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CLINICAL NEUROPHYSIOLOGY OF INFANCY, CHILDHOOD, AND ADOLESCENCE
Copyright © 2006, Elsevier Inc. ISBN 0-7506-7251-X
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Notice
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our knowledge, changes in practice, treatment, and drug therapy may become necessary or
appropriate. Readers are advised to check the most current information provided (i) on procedures
featured or (ii) by the manufacturer of each product to be administered, to verify the recommended
dose or formula, the method and duration of administration, and contraindications. It is the
responsibility of the practitioners, relying on their own experience and knowledge of the patient, to
make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all
appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Editors
assume any liability for any injury and/or damage to persons or property arising out of or related to any
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The Publisher
Library of Congress Cataloging-in-Publication Data
Clinical neurophysiology of infancy, childhood, and adolescence/Gregory L. Holmes,
Solomon L. Moshé, H. Royden Jones, Jr.—1st ed.
p. cm.
ISBN 0-7506-7251-X
1. Pediatric neurology. 2. Neurophysiology. 3. Electroencephalography. 4. Evoked
potentials (Electrophysiology) I. Holmes, Gregory L. II. Moshé, Solomon L. III. Jones, Jr., H. Royden
RJ488.C56 2006
618.92′8—dc22
2005042084
Acquisitions Editor:Susan Pioli
Developmental Editor:Kim J. Davis
Publishing Services Manager:Frank Polizzano
Senior Project Manager:Peter Faber
Design Direction:Steven Stave
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Dedicated to the many children who have passed through our
neurophysiology labs.
To my wife Colleen, for her enthusiasm and perseverance.
GLH
To my mentor and father-in-law Dr. Marvin Cornblath (1925–2005), my
wife Nancy, my son Jared, and all the children.
SLM
To my mom, a wonderful and vigorous, now 99-year-old, retired school
teacher who loves children dearly, our own kids Roy, Kate, Fred and
David, and to my wife Mary who is a terrific grandmother for Erik,
Kristin, Kendall, Sam, and Natalie.
HRJ
Contributors
P. IAN ANDREWS, MBBS, FRACP SAMUEL L. BRIDGERS, MD
Senior Lecturer, School of Women’s and Children’s Assistant Clinical Professor, Department of Neurology,
Health, University of New South Wales; Paediatric Yale University School of Medicine; Director, EEG
Neurologist, Division of Neurology, Sydney Children’s Laboratory, Hospital of St. Raphael, New Haven,
Hospital, Sydney, Australia Connecticut
Neuromuscular Transmission Defects Ambulatory Electroencephalography
WARREN T. BLUME, MD, FRCPC PHILIP J. BRUNQUELL, MD
Professor of Neurology and Paediatrics, Department of Associate Professor of Pediatrics and Neurology,
Clinical Neurosciences, University of Western Ontario; University of Connecticut School of Medicine,
Neurologist, Department of Clinical Neurosciences, Farmington, Connecticut; Medical Director, Clinical
University Hospital, London, Ontario, Canada Neurophysiology Laboratories, Connecticut Children’s
Normal Development of the Electroencephalogram: Infancy Medical Center, Hartford, Connecticut
Through Adolescence Head Trauma
CHARLES F. BOLTON, MD TED M. BURNS, MD
Adjunct Professor, Department of Medicine, Division of Assistant Professor, Department of Neurology, University
Neurology, Queen’s University, Kingston, Ontario, of Virginia, Charlottesville, Virginia
Canada Clinical Neurophysiology of Pediatric Polyneuropathies
Neuromuscular Problems of the Critically Ill Neonate, Child, Autonomic Testing in Childhood
and Adolescent Clinical Neurophysiology of Pediatric Polyneuropathies
ALEXIS D. BORO, MD EDUARDO M. CASTILLO, PHD
Assistant Professor, Department of Neurology, Albert Assistant Professor, Department of Neurosurgery,
Einstein College of Medicine; Attending Physician, University of Texas at Houston Medical School;
Department of Neurology, Montefiore Medical Center, Faculty, MEG Laboratory, Hermann Hospital,
Bronx, New York Houston, Texas
Basic Principles of Electroencephalography Magnetoencephalography
The Diagnosis of Brain Death
THOMAS O. CRAWFORD, MD
DEBORAH Y. BRADSHAW, MD Associate Professor of Neurology and Pediatrics,
Clinical Associate Professor, Department of Neurology, Departments of Neurology and Pediatrics, Johns
Upstate Medical University, Syracuse, New York Hopkins University; Associate Professor of Neurology
Clinical Neurophysiology of Pediatric Polyneuropathies and Pediatrics, Department of Neurology, Johns
Hopkins Hospital, Baltimore, Maryland
Spinal Muscular Atrophies and Other Disorders of the
Anterior Horn Cell
vii
viii Contributors
BASIL T. DARRAS, MD WILLIAM D. GOLDIE, MD
Professor of Neurology, Department of Neurology, Associate Clinical Professor, Departments of Pediatrics
Harvard Medical School; Director, Neuromuscular and Neurology, University of California—Los Angeles;
Program, Department of Neurology, Children’s Associate Clinical Professor, Division of Child
Hospital Boston, Boston, Massachusetts Neurology, Children’s Hospital—Los Angeles, Los
Neuromuscular Problems of the Critically Ill Neonate, Child, Angeles, California; Director, Child Neurology, and
and Adolescent Director, Clinical Neurophysiology, Ventura County
The Interrelation of DNA Analysis with Clinical Medical Center, Ventura, California
Neurophysiology in the Diagnosis of Chronic Neuromuscular Visual Evoked Potentials in Pediatrics—Normal
Disorder of Childhood Visual Evoked Potentials in Pediatrics—Abnormal
MICHAEL DUCHOWNY, MD SANDRA L. HELMERS, MD
Professor of Clinical Neurology, University of Miami Associate Professor, Department of Neurology, Emory
School of Medicine; Director, Comprehensive Epilepsy University School of Medicine; Associate Professor,
Program, Miami Children’s Hospital, Miami, Florida Department of Neurology, Grady Health System,
Long-Term Electroencephalogram and Video Monitoring Atlanta; Associate Professor, Department of Neurology,
Children’s Healthcare of Atlanta, Atlanta, Georgia
KARIN EDEBOL EEG-OLOFSSON, MD Brainstem Auditory Evoked Potentials in Pediatrics—Normal
Associate Professor, University of Uppsala, Institute of Intraoperative Neurophysiologic Monitoring Using Evoked
Neuroscience; Assistant Professor, Department of Potentials
Clinical Neurophysiology, Neurocentre, University Brainstem Auditory Evoked Potentials in Pediatrics—
Hospital, Uppsala, Sweden Abnormal
Transcranial Magnetic Stimulation: An Overview
Sphincter Dysfunction GREGORY L. HOLMES, MD
Professor of Medicine (Neurology) and Pediatrics,
ALAN B. ETTINGER, MD Dartmouth Medical School; Chief, Section of
Director, Comprehensive Epilepsy Center and Chief of Neurology, Dartmouth-Hitchcock Medical Center,
EEG, Department of Neurology, Long Island Jewish Lebanon, New Hampshire
Medical Center, New Hyde Park, New York; Chief of Basic Principles of Electroencephalography
EEG, Department of Neurology, North Shore Visual Analysis of the Neonatal Electroencephalogram
University Hospital, Manhasset, New York; Chief of Age-Specific Seizure Disorders
EEG and Epilepsy, Department of Neurology, Drug Effects on the Human Electroencephalogram
Huntington Hospital, Huntington, New York
Basic Principles of Electroencephalography PAUL A. L. S. HWANG, MDCM, MSC, FRCPC
Associate Professor of Neurology, University of Toronto
KEVIN J. FELICE, DO Epilepsy Program; Head of Paediatric Neurology,
Professor of Neurology and Director, Neuromuscular North York General Hospital, Toronto, Ontario, Canada
Program and EMG Laboratory, Department of Age-Specific Seizure Disorders
Neurology, University of Connecticut School of
Medicine, Farmington, Connecticut PRASANNA JAYAKAR, MD, PHD
Focal Neuropathies in Children Director, Neuroscience Center, Children’s Brain
Institute, Miami Children’s Hospital, Miami, Florida
ROBIN L. GILMORE, MD Long-Term Electroencephalogram and Video Monitoring
Staff Neurologist, Department of Neurology, Neurology
Center of Middle Tennessee; Staff Neurologist, H. ROYDEN JONES, JR., MD
Department of Medicine, Maury Regional Hospital, Jaime Ortiz-Patiño Chair in Neurology, Lahey Clinic,
Columbia, Tennessee Burlington, Massachusetts; Clinical Professor of
Somatosensory Evoked Potentials in Pediatrics—Normal Neurology, Harvard Medical School; Director,
Somatosensory Evoked Potentials in Pediatrics—Abnormal Electromyography Laboratory, Children’s Hospital
Boston, Boston, Massachusetts
The Floppy Infant
Plexopathies and Nerve Root Lesions
Focal Neuropathies in Children
Contributors ix
Clinical Neurophysiology of Pediatric Polyneuropathies WILLIAM N. MAY, MD, MBA
Neuromuscular Problems of the Critically Ill Neonate, Child, Associate Professor, Department of Pediatrics and
and Adolescent Neurology, University of Tennessee; Chief Medical
The Interrelation of DNA Analysis with Clinical Officer, Administration Department, Le Bonheur
Neurophysiology in the Diagnosis of Chronic Neuromuscular Children’s Medical Center, Methodist Healthcare—
Disorder of Childhood Memphis Hospitals, Memphis, Tennessee
Electroencephalography and Structural Disease of the Brain
SUSAN K. KLEIN, MD, PHD
Assistant Professor, Department of Pediatrics, Case FAYE MCNALL, MED, REEG T
Western Reserve University; Child Neurologist, Director of Education, American Society of
Department of Pediatrics, University Hospitals of Electroneurodiagnostic Technologists, Kansas City,
Cleveland—Rainbow Babies and Children’s Hospital, Missouri
Cleveland, Ohio Drug Effects on the Human Electroencephalogram
Neurophysiology of Language and Behavioral Disorders in
Children THOMAS A. MILLER, MD, FRCPC
Associate Professor, Department of Physical Medicine
SAMUEL E. KOSZER, MD and Rehabilitation, Schulich School of Medicine;
Associate Professor of Neurology, Section Head, Epilepsy Faculty of Medicine and Dentistry, University of
and Neurophysiology, Department of Neurology, Western Ontario; Director, Electrodiagnostic
Albany Medical College Hospital, Albany, New York Laboratory, Co-Director, Peripheral Nerve Clinic,
Visual Analysis of the Neonatal Electroencephalogram Consultant Physiatrist, Hand and Upper Limb Centre,
Visual Analysis of the Pediatric Electroencephalogram St. Josephs Health Care, London, Ontario, Canada
Plexopathies and Nerve Root Lesions
SURESH KOTAGAL, MD
Professor, Departments of Neurology and Pediatrics, SOLOMON L. MOSHÉ, MD
Mayo Clinic, Rochester, Minnesota Professor of Neurology, Neuroscience and Pediatrics,
Childhood Sleep-Wake Disorders Vice Chair, Department of Neurology, Albert Einstein
College of Medicine of Yeshiva University; Director,
EDWARD H. KOVNAR, MD Child Neurology and Clinical Neurophysiology at
Attending Physician, Department of Pediatric Neurology, Montefiore, The University Hospital of Albert Einstein
Children’s Hospital of Wisconsin, Milwaukee, College of Medicine and Jacobi Medical Center,
Wisconsin Bronx, New York
Drug Effects on the Human Electroencephalogram Basic Principles of Electroencephalography
Manifestations of Metabolic, Toxic, and Degenerative Visual Analysis of the Neonatal Electroencephalogram
Diseases Visual Analysis of the Pediatric Electroencephalogram
Infectious Diseases The Diagnosis of Brain Death
NANCY L. KUNTZ, MD HIROSHI OTSUBO, MD
Assistant Professor of Neurology and Pediatrics, Assistant Professor, Department of Paediatrics, University
Department of Neurology, Mayo College of Medicine; of Toronto; Director of Operations, Department of
Consultant in Child and Adolescent Neurology, Clinical Neurophysiology and Epilepsy Monitoring,
Department of Neurology, Mayo Clinic, Rochester, Division of Neurology, Hospital for Sick Children,
Minnesota Toronto, Ontario, Canada
Clinical Neurophysiology of the Motor Unit in Infants and Age-Specific Seizure Disorders
Children
Clinical Neurophysiology of Pediatric Polyneuropathies ANDREW C. PAPANICOLAOU, PHD
Autonomic Testing in Childhood Professor and Director, Division of Clinical
Muscle Disorders in Children: Neurophysiologic Neurosciences, Department of Neurosurgery,
Contributions to Diagnosis and Management University of Texas—Houston Medical School;
Director, MEG Center, Memorial-Hermann Hospital;
Director, Institute of Rehabilitation and Research;
Adjunct Professor, Department of Psychology,
University of Houston; Adjunct Professor, Department
of Linguistics, Rice University, Houston, Texas
Magnetoencephalography
x Contributors
MATTHEW PITT, MD, FRCP MARK S. SCHER, MD
Attending Physician, Clinical Neurophysiology, Great Professor of Pediatrics and Neurology, Department of
Ormond Street Hospital for Children NHS Trust, Pediatrics, Case School of Medicine; Division Chief,
London, United Kingdom Pediatric Neurology, Director, Pediatric/Epilepsy and
Maturational Changes vis-à-vis Neurophysiology Markers Fetal/Neonatal Neurology and Programs, Rainbow
and the Development of Peripheral Nerves Babies and Children’s Hospital, University Hospitals of
Cleveland, Cleveland, Ohio
SUSANA QUIJANO-ROY, MD, PhD Electroencephalography of the Newborn: Normal Features
Assistant, Faculty of Medicine, Université de Versailles Neonatal Electroencephalography: Abnormal Features
Saint-Quentin-en-Yvelines; Pediatric Neurologist,
Department of Pediatrics, Intensive Care and Neuro- KATHRYN J. SWOBODA, MD
respiratory Rehabilitation Department, Hôpital Associate Professor, Department of Neurology, University
Universitaire Raymond Poncaré, Garches, France; of Utah School of Medicine; Adjunct Associate
Assistant, Pediatric Neurophysiology Unit, Hôpital Professor, Department of Pediatrics, Primary
d’Enfants Armand-Trousseau, Paris, France Children’s Medical Center, Salt Lake City, Utah
Facial and Bulbar Weakness The Floppy Infant
FRANCIS RENAULT, MD ROBERTO TUCHMAN, MD
Associate Professor, Université Pierre et Marie Curie; Associate Professor, Department of Neurology, University
Head, Pediatric Neurophysiology Unit, Hôpital of Miami, Florida; Director, Autism Program,
d’Enfants Armand-Trousseau, Paris, France Department of Neurology, Miami Children’s Hospital
Facial and Bulbar Weakness Dan Marino Center, Weston, Florida
Neurophysiology of Language and Behavioral Disorders in
TREVOR J. RESNICK, MD Children
Associate Professor and Director, Division of Pediatric
Neurology, University of Miami School of Medicine; JAMES W. WHELESS, MD
Chief, Department of Neurology, Miami Children’s Professor and Chief of Pediatric Neurology, Le Bonheur
Hospital, Miami, Florida Chair in Pediatric Neurology, University of Tennessee
Long-Term Electroencephalogram and Video Monitoring Health Science Center; Director, Pediatric
Neuroscience Center; Director, Le Bonheur
JAMES J. RIVIELLO, JR., MD Comprehensive Epilepsy Center, Le Bonheur
Professor of Neurology, Department of Neurology, Children’s Medical Center; Clinical Director and Chief
Harvard Medical School; Director, Epilepsy Program, of Pediatric Neurology, St. Jude Children’s Research
Division of Epilepsy and Clinical Neurophysiology, Hospital, Memphis, Tennessee
Department of Neurology, Children’s Hospital Boston, Magnetoencephalography (MEG)
Boston, Massachusetts
Age-Specific Seizure Disorders ELAINE WYLLIE, MD
Drug Effects on the Human Electroencephalogram Head, Section of Pediatric Neurology and Pediatric
Infectious Diseases Epilepsy, Department of Neurology, Cleveland Clinic
Foundation, Cleveland, Ohio
MONIQUE M. RYAN, MBBS, M MED, FRACP Electroencephalography in the Evaluation for Epilepsy
Senior Lecturer, Discipline of Paediatrics and Child Surgery in Children
Health, University of Sydney; Paediatric Neurologist,
T. Y. Nelson Department of Neurology and LEON ZACHAROWICZ, MD, MA
Neurosurgery, Children’s Hospital at Westmead, Neurologist, Department of Psychiatry, North Shore
Sydney, Australia Child and Family Guidance Center, Roslyn Heights,
Autonomic Testing in Childhood New York
Visual Analysis of the Pediatric Electroencephalogram
DONALD B. SANDERS, MD
Professor, Division of Neurology, Duke University
Medical Center, Durham, North Carolina
Neuromuscular Transmission Defects
Preface
Neurophysiologic testing is an important component Rather one should strive to make a “clinical correlation”
of the clinical assessment of children with neurologic of the neurophysiologic data vis-à-vis the history and
disorders. Early in the history of clinical neurophysiology, examination findings. To this end, we have asked our
testing primarily involved electroencephalography (EEG), contributors to provide succinct descriptions of clinical
and later on measuring the speed of conduction along disorders where neurophysiologic testing is a valuable
peripheral nerves became available. This field has adjunct. Our authors have accepted this challenge and
dramatically expanded during the past decades and now have provided beautiful summaries of clinical features
additionally includes evoked potentials, electromyography and neurophysiologic findings for both common and
(EMG), magnetoencephalography, and magnetic stimulation. rare neurologic disorders. We made every effort to blend
The physiologic parameters measured in the child’s the details important to classic electrophysiologic
nervous system change rapidly from birth to the teenage techniques of EEG and EMG studies with the newest
years, with age-specific patterns expressed during discrete techniques such as magnetic stimulation and
developmental periods. Clinical neurophysiologists must magnetoencephalography.
be aware of the challenges in testing and interpreting Since the era of Hans Berger, who made the first EEG
neurophysiologic studies in a continuously evolving sys- recording at Jena, Germany, in 1924, and Edward
tem. Although many of the clinical neurophysiology tech- Lambert, in Rochester, Minnesota, who brought clinical
niques in adults can be extrapolated to children, there is a EMG to the fore in the early 1950s and later became the
need to have a textbook dedicated solely to the perfor- teacher of more than 50% of North American electro-
mance and interpretation of these various neuro- myographers, clinical neurophysiology has attracted
physiologic testing modalities in infancy and childhood. talented and prolific investigators. The early contributions
The wide diversity of clinical neurophysiologic studies in the field remain important and are frequently cited in
has made it impossible for a single physician to review this these chapters. We asked our contributing authors to
entire field in detail. We have been successful in obtaining balance the “classic, old,” but pertinent literature with
contributions from a wonderful group of authors with more recent studies. Although it is not possible to cite
expertise in all aspects of pediatric neurophysiology. All of every paper dealing with childhood clinical neuro-
our contributors have graciously accepted the difficult task physiology, our authors have succeeded in accurately and
of providing a state-of-the-art perspective of the key concisely surveying the neurophysiology literature.
elements appropriate to the performance and inter- This textbook was designed to be of value to both
pretation of clinical neurophysiologic studies in children of trainees and established clinicians. While we hope some
all ages. readers, particularly those in fellowships, will read the
Neurophysiologic studies provide an important exten- book cover to cover, it is likely that other colleagues will
sion to the clinical evaluation and are predicated on a find specific chapters of primary interest. By providing a
careful neurologic history and examination. These various systematic and critical approach to childhood clinical
parameters should never be interpreted in isolation from neurophysiologic studies, this volume should serve as a
the neurologic condition for which testing was obtained. stand-alone reference source of clinical neurophysiology
xi
xii Preface
information for professionals working with children who We greatly appreciated the efforts of Mr. Dennis Druin
have one of the many neurologic disorders that can be for his expertise in producing many of the illustrations in
better defined with neurophysiologic testing. this volume and the wonderful assistance provided by our
We extend our heartfelt thanks to all of the authors who support staff: Emily R. Clough at Dartmouth Medical
contributed to this volume. Because of each person’s well- School; Ms. Pat Clements, the supervisor of the EEG
deserved reputation in his or her respective fields of laboratory at Montefiore Medical Center; and Mrs. Mary
expertise, their contributions provide a special strength to Kreconus of the Lahey Clinic.
this first monograph dedicated to the principles of No project of this sort can come to fruition without the
pediatric clinical neurophysiology. Each clinical neuro- dedication of a top-notch executive publisher. Each of the
physiologist has provided a special dedication to this editors is particularly indebted to Susan Pioli for her faith
project, and for this the editors are most grateful. We know in this project and her unceasing urging, cajoling, and good
that no first effort is perfect, and we hope our readers will humor while asking us to bring this project to conclusion.
feel free to advise us of any areas of confusion or mistakes We also thank her colleague at Elsevier, Kim Davis, a
that we have inadvertently overlooked. We very much developmental editor who was most helpful as we entered
appreciate the alacrity that our authors applied to our the gun lap for this project.
ministrations as well as their good humor when we Lastly, we thank our many neurologic colleagues in our
occasionally applied pressure to come to closure. At times respective institutions who have provided us support and
one has to state there is enough paint on the canvas and constructive critique over the years. We are proud to have
move forward in hopes the next round will provide oppor- worked with each and every one of you!
tunity to enhance the color. That is often difficult to
achieve with such dedicated and conscientious colleagues, Gregory L. Holmes
who seek perfection in their given fields as they have with H. Royden Jones, Jr.
their participation in this venture. Solomon L. Moshé
1
Basic Principles of Electroencephalography
ALAN B. ETTINGER, ALEXIS D. BORO, GREGORY L.
HOLMES AND SOLOMON L. MOSHÉ
Successful electroencephalograph (EEG) interpretation maintain the correct metabolic milieu for neuronal
and analysis are predicated on a thorough understanding signaling); (2) the oligodendrocytes (which myelinate
of the basic concepts of electrical neurophysiology. This neurons); and (3) the microglia (which serve as the brain’s
chapter discusses the physiologic basis of the EEG, the macrophages and assist in brain recovery from injury).
fundamental principles of the electrical circuit, filters, Neurons are classified into three broad types on the
the EEG apparatus, electrodes and their application to the basis of the shape of the cell body and the patterns of the
scalp, special electrodes, digital technology, the EEG pen- dendrites and axons. These types are the multipolar,
writing apparatus, frequency and voltage considerations, pseudounipolar, and bipolar cells. Multipolar neurons are
testing the recording system, sources of the EEG, localiza- characterized by multiple dendrites that emerge from the
tion of activity, artifacts, electrical safety, and special consid- cell body, resulting in a polygonal shape. The cell body of
erations in performing the EEG in children. Definitions of a pseudounipolar neuron is round and gives rise to a single
terms used in the chapter are presented in Appendix I. dendritic process that divides close to the cell body into
a peripheral and central branch. The peripheral branch
transmits incoming sensory information while the central
PHYSIOLOGIC BASIS OF THE EEG branch relays information onward to its target in the
central nervous system. The two processes therefore act
The human brain contains more than 1012 neurons as a combined axon and dendrite. An example of a
interconnected and communicating with each other via pseudounipolar neuron is the cell that relays information
1015 synaptic connections. It is through this communi- from the periphery into the central nervous system in the
cation process, termed signaling, that electrical activity is dorsal root ganglion. Bipolar neurons have a round or oval-
generated, resulting in the human EEG. shaped cell body with a large process emanating from
The cells of the nervous system can be divided into two each end of the cell body. Bipolar cells occur in the reti-
major categories: neurons and neuroglial cells. Although nal and olfactory epithelium, vestibular ganglion, and
neurons come in many shapes and sizes, the major compo- auditory ganglion.
nents of most neurons consist of the dendrites (which Neurons are organized into neuronal ensembles of
receive information), the cell body (which processes and circuits that process specific kinds of information. Neurons
integrates the information), and the axon (which conducts that carry information into the circuit are termed afferent
signals to other brain regions). Neuroglial cells, often neurons, whereas neurons signaling information away
referred to as glia, may also be involved. The three major from the circuit are referred to as efferent neurons. Nerve
categories of glial cells are (1) the astrocytes (which cells that participate only in the local aspects of a circuit
3
4 Basic Principles and Maturational Change
are called interneurons. Processing circuits are combined (negatively charged ions) and cations (positively charged
to form systems that serve broader functions such as ions) inside the cell are not equal; therefore, there is a
memory, vision, and hearing. potential difference between the inside and outside of the
Clinical neurophysiologic studies are based on the cell—the membrane potential. In most neurons at rest
recording of both spontaneous electrical activity, as with the inside of the membrane is –70 mV compared with the
the EEG, and stimulated response, such as evoked poten- outside (resting membrane potential). Ions are therefore
tials. It is through the electrical signaling of information subjected to two forces driving them across the mem-
within these neuronal circuits that both spontaneous and brane: (1) a chemical driving force that depends on the
evoked electrical activity can be measured. This chapter concentration gradient across the membrane and (2) an
reviews some of the basic concepts of neuronal signaling electrical driving force that depends on the electrical
that are important to the understanding of clinical potential across the membrane. Ions flow from high-
neurophysiology. concentration areas to low-concentration areas (chemical
driving force), and they flow to areas of opposite charge,
where like charges repel and unlike charges attract
Basis of Brain Electrical Activity
(electrical driving force).
Membrane Polarity The flux of ions through ion channels is passive and
The atom is composed of three basic particles: neu- requires no metabolic energy. The kinetic properties of ion
trons, electrons, and protons. The net charge of the three permeation are described by the channel’s conductance,
particles is zero. Neutrons are neutral, electrons carry a which is determined by measuring the current (ion flux)
negative charge, and protons carry a positive charge. that flows through the open channel in response to a given
Upsetting this electrical balance by separating positive electrochemical driving force. The net electrochemical
and negatively charged ions results in forces aimed at driving force is determined by the electrical potential
reinstitution of the electrical equilibrium and thereby difference across the membrane and the concentration
a flow of charged ions. Ions may be separated by the gradient of the ions selective for the channel.
application of energy of variable types such as mechan- To illustrate these physiologic features, the flow of K+
ical, electrical, magnetic, or chemical. Electrical or ions is considered (Fig. 1-1). Because K+ ions are present
chemical energy can separate charges in nerve cell at a high concentration inside the cell, they tend to dif-
membranes.1 fuse from inside to outside the cell down their chemical
All neurons and glia have lipid bilayer membranes concentration gradient. As a result, the outside of the
separating the delicate internal machinery of the cell from membrane becomes positively charged compared with the
the external environment. The neuronal membrane is an inside of the membrane. Once K+diffusion has proceeded
excellent insulator and separates different concentrations to a certain point, a potential develops across the mem-
of ions inside the cell from those outside the cell. The brane at which the electrical force driving K+into the cell
activity of ion channels is fundamental to signaling in the exactly balances the chemical force driving K+ out of the
nervous system. The movement of ions that carry electrical cell; that is, the outward movement of K+ (driven by its
charge through ion channels results in voltage changes concentration gradient) is equal to the inward movement
across the membrane. of K+ (driven by the electrical potential difference across
Electrical potentials are generated across the mem- the membrane). This potential is called the potassium
branes of neurons because there are differences in the equilibrium potential(E ).
K
concentration of specific ions across the membrane and The equilibrium potential for any ion X can be
the membrane is selectively permeable to ion flow. Move- calculated from the Nernst equation,
ment of ions across the membrane occurs through ion
channels that consist of proteins that transverse the Ex = (RT/zF) ln ([X]o/[X]i)
neuronal membrane and allow certain ions to cross in the
direction of their concentration gradient. Na+ and Cl– are where R is the gas constant, T is the temperature, z is
more concentrated outside the cell, but K+ and organic the valence of the ion, F is the Faraday constant, and X
anions (consisting of amino acids and proteins) are more is the concentration of the ion inside (i) and outside (o)
concentrated inside the cell. Na+ and Cl– therefore tend the cell. Since RT/F is 25 mV at 25°C and the constant
to flow into the cell, whereas K+ tends to flow outward. for converting from natural logarithms to base 10 loga-
Because of the large size of the organic anions, flow rithms is 2.3, z is +1 for K+, and the concentration of free
through ion channels is not possible. However, ion flow K+ inside and outside the typical mammalian neuron is
is not strictly related to concentration gradients. Because around 100 mmol and 3 mmol, respectively, the Nernst
of the selective permeability of ion channels, anions equation can be rewritten as
