Front Cover

MOVEMENT DISORDERS 4

Copyright

BLUE BOOKS OF NEURO LOGY

CONTENTS

CONTRIBUTING AUTHORS

SERIES PREFACE

PREFACE

Section 1 CURRENT CONCEPTS IN THE ANATOMYAND PHYSIOLOGY OF THE BASALGANGLIA

Chapter 1 Functional Anatomyand Pathophysiologyof the Basal Ganglia

Introduction

Pathophysiology of the Parkinsonian State

Pathophysiology of the Dyskinetic State

Therapeutic Applications

Conclusions

REFERENCES

Section 2 PARKINSON'S DISEASE

Chapter 2 Genetics of Parkinson’s Disease—An Overview

Introduction

Monogenic Parkinsonism with a PARK Acronym

Parkinsonism Associated with Mutations in Non-PARK Genes

Genetic Susceptibility Factors for Parkinson Disease

Genetic Testing for Parkinsonism

Novel Therapeutic Strategies

REFERENCES

Chapter 3 α-Synuclein and Parkinson’s Disease

Introduction

SNCA Mutations

α-Synuclein Normal Localization, Regulation, and Function

Aggregate Formation

Animal Models

Association Studies: SNCA Genetics in Sporadic Disease

Further Considerations

Conclusions

REFERENCES

Chapter 4 PARK2: Parkin Mutations Responsiblefor Familial Parkinson’sDisease

Introduction

Clinical Features

Function of Parkin Protein

Parkin Gene Therapies for Synucleinopathies

Conclusions

REFERENCES

Chapter 5 PINK1 (PARK6) and Parkinson’s Disease

Clinical and Molecular Genetic Studies

Functional Studies

PINK1 Animal Models

REFERENCES

Chapter 6 DJ-1 (PARK7) and Parkinson’s Disease

Introduction

Genetics of PARK7—Nature and Frequency of DJ-1 Mutations

Neuroimaging of PARK7

Pathological Correlates of DJ-1 Mutations

Molecular Biology of DJ-1

DJ-1-Related Neurodegeneration in Model Organisms

REFERENCES

Chapter 7 LRRK2 and Parkinson’s Disease

PARK8 and LRRK2

Lrrk2 Protein Structure

Lrrk2 Pathogenic Mutations and Polymorphic Risk Factors—Families and Founders

Lrrk2 Pleomorphic Pathology

Lrrk2 Functional Neuroscience

Parsimonious Molecular Model of Lrrk2 Activity

Future Research

REFERENCES

Chapter 8 Environmental Factorsand Parkinson’s Disease

Introduction

Patterns in Populations

Risk Factor Investigations

Tobacco Use

Caffeine Use

Nonsteroidal Anti-inflammatory Drugs

Uric Acid

Physical Activity

Diet

Metabolic Conditions

Estrogen Status

Head Injury

Occupation

Complex Interactions

Shared Risks for Neurodegenerative Disorders

Conclusions

References

Chapter 9 Pathology of Parkinson’s Disease

Major Advances in Pathological Understanding of Parkinson’s Disease

Clinicopathological Types of Parkinson’s Disease

Clinicopathological Correlations in Parkinson’s Disease

HYPOTHESES ON PATHOGENESIS

Implications for Clinical Practice

REFERENCES

Chapter 10 Pathogenesis of Parkinson’s Disease

Introduction

Insights from Genetics

Observations beyond Known Parkinson’s Disease Genes

Conclusions

REFERENCES

Chapter 11 Imaging in Parkinson’s Disease

Introduction

Structural Imaging Approaches in Parkinsonian Disorders

Imaging Presynaptic Dopaminergic Function in Parkinson’s Disease

Resting Glucose Metabolism in Typical and Atypical Parkinson’s Disease

Detection of Preclinical Parkinson’s Disease

Mechanisms Underlying Fluctuations and Dyskinesias

Pharmacology of Depression in Parkinson’s Disease

Mechanisms Underlying Dementia in Parkinson’s Disease

Microglial Activation in Parkinson’s Disease

Conclusions

REFERENCES

Chapter 12 Dementia in Parkinson’s Disease

Introduction

Epidemiology of Dementia Associated with Parkinson’s Disease

Lewy Body Dementia Spectrum

Predicting Dementia in Parkinson’s Disease

Clinical Features of Dementia in Parkinson’s Disease

Diagnostic Criteria

Investigation of Dementia and Its Predictors

Pathological Basis of Dementia in Parkinson’s Disease

Management

Conclusions

REFERENCES

Chapter 13 Psychiatric Issues in Parkinson’s Disease

Introduction

Depression

Anxiety

Disorders of Sleep and Wakefulness

Apathy

Involuntary Emotional Expression Disorder

Impact of Deep Brain Stimulation

Conclusions

Acknowledgments

REFERENCES

Chapter 14 Nonmotor Aspectsof Parkinson’s Disease

Introduction

Smell Loss

Dysautonomia

Sleep Disturbances

Fatigue

Pain and Sensory Symptoms

Nonmotor Symptoms in the Premotor Phase of Parkinson’s Disease

Conclusions

REFERENCES

Chapter 15 Therapy of the Motor Featuresof Parkinson’s Disease

Introduction

Symptomatic Therapy of Early Parkinson’s Disease

Treatment of Advanced Parkinson’s Disease

Treatment of Unpredictable “Offs”, “On-Off” Fluctuations, and Delayed “On” Responses

Treatment of Dyskinesia

Future Treatment Options for Advanced Parkinson’s Disease

Nondopaminergic Motor Symptoms of Advanced Parkinson’s Disease

REFERENCES

Chapter 16 Surgical Therapyfor Parkinson’s Disease

Introduction

Surgical Indications

Surgical Targets

Surgical Options

Description of Deep Brain Stimulation

Anatomy and Pathophysiology

Mechanism of Action of Deep Brain Stimulation

Operative Procedure

Intraoperative Electrophysiological Mapping

Deep Brain Stimulation Outcomes

REFERENCES

Chapter 17 Cell-Based and Gene-Based Therapyfor Parkinson’s Disease

Introduction

Cell-based Therapies

Gene-based Therapy

Conclusions

REFERENCES

Chapter 18 Neuroprotection in Parkinson’s Disease

Introduction

Dopamine Agonists

Mitochondrial Function Enhancers

Levodopa

N-Methyl-d-Aspartate Receptor Antagonists

Immunophilins

Antiapoptotic Agents

Anti-inflammatory Drugs

Adenosine Antagonists

Calcium Channel Blockers

Timing of Treatment and Compensatory Mechanisms

Prospects for the Future

REFERENCES

Section 3 Multiple system emematrophy

Chapter 19 Etiology, Pathology,and Pathogenesis

Introduction

Etiology

Neuropathology

Pathogenesis

Conclusions

Acknowledgment

REFERENCES

Chapter 20 Multiple System Atrophy: Clinical Features and Management

Introduction

Clinical Features

Clinical Diagnostic Criteria

Differential Diagnostic Tests for Multiple System Atrophy

Management

REFERENCES

Section 4 PROGRESSIVE SUPRANUCLEAR PALSY

Chapter 21 Progressive Supranuclear Palsy

Introduction

Clinical Features

Molecular Genetics

Pathology

Treatment

REFERENCES

Section 5 CORTICOBASAL GANGLIONIC DEGENERATION

Chapter 22 Corticobasal GanglionicDegeneration

Introduction

Epidemiology and Demographics

Clinical Features

Differential Diagnoses

Diagnostic Investigations

Pathology

Genetics

Management

REFERENCES

Section 6 FRONTOTEMPORAL DEMENTIA

Chapter 23 Frontotemporal Dementia

Introduction

Epidemiology

Frontotemporal Dementia Associated with Motor Neuron Disease

Genetics

Pathology

Treatment

Acknowledgments

REFERENCES

Section 7 HUNTINGTON'S DISEASE

Chapter 24 Etiology, Pathology,and Pathogenesis

Introduction

Etiology

Pathology

Pathogenesis

Conclusions

REFERENCES

Chapter 25 Clinical Features and Care

Introduction

Population Characteristics, Genetic Basis, and Natural History

Clinical Diagnosis

Search for a Systemic Phenotype

Juvenile-onset Huntington’s Disease

Care of the Huntington’s Disease Patient and Family

Medical Care and Treatment of Manifest Huntington’s Disease

Participation in Huntington’s Disease Clinical Research

Conclusions

REFERENCES

Section 8 THE DYSTONIAS

Chapter 26 The Genetics and Pathogenesisof Dystonia

Introduction

Molecular Genetics of Primary Torsion Dystonia

Genetics of Dystonia-plus Syndromes

Overview of Pathogenesis and Treatment Targets

REFERENCES

Chapter 27 Management

Introduction

Medical Treatment

Surgical Treatment

REFERENCES

Section 9 OTHER MOVEMENT DISORDERS

Chapter 28 Paroxysmal Dyskinesias

Introduction

Paroxysmal Kinesigenic Dyskinesia

Paroxysmal Nonkinesigenic Dyskinesia (Paroxysmal Dystonic Choreoathetosis)

Paroxysmal Hypnogenic Dyskinesia (Nocturnal Paroxysmal Dyskinesia)

Miscellaneous Movement Disorders Occurring in Bursts or as Paroxysmal Attacks

REFERENCES

Chapter 29 Essential Tremor and Other Tremors

Introduction

Clinical Definitions

Physiological and Enhanced Physiological Tremor

Parkinsonian Tremors

PATHOPHYSIOLOGY

Dystonic Tremor

Primary Writing Tremor

Cerebellar Tremor Syndromes

Holmes’ Tremor

Tremor Syndromes in Peripheral Neuropathy

Palatal Tremor Syndromes

Drug-induced and Toxic Tremors

Psychogenic Tremor

Rare (or Undetermined) Tremor Syndromes

REFERENCES

Chapter 30 Other Choreas

Introduction

Pathophysiology of Chorea

Metabolic Causes

Autoimmune Disorders

Drug-induced Choreas

Infectious and Postinfectious Causes

Genetic Causes of Chorea

Other Pediatric Metabolic Causes of Chor

Treatment of Chorea

Conclusions

REFERENCES

Chapter 31 Restless Legs Syndrome

Introduction

Definition, Diagnosis, and Assessment of Restless Legs Syndrome

Pathophysiology of Restless Legs Syndrome

CORTICAL STRUCTURES

BASAL GANGLIA

BRAINSTEM AND SPINAL CORD

PERIPHERAL NERVOUS SYSTEM

Epidemiology and Genetics of Restless Legs Syndrome

Management of Restless Legs Syndrome

REFERENCES

Chapter 32 Startled People

Startle Response

Disorders of the First Component of the Startle Response

Disorders of the Second Component of the Auditory Startle Response

REFERENCES

Chapter 33 Psychogenic Movement Disorders

Introduction

Epidemiology and Risk Factors

Diagnostic Criteria for Psychogenic Movement Disorders

Evaluation of Patients with Psychogenic Movement Disorders

Specific Psychogenic Movement Disorders

Investigations in Psychogenic Movement Disorders

Treatment of Psychogenic Movement Disorders

REFERENCES

Chapter 34 Tics and Gilles de la Tourette Syndrome

Introduction

Associated Problems

Etiology

Neurobiology

Treatment

Conclusions

REFERENCES

INDEX