury, intrathecal hemorrhage, Relief of pain following PVP has also been reported
myelography (rare), intrathecal injections (glucocorti- in patients with vertebral metastases, myeloma, or
coids, anesthetics, or other agents), and foreign bodies. hemangiomas.
The MRI shows clumped nerve roots or loculations Osteosclerosis, an abnormally increased bone den-
of cerebrospinal uid within the thecal sac. Clumped sity often due to Pagets disease, is readily identiable
nerve roots may also occur with demyelinating poly- on routine x-ray studies and can sometimes be a source
neuropathy or neoplastic inltration. Treatment is usu- of back pain. It may be associated with an isolated
ally unsatisfactory. Microsurgical lysis of adhesions, dor- increase in alkaline phosphatase in an otherwise healthy
sal rhizotomy, dorsal root ganglionectomy, and epidural older person. Spinal cord or nerve root compression
steroids have been tried, but outcomes have been poor. can result from bony encroachment. It should not be
Dorsal column stimulation for pain relief has produced assumed that Pagets disease is the cause of a patients
varying results. back pain until other etiologies have been carefully
considered.

METABOLIC CAUSES
Osteoporosis and osteosclerosis REFERRED PAIN FROM VISCERAL DISEASE
Immobilization or underlying conditions such as osteo- Diseases of the thorax, abdomen, or pelvis may refer
malacia, the postmenopausal state, renal disease, mul- pain to the posterior portion of the spinal segment that
tiple myeloma, hyperparathyroidism, hyperthyroidism, innervates the diseased organ. Occasionally, back pain
may be the rst and only manifestation. Upper abdom- and prolapse) or produce sacral pain after prolonged 81
inal diseases generally refer pain to the lower thoracic standing.
or upper lumbar region (eighth thoracic to the rst Menstrual pain may be felt in the sacral region.
and second lumbar vertebrae), lower abdominal dis- Poorly localized, cramping pain can radiate down the
eases to the midlumbar region (second to fourth lum- legs. Pain due to neoplastic inltration of nerves is typi-
bar vertebrae), and pelvic diseases to the sacral region. cally continuous, progressive in severity, and unrelieved
Local signs (pain with spine palpation, paraspinal mus- by rest at night. Less commonly, radiation therapy of
cle spasm) are absent, and little or no pain accompanies pelvic tumors may produce sacral pain from late radia-
routine movements of the spine. tion necrosis of tissue. Low back pain that radiates into

CHAPTER 9
one or both thighs is common in the last weeks of
pregnancy.
Low thoracic or lumbar pain with abdominal Urologic sources of lumbosacral back pain include
disease chronic prostatitis, prostate cancer with spinal metas-
tasis, and diseases of the kidney or ureter. Lesions
Tumors of the posterior wall of the stomach or duo-
of the bladder and testes do not often produce back
denum typically produce epigastric pain, but midline
pain. Infectious, inammatory, or neoplastic renal dis-

Back and Neck Pain


back or paraspinal pain may occur if retroperitoneal
eases may produce ipsilateral lumbosacral pain, as can
extension is present. Fatty foods occaionally induce
renal artery or vein thrombosis. Paraspinal lumbar
back pain associated with biliary disease. Diseases
pain may be a symptom of ureteral obstruction due to
of the pancreas can produce right paraspinal back
nephrolithiasis.
pain (head of the pancreas involved) or left paraspi-
nal pain (body or tail involved). Pathology in retro-
peritoneal structures (hemorrhage, tumors, pyelone-
phritis) can produce paraspinal pain that radiates to OTHER CAUSES OF BACK PAIN
the lower abdomen, groin, or anterior thighs. A mass
in the iliopsoas region can produce unilateral lum- Postural back pain
bar pain with radiation toward the groin, labia, or There is a group of patients with nonspecic chronic
testicle. The sudden appearance of lumbar pain in a low back pain (CLBP) in whom no specic anatomic
patient receiving anticoagulants suggests retroperito- lesion can be found despite exhaustive investigation.
neal hemorrhage. These individuals complain of vague, diffuse back pain
Isolated low back pain occurs in some patients with prolonged sitting or standing that is relieved by
with a contained rupture of an abdominal aortic rest. Exercises to strengthen the paraspinal and abdomi-
aneurysm (AAA). The classic clinical triad of abdomi- nal muscles are sometimes helpful.
nal pain, shock, and back pain occurs in <20% of
patients. The typical patient at risk is an elderly male
smoker with back pain. Frequently, the diagnosis is Psychiatric disease
initially missed because the symptoms and signs can CLBP may be encountered in patients who seek nan-
be nonspecic. Misdiagnoses include nonspecic back cial compensation; in malingerers; or in those with
pain, diverticulitis, renal colic, sepsis, and myocardial concurrent substance abuse. Many patients with CLBP
infarction. A careful abdominal examination reveal- have a history of psychiatric illness (depression, anxiety
ing a pulsatile mass (present in 5075% of patients) is states), or childhood trauma (physical or sexual abuse)
an important physical nding. Patients with suspected that antedates the onset of back pain. Preoperative psy-
AAA should be evaluated with abdominal ultrasound, chological assessment has been used to exclude patients
CT, or MRI. with marked psychological impairments that predict a
poor surgical outcome from spine surgery.

Sacral pain with gynecologic and urologic


disease
IDIOPATHIC
Pelvic organs rarely cause low back pain, except for
gynecologic disorders involving the uterosacral liga- The cause of low back pain occasionally remains
ments. The pain is referred to the sacral region. Endo- unclear. Some patients have had multiple operations for
metriosis or uterine cancers may invade the uterosacral disk disease but have persistent pain and disability. The
ligaments. Pain associated with endometriosis is typi- original indications for surgery may have been question-
cally premenstrual and often continues until it merges able, with back pain only, no denite neurologic signs,
with menstrual pain. Uterine malposition may cause or a minor disk bulge noted on CT or MRI. Scoring
uterosacral ligament traction (retroversion, descensus, systems based upon neurologic signs, psychological
82 factors, physiologic studies, and imaging studies have Evidence-based guidelines suggest that over-the-
been devised to minimize the likelihood of unsuccessful counter medicines such as acetaminophen and NSAIDs
surgery. are first-line options for the treatment of ALBP. Skeletal
muscle relaxants, such as cyclobenzaprine or methocar-
bamol, may be useful, but sedation is a common side
effect. Limiting the use of muscle relaxants to nighttime
TREATMENT Back Pain only may be an option for some patients. Because of the
risk of abuse of some drugs in this category, including
ACUTE LOW BACK PAIN (ALBP) WITHOUT benzodiazepines and carisoprodol, short courses are
SECTION II

RADICULOPATHY ALBP is defined as pain of <3 generally recommended.


months duration. Full recovery can be expected in 85% It is unclear whether opioid analgesics and trama-
of adults with ALBP without leg pain. Most have purely dol are more effective than NSAIDs or acetaminophen
mechanical symptoms (i.e., pain that is aggravated by for treating ALBP; most of the available efficacy data
motion and relieved by rest). are for treatment of chronic back pain. Their use is best
The initial assessment excludes serious causes of reserved for patients who cannot tolerate acetamino-
Clinical Manifestations of Neurologic Disease

spine pathology that require urgent intervention, phen or NSAIDs, or for those with severe refractory pain.
including infection, cancer, or trauma. Risk factors for a As with muscle relaxants, these drugs are often sedat-
serious cause of ALBP are shown in Table 9-1. Labora- ing, so it may be useful to prescribe them at nighttime
tory and imaging studies are unnecessary if risk factors only. Side effects of short-term opioid use include nau-
are absent. CT or plain spine films are rarely indicated in sea, constipation, and pruritis; risks of long-term opioid
the first month of symptoms unless a spine fracture is use include hypersensitivity to pain, hypogonadism,
suspected. and dependency.
The prognosis is generally excellent. Many patients There is no evidence to support use of oral or
do not seek medical care and apparently improve on injected glucocorticoids for acute low back pain without
their own. Even among those seen in primary care, two- radiculopathy. Antiepileptic drugs, such as gabapentin,
thirds report being substantially improved after seven are not FDA approved for treating low back pain, and
weeks. This spontaneous improvement can mislead there is insufficient evidence to support their use in this
clinicians and researchers about the efficacy of treat- setting.
ment interventions. Perhaps as a result, many ineffective Nonpharmacologic treatments for acute low back
treatments have become widespread in the past, such pain include spinal manipulation, physical therapy,
as bed rest, lumbar traction, sacroiliac fusion, and coc- massage, acupuncture, transcutaneous electrical nerve
cygectomy. stimulation, ultrasound, diathermy, and magnets. Spi-
Clinicians should reassure patients that improve- nal manipulation appears to be roughly equivalent to
ment is very likely, and instruct them in self-care. Edu- conventional medical treatments and may be a useful
cation is an important part of treatment. Satisfaction alternative for patients who wish to avoid or who can-
and the likelihood of follow-up increase when patients not tolerate drug therapy. There is little evidence to sup-
are educated about prognosis, treatment methods, port the use of physical therapy, massage, acupuncture,
activity modifications, and strategies to prevent future laser therapy, therapeutic ultrasound, magnets, corsets,
exacerbations. In one study, patients who felt they did or lumbar traction. Though important for chronic pain,
not receive an adequate explanation for their symp- back exercises for acute back pain are generally not sup-
toms wanted further diagnostic tests. In general, bed ported by clinical evidence. There is no useful evidence
rest should be avoided, or kept to a day or two at most, regarding the value of ice or heat applications for ALBP;
for relief of severe symptoms. Several randomized trials many patients report temporary symptomatic relief
suggest that bed rest does not accelerate the pace of from ice, and heat may produce a short-term reduction
recovery. In general, the best activity recommendation in pain after the first week.
is for walking and early resumption of normal physical
activity, avoiding only strenuous manual labor. Possible CHRONIC LOW BACK PAIN WITHOUT
advantages of early ambulation for acute back pain RADICULOPATHY Chronic low back pain is
include maintenance of cardiovascular conditioning, defined as pain lasting >12 weeks; it accounts for 50% of
improved disk and cartilage nutrition, improved bone total back pain costs. Risk factors include obesity, female
and muscle strength, and increased endorphin levels. gender, older age, prior history of back pain, restricted
Specific back exercises or early vigorous exercise have spinal mobility, pain radiating into a leg, high levels of
not shown benefits for acute back pain, but may be use- psychological distress, poor self-rated health, minimal
ful for chronic pain. Application of heat by heating pads physical activity, smoking, job dissatisfaction, and wide-
or heated blankets is sometimes helpful. spread pain. In general, the same treatments that are
recommended for acute low back pain can be useful for acupuncture, and massage. The role of complementary 83
patients with chronic low back pain. In this setting, how- and alternative medicine approaches, aside from spi-
ever, the benefit of opioid therapy or muscle relaxants is nal manipulation, remains unclear. Biofeedback has not
less clear. been studied rigorously. As with acute back pain, spinal
Evidence supports the use of exercise therapy, manipulation may on average offer benefits similar to
and this can be one of the mainstays of treatment for conventional care. Rigorous recent trials of acupunc-
chronic back pain. Effective regimens have generally ture suggest that true acupuncture is not superior to
included a combination of gradually increasing aerobic sham acupuncture, but that both may offer an advan-
exercise, strengthening exercises, and stretching exer- tage over routine care. Whether this is due entirely to

CHAPTER 9
cises. Motivating patients is sometimes challenging, and placebo effects or to stimulation provided even by sham
supervised exercise is best, for example, with a support- acupuncture is uncertain. Some trials of massage ther-
ive physical therapist. In general, activity tolerance is apy have been encouraging, but this has been less well
the primary goal, while pain relief is secondary. Exercise studied than manipulation or acupuncture.
programs can reverse atrophy in paraspinal muscles and Studies of transcutaneous electrical nerve stimula-
strengthen extensors of the trunk. Supervised inten- tion (TENS) have reached conflicting conclusions, but a

Back and Neck Pain


sive physical exercise or work hardening regimens recent evidence-based guideline suggested that there
have been effective in returning some patients to work, was no convincing evidence for its efficacy in treating
improving walking distance, and reducing pain. In addi- chronic back pain.
tion, some forms of yoga have been evaluated in ran- Various injections, including epidural glucocorti-
domized trials and may be helpful for patients who are coid injections, facet joint injections, and trigger point
interested. injections, have been used for treating chronic low back
Medications for chronic low back pain may include pain. However, in the absence of radiculopathy, there
acetaminophen, NSAIDs, and tricyclic antidepres- is no evidence that epidural glucocorticoids are effec-
sants. Trials of the latter suggest some benefit even for tive for treating chronic back pain. Several randomized
patients without evidence of depression. Trials do not trials suggest that facet joint injections are not more
support the efficacy of selective serotonin reuptake effective than saline injections, and recent evidence-
inhibitors for back pain. However, depression is com- based guidelines recommend against their use. Simi-
mon among patients with chronic pain and should be larly, there is little evidence to support the use of trigger
appropriately treated. point injections. Injection studies are sometimes used
Cognitive-behavioral therapy is based on evidence diagnostically to help determine the anatomic source
that psychological and social factors, as well as somatic of back pain. Reproduction of the patients typical pain
pathology, are important in the genesis of chronic pain with discography has been used as evidence that a
and disability. The patients attitudes and beliefs, psy- specific disk is the pain generator. Pain relief following
chological distress, and patterns of illness behavior may a foraminal nerve root block or glucocorticoid injection
all influence responses to chronic pain. Thus, in addi- into a facet has been similarly used as evidence that the
tion to addressing pathophysiologic mechanisms, psy- facet joint or nerve root is the source. However, the pos-
chological treatments are aimed at reducing disability sibility that the injection response was a placebo effect
by modifying cognitive processes and environmental or due to systemic absorption of the glucocorticoids is
contingencies. Cognitive-behavioral therapy includes often not excluded.
efforts to identify and modify patients thinking about Another category of intervention for chronic back
their pain and disability by strategies that may involve pain includes electrothermal and radiofrequency thera-
imagery, attention diversion, or modifying maladaptive pies. Intradiskal therapy has been proposed using both
thoughts, feelings, and beliefs. This approach includes types of energy to thermocoagulate and destroy nerves
educating patients about a multidimensional view of in the intervertebral disk, using specially designed cath-
pain, identifying pain-eliciting or pain-aggravating eters or electrodes. A systematic review has suggested
thoughts and feelings, using coping strategies and that current evidence does not support the use of these
relaxation techniques, and even hypnosis. A systematic intradiskal therapies.
review concluded that such treatments are more effec- Radiofrequency denervation is sometimes used to
tive than a waiting list control group for short-term pain destroy nerves that are thought to mediate pain, and
relief; however, long-term results remain unclear. Behav- this technique has been used for facet joint pain (with
ioral treatments may have effects similar in magnitude the target nerve being the medial branch of the primary
to exercise therapy. dorsal ramus), for back pain thought to arise from the
Back pain is the most common reason for seeking intervertebral disk (ramus communicans), and radicular
complementary and alternative treatments. The most back pain (dorsal root ganglia). A few small trials have
common of these for back pain are spinal manipulation, resulted in conflicting results for facet joint pain. The
84 evidence for presumed diskogenic pain and for radicu- TENS, lumbar supports, traction, radiofrequency facet
lar pain is similarly meager. A trial for patients with joint denervation, intradiskal electrothermal therapy, or
chronic radicular pain found no difference between intradiskal radiofrequency thermocoagulation. Similarly,
radiofrequency denervation of the dorsal root ganglia these treatments are not recommended in guidelines
and sham treatment. Recent systematic reviews have from the American College of Physicians and the Ameri-
thus concluded that there is insufficient evidence to reli- can Pain Society. On the other hand, exercise therapy
ably evaluate these interventional therapies. and treatment of depression appear to be underused.
Surgical intervention for chronic low back pain in the
absence of radiculopathy has been evaluated in a small LOW BACK PAIN WITH RADICULOPATHY A
SECTION II

number of randomized trials, all conducted in Europe. common cause of back pain with radiculopathy is a her-
Each of these studies included patients with back pain niated disk with nerve root impingement, resulting in
and a degenerative disk, but no sciatica. Three of the back pain with radiation down the leg. The prognosis
four trials concluded that lumbar fusion surgery was no for acute low back pain with radiculopathy due to disk
more effective than highly structured, rigorous rehabili- herniation (sciatica) is generally favorable, with most
tation combined with cognitive-behavioral therapy. The patients demonstrating substantial improvement over a
Clinical Manifestations of Neurologic Disease

fourth trial found an advantage of fusion surgery over matter of months. Serial imaging studies suggest spon-
haphazard usual care, which appeared to be less effec- taneous regression of the herniated portion of the disk
tive than the structured rehabilitation in other trials. in two-thirds of patients over 6 months. Nonetheless,
Given conflicting evidence, indications for surgery for there are several important treatment options for pro-
chronic back pain alone have remained controversial. viding symptom relief while this natural healing process
Both U.S. and British guidelines suggest considering unfolds.
referral for an opinion on spinal fusion for people who Resumption of normal activity as much as possible
have completed an optimal nonsurgical treatment pro- is usually the best activity recommendation. Random-
gram (including combined physical and psychological ized trial evidence suggests that bed rest is ineffective
treatment) and who have persistent severe back pain for for treating sciatica as well as for back pain alone. Acet-
which they would consider surgery. aminophen and NSAIDs are appropriate for pain relief,
The newest surgical treatment for degenerated disks although severe pain may require short courses of opi-
with back pain is disk replacement with prosthetic disks. oid analgesics.
These are generally designed as metal plates with a Epidural glucocorticoid injections have a role in pro-
polyethylene cushion sandwiched in between. The tri- viding temporary symptom relief for sciatica due to a
als that led to approval of these devices compared them herniated disk. Although randomized trial evidence is
to spine fusion, and concluded that the artificial disks conflicting, there appears to be some overall short-term
were not inferior. Serious complications appeared to be benefit for pain relief of sciatica. However, there does
somewhat more likely with the artificial disk. This treat- not appear to be a benefit in terms of reducing sub-
ment remains controversial for low back pain. sequent surgical interventions. Diagnostic nerve root
Intensive multidisciplinary rehabilitation programs blocks have been advocated to determine if pain origi-
may involve daily or frequent care involving physical nates from a specific nerve root. However, improvement
therapy, exercise, cognitive-behavioral therapy, a work- may result even when the nerve root is not responsible
place evaluation, and other interventions. For patients for the pain; this may occur as a placebo effect, from
who have not responded to other interventions, such a pain-generating lesion located distally along the
programs appear to offer some benefit. Systematic peripheral nerve, or from anesthesia of the sinuverte-
reviews suggest that the evidence is limited and effects bral nerve. The utility of diagnostic nerve root blocks
are moderate. remains a subject of debate.
Some observers have raised concern that chronic Surgical intervention is indicated for patients who
back pain may often be overtreated. The use of opioids, have progressive motor weakness, demonstrated on
epidural glucocorticoid injections, facet joint injections, clinical examination or EMG, as a result of nerve root
and surgical intervention has increased rapidly in the injury. Urgent surgery is recommended for patients who
past decade, without corresponding population-level have evidence of the cauda equina syndrome or spinal
improvements in pain or functioning among patients cord compression, generally suggested by bowel or
with back pain. In each case, randomized trials provide bladder dysfunction, diminished sensation in a saddle
only minimal support for these treatments in the set- distribution, a sensory level, bilateral leg weakness, or
ting of chronic back pain without radiculopathy. For low bilateral leg spasticity.
back pain without radiculopathy, new British guidelines Surgery is also an important option for patients who
explicitly recommend against use of selective sero- have disabling radicular pain despite optimal conserva-
tonin reuptake inhibitors (SSRIs), any type of injection, tive treatment. Sciatica is perhaps the most common rea-
son for recommending spine surgery. Because patients TRAUMA TO THE CERVICAL SPINE 85
with a herniated disk and sciatica generally experience Trauma to the cervical spine (fractures, subluxation)
rapid improvement over a matter of weeks, most experts places the spinal cord at risk for compression. Motor
do not recommend considering surgery unless the vehicle accidents, violent crimes, or falls account for
patient has failed to respond to 68 weeks of appropri- 87% of cervical spinal cord injuries (Chap. 35). Immedi-
ate nonsurgical management. For patients who have not ate immobilization of the neck is essential to minimize
improved, randomized trials indicate that, compared to further spinal cord injury from movement of unstable
nonsurgical treatment, surgery results in more rapid pain cervical spine segments. The decision to obtain imag-
relief. However, after the first year or two of follow-up, ing should be based upon the nature of the injury. The

CHAPTER 9
patients with sciatica appear to have much the same level NEXUS low-risk criteria established that normally alert
of pain relief and functional improvement with or with- patients without palpation tenderness in the midline;
out surgery. Thus, both treatment approaches are reason- intoxication; neurologic decits; and painful distracting
able, and patient preferences should play a major role injuries had a very low likelihood of a clinically signi-
in decision making. Some patients will want the fastest cant traumatic injury to the cervical spine. The Cana-
possible relief and find surgical risks acceptable. Others dian C-spine rule recommends that imaging should be

Back and Neck Pain


will be more risk-averse and more tolerant of symptoms, obtained following neck region trauma if the patient
and will choose watchful waiting if they understand that is >65 years old, has limb paresthesias, or a dangerous
improvement is likely in the end. mechanism for the injury (e.g., bicycle collision with
The usual surgical procedure is a partial hemilami- tree or parked car, fall from height >3 feet or 5 stairs,
nectomy with excision of the prolapsed disk. Fusion of diving accident). A CT scan is the diagnostic procedure
the involved lumbar segments should be considered of choice for detection of acute fractures. When trau-
only if significant spinal instability is present (i.e., degen- matic injury to the vertebral arteries or cervical spinal
erative spondylolisthesis). The costs associated with cord is suspected, visualization by MRI with MR angi-
lumbar interbody fusion have increased dramatically in ography is preferred.
recent years. There are no large prospective, random- Whiplash injury is due to rapid exion and extension
ized trials comparing fusion to other types of surgical of the neck, usually in automobile accidents, and causes
intervention. In one study, patients with persistent low cervical musculoligamental injury. This diagnosis should
back pain despite an initial diskectomy fared no better not be applied to patients with fractures, disk hernia-
with spine fusion than with a conservative regimen of tion, head injury, focal neurologic ndings, or altered
cognitive intervention and exercise. Artificial disks have consciousness. Up to 50% of persons reporting whip-
been in use in Europe for the past decade; their utility lash injury acutely have persistent neck pain 1 year later.
remains controversial in the United States. Once personal compensation for pain and suffering was
removed from the Australian health care system, the
prognosis for recovery at 1 year from whiplash injury
improved also. Imaging of the cervical spine is not cost-
PAIN IN THE NECK AND SHOULDER effective acutely but is useful to detect disk herniations
(Table 9-4) Neck pain, which usually arises from when symptoms persist for >6 weeks following the
diseases of the cervical spine and soft tissues of the injury. Severe initial symptoms have been associated
neck, is common. Neck pain arising from the cervical with a poor long-term outcome.
spine is typically precipitated by movement and may
be accompanied by focal tenderness and limitation of CERVICAL DISK DISEASE
motion. Pain arising from the brachial plexus, shoul-
der, or peripheral nerves can be confused with cervi- Herniation of a lower cervical disk is a common cause
cal spine disease, but the history and examination usu- of neck, shoulder, arm, or hand pain or tingling. Neck
ally identify a more distal origin for the pain. Cervical pain, stiffness, and a range of motion limited by pain
spine trauma, disk disease, or spondylosis with inter- are the usual manifestations. A herniated cervical disk
vertebral foraminal narrowing may be asymptomatic is responsible for 25% of cervical radiculopathies.
or painful and can produce a myelopathy, radiculopa- Extension and lateral rotation of the neck narrows the
thy, or both. The same risk factors for a serious cause ipsilateral intervertebral foramen and may reproduce
of low back pain are thought to apply to neck pain radicular symptoms (Spurlings sign). In young persons,
with the addition that neurologic signs of myelopa- acute nerve root compression from a ruptured cervical
thy (incontinence, sensory level, spastic legs) may also disk is often due to trauma. Cervical disk herniations are
occur. Lhermittes sign, an electrical shock down the usually posterolateral near the lateral recess. The cervi-
spine with neck exion, suggests cervical spinal cord cal nerve roots most commonly affected are C7 and C6.
involvement from any cause. Typical patterns of reex, sensory, and motor changes
86 TABLE 9-4
CERVICAL RADICULOPATHYNEUROLOGIC FEATURES
EXAMINATION FINDINGS
CERVICAL
NERVE ROOTS REFLEX SENSORY MOTOR PAIN DISTRIBUTION
a
C5 Biceps Over lateral deltoid Supraspinatus (initial arm abduction) Lateral arm, medial
Infraspinatusa (arm external rotation) scapula
Deltoida (arm abduction)
Biceps (arm exion)
SECTION II

C6 Biceps Thumb, index ngers Biceps (arm exion) Lateral forearm, thumb,
Radial hand/forearm Pronator teres (internal forearm rotation) index nger
C7 Triceps Middle ngers Tricepsa (arm extension) Posterior arm, dorsal
Dorsum forearm Wrist extensorsa forearm, lateral hand
Extensor digitoruma (nger extension)
C8 Finger exors Little nger Abductor pollicis brevis (abduction D1) 4th and 5th ngers,
Clinical Manifestations of Neurologic Disease

Medial hand and fore- First dorsal interosseous (abduction D2) medial forearm
arm Abductor digiti minimi (abduction D5)
T1 Finger exors Axilla and medial arm Abductor pollicis brevis (abduction D1) Medial arm, axilla
First dorsal interosseous (abduction D2)
Abductor digiti minimi (abduction D5)

a
These muscles receive the majority of innervation from this root.

that accompany specic cervical nerve root lesions are with symptoms or signs in the legs only. MRI is the
summarized in Table 9-4. While the classic patterns study of choice to dene the anatomic abnormalities,
are clinically helpful, there are numerous exceptions but plain CT is adequate to assess bony spurs, forami-
because (1) there is overlap in function between adja- nal narrowing, lateral recess stenosis, or OPLL. EMG
cent nerve roots, (2) symptoms and signs may be evi- and nerve conduction studies can localize and assess
dent in only part of the injured nerve root territory, and the severity of the nerve root injury.
(3) the location of pain is the most variable of the clini-
cal features.
OTHER CAUSES OF NECK PAIN
CERVICAL SPONDYLOSIS Rheumatoid arthritis (RA) of the cervical apophyseal
Osteoarthritis of the cervical spine may produce neck joints produces neck pain, stiffness, and limitation of
pain that radiates into the back of the head, shoul- motion. In advanced RA, synovitis of the atlantoaxial
ders, or arms, or may be the source of headaches in joint (C1-C2; Fig. 9-2) may damage the transverse liga-
the posterior occipital region (supplied by the C2-C4 ment of the atlas, producing forward displacement of
nerve roots). Osteophytes, disk protrusions, or hyper- the atlas on the axis (atlantoaxial subluxation). Radio-
trophic facet or uncovertebral joints may alone or in logic evidence of atlantoaxial subluxation occurs in 30%
combination compress one or several nerve roots at of patients with RA. Not surprisingly, the degree of
the intervertebral foramina (Fig. 9-6); this compres- subluxation correlates with the severity of erosive dis-
sion accounts for 75% of cervical radiculopathies. The ease. When subluxation is present, careful assessment is
roots most commonly affected are C7 and C6. Nar- important to identify early signs of myelopathy. Occa-
rowing of the spinal canal by osteophytes, ossica- sional patients develop high spinal cord compression
tion of the posterior longitudinal ligament (OPLL), or leading to quadriparesis, respiratory insufciency, and
a large central disk may compress the cervical spinal death. Surgery should be considered when myelopa-
cord. Combinations of radiculopathy and myelopathy thy or spinal instability is present. MRI is the imaging
may be present. When little or no neck pain accompa- modality of choice.
nies cord compression, the diagnosis may be confused Ankylosing spondylitis can cause neck pain and less
with amyotrophic lateral sclerosis (Chap. 32), multiple commonly atlantoaxial subluxation; surgery may be
sclerosis (Chap. 39), spinal cord tumors, or syringomy- required to prevent spinal cord compression. Acute
elia (Chap. 35). The possibility of cervical spondylosis herpes zoster presents as acute posterior occipital or
should be considered even when the patient presents neck pain prior to the outbreak of vesicles. Neoplasms
metastatic to the cervical spine, infections (osteomyelitis supraclavicular pain radiating down the arm, numb- 87
and epidural abscess), and metabolic bone diseases may be ness of the fourth and fth ngers or medial forearm,
the cause of neck pain. Neck pain may also be referred and weakness of intrinsic hand muscles innervated by
from the heart with coronary artery ischemia (cervical the ulnar and median nerves. Delayed radiation injury
angina syndrome). may produce similar ndings, although pain is less often
present and almost always less severe. A Pancoast tumor
of the lung is another cause and should be considered,
THORACIC OUTLET especially when a Horners syndrome is present. Supra-
The thoracic outlet contains the rst rib, the subclavian scapular neuropathy may produce severe shoulder pain,

CHAPTER 9
artery and vein, the brachial plexus, the clavicle, and the weakness, and wasting of the supraspinatus and infra-
lung apex. Injury to these structures may result in pos- spinatus muscles. Acute brachial neuritis is often confused
tural or movement-induced pain around the shoulder with radiculopathy; the acute onset of severe shoulder
and supraclavicular region. True neurogenic thoracic outlet or scapular pain is followed typically over days by weak-
syndrome (TOS) is an uncommon disorder resulting from ness of the proximal arm and shoulder girdle muscles
compression of the lower trunk of the brachial plexus innervated by the upper brachial plexus. The onset is
often preceded by an infection. The long thoracic nerve

Back and Neck Pain


or ventral rami of the C8 or T1 nerve roots most often
by an anomalous band of tissue connecting an elongate may be affected; the latter results in a winged scapula.
transverse process at C7 with the rst rib. Pain is mild Brachial neuritis may also present as an isolated paralysis
or absent. Signs include weakness and wasting of intrin- of the diaphragm or with involvement of other nerves
sic muscles of the hand and diminished sensation on the of the upper limb. Recovery is generally good but may
palmar aspect of the fth digit. An anteroposterior cer- take up to 3 years to be complete.
vical spine x-ray will show the elongate C7 transverse Occasional cases of carpal tunnel syndrome pro-
process, and EMG and nerve conduction studies con- duce pain and paresthesias extending into the forearm,
rm the diagnosis. Treatment consists of surgical resec- arm, and shoulder resembling a C5 or C6 root lesion.
tion of the anomalous band. The weakness and wasting Lesions of the radial or ulnar nerve can mimic a radic-
of intrinsic hand muscles typically does not improve, ulopathy at C7 or C8, respectively. EMG and nerve
but surgery halts the insidious progression of weakness. conduction studies can accurately localize lesions to the
Arterial TOS results from compression of the subclavian nerve roots, brachial plexus, or peripheral nerves.
artery by a cervical rib resulting in poststenotic dilatation For further discussion of peripheral nerve disorders,
of the artery and thrombus formation. Blood pressure is see Chap. 45.
reduced in the affected limb, and signs of emboli may be
present in the hand. Neurologic signs are absent. Ultra-
SHOULDER
sound can conrm the diagnosis noninvasively. Treat-
ment is with thrombolysis or anticoagulation (with or Pain arising from the shoulder can on occasion mimic
without embolectomy) and surgical excision of the cer- pain from the spine. If symptoms and signs of radiculop-
vical rib compressing the subclavian artery. Venous TOS athy are absent, then the differential diagnosis includes
is due to subclavian vein thrombosis resulting in swell- mechanical shoulder pain (tendonitis, bursitis, rota-
ing of the arm and pain. The vein may be compressed by tor cuff tear, dislocation, adhesive capsulitis, and cuff
a cervical rib or anomalous scalene muscle. Venography impingement under the acromion) and referred pain
is the diagnostic test of choice. Disputed TOS includes a (subdiaphragmatic irritation, angina, Pancoast tumor).
large number of patients with chronic arm and shoulder Mechanical pain is often worse at night, associated with
pain of unclear cause. The lack of sensitive and specic local shoulder tenderness and aggravated by abduction,
ndings on physical examination or laboratory markers internal rotation, or extension of the arm. Pain from
for this condition frequently results in diagnostic uncer- shoulder disease may radiate into the arm or hand, but
tainty. The role of surgery in disputed TOS is controver- sensory, motor, and reex changes are absent.
sial. Multidisciplinary pain management is a conservative
approach, although treatment is often unsuccessful.
TREATMENT Neck Pain without Radiculopathy

BRACHIAL PLEXUS AND NERVES The evidence regarding treatment for neck pain is less
complete than that for low back pain. As with low back
Pain from injury to the brachial plexus or peripheral
pain, spontaneous improvement is the norm for acute
nerves of the arm can occasionally mimic pain of cer-
neck pain, and the usual goal of therapy is to provide
vical spine origin. Neoplastic inltration of the lower
symptom relief while natural healing processes proceed.
trunk of the brachial plexus may produce shoulder or
88 The evidence in support of nonsurgical treatments TREATMENT Neck Pain with Radiculopathy
for whiplash-associated disorders is generally of poor
quality and neither supports nor refutes the effective- The natural history of neck pain even with radiculopa-
ness of common treatments used for symptom relief. thy is favorable, and many patients will improve with-
Gentle mobilization of the cervical spine combined out specific therapy. Although there are no randomized
with exercise programs may be more beneficial than trials of NSAIDs for neck pain, a course of NSAIDs, with
usual care. Evidence is insufficient to recommend for or or without muscle relaxants, may be appropriate initial
against the use of cervical traction, neck collars, TENS, therapy. Other nonsurgical treatments are commonly
ultrasound, diathermy, or massage. The role of acupunc- used, including opioid analgesics, oral glucocorticoids,
SECTION II

ture for neck pain also remains ambiguous, with poor- cervical traction, and immobilization with a hard or soft
quality studies and conflicting results. cervical collar. However, there are no randomized tri-
For patients with neck pain unassociated with als to establish the effectiveness of these treatments in
trauma, supervised exercise, with or without mobiliza- comparison to natural history alone. Soft cervical collars
tion, appears to be effective. Exercises often include can be modestly helpful by limiting spontaneous and
shoulder rolls and neck stretches. Although there is rela- reflex neck movements that exacerbate pain.
Clinical Manifestations of Neurologic Disease

tively little evidence about the use of muscle relaxants, As for lumbar radiculopathy, epidural glucocorti-
analgesics, and NSAIDs in neck pain, many clinicians coids may provide short-term symptom relief in cervical
use these medications in much the same way as for low radiculopathy. If cervical radiculopathy is due to bony
back pain. compression from cervical spondylosis with foraminal
Low-level laser therapy directed at areas of tender- narrowing, then surgical decompression is generally
ness, local acupuncture points, or a grid of predeter- indicated to forestall progression of neurologic signs.
mined points is a controversial approach to the treat- Surgical treatment can produce rapid and substan-
ment of neck pain. The putative benefits might be tial symptom relief, although it is unclear whether long-
mediated by anti-inflammatory effects, reduction of term outcomes are improved over nonsurgical therapy.
skeletal muscle fatigue, or inhibition of transmission at Reasonable indications for cervical disk surgery include
neuromuscular junctions. A 2009 meta-analysis sug- a progressive radicular motor deficit, functionally limit-
gested that this treatment may provide greater pain ing pain that fails to respond to conservative manage-
relief than sham therapy for both acute and chronic ment, or spinal cord compression.
neck pain. Comparison to other conservative treatment Surgical treatments include anterior cervical diskec-
measures is needed. tomy alone, laminectomy with diskectomy, diskectomy
Although some surgical studies have proposed a with fusion, and disk arthroplasty (implanting an artifi-
role for anterior diskectomy and fusion in patients with cial cervical disk). Fusions can be performed with a vari-
neck pain, these studies generally have not been rigor- ety of techniques. The risk of subsequent radiculopathy
ously conducted. A systematic review suggested that or myelopathy at cervical segments adjacent to a fusion
there was no valid clinical evidence to support either is 3% per year and 26% per decade. Although this risk
cervical fusion or cervical disk arthroplasty in patients is sometimes portrayed as a late complication of sur-
with neck pain without radiculopathy. Similarly, there is gery, it may also reflect the natural history of degenera-
no evidence to support radiofrequency neurotomy or tive cervical disk disease. The durability of disk prosthe-
cervical facet injections for neck pain without radicu- ses is uncertain. Available data do not strongly support
lopathy. one surgical technique over another.
CHAPTER 10

SYNCOPE

Roy Freeman

Syncope is a transient, self-limited loss of consciousness for syncope-related hospitalization in the United States
due to acute global impairment of cerebral blood ow. is $2 billion. Syncope has a lifetime cumulative inci-
The onset is rapid, duration brief, and recovery spon- dence of up to 35% in the general population. The peak
taneous and complete. Other causes of transient loss of incidence in the young occurs between ages 10 and 30
consciousness need to be distinguished from syncope; years, with a median peak around 15 years. Neurally
these include seizures, vertebrobasilar ischemia, hypox- mediated syncope is the etiology in the vast majority of
emia, and hypoglycemia. A syncopal prodrome (presyn- these cases. In elderly adults, there is a sharp rise in the
cope) is common, although loss of consciousness may incidence of syncope after 70 years.
occur without any warning symptoms. Typical pre- In population-based studies, neurally mediated syn-
syncopal symptoms include dizziness, lightheadedness cope is the most common cause of syncope. The inci-
or faintness, weakness, fatigue, and visual and auditory dence is slightly higher in females than males. In young
disturbances. The causes of syncope can be divided into subjects there is often a family history in rst-degree
three general categories: (1) neurally mediated syncope relatives. Cardiovascular disease due to structural disease
(also called reex syncope), (2) orthostatic hypotension, or arrhythmias is the next most common cause in most
and (3) cardiac syncope. series, particularly in emergency room settings and in
Neurally mediated syncope comprises a heteroge- older patients. Orthostatic hypotension also increases in
neous group of functional disorders that are character- prevalence with age because of the reduced baroreex
ized by a transient change in the reexes responsible for responsiveness, decreased cardiac compliance, and atten-
maintaining cardiovascular homeostasis. Episodic vaso- uation of the vestibulosympathetic reex associated with
dilation and bradycardia occur in varying combinations, aging. In the elderly, orthostatic hypotension is substan-
resulting in temporary failure of blood pressure control. tially more common in institutionalized (5468%) than
In contrast, in patients with orthostatic hypotension due community dwelling (6%) individuals, an observation
to autonomic failure, these cardiovascular homeostatic most likely explained by the greater prevalence of pre-
reexes are chronically impaired. Cardiac syncope may disposing neurologic disorders, physiologic impairment,
be due to arrhythmias or structural cardiac diseases that and vasoactive medication use among institutionalized
cause a decrease in cardiac output. The clinical features, patients.
underlying pathophysiologic mechanisms, therapeu- The prognosis after a single syncopal event for all
tic interventions, and prognoses differ markedly among age groups is generally benign. In particular, syncope
these three causes. of noncardiac and unexplained origin in younger indi-
viduals has an excellent prognosis; life expectancy is
unaffected. By contrast, syncope due to a cardiac cause,
either structural heart disease or primary arrhythmic dis-
EPIDEMIOLOGY AND NATURAL
ease, is associated with an increased risk of sudden car-
HISTORY
diac death and mortality from other causes. Similarly,
Syncope is a common presenting problem, account- mortality rate is increased in individuals with syncope
ing for approximately 3% of all emergency room vis- due to orthostatic hypotension related to age and the
its and 1% of all hospital admissions. The annual cost associated comorbid conditions (Table 10-1).

89
90 TABLE 10-1 From the clinical standpoint, a fall in systemic systolic
blood pressure to 50 mmHg or lower will result in
HIGH-RISK FEATURES INDICATING
syncope. A decrease in cardiac output and/or systemic
HOSPITALIZATION OR INTENSIVE EVALUATION
OF SYNCOPE vascular resistancethe determinants of blood pres-
surethus underlies the pathophysiology of syncope.
Chest pain suggesting coronary ischemia
Common causes of impaired cardiac output include
Features of congestive heart failure decreased effective circulating blood volume; increased
Moderate or severe valvular disease thoracic pressure; massive pulmonary embolus; cardiac
Moderate or severe structural cardiac disease brady- and tachyarrhythmias; valvular heart disease; and
SECTION II

Electrocardiographic features of ischemia myocardial dysfunction. Systemic vascular resistance


may be decreased by central and peripheral autonomic
History of ventricular arrhythmias
nervous system diseases, sympatholytic medications, and
Prolonged QT interval (>500 ms) transiently during neurally mediated syncope. Increased
Repetitive sinoatrial block or sinus pauses cerebral vascular resistance, most frequently due to
Persistent sinus bradycardia hypocarbia induced by hyperventilation, may also con-
tribute to the pathophysiology of syncope.
Clinical Manifestations of Neurologic Disease

Trifascicular block
The sequence of changes on the electroencephalo-
Atrial brillation
gram of syncopal subjects during syncope comprises
Nonsustained ventricular tachycardia background slowing (often of high amplitude), followed
Family history of sudden death by attenuation or cessation of cortical activity prior to
Preexcitation syndromes return of slow waves, and then normal activity. Despite
the presence of myoclonic movements and other motor
Brugada pattern on ECG
activity, electroencephalographic seizure discharges are
not present in syncopal subjects.
PATHOPHYSIOLOGY
The upright posture imposes a unique physiologic stress CLASSIFICATION
upon humans; most, although not all, syncopal episodes
occur from a standing position. Standing results in pool- NEURALLY MEDIATED SYNCOPE
ing of 5001000 mL of blood in the lower extremi- Neurally mediated syncope is the nal pathway of a
ties and splanchnic circulation. There is a decrease complex central and peripheral nervous system reex arc.
in venous return to the heart and reduced ventricu- There is a sudden, transient change in autonomic efferent
lar lling that result in diminished cardiac output and activity characterized by increased parasympathetic out-
blood pressure. These hemodynamic changes provoke ow causing bradycardia and sympathoinhibition causing
a compensatory reex response, initiated by the baro- vasodilation. The change in autonomic efferent activity
receptors in the carotid sinus and aortic arch, resulting leads to a decrease in blood pressure and a subsequent fall
in increased sympathetic outow and decreased vagal in cerebral blood ow to below the limits of autoregula-
nerve activity (Fig. 10-1). The reex increases periph- tion (Fig. 10-2). In order to elicit this reex, a normal
eral resistance, venous return to the heart, and cardiac or functioning autonomic nervous system is necessary;
output and thus limits the fall in blood pressure. If this this is in contrast to the situation in autonomic failure.
response fails, as is the case chronically in orthostatic The triggers of the afferent limb of the reex arc vary and
hypotension and transiently in neurally mediated syn- may be clearly dened, e.g., the carotid sinus, the gastro-
cope, cerebral hypoperfusion occurs. intestinal tract, or the bladder. In many cases, however,
Syncope is a consequence of global cerebral hypo- the afferent arc is less easily recognized and, under many
perfusion and thus represents a failure of cerebral blood circumstances, the cause is multifactorial. Under these
ow autoregulatory mechanisms. Myogenic factors, circumstances it is likely that multiple afferent pathways
local metabolites, and to a lesser extent autonomic neu- converge on the central autonomic network within the
rovascular control are responsible for the autoregulation medulla that integrates the neural impulses and mediates
of cerebral blood ow (Chap. 28). Typically cerebral the vasodepressor-bradycardic response.
blood ow ranges from 50 to 60 mL/min per 100 g
brain tissue and remains relatively constant over perfu-
Classication of neurally mediated syncope
sion pressures ranging from 50 to 150 mmHg. Cessation
of blood ow for 68 s will result in loss of conscious- Neurally mediated syncope may be subdivided based on
ness, while impairment of consciousness ensues when the afferent pathway and provocative trigger. Vasova-
blood ow decreases to 25 mL/min per 100 g brain gal syncope (the common faint) is provoked by intense
tissue. emotion, pain, and/or orthostatic stress, whereas the
91

CHAPTER 10
Syncope
FIGURE 10-1
The Baroreex. A decrease in arterial pressure unloads the excitatory pathway) and from there to the rostral ventrolat-
baroreceptorsthe terminals of afferent bers of the glos- eral medulla (RVLM) (an inhibitory pathway). The activation of
sopharyngeal and vagus nervesthat are situated in the RVLM presympathetic neurons in response to hypotension
carotid sinus and aortic arch. This leads to a reduction in is thus predominantly due to disinhibition. In response to a
the afferent impulses that are relayed from these mechano- sustained fall in blood pressure, vasopressin release is medi-
receptors through the glossopharyngeal and vagus nerves ated by projections from the A1 noradrenergic cell group in
to the nucleus of the tractus solitarius (NTS) in the dorso- the ventrolateral medulla. This projection activates vasopres-
medial medulla. The reduced baroreceptor afferent activity sin-synthesizing neurons in the magnocellular portion of the
produces a decrease in vagal nerve input to the sinus node paraventricular nucleus (PVN) and the supraoptic nucleus
that is mediated by the neuroanatomical connections of the (SON) of the hypothalamus. Blue denotes sympathetic neu-
NTS to the nucleus ambiguus (NA). There is an increase in rons and green parasympathetic neurons. (From R Freeman:
sympathetic efferent activity that is mediated by the NTS N Engl J Med 358:615, 2008.)
projections to the caudal ventrolateral medulla (CVLM) (an

situational reex syncopes have specic localized stim- Alternately, neurally mediated syncope may be sub-
uli that provoke the reex vasodilation and bradycardia divided based on the predominant efferent pathway.
that leads to syncope. The underlying mechanisms have Vasodepressor syncope describes syncope predominantly
been identied and pathophysiology delineated for most due to efferent, sympathetic, vasoconstrictor failure; car-
of these situational reex syncopes. The afferent trigger dioinhibitory syncope describes syncope predominantly
may originate in the pulmonary system, gastrointesti- associated with bradycardia or asystole due to increased
nal system, urogenital system, heart, and carotid artery vagal outow; while mixed syncope describes syncope
(Table 10-2). Hyperventilation leading to hypocarbia in which there are both vagal and sympathetic reex
and cerebral vasoconstriction, and raised intrathoracic changes.
pressure that impairs venous return to the heart, play a
central role in many of the situational reex syncopes.
Features of neurally mediated syncope
The afferent pathway of the reex arc differs among
these disorders, but the efferent response via the vagus In addition to symptoms of orthostatic intolerance such
and sympathetic pathways is similar. as dizziness, lightheadedness, and fatigue, premonitory
92 125
120

100
100

HR (bpm)
HR (bpm)
80
75 60

50 40

20
25
120
150
SECTION II

125 100

BP (mm Hg)
BP (mm Hg)

100 80
75 60
50
40
25
20
Clinical Manifestations of Neurologic Disease

60 120 180 240 300 360 120 140 160 180 200
A Time (sec) B Time (sec)

FIGURE 10-2
A. The paroxysmal hypotensive-bradycardic response tilt table. B. The same tracing expanded to show 80 s of the
that is characteristic of neurally mediated syncope. Non- episode (from 80 to 200 s). BP, blood pressure; bpm, beats
invasive beat-to-beat blood pressure and heart rate are per minute; HR, heart rate.
shown over 5 min (from 60 to 360 s) of an upright tilt on a

features of autonomic activation may be present in syncope. Isometric counterpressure maneuvers of the
patients with neurally mediated syncope. These include limbs (leg crossing or handgrip and arm tensing) may
diaphoresis, pallor, palpitations, nausea, hyperventila- raise blood pressure and, by maintaining pressure in the
tion, and yawning. During the syncopal event, proximal autoregulatory zone, avoid or delay the onset of syn-
and distal myoclonus (typically arrhythmic and multifo- cope. Randomized controlled trials support this inter-
cal) may occur, raising the possibility of epilepsy. The vention.
eyes typically remain open and usually deviate upward. Fludrocortisone, vasoconstricting agents, and beta-
Urinary but not fecal incontinence may occur. Postictal adrenoreceptor antagonists are widely used by experts
confusion is rare, although visual and auditory halluci- to treat refractory patients, although there is no consis-
nations are sometimes reported. tent evidence from randomized, controlled trials for any
While some predisposing factors and provocative stim- pharmacotherapy to treat neurally mediated syncope.
uli are well established (for example, motionless upright Because vasodilation is the dominant pathophysiologic
posture, warm ambient temperature, intravascular vol- syncopal mechanism in most patients, use of a cardiac
ume depletion, alcohol ingestion, hypoxemia, anemia, pacemaker is rarely beneficial. Possible exceptions are
pain, the sight of blood, venipuncture, and intense emo- older patients in whom syncope is associated with asys-
tion), the underlying basis for the widely different thresh- tole or severe bradycardia, and patients with prominent
olds for syncope among individuals exposed to the same cardioinhibition due to carotid sinus syndrome. In these
provocative stimulus is not known. A genetic basis for patients, dual-chamber pacing may be helpful.
neurally mediated syncope may exist; several studies have
reported an increased incidence of syncope in rst-degree
relatives of fainters, but no gene or genetic marker has
been identied, and environmental, social, and cultural
ORTHOSTATIC HYPOTENSION
factors have not been excluded by these studies.
Orthostatic hypotension, dened as a reduction in
systolic blood pressure of at least 20 mmHg or dia-
stolic blood pressure of at least 10 mmHg within
TREATMENT Neurally Mediated Syncope 3 min of standing or head-up tilt on a tilt table, is a
manifestation of sympathetic vasoconstrictor (auto-
Reassurance, avoidance of provocative stimuli, and
nomic) failure (Fig. 10-3). In many (but not all)
plasma volume expansion with fluid and salt are the
cases, there is no compensatory increase in heart rate
cornerstones of the management of neurally mediated
despite hypotension; with partial autonomic failure,
TABLE 10-2 93
CAUSES OF SYNCOPE
A. Neurally Mediated Syncope
Vasovagal syncope
Provoked fear, pain, anxiety, intense emotion, sight of blood, unpleasant sights and odors, orthostatic
stress
Situational reex syncope
Pulmonary
Cough syncope, wind instrument players syncope, weightlifters syncope, mess tricka and faint-

CHAPTER 10
ing lark,b sneeze syncope, airway instrumentation
Urogenital
Postmicturition syncope, urogenital tract instrumentation, prostatic massage
Gastrointestinal
Swallow syncope, glossopharyngeal neuralgia, esophageal stimulation, gastrointestinal tract instru-
mentation, rectal examination, defecation syncope
Cardiac

Syncope
Swallow syncope, glossopharyngeal neuralgia, esophageal stimulation, gastrointestinal tract instru-
mentation, rectal examination, defecation syncope
Carotid sinus
Carotid sinus sensitivity, carotid sinus massage
Ocular
Ocular pressure, ocular examination, ocular surgery
B. Orthostatic Hypotension
Primary autonomic failure due to idiopathic central and peripheral neurodegenerative diseasesthe
synucleinopathies
Lewy body diseases
Parkinsons disease
Lewy body dementia
Pure autonomic failure
Multiple system atrophy (the Shy-Drager syndrome)
Secondary autonomic failure due to autonomic peripheral neuropathies
Diabetes
Hereditary amyloidosis (familial amyloid polyneuropathy)
Primary amyloidosis (AL amyloidosis; immunoglobulin light chain associated)
Hereditary sensory and autonomic neuropathies (HSAN) (especially type IIIfamilial dysautonomia)
Idiopathic immune-mediated autonomic neuropathy
Autoimmune autonomic ganglionopathy
Sjgrens syndrome
Paraneoplastic autonomic neuropathy
HIV neuropathy
Postprandial hypotension
Iatrogenic (drug-induced)
Volume depletion
C. Cardiac Syncope
Arrhythmias
Sinus node dysfunction
Atrioventricular dysfunction
Supraventricular tachycardias
Ventricular tachycardias
Inherited channelopathies
Cardiac structural disease
Valvular disease
Myocardial ischemia
Obstructive and other cardiomyopathies
Atrial myxoma
Pericardial effusions and tamponade
a
Hyperventilation for 1 min, followed by sudden chest compression.
b
Hyperventilation (20 breaths) in a squatting position, rapid rise to standing, then Valsalva.
94 75 74

72

HR (bpm)

HR (bpm)
70
70

65 68
200 180
SECTION II

150 150
BP (mm Hg)

BP (mm Hg)
100 120

50 90
Clinical Manifestations of Neurologic Disease

0 60

60 120 180 240 300 360 180 190 200 210 220
A Time (sec) Time (sec)
B

FIGURE 10-3
A. The gradual fall in blood pressure without a compen- upright tilt on a tilt table. B. The same tracing expanded to
satory heart rate increase that is characteristic of ortho- show 40 s of the episode (from 180 to 220 s). BP, blood pres-
static hypotension due to autonomic failure. Blood pressure sure; bpm, beats per minute; HR, heart rate.
and heart rate are shown over 5 min (from 60 to 360 s) of an

heart rate may increase to some degree but is insuf- occur suddenly, suggesting the possibility of a seizure or
cient to maintain cardiac output. A variant of ortho- cardiac cause.
static hypotension is delayed orthostatic hypoten- Supine hypertension is common in patients with
sion which occurs beyond 3 min of standing; this may orthostatic hypotension due to autonomic failure,
reect a mild or early form of sympathetic adrener- affecting over 50% of patients in some series. Ortho-
gic dysfunction. In some cases, orthostatic hypoten- static hypotension may present after initiation of ther-
sion occurs within 15 s of standing (so-called initial apy for hypertension, and supine hypertension may fol-
orthostatic hypotension), a nding that may repre- low treatment of orthostatic hypotension. However,
sent a transient mismatch between cardiac output and in other cases, the association of the two conditions
peripheral vascular resistance and does not represent is unrelated to therapy; it may in part be explained by
autonomic failure. baroreex dysfunction in the presence of residual sym-
Characteristic symptoms of orthostatic hypotension pathetic outow, particularly in patients with central
include light-headedness, dizziness, and presyncope autonomic degeneration.
(near-faintness) occurring in response to sudden pos-
tural change. However, symptoms may be absent or
Causes of neurogenic orthostatic hypotension
nonspecic, such as generalized weakness, fatigue, cog-
nitive slowing, leg buckling, or headache. Visual blur- Causes of neurogenic orthostatic hypotension include
ring may occur, likely due to retinal or occipital lobe central and peripheral autonomic nervous system dys-
ischemia. Neck paintypically in the suboccipital, pos- function (Chap. 33). Autonomic dysfunction of other
terior cervical, and shoulder region (the coat-hanger organ systems (including the bladder, bowels, sexual
headache)most likely due to neck muscle ischemia, organs, and sudomotor system) of varying severity fre-
may be the only symptom. Patients may report ortho- quently accompanies orthostatic hypotension in these
static dyspnea (thought to reect ventilation-perfusion disorders (Table 10-2).
mismatch due to inadequate perfusion of ventilated The primary autonomic degenerative disorders are
lung apices) or angina (attributed to impaired myo- multiple system atrophy (the Shy-Drager syndrome;
cardial perfusion even with normal coronary arteries). Chap. 33), Parkinsons disease (Chap. 30), demen-
Symptoms may be exacerbated by exertion, prolonged tia with Lewy bodies (Chap. 29), and pure auto-
standing, increased ambient temperature, or meals. Syn- nomic failure (Chap. 33). These are often grouped
cope is usually preceded by warning symptoms, but may together as synucleinopathies due to the presence of
alpha-synuclein, a small protein that precipitates pre- CARDIAC SYNCOPE 95
dominantly in the cytoplasm of neurons in the Lewy
body disorders (Parkinsons disease, dementia with Cardiac (or cardiovascular) syncope is caused by
Lewy bodies, and pure autonomic failure) and in the arrhythmias and structural heart disease. These may
glia in multiple system atrophy. occur in combination because structural disease ren-
Peripheral autonomic dysfunction may also accom- ders the heart more vulnerable to abnormal electrical
pany small ber peripheral neuropathies such as those activity.
seen in diabetes, amyloid, immune-mediated neuropa-
thies, hereditary sensory and autonomic neuropathies Arrhythmias

CHAPTER 10
(HSAN; particularly HSAN type III; familial dysauto-
nomia), and inammatory neuropathies (Chaps. 46 and Bradyarrhythmias that cause syncope include those due to
47). Less frequently, orthostatic hypotension is associ- severe sinus node dysfunction (e.g., sinus arrest or sino-
ated with the peripheral neuropathies that accompany atrial block) and atrioventricular block (e.g., Mobitz type
vitamin B12 deciency, neurotoxic exposure, HIV and II, high-grade, and complete AV block). The bradyar-
other infections, and porphyria. rhythmias due to sinus node dysfunction are often asso-
ciated with an atrial tachyarrhythmia, a disorder known

Syncope
Patients with autonomic failure and the elderly are
susceptible to falls in blood pressure associated with as the tachycardia-bradycardia syndrome. A prolonged
meals. The magnitude of the blood pressure fall is exac- pause following the termination of a tachycardic epi-
erbated by large meals, meals high in carbohydrate, and sode is a frequent cause of syncope in patients with the
alcohol intake. The mechanism of postprandial syncope tachycardia-bradycardia syndrome. Medications of sev-
is not fully elucidated. eral classes may also cause bradyarrhythmias of sufcient
Orthostatic hypotension is often iatrogenic. Drugs severity to cause syncope. Syncope due to bradycardia or
from several classes may lower peripheral resistance asystole is referred to as a Stokes-Adams attack.
(e.g., alpha-adrenoreceptor antagonists used to treat Ventricular tachyarrhythmias frequently cause syn-
hypertension and prostatic hypertrophy; antihyperten- cope. The likelihood of syncope with ventricular tachy-
sive agents of several classes; nitrates and other vasodi- cardia is in part dependent on the ventricular rate; rates
lators; tricyclic agents and phenothiazines). Iatrogenic below 200 beats per min are less likely to cause syn-
volume depletion due to diuresis and volume depletion cope. The compromised hemodynamic function during
due to medical causes (hemorrhage, vomiting, diarrhea, ventricular tachycardia is caused by ineffective ventricu-
or decreased uid intake) may also result in decreased lar contraction, reduced diastolic lling due to abbrevi-
effective circulatory volume, orthostatic hypotension, ated lling periods, loss of atrioventricular synchrony,
and syncope. and concurrent myocardial ischemia.
Several disorders associated with cardiac electro-
physiologic instability and arrhythmogenesis are due to
mutations in ion channel subunit genes. These include
TREATMENT Orthostatic Hypotension the long QT syndrome, Brugada syndrome, and cat-
echolaminergic polymorphic ventricular tachycardia.
The first step is to remove reversible causesusually The long QT syndrome is a genetically heterogeneous
vasoactive medications (Table 33-6). Next, nonphar- disorder associated with prolonged cardiac repolariza-
macologic interventions should be introduced. These tion and a predisposition to ventricular arrhythmias.
interventions include patient education regarding Syncope and sudden death in patients with long QT
staged moves from supine to upright; warnings about syndrome result from a unique polymorphic ventricular
the hypotensive effects of meal ingestion; instructions tachycardia called torsades des pointes that degenerates
about the isometric counterpressure maneuvers that into ventricular brillation. The long QT syndrome has
increase intravascular pressure (see earlier in this chap- been linked to genes encoding K+ channel -subunits,
ter); and raising the head of the bed to reduce supine K+ channel -subunits, voltage-gated Na+ channel, and
hypertension. Intravascular volume should be expanded a scaffolding protein, ankyrin B (ANK2). Brugada syn-
by increasing dietary fluid and salt. If these nonpharma- drome is characterized by idiopathic ventricular bril-
cologic measures fail, pharmacologic intervention with lation in association with right ventricular electrocar-
fludrocortisone acetate and vasoconstricting agents diogram (ECG) abnormalities without structural heart
such as midodrine and pseudoephedrine should be disease. This disorder is also genetically heterogeneous,
introduced. Some patients with intractable symptoms although it is most frequently linked to mutations in
require additional therapy with supplementary agents the Na+ channel -subunit, SCN5A. Catecholamin-
that include pyridostigmine, yohimbine, desmopressin ergic polymorphic tachycardia is an inherited, geneti-
acetate (DDAVP), and erythropoietin (Chap. 33). cally heterogeneous disorder associated with exercise-
or stress-induced ventricular arrhythmias, syncope, or
96 sudden death. Acquired QT interval prolongation, most intestinal, pulmonary, urogenital, pupillary, and cutane-
commonly due to drugs, may also result in ventricular ous manifestations that are similar to the premonitory
arrhythmias and syncope. features of syncope. Furthermore, the cardiovascular
manifestations of autonomic epilepsy include clinically
Structural disease significant tachycardias and bradycardias that may be of
Structural heart disease, (e.g., valvular disease, myocar- sufficient magnitude to cause loss of consciousness. The
dial ischemia, hypertrophic and other cardiomyopathies, presence of accompanying nonautonomic auras may
cardiac masses such as atrial myxoma, and pericardial help differentiate these episodes from syncope.
effusions) may lead to syncope by compromising cardiac Loss of consciousness associated with a seizure usu-
SECTION II

output. Structural disease may also contribute to other ally lasts longer than 5 min and is associated with pro-
pathophysiologic mechanisms of syncope. For example, longed postictal drowsiness and disorientation, whereas
cardiac structural disease may predispose to arrhyth- reorientation occurs almost immediately after a synco-
mogenesis; aggressive treatment of cardiac failure with pal event. Muscle aches may occur after both syncope
diuretics and/or vasodilators may lead to orthostatic and seizures, although they tend to last longer follow-
hypotension; and inappropriate reex vasodilation may ing a seizure. Seizures, unlike syncope, are rarely pro-
Clinical Manifestations of Neurologic Disease

occur with structural disorders such as aortic stenosis voked by emotions or pain. Incontinence of urine may
and hypertrophic cardiomyopathy, possibly provoked occur with both seizures and syncope; however, fecal
by increased ventricular contractility. incontinence does not occur with syncope.
Hypoglycemia may cause transient loss of conscious-
ness, typically in individuals with type 1 or type 2 diabe-
tes treated with insulin. The clinical features associated
TREATMENT Cardiac Syncope
with impending or actual hypoglycemia include tremor,
Treatment of cardiac disease depends upon the under- palpitations, anxiety, diaphoresis, hunger, and paresthe-
lying disorder. Therapies for arrhythmias include cardiac sias. These symptoms are due to autonomic activation
pacing for sinus node disease and AV block, and abla- to counter the falling blood glucose. Hunger, in par-
tion, anti-arrhythmic drugs, and cardioverter-defibril- ticular, is not a typical premonitory feature of syncope.
lators for atrial and ventricular tachyarrhythmias. These Hypoglycemia also impairs neuronal function, lead-
disorders are best managed by physicians with special- ing to fatigue, weakness, dizziness, and cognitive and
ized skills in this area. behavioral symptoms. Diagnostic difficulties may occur
in individuals in strict glycemic control; repeated hypo-
glycemia impairs the counterregulatory response and
leads to a loss of the characteristic warning symptoms
APPROACH TO THE
Syncope that are the hallmark of hypoglycemia.
PATIENT
Patients with cataplexy experience an abrupt partial
DIFFERENTIAL DIAGNOSIS Syncope is easily or complete loss of muscular tone triggered by strong
diagnosed when the characteristic features are present; emotions, typically anger or laughter. Unlike syncope,
however, several disorders with transient real or apparent consciousness is maintained throughout the attacks,
loss of consciousness may create diagnostic confusion. which typically last between 30 s and 2 min. There are
Generalized and partial seizures may be confused no premonitory symptoms. Cataplexy occurs in 6075%
with syncope; however, there are a number of differenti- of patients with narcolepsy.
ating features. Whereas tonic-clonic movements are the The clinical interview and interrogation of eyewit-
hallmark of a generalized seizure, myoclonic and other nesses usually allow differentiation of syncope from
movements also may occur in up to 90% of syncopal falls due to vestibular dysfunction, cerebellar disease,
episodes. Myoclonic jerks associated with syncope may extrapyramidal system dysfunction, and other gait dis-
be multifocal or generalized. They are typically arrhyth- orders. If the fall is accompanied by head trauma, a
mic and of short duration (<30 s). Mild flexor and exten- postconcussive syndrome, amnesia for the precipitat-
sor posturing also may occur. Partial- or partial-complex ing events, and/or the presence of loss of consciousness
seizures with secondary generalization are usually pre- may contribute to diagnostic difficulty.
ceded by an aura, commonly an unpleasant smell; fear Apparent loss of consciousness can be a manifesta-
anxiety; abdominal discomfort or other visceral sensa- tion of psychiatric disorders such as generalized anxiety,
tions. These phenomena should be differentiated from panic disorders, major depression, and somatization dis-
the premonitory features of syncope. order. These possibilities should be considered in indi-
Autonomic manifestations of seizures (autonomic viduals who faint frequently without prodromal symp-
epilepsy) may provide a more difficult diagnostic chal- toms. Such patients are rarely injured despite numerous
lenge. Autonomic seizures have cardiovascular, gastro- falls. There are no clinically significant hemodynamic
changes concurrent with these episodes. In contrast, syncope and in patients over age 50 years with recur- 97
transient loss of consciousness due to vasovagal syn- rent syncope of unknown etiology. This test should only
cope precipitated by fear, stress, anxiety, and emotional be carried out under continuous ECG and blood pres-
distress is accompanied by hypotension, bradycardia, or sure monitoring and should be avoided in patients with
both. carotid bruits, plaques, or stenosis.

INITIAL EVALUATION The goals of the initial Cardiac Evaluation ECG monitoring is indicated
evaluation are to determine whether the transient loss for patients with a high pretest probability of arrhyth-
of consciousness was due to syncope; to identify the mia causing syncope. Patients should be monitored in

CHAPTER 10
cause; and to assess risk for future episodes and serious hospital if the likelihood of a life-threatening arrhythmia
harm (Table 10-1). The initial evaluation should include a is high, e.g., patients with severe structural or coronary
detailed history, thorough questioning of eyewitnesses, artery disease, nonsustained ventricular tachycardia, tri-
and a complete physical and neurologic examination. fascicular heart block, prolonged QT interval, Brugadas
Blood pressure and heart rate should be measured in syndrome ECG pattern, and family history of sudden
the supine position and after 3 min of standing to deter- cardiac death. Outpatient Holter monitoring is recom-

Syncope
mine whether orthostatic hypotension is present. An ECG mended for patients who experience frequent syncopal
should be performed if there is suspicion of syncope due episodes (one or more per week), whereas loop record-
to an arrhythmia or underlying cardiac disease. Relevant ers, which continually record and erase cardiac rhythm,
electrocardiographic abnormalities include bradyarrhyth- are indicated for patients with suspected arrhythmias
mias or tachyarrhythmias, atrioventricular block, isch- with low risk of sudden cardiac death. Loop record-
emia, old myocardial infarction, long QT syndrome, and ers may be external (recommended for evaluation of
bundle branch block. This initial assessment will lead to episodes that occur at a frequency of greater than one
the identification of a cause of syncope in approximately per month) or implantable (if syncope occurs less fre-
50% of patients and also allows stratification of patients quently).
at risk for cardiac mortality. Echocardiography should be performed in patients
with a history of cardiac disease or if abnormalities
Laboratory Tests Baseline laboratory blood tests are found on physical examination or the electrocar-
are rarely helpful in identifying the cause of syncope. diogram. Echocardiographic diagnoses that may be
Blood tests should be performed when specific disor- responsible for syncope include aortic stenosis, hyper-
ders, e.g., myocardial infarction, anemia, and secondary trophic cardiomyopathy, cardiac tumors, aortic dissec-
autonomic failure, are suspected (Table 10-2). tion, and pericardial tamponade. Echocardiography also
has a role in risk stratification based on the left ventricu-
Autonomic Nervous System Testing (Chap. lar ejection fraction.
33) Autonomic testing including tilt table testing can be Treadmill exercise testing with ECG and blood pres-
performed in specialized centers. Autonomic testing is sure monitoring should be performed in patients who
helpful to uncover objective evidence of autonomic fail- have experienced syncope during or shortly after
ure and also to demonstrate a predisposition to neurally exercise. Treadmill testing may help identify exercise-
mediated syncope. Autonomic testing includes assess- induced arrhythmias (e.g., tachycardia-related AV block)
ments of parasympathetic autonomic nervous system and exercise-induced exaggerated vasodilation.
function (e.g., heart rate variability to deep respiration Electrophysiologic studies are indicated in patients
and a Valsalva maneuver), sympathetic cholinergic func- with structural heart disease and ECG abnormali-
tion (e.g., thermoregulatory sweat response and quan- ties in whom noninvasive investigations have failed
titative sudomotor axon reflex test), and sympathetic to yield a diagnosis. Electrophysiologic studies have
adrenergic function (e.g., blood pressure response to low sensitivity and specificity and should only be
a Valsalva maneuver and a tilt table test with beat-to- performed when a high pretest probability exists.
beat blood pressure measurement). The hemodynamic Currently, this test is rarely performed to evaluate
abnormalities demonstrated on tilt table test (Figs. patients with syncope.
10-2 and 10-3) may be useful in distinguishing ortho-
static hypotension due to autonomic failure from the Psychiatric Evaluation Screening for psychiat-
hypotensive bradycardic response of neurally mediated ric disorders may be appropriate in patients with recur-
syncope. Similarly, the tilt table test may help identify rent unexplained syncope episodes. Tilt table testing,
patients with syncope due to delayed or initial ortho- with demonstration of symptoms in the absence of
static hypotension. hemodynamic change, may be useful in reproduc-
Carotid sinus massage should be considered in ing syncope in patients with suspected psychogenic
patients with symptoms suggestive of carotid sinus syncope.
CHAPTER 11

DIZZINESS AND VERTIGO

Mark F. Walker Robert B. Daroff

Dizziness is a common, vexing symptom, and epidemi- (e.g., arrhythmia, transient ischemic attack/stroke)? (2)
ologic data indicate that more than 20% of adults expe- is it vestibular? and (3) if vestibular, is it peripheral or
rience dizziness within a given year. The diagnosis is central? A careful history and examination often pro-
frequently challenging, in part because patients use the vide enough information to answer these questions and
term to refer to a variety of different sensations, includ- determine whether additional studies or referral to a
ing feelings of faintness, spinning, and other illusions specialist is necessary.
of motion, imbalance, and anxiety. Other descriptive
words, such as light-headedness, are equally ambiguous,
referring in some cases to a presyncopal sensation due APPROACH TO THE
to hypoperfusion of the brain and in others to disequi- PATIENT Dizziness
librium and imbalance. Patients often have difculty
HISTORY When a patient presents with dizziness,
distinguishing among these various symptoms, and the
words they choose do not describe the underlying etiol- the first step is to delineate more precisely the nature
ogy reliably. of the symptom. In the case of vestibular disorders, the
Vascular disorders cause presyncopal dizziness as a physical symptoms depend on whether the lesion is
result of cardiac dysrhythmia, orthostatic hypotension, unilateral or bilateral and whether it is acute or chronic
medication effects, or another cause. Such presynco- and progressive. Vertigo, an illusion of self or environ-
pal sensations vary in duration; they may increase in mental motion, implies asymmetry of vestibular inputs
severity until loss of consciousness occurs, or they may from the two labyrinths or in their central pathways and
resolve before loss of consciousness if the cerebral isch- is usually acute. Symmetric bilateral vestibular hypo-
emia is corrected. Faintness and syncope, which are function causes imbalance but no vertigo. Because of
discussed in detail in Chap. 10, should always be con- the ambiguity in patients descriptions of their symp-
sidered when one is evaluating patients with brief epi- toms, diagnosis based simply on symptom character is
sodes of dizziness or dizziness that occurs with upright typically unreliable. The history should focus closely on
posture. other features, including whether dizziness is parox-
Vestibular causes of dizziness may be due to periph- ysmal or has occurred only once, the duration of each
eral lesions that affect the labyrinths or vestibular nerves episode, any provoking factors, and the symptoms that
or to involvement of the central vestibular pathways. accompany the dizziness.
They may be paroxysmal or due to a xed unilateral or Causes of dizziness can be divided into episodes
bilateral vestibular decit. Acute unilateral lesions cause that last for seconds, minutes, hours, or days. Com-
vertigo due to a sudden imbalance in vestibular inputs mon causes of brief dizziness (seconds) include benign
from the two labyrinths. Bilateral lesions cause imbal- paroxysmal positional vertigo (BPPV) and orthostatic
ance and instability of vision when the head moves hypotension, both of which typically are provoked by
(oscillopsia). Other causes of dizziness include nonvestib- changes in position. Attacks of migrainous vertigo and
ular imbalance and gait disorders (e.g., loss of proprio- Mnires disease often last hours. When episodes are
ception from sensory neuropathy, parkinsonism) and of intermediate duration (minutes), transient ischemic
anxiety. attacks of the posterior circulation should be consid-
In evaluating patients with dizziness, questions to ered, although these episodes also could be due to
consider include the following: (1) is it dangerous migraine or a number of other causes.

98
TABLE 11-1 99
FEATURES OF PERIPHERAL AND CENTRAL VERTIGO
PERIPHERAL (LABYRINTH OR
SIGN OR SYMPTOM VESTIBULAR NERVE) CENTRAL (BRAINSTEM OR CEREBELLUM)

Direction of associated nystagmus Unidirectional; fast phase opposite Bidirectional (direction-changing) or uni-
lesiona directional
Purely horizontal nystagmus without Uncommon May be present
torsional component

CHAPTER 11
Purely vertical or purely torsional Never presentb May be present
nystagmus
Visual xation Inhibits nystagmus No inhibition
Tinnitus and/or deafness Often present Usually absent
Associated central nervous system None Extremely common (e.g., diplopia, hic-
abnormalities cups, cranial neuropathies, dysarthria)

Dizziness and Vertigo


Common causes Benign paroxysmal positional vertigo, Vascular, demyelinating, neoplasm
infection (labyrinthitis), vestibular neu-
ritis, Mnires disease, labyrinthine
ischemia, trauma, toxin

a
In Mnires disease, the direction of the fast phase is variable.
b
Combined vertical-torsional nystagmus suggests BPPV.

Symptoms that accompany vertigo may be help- opposite direction that resets the position of the eyes in
ful in distinguishing peripheral vestibular lesions from the orbits. Table 11-1 lists features that help distinguish
central causes. Unilateral hearing loss and other aural peripheral vestibular nystagmus from central nystagmus.
symptoms (ear pain, pressure, fullness) typically point Except in the case of acute vestibulopathy (e.g., vestibular
to a peripheral cause. Because the auditory pathways neuritis), if primary position nystagmus is easily seen in
quickly become bilateral upon entering the brainstem, the light, it is probably due to a central cause. Two forms
central lesions are unlikely to cause unilateral hearing of nystagmus that are characteristic of lesions of the cer-
loss (unless the lesion lies near the root entry zone of ebellar pathways are vertical nystagmus with downward
the auditory nerve). Symptoms such as double vision, fast phases (downbeat nystagmus) and horizontal nys-
numbness, and limb ataxia suggest a brainstem or cer- tagmus that changes direction with gaze (gaze-evoked
ebellar lesion. nystagmus).
Specialists find that the most useful bedside test of
EXAMINATION Because dizziness and imbalance peripheral vestibular function is the head impulse test, in
can be a manifestation of a variety of neurologic disor- which the vestibuloocular reflex (VOR) is assessed with
ders, the neurologic examination is important in the eval- small-amplitude (approximately 20 degrees) rapid head
uation of these patients. Particular focus should be given rotations; beginning in the primary position, the head is
to assessment of eye movements, vestibular function, rotated to the left or right while the patient is instructed
and hearing. The range of eye movements and whether to fixate on the examiners face. If the VOR is deficient, a
they are equal in each eye should be observed. Peripheral catch-up saccade is seen at the end of the rotation. This
eye movement disorders (e.g., cranial neuropathies, eye test can identify both unilateral (deficient VOR when the
muscle weakness) are usually disconjugate (different in head is rotated toward the weak side) and bilateral ves-
the two eyes). One should check pursuit (the ability to fol- tibular hypofunction.
low a smoothly moving target) and saccades (the ability All patients with episodic dizziness, especially if it is
to look back and forth accurately between two targets). provoked by positional change, should be tested with
Poor pursuit or inaccurate (dysmetric) saccades usually the Dix-Hallpike maneuver. The patient begins in a sit-
indicates central pathology, often involving the cerebel- ting position with the head turned 45 degrees; holding
lum. Finally, one should look for spontaneous nystagmus, the back of the head, the examiner then gently low-
an involuntary back-and-forth movement of the eyes. ers the patient into a supine position with the head
Most often nystagmus is of the jerk type, in which a slow extended backward by about 20 degrees, and observes
drift (slow phase) in one direction alternates with a rapid for nystagmus; after 30 s the patient is raised to the sit-
saccadic movement (quick phase or fast phase) in the ting position and after a 1-min rest the procedure is
100 repeated with the head turned to the other side. Use
hemorrhage), which may be life-threatening, or periph-
of Frenzel eyeglasses (self-illuminated goggles with
eral, affecting the vestibular nerve or labyrinth. Attention
convex lenses that blur the patients vision but allow
should be given to any symptoms or signs that point to
the examiner to see the eyes greatly magnified) can
central dysfunction (diplopia, weakness or numbness, dys-
improve the sensitivity of the test. If transient upbeating
arthria). The pattern of spontaneous nystagmus, if pres-
and torsional nystagmus are elicited in the supine posi-
ent, may be helpful (Table 11-1). If the head impulse test
tion, posterior canal BPPV can be diagnosed confidently
is normal, an acute peripheral vestibular lesion is unlikely.
and treated with a repositioning maneuver, and addi-
However, a central lesion cannot always be excluded with
tional testing can be avoided.
certainly on the basis of symptoms and examination alone;
SECTION II

Dynamic visual acuity is a functional test that can


thus, older patients with vascular risk factors who pres-
be useful in assessing vestibular function. Visual acuity
ent with an acute vestibular syndrome generally should be
is measured with the head still and when the head is
evaluated for the possibility of stroke even when there are
rotated back and forth by the examiner (about 12 Hz).
no specic ndings that indicate a central lesion.
A drop in visual acuity during head motion of more than
Most patients with vestibular neuritis recover spon-
one line on a near card or Snellen chart is abnormal.
taneously, but glucocorticoids can improve outcome if
administered within 3 days of symptom onset. Antivi-
Clinical Manifestations of Neurologic Disease

The choice of ancillary tests should be guided by the


history and examination findings. Audiometry should
ral medications are of no proven benet unless there is
be performed whenever a vestibular disorder is sus-
evidence to suggest herpes zoster oticus (Ramsay Hunt
pected. Unilateral sensorineural hearing loss supports a
syndrome). Vestibular suppressant medications may
peripheral disorder (e.g., vestibular schwannoma). Pre-
reduce acute symptoms but should be avoided after the
dominantly low-frequency hearing loss is characteristic
rst several days as they may impede central compen-
of Mnires disease. Electro- or videonystagmography
sation and recovery. Patients should be encouraged to
includes recordings of spontaneous nystagmus (if pres-
resume a normal level of activity as soon as possible, and
ent), pursuit, and saccades; caloric testing to assess the
directed vestibular rehabilitation therapy may accelerate
responses of the two horizontal semicircular canals; and
improvement.
measurement of positional nystagmus. Patients with
unexplained unilateral hearing loss or vestibular hypo- Benign paroxysmal positional vertigo
function should undergo magnetic resonance imaging
BPPV is a common cause of recurrent vertigo. Episodes
of the internal auditory canals, including administration
are brief (<1 min and typically 1520 s) and are always
of gadolinium, to rule out a schwannoma.
provoked by changes in head position relative to grav-
ity, such as lying down, rolling over in bed, rising from a
supine position, and extending the head to look upward.
The attacks are caused by free-oating otoconia (calcium
TREATMENT Dizziness carbonate crystals) that have been dislodged from the
utricular macula and have moved into one of the semi-
Treatment of vestibular symptoms should be driven by circular canals, usually the posterior canal. When head
the underlying diagnosis. Simply treating dizziness with position changes, gravity causes the otoconia to move
vestibular suppressant medications is often not helpful within the canal, producing vertigo and nystagmus. With
and may make the symptoms worse. The diagnostic and posterior canal BPPV, the nystagmus beats upward and
specific treatment approaches for the most commonly torsionally (the upper poles of the eyes beat toward the
encountered vestibular disorders are discussed next. affected ear). Less commonly, the otoconia enter the
horizontal canal, resulting in a horizontal nystagmus
when the patient is lying with either ear down. Superior
(also called anterior) canal involvement is rare. BPPV is
Acute prolonged vertigo
treated with repositioning maneuvers that utilize gravity
An acute unilateral vestibular lesion causes constant ver- to remove the otoconia from the semicircular canal. For
tigo, nausea, vomiting, oscillopsia (motion of the visual posterior canal BPPV, the Epley maneuver is the most
scene), and imbalance. These symptoms are due to a commonly used procedure. For more refractory cases of
sudden asymmetry of inputs from the two labyrinths BPPV, patients can be taught a variant of this maneuver
or in their central connections, simulating a continuous that they can perform alone at home.
rotation of the head. Unlike BPPV, the vertigo persists
even when the head is not moving.
Vestibular migraine
When a patient presents with an acute vestibular syn-
drome, the most important question is whether the Vestibular symptoms occur frequently in migraine,
lesion is central (e.g., a cerebellar or brainstem infarct or sometimes as a headache aura but often independent of
headache. The duration of vertigo may be from min- loss of balance, particularly in the dark, where vestibular 101
utes to hours, and some patients also experience more input is most critical, and oscillopsia during head move-
prolonged periods of disequilibrium (lasting days to ment, such as while walking or riding in a car. Bilateral
weeks). Motion sensitivity and sensitivity to visual vestibular hypofunction may be (1) idiopathic and pro-
motion (e.g., movies) are common in patients with ves- gressive, (2) part of a neurodegenerative disorder, or (3)
tibular migraine. Although data from controlled stud- iatrogenic, due to medication ototoxicity (most com-
ies are generally lacking, vestibular migraine typically is monly gentamicin or other aminoglycoside antibiotics).
treated with medications that are used for prophylaxis Other causes include bilateral vestibular schwannomas
of migraine headaches. Antiemetics may be helpful to (neurobromatosis type 2), autoimmune disease, men-

CHAPTER 11
relieve symptoms at the time of an attack. ingeal-based infection or tumor, and other toxins. It
also may occur in patients with peripheral polyneuropa-
Mnires disease thy; in these patients, both vestibular loss and impaired
proprioception may contribute to poor balance. Finally,
Attacks of Mnires disease consist of vertigo, hearing unilateral processes such as vestibular neuritis and
loss, and pain, pressure, or fullness in the affected ear. Mnires disease may involve both ears sequentially,
The hearing loss and aural symptoms are key features resulting in bilateral vestibulopathy.

Dizziness and Vertigo


that distinguish Mnires disease from other peripheral Examination ndings include diminished dynamic
vestibulopathies. Audiometry at the time of an attack visual acuity (see earlier in this chapter) due to loss of
shows a characteristic asymmetric low-frequency hear- stable vision when the head is moving, abnormal head
ing loss; hearing commonly improves between attacks, impulse responses in both directions, and a Romberg
although permanent hearing loss may occur eventually. sign. In the laboratory, responses to caloric testing are
Mnires disease is thought to be due to excess uid reduced. Patients with bilateral vestibular hypofunction
(endolymph) in the inner ear, hence the term endolym- should be referred for vestibular rehabilitation therapy.
phatic hydrops. Patients suspected of having Mnires Vestibular suppressant medications should not be used,
disease should be referred to an otolaryngologist for fur- as they will increase the imbalance. Evaluation by a
ther evaluation. Diuretics and sodium restriction are the neurologist is important not only to conrm the diag-
initial treatments. If attacks persist, injections of genta- nosis but also to consider any other associated neuro-
micin into the middle ear are typically the next line of logic abnormalities that may clarify the etiology.
therapy. Full ablative procedures (vestibular nerve sec-
tion, labyrinthectomy) seldom are required.
Psychosomatic dizziness

Vestibular schwannoma Psychological factors play an important role in chronic


dizziness. First, dizziness may be a somatic manifesta-
Vestibular schwannomas (sometimes less correctly termed tion of a psychiatric condition such as major depres-
acoustic neuromas) and other tumors at the cerebellopon- sion, anxiety, or panic disorder. Second, patients may
tine angle cause slowly progressive unilateral sensori- develop anxiety and autonomic symptoms as a conse-
neural hearing loss and vestibular hypofunction. These quence or comorbidity of an independent vestibular
patients typically do not have vertigo, because the disorder. One particular form of this has been termed
gradual vestibular decit is compensated centrally as it variously phobic postural vertigo, psychophysiologic vertigo, or
develops. The diagnosis often is not made until there is chronic subjective dizziness. These patients have a chronic
sufcient hearing loss to be noticed. The examination feeling (months or longer) of dizziness and disequilib-
will show a decient Halmagyi-Curthoys head impulse rium, an increased sensitivity to self-motion and visual
response when the head is rotated toward the affected motion (e.g., movies), and a particular intensication of
side. Any patient with unexplained asymmetric vestibu- symptoms when moving through complex visual envi-
lar function (e.g., no prior history of vestibular neuritis) ronments such as supermarkets (visual vertigo). Although
or asymmetric sensorineural hearing loss (documented there may be a past history of an acute vestibular disor-
on audiometry) should undergo MRI of the internal der (e.g., vestibular neuritis), the neurootologic exami-
auditory canals, including gadolinium administration, to nation and vestibular testing are normal or indicative
rule out a schwannoma. of a compensated vestibular decit, indicating that the
ongoing subjective dizziness cannot be explained by a
primary vestibular disorder. Anxiety disorders are com-
Bilateral vestibular hypofunction
mon in patients with chronic dizziness and contribute
Patients with bilateral loss of vestibular function also substantially to the morbidity. Thus, treatment with
typically do not have vertigo, since vestibular func- antianxiety medications (selective serotonin reuptake
tion is lost on both sides simultaneously, thus there is inhibitors [SSRIs]) and cognitive/behavioral therapy
no asymmetry of vestibular input. Symptoms include may be helpful. Vestibular rehabilitation therapy is also
102 sometimes benecial. Vestibular suppressant medications TABLE 11-2
generally should be avoided. This condition should be
TREATMENT OF VERTIGO
suspected when the patient states, My dizziness is so
bad, Im afraid to leave my house (agoraphobia). Gen- AGENTa DOSEb
eral treatment of vertigo consists of vestibular suppres- Antihistamines
sant medications and vestibular rehabilitation therapy.
Meclizine 2550 mg 3 times daily
Dimenhydrinate 50 mg 12 times daily
Promethazine 25 mg 23 times daily
TREATMENT Vertigo (also can be given rectally
SECTION II

and IM)
Table 11-2 provides a list of commonly used medica- Benzodiazepines
tions for suppression of vertigo. As noted, these medi- Diazepam 2.5 mg 13 times daily
cations should be reserved for short-term control of Clonazepam 0.25 mg 13 times daily
active vertigo, such as during the first few days of acute Anticholinergic
vestibular neuritis, or for acute attacks of Mnires dis-
Scopolamine transdermalc Patch
Clinical Manifestations of Neurologic Disease

ease. They are less helpful for chronic dizziness and, as


previously stated, may hinder central compensation. Physical therapy
An exception is that benzodiazepines may attenuate Repositioning maneuversd
psychosomatic dizziness and the associated anxiety, Vestibular rehabilitation
although SSRIs are generally preferable in such patients. Other
Vestibular rehabilitation therapy promotes central
Diuretics and/or low-
adaptation processes that compensate for vestibular
sodium (1 g/d) diete
loss and also may help habituate motion sensitivity and
other symptoms of psychosomatic dizziness. The gen- Antimigrainous drugsf
eral approach is to use a graded series of exercises that Methylprednisoloneg 100 mg daily days 13;
progressively challenge gaze stabilization and balance. 80 mg daily days 46;
60 mg daily days 79;
40 mg daily days 1012;
20 mg daily days 1315;
10 mg daily days 1618,
20, 22
Selective serotonin reup-
take inhibitorsh

a
All listed drugs are approved by the U.S. Food and Drug Adminis-
tration, but most are not approved for the treatment of vertigo.
b
Usual oral (unless otherwise stated) starting dose in adults; a
higher maintenance dose can be reached by a gradual increase.
c
For motion sickness only.
d
For benign paroxysmal positional vertigo.
e
For Mnires disease.
f
For vestibular migraine.
g
For acute vestibular neuritis (started within three days of onset).
h
For psychosomatic vertigo.
CHAPTER 12

WEAKNESS AND PARALYSIS

Michael J. Aminoff

Normal motor function involves integrated muscle Myopathic weakness is generally most marked in proxi-
activity that is modulated by the activity of the cere- mal muscles, whereas weakness from impaired neu-
bral cortex, basal ganglia, cerebellum, and spinal cord. romuscular transmission has no specic pattern of
Motor system dysfunction leads to weakness or paral- involvement. Weakness often is accompanied by other
ysis, which is discussed in this chapter, or to ataxia neurologic abnormalities that help indicate the site of
(Chap. 31) or abnormal movements (Chap. 30). The the responsible lesion. These abnormalities include
mode of onset, distribution, and accompaniments of changes in tone, muscle bulk, muscle stretch reexes,
weakness help suggest its cause. and cutaneous reexes (Table 12-1).
Weakness is a reduction in the power that can be Tone is the resistance of a muscle to passive stretch.
exerted by one or more muscles. Increased fatigabil- Central nervous system (CNS) abnormalities that cause
ity or limitation in function due to pain or articular weakness generally produce spasticity, an increase in
stiffness often is confused with weakness by patients. tone associated with disease of upper motor neurons.
Increased fatigability is the inability to sustain the perfor- Spasticity is velocity-dependent, has a sudden release
mance of an activity that should be normal for a person after reaching a maximum (the clasp-knife phenom-
of the same age, sex, and size. Increased time is required enon), and predominantly affects the antigravity mus-
sometimes for full power to be exerted, and this brady- cles (i.e., upper-limb exors and lower-limb exten-
kinesia may be misinterpreted as weakness. Severe pro- sors). Spasticity is distinct from rigidity and paratonia,
prioceptive sensory loss also may lead to complaints two other types of hypertonia. Rigidity is increased
of weakness because adequate feedback information tone that is present throughout the range of motion
about the direction and power of movements is lacking. (a lead pipe or plastic stiffness) and affects ex-
Finally, apraxia, a disorder of planning and initiating a ors and extensors equally; it sometimes has a cogwheel
skilled or learned movement unrelated to a signicant quality that is enhanced by voluntary movement of the
motor or sensory decit (Chap. 18), sometimes is mis- contralateral limb (reinforcement). Rigidity occurs with
taken for weakness. certain extrapyramidal disorders, such as Parkinsons
Paralysis indicates weakness that is so severe that disease. Paratonia (or gegenhalten) is increased tone that
a muscle cannot be contracted at all, whereas paresis varies irregularly in a manner that may seem related to
refers to weakness that is mild or moderate. The pre- the degree of relaxation, is present throughout the range
x hemi- refers to one-half of the body, para- to of motion, and affects exors and extensors equally; it
both legs, and quadri- to all four limbs. The sufx usually results from disease of the frontal lobes. Weak-
-plegia signies severe weakness or paralysis. ness with decreased tone (accidity) or normal tone occurs
The distribution of weakness helps to indicate the with disorders of motor units. A motor unit consists of a
site of the underlying lesion. Weakness from involve- single lower motor neuron and all the muscle bers that
ment of upper motor neurons occurs particularly in the it innervates.
extensors and abductors of the upper limb and the ex- Muscle bulk generally is not affected in patients with
ors of the lower limb. Lower motor neuron weakness upper motor neuron lesions, although mild disuse
does not have this selectivity but depends on whether atrophy eventually may occur. By contrast, atrophy is
involvement is at the level of the anterior horn cells, often conspicuous when a lower motor neuron lesion
nerve root, limb plexus, or peripheral nerveonly is responsible for weakness and also may occur with
muscles supplied by the affected structure are weak. advanced muscle disease.
103
104 TABLE 12-1
SIGNS THAT DISTINGUISH THE ORIGIN OF WEAKNESS
SIGN UPPER MOTOR NEURON LOWER MOTOR NEURON MYOPATHIC

Atrophy None Severe Mild


Fasciculations None Common None
Tone Spastic Decreased Normal/decreased
Distribution of weakness Pyramidal/regional Distal/segmental Proximal
SECTION II

Tendon reexes Hyperactive Hypoactive/absent Normal/hypoactive


Babinski sign Present Absent Absent

Muscle stretch (tendon) reexes are usually increased and jaw muscles almost always are spared. With bilateral
with upper motor neuron lesions, although they may corticobulbar lesions, pseudobulbar palsy often develops:
Clinical Manifestations of Neurologic Disease

be decreased or absent for a variable period immediately dysarthria, dysphagia, dysphonia, and emotional labil-
after onset of an acute lesion. This is usuallybut not ity accompany bilateral facial weakness and a brisk jaw
invariablyaccompanied by abnormalities of cutaneous jerk. Spasticity accompanies upper motor neuron weak-
reexes (such as supercial abdominals; Chap. 1) and, in ness but may not be present in the acute phase. Upper
particular, by an extensor plantar (Babinski) response. motor neuron lesions also affect the ability to perform
The muscle stretch reexes are depressed in patients rapid repetitive movements. Such movements are slow
with lower motor neuron lesions when there is direct and coarse, but normal rhythmicity is maintained.
involvement of specic reex arcs. The stretch reexes Finger-nose-nger and heel-knee-shin maneuvers are
generally are preserved in patients with myopathic performed slowly but adequately.
weakness except in advanced stages, when they some-
times are attenuated. In disorders of the neuromuscu-
lar junction, the intensity of the reex responses may Lower motor neuron weakness
be affected by preceding voluntary activity of affected This pattern results from disorders of cell bodies of
muscles; that activity may lead to enhancement of ini- lower motor neurons in the brainstem motor nuclei and
tially depressed reexes in Lambert-Eaton myasthenic the anterior horn of the spinal cord or from dysfunc-
syndrome and, conversely, to depression of initially nor- tion of the axons of these neurons as they pass to skel-
mal reexes in myasthenia gravis (Chap. 47). etal muscle (Fig. 12-2). Weakness is due to a decrease
The distinction of neuropathic (lower motor neuron) in the number of muscle bers that can be activated
from myopathic weakness is sometimes difcult clinically, through a loss of motor neurons or disruption of their
although distal weakness is likely to be neuropathic, and connections to muscle. Loss of motor neurons does
symmetric proximal weakness myopathic. Fasciculations not cause weakness but decreases tension on the muscle
(visible or palpable twitch within a muscle due to the spindles, which decreases muscle tone and attenuates
spontaneous discharge of a motor unit) and early atro- the stretch reexes elicited on examination. An absent
phy indicate that weakness is neuropathic. stretch reex suggests involvement of spindle afferent
bers.
When a motor unit becomes diseased, especially in
PATHOGENESIS anterior horn cell diseases, it may discharge spontane-
ously, producing fasciculations that may be seen or felt
Upper motor neuron weakness
clinically or recorded by electromyography (EMG).
This pattern of weakness results from disorders that When motor neurons or their axons degenerate, the
affect the upper motor neurons or their axons in the denervated muscle bers also may discharge spontane-
cerebral cortex, subcortical white matter, internal cap- ously. These single muscle ber discharges, or brilla-
sule, brainstem, or spinal cord (Fig. 12-1). These tion potentials, cannot be seen or felt but can be recorded
lesions produce weakness through decreased activation with EMG. If lower motor neuron weakness is pres-
of the lower motor neurons. In general, distal muscle ent, recruitment of motor units is delayed or reduced,
groups are affected more severely than are proximal with fewer than normal activated at a particular dis-
ones, and axial movements are spared unless the lesion charge frequency. This contrasts with weakness of the
is severe and bilateral. With corticobulbar involve- upper motor neuron type, in which a normal number
ment, weakness usually is observed only in the lower of motor units is activated at a given frequency but with
face and tongue; extraocular, upper facial, pharyngeal, a diminished maximal discharge frequency.
Corticospinal 105

Sh Trunk
Hip

der

Wr ow
tract

oul

Fin ist
El b

um s
Th ger
Knee

b
ck
Ankle Ne
Brow
Toes
Eyelid
Nares
Lips
Tongue
Larynx

CHAPTER 12
Red nucleus
Reticular nuclei
Vestibular nuclei

Weakness and Paralysis


Vestibulospinal tract Rubrospinal tract

Lateral corticospinal
Reticulospinal tract tract

Lateral
corticospinal tract

Rubrospinal
(ventrolateral)
tract
Ventromedial
bulbospinal
tracts

FIGURE 12-1
The corticospinal and bulbospinal upper motor neuron involved in the execution of learned, ne movements. Cor-
pathways. Upper motor neurons have their cell bodies in ticobulbar neurons are similar to corticospinal neurons but
layer V of the primary motor cortex (the precentral gyrus, or innervate brainstem motor nuclei.
Brodmanns area 4) and in the premotor and supplemental Bulbospinal upper motor neurons inuence strength and
motor cortex (area 6). The upper motor neurons in the pri- tone but are not part of the pyramidal system. The descend-
mary motor cortex are somatotopically organized, as illus- ing ventromedial bulbospinal pathways originate in the tec-
trated on the right side of the gure. tum of the midbrain (tectospinal pathway), the vestibular
Axons of the upper motor neurons descend through the nuclei (vestibulospinal pathway), and the reticular formation
subcortical white matter and the posterior limb of the inter- (reticulospinal pathway). These pathways inuence axial and
nal capsule. Axons of the pyramidal or corticospinal system proximal muscles and are involved in the maintenance of
descend through the brainstem in the cerebral peduncle of posture and integrated movements of the limbs and trunk.
the midbrain, the basis pontis, and the medullary pyramids. The descending ventrolateral bulbospinal pathways, which
At the cervicomedullary junction, most pyramidal axons originate predominantly in the red nucleus (rubrospinal path-
decussate into the contralateral corticospinal tract of the lat- way), facilitate distal limb muscles. The bulbospinal system
eral spinal cord, but 1030% remain ipsilateral in the anterior sometimes is referred to as the extrapyramidal upper motor
spinal cord. Pyramidal neurons make direct monosynaptic neuron system. In all gures, nerve cell bodies and axon ter-
connections with lower motor neurons. They innervate most minals are shown, respectively, as closed circles and forks.
densely the lower motor neurons of hand muscles and are

Myopathic weakness distribution and is inuenced by preceding activity of the


Myopathic weakness is produced by disorders of the affected muscle. At a muscle ber, if the nerve termi-
muscle bers. Disorders of the neuromuscular junctions nal releases a normal number of acetylcholine molecules
also produce weakness, but this is variable in degree and presynaptically and a sufcient number of postsynaptic
106 desired power. Some myopathies produce weakness
Afferent through loss of contractile force of muscle bers or
neuron
through relatively selective involvement of type II (fast)
bers. These myopathies may not affect the size of indi-
vidual motor unit action potentials and are detected by
a discrepancy between the electrical activity and force

of a muscle.
Diseases of the neuromuscular junction, such as

myasthenia gravis, produce weakness in a similar man-
SECTION II

Alpha and gamma ner, but the loss of muscle bers is functional (due to
motor neurons inability to activate them) rather than related to muscle
ber loss. The number of muscle bers that are acti-
vated varies over time, depending on the state of rest of
Motor end plates on the neuromuscular junctions. Thus, fatigable weakness
voluntary muscle is suggestive of myasthenia gravis or other disorders of
(extrafusal fibers) the neuromuscular junction.
Clinical Manifestations of Neurologic Disease

Muscle spindle
(intrafusal fibers)
Hemiparesis
FIGURE 12-2 Hemiparesis results from an upper motor neuron lesion
Lower motor neurons are divided into a and g types. above the midcervical spinal cord; most such lesions
The larger motor neurons are more numerous and inner- are above the foramen magnum. The presence of other
vate the extrafusal muscle bers of the motor unit. Loss of neurologic decits helps localize the lesion. Thus, lan-
motor neurons or disruption of their axons produces lower guage disorders, cortical sensory disturbances, cogni-
motor neuron weakness. The smaller, less numerous motor tive abnormalities, disorders of visual-spatial integration,
neurons innervate the intrafusal muscle bers of the muscle apraxia, or seizures point to a cortical lesion. Homon-
spindle and contribute to normal tone and stretch reexes. ymous visual eld defects reect either a cortical or a
The motor neuron receives direct excitatory input from cor-
subcortical hemispheric lesion. A pure motor hemi-
ticomotoneurons and primary muscle spindle afferents. The
paresis of the face, arm, and leg often is due to a small,
and motor neurons also receive excitatory input from other
discrete lesion in the posterior limb of the internal cap-
descending upper motor neuron pathways, segmental sen-
sule, cerebral peduncle, or upper pons. Some brainstem
sory inputs, and interneurons. The motor neurons receive
direct inhibition from Renshaw cell interneurons, and other
lesions produce crossed paralyses, consisting of ipsi-
interneurons indirectly inhibit the and motor neurons.
lateral cranial nerve signs and contralateral hemiparesis
A tendon reex requires the function of all the illustrated (Chap. 27). The absence of cranial nerve signs or facial
structures. A tap on a tendon stretches muscle spindles weakness suggests that a hemiparesis is due to a lesion in
(which are tonically activated by motor neurons) and acti- the high cervical spinal cord, especially if it is associated
vates the primary spindle afferent neurons. These neurons with ipsilateral loss of proprioception and contralateral
stimulate the motor neurons in the spinal cord, producing a loss of pain and temperature sense (the Brown-Squard
brief muscle contraction, which is the familiar tendon reex. syndrome).
Acute or episodic hemiparesis usually results from isch-
emic or hemorrhagic stroke but also may relate to
acetylcholine receptors are opened, the end plate reaches hemorrhage occurring into brain tumors or may be a
threshold and thereby generates an action potential that result of trauma; other causes include a focal structural
spreads across the muscle ber membrane and into the lesion or an inammatory process as in multiple scle-
transverse tubular system. This electrical excitation activates rosis, abscess, or sarcoidosis. Evaluation (Fig. 12-3)
intracellular events that produce an energy-dependent begins immediately with a CT scan of the brain and
contraction of the muscle ber (excitation-contraction laboratory studies. If the CT is normal and an ischemic
coupling). stroke is unlikely, MRI of the brain or cervical spine is
Myopathic weakness is produced by a decrease in the performed.
number or contractile force of muscle bers activated Subacute hemiparesis that evolves over days or weeks
within motor units. With muscular dystrophies, inam- has an extensive differential diagnosis. A common cause
matory myopathies, or myopathies with muscle ber is subdural hematoma, especially in elderly or anticoag-
necrosis, the number of muscle bers is reduced within ulated patients, even when there is no history of trauma.
many motor units. On EMG, the size of each motor Infectious possibilities include cerebral abscess, fungal
unit action potential is decreased, and motor units must granuloma or meningitis, and parasitic infection. Weak-
be recruited more rapidly than normal to produce the ness from primary and metastatic neoplasms may evolve
107
DISTRIBUTION OF WEAKNESS

Hemiparesis Paraparesis Quadriparesis Monoparesis Distal Proximal Restricted

Alert

UMN signs LMN signs* Yes No UMN signs LMN signs*

CHAPTER 12
Cerebral signs

Yes No
UMN signs LMN signs*

EMG and NCS

Weakness and Paralysis


UMN pattern LMN pattern Myopathic pattern

Anterior horn, Muscle or


Brain CT
Spinal MRI root, or peripheral neuromuscular
or MRI nerve disease junction disease

* or signs of myopathy

If no abnormality detected, consider spinal MRI.

If no abnormality detected, consider myelogram or brain MRI.

FIGURE 12-3
An algorithm for the initial workup of a patient with weak- LMN, lower motor neuron; MRI, magnetic resonance imaging;
ness. CT, computed tomography; EMG, electromyography; NCS, nerve conduction studies; UMN, upper motor neuron.

over days to weeks. AIDS may present with subacute Acute paraparesis may not be recognized as due to spi-
hemiparesis due to toxoplasmosis or primary CNS lym- nal cord disease at an early stage if the legs are accid
phoma. Noninfectious inammatory processes such as and areexic. Usually, however, there is sensory loss
multiple sclerosis or, less commonly, sarcoidosis merit in the legs with an upper level on the trunk, a dissoci-
consideration. If the brain MRI is normal and there are ated sensory loss suggestive of a central cord syndrome,
no cortical and hemispheric signs, MRI of the cervical or exaggerated stretch reexes in the legs with normal
spine should be undertaken. reexes in the arms. It is important to image the spinal
Chronic hemiparesis that evolves over months usually is cord (Fig. 12-3). Compressive lesions (particularly epi-
due to a neoplasm or vascular malformation, a chronic dural tumor, abscess, and hematoma but also a prolapsed
subdural hematoma, or a degenerative disease. If an intervertebral disk and vertebral involvement by malig-
MRI of the brain is normal, the possibility of a foramen nancy or infection), spinal cord infarction (propriocep-
magnum or high cervical spinal cord lesion should be tion usually is spared), an arteriovenous stula or other
considered. vascular anomaly, and transverse myelitis are among the
possible causes (Chap. 35).
Diseases of the cerebral hemispheres that produce
Paraparesis
acute paraparesis include anterior cerebral artery isch-
An intraspinal lesion at or below the upper thoracic emia (shoulder shrug also is affected), superior sagittal
spinal cord level is most commonly responsible, but a sinus or cortical venous thrombosis, and acute hydro-
paraparesis also may result from lesions at other loca- cephalus. If upper motor neuron signs are associated
tions that disturb upper motor neurons (especially with drowsiness, confusion, seizures, or other hemi-
parasagittal intracranial lesions) and lower motor neu- spheric signs, MRI of the brain should be undertaken.
rons (anterior horn cell disorders, cauda equina syn- Paraparesis may result from a cauda equina syndrome,
dromes due to involvement of nerve roots derived for example, after trauma to the low back, a mid-
from the lower spinal cord [Chap. 35], and peripheral line disk herniation, or an intraspinal tumor; although
neuropathies). sphincters are affected, hip exion often is spared, as is
108 sensation over the anterolateral thighs. Rarely, parapa- TABLE 12-2
resis is caused by a rapidly evolving anterior horn cell CAUSES OF EPISODIC GENERALIZED WEAKNESS
disease (such as poliovirus or West Nile virus infec- 1. Electrolyte disturbances, e.g., hypokalemia, hyperka-
tion), peripheral neuropathy (such as Guillain-Barr lemia, hypercalcemia, hypernatremia, hyponatremia,
syndrome; Chap. 46), or myopathy (Chap. 48). In such hypophosphatemia, hypermagnesemia
cases, electrophysiologic studies are diagnostically help- 2. Muscle disorders
ful and refocus the subsequent evaluation.
a. Channelopathies (periodic paralyses)
Subacute or chronic paraparesis with spasticity is caused
by upper motor neuron disease. When there is associ- b. Metabolic defects of muscle (impaired carbohydrate
or fatty acid utilization; abnormal mitochondrial
SECTION II

ated lower-limb sensory loss and sphincter involvement,


function)
a chronic spinal cord disorder is likely (Chap. 35). If an
MRI of the spinal cord is normal, MRI of the brain 3. Neuromuscular junction disorders
may be indicated. If hemispheric signs are present, a a. Myasthenia gravis
parasagittal meningioma or chronic hydrocephalus is b. Lambert-Eaton myasthenic syndrome
likely and MRI of the brain is the initial test. In the 4. Central nervous system disorders
rare situation in which a long-standing paraparesis has a
Clinical Manifestations of Neurologic Disease

a. Transient ischemic attacks of the brainstem


lower motor neuron or myopathic etiology, the local-
ization usually is suspected on clinical grounds by the b. Transient global cerebral ischemia
absence of spasticity and conrmed by EMG and nerve c. Multiple sclerosis
conduction tests.

Quadriparesis or generalized weakness MRI of the cervical cord. If weakness is lower motor
neuron, myopathic, or uncertain in origin, the clinical
Generalized weakness may be due to disorders of the approach begins with blood studies to determine the
CNS or the motor unit. Although the terms quadri- level of muscle enzymes and electrolytes and an EMG
paresis and generalized weakness often are used inter- and nerve conduction study.
changeably, quadriparesis is commonly used when
an upper motor neuron cause is suspected, and gen- Subacute or chronic quadriparesis
eralized weakness when a disease of the motor unit is When quadriparesis due to upper motor neuron disease
likely. Weakness from CNS disorders usually is associ- develops over weeks, months, or years, the distinction
ated with changes in consciousness or cognition, with between disorders of the cerebral hemispheres, brain-
spasticity and brisk stretch reexes, and with alterations stem, and cervical spinal cord is usually possible clini-
of sensation. Most neuromuscular causes of general- cally. An MRI is obtained of the clinically suspected site
ized weakness are associated with normal mental func- of pathology. EMG and nerve conduction studies help
tion, hypotonia, and hypoactive muscle stretch reexes. distinguish lower motor neuron disease (which usually
The major causes of intermittent weakness are listed presents with weakness that is most profound distally)
in Table 12-2. A patient with generalized fatigabil- from myopathic weakness, which is typically proximal.
ity without objective weakness may have the chronic
fatigue syndrome (Chap. 52).
Monoparesis
Acute quadriparesis
Acute quadriparesis with onset over minutes may result Monoparesis usually is due to lower motor neuron dis-
from disorders of upper motor neurons (e.g., anoxia, ease, with or without associated sensory involvement.
hypotension, brainstem or cervical cord ischemia, trauma, Upper motor neuron weakness occasionally presents
and systemic metabolic abnormalities) or muscle (electro- as a monoparesis of distal and nonantigravity muscles.
lyte disturbances, certain inborn errors of muscle energy Myopathic weakness rarely is limited to one limb.
metabolism, toxins, and periodic paralyses). Onset over
hours to weeks may, in addition to these disorders, be Acute monoparesis
due to lower motor neuron disorders. Guillain-Barr If the weakness is predominantly in distal and nonan-
syndrome (Chap. 46) is the most common lower motor tigravity muscles and is not associated with sensory
neuron weakness that progresses over days to 4 weeks; impairment or pain, focal cortical ischemia is likely
the nding of an elevated protein level in the cerebrospi- (Chap. 27); diagnostic possibilities are similar to those
nal uid is helpful but may be absent early in the course. for acute hemiparesis. Sensory loss and pain usually
In obtunded patients, evaluation begins with a CT accompany acute lower motor neuron weakness; the
scan of the brain. If upper motor neuron signs are pres- weakness commonly is localized to a single nerve root
ent but the patient is alert, the initial test is usually an or peripheral nerve within the limb but occasionally
reects plexus involvement. If lower motor neuron of the neuromuscular junction (such as myasthenia 109
weakness is suspected or the pattern of weakness is gravis [Chap. 47]), may present with symmetric proxi-
uncertain, the clinical approach begins with an EMG mal weakness often associated with ptosis, diplopia, or
and a nerve conduction study. bulbar weakness and uctuating in severity during the
day. The extreme fatigability present in some cases of
Subacute or chronic monoparesis myasthenia gravis may even suggest episodic weak-
Weakness and atrophy that develop over weeks or ness, but strength rarely returns fully to normal. In
months are usually of lower motor neuron origin. If anterior horn cell disease, proximal weakness is usu-
they are associated with sensory symptoms, a peripheral ally asymmetric, but it may be symmetric if familial.

CHAPTER 12
cause (nerve, root, or plexus) is likely; in the absence Numbness does not occur with any of these diseases.
of such symptoms, anterior horn cell disease should be The evaluation usually begins with determination of
considered. In either case, an electrodiagnostic study the serum creatine kinase level and electrophysiologic
is indicated. If weakness is of the upper motor neuron studies.
type, a discrete cortical (precentral gyrus) or cord lesion
may be responsible, and an imaging study of the appro-
Weakness in a restricted distribution

Weakness and Paralysis


priate site is performed.
Weakness may not t any of these patterns, being lim-
ited, for example, to the extraocular, hemifacial, bul-
Distal weakness bar, or respiratory muscles. If it is unilateral, restricted
Involvement of two or more limbs distally suggests weakness usually is due to lower motor neuron or
lower motor neuron or peripheral nerve disease. Acute peripheral nerve disease, such as in a facial palsy or
distal lower limb weakness results occasionally from an an isolated superior oblique muscle paresis. Weakness
acute toxic polyneuropathy or cauda equina syndrome. of part of a limb usually is due to a peripheral nerve
Distal symmetric weakness usually develops over weeks, lesion such as carpal tunnel syndrome or another
months, or years and, when associated with numb- entrapment neuropathy. Relatively symmetric weak-
ness, is due to diseases of peripheral nerves (Chap. 45). ness of extraocular or bulbar muscles usually is due to
Anterior horn cell disease may begin distally but is typi- a myopathy (Chap. 48) or neuromuscular junction dis-
cally asymmetric and without accompanying numb- order (Chap. 47). Bilateral facial palsy with areexia
ness (Chap. 32). Rarely, myopathies present with dis- suggests Guillain-Barr syndrome (Chap. 46). Wors-
tal weakness (Chap. 48). Electrodiagnostic studies help ening of relatively symmetric weakness with fatigue
localize the disorder (Fig. 12-3). is characteristic of neuromuscular junction disorders.
Asymmetric bulbar weakness usually is due to motor
neuron disease. Weakness limited to respiratory mus-
Proximal weakness cles is uncommon and usually is due to motor neuron
Myopathy often produces symmetric weakness of the disease, myasthenia gravis, or polymyositis/dermato-
pelvic or shoulder girdle muscles (Chap. 48). Diseases myositis (Chap. 49).
CHAPTER 13

GAIT AND BALANCE DISORDERS

Lewis Sudarsky

PREVALENCE, MORBIDITY, AND capacity is limited in primates. Step generation in pri-


MORTALITY mates is dependent on locomotor centers in the pontine
tegmentum, midbrain, and subthalamic region. Loco-
Gait and balance problems are common in the elderly motor synergies are executed through the reticular for-
and contribute to the risk of falls and injury. Gait dis- mation and descending pathways in the ventromedial
orders have been described in 15% of individuals older spinal cord. Cerebral control provides a goal and pur-
than age 65 years. By age 80 years, one person in four pose for walking and is involved in avoidance of obsta-
will use a mechanical aid to assist ambulation. Among cles and adaptation of locomotor programs to context
those 85 and older, the prevalence of gait abnormality and terrain.
approaches 40%. In epidemiologic studies, gait disorders Postural control requires the maintenance of the
are consistently identied as a major risk factor for falls center of mass over the base of support through the
and injury. gait cycle. Unconscious postural adjustments main-
A substantial number of older persons report insecure tain standing balance: long latency responses are mea-
balance and experience falls and fear of falling. Prospec- surable in the leg muscles, beginning 110 ms after a
tive studies indicate that 30% of those age >65 years fall perturbation. Forward motion of the center of mass
each year; the proportion is even higher in frail elderly provides propulsive force for stepping, but failure
and nursing home patients. Each year, 8% of individ- to maintain the center of mass within stability limits
uals age >75 years suffer a serious fall-related injury. results in falls. The anatomic substrate for dynamic
Hip fractures often result in hospitalization and nursing balance has not been well dened, but the vestibular
home admission. For each person who is physically dis- nucleus and midline cerebellum contribute to balance
abled, there are others whose functional independence control in animals. Human patients with damage to
is constrained by anxiety and fear of falling. Nearly these structures have impaired balance with standing
one in ve elderly individuals voluntarily limits activity and walking.
because of fear of falling. With loss of ambulation, there Standing balance depends on good-quality sensory
is a diminished quality of life and increased morbidity information about the position of the body center with
and mortality rates. respect to the environment, support surface, and gravi-
tational forces. Sensory information for postural control
is primarily generated by the visual system, the vestibu-
ANATOMY AND PHYSIOLOGY
lar system, and by proprioceptive receptors in the mus-
Upright bipedal gait depends on the successful integra- cle spindles and joints. A healthy redundancy of sensory
tion of postural control and locomotion. These func- afferent information is generally available, but loss of
tions are widely distributed in the central nervous sys- two of the three pathways is sufcient to compromise
tem. The biomechanics of bipedal walking are complex, standing balance. Balance disorders in older individuals
and the performance is easily compromised by neuro- sometimes result from multiple insults in the periph-
logic decit at any level. Command and control centers eral sensory systems (e.g., visual loss, vestibular decit,
in the brainstem, cerebellum, and forebrain modify the peripheral neuropathy), critically degrading the quality
action of spinal pattern generators to promote stepping. of afferent information needed for balance stability.
While a form of ctive locomotion can be elicited Older patients with cognitive impairment from
from quadrupedal animals after spinal transection, this neurodegenerative diseases appear to be particularly
110
prone to falls and injury. Frailty, muscle weakness, Cautious gait 111
and deconditioning also contribute to the risk. It has
been shown that older people who continue walking The term cautious gait is used to describe the patient who
while talking are at increased risk for falls. There is a walks with an abbreviated stride and lowered center of
growing literature on the use of attentional resources mass, as if walking on a slippery surface. This disorder is
to manage gait and balance. Walking is generally con- both common and nonspecic. It is, in essence, an adap-
sidered to be unconscious and automatic, but the abil- tation to a perceived postural threat. There may be an
ity to walk while attending a cognitive task (dual-task associated fear of falling. In one study, this disorder was
walking) may be compromised in frail elderly with a observed in more than one-third of older patients with

CHAPTER 13
history of falls. Older patients with decits in execu- a higher level gait disturbance. Physical therapy often
tive function may have particular difculty in managing improves walking to the degree that follow-up observa-
the attentional resources needed for dynamic balance tion may reveal a more specic underlying disorder.
when distracted.
Stiff-legged gait
DISORDERS OF GAIT Spastic gait is characterized by stiffness in the legs, an

Gait and Balance Disorders


The heterogeneity of gait disorders observed in clini- imbalance of muscle tone, and a tendency to circum-
cal practice reects the large network of neural systems duct and scuff the feet. The disorder reects compro-
involved in the task. Walking is vulnerable to neurologic mise of corticospinal command and overactivity of spi-
disease at every level. Gait disorders have been classi- nal reexes. The patient may walk on his or her toes. In
ed descriptively, based on the abnormal physiology and extreme instances, the legs cross due to increased tone
biomechanics. One problem with this approach is that in the adductors. Upper motor neuron signs are present
many failing gaits look fundamentally similar. This over- on physical examination. Shoes often reect an uneven
lap reects common patterns of adaptation to threatened pattern of wear across the outside. The disorder may be
balance stability and declining performance. The gait dis- cerebral or spinal in origin.
order observed clinically must be viewed as the product of a neu- Myelopathy from cervical spondylosis is a common
rologic decit and a functional adaptation. Unique features of cause of spastic or spastic-ataxic gait. Demyelinating dis-
the failing gait are often overwhelmed by the adaptive ease and trauma are the leading causes of myelopathy in
response. Some of the common patterns of abnormal gait younger patients. In a chronic progressive myelopathy
are summarized next. Gait disorders can also be classied of unknown cause, workup with laboratory and imag-
by etiology, as listed in Table 13-1. ing tests may establish a diagnosis. A family history
should suggest hereditary spastic paraplegia (HSP; Chap.
32). Genetic testing is now available for some of the
common HSP mutations. Tropical spastic paraparesis
related to the retrovirus HTLV-I is endemic in parts of
TABLE 13-1 the Caribbean and South America. A structural lesion,
such as tumor or spinal vascular malformation, should
ETIOLOGY OF GAIT DISORDERS
be excluded with appropriate testing. Spinal cord disor-
CASES PERCENT ders are discussed in detail in Chap. 35.
Sensory decits 22 18.3 With cerebral spasticity, asymmetry is common,
involvement of the upper extremities is usually observed,
Myelopathy 20 16.7
and dysarthria is often an associated feature. Common
Multiple infarcts 18 15.0 causes include vascular disease (stroke), multiple sclero-
Parkinsonism 14 11.7 sis, and perinatal injury to the nervous system (cerebral
Cerebellar degeneration 8 6.7 palsy).
Hydrocephalus 8 6.7 Other stiff-legged gaits include dystonia (Chap. 48)
and stiff-person syndrome. Dystonia is a disorder char-
Toxic/metabolic 3 2.5
acterized by sustained muscle contractions, resulting in
Psychogenic 4 3.3 repetitive twisting movements and abnormal posture. It
Other 6 5.0 often has a genetic basis. Dystonic spasms produce plan-
Unknown cause 17 14.2 tar exion and inversion of the feet, sometimes with
Total 120 100%
torsion of the trunk. In autoimmune stiff-person syn-
drome (Chap. 44), there is exaggerated lordosis of the
Source: Reproduced with permission from J Masdeu et al: Gait
lumbar spine and overactivation of antagonist muscles,
Disorders of Aging: With Special Reference to Falls. Boston, Little which restricts trunk and lower limb movement and
Brown, 1995. results in a wooden or xed posture.
112 Parkinsonism and freezing gait Communicating hydrocephalus in adults also pres-
ents with a gait disorder of this type. Other features of
Parkinsons disease (Chap. 30) is common, affecting the diagnostic triad (mental change, incontinence) may
1% of the population age >55 years. The stooped pos- be absent in the initial stages. MRI demonstrates ven-
ture and shufing gait are characteristic and distinctive tricular enlargement, an enlarged ow void about the
features. Patients sometimes accelerate (festinate) with aqueduct, and a variable degree of periventricular white
walking or display retropulsion. There may be difculty matter change. A lumbar puncture or dynamic test is
with gait initiation (freezing) and a tendency to turn necessary to conrm the presence of hydrocephalus.
en bloc. Imbalance and falls may develop as the disease
progresses over years. Gait freezing is described in 7% of
SECTION II

Parkinsons patients within 2 years of onset and 26% by Cerebellar gait ataxia
the end of 5 years. Freezing of gait is even more com- Disorders of the cerebellum have a dramatic impact on
mon in some of the Parkinsons-related neurodegen- gait and balance. Cerebellar gait ataxia is characterized
erative disorders, such as progressive supranuclear palsy, by a wide base of support, lateral instability of the trunk,
multiple-system atrophy, and corticobasal degeneration. erratic foot placement, and decompensation of balance
These patients frequently present with axial stiffness, when attempting to walk tandem. Difculty main-
Clinical Manifestations of Neurologic Disease

postural instability, and a shufing gait while lacking the taining balance when turning is often an early feature.
characteristic pill-rolling tremor of Parkinsons disease. Patients are unable to walk tandem heel to toe, and dis-
Falls within the rst year suggest the possibility of pro- play truncal sway in narrow-based or tandem stance.
gressive supranuclear palsy. They show considerable variation in their tendency to
Hyperkinetic movement disorders also produce char- fall in daily life.
acteristic and recognizable disturbances in gait. In Hun- Causes of cerebellar ataxia in older patients include
tingtons disease (Chap. 29), the unpredictable occur- stroke, trauma, tumor, and neurodegenerative disease,
rence of choreic movements gives the gait a dancing including multiple-system atrophy (Chaps. 30 and 33)
quality. Tardive dyskinesia is the cause of many odd, and various forms of hereditary cerebellar degenera-
stereotypic gait disorders seen in patients chronically tion (Chap. 31). A short expansion at the site of the
exposed to antipsychotics and other drugs that block the fragile X mutation (fragile X pre-mutation) has been
D2 dopamine receptor. associated with gait ataxia in older men. Alcoholic cer-
ebellar degeneration can be screened by history and
often conrmed by MRI. In patients with ataxia, MRI
Frontal gait disorder
demonstrates the extent and topography of cerebellar
Frontal gait disorder, sometimes known as gait apraxia, atrophy.
is common in the elderly and has a variety of causes.
The term is used to describe a shufing, freezing gait
Sensory ataxia
with imbalance and other signs of higher cerebral dys-
function. Typical features include a wide base of sup- As reviewed earlier, balance depends on high-quality
port, short stride, shufing along the oor, and dif- afferent information from the visual and the vestibular
culty with starts and turns. Many patients exhibit systems and proprioception. When this information is
difculty with gait initiation, descriptively character- lost or degraded, balance during locomotion is impaired
ized as the slipping clutch syndrome. The term lower and instability results. The sensory ataxia of tabetic
body parkinsonism is also used to describe such patients. neurosyphilis is a classic example. The contemporary
Strength is generally preserved, and patients are able equivalent is the patient with neuropathy affecting
to make stepping movements when not standing and large bers. Vitamin B12 deciency is a treatable cause
maintaining balance at the same time. This disorder is of large-ber sensory loss in the spinal cord and periph-
best considered a higher level motor control disorder, as eral nervous system. Joint position and vibration sense
opposed to an apraxia (Chap. 18). are diminished in the lower limbs. The stance in such
The most common cause of frontal gait disorder is patients is destabilized by eye closure; they often look
vascular disease, particularly subcortical small-vessel down at their feet when walking and do poorly in the
disease. Lesions are frequently found in the deep fron- dark. Patients have been described with imbalance from
tal white matter and centrum ovale. Gait disorder may bilateral vestibular loss, caused by disease or by expo-
be the salient feature in hypertensive patients with sure to ototoxic drugs. Table 13-2 compares sensory
ischemic lesions of the deep hemisphere white matter ataxia with cerebellar ataxia and frontal gait disorder.
(Binswangers disease). The clinical syndrome includes Some frail older patients exhibit a syndrome of imbal-
mental change (variable in degree), dysarthria, pseudo- ance from the combined effect of multiple sensory de-
bulbar affect (emotional disinhibition), increased tone, cits. Such patients have disturbances in proprioception,
and hyperreexia in the lower limbs. vision, and vestibular sense that impair postural support.
TABLE 13-2 long-acting benzodiazepines, affect postural control and 113
increase the risk for falls. These disorders are important
FEATURES OF CEREBELLAR ATAXIA, SENSORY
to recognize because they are often treatable.
ATAXIA, AND FRONTAL GAIT DISORDERS
CEREBELLAR SENSORY
ATAXIA ATAXIA FRONTAL GAIT Psychogenic gait disorder
Base of Wide-based Narrow Wide-based Psychogenic disorders are common in neurologic prac-
support base, looks tice, and the presentation often involves gait. Some
down patients with extreme anxiety or phobia walk with

CHAPTER 13
Velocity Variable Slow Very slow exaggerated caution with abduction of the arms, as
Stride Irregular, Regular Short, shufing if walking on ice. This inappropriately overcautious
lurching with path gait differs in degree from the gait of the patient who
deviation is insecure and making adjustments for imbalance.
Romberg +/ Unsteady, +/ Depressed patients exhibit primarily slowness, a mani-
falls festation of psychomotor retardation, and lack of pur-
Heel shin Abnormal pose in their stride. Hysterical gait disorders are among

Gait and Balance Disorders


+/ Normal
the most spectacular encountered. Odd gyrations of
Initiation Normal Normal Hesitant
posture with wastage of muscular energy (astasia-abasia),
Turns Unsteady +/ Hesitant, extreme slow motion, and dramatic uctuations over
multistep time may be observed in patients with somatoform dis-
Postural + +++ ++++ orders and conversion reaction.
instability
Poor postural
synergies APPROACH TO THE
getting up from PATIENT Slowly Progressive Disorder of Gait
a chair
When reviewing the history, it is helpful to inquire about
Falls Late event Frequent Frequent
the onset and progression of disability. Initial awareness
of an unsteady gait often follows a fall. Stepwise evolu-
tion or sudden progression suggests vascular disease.
Gait disorder may be associated with urinary urgency
Neuromuscular disease and incontinence, particularly in patients with cervical
spine disease or hydrocephalus. It is always important
Patients with neuromuscular disease often have an to review the use of alcohol and medications that affect
abnormal gait, occasionally as a presenting feature. With gait and balance. Information on localization derived
distal weakness (peripheral neuropathy) the step height from the neurologic examination can be helpful to nar-
is increased to compensate for footdrop, and the sole row the list of possible diagnoses.
of the foot may slap on the oor during weight accep- Gait observation provides an immediate sense of the
tance. Neuropathy may be associated with a degree patients degree of disability. Characteristic patterns of
of sensory imbalance, as described earlier. Patients abnormality are sometimes observed, though failing
with myopathy or muscular dystrophy more typically gaits often look fundamentally similar. Cadence (steps/
exhibit proximal weakness. Weakness of the hip gir- min), velocity, and stride length can be recorded by tim-
dle may result in a degree of excess pelvic sway during ing a patient over a fixed distance. Watching the patient
locomotion. get out of a chair provides a good functional assess-
ment of balance.
Toxic and metabolic disorders Brain imaging studies may be informative in patients
with an undiagnosed disorder of gait. MRI is sensitive
Alcohol intoxication is the most common cause of for cerebral lesions of vascular or demyelinating disease
acute walking difculty. Chronic toxicity from medi- and is a good screening test for occult hydrocepha-
cations and metabolic disturbances can impair motor lus. Patients with recurrent falls are at risk for subdural
function and gait. Mental status changes may be pres- hematoma. Many elderly patients with gait and balance
ent, and examination may reveal asterixis or myoclonus. difficulty have white matter abnormalities in the peri-
Static equilibrium is disturbed, and such patients are ventricular region and centrum semiovale. While these
easily thrown off balance. Disequilibrium is particularly lesions may be an incidental finding, a substantial bur-
evident in patients with chronic renal disease and those den of white matter disease will ultimately impact cere-
with hepatic failure, in whom asterixis may impair pos- bral control of locomotion.
tural support. Sedative drugs, especially neuroleptics and
114 DISORDERS OF BALANCE impairment and the use of sedative medications substan-
tially increase the risk for falls.
Balance is the ability to maintain equilibrium: a state in
which opposing physical forces cancel. In physiology,
this is taken to mean the ability to control the center of FALLS
mass with respect to gravity and the support surface. In
Falls are common in the elderly; 30% of people older
reality, we are not consciously aware of what or where
than age 65 years living in the community fall each
our center of mass is, but everyone, including gymnasts,
year. Modest changes in balance function have been
gure skaters, and platform divers, moves so as to man-
described in t older subjects as a result of normal aging.
age it. Imbalance implies a disturbance of equilibrium.
SECTION II

Subtle decits in sensory systems, attention, and motor


Disorders of balance present with difculty maintain-
reaction time contribute to the risk, and environmen-
ing posture standing and walking and with a subjective
tal hazards abound. Epidemiologic studies have iden-
sense of disequilibrium, a form of dizziness.
tied a number of risk factors for falls, summarized in
The cerebellum and vestibular system organize anti-
Table 13-3. A fall is not a neurologic problem, nor
gravity responses needed to maintain the upright pos-
reason for referral to a specialist, but there are circum-
ture. As reviewed earlier in this chapter, these responses
Clinical Manifestations of Neurologic Disease

stances in which neurologic evaluation is appropriate.


are physiologically complex, and the anatomic represen-
In a classic study, 90% of fall events occurred among
tation is not well understood. Failure, resulting in dis-
10% of individuals, a group known as recurrent fallers.
equilibrium, can occur at several levels: cerebellar, ves-
Some of these are frail older persons with chronic dis-
tibular, somatosensory, and higher level disequilibrium.
eases. Recurrent falls sometimes indicate the presence
Patients with hereditary ataxia or alcoholic cerebellar
of serious balance impairment. Syncope, seizure, or falls
degeneration do not generally complain of dizziness,
related to loss of consciousness require appropriate eval-
but balance is visibly impaired. Neurologic examination
uation and treatment (Chaps. 10 and 26).
will reveal a variety of cerebellar signs. Postural com-
The descriptive classication of falls is as difcult as
pensation may prevent falls early on, but falls inevita-
the classication of gait disorders, for many of the same
bly occur with disease progression. The progression of
reasons. Postural control systems are widely distributed,
a neurodegenerative ataxia is often measured by the
and a number of disease-related abnormalities occur.
number of years to loss of stable ambulation. Vestibular
Unlike gait problems that are apparent on observation,
disorders (Chap. 11) have symptoms and signs in three
falls are rarely observed in the ofce. The patient and
categories: (1) vertigo, the subjective appreciation or
family may have limited information about what trig-
illusion of movement; (2) nystagmus, a vestibulo-ocu-
gered the fall. Injuries can complicate the physical
lomotor sign; and (3) poor standing balance, an impair-
examination. While there is no standard nosology of
ment of vestibulospinal function. Not every patient
falls, common patterns can be identied.
has all manifestations. Patients with vestibular decits
related to ototoxic drugs may lack vertigo or obvious
nystagmus, but balance is impaired on standing and
walking, and the patient cannot navigate in the dark.
TABLE 13-3
Laboratory testing is available to explore vestibulo-ocu-
lomotor and vestibulospinal decits. RISK FACTORS FOR FALLS, A META-ANALYSIS:
Somatosensory decits also produce imbalance and SUMMARY OF SIXTEEN CONTROLLED STUDIES
falls. There is often a subjective sense of insecure bal- RISK FACTOR MEAN RR (OR) RANGE
ance and fear of falling. Postural control is compro- Weakness 4.9 1.910.3
mised by eye closure (Rombergs sign); these patients
Balance decit 3.2 1.65.4
also have difculty navigating in the dark. A dramatic
example is the patient with autoimmune subacute sen- Gait disorder 3.0 1.74.8
sory neuropathy, sometimes a paraneoplastic disor- Visual decit 2.8 1.17.4
der (Chap. 44). Compensatory strategies enable such Mobility limitation 2.5 1.05.3
patients to walk in the virtual absence of propriocep-
Cognitive impairment 2.4 2.04.7
tion, but the task requires active visual monitoring.
Patients with higher level disorders of equilibrium have Impaired functional status 2.0 1.03.1
difculty maintaining balance in daily life and may pres- Postural hypotension 1.9 1.03.4
ent with falls. There may be reduced awareness of bal-
ance impairment. Classic examples include patients Abbreviations: OR, odds ratios from retrospective studies; RR, rela-
tive risks from prospective studies.
with progressive supranuclear palsy and normal pressure Source: Reproduced with permission from J Masdeu et al: Gait
hydrocephalus. Patients on sedating medications are Disorders of Aging: With Special Reference to Falls. Boston, Little
also in this category. In prospective studies, cognitive Brown, 1995.
Slipping, tripping, and mechanical falls stick to the oor and the center of mass keeps moving, 115
resulting in a disequilibrium from which the patient has
Slipping on icy pavement, tripping on obstacles, and falls difculty recovering. This sequence of events can result
related to obvious environmental factors are often termed in a forward fall. Gait freezing can also occur as the
mechanical falls. They occasionally occur in healthy indi- patient attempts to turn and change direction. Similarly,
viduals with good balance compensation. Frequent trip- the patient with Parkinsons disease and festinating gait
ping falls raise suspicion about an underlying neurologic may nd his feet unable to keep up, resulting in a for-
decit. Patients with spasticity, leg weakness, or footdrop ward fall.
experience tripping falls.

CHAPTER 13
Weakness and frailty Falls related to sensory decit
Patients who lack strength in antigravity muscles have Patients with somatosensory, visual, or vestibular de-
difculty rising from a chair, fatigue easily when walk- cits are prone to falls. These patients have particular dif-
ing, and have difculty maintaining their balance after a culty dealing with poor illumination or walking on
perturbation. These patients are often unable to get up uneven ground. These patients often express subjective

Gait and Balance Disorders


after a fall and may be on the oor for an hour or more imbalance, apprehension, and fear of falling. Decits in
before help arrives. Deconditioning of this sort is often joint position and vibration sense are apparent on physi-
treatable. Resistance strength training can increase mus- cal examination.
cle mass and leg strength in people in their eighties and
nineties.
Interventions to Reduce the Risk of Falls
TREATMENT
Drop attacks and collapsing falls and Injury
Drop attacks are sudden collapsing falls without loss of Efforts should be made to define the etiology of the gait
consciousness. Patients who collapse from lack of pos- disorder and mechanism of the falls. Standing blood
tural tone present a diagnostic challenge. The patient pressure should be recorded. Specific treatment may
may report that his or her legs just gave out underneath; be possible, once a diagnosis is established. Therapeutic
the family may describe the patient as collapsing in a intervention is often recommended for older patients at
heap. Orthostatic hypotension may be a factor in some substantial risk for falls, even if no neurologic disease is
such falls. Asterixis or epilepsy may impair postural sup- identified. A home visit to look for environmental haz-
port. A colloid cyst of the third ventricle can present ards can be helpful. A variety of modifications may be
with intermittent obstruction of the foramen of Mon- recommended to improve safety, including improved
roe, resulting in a drop attack. While collapsing falls are lighting and the installation of grab bars and nonslip
more common in older patients with vascular risk fac- surfaces.
tors, they should not be confused with vertebrobasilar Rehabilitation interventions attempt to improve
ischemic attacks. muscle strength and balance stability and to make the
patient more resistant to injury. High-intensity resis-
tance strength training with weights and machines
Toppling falls is useful to improve muscle mass, even in frail older
Some patients maintain tone in antigravity muscles but patients. Improvements are realized in posture and
fall over like a tree trunk, as if postural defenses had dis- gait, which should translate to reduced risk of falls and
engaged. There may be a consistent direction to such injury. Sensory balance training is another approach
falls. The patient with cerebellar pathology may lean to improve balance stability. Measurable gains can be
and topple over toward the side of the lesion. Patients achieved in a few weeks of training, and benefits can
with lesions of the vestibular system or its central path- be maintained over 6 months by a 10- to 20-min home
ways may experience lateral pulsion and toppling falls. exercise program. This strategy is particularly success-
Patients with progressive supranuclear palsy often fall ful in patients with vestibular and somatosensory bal-
over backward. Falls of this nature occur in patients ance disorders. The Yale Health and Aging study used a
with advanced Parkinsons disease once postural insta- strategy of targeted, multiple risk factor abatement to
bility has developed. reduce falls in the elderly. Prescription medications were
adjusted, and home-based exercise programs were tai-
lored to the patients needs, based on an initial geriat-
Gait freezing ric assessment. The program realized a 44% reduction
in falls, compared with a control group of patients who
Another fall pattern in Parkinsons disease and related
had periodic social visits.
disorders is the fall due to freezing of gait. The feet
CHAPTER 14

VIDEO LIBRARY OF GAIT DISORDERS

Gail Kang Nicholas B. Galianakis Michael Geschwind

Problems with gait and balance are major causes of falls, ameliorate the underlying cause. In this video, examples
accidents, and resulting disability, especially in later life, of gait disorders due to Parkinsons disease, other extra-
and are often harbingers of neurologic disease. Early pyramidal disorders, and ataxias, as well as other common
diagnosis is essential, especially for treatable conditions, gait disorders, are presented. Videos for this chap-
as it may permit the institution of prophylactic mea- ter can be accessed at the following link: http://www
sures to prevent dangerous falls, and also to reverse or .mhprofessional.com/mediacenter/.

116
CHAPTER 15

NUMBNESS, TINGLING, AND SENSORY LOSS

Michael J. Aminoff Arthur K. Asbury

Normal somatic sensation reects a continuous monitor- lost in sensory nerve bers. If the rate of loss is slow,
ing process, little of which reaches consciousness under lack of cutaneous feeling may be unnoticed by the
ordinary conditions. By contrast, disordered sensation, patient and difcult to demonstrate on examination,
particularly when experienced as painful, is alarming and even though few sensory bers are functioning; if it is
dominates the patients attention. Physicians should be rapid, both positive and negative phenomena are usually
able to recognize abnormal sensations by how they are conspicuous. Subclinical degrees of sensory dysfunction
described, know their type and likely site of origin, and may be revealed by sensory nerve conduction studies or
understand their implications. Pain is considered sepa- somatosensory evoked potentials (Chap. 5).
rately in Chap. 7. Whereas sensory symptoms may be either positive
or negative, sensory signs on examination are always a
measure of negative phenomena.
POSITIVE AND NEGATIVE SYMPTOMS
Abnormal sensory symptoms can be divided into two
TERMINOLOGY
categories: positive and negative. The prototypical posi-
tive symptom is tingling (pins and needles); other posi- Words used to characterize sensory disturbance are
tive sensory phenomena include altered sensations that descriptive and based on convention. Paresthesias and
are described as pricking, bandlike, lightning-like shoot- dysesthesias are general terms used to denote posi-
ing feelings (lancinations), aching, knifelike, twisting, tive sensory symptoms. The term paresthesias typically
drawing, pulling, tightening, burning, searing, electrical, refers to tingling or pins-and-needles sensations but may
or raw feelings. Such symptoms are often painful. include a wide variety of other abnormal sensations,
Positive phenomena usually result from trains of im- except pain; it sometimes implies that the abnormal
pulses generated at sites of lowered threshold or height- sensations are perceived spontaneously. The more gen-
ened excitability along a peripheral or central sensory eral term dysesthesias denotes all types of abnormal sen-
pathway. The nature and severity of the abnormal sen- sations, including painful ones, regardless of whether a
sation depend on the number, rate, timing, and distri- stimulus is evident.
bution of ectopic impulses and the type and function Another set of terms refers to sensory abnormalities
of nervous tissue in which they arise. Because positive found on examination. Hypesthesia or hypoesthesia refers
phenomena represent excessive activity in sensory path- to a reduction of cutaneous sensation to a specic type
ways, they are not necessarily associated with a sensory of testing such as pressure, light touch, and warm or
decit (loss) on examination. cold stimuli; anesthesia, to a complete absence of skin
Negative phenomena represent loss of sensory func- sensation to the same stimuli plus pinprick; and hypal-
tion and are characterized by diminished or absent gesia or analgesia, to reduced or absent pain perception
feeling that often is experienced as numbness and by (nociception), such as perception of the pricking quality
abnormal ndings on sensory examination. In disor- elicited by a pin. Hyperesthesia means pain or increased
ders affecting peripheral sensation, it is estimated that at sensitivity in response to touch. Similarly, allodynia
least one-half the afferent axons innervating a particular describes the situation in which a nonpainful stimulus,
site are lost or functionless before a sensory decit can once perceived, is experienced as painful, even excru-
be demonstrated by clinical examination. This thresh- ciating. An example is elicitation of a painful sensation
old varies in accordance with how rapidly function is by application of a vibrating tuning fork. Hyperalgesia
117
118 denotes severe pain in response to a mildly noxious spinal cord and make their rst synapse in the gracile or
stimulus, and hyperpathia, a broad term, encompasses all cuneate nucleus of the lower medulla. Axons of second-
the phenomena described by hyperesthesia, allodynia, order neurons decussate and ascend in the medial lemnis-
and hyperalgesia. With hyperpathia, the threshold for a cus located medially in the medulla and in the tegmen-
sensory stimulus is increased and perception is delayed, tum of the pons and midbrain and synapse in the VPL
but once felt, it is unduly painful. nucleus; third-order neurons project to parietal cortex.
Disorders of deep sensation arising from muscle spin- This large-ber system is referred to as the posterior col-
dles, tendons, and joints affect proprioception (position umnmedial lemniscal pathway (lemniscal, for short). Note
sense). Manifestations include imbalance (particularly that although the lemniscal and the anterolateral pathways
SECTION II

with eyes closed or in the dark), clumsiness of precision both project up the spinal cord to the thalamus, it is the
movements, and unsteadiness of gait, which are referred (crossed) anterolateral pathway that is referred to as the
to collectively as sensory ataxia. Other ndings on exam- spinothalamic tract by convention.
ination usually, but not invariably, include reduced or Although the ber types and functions that make up
absent joint position and vibratory sensibility and absent the spinothalamic and lemniscal systems are relatively
deep tendon reexes in the affected limbs. The Rom- well known, many other bers, particularly those asso-
berg sign is positive, which means that the patient sways ciated with touch, pressure, and position sense, ascend
Clinical Manifestations of Neurologic Disease

markedly or topples when asked to stand with feet close in a diffusely distributed pattern both ipsilaterally and
together and eyes closed. In severe states of deafferenta- contralaterally in the anterolateral quadrants of the spi-
tion involving deep sensation, the patient cannot walk nal cord. This explains why a complete lesion of the
or stand unaided or even sit unsupported. Continuous posterior columns of the spinal cord may be associated
involuntary movements (pseudoathetosis) of the out- with little sensory decit on examination.
stretched hands and ngers occur, particularly with eyes
closed.

EXAMINATION OF SENSATION
ANATOMY OF SENSATION
The main components of the sensory examination are
Cutaneous afferent innervation is conveyed by a rich tests of primary sensation (pain, touch, vibration, joint
variety of receptors, both naked nerve endings (noci- position, and thermal sensation [Table 15-1]).
ceptors and thermoreceptors) and encapsulated terminals Some general principles pertain. The examiner must
(mechanoreceptors). Each type of receptor has its own depend on patient responses, particularly when testing
set of sensitivities to specic stimuli, size and distinctness cutaneous sensation (pin, touch, warm, or cold), and
of receptive elds, and adaptational qualities. Much of this complicates interpretation. Further, examination
the knowledge about these receptors has come from the may be limited in some patients. In a stuporous patient,
development of techniques to study single intact nerve for example, sensory examination is reduced to observ-
bers intraneurally in awake, unanesthetized human ing the briskness of withdrawal in response to a pinch
subjects. It is possible not only to record from but also or another noxious stimulus. Comparison of response
to stimulate single bers in isolation. A single impulse, on one side of the body to that on the other is essential.
whether elicited by a natural stimulus or evoked by In an alert but uncooperative patient, it may not be
electrical microstimulation in a large myelinated afferent possible to examine cutaneous sensation, but some idea
ber, may be both perceived and localized. of proprioceptive function may be gained by noting the
Afferent bers of all sizes in peripheral nerve trunks patients best performance of movements requiring bal-
traverse the dorsal roots and enter the dorsal horn of ance and precision. Frequently, patients present with
the spinal cord (Fig. 15-1). From there the smaller sensory symptoms that do not t an anatomic localiza-
bers take a route to the parietal cortex different from tion and that are accompanied by either no abnormali-
that of the larger bers. The polysynaptic projections of ties or gross inconsistencies on examination. The exam-
the smaller bers (unmyelinated and small myelinated), iner should consider whether the sensory symptoms
which subserve mainly nociception, temperature sensibil- are a disguised request for help with psychological or
ity, and touch, cross and ascend in the opposite anterior situational problems. Discretion must be used in pur-
and lateral columns of the spinal cord, through the brain- suing this possibility. Finally, sensory examination of a
stem, to the ventral posterolateral (VPL) nucleus of the patient who has no neurologic complaints can be brief
thalamus and ultimately project to the postcentral gyrus and consist of pinprick, touch, and vibration testing in
of the parietal cortex (Chap. 7). This is the spinothalamic the hands and feet plus evaluation of stance and gait,
pathway or anterolateral system. The larger bers, which including the Romberg maneuver. Evaluation of stance
subserve tactile and position sense and kinesthesia, project and gait also tests the integrity of motor and cerebellar
rostrally in the posterior column on the same side of the systems.
119
Leg
Trunk Postcentral
cortex

Arm
Internal
capsule

Face

CHAPTER 15
Thalamus

Ventral
posterolateral
nucleus of

Numbness, Tingling, and Sensory Loss


thalamus

MIDBRAIN

Reticulothalamic pathway

Principal sensory
nucleus of V

PONS

Medial lemniscus
Nucleus
gracilis

Nucleus
cuneatus
MEDULLA
Nucleus
Spinothalamic tract
of spinal
tract V

SPINAL CORD

Spinothalamic tract

FIGURE 15-1
The main somatosensory pathways. The spinothalamic tract) to nuclei in the medulla, pons, and mesencephalon
tract (pain, thermal sense) and the posterior columnlemniscal and nuclear terminations of the tract are indicated. (From AH
system (touch, pressure, joint position) are shown. Offshoots Ropper, RH Brown, in Adams and Victors Principles of Neu-
from the ascending anterolateral fasciculus (spinothalamic rology, 9th ed. New York, McGraw-Hill, 2009.)

Primary sensation Temperature sensation to both hot and cold is best


tested with small containers lled with water of the
(See Table 15-1) The sense of pain usually is tested desired temperature. This is impractical in most settings.
with a clean pin, with the patient asked to focus on the An alternative way to test cold sensation is to touch a
pricking or unpleasant quality of the stimulus, not just metal object, such as a tuning fork at room temperature,
the pressure or touch sensation elicited. Areas of hypal- to the skin. For testing warm temperatures, the tuning
gesia should be mapped by proceeding radially from the fork or another metal object may be held under warm
most hypalgesic site (Figs. 15-2, 15-3 and 15-4). water of the desired temperature and then used. The
120 TABLE 15-1
TESTING PRIMARY SENSATION
SENSE TEST DEVICE ENDINGS ACTIVATED FIBER SIZE MEDIATING CENTRAL PATHWAY

Pain Pinprick Cutaneous nociceptors Small SpTh, also D


Temperature, heat Warm metal object Cutaneous thermoreceptors Small SpTh
for hot
Temperature, cold Cold metal object Cutaneous thermoreceptors Small SpTh
for cold
SECTION II

Touch Cotton wisp, ne brush Cutaneous mechanorecep- Large and small Lem, also D and SpTh
tors, also naked endings
Vibration Tuning fork, 128 Hz Mechanoreceptors, espe- Large Lem, also D
cially pacinian corpuscles
Joint position Passive movement of Joint capsule and tendon Large Lem, also D
specic joints endings, muscle spindles
Clinical Manifestations of Neurologic Disease

Abbreviations: D, diffuse ascending projections in ipsilateral and contralateral anterolateral columns; SpTh, spinothalamic projection, contralat-
eral; Lem, posterior column and lemniscal projection, ipsilateral.

Greater
Lesser n. } occipital nerves
I
Great auricular n.
II
Great auricular n.
Ant. cut. n. of neck
III C5
Ant. cut. n. of neck T1 Supraclavicular ns.
C6
T2
Post.
Supraclavicular ns. Axillary n. 3
cut.
(circumflex) 4
Axillary n. rami Lat. Med. cut. n. of arm
T2 5
(circumflex) Ant. of cut. & intercostobrachial n.
3 6
4 Med. cut. n. of arm Post cut. n. of arm thor.rami
7
cut. & intercostobrachial n. (from radial n.) ns.
Lower lat.cut. n. of arm Lat. 5 8
9 Post. cut. n. of forearm
(from radial n.) rami 6
Lower 10 (from radial n.)
7 L1
of Lat. cut. of arm 11
cut. 8 Lat. cut. n. of forearm
(from radial n.) 12 Med.
thor. 9 cut. n. (from musculocut n.)
Med. cut. n. S1
Lat. cut. of forearm of forearm Post. rami of
ns. 10 of
(from musculocut. n.) Iliohypo- lumbar sacral Radial n.
rami 11 forearm
gastric n. & coccygeal ns.
12
Iliohypo- Radial n. Ulnar n.
Ilio-
gastric n. Inf. med.
inguinal n.
cluneal n. Inf. lat.
Femoral Genital Median n.
cluneal ns.
branch branch of
of genito- genitofem. Inf. med. n. of thigh Median n.
femoral n. n.
Ulnar n.
(lumbo-inguinal n.) Obturator n.
Dorsal n. of penis Post cut. n. of thigh
Lat. cut. n. of thigh
Intermed. & med. cut. ns. Scrotal branch of perineal n. Med. cut. n. of thigh
of thigh (from femoral n.) (from femoral n.)
Lat. cut. n.of calf
Obturator n. (from common femoral n.)
Saphenous n. Lat. plantar n.
(from femoral n.) Lat.cut. n. of calf Med.
(from common peroneal n.) Saphenous n.
plantar n. Lat.
(from femoral n.) plantar n.
Superficial
peroneal
Superficial peroneal n. n.
(from common peroneal n.)
Deep peroneal n. Supercial peroneal n.
(from common peroneal n.) (from common peroneal n.) Saphenous n.
Sural n. (from tibial n.) Calcanean branches
of tibial & sural ns. Sural n.

Med. & lat. plantar ns. Sural n.


Calcanean branches of
(from posttibial n.) (from tibial n.)
sural & tibial ns.

FIGURE 15-2
The cutaneous elds of peripheral nerves. (Reproduced by permission from W Haymaker, B Woodhall: Peripheral Nerve Inju-
ries, 2nd ed. Philadelphia, Saunders, 1953.)
121
C3

C5 C4
C3
C6

C
T1

6
C5 C7 C5
C3
C6 C8
C4 T1
T2 C4
T2 T3
T4
C5 T3 T5
T4 T6

CHAPTER 15
T5 T7 C5 C3
T6 T8 C4
T7 T9 T2 C5 C
T8 T10 6
T9 T11 C7
T1 T10 T12 C8
C6 L1 T1 C6
T11 L C6
L3 2 C7
T12
S1 C8 C8
L1 S2

Numbness, Tingling, and Sensory Loss


C7 C8
S5 S4
S3
L2

L2 L1
S2 L1
L3 L2
L3 L34
L
L3 L4 L5 L5
S S3
2 S1 S
2 S4
L4 S2 S5
L2 L1
L3
L5 L4 L4 L5 S1 S2 L2 L5 S1 S2
L5 L4 L3

L3
S1

L4
L5 S1 S2
S1 L5 S2 L4
S1
L5

FIGURE 15-3 L5 S
S1 S2 L4
L5 2
Distribution of the sensory spinal roots on the surface of
the body (dermatomes). (From D Sinclair: Mechanisms of L L5 S1 L5
4 L
Cutaneous Sensation. Oxford, UK, Oxford University Press, 4
1981; with permission from Dr. David Sinclair.)
FIGURE 15-4
Dermatomes of the upper and lower extremities, outlined
appreciation of both cold and warmth should be tested by the pattern of sensory loss following lesions of single
because different receptors respond to each. nerve roots. (From JJ Keegan, FD Garrett: Anat Rec 102:409,
Touch usually is tested with a wisp of cotton or a 1948.)
ne camel hair brush. In general, it is better to avoid
testing touch on hairy skin because of the profusion of extended and eyes closed. Normal individuals can do
the sensory endings that surround each hair follicle. this accurately, with errors of 1 cm or less.
Joint position testing is a measure of proprioception, The sense of vibration is tested with a tuning fork
one of the most important functions of the sensory sys- that vibrates at 128 Hz. Vibration usually is tested over
tem. With the patients eyes closed, joint position is bony points, beginning distally; in the feet it is tested
tested in the distal interphalangeal joint of the great toe over the dorsal surface of the distal phalanx of the big
and ngers. If errors are made in recognizing the direc- toes and at the malleoli of the ankles, and in the hands
tion of passive movements, more proximal joints are dorsally at the distal phalanx of the ngers. If abnormal-
tested. A test of proximal joint position sense, primar- ities are found, more proximal sites can be examined.
ily at the shoulder, is performed by asking the patient Vibratory thresholds at the same site in the patient and
to bring the two index ngers together with arms the examiner may be compared for control purposes.
122 Quantitative sensory testing
Effective sensory testing devices are now available com- objects and coins in one hand but can do so in the other
mercially. Quantitative sensory testing is particularly are said to have astereognosis of the abnormal hand.
useful for serial evaluation of cutaneous sensation in
clinical trials. Threshold testing for touch and vibra-
tory and thermal sensation is the most widely used
application. LOCALIZATION OF SENSORY
ABNORMALITIES
SECTION II

Sensory symptoms and signs can result from lesions at


Cortical sensation almost any level of the nervous system from the parietal
cortex to the peripheral sensory receptor. Noting the
The most commonly used tests of cortical function distribution and nature of sensory symptoms and signs
are two-point discrimination, touch localization, and is the most important way to localize their source. Their
bilateral simultaneous stimulation and tests for graphes- extent, conguration, symmetry, quality, and severity
thesia and stereognosis. Abnormalities of these sensory are the key observations.
Clinical Manifestations of Neurologic Disease

tests, in the presence of normal primary sensation in an Dysesthesias without sensory ndings by examination
alert cooperative patient, signify a lesion of the pari- may be difcult to interpret. To illustrate, tingling dys-
etal cortex or thalamocortical projections to the pari- esthesias in an acral distribution (hands and feet) can be
etal lobe. If primary sensation is altered, these cortical systemic in origin, e.g., secondary to hyperventilation,
discriminative functions usually will be abnormal also. or induced by a medication such as acetazolamide. Dis-
Comparisons should always be made between analo- tal dysesthesias also can be an early event in an evolv-
gous sites on the two sides of the body because the ing polyneuropathy or may herald a myelopathy, such
decit with a specic parietal lesion is likely to be uni- as from vitamin B12 deciency. Sometimes distal dyses-
lateral. Interside comparisons are important for all cor- thesias have no denable basis. In contrast, dysesthesias
tical sensory testing. that correspond in distribution to a particular periph-
Two-point discrimination is tested with special calipers, eral nerve territory denote a lesion of that nerve trunk.
the points of which may be set from 2 mm to several For instance, dysesthesias restricted to the fth digit and
centimeters apart and then applied simultaneously to the the adjacent one-half of the fourth nger on one hand
site to be tested. The pulp of the ngertips is a common reliably point to disorder of the ulnar nerve, most com-
site to test; a normal individual can distinguish about monly at the elbow.
3-mm separation of points there.
Touch localization is performed by light pressure for an
Nerve and root
instant with the examiners ngertip or a wisp of cot-
ton wool; the patient, whose eyes are closed, is required In focal nerve trunk lesions severe enough to cause a
to identify the site of touch with the ngertip. Bilateral decit, sensory abnormalities are readily mapped and
simultaneous stimulation at analogous sites (e.g., the dor- generally have discrete boundaries (Figs. 15-2, 15-3 and
sum of both hands) can be carried out to determine 15-4). Root (radicular) lesions frequently are accom-
whether the perception of touch is extinguished con- panied by deep, aching pain along the course of the
sistently on one side or the other. The phenomenon related nerve trunk. With compression of a fth lumbar
is referred to as extinction or neglect. Graphesthesia refers (L5) or rst sacral (S1) root, as from a ruptured inter-
to the capacity to recognize with eyes closed letters vertebral disk, sciatica (radicular pain relating to the sci-
or numbers drawn by the examiners ngertip on the atic nerve trunk) is a common manifestation (Chap. 9).
palm of the hand. Once again, interside comparison is With a lesion affecting a single root, sensory decits
of prime importance. Inability to recognize numbers or may be minimal or absent because adjacent root territo-
letters is termed agraphesthesia. ries overlap extensively.
Stereognosis refers to the ability to identify common Isolated mononeuropathies may cause symptoms
objects by palpation, recognizing their shape, texture, beyond the territory supplied by the affected nerve, but
and size. Common standard objects such as keys, paper abnormalities on examination typically are conned to
clips, and coins are best used. Patients with normal ste- appropriate anatomic boundaries. In multiple mono-
reognosis should be able to distinguish a dime from a neuropathies, symptoms and signs occur in discrete ter-
penny and a nickel from a quarter without looking. ritories supplied by different individual nerves andas
Patients should be allowed to feel the object with only more nerves are affectedmay simulate a polyneu-
one hand at a time. If they are unable to identify it in ropathy if decits become conuent. With polyneu-
one hand, it should be placed in the other for compari- ropathies, sensory decits are generally graded, distal,
son. Individuals who are unable to identify common and symmetric in distribution (Chap. 45). Dysesthesias,
followed by numbness, begin in the toes and ascend Bilateral spinothalamic tract involvement occurs with 123
symmetrically. When dysesthesias reach the knees, they lesions affecting the center of the spinal cord, such as in
usually also have appeared in the ngertips. The process syringomyelia. There is a dissociated sensory loss with
appears to be nerve lengthdependent, and the decit impairment of pinprick and temperature appreciation
is often described as stocking-glove in type. Involve- but relative preservation of light touch, position sense,
ment of both hands and feet also occurs with lesions of and vibration appreciation.
the upper cervical cord or the brainstem, but an upper Dysfunction of the posterior columns in the spinal
level of the sensory disturbance may then be found on cord or of the posterior root entry zone may lead to
the trunk and other evidence of a central lesion may be a bandlike sensation around the trunk or a feeling of

CHAPTER 15
present, such as sphincter involvement or signs of an tight pressure in one or more limbs. Flexion of the
upper motor neuron lesion (Chap. 12). Although most neck sometimes leads to an electric shocklike sen-
polyneuropathies are pansensory and affect all modali- sation that radiates down the back and into the legs
ties of sensation, selective sensory dysfunction according (Lhermittes sign) in patients with a cervical lesion
to nerve ber size may occur. Small-ber polyneuropa- affecting the posterior columns, such as from multiple
thies are characterized by burning, painful dysesthesias sclerosis, cervical spondylosis, or recent irradiation to
with reduced pinprick and thermal sensation but with the cervical region.

Numbness, Tingling, and Sensory Loss


sparing of proprioception, motor function, and deep
tendon reexes. Touch is involved variably; when it is Brainstem
spared, the sensory pattern is referred to as exhibiting
sensory dissociation. Sensory dissociation may occur with Crossed patterns of sensory disturbance, in which one
spinal cord lesions as well as small-ber neuropathies. side of the face and the opposite side of the body are
Large-ber polyneuropathies are characterized by vibra- affected, localize to the lateral medulla. Here a small
tion and position sense decits, imbalance, absent ten- lesion may damage both the ipsilateral descending tri-
don reexes, and variable motor dysfunction but pres- geminal tract and the ascending spinothalamic bers
ervation of most cutaneous sensation. Dysesthesias, if subserving the opposite arm, leg, and hemitorso (see
present at all, tend to be tingling or bandlike in quality. Lateral medullary syndrome in Fig. 27-10). A lesion
Sensory neuronopathy is characterized by widespread in the tegmentum of the pons and midbrain, where the
but asymmetric sensory loss occurring in a non-length- lemniscal and spinothalamic tracts merge, causes pansen-
dependent manner so that it may occur proximally or sory loss contralaterally.
distally and in the arms, legs, or both. Pain and numbness
progress to sensory ataxia and impairment of all sensory Thalamus
modalities with time. This condition is usually paraneo-
plastic or idiopathic in origin (Chaps. 44 and 45). Hemisensory disturbance with tingling numbness from
head to foot is often thalamic in origin but also can arise
from the anterior parietal region. If abrupt in onset,
Spinal cord
the lesion is likely to be due to a small stroke (lacu-
(See also Chap. 35) If the spinal cord is transected, all nar infarction), particularly if localized to the thalamus.
sensation is lost below the level of transection. Bladder Occasionally, with lesions affecting the VPL nucleus or
and bowel function also are lost, as is motor function. adjacent white matter, a syndrome of thalamic pain, also
Hemisection of the spinal cord produces the Brown- called Djerine-Roussy syndrome, may ensue. The per-
Squard syndrome, with absent pain and temperature sistent, unrelenting unilateral pain often is described in
sensation contralaterally and loss of proprioceptive sen- dramatic terms.
sation and power ipsilaterally below the lesion (see Figs.
15-1 and 35-1).
Cortex
Numbness or paresthesias in both feet may arise
from a spinal cord lesion; this is especially likely when With lesions of the parietal lobe involving either the
the upper level of the sensory loss extends to the trunk. cortex or the subjacent white matter, the most promi-
When all extremities are affected, the lesion is probably nent symptoms are contralateral hemineglect, hemi-
in the cervical region or brainstem unless a peripheral inattention, and a tendency not to use the affected hand
neuropathy is responsible. The presence of upper motor and arm. On cortical sensory testing (e.g., two-point
neuron signs (Chap. 12) supports a central lesion; a discrimination, graphesthesia), abnormalities are often
hyperesthetic band on the trunk may suggest the level found but primary sensation is usually intact. Anterior
of involvement. parietal infarction may present as a pseudothalamic syn-
A dissociated sensory loss can reect spinothalamic drome with contralateral loss of primary sensation from
tract involvement in the spinal cord, especially if the head to toe. Dysesthesias or a sense of numbness may
decit is unilateral and has an upper level on the torso. also occur and, rarely, a painful state.
124 Focal sensory seizures unilateral; commonly begin in the arm or hand, face, or
foot; and often spread in a manner that reects the corti-
These seizures generally are due to lesions in the area cal representation of different bodily parts, as in a Jack-
of the postcentral or precentral gyrus. The principal sonian march. Duration of seizures is variable; seizures
symptom of focal sensory seizures is tingling, but addi- may be transient, lasting only for seconds, or persist for
tional, more complex sensations may occur, such as a an hour or more. Focal motor features may supervene,
rushing feeling, a sense of warmth, or a sense of move- often becoming generalized with loss of consciousness
ment without detectable motion. Symptoms typically are and tonic-clonic jerking.
SECTION II
Clinical Manifestations of Neurologic Disease
CHAPTER 16

CONFUSION AND DELIRIUM

S. Andrew Josephson Bruce L. Miller

Confusion, a mental and behavioral state of reduced which patients are withdrawn and quiet, with promi-
comprehension, coherence, and capacity to reason, nent apathy and psychomotor slowing.
is one of the most common problems encountered in This dichotomy between subtypes of delirium is a
medicine, accounting for a large number of emergency useful construct, but patients often fall somewhere a