-- Parkinson's Disease -- NCBI Bookshelf

Acknowledgments
Contributors
Dedication
Foreword
Preface
Chapter 1 James Parkinson: The Man and the Essay Stewart A. Factor, D.O. and William J. Weiner, M.D.
- Introduction
- The Man
- The Essay
- Acknowledgments
- References
Chapter 2 Paralysis Agitans in the Nineteenth Century Elan D. Louis, M.D.
- Introduction
- Background
- Literature Review
- Conclusion
- Acknowledgments
- References
Chapter 3 Charcot and Parkinson's Disease Christopher G. Goetz
- Introduction
- Tremorous Diseases
- References
Chapter 4 Twentieth Century – Timeline for PD William J. Weiner, M.D. and Stewart A. Factor, D.O.
Chapter 5 Epidemiology of Parkinsonism M.L. Rajput, MS and A.H. Rajput, FRCPC
- Selection of Location and Population
- Diagnosis of Parkinsonism and Parkinson Syndrome Variants
- Progression of Parkinsonism and Staging of Disease
- Manpower Consideration for Epidemiologic Studies
- Objectives of Epidemiologic Studies
- Incidence of Parkinsonism
- Life Expectancy in Parkinsonism
- Prevalence of Parkinsonism
- Health Services Needs
- Race and Gender
- Analytic and Clinical Epidemiology
- References
Chapter 6 Cardinal Features of Early Parkinson's Disease Pramod Kr. Pal, M.D., D.M., Ali Samii, M.D., F.R.C.P.C., Donald B. Calne, D.M., F.R.C.P.C., Pramar Kr. Pal, and Ali Samii, M.D.
- Parkinsonian Syndrome and the Definition of Parkinson's Disease
- Aging and Parkinson's Disease
- Clinical Features
- Differential Diagnosis
- Diagnosis of Early Idiopathic Parkinsonism
- Conclusion
- Acknowledgments
- References
Chapter 7 Gait Disturbances Nir Giladi, MD
- Introduction
- Gait Disturbances as Part of the Clinical Syndrome
- Assessment of Gait
- Treatment of Parkinsonian Gait
- Functional Neurosurgery for Gait Disturbances
- Acknowledgments
- References
Chapter 8 Sensory Symptoms Richard M. Zweig, M.D.
- Introduction
- Case Report
- Frequency, Location, and Quality of Somatosensory Symptoms
- Pathophysiology
- Evaluation and Treatment of Somatosensory Symptoms
- References
Chapter 9 Speech, Voice, and Swallowing Disorders Lorraine Olson Ramig, Professor, Stefanie Countryman, Speech-Language Pathologist, Cynthia Fox, Speech-Language Pathologist, and Shimon Sapir, Ph.D., CCC-SLP
- Introduction
- Speech and Voice Characteristics in Parkinson's Disease
- Treatment
- Conclusion
- Acknowledgments
- References
Chapter 10 Gastrointestinal Features Eamonn M.M. Quigley, MD, FRCP, FACP, FACG
- Introduction and Background
- An Overview of Gastrointestinal Motor Function
- Gastrointestinal Dysfunction in Parkinson's Disease – Historical Background and Principal Features
- Dysphagia in Parkinson's Disease
- Nausea, Vomiting, Dyspepsia, and Gastric Function in Parkinson's Disease
- Constipation, Difficult Defecation, and Colonic And Anorectal Function
- The Pathophysiology of Gastrointestinal Dysfunction in Parkinson's Disease – Available Evidence and Future Prospects
- Management of Gastrointestinal Complications in Parkinson's Disease
- Conclusion
- References
Chapter 11 Autonomic Nervous System Dysfunction Jean Pintar Hubble, M.D. and Carolyn Weeks, B.S.
- Introduction
- Neuropathology of Autonomic Dysfunction in Parkinson's Disease
- Thermoregulatory Dysfunction and Skin Changes
- Pupillary Changes
- Gastrointestinal Dysfunction and Weight Loss
- Cardiovascular Function
- Urinary Bladder Dysfunction
- Sexual Dysfunction
- References
Chapter 12 Sleep Disorders Cynthia L. Comella, M.D., A.B.S.M.
- Sleep Disturbances Related to Symptoms of Parkinson's Disease
- Delayed Sleep Onset
- Sleep Apnea
- The Effect of Dopaminergic Therapy on Sleep in Parkinson's Disease
- Sleep Disturbance – Hallucinations Syndrome in Parkinson's Disease Patients on Chronic Dopaminergic Therapy
- Sleep Benefit in Parkinson's Disease
- REM Sleep Behavior Disorder in Parkinson's Disease
- Excessive Daytime Sleepiness in Parkinson's Disease
- References
Chapter 13 Natural History Andrew Feigin, M.D. and David Eidelberg, M.D.
- Introduction
- Preclinical Period
- Clinical Presentation
- Rate of Progression
- Disease Duration and Mortality
- Conclusion
- Acknowledgments
- References
Chapter 14 Quantitative Measures and Rating Scales Stephen T. Gancher, M.D.
- Introduction
- Early Standardized Ratings
- The Unified Parkinsons Disease Rating Scale
- The Capit Rating Scale
- Ratings of Dyskinesias
- Diary Ratings
- Administration
- Unified Parkinson's Disease Rating Scale (UPDRS)
- Modified Hoehn And Yahr Staging
- Modified Schwab and England Activities of Daily Living Scale
- Dyskinesia Rating Scale ()
- References
Chapter 15 Dementia Karen Marder, M.D., M.P.H. and Diane M. Jacobs, Ph.D.
- Defining Dementia in Parkinson's Disease
- Neuropsychologic Characteristics of Dementia in Parkinson's Disease
- Role of Dopamine in Cognitive Dysfunction
- Progression of Cognitive Impairment in PD
- Prevalence of Dementia
- Incidence of Dementia
- Risk of Dementia Compared to Age-matched Controls
- Mortality
- Risk Factors for Dementia in Parkinson's Disease
- Pathology
- Neuroimaging
- Treatment of Cognitive Impairment
- Depression and Dementia
- Conclusion
- References
Chapter 16 Dementia with Lewy Bodies, Alzheimer's Disease and Their Relationship to Parkinson's Disease Douglas Galasko, M.D.
- Introduction
- Neuropathologic Findings in Dementia with Lewy Bodies
- Clinical Features of Dementia with Lewy Bodies
- Patterns of Cognitive Impairment in Dementia with Lewy Bodies
- Neuroimaging Studies of Dementia with Lewy Bodies
- Management of Patients with Dementia with Lewy Bodies
- References
Chapter 17 Depression Tiffany W. Chow, Donna L. Masterman, and Jeffrey L. Cummings, M.D.
- Introduction
- Risk Factors for Depression in PD
- Cognition and Depression in PD
- Relation of Depression to On–Off Phenomena
- Neurobiologic Basis of Depression in PD
- Metabolic Studies of Depression in PD
- Treatment of Depression in PD
- Conclusion
- Acknowledgments
- References
Chapter 18 Anxiety and Panic Irene Hegeman Richard, M.D. and Roger Kurlan, M.D.
- Introduction
- Anxiety in PD
- Conclusion
- References
Chapter 19 Apathy and Amotivation Lisa M. Shulman, M.D.
- Clinical Correlates of Apathy in Parkinson's Disease
- Causes of Apathy
- Apathy vs. Depression
- Apathy in Medical, Neurologic, and Psychiatric Disorders
- Recognition of Apathy and Amotivation
- The Management of Apathy and Amotivation
- The Effect of Motivation on Living with Chronic Illness
- Conclusion
- References
Chapter 20 Pathology Kevin D. Barron, M.D.
- Historical Development
- Histopathology
- Dementia and PD
- Causation
- Other Diseases Associated with Parkinsonian Symptomatology
- References
Chapter 21 Neurochemistry Jose Martin Rabey, M.D. and Richard Stanley Burns, M.D.
- Anatomy of the Basal Ganglia and Related Circuits
- Dopaminergic Systems
- Dopamine Metabolism
- Dopamine, Neuromelanin, and Tyrosine Hydroxylase
- Protein Synthesis
- Dopamine Metabolites
- Dopamine Receptors
- Dopamine Transporter
- Nigrostriatal Dopamine System and Parkinsonian Symptoms
- Other Neurotransmitters and Receptors
- Lewy Bodies
- Conclusion
- References
Chapter 22 Basal Ganglia Anatomy and Physiology Thomas Wichmann, M.D., Ph.D., Yoland Smith, Ph.D., and Jerrold L. Vitek, M.D., Ph.D.
- Introduction
- Structure and Function of Basal Ganglia Circuits
- Pathophysiology of Parkinson's Disease
- Conclusions
- References
Chapter 23 Dopamine Receptor Diversity Deborah C. Mash
- Introduction
- Molecular Characterization of Dopamine Receptors
- Neuroanatomic Localization of Dopamine Receptor Protein and mRNA
- Pharmacologic Selectivity
- References
Chapter 24 Problems in Diagnosis Andrew J. Lees, M.D.
- Recent Clinicopathologic Studies
- Helpful Clinical Pointers for the Diagnosis of Parkinson's Disease
- The Neurologic Examination
- Lewy Body Dementia
- Ancillary Investigations
- Concluding Remarks
- References
Chapter 25 Single Photon Emission Tomography and Dopamine Transporter Imaging Kenneth Marek, M.D.
- Diagnosis and Disease Severity
- Parkinson's Disease Progression
- Preclinical Parkinson's Disease
- Future Directions
- References
Chapter 26 Positron Emission Tomography Mark Guttman, M.D., F.R.C.P.C.
- Introduction
- PET Methodology
- PET Ligands to Study Parkinson's Disease
- Postsynaptic Dopaminergic Studies in Parkinson's Disease
- Differential Diagnosis of PD with PET
- PET Measurements to Assess Therapeutics in Parkinson's Disease
- Conclusions
- Bibliography
Chapter 27 Etiology: The Role of Environment and Genetics Caroline M. Tanner, M.D., Ph.D.
- Introduction
- Challenges in Investigating Parkinson's Disease
- Parkinsonism of Known Cause
- Clues to the Cause of Parkinson's Disease from Epidemiologic Studies
- Risk Factors from Analytic Studies
- Conclusion
- References
Chapter 28 Pathogenesis: Oxidative Stress, Mitochondrial Dysfunction, and Excitotoxicity David K. Simon, M.D., Ph.D. and M. Flint Beal, M.D.
- The Oxidative Stress Hypothesis
- Markers of Oxidative Damage in Parkinson's Disease
- Impaired Energy Metabolism in Parkinson's Disease
- Other Potential Sources of Oxidative Stress
- Excitotoxicity
- Conclusions
- References
Chapter 29 Apoptosis Robert E. Burke, M.D.
- The Concept of Apoptosis
- Apoptosis Occurs in Dopamine Neurons of the Substantia Nigra during Normal Development
- Apoptosis in Animal Models of Parkinsonism
- Molecular Correlates of Apoptosis in SNpc Neurons
- Apoptosis in Parkinson's Disease: Does It Play a Role in Neuron Death?
- Relevance of Apoptosis to Other Aspects of Parkinson's Disease
- Conclusions
- Acknowledgments
- References
Chapter 30 The Impact of MPTP on Parkinson's Disease Research: Past, Present, and Future J. William Langston, M.D.
- Introduction
- The Discovery of the Biologic Effects of MPTP
- What Have We Learned from MPTP-induced Parkinsonism in Humans?
- Aging and MPTP
- Species Susceptibility
- Intranigral Selective Vulnerability
- Epidemiologic Investigations
- Conclusions
- References
Chapter 31 Cerebrospinal Fluid Toxicity: Clues to Pathogenesis Ronald E. Pfeiffer, M.D. and Ruyi Hao, M.D., Ph.D.
- Introduction
- Cell Culture Studies
- Candidate Neurotoxins
- Conclusion
- References
Chapter 32 Levodopa: 30 Years of Progress Tanya Simuni, M.D. and Howard Hurtig, M.D.
- Introduction
- Historical Review
- The Biochemistry and Metabolism of Levodopa
- Complications of Levodopa Therapy
- A Continuing Controversy: Is Levodopa Toxic?
- Refinement of Levodopa Therapy: Enzyme Inhibition
- Conclusions
- References
Chapter 33 Amantadine and Anticholinergics Charles H. Adler, M.D., Ph.D.
- Amantadine and Anticholinergics
- Amantadine
- Anticholinergics
- References
Chapter 34 Monoamine Oxidase Inhibitors Theresa A. Zesiewicz, M.D. and Robert A. Hauser, M.D.
- Introduction and History
- Monoamine Oxidase: Biochemistry and Mechanism of Action
- Monoamine Oxidase: Anatomy and Localization
- Monoamine Oxidase Inhibitors: Reversible and Irreversible
- Monoamine Oxidase Inhibitors: Hypertensive Crisis
- Other MAO Inhibitors
- Conclusion
- Acknowledgment
- References
Chapter 35 Dopamine Agonists Puiu F. Nisipeanu and Amos D. Korczyn
- Protective Effects of Dopamine Agonists
- Adverse Effects of Dopamine Agonists
- Drug Interactions
- Other Dopamine Agonists
- Nonergot Drugs
- Comparison of Dopamine Agonists
- Comparison Of Dopamine Agonists with Levodopa
- Conclusions
- References
Chapter 36 Catechol-O-Methyltransferase (COMT) Inhibitors Cheryl Waters, M.D., F.R.C.P.(C)
- Limitations of Levodopa
- Rationale for COMT Inhibitors
- Clinical Studies with COMT Inhibitors
- Safety of COMT Inhibitors
- Differences between Tolcapone and Entacapone
- Patient Selection Criteria
- Comparisons of COMT Inhibitors with Other Therapies for Parkinson's Disease
- Conclusion
- References
Chapter 37 Atypical Antipsychotics Joseph H. Friedman, M.D. and Herbert Y. Meltzer, M.D.
- Introduction
- Psychosis
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
- Other Drugs for Treating Levodopa Psychosis
- Tremor
- Other Motor Aspects of Parkinson's Disease
- Conclusion
- Addendum
- References
Chapter 38 Excitatory Amino Acid Receptor Antagonists Fabio Blandini and J. Timothy Greenamyre
- Introduction
- Excitatory Neurotransmission in the Central Nervous System
- Glutamate-mediated Transmission in the Basal Ganglia: Relevance to PD Pathophysiology
- The Role of Glutamate-mediated Toxicity in the Etiopathogenesis of PD
- Prospects of Glutamate Antagonists for PD Therapy
- Conclusion
- References
Chapter 39 Other Therapies Eric Siemers, M.D. and Allison Brashear, M.D.
- Introduction
- Treatment of Dementia Associated with Parkinson's Disease
- Treatment of Dystonia Associated with Parkinson's Disease
- Treatment of Autonomic Failure
- Other Treatments for Motor Symptoms and Fluctuations
- Use of L-Threodops
- Alternative Experimental Treatments of Parkinson's Disease
- References
Chapter 40 Motor Fluctuations and Dyskinesia John G. Nutt, M.D.
- Introduction
- Prevalence of Fluctuations and Dyskinesia
- Development of Motor Fluctuations
- Development of Levodopa-induced Dyskinesia
- Treatment of Fluctuations and Dyskinesia
- Acknowledgments
- References
Chapter 41 Fluctuations of Nonmotor Symptoms Jacob I. Sage, M.D.
- General Principles
- Nonmotor Phenomena Associated with the “On” State ()
- Nonmotor Fluctuations Associated with the "Off" State
- Treatment
- References
Chapter 42 Psychosis and Related Problems Eric S. Molho, M.D.
- Introduction
- Drug-induced Psychosis: Terminology, History, and Frequency
- Clinical Features
- Mechanisms of Psychosis
- Treatment of Psychosis: General Considerations
- Treatment: Summary
- Mania
- Hypersexuality
- Acknowledgment
- References
Chapter 43 Status of Protective Therapies Andrew D. Siderowf, M.D. and Matthew B. Stern, M.D.
- Definition of Neuroprotection and Relevance to Parkinson's Disease
- Mechanisms of Neuronal Injury in Parkinson's Disease
- Neuroprotective Therapy for Parkinson's Disease
- Future Strategies
- Conclusion
- References
Chapter 44 Treatment Approaches for Early Parkinson's Disease J. Eric Ahlskog, Ph.D., M.D.
- Introduction
- General Neuroprotective Strategies
- Strategies for Reducing Motor Complications: Dyskinesias, Fluctuations
- Recommendations for Treatment of the Early PD Patient
- Conclusion
- References
Chapter 45 Progress in Gene Therapy M. Maral Mouradian, M.D.
- Introduction
- Methods of Gene Transfer to the Brain
- Viral Vectors
- Cell Vehicles for ex Vivo Gene Transfer for Parkinson's Disease
- Candidate Therapeutic Genes for PD
- Comparison of in Vivo and ex Vivo Gene Transfer Approaches
- Future Considerations
- References
Chapter 46 Tobacco Smoking, Nicotine, and Neuroprotection Peter A. LeWitt, M.D.
- Introduction
- Epidemiologic Studies of the Relationship between Smoking and Parkinson's Disease
- The Magnitude of Smoking's Effects at Reducing Risk for Parkinson's Disease
- Consistency among Studies of Reduced Risk for Parkinson's Disease in Smokers
- Specificity of Cause-and-Effect Relationship between Smoking and Reduced Risk for Parkinson's Disease
- The Chain of Events Underlying Smoking and the Risk for Parkinson's Disease
- Gradation of Biologic Effect from Smoking in Lowering the Risk for Parkinson's Disease
- The Biologic Plausibility of Smoking in Reducing the Risk for Developing Parkinson's Disease
- Coherence of Smoking's Reduction in the Risk for Parkinson's Disease and the Natural History and Biology of the Disease
- Experimental Evidence Exploring the Relationship between Smoking and the Risk of Developing Parkinson's Disease
- Relevant Analogies to Other Neurodegenerative Disease
- Conclusions
- References
Chapter 47 Stereotactic Pallidotomy and Thalamotomy Jung Y. Park, M.D., Andres M. Lozano, M.D., and Anthony E. Lang, M.D.
- Introduction
- Historical Background
- Rationale of Surgery
- Indications and Patient Selection for Surgery
- Surgical Techniques for Pallidotomy and Thalamotomy
- Clinical Results
- Conclusion
- References
Chapter 48 Thalamic Stimulation William C. Koller, M.D., Ph.D., Kelly Lyons, Ph.D., Rajesh Pahwa, M.D., and Steven Wilkinson SF, M.D.
- Clinical Background
- Patient Selection for DBS
- Surgical Procedure
- Team Approach
- Clinical Trials
- Thalamotomy vs. DBS of the Thalamus
- Mechanism of Action
- Advantages and Disadvantages of Deep Brain Stimulation
- Costs
- Regulatory Status
- Conclusion
- References
Chapter 49 Pallidal and Subthalamic Stimulation John P. Hammerstad, M.D.
- A Brief Historical Account
- Techniques
- Results of Treatment Trials: GPi Stimulation
- Results of Treatment Trials: Stimulation of the Subthalamic Nucleus
- Adverse Effects of Deep Brain Stimulation
- Outcomes Remaining to Be Answered
- References
Chapter 50 Neural Transplantation J. Stephen Fink, M.D., Ph.D.
- Introduction
- Human Fetal Transplants in Parkinson's Disease
- Other Cell Sources for Parkinson's Disease
- Transplantation for Other Neurodegenerative Diseases
- Summary: Prospects for New Cell Sources
- References
Chapter 51 Juvenile and Young-Onset Parkinsonism Oscar S. Gershanik, M.D.
- Introduction
- Historical Background
- Clinical Features
- Diagnostic Challenges
- Pathology
- Epidemiology and Genetics
- Response to Medications, Therapeutic Strategies
- Special Situations and Needs of the Young Patient
- References
Chapter 52 Is There a Familial Form of Parkinson's Disease? Lawrence I. Golbe, M.D.
- How Familial Is Parkinson's Disease?
- Are Familial Clusters Genetic in Origin?
- Clinically Inapparent PD
- Fluorodopa PET and Clinical Genetics
- Known Parkinson's Disease Genes or Loci
- Conclusions
- References
Chapter 53 Parkinson's Plus Syndromes David Riley, M.D.
- Introduction
- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Cortical-Basal Ganglionic Degeneration
- Frontotemporal Dementia with Parkinsonism
- Conclusion
- References
Chapter 54 Symptomatic Parkinsonism William T. Garrett, M.D. and Kapil D. Sethi, M.D., F.R.C.P (U.K.)
- Introduction
- Infection
- Drug-induced Parkinsonism
- Toxin-induced Parkinsonism
- MPTP
- Structural Lesions
- Miscellaneous Causes of Secondary Parkinsonism
- References
Chapter 55 Quality of Life: Issues and Measurement Mickie Welsh, R.N. DNSc.
- Historical Perspective
- What Is Quality of Life?
- Quality of Life in Parkinson's Disease
- Applying Quality of Life Concepts
- Assessing Quality of Life in the Clinical Setting
- Quantifying Quality of Life in Parkinson's Disease
- Methodological Considerations
- Integrating Quality-of-Life Research into Practice
- Future Applications
- References
Chapter 56 Family Caregiving Julie H. Carter, M.N. ANP, Patricia G. Archbold, R.N, D.N.Sc, F.A.A.N., and Barbara J. Stewart, Ph.D.
- Family Caregiving in Parkinson's Disease
- Demographic Trends in Family Caregiving for the Twenty-First Century
- Important Role of Family Caregiving in Chronic Illness
- The Risks Associated with Family Caregiving
- Predictors of Caregiver Strain
- Caregiver Role Strain
- Caregiver Characteristics
- The Caregiving Situation
- Assessment
- Interventions
- Conclusion
- References
Chapter 57 Economic Impact of Parkinson's Disease: Implications for Interventions Andrew Siderowf, M.D. and Robert G. Holloway, M.D.
- Introduction
- Economic Burden of Parkinson's Disease
- Direct and Indirect Cost of Parkinson's Disease
- Influence of Clinical Features on Resource Use
- Cost of Medications and Surgery for Parkinson's Disease
- Cost Effectiveness Research for Parkinson's Disease
- Cost-Effectiveness of PD-related Medications
- Surgery for Parkinson's Disease
- Implications of Cost-Effectiveness Research
- Summary
- References
Chapter 58 Driving Stewart A. Factor, D.O. and William J. Weiner, M.D.
- Introduction
- Driving and the Elderly
- Driving in Parkinson's Disease
- Conclusion
- Acknowledgments
- References

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