handbook of parkinsons disease, third edition

Handbook of
Parkinson's
Disease
Third Edition

edited by

Rajesh Pahwa
University of Kansas Medical Center
Kansas City, Kansas, U.S.A.

Kelly E. Lyons
University of Kansas Medical Center
Kansas City, Kansas, U.S.A.

William C. Roller
Mount Sinai School of Medicine
New York, Ne\v York, U.S.A.

MARCEL DEKKER, INC.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.

NEW YORK • BASEL


The previous edition was Handbook ofParkmson 's Disease Second Edition, Revised and
Expanded (William C Koller, ed ), 1992
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the Library of Congress

ISBN: 0-8247-4242-7
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NEUROLOGICAL DISEASE AND THERAPY

Advisory Board

Louis R. Caplan, M.D.

William C. Koller, M.D.

Professor of Neurology
Harvard University School of Medicine

Mount Sinai School of Medicine
New York, New York

Beth Israel Deaconess Medical Center
Boston, Massachusetts

John C. Morris, M.D.
Friedman Professor of Neurology
Co-Director, Alzheimer's Disease Research

Center
Washington University School of Medicine
St Louis, Missouri

Bruce Ransom, M.D., Ph.D.
Warren Magnuson Professor
Chair, Department of Neurology
University of Washington School of

Medicine
Seattle, Washington

Kapil Sethi, M.D.

Mark Tuszynski, M.D., Ph.D.

Professor of Neurology
Director, Movement Disorders Program

Associate Professor of Neurosciences

Medical College of Georgia
Augusta, Georgia

Director, Center for Neural Repair
University of California-San Diego

La Jolla, California

1. Handbook of Parkinson's Disease, edited by William C. Koller
2. Medical Therapy of Acute Stroke, edited by Mark Fisher
3. Familial Alzheimer's Disease: Molecular Genetics and Clinical Perspectives, edited by Gary D. Miner, Ralph W Richter, John P. Blass,
Jimmie L. Valentine, and Linda A. Winters-Miner
4. Alzheimer's Disease: Treatment and Long-Term Management, edited by
Jeffrey L Cummings and Bruce L. Miller
5. Therapy of Parkinson's Disease, edited by William C. Koller and George
Paulson
6. Handbook of Sleep Disorders, edited by Michael J. Thorpy

7. Epilepsy and Sudden Death, edited by Claire M. Lathers and Paul L.
Schraeder
8. Handbook of Multiple Sclerosis, edited by Stuart D. Cook
9. Memory Disorders. Research and Clinical Practice, edited by Takehiko
Yanagihara and Ronald C. Petersen
10. The Medical Treatment of Epilepsy, edited by Stanley R. Resor, Jr., and
Henn Kutt
11. Cognitive Disorders: Pathophysiology and Treatment, edited by Leon J.
Thai, Walter H Moos, and Elkan R. Gamzu
12. Handbook of Amyotrophic Lateral Sclerosis, edited by Richard Alan
Smith
13. Handbook of Parkinson's Disease: Second Edition, Revised and Expanded, edited by William C. Koller

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14. Handbook of Pediatric Epilepsy, edited by Jerome V. Murphy and Fereydoun Dehkharghani
15. Handbook of Tourette's Syndrome and Related Tic and Behavioral
Disorders, edited by Roger Kurlan
16. Handbook of Cerebellar Diseases, edited by Richard Lechtenberg
17. Handbook of Cerebrovascular Diseases, edited by Harold P. Adams, Jr.
18. Parkinsonian Syndromes, edited by Matthew B. Stem and William C.
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19. Handbook of Head and Spine Trauma, edited by Jonathan Greenberg
20. Brain Tumors: A Comprehensive Text, edited by Robert A. Morantz and
John W. Walsh
21. Monoamine Oxidase Inhibitors in Neurological Diseases, edited by Abraham Lieberman, C. Warren Olanow, Moussa B. H. Youdim, and Keith
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22. Handbook of Dementing Illnesses, edited by John C. Morris
23. Handbook of Myasthenia Gravis and Myasthenic Syndromes, edited by

Robert P. Lisak
24. Handbook of Neurorehabilitation, edited by David C. Good and James R.
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26. Principles of Neurotoxicology, edited by Louis W. Chang
27. Handbook of Neurovirology, edited by Robert R. McKendall and William
G. Stroop
28. Handbook of Neuro-Urology, edited by David N. Rushton
29. Handbook of Neuroepidemiology, edited by Philip B. Gorelick and Milton
Alter
30. Handbook of Tremor Disorders, edited by Leslie J. Findley and William
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31. Neuro-Ophthalmological Disorders: Diagnostic Work-Up and Management,
edited by Ronald J. Tusa and Steven A. Newman
32. Handbook of Olfaction and Gustation, edited by Richard L. Doty
33. Handbook of Neurological Speech and Language Disorders, edited by
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34. Therapy of Parkinson's Disease: Second Edition, Revised and Expanded, edited by William C. Koller and George Paulson
35. Evaluation and Management of Gait Disorders, edited by Barney S.
Spivack
36. Handbook of Neurotoxicology, edited by Louis W. Chang and Robert S.
Dyer
37. Neurological Complications of Cancer, edited by Ronald G. Wiley
38. Handbook of Autonomic Nervous System Dysfunction, edited by Amos
D. Korczyn
39. Handbook of Dystonia, edited by Joseph King Ching Tsui and Donald B.
Calne
40. Etiology of Parkinson's Disease, edited by Jonas H. Ellenberg, William C.
Koller, and J. William Langston

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


41. Practical Neurology of the Elderly, edited by Jacob I. Sage and Margery
H.Mark
42. Handbook of Muscle Disease, edited by Russell J. M. Lane

43. Handbook of Multiple Sclerosis: Second Edition, Revised and Expanded,
edited by Stuart D. Cook
44. Central Nervous System Infectious Diseases and Therapy, edited by
Karen L Roos

45. Subarachnoid Hemorrhage: Clinical Management, edited by Takehiko
Yanagihara, David G. Piepgras, and John L D. Atkmson
46. Neurology Practice Guidelines, edited by Richard Lechtenberg and
Henry S. Schutta

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Engler, Jonathan Cole, and W. Louis Merton
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Goldstem
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50. Handbook of Ataxia Disorders, edited by Thomas Klockgether

51. The Autonomic Nervous System in Health and Disease, David S.
Goldstein
52. Axonal Regeneration in the Central Nervous System, edited by Nicholas
A. Ingoglia and Manon Murray

53. Handbook of Multiple Sclerosis: Third Edition, edited by Stuart D. Cook
54. Long-Term Effects of Stroke, edited by Julien Bogousslavsky
55. Handbook of the Autonomic Nervous System in Health and Disease,
edited by C. Liana Bolis, Julio Licinio, and Stefano Govoni
56. Dopamine Receptors and Transporters: Function, Imaging, and Clinical
Implication, Second Edition, edited by Anita Sidhu, Marc Laruelle, and

Philippe Vernier
57. Handbook of Olfaction and Gustation: Second Edition, Revised and Expanded, edited by Richard L Doty

58. Handbook of Stereotactic and Functional Neurosurgery, edited by Michael Schulder
59. Handbook of Parkinson's Disease' Third Edition, edited by Rajesh Pahwa, Kelly E. Lyons, and William C. Koller

Additional Volumes in Preparation

Clinical Neurovirology, edited by AVI Nath and Joseph R. Berger

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


We would like to thank our parents, Vidya and Badrinath Pahwa
and Thomas and Elaine Lyons, for their many years of continued
encouragement, understanding and support throughout our careers.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Foreword

Parkinson’s disease is a common neurological condition that is becoming
more common as the population ages. It is a chronic condition and can be a
source of significant disability. Fortunately, for many decades there has
been some understanding of the pathophysiology of Parkinson’s disease,
and useful therapies have been available. Better therapies and definitive
curative therapies, however, are yet to come. For these reasons, Parkinson’s
disease has been the focus of considerable research effort, and we have seen
a virtual explosion of progress in recent years.
The identification of genetic disorders that lead to Parkinson’s disease
has triggered the rush to research into molecular biology and cell biology of
the basal ganglia and neurodegeneration. Imaging has led to greater insights
about brain organization and neurotransmitter function. Physiological
investigations have told us more about the genesis of the motor disorder of
bradykinesia. New emphasis has been placed on the nonmotor aspects of
parkinsonian symptomatology, which will help lead to a better quality of life
for patients. All this new information has opened the door to new
possibilities and to the development of new therapeutics.
However, the new therapies that have appeared in the last decade
make the management of the patient with Parkinson’s disease more
complex, sophisticated, and difficult for the clinician. Which of the various
alternatives is best for the individual patient at hand? How should therapy
be initiated? Is there anything that will help prevent progression of the
disorder as well as ameliorate symptoms? What should be done with

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


agonists, with COMT inhibitors? How should complications, such as
dyskinesias, be managed? How should cognitive dysfunction or depression
be managed? What is the role of the different surgical options? When should

they be employed and which one is best for the individual patient?
To help basic scientists and clinicians to keep up to date, information
must be current, authoritative, and cohesively presented. To this end, the
third edition of the Handbook of Parkinson’s Disease is a welcome addition
to the literature. It deals with all the aspects of understanding and managing
this multifaceted disorder, and should be read from cover to cover and
consulted for specific problems. The book will serve as an ideal reference for
those working with Parkinson’s disease.
Mark Hallett
Chief, Human Motor Control Section
Medical Neurology Branch
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, Maryland

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Preface

Parkinson’s disease is a progressive neurodegenerative condition with often
devastating symptoms. In recent years, our knowledge of the disease has
increased tremendously. We have achieved a greater understanding of its
neurochemistry, neurophysiology, and neuropathology. Genes have been
identified that are involved in the pathogenesis of some forms of familial
autosomal dominant and autosomal recessive Parkinson’s disease. Advancements in neuropsychological and neuroimaging techniques have led to
improvements in diagnostic accuracy. Therapeutics have come a long way,
too. New medications have been approved, new compounds and therapeutic
approaches are under investigation, and we have a better understanding of
the use of surgical procedures in Parkinson’s disease, particularly deep brain

stimulation. In spite of these advances, there continue to be many
complications associated with the long-term management of both motor
and nonmotor symptoms of the disease and treatment remains a challenge.
We present in this edition of the Handbook of Parkinson’s Disease the
most up-to-date information on the scientific and therapeutic aspects of the
disease. The third edition offers a more integrated approach to managing
parkinsonian symptoms. There is comprehensive coverage of the latest
pharmacological and surgical therapeutics as well as the newest technologies
in diagnostic imaging. It is our hope that this volume, in the tradition of the
first two editions, will serve as a reference source for physicians, researchers,
and other healthcare professionals seeking answers to the many questions
related to the understanding and treatment of Parkinson’s disease.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


We thank each of the authors for their time and commitment in
preparing state-of-the-art reviews of the most pertinent aspects of
Parkinson’s disease. We would also like to thank Jinnie Kim, Ann Pulido,
and the other Marcel Dekker, Inc., staff who assisted in the preparation of
this book.
Rajesh Pahwa
Kelly E. Lyons
William C. Koller

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Contributors

Joseph S. Chung, M.D Division of Movement Disorders, University of
Southern California–Keck School of Medicine, Los Angeles, California,
U.S.A.
Richard B. Dewey, Jr., M.D. Clinical Center for Movement Disorders,
University of Texas Southwestern Medical School, Dallas, Texas, U.S.A.
Dennis W. Dickson, M.D. Department of Pathology, Mayo Clinic,
Jacksonville, Florida, U.S.A.
Elmyra V. Encarnacion, M.D. Experimental Therapeutics Branch, Parkinson’s Disease and Movement Disorders Center, Neurology Department,
University of South Florida and Tampa General Healthcare, Tampa,
Florida, U.S.A.
Stewart A. Factor, D.O. Parkinson’s Disease and Movement Disorders
Center, Albany Medical Center, Albany, New York, U.S.A.
Matthew Farrer, Ph.D. Department of Neuroscience, Mayo Clinic,
Jacksonville, Florida, U.S.A. and Mayo Medical School, Rochester,
Minnesota, U.S.A.
Christopher G. Goetz, M.D. Department of Neurological Sciences, Rush
University, Chicago, Illinois, U.S.A.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Jay M. Gorell, M.D. Department of Neurology, Henry Ford Health
Sciences Center, Henry Ford Health System and NIEHS Center for
Molecular Toxicology with Human Applications, Wayne State University,
Detroit, Michigan, U.S.A.
Ruth Hagestuen, R.N., M.A. The National Parkinson Foundation, Miami,
Florida, U.S.A.
Robert A. Hauser, M.D. Division of Movement Disorders, Departments of
Neurology, Pharmacology and Experimental Pharmacology, University of
South Florida and Tampa General Healthcare, Tampa Florida, U.S.A.

Michael W. Jakowec, Ph.D. Department of Neurology and Department of
Cell and Neurobiology, University of Southern California–Keck School of
Medicine, Los Angeles, California, U.S.A.
Joseph Jankovic, M.D. Department of Neurology, Baylor College of
Medicine, Houston, Texas, U.S.A.
Danna Jennings, M.D Department of Neurology, The Institute for
Neurodegenerative Disorders, New Haven, Connecticut, U.S.A.
Marjorie L. Johnson, M.A./C.C.C.-S.L.P. Struthers Parkinson’s Center,
Minneapolis, Minnesota, U.S.A.
Jorge L. Juncos, M.D. Department of Neurology and Wesley Woods
Geriatric Center, Emory University School of Medicine, Atlanta, Georgia,
U.S.A.
Anthony E. Lang, M.D., F.R.P.C. Division of Neurology, Department of
Medicine, The Toronto Western Hospital, University of Toronto, Toronto,
Ontario, Canada
Mark F. Lew, M.D. Department of Neurology, Univesity of Southern
California–Keck School of Medicine, Los Angeles, California, U.S.A.
Kelly E. Lyons, Ph.D. Department of Neurology, University of Kansas
Medical Center, Kansas City, Kansas, U.S.A.
Kenneth Marek, M.D. Department of Neurology, The Institute for
Neurodegenerative Disorders, New Haven, Connecticut, U.S.A.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Deborah C. Mash, Ph.D. Department of Neurology and Molecular and
Cellular Pharmacology, University of Miami School of Medicine, Miami,
Florida, U.S.A.
Erwin B. Montgomery, Jr., M.D. American Parkinson Disease Association
Advanced Center for Research, Departments of Neurology and Neuroscience, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.

William Ondo, M.D. Department of Neurology, Baylor College of
Medicine, Houston, Texas, U.S.A.
Rajesh Pahwa, M.D. Department of Neurology, University of Kansas
Medical Center, Kansas City, Kansas, U.S.A.
Giselle M. Petzinger, M.D. Department of Neurology, University of
Southern California–Keck School of Medicine, Los Angeles, California,
U.S.A.
Ronald F. Pfeiffer, M.D. Department of Neurology, University of
Tennessee Health Science Center, Memphis, Tennessee, U.S.A.
Alex Rajput, M.D. Department of Neurology, University of Saskatchewan,
Saskatoon, Saskatchewan, Canada
Ali H. Rajput, M.B.B.S. Department of Neurology, University of
Saskatchewan, Saskatoon, Saskatchewan, Canada
Michele Rajput, Ph.D. University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Jayaraman Rao, M.D. Louisiana State University Health Sciences Center,
New Orleans, Louisiana, U.S.A.
Benjamin A. Rybicki, Ph.D. Biostatistics and Research Epidemiology,
Henry Ford Health Sciences Center, Henry Ford Health System, Detroit,
Michigan, U.S.A.
Michael Samuel, B.M.B.Ch., M.R.C.P., M.D. Division of Neurology,
Department of Medicine, The Toronto Western Hospital, University of
Toronto, Toronto, Ontario, Canada.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Anthony J. Santiago, M.D. Parkinson’s Disease and Movement Disorders
Center, Albany Medical Center, Albany, New York, U.S.A.
John Seibyl, M.D. Department of Neurology, The Institute for Neurodegenerative Disorders, New Haven, Connecticut, U.S.A.
Kapil D. Sethi, M.D., F.R.C.P. Medical College of Georgia, Augusta,

Georgia, U.S.A.
Mark A. Stacy, M.D. Muhammad Ali Parkinson Research Center, Barrow
Neurological Institute, Phoenix, Arizona, U.S.A.
Alexander I. Tro¨ster, Ph.D. Departments of Psychiatry and Behavioral
Sciences and of Neurological Surgery, University of Washington School of
Medicine, Seattle, Washington, U.S.A.
Daryl Victor, M.D. Division of Movement Disorders, Department of
Neurology, Columbia University, New York, New York, U.S.A.
Cheryl Waters, M.D., F.R.C.P.(C) Division of Movement Disorders,
Department of Neurology, Columbia University, New York, New York,
U.S.A.
Ray L. Watts, M.D. Department of Neurology and Wesley Woods
Geriatric Center, Emory University School of Medicine, Atlanta, Georgia,
U.S.A.
Rosemary L. Wichmann, P.T. Struthers Parkinson’s Center, Minneapolis,
Minnesota, U.S.A.
Steven Paul Woods, Psy.D. Department of Psychiatry and Behavioral
Sciences, University of Washington School of Medicine, Seattle, Washington, U.S.A.
Zbigniew K. Wszolek, M.D. Department of Neurology, Mayo Clinic,
Jacksonville, Florida, U.S.A. and Mayo Medical School, Rochester,
Minnesota, U.S.A.
Allan D. Wu, M.D. Department of Neurology, Univesity of Southern
California–Keck School of Medicine, Los Angeles, California, U.S.A.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


Contents

Foreword Mark Hallett

Preface
Contributors

BACKGROUND
1. Early Iconography of Parkinson’s Disease
Christopher G. Goetz
CLINICAL ASPECTS
2. Epidemiology of Parkinsonism
Ali H. Rajput, Alex Rajput, and Michele Rajput
3. Differential Diagnosis of Parkinsonism
Kapil D. Sethi
4. Pathophysiology and Clinical Assessment of Parkinsonian
Symptoms and Signs
Joseph Jankovic

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


5. Nonmotor Symptoms of Parkinson’s Disease
Richard B. Dewey, Jr
6. Neuropsychological Aspects of Parkinson’s Disease and
Parkinsonian Syndromes
Alexander I. Tro¨ster and Steven Paul Woods
7. Management of Neurobehavioral Symptoms in
Parkinson’s Disease
Jorge L. Juncos and Ray L. Watts
8. Neuroimaging in Parkinson’s Disease
Kenneth Marek, Danna Jennings, and John Seibyl
PATHOLOGY AND NEUROCHEMISTRY
9. Neuropathology of Parkinsonism

Dennis W. Dickson
10. Neurochemistry of Nigral Degeneration
Jayaraman Rao
11. Neurophysiology/Circuitry
Erwin B. Montgomery, Jr.
12. Animal Models of Parkinson’s Disease and Related Disorders
Giselle M. Petzinger and Michael W. Jakowec
13. Dopamine Receptor Diversity: Anatomy, Function, and
Relevance to Parkinson’s Disease
Deborah C. Mash
ETIOLOGY
14. Genetics
Zbigniew K. Wszolek and Matthew Farrer
15. Environmental Risk Factors for Parkinson’s Disease
Jay M. Gorell and Benjamin A. Rybicki

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


MEDICATIONS
16. Amantadine and Anticholinergics
Joseph S. Chung, Allan D. Wu, and Mark F. Lew
17. Levodopa
Anthony J. Santiago and Stewart A. Factor
18. Dopamine Agonists
Mark A. Stacy
19. Monoamine Oxidase Inhibitors in Parkinson’s Disease
Daryl Victor and Cheryl Waters
20. Catechol-O-Methyltransferase in Parkinson’s Disease
Ronald F. Pfeiffer

21. Investigational Pharmacological Treatments for Parkinson’s
Disease
William Ondo
SURGICAL THERAPY
22. Lesion Surgeries
Michael Samuel and Anthony E. Lang
23. Deep Brain Stimulation in Parkinson’s Disease
Rajesh Pahwa and Kelly E. Lyons
24. Neural Transplantation in Parkinson’s Disease
Elmyra V. Encarnacion and Robert A. Hauser

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


OTHER FORMS OF TREATMENT
25. Parkinson’s Disease Symptom Management: An Interdisciplinary
Approach
Ruth A. Hagestuen, Rosemary L. Wichmann,
and Marjorie L. Johnson

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


1
Early Iconography of Parkinson’s Disease
Christopher G. Goetz
Rush University, Chicago, Illinois, U.S.A.

Parkinson’s disease was first described in a medical context in 1817 by James
Parkinson, a general practitioner in London. Numerous essays have been

written about Parkinson himself and the early history of Parkinson’s disease
(Paralysis agitans), or the shaking palsy. Rather than repeat or resynthesize
such prior studies, this introductory chapter focuses on a number of
historical visual documents with descriptive legends. Some of these are
available in prior publications, but the entire collection has not been
presented before. As a group, they present materials from the nineteenth
century and will serve as a base on which the subsequent chapters that cover
the progress of the twentieth and budding twenty-first centuries are built.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


HISTORICAL AND LITERARY PRECEDENTS

FIGURE 1 Franciscus de le Bo¨e (1614–1672). Also known as Sylvius de le Bo¨e
and Franciscus Sylvius, this early physician was Professor of Leiden and a
celebrated anatomist. In his medical writings he also described tremors, and he
may be among the very earliest writers on involuntary movement disorders (1).

FIGURE 2 Franc¸ois Boissier de Sauvages de la Croix (1706–1767). Sauvages
was cited by Parkinson himself and described patients with ‘‘running disturbances
of the limbs,’’ scelotyrbe festinans. Such subjects had difficulty walking, moving
with short and hasty steps. He considered the problem to be due to diminished
flexibility of muscle fibers, possibly his manner of describing rigidity (1,2).

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


FIGURE 3 William Shakespeare. A brilliant medical observer as well as writer,
Shakespeare described many neurological conditions, including epilepsy, somnambulism, and dementia. In Henry VI, first produced in 1590, the character Dick

notices that Say is trembling: ‘‘Why dost thou quiver, man,’’ he asks, and Say
responds, ‘‘The palsy and not fear provokes me’’ (1). Jean-Martin Charcot
frequently cited Shakespeare in his medical lectures and classroom presentations
and disputed the concept that tremor was a natural accompaniment of normal
aging. He rejected ‘‘senile tremor’’ as a separate nosographic entity. After
reviewing his data from the Salpeˆtrie`re service where 2000 elderly inpatients lived,
he turned to Shakespeare’s renditions of elderly figures (3,4): ‘‘Do not commit the
error that many others do and misrepresent tremor as a natural accompaniment of
old age. Remember that our venerated Dean, Dr. Chevreul, today 102 years old,
has no tremor whatsoever. And you must remember in his marvelous descriptions
of old age (Henry IV and As You Like It), the master observer, Shakespeare, never
speaks of tremor.’’

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


FIGURE 4 Wilhelm von Humboldt (1767–1835). A celebrated academic
reformer and writer, von Humboldt, lived in the era of Parkinson and described
his own neurological condition in a series of letters, analyzed by Horowski (5). The
statue by Friedrich Drake shown in the figure captures the hunched, flexed posture
of Parkinson’s disease, but von Humboldt’s own words capture the tremor and
bradykinesia of the disease (6):
Trembling of the hands . . . occurs only when both or one of them is
inactive; at this very moment, for example, only the left one is trembling
but not the right one that I am using to write. . . . If I am using my hands
this strange clumsiness starts which is hard to describe. It is obviously
weakness as I am unable to carry heavy objects as I did earlier on, but it
appears with tasks that do not need strength but consist of quite fine
movements, and especially with these. In addition to writing, I can
mention rapid opening of books, dividing of fine pages, unbuttoning and

buttoning up of clothes. All of these as well as writing proceed with
intolerable slowness and clumsiness.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


JAMES PARKINSON

FIGURE 5 Front piece of James Parkinson’s An Essay on the Shaking Palsy
(from Ref. 7). This short monograph is extremely difficult to find in its original 1817
version, but it has been reproduced many times. In the essay, Parkinson describes
a small series of subjects with a distinctive constellation of features. Although he
had the opportunity to examine a few of the subjects, some of his reflections were
based solely on observation.

FIGURE 6 St. Leonard’s Church (from Ref. 8). The Shoreditch parish church
was closely associated with James Parkinson’s life, and he was baptized, married,
and buried there.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.


FIGURE 7 (Top) John Hunter, painted by J. Reynolds (from Ref. 9). Hunter was
admired by Parkinson, who transcribed the surgeon’s lectures in his 1833
publication called Hunterian Reminiscences (Bottom). In these lectures, Hunter
offered observations on tremor. The last sentence of Parkinson’s Essay reads (7):
‘‘. . . but how few can estimate the benefits bestowed on mankind by the labours of
Morgagni, Hunter or Baillie.’’ Currier has posited that Parkinson’s own interest in
tremor was first developed under the direct influence of Hunter (11).

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FIGURE 8 James Parkinson’s home (from Ref. 12). No. 1 Hoxton Square,
London, formerly Shoreditch, today carries a plaque honoring the birthplace of
Parkinson.

FIGURE 9 James Parkinson as paleontologist (from Ref. 13). An avid geologist
and paleontologist, Parkinson published numerous works on fossils, rocks, and
minerals. He was an honorary member of the Wernerian Society of Natural History
of Edinburgh and the Imperial Society of Naturalists of Moscow.

Copyright 2003 by Marcel Dekker, Inc. All Rights Reserved.