The Physiological Basis of Rehabilitation Medicine

The Physiological Basis of Rehabilitation Medicine

Second Edition

John A. Downey, M.D., D.Phil. (Oxon)

Simon Baruch Professor of Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

Stanley J. Myers, M.D.

A. David Gurewitsch Professor of Clinical Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

Erwin G. Gonzalez, M.D.

Professor of Rehabilitation Medicine, Mount Sinai School of Medicine, City University of New York

Director, Department of Physical Medicine and Rehabilitation, Beth Israel Medical Center, New York, New York

James S. Lieberman, M.D.

H. K. Corning Professor of Rehabilitation Medicine Research, Chairman, Department of Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University

Director, Rehabilitation Medicine Service, The Presbyterian Hospital in the City of New York, New York, New York

Butterworth-Heinemann

Table of Contents

Cover image

Title page

Copyright

Dedication

Contributing Authors

Preface

Acknowledgments

Chapter 1: Upper and Lower Motor Neurons

Publisher Summary

The Lower Motor Neuron

Lesions of the Lower Motor Neuron

The Upper Motor Neuron

Analysis of the Upper Motor Neuron

Chapter 2: Anatomy and Physiology of the Vascular Supply to the Brain

Publisher Summary

Brain Anatomy

Study of Brain Vascular Physiology

Determinants of Cerebral Blood Flow

Vascular Anatomy and Ischemic Syndromes

Chapter 3: Cerebellum and Basal Ganglia

Publisher Summary

The Cerebellum

The Basal Ganglia

Chapter 4: The Autonomic Nervous System

Publisher Summary

Terminology

Anatomic Organization (Figure 4-1)

Physiologic Basis of Autonomic Function

Functions of the Autonomic Nervous System

Autonomic Assessment Based on Cardiovascular Responses to Standard Tests

Temperature Regulation (Table 4-8)

Chapter 5: Skeletal Muscle: Structure, Chemistry, and Function

Publisher Summary

Muscle Development

Muscle Structure

Internal Noncontractile Structures

Skeletal Muscle Proteins

Muscle Contraction

Energy Production

Chapter 6: Receptors in Muscle and Their Role in Motor Control

Publisher Summary

Sensory Receptors in Muscle

Functional Properties of Spindles and Tendon Organs

Reflex Connections of Spindles and Tendon Organs

The Stretch Reflex in Motor Control

Conclusion

Chapter 7: Cardiopulmonary Physiology

Publisher Summary

Heart

The Peripheral Circulation

The Lungs

Chapter 8: Physiology of Synovial Joints and Articular Cartilage

Publisher Summary

Joint Structures and Anatomy

Ultrastructure of Articular Cartilage

Mechanical Behavior of Articular Cartilage

Theoretical Models of Material Behavior

Mechanical Properties of Normal Cartilage

Lubrication of Synovial Joints

Response of Cartilage to Immobilization

Response of Cartilage to Aging and Osteoarthritis

Effects of Osteoarthritis on Biomechanical Properties of Cartilage

Chapter 9: Physiology of the Skin

Publisher Summary

Embryonic Development1

Cellular and Glandular Components

Chapter 10: Nerve Conduction and Neuromuscular Transmission

Publisher Summary

Volume Conduction

Conduction Velocity

Applied Aspects

Additional Stimulation Techniques

Late Responses

Clinical Correlations

A Technique of Nerve Conduction Development

Neuromuscular Transmission

Chapter 11: The Motor Unit and Muscle Action Potentials

Publisher Summary

Motor Unit

Recording of Muscle Action Potentials

Muscle Action Potentials—EMG Findings

Analysis of the Electromyogram and Special EMG

Clinical Applications

Chapter 12: Evoked Potentials

Publisher Summary

Visual Evoked Potentials

Publisher Summary

Test Procedure

Clinical Applications of Visual Evoked Potentials

Auditory Evoked Potentials

Publisher Summary

Classification

Anatomic-Physiologic Basis

Auditory Evoked Potentials Other Than BAEPs

Brain Stem Auditory Evoked Potentials

Middle Latency Auditory Evoked Potentials

Late Latency Auditory Evoked Potentials

Long Latency (Cognitive) Auditory Evoked Potentials

Conclusion

Somatosensory and Motor Evoked Potentials

Publisher Summary

Somatosensory Evoked Potential

Motor Evoked Potentials

Conclusion

Chapter 13: Human Thermoregulation

Publisher Summary

Temperature Measurement

Regulation of Body Temperature

Regulation of Body Temperature During Exercise

Summary

Chapter 14: Control of the Circulation in the Limbs

Publisher Summary

Hemodynamic Fundamentals of Blood Flow

Features of Arteries and Veins

Cellular Aspects of Vessel Function

Hormones and Other Vasoactive Influences on Smooth Muscle Tone

Systemic Elements of Circulatory Control

Distribution of the Limb Circulation

Functional Regulation of Blood Flow

Chapter 15: Exercise and Fatigue

Publisher Summary

General Principles of Exercise

Specific Types of Exercise

Fatigue

Conclusion

Chapter 16: Energy Expenditure During Ambulation

Publisher Summary

Normal Gait

Energy Sources and Metabolism

Energy Measurement

Methods of Measuring Energy Expenditure

Energy Expenditure in Normal Persons

Levels of Activity Measured by Magnitude of Energy Cost

Energy Expenditure with Disability

Summary

Conclusion

Chapter 17: Physiologic Changes Associated with Bed Rest and Major Body Injury

Physiology of Bed Rest

An Overview of the Response to Injury

Chapter 18: Obesity and Weight Control

Publisher Summary

Classification of Obesity

Physiologic Risks

Dietary Regimens

Exercise Programs

Exercise and Safety

Other Considerations

Summary

Chapter 19: Urogenital Physiology

Publisher Summary

Genitourinary Anatomy

Genitourinary Neurophysiology

Physiology of Voiding

Pathophysiology of Lower Urinary Tract Symptoms

Physiology of Sexual Function

Chapter 20: Autonomic Function in the Isolated Spinal Cord

Publisher Summary

Organization of the Autonomic Nervous System

Renovascular Function

Cardiovascular Function

Pulmonary Function

Temperature Regulation

Gastrointestinal Function

Sexual Function

Micturition

Summary

Chapter 21: Peripheral Nerve Regeneration

Publisher Summary

Anatomy and Physiology of the Peripheral Nervous System

Peripheral Nerve Degeneration

Primary Growth Versus Nerve Regeneration

Peripheral Nerve Regeneration

Reinnervation of Muscle

Conclusions

Chapter 22: Biofeedback

Publisher Summary

Examining the Concept of Feedback

Other Feedback Options

Applications of Muscle Biofeedback

On Treatment Strategy

The Concept of Kinesiologic Electromyography

How Might Muscle Feedback Work?

Chapter 23: The Physiologic Aspects and Clinical Application of Functional Electrical Stimulation in Rehabilitation

Publisher Summary

History

Motor System Anatomy and Physiology

Components of Functional Neuromuscular Stimulation Systems

Alterations in Exercise Capacity Following Spinal Cord Injury

Conclusion

Chapter 24: Central Nervous System Plasticity and Cognitive Remediation

Publisher Summary

Central Nervous System Plasticity

Learning and Cognitive Remediation

Behavioristic and Cognitive Frames of Reference

Visual and Auditory Aspects of Learning

A Sampling of Treatment Methods for Remediation of Perceptual Disorders

The Executive Functions

Procedural and Declarative Knowledge

Procedural Knowledge, Declarative Knowledge and Remediation of the Executive Functions

Attentional Processes: The Principal Brain Loci

The Management of Attentional Disorders: A Sampling of Remediational Approaches

Memory and Learning

Kandel Synapses and Conditioning

Hebb Synapses and Long-Term Potentiation

The Remediation of Memory Deficits: A Sampling of Treatment Methods

Chapter 25: Aging of the Reproductive System in Women: Menopause

Publisher Summary

Definitions

Age at Natural Menopause

The Transition to Menopause

Multiple Effects of Decreased Estrogen Level

Hot Flashes

Sleep Patterns

Sexual Functioning

Conclusions

Chapter 26: Aphasia, Apraxia, and Agnosia

Publisher Summary

Handedness and Cerebral Dominance

Aphasia: Definition and Historical Background

Examination of the Patient

Aphasie Syndromes

Apraxia

Agnosias and Disorders of Spatial Perception and Manipulation

Calculation and Music

Aphasia Treatment

Chapter 27: Skeletal Physiology and Osteoporosis

Publisher Summary

Physiology of Bone Metabolism

Metabolic Bone Disease

Treatment

Chapter 28: Biology of Aging in Humans

Publisher Summary

Systemic Changes Associated with Aging

The Role of Exercise in Aging

Conclusion

Chapter 29: Pain and Suffering

Publisher Summary

Introduction to Clinical Pain

Evaluating the Complaint of Pain

Experimentally Induced Pain

Index

Copyright

Copyright © 1994 by Butterworth-Heinemann.

A member of the Reed Elsevier group

All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.

Every effort has been made to ensure that the drug dosage schedules within this text are accurate and conform to standards accepted at time of publication. However, as treatment recommendations vary in the light of continuing research and clinical experience, the reader is advised to verify drug dosage schedules herein with information found on product information sheets. This is especially true in cases of new or infrequently used drugs.

Recognizing the importance of preserving what has been written, it is the policy of Butterworth-Heinemann to have the books it publishes printed on acid-free paper, and we exert our best efforts to that end.

Library of Congress Cataloging-in-Publication Data

The Physiological basis of rehabilitation medicine / edited by John A.

Downey … [et al.]. —2nd ed.

p. cm.

Includes bibliographical references and index.

ISBN 1-56372-080-9 (alk. paper)

1. Medical rehabilitation. 2. Human physiology. I. Downey, John A., 1930-

[DNLM: 1. Physiology. 2. Pathology. 3. Rehabilitation. QZ 140 P578 1994]

RM930.P48 1994

612′.0024617—dc20

DNLM/DLC

for Library of Congress 93-37020

CIP

British Library Cataloging-in-Publication Data.

A catalogue record for this book is available from the British Library.

Butterworth-Heinemann

80 Montvale Avenue

Stoneham, MA 02180

10 9 8 7 6 5 4 3 2 1

Printed in the United States of America

Dedication

To Robert C. Darling, the first Simon Baruch Professor of Rehabilitation Medicine at Columbia University’s College of Physicians and Surgeons and founder of its Department of Rehabilitation Medicine.

Dr. Darling graduated from Harvard College and Harvard Medical School with high honors. After medical residency at The Presbyterian Hospital he became a distinguished colleague of Nobel prize winners Doctors Andre Cournand and Dickinson Richards, during which time he contributed much t the elucidation of pulmonary and cardiovascular function. He later continued his work in exercise and environmental physiology at the Harvard Fatigue Laboratory, whence came much of the foundation of these fields in modern medicine. He rose to become director of that laboratory before returning to Columbia-Presbyterian Medical Center, where he was asked to develop and found the Department of Rehabilitation Medicine at Columbia University. His work in academics, medicine, and science exemplifies the ideal for the future direction of rehabilitation medicine.

Contributing Authors

Jose A. Alonso, M.D.,     Assistant Professor of Clinical Rehabilitation, Medicine, College of Physicians and Surgeons, Columbia University, Assistant Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

Jerry G. Blaivas, M.D.,     Department of Urology, New York Hospital/Cornell Medical Center, New York, New York

Joanne Borg-Stein, M.D.,     Assistant Professor of Rehabilitation Medicine, Tufts University School of Medicine, Medical Director, Spaulding and Newton Wellesley Hospital, Rehabilitation Center, Spaulding Rehabilitation Hospital, Boston, Massachusetts, Associate Chief, Physical Medicine and Rehabilitation, Newton, Wellesley Hospital, Newton, Massachusetts

Assistant Professor. Richard Borkow, M.D.,     Department of Rehabilitation Medicine, Albert Einstein College of Medicine, Bronx, New York

Anne Breuer, M.D.,     Clinical Assistant Professorof Orthopaedics and Rehabilitation, University of Miami School of Medicine, Miami, Florida

John CM. Brust, M.D.,     Professor of Clinical Neurology, College of Physicians and Surgeons, Columbia University, Director, Department of Neurology Harlem Hospital Center, New York, New York

Eisworth R. Buskirk, Ph.D.,     Professor of Applied Physiology, Emeritus, Noll Laboratory for Human Performance, Research, The Pennsylvania State University, University Park, Pennsylvania

Malcolm B. Carpenter, M.D.,     Professor and Chairman Emeritus, Department of Anatomy, Uniformed Services University, Bethesda, Maryland

Arminius Cassvan, M.D.

Associate Professor of Clinical Rehabilitation, Medicine, State University of New York, Stony Brook, Stony Brook, New York

Chief, Rehabilitation Medicine, Franklin Hospital Medical Center, Valley Stream, New York

Director, Rehabilitation Medicine, Hempstead General Hospital Medical Center, Hempstead, New York

Yasoma Challenor, M.D.

Clinical Professor of Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, New York, New York

Director Department of Rehabilitation Medicine, Blythedale Children’s Hospital, Valhalla, New York

W. Crawford, Clark,     Associate Professor of Medical Psychology, College of Physicians and Surgeons, Columbia University, Research Scientist VI Department of Biopsychology, New York State Psychiatric Institute, New York, New York

Paul J. Corcoran, M.D.

Visiting Professor and Interim Director, Division of Physical Medicine and Rehabilitation, Harvard Medical School, Clinical Director

Department of Rehabilitation Medicine, Spaulding Rehabilitation Hospital, Boston, Massachusetts

Felicia Cosman, M.D.

Assistant Professor of Medicine, Regional Bone Center, College of Physicians and Surgeonsm Columbia University New York, New York

Regional Bone Center, Helen Hayes Hospital, West Haverstraw, New York

Lucien J. Cote, M.D.,     Associate Professor Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York

John A. Downey, M.D., D.Phil. (Oxon),     Simon Baruch Professor of Rehabilitation, Medicine College of Physicians and Surgeons, Columbia University, Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

Robert J. Downey, M.D.,     Fellow, Cardiothoracic Surgery, College of Physicians and Surgeons, Columbia University, New York, New York

Erwin G. Gonzalez, M.D.

Professor of Rehabilitation Medicine, Mount Sinai School of Medicine, City University of New York

Director, Department of Physical Medicine and Rehabilitation Beth Israel Medical Center, New York, New York

James Gordon, Ed.D., P.T.,     Assistant Professor Program in Physical Therapy, Research Scientist, Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University New York, New York

Leonard C. Harber, M.D.,     Rhodebeck Professor of Dermatology, College of Physicians and Surgeons, Columbia University, Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

Martha E. Heath, Ph.D.

Department of Environmental Medicine, Navy Medical Research Institute, Bethesda, Maryland

Associate Research Scientist, Department of Rehabilitation Medicine College of Physicians and Surgeons, Columbia University, New York, New York

Mazher M. Jaweed, Ph.D.,     Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas

E. Ralph Johnson, M.D.,     Associate Professor and Acting Chairman, Physical Medicine and Rehabilitation, University of California, Davis, School of Medicine, Davis, California, Attending Physician, Physical Medicine and Rehabilitation, University of California, Davis, Medical Center, Sacramento, California

Steven A. Kaplan, M.D.,     Assistant Professor of Urology, College of Physicians and Surgeons, Columbia University, Director, Neuro-Urology and Prostate Center, The Presbyterian Hospital in the City of New York New York, New York

David D. Kilmer, M.D.,     Assistant Professor of Physical Medicine and Rehabilitation, University of California, Davis, School of Medicine, Davis, California

Fredi Kronenberg, Ph.D.,     Assistant Professor of Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, New York, New York

Daniel E. Lemons, Ph.D.,     Associate Professor of Biology, City College of the City University of New York, New York, New York

James S. Lieberman, M.D.,     H.K. Corning Professor of Rehabilitation, Medicine Research, Chairman, Department of Rehabilitation, Medicine, College of Physicians and Surgeons, Columbia University, Director, Rehabilitation Medicine Service The Presbyterian Hospital in the City of New York, New York, New York

Cynthia Lien, M.D.,     Assistant Professor of Anesthesiology, Cornell University Medical College, Associate Attending Anesthesiologist, The New York Hospital, New York, New York

Robert Lindsay, M.B.Ch.B., Ph.D., F.R.C.P.,     Professor of Medicine, College of Physicians and Surgeons, Columbia University, Chief, Department of Internal Medicine, Helen Hayes Hospital, New York, New York

Robert E. Lovelace, M.D., F.R.C.P. (Lond),     Professor of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York

Brenda S. Mallory,     Assistant Professor of Rehabilitation, College of Physicians and Surgeons, Columbia University, Assistant Attending Physician, The Presbyterian Hospital in the City of New York, New York, New York

J.P. Mohr, M.D.,     Sciarra Professor of Clinical Neurology, College of Physicians and Surgeons, Columbia University, New York, New York

Jonathan R. Moldover, M.D.,     Associate Clinical Professor of Rehabilitation, Medicine, College of Physicians and Surgeons, Columbia University, New York, New York Chief, Rehabilitation Medicine, Helen Hayes Hospital, West Haverstraw, New York

C. Van Mow, Ph.D., B.A.E.,     Professor of Mechanical Engineering and Orthopaedic Bioengineering, Director, Orthopaedic Research Laboratory, College of Physicians and Surgeons, Columbia University, New York, New York

Stanley J. Myers, M.D.A.,     David Gurewitsch Professor of Clinical, Rehabilitation Medicine, College of Physicians and Surgeons, Columbia University, Attending Physician, The Presbyterian, Hospital in the City of New York, New York, New York

Janet H. Prystowsky, M.D., Ph.D.,     Irving Assistant Professor of Dermatology, Columbia University, Assistant Attending Physician, Department of Dermatology, The Presbyterian Hospital in the City of New York, New York, New York

Kristjan T. Ragnarsson, M.D.,     Dr. Lucy G. Moses Professor and Chairman, Department of Rehabilitation Medicine, Mount Sinai School of Medicine City University of New York, New York, New York

Joel Stein, M.D.,     Instructor in Medicine, Division of Physical Medicine and Rehabilitation, Harvard Medical School, Attending Physician, Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, Massachusetts

N. Venketasubramanian, M.D.,     Post-doctoral Fellow, Department of Neurology, College of Physicians and Surgeons, Columbia University New York, New York, Tan Tok Seng Hospital, Singapore

Charles Weissman, M.D.,     Associate Professor of Clinical Anesthesiology, and Clinical Medicine, College of Physicians and Surgeons, Columbia University, New York, New York

Steven L. Wolf, Ph.D., F.A.P.T.A.,     Professor and Director of Research, Department of Rehabilitation Medicine, Professor, Department of Medicine, Associate Professor, Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia

William L. Young, M.D.,     Associate Professor of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York

Jerald R. Zimmerman, M.D.,     Assistant Professor of Physical Medicine and Rehabilitation, UMDNJ—New Jersey Medical School, Newark, New Jersey, Clinical Chief of Orthopaedic Rehabilitation, Kessler Institute for Rehabilitation, West Orange, New Jersey

Preface

Rehabilitation medicine is the area of specialty concerned with the management of patients with impairments of function due to disease or trauma. A careful distinction should be made between impairments, which are the physical losses themselves, and disabilities, which are the effects of impairments on overall function of the individual. Understanding and utilization of this distinction require knowledge of the manner in which the human body adapts to and compensates for the peculiar forms of stress which the original injury has produced. In this way, physiology is the parent basic science in this area of medicine.

This book is a compilation of essays on selected physiologic topics most pertinent to adaptation and compensatory adjustments in patients with neurological, musculoskeletal and circulatory impairments. In some instances these physiologic topics address reduction of the impairments themselves, but more often they relate to the principles of compensatory adaptations that can reduce the resulting disability. The chapters are not designed to be directly applicable to immediate practice; they are compendia of background knowledge on which the practitioner can build.

The range of topics has been chosen by criteria not wholly logical or comprehensive. An encyclopedic approach obviously would have been impossible in a single volume of modest dimensions. There is an insufficient body of basic knowledge in some topics of importance to justify a chapter. For other topics on which there may be sufficient knowledge in scattered sources, the editors could not discover an appropriate author. Selectivity also resulted from the editors’ bias, which favors the areas of their personal experiences. We have chosen, when possible, topics on which there is important new evidence and data, but we have avoided areas in which the evidence is so recent that it is likely to be modified or possibly disproved in the near future. In this way, we may have missed some exciting and useful frontiers of knowledge, we hope our book will have more than fleeting validity.

In this volume physiology is interpreted broadly. Where structure and functions are closely linked, as in studies of the central nervous system, we have considered neuroanatomy as a physiologic topic. Where function is not associated with any local definite structure as in psychology, we have still considered human motivation as a physiologic subject, as long as it is based on sound observation, in a system in which stimulus leads to a predictable response.

The contributors were asked to cover thoroughly their assigned areas and not to oversimplify. Yet the result of their efforts, and of the efforts of the editors, is a presentation of material that is easily understandable to physicians and other health professionals with a scientific background. References listed at the conclusion of each chapter are designed to allow any student or practitioner who so desires to explore the topic in greater depth.

Another reason for a book on physiology for practitioners in rehabilitation medicine lies in the nature of therapy in this area of medicine. Treatment by drugs and diet lends itself to controlled therapeutic trials with carefully constructed controls. Treatment by exercise devices, physical agents, and environmental manipulation, since these require active participation and knowledge on the part of the patient, presents greater difficulties to construction of controls, although efforts along these lines are being made and should continue. Rehabilitation medicine depends heavily for its scientific base on knowledge of normal responses to physiologic stimuli and deduction therefrom as to the likely response of patients. Various efforts are needed to reduce empiricism, to discard traditions not in accord with modern scientific fact, and to build up a body of validated knowledge peculiar to this growing area of medical need.

The preceding paragraphs, modified from the first edition, set forth the goal shared by the current editors, who are pr fessors of rehabilitation medicine: to continue the physiologic approach to the teaching of medical students and young physicians. To solidify this interest and emphasis, many of the chapters in this edition, as in the first, are authored or coauthored by specialists currently or formerly of this department and by others who were trained in this tradition.

JOHN A. DOWNEY

Acknowledgments

The editors wish to acknowledge their indebtedness to many former colleagues and students. JAD wishes particularly to mention Dr. John B. Armstrong, FRCP(C), and the late Professors E. C. Eppinger, Sir George Pickering, FRS, and R. F. Loeb and to acknowledge that much of his contribution to this edition was developed and produced during a sabbatical spent as Visiting Professor at the International Center for the Disabled in New York City. This institution was the first comprehensive medical and vocational rehabilitation facility, and it remains one of the foremost in the United States. There, Dr. Downey received much of his earliest training, and it afforded the ideal atmosphere for academic and intellectual pursuits. SJM wishes to acknowledge the late Dr. A. David Gurewitsch for his example of what a clinician should be. Though not a scientist, he set an example of the practice of the art of medicine, which is the end result of this book. EGG would like to acknowledge all former residents trained by him during the 12 years he directed the rehabilitation medicine residency program at Columbia-Presbyterian, whose constant quest for scientific rationale served as inspiration to update the book; Dr. Robert Newman, President of Beth Israel Medical Center for allowing the time needed to complete the work; and Agustin Hernandez for his literary assistance. JSL would like to acknowledge his mentors, Professors Gilbert H. Glaser, Sid Gilman, and William M. Fowler, Jr., who were instrumental in developing his interest in and knowledge of the physiology of the nervous system and of muscle.

The editors wish to acknowledge their appreciation to Mr. Peter F. Skinner of the International Center for the Disabled for his incisive and expert editorial contributions, and to Ms. Rosemary Bleha of The Presbyterian Hospital for her organizational and administrative assistance.

JOHN A. DOWNEY, M.D., STANLEY J. MYERS, M.D., ERWIN G. GONZALEZ, M.D. and JAMES S. LIEBERMAN, M.D.

Chapter 1

Upper and Lower Motor Neurons

MALCOLM B. CARPENTER

This work was supported by research grants CO7005 from the Department of Defense, Uniformed Services University of the Health Sciences, and NS-26658 from the National Institutes of Health, Bethesda, Maryland. The opinions and assertions contained herein are the private ones of the author and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. Experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, NIH Pub. No. 80-23.

Publisher Summary

This chapter presents an overview of the upper and lower motor neurons. Anterior horn cells and their peripheral processes (axons), which innervate striated muscle, constitute anatomic and physiologic units referred to as the final common motor pathway or the lower motor neuron. The concept of the lower motor neuron is not limited to spinal cord. Motor cranial nerve nuclei, which innervate muscles in the head and neck, also are classified as lower motor neurons. Anterior horn cells, which are the prototype for all motor neurons, lie in cell columns in the anterior gray horn of the spinal cord. Several distinct cell columns are evident in the anterior horn. A medial cell column extending throughout the length of the spinal cord, which is divisible into cell groups, innervates the long and short axial muscles. The lateral cell column innervates the remaining body musculature. In the thoracic region, the lateral cell column is small and innervates the intercostal and anterolateral trunk musculature. All the descending fibers systems that can influence or modify activities of the lower motor neuron constitute the upper motor neuron.

Loss of motor function in parts of the body owing to a neural lesion is a distressing and fearful event for anyone. A lesion involving the motor systems is evidenced by loss of voluntary movement, muscle weakness, loss of muscle tone, loss or alteration of reflex activity, abnormal postures, and ultimately substitution of inferior and awkward motor activity. Evaluation of loss or disturbances of motor function should begin by determining the site of the lesion. The location of the lesion frequently provides clues to its nature and insights into the specific pathology. Because disturbances of voluntary motor function may involve either the upper or lower motor neuron, the first step is to distinguish which is involved. This relatively simple, yet frequently puzzling, distinction is one of the cornerstones of clinical neurology.

The Lower Motor Neuron

Anterior horn cells and their peripheral processes (axons), which innervate striated muscle, constitute anatomic and physiologic units referred to as the final common motor pathway, or the lower motor neuron. The concept of the lower motor neuron is not limited to spinal cord. Motor cranial nerve nuclei, which innervate muscles in the head and neck, also are classified as lower motor neurons.

Anterior horn cells, the prototype for all motor neurons, lie in cell columns in the anterior gray horn of the spinal cord. Several distinct cell columns are evident in the anterior horn. A medial cell column extending throughout the length of the spinal cord, divisible into cell groups, innervates the long and short axial muscles. The lateral cell column innervates the remaining body musculature. In the thoracic region the lateral cell column is small and innervates the intercostal and anterolateral trunk musculature. In the cervical and lumbosacral enlargements the lateral cell column enlarges and consists of several large subgroups. Cell groups of the lateral cell column in the cord enlargements innervate the muscles of the extremities. Cells of the lateral column, located anteriorly and peripherally, innervate extensor and abductor muscle groups; cells located dorsal and central to these innervate flexor and adductor muscle groups (Figure 1-1). The spinal gray matter has cytoarchitectural lamination that divides it into separate zones.¹,² Anterior horn cells lie with Rexed’s lamina IX, characterized by large motor neurons, 30 to 100 μ in diameter (Figure 1-2). These large multipolar neurons have coarse Nissl granules, large central nuclei, and multiple dendrites that extend beyond the limits of lamina IX. Axons of these cells emerge via the ventral root and become mixed with dorsal root fibers distal to the dorsal root ganglion. Spinal nerves containing both motor and sensory fibers are referred to as mixed spinal nerves. Fibers of the mixed spinal nerve divide into dorsal and ventral primary rami (Figure 1-3). In the spinal enlargements the primary rami participate in plexus formation, resulting in the formation of the brachial and lumbosacral plexuses. Nerves given off from these plexuses provide innervation for the muscles of the upper and lower extremities.

Figure 1-1 Diagram of the motor nuclei of the anterior gray horn in a lower cervical spinal segment. On the left, the approximate locations of neurons innervating different muscle groups are shown. On the right, groups of motor neurons are indicated by numbers. Both alpha and gamma fibers are shown emerging from the anterior horn. (From Carpenter MB. Core Text of Neuroanatomy, ed 3. Baltimore: Williams & Wilkins, 1985.)

Figure 1-2 Drawing of a transverse section of the spinal cord at C-8 with the laminae of Rexed on the right and the position of the principal descending tracts indicated on the left.

Figure 1-3 Schematic diagram of a thoracic spinal nerve showing peripheral branches and central connections. (From Noback CR, Demarest RJ. The Human Nervous System, ed 3. New York: McGraw-Hill, 1981.)

Not all cells in the anterior gray horn innervate striated muscle. Some, usually smaller than motor neurons, have processes confined to the spinal cord. These cells, referred to as internuncial neurons, have axons that project to other segments, to the opposite side of the spinal cord, or to motor neurons. Cells whose axons emerge from the spinal cord are known as root cells; these cells subserve effector functions. Root cells of the anterior horn are of two types: (1) alpha (α) motor neurons give rise to large fibers that innervate striatal (extrafusal) muscle and (2) gamma (γ) motor neurons innervate muscle spindles (intrafusal; Figures 1-2 and 1-4). The spectrum of myelinated fibers in the ventral roots indicates two groups of fibers. Approximately 70% of the fibers are between 8 and 13 μm in diameter and are classified as alpha fibers; the remaining 30% of the fibers, 3 to 8 μm in diameter, are designated gamma fibers. In addition, the ventral roots in thoracic and upper lumbar spinal segments contain unmyelinated or poorly myelinated preganglionic sympathetic fibers. Sacral ventral roots (S-2, S-3, and S-4) contain similar poorly myelinated preganglionic parasympathetic fibers. These preganglionic fibers project to various autonomic ganglia.

Figure 1-4 Schematic diagram of the sensory and motor elements involved in the patellar tendon reflex. Muscle spindle afferents are shown entering only the L-3 spinal segment; Golgi tendon organ afferents are shown entering only the L-2 segment. In this monosynaptic reflex afferent fibers enter L-2, L-3, and L-4 spinal segments and efferent fibers from the anterior horn cells at these same levels project to the extrafusal muscle fibers of the quadriceps femoris. Efferent fibers from L-4 projecting to the hamstrings represent part of the pathway involved in reciprocal inhibition. The small diagram on the left illustrates the gamma loop. Contractions of the polar parts of the muscle spindle initiate an afferent volley conducted centrally to alpha motor neurons. Discharge of the alpha motor neuron is conveyed to the motor end-plate of the same muscle. The gamma efferent fiber controls the sensitivity of the muscle spindle. (From Carpenter MB. Core Text of Neuroanatomy, ed 3. Baltimore: Williams & Wilkins, 1985.)

Alpha motor neurons are cholinergic and terminate upon skeletal muscle fibers in small, flattened expansions known as motor end-plates, which constitute the so-called myoneural junction. Electrical stimulation of a motor nerve causes quanta of acetylcholine (ACh) to be liberated at the myoneural junction, which produces contractions of muscle fibers. Following the contractions, acetylcholinesterase (AChE) hydrolyzes the ACh. Stimulation of a muscle nerve with graded shocks results in twitches of the muscle related directly to the strength of the stimulus, until the alpha spike reaches its full potential. Increasing the size of the stimulus does not produce a stronger contraction, even though gamma fibers may be discharged. Thus, impulses conducted by alpha motor fibers are related to the contractile elements of striated muscle and gamma motor neurons do not contribute directly to muscle contraction. Gamma fibers are distributed to the polar (contractile) portions of the muscle spindles. Contraction of the polar portions of the muscle spindle may be sufficient to cause the discharge of muscle spindle afferent fibers (group IA), but these contractions do not directly alter muscle tension or length. Impulses conducted by group IA enter the spinal cord via the dorsal root and distribute collaterals directly on alpha motor neurons. This two neuron linkage (one sensory neuron in the dorsal root ganglion and one motor neuron in the ventral horn) establishes part of the so-called gamma loop. The loop is closed by gamma efferent fibers, which arise from cells in the anterior horn and pass directly to polar parts of the muscle spindle (see Figure 1-4). Thus, impulses conveyed by gamma motor neurons can indirectly excite alpha motor neurons by causing the muscle spindle to fire. Part of this mechanism forms the basis for the myotatic (or stretch) reflex. Only part of the afferents from the muscle spindle pass to the anterior horn; a large part of the afferent volley ascends via relays in the spinal cord to the cerebellum.

The myotatic or deep tendon reflex is a monosynaptic reflex dependent on two neurons: one neuron in the dorsal root ganglion that receives afferent impulses from the muscle spindle and the alpha motor neuron that innervates the striated muscle containing the muscle spindles. Sudden, abrupt stretching of a muscle produced by sharply tapping the tendon of the muscle, causes stretching of the muscle spindle and discharge of the group IA fibers. The IA fibers make synaptic contact with the alpha motor neurons in the anterior horn, and after a brief delay impulses pass peripherally via the ventral root back to the same muscle and cause it to contract (see Figure 1-4). The myotatic reflex is a segmental, monosynaptic reflex that usually involves two or three spinal segments, because most muscles are innervated by fibers arising from several adjacent spinal segments. The segment of a muscle innervated by afferent fibers from a single spinal segment constitutes a myotome. This unit is similar to a dermatome, the cutaneous area innervated by fibers that arise from a single dorsal root ganglion. Both myotomes and dermatomes have considerable overlap of innervation provided by nerve fibers arising from adjacent spinal segments.

Afferent fibers derived from dorsal root ganglia constitute one of the major sources of input to the lower motor neuron (Figure 1-5). Input via the dorsal root conveys impulses from a variety of different receptors, both superficial and deep. Impulses conveyed by group IB fibers from the Golgi tendon organ end upon internuncial neurons, rather than upon alpha motor neurons. Group IB fibers establish a disynaptic relationship with anterior horn cells (see Figure 1-4). Golgi tendon organs are stretch receptors, as the muscle spindles are, but they exhibit a much higher threshold and unlike the muscle spindle have no known efferent innervation. These stretch receptors, unlike the muscle spindles, can be caused to discharge by either contracting or stretching the muscle. The Golgi tendon organ has been conceived as being in series with striated muscle fibers, whereas the muscle spindle appears to be arranged in parallel.³ Impulses conveyed by group IB fibers have a disynaptic inhibitory influence on alpha motor neurons; group IA fibers have a monosynaptic excitatory action on these neurons. The inhibitory influence of the Golgi tendon organ on spinal motor neurons is of clinical importance for understanding the melting away of resistance to passive movement in spasticity.

Figure 1-5 Drawing of a segment of the spinal cord shows nerve roots, ganglia, and meninges. (From Carpenter MB. Core Text of Neuroanatomy, ed 3. Baltimore: Williams & Wilkins, 1985.)

Impulses from receptors concerned with painful or noxious stimuli also enter the spinal cord via the dorsal root (see Figure 1-5). Many of these fibers, considered to have substance P as their neurotransmitter, terminate in Rexed’s lamina I.⁴,⁵ Even though opiate-binding sites are distributed in parts of laminae I and II and the central nervous system contains endogenous opiods such as enkephalin,⁶ some afferents from these receptors reach the lower motor neuron. Noxious and painful stimuli produce powerful contractions of flexor muscle groups, which effect withdrawal from the offending stimulus. The flexion reflex produces powerful contractions of ipsilateral flexor muscles and relaxation of ipsilateral extensor muscles in a reciprocal fashion, so that an entire limb may be withdrawn. Afferent input in the flexor reflex arises from broad receptive fields, is conveyed by small fibers (secondary muscle spindle and cutaneous afferents), and involves multisynaptic articulations with both flexor and extensor motor neurons. This reflex is characterized by longer synaptic delays and diffuseness of efferent discharge. There is sustained firing of motor units, which may outlast the stimulus. Noxious stimuli applied to a peripheral part of a limb result in powerful flexor responses in all parts of the extremity.

The crossed extensor reflex is regarded as part of the flexor reflex.⁷ Collateral fibers involved in the flexor reflex cross in the spinal cord and establish reciprocal connections opposite to those that prevail ipsilaterally. Contralateral excitation involves extensor muscles; inhibition prevails upon flexor motor neurons. In the case of the lower extremity, the crossed extensor response serves to support the body when the ipsilateral lower limb is flexed. Segmental input to the lower motor neuron is profuse, direct and indirect, and largely, but not exclusively, ipsilateral. Muscle spindle afferents (group IA) project directly to the lower motor neuron, whereas most other receptors, including the Golgi tendon organ (group IB), influence lower motor neurons indirectly via internuncial neurons. Group IA and IB fibers influence ipsilateral cell groups of the spinal cord, whereas other sensory receptors are distributed by multisynaptic circuits to both sides of the spinal cord. The lower motor neuron also is under powerful suprasegmental control via descending systems. These systems are discussed in conjunction with upper motor neuron.

Lesions of the Lower Motor Neuron

Lesions selectively involving the lower motor neuron result in weakness or paralysis, loss of muscle tone, loss of reflexes, and muscle atrophy. All of these changes are confined to the affected muscles. Weakness or paralysis, occurring in the affected muscles, has a direct relationship to the extent and severity of the lesion. Because anterior horn cells that innervate a single muscle extend longitudinally through several spine segments, and because several such cell columns exist at each level, a lesion confined to one spinal segment causes some weakness, but not complete paralysis, in the several muscles that it innervates. Complete paralysis of a muscle occurs only when the lesions involve the column of cells in several segments that innervate a particular muscle, or ventral root fibers from these cells. Because most appendicular muscles are innervated by fibers arising from three spinal segments, complete paralysis of a muscle resulting from a spinal lesion in the anterior horn indicates involvement of several segments. Neighboring cell columns are likely to be involved at each level, resulting in paralysis of a group of muscles rather than an individual one.

Because the lower motor neuron consists of the anterior horn cells and their axons, which emerge via the ventral root, it is sometimes necessary to distinguish motor deficits that occur as a consequence of lesions in spinal segments from those that involve the ventral root, spinal nerves, and peripheral nerves (see Figures 1-3 and 1-5). Lesions of the ventral root usually produce the same motor deficits as destruction of the corresponding anterior horn cells. These two types of lesions are not the same in certain spinal regions (thoracolum bar and sacral), because in these regions preganglionic autonomic fibers arise from cell groups in the lateral horn but exit via the ventral root. Thus, a lesion involving the ventral root at T-1 produces Horner’s syndrome (miosis, pseudoptosis, apparent enopthalmos, and dryness of the skin over the face) in addition to some weakness in the small muscles of the hand. These autonomic disturbances might not occur with a spinal lesion confined to the anterior horn at T-1. Section of a single ventral root, for example C-5, would produce weakness in the supraspinatus, infraspinatus, subscapularis, biceps brachii, and brachioradialis muscles, but not complete paralysis of any of these muscles. This pattern of distribution is unique to C-5 ventral root fibers and different from that of any single peripheral nerve.

Lesions of mixed spinal nerves produce motor and sensory deficits that correspond to those of combined dorsal and ventral root lesions (see Figure 1-3). The motor deficits correspond almost exactly to those resulting from lesions of the ventral root, but the sensory disturbances follow a dermatomal distribution and tend to be less extensive because of the characteristic overlapping nature of dermatomes. A lesion involving a single dorsal root such as C-5 would not result in detectable sensory loss, because dorsal root fibers from C-4 and C-6 cover most of the C-5 area.⁸,⁹

These observations are in sharp contrast with the motor and sensory deficits resulting from a peripheral nerve lesion (Figure 1-3), deficits that correspond to the peripheral distribution of the particular nerve distal to the injury. An ulnar nerve injury near the wrist would produce paralysis of the adductor pollicis, the deep head of the flexor pollicis brevis, the interossei, the inner lumbrical muscles, and the muscles of the hypothenar eminence, along with loss of sensation in all of the little finger, the ulnar half of the ring finger, and corresponding portions of the dorsal and volar surfaces of the hand.

Loss of muscle tone, hypotonia, is a characteristic and constant finding in lower motor neuron lesions. The muscle is flaccid, soft and offers no resistance to passive movement. The reduction in muscle tone results from the withdrawal of streams of efferent impulses that are normally transmitted to the muscle which maintain its tone. The gamma loop, which helps to maintain tone, has been broken. Reflexes in the affected muscles are greatly diminished, and usually lost (areflexia), in lower motor neuron lesions because the reflex arc is interrupted. In this type of lesion the effector limb of the reflex arc has been destroyed.

Although paralysis, hypotonia, and areflexia occur almost immediately following a lower motor neuron lesion, atrophy, or muscle wasting, does not become evident for a week or two. Atrophy occurs gradually and in time is obvious on inspection. Why muscles undergo atrophy is not fully understood, but it seems likely that the morphological and functional properties of muscle are dependent on the transmitter substance (ACh) liberated at the motor end-plates. Some degree of muscle wasting occurs when muscles are not used (disuse atrophy). This type of muscle atrophy is seen in limbs immobolized for a time in a plaster cast, in muscles whose tendons have been cut, and in upper motor neuron paralysis of long duration.

In some diseases involving the lower motor neuron the muscles supplied by these neurons exhibit small, localized, spontaneous contractions known as fasciculations. These small muscle twitches, visible beneath the skin, represent the discharge of groups of muscle fibers. Fasciculations occur asynchronously in parts of different muscles and are thought to be due to triggering mechanisms within the motor neuron. It is possible that these small contractions may be due to leakage of small quanta of acetylcholine at the motor end-plates of a diseased neuron. Fasciculations commonly are seen in amyotrophic lateral sclerosis and sometimes in acute inflammatory lesions of peripheral nerves, but usually they are not seen when anterior horn cells are rapidly destroyed, as in poliomyelitis. The term fibrillation, misused as the equivalent of fasciculation, refers to the small (10 to 200-μV) potentials of 1 to 2 msec duration that occur irregularly and asynchronously in electromyograms of denervated muscle. These potentials represent spontaneous activation of single muscle fibers and produce no detectable shortening of muscles.

From this discussion it is apparent that the lower motor neuron exerts important trophic, metabolic, chemical, and electrical influences on striated muscle. One of the most striking effects of muscle denervation is the supersensitivity that develops to acetylcholine (ACh).

The Upper Motor Neuron

All of the descending fibers systems that can influence or modify activities of the lower motor neuron constitute the upper motor neuron. This is a more inclusive definition than that used by most clinicians who equate the upper motor neuron solely with the corticospinal tract. The narrower concept has developed because the corticospinal tract is so large and the functional roles of other descending systems have not been clearly defined. Increasing information on non-pyramidal systems makes it necessary to consider the upper motor neuron in the broadest sense. Descending influences transmitted to spinal levels by a group of heterogeneous spinal tracts are concerned mainly with (1) voluntary motor control, (2) modification of muscle tone, (3) maintenance of posture and equilibrium, (4) suprasegmental control of reflexes, (5) innervation of viscera and autonomic structures, and (6) modification of sensory signals transmitted centrally. With one exception, all descending spinal tracts arise from the three most caudal segments of the brain stem. The exception is the corticospinal tract.

Corticospinal System

The corticospinal system consists of all fibers that originate from cells in the cerebral cortex, pass through the medullary pyramids, and enter the spinal cord (Figure 1-6). This massive fiber system constitutes the largest and most important descending system in the neuraxis. Each medullary pyramid in humans contains approximately 1 million fibers, which project to spinal levels via three separate tracts. The largest number of fibers, approximately 90%, cross in the corticospinal decussation and descend contralaterally as the lateral corticospinal tract. A smaller bundle of fibers (8%) descends directly into the anterior funiculus, where it forms the anterior corticospinal tract. These fibers cross in small fascicles within cervical spinal segments (see Figure 1-2). Remaining fibers in the medullary pyramids descend uncrossed into the lateral funiculus of the spinal cord as the anterolateral corticospinal tract. Fibers of the corticospinal tract originate from pyramidal cells in layer V of the primary motor area (area 4), the premotor area (area 6), and from somatosensory regions of the parietal lobe.¹⁰,¹¹ Pyramidal cells contributing to the tract show great variation in size and occur in clusters; the largest cells, found in area 4, are referred to as the giantopyramidal cells of Betz. Giant pyramidal cells in the human brain are not distributed uniformly; the largest number is found superiorly in the leg area and the smallest number inferiorly in the face area. Though the primary motor cortex appears somatotopically organized in that electrical stimulation of specific regions gives rise to localized movements on the opposite side of the body, anatomically this tract is not somatotopically organized. Movements elicited by electrical stimulation of the motor cortex in patients under local anesthesia, interpreted as voluntary movements, usually involve groups of muscles. Fibers of the corticospinal tract largely descend in the dorsal part of the lateral funiculus and enter the spinal gray matter in the intermediate zone (lamina VII), from which site they are distributed to laminae IV, V, VII and parts of lamina IX (see Figure 1-2).¹²,¹³ Fibers projecting directly to lamina IX, which contains large motor neurons, appear greatest in the cord enlargements and are most abundant in dorsolateral regions, which innervate distal musculature. Corticospinal fibers projecting to laminae in the dorsal horn arise predominantly from sensory cortical areas.¹⁴

Figure 1-6 Schematic drawing of the lateral surface of the brain, indicating the origin and course of the corticospinal tract.

A recent finding of much importance concerning the CST is that virtually all corticospinal neurons have multiple collateral branches that terminate at several levels of the spinal cord.¹⁵,¹⁶ This observation explains why tracers injected at one spinal level retrogradely label cortical neurons scattered over a wide area. It also explains why a microlesion in one region of the motor cortex produces degeneration distributed over as many as nine spinal segments. These data clearly indicate that the CST is not somatotopically organized and the tract does not consist of private lines from cortical neurons to spinal motor neurons. Cortical motor neurons exert multiple influences on different groups of motor neurons in widely separate spinal segments via axonal collaterals.

Phylogenetically, the corticospinal tract is a relatively recent development in the central nervous system that is found only in mammals. In humans at birth the tract is immature and unmyelinated. It takes approximately 2 years for the tract to become fully developed and myelinated. It is during this period of postnatal development that the infant learns to stand and walk and acquires fine motor skills.¹⁷ Signals conveyed by the CST are thought to be concerned with discrete movements of parts of the body that display an almost unlimited range and versatility. The tract has the largest number of fibers concerned with motor function, extends the length of the neuraxis, and passes through or near every major division of the central nervous system except the cerebellum. It is for these reasons that the corticospinal tract is frequently involved by a variety of pathologic processes. Lesions involving the corticospinal tract almost invariably involve adjacent structures and produce varying degrees of paralysis, alterations of muscle tone, and modifications of reflexes. Involvement of adjacent structures often helps to localize the site of a lesion involving this long pathway.

In comparison to the corticospinal system the nonpyramidal descending tracts are small. These tracts arise from nuclei in the midbrain (red nucleus), pons, and medulla (vestibular nuclei and reticular formation).

Rubrospinal Tract

This tract arises from an oval collection of neurons that occupies the central part of the midbrain tegmentum (Figure 1-7). Large cells in caudal parts of the nucleus give rise to fibers that cross the midline immediately and descend to spinal levels in the lateral funiculus. These fibers are partially intermingled with those of the corticospinal fibers (Figure 1-2). The rubrospinal tract has been considered to be somatotopically organized in the sense that cells in dorsal parts of the nucleus project to cervical spinal segments whereas those in ventral regions terminate in lumbosacral segments.¹⁸ Fibers of the tract enter the intermediate zone of the spinal gray and are distributed within Rexed’s laminae IV, V, VI, and VII.¹⁹,²⁰ Terminations are on internuncial neurons. The somatotopic features of this tract have been somewhat blurred by the observation that some cells in the red nucleus have axonal collaterals projecting to several spinal segments.²⁰

Figure 1-7 Schematic diagram of the rubrospinal tract.

The red nucleus receives input from two sources, the cerebral cortex and some of the deep cerebellar nuclei. Corticorubral fibers from the motor cortex descend ipsilaterally and are somatotopically organized.²¹ Thus, corticorubral and rubrospinal fibers together constitute a somatotopically organized nonpyramidal linkage from the motor cortex to spinal levels that exert effects contralaterally, because the rubrospinal tract is crossed. A second input to the red nucleus arises from the emboliform and globose nuclei of the cerebellum; these fibers are crossed and link portions of the opposite cerebellar cortex (i.e., paravermal) with the red nucleus.²² Cerebellar influences on cells of the red nucleus are expressed ipsilaterally because cerebellar efferent fibers and rubrospinal fibers are both crossed.

The most important function of the rubrospinal tract is maintaining muscle tone, particularly contralateral flexor muscle tone. Stimulation of the red nucleus produces flexion in the contralateral limbs.²³,²⁴ Microelectrode studies indicate excitatory postsynaptic potential in contralateral flexor alpha motor neurons and inhibitory postsynaptic potentials in extensor alpha motor neurons.²⁵ Both of these effects on contralateral alpha motor neurons are mediated by internuncial neurons, as fibers of the rubrospinal tract do not terminate directly on motor neurons.

Vestibulospinal Tract

The vestibular nuclei constitute a complex in the lateral part of the floor of the fourth ventricle of the pons and medulla (Figure 1-8). The four major nuclei of this complex receive afferents from the vestibular apparatus (semicircular ducts and the otoliths) concerned with maintenance of equilibrium, posture, and orientation in three-dimensional space. In addition, parts of these nuclei receive input from portions of the cerebellar cortex and the most medial deep cerebellar nucleus (fastigial nucleus). The vestibulospinal tract arises mainly from the giant cells of the lateral vestibular nucleus and descends in the ventral part of the lateral funiculus of the spinal cord (see Figures 1-2 and 1-8). This tract has been regarded as somatotopically organized and is present in all spinal segments.²⁶ Fibers of the tract enter the medial part of the anterior horn and are distributed to Rexed’s laminae VII, VIII, and parts of IX.²⁷–²⁹ The somatotopic features of the vestibulospinal tract now appear less precise than as originally conceived, because some fibers appear to originate from other vestibular nuclei, and axons descending in the spinal cord give collaterals to multiple spinal segments.²⁹–³¹ There is evidence that vestibulospinal fibers terminate directly upon the somata and dendrites of large extensor motor neurons and have a threefold to fourfold greater influence on cervical and lumbosacral spinal segments. Impulses conveyed by the VST produce increases in ipsilateral extensor muscle tone.

Figure 1-8 Schematic drawing of the brain stem and cervical spinal cord showing the locations of the vestibular nuclei in the floor of the fourth ventricle and the course of the vestibulospinal tract. S, L, M, and I indicate the superior, lateral, medial, and inferior vestibular nuclei, respectively.

Vestibular ganglion cells, which innervate the macula of the utricle, appear to project exclusively to the ventral part of the lateral vestibular nucleus.³² This suggests that stimuli that excite the utricle, such as head tilt, gravity, and linear acceleration, must play an important role in maintaining extensor muscle tone. Direct input to dorsal regions of the lateral vestibular nucleus is derived from Purkinje cells in the anterior lobe vermis of the cerebellum.³³ This pathway exerts inhibitory influences on cells of the lateral vestibular nucleus mediated by the neurotransmitter γ-aminobutyric acid.³⁴ The fastigial nucleus of the cerebellum projects crossed and uncrossed fibers fairly symmetrically to ventral parts of both lateral vestibular nuclei and appears to have excitatory influences mediated by glutamic acid.³⁵,³⁶ Thus, the excitatory influences of the vestibular end-organ can be modulated directly by cerebellar inputs. Lesions of the anterior lobe of the cerebellum in experimental animals produce increases in extensor muscle tone that resembles decerebrate rigidity.

Reticulospinal Tracts

Anatomically, the term reticular formation is used to designate the core of the brain stem characterized by aggregations of cells of various sizes enmeshed in a fiber network. The matrix that forms the reticular formation is phylogenetically the oldest part of the brain stem and is surrounded by newer pathways concerned with specific functions. Development of the reticular formation parallels the process of encephalization. For many years the organization of the reticular formation was considered to be diffuse and nonspecific. In the late 1950s it became apparent that the reticular formation could be divided into regions that possessed a specific cytoarchitecture, distinctive fiber connections, and unique internal features.³⁷,³⁸ The reticular formation can be regarded as the principal integrator of motor, sensory, and visceral activities in the brain stem. Basically, the reticular formation can be divided into four main subdivisions: (1) a lateral sensory part, (2) a medial effector or motor part, (3) a paramedian part related largely to the cerebellum, and (4) the raphe nuclei, which contain a variety of different neurotransmitters.

Spinal projections arise from the medial zone of the pontine and medullary reticular formation. Medullary reticulospinal fibers arise from a large collection of cells in the medial two thirds of the reticular formation, dorsal to the inferior olivary complex, and project largely uncrossed to all levels of the spinal cord (Figure 1-9). Fibers from this tract descend in the anterior part of the lateral funiculus and terminate largely on internuncial neurons in lamina VII, although some end upon processes of cells in lamina IX (see Figure 1-2). Pontine reticulospinal fibers arise from a corresponding larger medial regions of the pontine reticular formation. Virtually all fibers of the pontine reticulospinal tracts are uncrossed, descend in the ventral funiculus near the midline, and end on internuncial neurons in laminae VII and VIII (see Figures 1-2 and 1-9). Unlike some fibers of the rubrospinal and vestibulospinal tracts, none of the reticulospinal fibers are somatotopically organized.

Figure 1-9 Schematic diagram of sections of the lower brain stem indicating the origin, course, and regions of termination of the reticulospinal tracts.

One of the characteristic features of the reticular formation is that it receives signals from multiple sources, which include virtually all types of receptors, the cerebellum, and the cerebral cortex. Sensory input to the reticular formation loses its identification with specific stimuli. Functions of the reticular formation are multiple, but some can be related to specific subdivisions. The reticular formation can (1) facilitate or inhibit voluntary motor activity, (2) modify muscle tone and reflex activity, (3) exert a variety of different autonomic responses, and (4) facilitate or inhibit central transmission of sensory signals. Major inhibitory functions appear to be related to the medullary reticular formation. Inhibition concerns most forms of motor activity, including myotatic and flexor reflexes and muscle tone. Reductions in muscle tone and deep tendon reflexes appear to be mediated by medullary reticulospinal fibers that inhibit gamma motor neurons, which influence the muscle spindle and alpha motor neurons via the gamma loop.

A far larger region of the brain stem reticular formation facilitates motor responses, muscle tone, and somatic spinal reflexes. The facilitatory region includes most of the pontine reticular formation and extends into the caudal midbrain. The facilitatory region of the reticular formation includes neurons that do not project directly to spinal cord; thus, effects from these regions must involve polysynaptic pathways. Most of the effects from the facilitatory region appear to involve internuncial neurons at various spinal levels. Not all of the influences of the reticular formation are directed toward modification of spinal neuronal activities. Large regions of both the medullary and pontine reticular formation exert powerful ascending influences that control the electrical excitability of broad regions of the cerebral cortex and affect the state of alertness and behavioral arousal.

Descending Autonomic Pathways

It has been difficult to distinguish reticular neurons concerned exclusively with autonomic functions, but modern axoplasmic transport methods and immunocytochemical techniques have yielded important information. The principal nuclei giving rise to descending autonomic fibers are (1) several regions of the hypothalamus, (2) portions of the parasympathetic nuclei of the oculomotor nuclear complex, (3) the locus ceruleus, (4) parts of the nucleus solitarius, and (5) collections of catecholamine neurons in the ventrolateral lower brain stem. In addition, the raphe nuclei, which contain cells rich in serotonin, project bilaterally to spinal levels and modulate pain mechanisms.³⁹ Large cells in the paraventricular and posterior regions of the hypothalamus project directly to spinal levels, where some of these fibers end on autonomic neurons.⁴⁰ Some parasympathetic neurons in the oculomotor nucleus project to spinal levels and end in parts of laminae I and V.⁴⁰,⁴¹ The locus ceruleus, recognized as a principal source of noradrenergic fibers widely distributed in the neuraxis, projects to parts of the anterior and posterior horns and the intermediolateral cell column, which gives rise to preganglionic sympathetic fibers.⁴²

Descending fibers from the nucleus solitarius project fibers to neurons of the phrenic nerve nucleus and to anterior horn cells in the thoracic region; these crossed projections are concerned with excitation of inspiratory motor neurons.⁴³ Ventrolateral noradrenergic neurons located near the facial nucleus project bilaterally to the intermediolateral cell column in thoracic and upper lumbar spinal segments.⁴⁴ Very few lesions in the brain stem and spinal cord fail to involve the descending autonomic fiber system.

Upper Motor Neuron Lesions

Lesions involving the upper motor neuron at a variety of locations produce paralysis, alterations of muscle tone, and changes in reflex activity. These lesions are rarely selective, are usually incomplete, and frequently involve adjacent structures. The degree of paresis or paralysis is not always directly related to the size of the lesions or the extent of involvement of the corticospinal tract.⁴⁵ Lesions of the upper motor neuron may result from vascular disease, trauma, neoplasms, or infectious and degenerative disease. Unilateral lesions in the cerebral hemisphere or brain stem produce contralateral paralysis, usually hemiplegia. Spinal lesions, most commonly the result of trauma, usually are bilateral and cause paraplegia.

The most common lesion involving the upper motor neuron is the so-called cerebrovascular accident. Thrombosis of a major cerebral artery, commonly the middle cerebral artery or the main trunk of the internal carotid artery, deprives regions of the brain of blood and oxygen, causing necrosis. Tissues surrounding the infarcted area become congested and edematous. In the majority of patients the onset is sudden. Initial symptoms are both focal and general. Generalized symptoms include headache, nausea, vomiting, convulsions, and coma. Focal symptoms, such as paralysis, sensory loss, and disturbances of speech, usually are related to the site of the lesion. Immediately after the vascular lesion, usually called a stroke, the paralyzed limbs are completely flaccid and the myotatic reflexes are depressed or absent. The plantar response, elicited by stroking the sole of