Parkinson Disease

Description:

Parkinson Disease is a comprehensive introduction to the biology and clinical features of Parkinson disease (PD). This book is aimed at clinicians in training, general neurologists seeking a useful guide to PD, and scientists seeking an overview of clinical aspects of PD. Topics covered include nosology of PD, PD epidemiology, pathology and pathophysiology of PD, and theories of PD pathogenesis. Clinical features, including the many non-motor features, natural history of disease progression, clinical pharmacology, and management of PD receive coverage. Important themes are heterogeneity of PD, the multi-focal nature of PD pathology, the diversity of clinical features, dopaminergic signaling and the impacts of dopaminergic deficiency, the importance of non-motor features, limitations of existing treatment modalities, and the necessity of approaching PD as a multi-system disorder. The description and discussion of the many aspects of Parkinson disease (PD) is dogged by the fact that PD is an ambiguous concept. This book intends to be a useful overview, bridging the gap between general textbooks and specific topical reviews.

Table of Contents:

Contents

Preface

1. Definition, History, Nosology, and Classification

Introduction and Definition

Brief History of PD

Nosology and Classification Scheme

Classification Level 1: Pism—Division into Complex Pism and Simple Pism

Classification Level 2: Specific Diagnosis Based on Etiology

Ambiguities and Future Directions

Conclusion

2. Epidemiology

Introduction

Prevalence

Incidence

Mortality

Risk Factors

Implications for Understanding Etiopathogenesis and Anticipating the Future Burden of PD

3. Pathology

Introduction

The Aging Brain

Gross Pathology, Lewy Pathology, and α-Synucleinopathy

Substantia Nigra Pars Compacta Pathologies

Incidental Lewy Body Disease

The Braak et al. Staging System

Synucleinopathy Outside the Brain

Non-Synucleinopathy Pathologies

4. Pathophysiology I: Basal Ganglia Architecture and the Standard Model

Introduction

Basic Basal Ganglia Architecture

The “Standard” Model of Basal Ganglia Pathophysiology

Complexities of Basal Ganglia Architecture

Conclusion

5. Pathophysiology II: Neurotransmitter System Dysfunctions

Introduction

Nigrostriatal Dopamine Signaling Functions

Habit Formation and Chunking

Cholinergic Projection System Dysfunctions

Serotoninergic System Dysfunctions

Conclusion and Future Challenges

6. Genetics of Parkinson Disease

Introduction

Dominant Forms of PD

Recessive Forms of PD

Glucocerebrosidase (GBA)

PD Genetic Risk Factors

Implications of PD Genetic Research

7. Pathogenesis

Neuronal Vulnerability

α-Synuclein

The Prion-Like Hypothesis

Mitochondrial Dysfunction

Oxidative Stress

Endolysosomal Dysfunction

Neuroinflammation

Neuroprotection Trials

Conclusion

8. Prodromal Parkinson Disease

Introduction

REM Sleep Behavior Disorder

Observational Studies

REM Sleep Behavior Disorder Cohort Studies

Genetic Cohort Studies

Pure Autonomic Failure

Conclusion

9. Clinical Features I: Initial Evaluation

Presentation Features

Nature of Diagnosis and Diagnostic Criteria

History

Examination

Differential Diagnosis

Treatment Responsiveness

Diagnostic Accuracy

10. Clinical Features II: Non-Motor Features

Introduction

Cognitive Impairments

Neuropsychiatric Disorders

Sleep Disorders and Excessive Daytime Somnolence

Pain and Akathisia

Fatigue

Autonomic Disorders

Visual Disorders

Oral Health

Conclusion

11. Clinical Features III: Natural History

Introduction

Assessing PD Progression

PD Progression: Clinically Salient Features

Subgroups

Natural History Summary

Continuing Care

End-of-Life Care

12. Pharmacology I: L-Dopa Pharmacokinetics and Pharmacodynamics

Introduction

Dopaminergic Neurotransmission

L-Dopa Pharmacokinetics

L-Dopa Pharmacodynamics

Peak Dose Dyskinesias

Interactions of L-Dopa Pharmacokinetics, Pharmacodynamics, and Disease Progression

Conclusion and Future Directions

13. Pharmacology II: Treating Parkinson Disease

Introduction

Using L-Dopa

When the Honeymoon Is Over

L-Dopa Adjuncts

Dopamine Agonists

Cholinergic Agents

Other Symptomatic Therapies

Future Directions

14. Surgery

Introduction

Deep Brain Stimulation: Rationale and Possible Mechanisms

Deep Brain Stimulation: Indications

Deep Brain Stimulation: Procedures

Deep Brain Stimulation: STN DBS Benefits

Deep Brain Stimulation: GPi DBS Benefits and STN Versus GPi DBS

Deep Brain Stimulation: Adverse Events

Lesional Procedures

Cell-Based and Gene Therapies

Future Directions

Coda: Looking Ahead

Disease Heterogeneity

Epidemiology

Treatments

Basic and Clinical Research Synergies

Index