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Library of Congress Cataloging-in-Publication Data

Names: Schapira, Anthony H. V. (Anthony Henry Vernon), editor. | Wszolek, Zbigniew K., editor. | Dawson, Ted Murray editor. | Wood, N. W. (Nicholas W.), editor.
Title: Neurodegeneration / edited by Anthony Schapira, Zbigniew Wszolek, Ted Dawson, Nicholas Wood.
Other titles: Neurodegeneration (Schapira)
Description: Oxford, UK; Hoboken, NJ: John Wiley & Sons Ltd, 2017. | Includes bibliographical references and index.
Identifiers: LCCN 2016041714 (print) | LCCN 2016043003 (ebook) | ISBN 9780470672686 (cloth : alk. paper) | ISBN 9781118661925 (Adobe PDF) | ISBN 9781118661918 (ePub)
Subjects: | MESH: Neurodegenerative Diseases–physiopathology
Classification: LCC RC355 (print) | LCC RC355 (ebook) | NLM WL 358.5 | DDC 616.8—dc23
LC record available at https://lccn.loc.gov/2016041714

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CONTENTS

List of Contributors

Preface

Dedication

Chapter 1 Pathology of Brain Aging

Introduction
Brain pathologies in aging
Genetics and the environment: risk factors and potential therapeutic targets
Summary
References

Chapter 2 Protein Aggregation and Neurodegeneration: Tauopathies and Synucleinopathies

Introduction
Amyloids
Tauopathies
Synucleinopathies
Experimental transmission of tauopathy and synucleinopathy
Additional therapeutic implications
Acknowledgments
References

Chapter 3 Prion Degeneration

Clinical definition and epidemiology
Spectrum of clinical phenotype
Pathology/pathophysiology of prion diseases
Clinical prodrome and biomarkers
Examination and investigations (including imaging)
Diagnosis and prognosis
Treatment options (including comorbid conditions)
Future developments
References

Chapter 4 Excitotoxicity

Clinical definition and epidemiology
Spectrum of clinical phenotype
Pathology/pathophysiology specific to the disease
Diagnostic considerations in excitotoxicity
Treatment approaches
Future developments
Acknowledgment
References

Chapter 5 Etiology and Pathogenesis of Parkinson Disease

Introduction
Experimental models for studying PD
Genetics and the development of PD
Mitochondria
Neuroinflammation, immunity, and the widespread Lewy body pathology in PD
Prion-like mechanism of α-synuclein spread
Environmental risk factors
Recurrent themes
References

Chapter 6 Parkinson Disease: Treatment Options – Surgical Therapy

Introduction
Standard surgical targets for Parkinson disease: the pallidum and subthalamic nucleus
Patient selection
Emerging targets for Parkinson disease: the pedunculopontine area
Experimental surgery for Parkinson disease: some potential future directions
Summary
References

Chapter 7 Multiple System Atrophy: Clinical, Genetics, and Neuropathology

History and definition
Spectrum of clinical phenotype
Pathology/pathophysiology specific to the disease
Investigations
Diagnosis and prognosis
Treatment options
Future and experimental developments
Conclusions
References

Chapter 8 Progressive Supranuclear Palsy

Introduction
Clinical definition and epidemiology
Spectrum of the clinical phenotype
Pathology
Clinical prodrome and biomarkers
Examination and investigations
Diagnosis and prognosis
Treatments
Future developments
Conclusions
Acknowledgement
References

Chapter 9 Dementia with Lewy Bodies

Clinical definition
Epidemiology
Spectrum of clinical phenotypes of DLB
Pathology and pathophysiology
Biomarkers
Diagnosis
Prognosis
Treatment options and management
Future development
References

Chapter 10 Corticobasal Degeneration

Clinical definition and epidemiology
Spectrum of clinical phenotype
Pathology/pathophysiology of CBD
Biomarkers
Examination and investigations
Diagnosis and prognosis
Treatment
Future developments
References

Chapter 11 Alzheimer’s Disease

Clinical definition
Epidemiology
AD Criteria
Atypical phenotype
Pathophysiology of AD
Neuropathology of AD
Genetics of AD
Environment
Diagnosis
Management
The future in Alzheimer’s disease
References

Chapter 12 Frontotemporal Dementia

Introduction
Clinical definition and epidemiology
Spectrum of clinical phenotype
Pathology /pathophysiology
Clinical prodrome and biomarkers
Morphologic and functional imaging
Diagnosis and prognosis
Treatment options
Future developments
References

Chapter 13 Prion Diseases and Other Rapidly Progressive Dementias

Prion diseases
Non-prion, rapidly progressive dementias
References

Chapter 14 Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis

Clinical definition and epidemiology
Spectrum of the clinical phenotype
Pathophysiology
Examination and investigations
Diagnosis and prognosis
Treatment
References

Chapter 15 Hereditary Spastic Paraplegia

Introduction
Neuropathology
Conclusions
Acknowledgments
References

Chapter 16 Spinal Muscular Atrophy

Introduction
Genetic basis of disease
Epidemiology
Clinical characteristics
Pathology
Diagnosis
Medical care and treatment
Disease pathophysiology
Animal models
Disease mechanisms
Therapeutics development
Concluding remarks
References

Chapter 17 Spinal and Bulbar Muscular Atrophy (Kennedy Disease)

Clinical definition and epidemiology
Clinical phenotype
Pathology and pathogenesis
Examination and laboratory investigations
Diagnosis and prognosis
Treatment
Future developments
References

Chapter 18 Optic Neuropathies

Introduction
Leber’s hereditary optic neuropathy (LHON)
Dominant optic atrophy
Optic neuropathy and hereditary neuropathy
Optic neuropathy and other central nervous system degenerative disorders
References

Chapter 19 Peripheral Nerve Neuropathies Including Charcot–Marie–Tooth Disease

Clinical definition, epidemiology, and causes of peripheral neuropathies
Spectrum of peripheral neuropathy phenotypes
Molecular genetics of inherited peripheral neuropathies
Chronic inflammatory demyelinating polyradiculoneuropathy and Guillain–Barré syndrome: acquired inflammatory demyelinating neuropathies
Identification of biomarkers in peripheral neuropathies
Investigation of peripheral neuropathies
Diagnosis of peripheral neuropathies
Treatment options in peripheral neuropathies
Future developments in peripheral neuropathies
References

Chapter 20 Axonal Loss and Neurodegeneration in Multiple Sclerosis

Clinical definition and epidemiology
Spectrum of clinical phenotype
Genetic and environmental influences in MS
Neurodegeneration in MS
Diagnosis and disease progression
Treatment options
Future developments
Acknowledgments
References

Chapter 21 Huntington’s Disease and Other Choreas

Huntington’s disease
Other degenerative choreas
Conclusions and the future
References

Chapter 22 Spinocerebellar Ataxias

Clinical definition and epidemiology
Spectrum of clinical and pathological phenotypes
Diagnostic examination and investigations
SCA genetics and pathogenesis
Approaches to therapy
References

Chapter 23 Ataxia Telangiectasia

Clinical definition and epidemiology
Spectrum of clinical phenotype and genetics
Pathology/pathophysiology specific to the disease
Clinical biomarkers
Examination and investigations (including imaging)
Diagnosis and prognosis
Treatment options
References

Chapter 24 Niemann–Pick Disease

Introduction
Primary acid sphingomyelinase deficiencies– Niemann–Pick diseases type A and B
Endosomal/lysosomal trafficking deficiency – Niemann–Pick disease, type C
References

Chapter 25 X-linked Adrenoleukodystrophy

Clinical definition and epidemiology
Spectrum of clinical phenotype
Pathology/pathophysiology specific to the disease
Examination, investigations (including imaging)
Diagnosis and prognosis
Treatment options (including comorbid conditions)
Future developments
References

Chapter 26 Neurodegeneration with Brain Iron Accumulation, Wilson Disease, and Manganism

Neurodegenerative disorders with brain iron accumulation (NBIA)
Manganism
Wilson disease
References

Index

EULA

List of Tables

CHAPTER 1

Table 1.1 Subtypes and locations of Alzheimer’s disease (AD) neuropathologic changes in aging and in different stages of AD.

CHAPTER 3

Table 3.1 Phenotypes of current human prion diseases.
Table 3.2 Mutations and polymorphisms of PRNP
Table 3.3 Diagnostic criteria of prion disease.

CHAPTER 4

Table 4.1 Modification of expression of proteins involved in excitoprotective cellular stress adaptation, as affected by energy restriction, exercise, and cognitive stimulation.

CHAPTER 6

Table 6.1 Effects of unilateral PPN DBS on UPDRS part II subscores (falling and freezing) after 3 and 12 months of stimulation.

CHAPTER 7

Table 7.1 Diagnostic criteria of MSA.
Table 7.2 Features supporting (red flags) and not supporting a diagnosis of MSA.
Table 7.3 Clinicopathological correlations of MSA.
Table 7.4 Structural and functional imaging in MSA.
Table 7.5 Symptomatic management of MSA. Adapted from Wenning & Stefanova 2009 [44] and Flabeau et al. 2010 [135].

CHAPTER 9

Table 9.1 Criteria for the clinical diagnosis of dementia with Lewy bodies (DLB).
Table 9.2 The neuropathological diagnosis of DLB. The table depicts the neuropathological certainty of the DLB diagnosis.
Table 9.3 Symptoms in DLB, their pharmacological management, and complications.

CHAPTER 11

Table 11.1 Stages of preclinical criteria.
Table 11.2 MCI criteria incorporating biomarkers.
Table 11.3 AD dementia criteria incorporating biomarkers.
Table 11.4 Differential diagnosis of dementia.
Table 11.5 Commonly used drugs that may cause memory loss.
Table 11.6 FDA-approved medications for AD.

CHAPTER 12

Table 12.1 Summary of behavioral variant frontotemporal dementia and primary progressive aphasia.
Table 12.2 Clinical, imaging, and pathological characteristics of major forms of monogenic FTD.
Table 12.3 Simplified pathologic classification of frontotemporal lobar degeneration.

CHAPTER 13

Table 13.1 Codon 129 status in CJD and controls.
Table 13.2 CSF 14-3-3 abnormality by prion disease state.
Table 13.3 Causes of rapidly progressive dementia (RPD) in a cohort of patients referred for evaluation of possible prion disease.
Table 13.4 Typical results of diagnostic tests in common conditions that cause RPD.

CHAPTER 14

Table 14.1 Nomenclature of idiopathic adult motor neuron disease [6, 126, 329].
Table 14.2 El Escorial criteria for the diagnosis of ALS, original and revised criteria [13, 14].
Table 14.3 Epidemiology of ALS [18–20, 28, 330].
Table 14.4 Genetic forms of ALS.
Table 14.5 Biomarkers for the evaluation of upper and lower motor neuron involvement and cognitive dysfunction in ALS and PLS.
Table 14.6 El Escorial guidelines for electrophysiological testing in the diagnosis of ALS.
Table 14.7 ALS Functional Rating Scale – revised version (ALSFRS-R).

CHAPTER 15

Table 15.1 Identified SPG gene products, grouped functionally.

CHAPTER 16

Table 16.1 SMA disease classification.

CHAPTER 17

Table 17.1A Clinical features of SBMA cases observed personally.
Table 17.1B Laboratory features of SBMA cases observed personally.

CHAPTER 19

Table 19.1 Classification of CMT, HNPP, and HNA and associated protein functions. Adapted from [8, 30].
Table 19.2 Classification of dHMNs and associated protein functions.
Table 19.3 Classification of HSAN and associated protein functions.

CHAPTER 21

Table 21.1 Clinical features of Huntington’s disease.
Table 21.2 Prevalence of neuropsychiatric symptomatology in Huntington’s disease (adapted from van Duijn et al. 2007 [40]).
Table 21.3 Clinical staging of Huntington’s disease, the Total Functional Capacity rating scale (adapted with permission from [14]).
Table 21.4 Drug management of movement disorder
Table 21.5 Drug management of neuropsychiatric disease.
Table 21.6 Non-drug based management of Huntington’s disease.
Table 21.7 Relationship of CAG size to phenotype.
Table 21.8 Risk for a healthy individual at 50% prior risk of Huntington’s disease carrying the HD gene at different ages.
Table 21.9 Mouse models of Huntington’s disease.
Table 21.10 Completed clinical trials in Huntington’s disease.
Table 21.11 Principal causes of Huntington’s disease look-alike cases [2].

CHAPTER 22

Table 22.1 Aid to differential diagnosis by clinical presentation in SCA.
Table 22.2 Spinocerebellar ataxias (the most common forms are in bold type).
Table 22.3 Manipulations of SCA transgenic models to evaluate pathogenesis and potential therapy.

CHAPTER 23

Table 23.1 Types of ataxia telangiectasia caused by ATM mutation and identified mutations associated with them.

CHAPTER 25

Table 25.1 Clinical phenotypes in males with X-ALD [4, 5].

Neurodegeneration

Anthony Schapira, MD, DSc, FRCP, FMedSci

Zbigniew Wszolek, MD

Ted M. Dawson, MD, PhD

Nicholas Wood, FRCP, PhD, FMedSci