Pathophysiology, Pharmacology and Biochemistry of Dyskinesia

Contributors

Preface

An Introduction to Dyskinesia—The Clinical Spectrum

I Introduction

II Akathisia

III Ballism

IV Chorea

V Dystonia

VI Jumpy Stumps

VII Levodopa-Induced Dyskinesias

VIII Assessment of Dyskinesia

IX Moving Toes and Moving Fingers

X Myoclonus

XI Myokymia

XII Myorhythmia

XIII Stereotypy

XIV Tardive dyskinesia

XV Tics

XVI Tremor

XVII Conclusion

L-Dopa-Induced Dyskinesia—Clinical Presentation, Genetics, and Treatment

I Introduction

II Historical Aspects

III Epidemiology

IV Risk Factors

V Genetics of Dyskinesia

VI Classification

VII Clinical Characteristics

VIII Treatment

Experimental Models of L-DOPA-Induced Dyskinesia

I Historical Development of a Model of L-DOPA-Induced Dyskinesia

II MPTP-Lesioned Primate Model of L-DOPA-Induced Dyskinesia

III Unilateral 6-OHDA Lesioned Rodent Model of L-DOPA-Induced Dyskinesia

IV Critique of Toxin-Based Models of L-DOPA-Induced Dyskinesia

V Alternative Models of L-DOPA-Induced Dyskinesia

VI Future Modeling of L-DOPA-Induced Dyskinesia

VII Conclusions

Molecular Mechanisms of L-DOPA-Induced Dyskinesia

I Introduction

II Basal Ganglia and Medium Spiny Neurons

III LID and Hyperactivity of D1R/cAMP Signaling

IV Increased ERK Signaling in LID: Transcriptional and Translational Changes

V Glutamate NMDA Receptors and LID

VI mGluR5

VII Controlling Dyskinesia by Acting on the MSNs of the Indirect Pathway

VIII Cannabinoid CB1 Receptors

IX Pre-Synaptic Mechanisms: Serotonin Receptors

X Conclusions

New Approaches to Therapy

I Introduction

II Factors that Control the Priming and Expression of LID

III Modifying LID Through Dopaminergic Approaches

IV Nondopaminergic Approaches to LID

V Conclusions

Surgical Approach to L-Dopa-Induced Dyskinesias

I Introduction

II Brief Overview of LID

III Surgical Treatment of LID: Efficacy and Mechanisms of Action by Target

IV Surgical Approach to the Patient With LID

V Conclusion

Clinical and Experimental Experiences of Graft-Induced Dyskinesia

I Introduction

II Transplantation for Parkinson’s Disease

III The Clinical Phenomena of GID

IV Animal Models of GID

V Understanding the Cause of GID

VI Strategies for Dealing with GID

VII Final Considerations

Tardive Dyskinesia: Clinical Presentation and Treatment

I Introduction

II Clinical Features

III Differential Diagnosis

IV Pathophysiology

V Tardive Dyskinesia Treatments

VI Prevention and Treatment of Tardive Dyskinesia in Clinical Practice

VII Conclusion

Epidemiology and Risk Factors for (Tardive) Dyskinesia

I Introduction

II Spontaneous Dyskinesia in Psychiatry

III Discussion

IV Conclusion

Genetics of Tardive Dyskinesia

I Introduction

II Genes Involved in Pharmacokinetics

III Genes Involved in Pharmacodynamics

IV Oxidative-Stress-Related Genes

V Other Genes Reported to be Associated with TD

VI The Genome-Wide Association Approach

VII Future Research: Copy-number Variations and Epigenetics

VIII TD as a Phenotype

IX Conclusion

Animal Models of Tardive Dyskinesia

I Introduction

II Limitations

III Conclusion

Surgery for Tardive Dyskinesia

I Introduction

II Lesioning Surgery

III Deep Brain Stimulation

IV Conclusion

Huntington’s Disease: Clinical Presentation and Treatment

I Clinical Presentation and Genetics

II The Clinical Phenotype and its Management

III The Atypical Phenotype, including Juvenile Huntington’s Disease

IV Advanced Disease and End of Life Issues

V Looking to the Future: Research into New Treatments for Huntington’s Disease

VI Conclusions

Genetics and Neuropathology of Huntington’s Disease

I Introduction

II The HD Gene

III Normal CAG Repeat Length

IV CAG Repeat Length and Disease Onset and Progression

V CAG Repeat Instability

VI Genetic Modifiers of CAG Repeat Instability

VII Genetic Modifiers of HD Age-of-Onset

VIII HD: A True Dominant Gain-of-Function Disorder?

IX Expression of Huntingtin in Normal and HD Human brain

X HD Brain Pathology and the Vonsattel Grading System

XI Basal Ganglia Pathology in HD

XII Other Telencephalic Areas in HD

XIII Brainstem Areas in HD

XIV HD and Neurogenesis

XV Neuroinflammatory Neuropathology in HD

Pathogenic Mechanisms in Huntington’s Disease

I Introduction

II The HTT Gene Product

III The Mutant Htt Protein and its Downstream Effects

IV Conclusions

Experimental Models of HD and Reflection on Therapeutic Strategies

I Introduction

II Mouse Models of HD

III Methodological Considerations for Mouse Therapeutic Trials

IV Existing Clinical Management

V Mechanisms of Cell Death and Potential Therapeutic Targets in HD

VI Conclusion

Cell-Based Treatments for Huntington’s Disease

I Introduction

II Present Status

III Future Developments

IV Conclusion

Clinical Phenomenology of Dystonia

I Historical Review

II Definition and Classification

III Clinical Features in Different Subtypes of Focal and Segmental Dystonia

IV Neuropsychiatric Features of Dystonia

V Conclusions

Genetics and Pharmacological Treatment of Dystonia

I Primary Torsion Dystonia

II Dystonia-Plus Syndromes without Brain Degeneration

III Dystonia as a Feature of Degenerative Genetic Syndromes

IV Treatment of Dystonia

Experimental Models of Dystonia

I Introduction

II Models of Genetic Engineering

III Spontaneous Mutants

IV Pharmacological and Neural Lesion Models

V Conclusions

Surgical Treatment of Dystonia

I Background

II Classification

III Medical Treatment of Dystonia

IV Surgical Treatment of Dystonia

V Deep Brain Stimulation (DBS) for Dystonia

VI DBS for Dystonia – Clinical Overview

VII Conclusion

Uncited

Index

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