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Parkinson's Disease

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Contents

Contributors

Preface

Chapter One: Hallmarks of Clinical Aspects of Parkinson´s Disease Through Centuries

1. Introduction

1.1. Before James Parkinson

1.2. The 20th Century

2. Introduction of Levodopa and New Motor Features

2.1. The Conundrum of Atypical Parkinsonism: A Diagnostic Riddle

3. Concluding Remarks

References

Chapter Two: The Motor Syndrome of Parkinson´s Disease

1. Introduction

2. Motor Symptoms of PD

2.1. Bradykinesia

2.2. Tremor

2.3. Rigidity

2.4. Gait and Axial Disturbances

2.5. Motor Complications of PD

3. Summary

References

Chapter Three: The Nonmotor Features of Parkinson´s Disease

1. Impact of Nonmotor Symptoms on Quality of Life in Parkinson´s Disease

2. PD Is a Nonmotor and Motor Disorder: Aspects of Pathophysiology

3. Nonmotor Symptoms in PD: The Clinical Aspects

4. Nonmotor Symptoms and Gender Association

5. Classification of Nonmotor Symptoms of PD

6. Nonmotor Symptoms Measurement in Clinics

7. Nonmotor Fluctuations

8. Biomarkers

9. Treatment of Nonmotor Symptoms

10. Nonmotor Subtyping of Parkinsons

11. Multidisciplinary Care and Nonmotor Symptoms of PD

12. Drug-Induced Nonmotor Symptoms of PD

13. Conclusions

References

Chapter Four: The New Diagnostic Criteria for Parkinson´s Disease

1. Parkinson´s Disease Diagnosis: How Accurate Are We?

2. Prior Diagnostic Criteria

3. Rationale for New Criteria

4. Underlying Assumptions of MDS Criteria: Definition of PD

5. Clinical Diagnostic Criteria: Overall Design

5.1. Supportive Criteria

5.1.1. Clear and Dramatic Response to Dopamine Therapy

5.1.2. Levodopa-Induced Dyskinesia

5.1.3. Rest Tremor of a Limb

5.1.4. Diagnostic Testing

6. Negative Criteria

7. Absolute Exclusions

8. Red Flags

9. The MDS Prodromal Criteria

10. Conclusions

References

Chapter Five: Advances in the Clinical Differential Diagnosis of Parkinson´s Disease

1. Introduction

2. Phenotypic Variability and Clinical Heterogeneity of Parkinson´s Disease

2.1. Age at Onset

2.2. Motor Phenotypes

2.3. Response to Dopaminergic Medication

2.4. Nonmotor Phenotypes

2.5. Genetic Parkinson´s Disease

3. Differential Diagnosis of Parkinson´s Disease

3.1. Tremor Syndromes

3.2. Atypical Parkinsonism

3.2.1. Multiple System Atrophy

3.2.2. Progressive Supranuclear Palsy

3.2.3. Corticobasal Degeneration

3.3. Secondary Parkinsonism

4. Other Rarer Differential Diagnoses

5. Summary

References

Chapter Six: Clinical Assessments in Parkinson´s Disease: Scales and Monitoring

1. Introduction

2. Measurement: Concepts and Need

3. PD as an Object for Measurement

3.1. Subjective Measures for PD: Rating Scales and Questionnaires

3.2. Global Evaluations

3.2.1. Hoehn and Yahr Staging Scale (HY)

3.2.2. Clinical Impression of Severity Index

3.3. Comprehensive Scales

3.3.1. Unified Parkinson´s Disease Rating Scale

3.3.2. Movement Disorders Society Sponsored Revision of the Unified Parkinson´s Disease Rating Scale

3.4. Scales for Motor and Functional Assessment

3.4.1. Scales for Outcomes in Parkinson´s Disease-Motor (SCOPA-Motor)

3.4.2. Schwab & England Activities of Daily Living Scale

3.4.3. Self-Assessment Parkinson´s Disease Disabilities Scale

3.4.4. Postural Instability and Gait Difficulty Score

3.4.5. Freezing of Gait Questionnaire

3.5. Comprehensive NMS Assessments

3.5.1. Nonmotor Symptoms Questionnaire

3.5.2. Nonmotor Symptoms Scale

3.6. Scales for Motor Complications

3.6.1. Unified Dyskinesia Rating Scale

3.6.2. The Wearing-Off Questionnaires

3.7. Other Scales and Questionnaires

4. Objective Measures for PD: The Rationales

4.1. The Rationales

4.2. Objective Measures of Cardinal Features in PD

4.2.1. Parkinsonian Tremor

4.2.2. Bradykinesia

4.2.3. Gait Dysfunction and Postural Instability

4.3. Objective Measures for Nonmotor and Associated Features of PD

4.3.1. Sleep Disorders

4.3.2. Autonomic Dysfunction

4.3.3. Fatigue

4.3.4. Cognitive Function

4.4. Ambulatory Monitoring in PD: Clinical Implications

4.4.1. Ambulatory Assessment of Motor and Nonmotor Fluctuations

4.4.2. Ambulatory Activity Assessment

4.4.3. Home Monitoring

5. Conclusion

Acknowledgments

References

Chapter Seven: Biomarkers of Parkinson´s Disease: An Introduction

1. Introduction

2. The Types of Biomarkers

3. Neuroimaging

4. Neuroinflammation

5. The Future

Acknowledgments

References

Chapter Eight: Genetics of Parkinson´s Disease: Genotype-Phenotype Correlations

1. Introduction

2. Monogenic Forms With a Picture Largely Restricted to Parkinsonism

2.1. Autosomal Dominant Forms

2.1.1. SNCA

2.1.2. LRRK2

2.1.3. GBA

2.1.4. VPS35

2.2. Autosomal Recessive Forms

2.2.1. Parkin

2.2.2. PINK1

2.2.3. DJ-1

2.2.4. VPS13C

3. Monogenic Forms With Additional Clinical Features

4. Involvement of Genes Linked to the Dopamine Biosynthesis Pathway

5. GWAS and Lowly Simple Case Control Association Studies

6. Conclusion

References

Chapter Nine: Imaging in Parkinson´s Disease

1. Idiopathic Parkinson´s Disease: Introduction

1.1. Molecular Imaging

1.1.1. Dopaminergic System

1.1.2. Serotonergic System

1.1.3. Cholinergic System

1.1.4. Neuroinflammation

1.1.5. Misfolded Proteins

1.1.6. Other Systems

1.1.6.1. Glutamate

1.1.6.2. Cannabinoid

1.1.6.3. Opioid

1.1.6.4. Adenosine

1.1.6.5. Phosphodiesterases

1.1.6.6. Sigma 1 Receptors

1.2. Magnetic Resonance Imaging

1.2.1. Volumetric MRI

1.2.2. Iron Deposition and Neuromelanin

1.2.3. Structural Connectivity

1.2.4. Functional Connectivity

1.2.5. Task-Related Functional MRI

2. Conclusions and Future Directions

Acknowledgments

References

Chapter Ten: Cerebrospinal Fluid Biomarkers of Cognitive Decline in Parkinson´s Disease

1. Introduction

2. β-Amyloid 1-42

2.1. Cross-Sectional Studies

2.2. Longitudinal Studies

3. T-Tau and P-Tau

4. Total α-Syn and Oligomeric α-Syn

5. Other CSF Biomarkers

6. Lumbar Puncture Safety

7. Conclusion

References

Chapter Eleven: Hallmarks of Treatment Aspects: Parkinson´s Disease Throughout Centuries Including l-Dopa

1. Introduction

2. Anticholinergics

2.1. Treatment of PD With Natural Antimuscarinic Alkaloids

2.2. Introduction of Synthetic Anticholinergics and Antihistaminics

2.3. The Mechanism of Action of the Anticholinergics

3. Amantadine

3.1. Amantadine as an Antiviral Agent

3.2. Amantadine as a Treatment for PD

3.3. Effect of Amantadine on l-Dopa-Induced Dyskinesia

4. Apomorphine

4.1. The Birth of Apomorphine and Its Use as an Antiparkinsonian Agent

4.2. Apomorphine as a Treatment for Motor Complications

4.3. Novel Formulations of Apomorphine

5. L-Dopa

5.1. Discovery of Striatal Dopamine Deficiency in Patients With PD

5.2. Use of L-Dopa in Patients With Parkinsonism

5.3. Complications of Long-Term L-Dopa Therapy and Strategies to Enhance the Effectiveness and Reduce the Adverse Effects ...

5.3.1. DDI

5.3.2. COMT Inhibitor

5.3.3. MAO-B Inhibitor

5.3.4. Sustained Release Form of L-Dopa

5.3.5. Soluble Form of L-Dopa

5.3.6. Duodenal Infusion

5.4. Novel Formulations of L-Dopa

5.4.1. Dual-Release Formulation

5.4.2. Inhalation Powder Formulation

5.4.3. Skin Patch

6. Dopamine Agonists

6.1. Ergot-Derived Dopamine Agonists

6.2. Adverse Effects of Ergot-Derived Dopamine Agonists

6.3. Nonergot-Derived Dopamine Agonists

6.4. Adverse Effects of nonergot-Derived Dopamine Agonists

7. CDS Strategy and Then Transition to CDD Strategy

References

Chapter Twelve: Treatment Strategies in Early Parkinson´s Disease

1. Introduction

2. Pharmacological Therapy

2.1. Levodopa

2.2. Dopamine Agonists

2.3. Monoamine Oxidase-B Enzyme Inhibitors

2.4. COMT Enzyme Inhibitors

2.5. Amantadine

2.6. Anticholinergics

2.7. Studies on Possible Neuroprotective Agents

3. Nonpharmacological Therapies

4. Summary of the Guidelines Available

References

Chapter Thirteen: Treatment of Nonmotor Symptoms in Parkinson´s Disease

1. Introduction

2. Sleep Disturbances

3. Cognitive Impairment

4. Depressive Symptoms and Anxiety

5. Orthostatic Hypotension

6. Urinary Dysfunction

7. Gastrointestinal Dysfunction

8. Nutrition and Parkinson´s disease

9. Conclusion: Nonmotor Subtype-Specific Treatment in Parkinson´s disease?

References

Chapter Fourteen: Treatment of Older Parkinson´s Disease

1. Introduction

2. Treatment Strategies for Older PD Patients

2.1. Management of Motor Symptoms

2.1.1. Levodopa and Other Dopaminergic Agents

2.1.2. Continuous Drug Delivery Systems and Deep Brain Stimulation

2.2. Management of NMSs in Old Patients

2.2.1. Cognitive Impairment

2.2.2. Psychosis in Older Patients With PD

2.2.3. Affective Disorders

2.2.4. Bladder and Bowel Problems

2.2.5. Bulbar, Autonomic, and Sleep Disturbances

2.2.6. Adherence to Treatment: A Big Issue in Elderly Patients

2.3. Emergencies, Hospital Admissions, and Perioperative Issues in Older Patients With PD

3. Conclusion

References

Chapter Fifteen: New Symptomatic Treatments for the Management of Motor and Nonmotor Symptoms of Parkinson´s Disease

1. Introduction

2. New Dopaminergic Approaches to the Treatment of Motor Symptoms in PD

2.1. New Formulations and Delivery Systems for L-Dopa

2.1.1. Duodopa-Percutaneous Delivery

2.1.2. IPX-066/Rytary-Oral Extended Release L-Dopa/Carbidopa

2.1.3. ND0612—Liquid L-Dopa/Carbidopa

2.1.4. Oral L-Dopa-Ongoing Trials

2.2. Enzyme Inhibitors

2.2.1. Opicapone (Ongentys)

2.2.2. Xadago/Safinamide

2.3. Dopamine Agonists

2.3.1. D1-Agonists: Dihydrexidine, A-68930, A77636, Rotigotine, CVT-301

2.3.2. CVT-301

2.3.3. Apomorphine-Based Therapies

2.3.3.1. Sublingual Apomorphine: APL-130277

2.3.3.2. Inhaled Apomorphine: VR040

2.3.3.3. ND0701 (Neuroderm, Israel)

2.3.3.4. Lipophilic Prodrugs of Apomorphine: DLA, DPA, FKK01PD

2.3.3.5. L-Dopa Prodrug: XP21279

3. New Nondopaminergic Approaches to the Treatment of Motor Symptoms in PD

3.1. Treatment of Dyskinesia

3.1.1. Amantadine HCl (ADS-5102)

3.1.2. ASX48621-201 (Dipraglurant-IR)

3.1.3. Amantadine and Topiramate

3.1.4. AVP-923

3.2. Treatment of Freezing of Gait

3.2.1. Methylphenidate (Ritaline)

3.3. Treatment of Motor Fluctuations

3.4. Gene Therapy

3.4.1. AAV2-GAD

3.4.2. AAV2-NRTN

3.4.3. AAV2-hAADC

3.5. Physical Amendment of Readily Existing Pharmacological Compounds

3.5.1. Accordion Pill

3.5.2. ND0611/0612

4. New Therapeutic Targets for the Treatment of Nonmotor Symptoms in PD

4.1. Cognitive Decline

4.1.1. Atomoxetine

4.1.2. Droxidopa

4.1.3. Piribedil

4.1.4. SYN-120

4.1.5. Pimavanserin

4.2. Swallowing Problems and Sialorrhea

4.2.1. Tropicamide

4.3. Gastrointestinal Dysfunction

4.3.1. Camicinal

4.3.2. Relamorelin

4.4. Impulse Control Disorder

4.4.1. Naltrexone

4.5. Psychosis

4.5.1. Pimavanserin

References

Chapter Sixteen: Device-Aided Treatment Strategies in Advanced Parkinson´s Disease

1. Introduction

2. Deep Brain Stimulation

2.1. DBS: Historical Review

2.2. Mechanism of Action of DBS

2.3. When Is Surgery Appropriate?

2.4. Outcomes/Proof of Efficacy

2.5. Targets for DBS

2.6. Pedunculopontine Nucleus Stimulation

2.7. The New Phenotype of Advanced PD After DBS

2.8. Complications of DBS

2.9. Surgery-Related Complications

2.10. Hardware-Related Complications

2.11. Stimulation-Related Complications

3. Levodopa-Carbidopa Intestinal Gel

3.1. The Basics

3.2. The Effect on Quality of Life

3.3. The Effect on Motor Symptoms

3.4. The Effect on Nonmotor Symptoms

3.5. Safety

3.6. The Indications, the Contraindications, and the ``Ideal´´ Patient

4. Continuous Subcutaneous Apomorphine Infusion

4.1. The Basics

4.2. The Effect on Quality of Life

4.3. The Effect on Motor Symptoms

4.4. The Effect on Nonmotor Symptoms

4.5. Safety

4.6. The Indications, the Contraindications, and the ``Ideal´´ Patient

5. Conclusions

References

Chapter Seventeen: Palliative Care for Patients and Families With Parkinson´s Disease

1. Parkinson´s Disease

1.1. Epidemiology and Diagnosis

1.2. Clinical Features

1.3. PD Clinical States and Progression

2. Traditional Therapeutic Approaches

2.1. Pharmacological Interventions

2.2. Nonpharmacological Interventions

3. Gaps in Therapeutic Approaches

3.1. Burden of the Disease

3.2. Access to Information

3.3. Support to Family

3.4. Experience of Healthcare Services

4. Concept of Palliative Care

5. Clinical Trials in Palliative Care

6. Misconceptions Associated With Palliative Care

6.1. Palliative Care vs Terminal/Hospice Care

6.2. Holistic Approach vs Symptomatic Approach

6.3. Palliative Care vs Oncology Care

7. Concept of Palliative Care in Neurodegenerative Diseases

8. Palliative Care as Part of Therapeutic Interventions in PD

8.1. Concept

8.2. Models of Palliative Care Delivery in PD

8.3. Time to Referral to Specialist Palliative Care Services

8.4. Palliative Care Multidisciplinary Team in PD Management

8.5. New Initiatives

9. Addressing Symptom Burden in Advanced-PD: Outcomes and Measures

10. Implication for Clinical Practice and for Research

11. Conclusion

References

Chapter Eighteen: Multidisciplinary Care in Parkinson´s Disease

1. Introduction

2. Current Approach to Parkinson´s Disease Care

2.1. Parkinson´s Disease Nurse Specialist

2.2. Speech and Language Therapists

2.3. Physiotherapy

2.4. Occupational Therapy

2.5. Palliative Care

3. Limitations and Barriers

4. Future of MDTs in Parkinson´s Disease

References

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