Paraneoplastic Neurologic Disorders

1st Edition, Volume 200 - March 15, 2024
Imprint: Elsevier
Editors: Bruno Giometto, Sean J. Pittock
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 2 3 9 1 2 - 4
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 4 2 1 7 - 9

Paraneoplastic Neurological Disorders, Volume 200 covers new, recent descriptions of autoantibodies against neuronal cell surface antigens (only partly associated with paraneopl… Read more

Purchase options

BLOOM INTO SPRING SAVINGS

Save up to 25% on books and eBooks!

Shop now

Institutional subscription on ScienceDirect

Request a sales quote

Paraneoplastic Neurological Disorders, Volume 200 covers new, recent descriptions of autoantibodies against neuronal cell surface antigens (only partly associated with paraneoplastic disorders) and the introduction of new immuno-oncological drugs that can contribute to diseases that are pathogenetically indistinguishable from paraneoplastic syndromes. Besides investigating the pathogenetic mechanisms of these disorders, this book also explores what the introduction of new drugs used in immune checkpoint inhibitor cancer therapy are teaching us in terms of immunopathogenesis. Following sections present individual syndromes (phenotypical clinical manifestations) of the CNS, PNS, NMJ, and muscle.

Finally, the book investigates the role of antibody markers that differentiate by cytoplasmic, nuclear, and neuronal cell surface reactivities. Side effects of the new immuno-oncological drugs increasingly used in cancer therapy are also covered.

Cover image
Title page
Table of Contents
Series Page
Copyright
Handbook of Clinical Neurology 3rd Series
Foreword
Preface
Contributors
Section I: Introduction and overview
Chapter 1 Introduction and overview of immunopathological mechanisms and future directions
Abstract
Immunopathogenic Mechanism of Paraneoplastic Neurologic Disorders
Cytotoxic T Cell-Mediated PND-Associated with Antibodies Targeting Nuclear or Cytoplasmic Antigens
Antibody-Mediated Paraneoplastic Neurologic Disorders
The Growing Number and Complexity of Neural Antibodies with Cancer Associations
Greatest Unmet Need in Paraneoplastic Neurologic Disorders
The Next Decade: Novel Biologics, Tolerization, and CAR-T Therapies
A Brief Synopsis of Chapters
References
Chapter 2 Changing landscape in the field of paraneoplastic neurology: Personal perspectives over a 35-year career
Abstract
Introduction
From Anecdotal Observations to Clinical-Pathologic Characterization of the Remote Effects of Cancer on the Nervous System
The Immunologic Era of the Paraneoplastic Syndromes
The Identification of Onconeuronal Antigens and the Impact of Specific Antibodies in the Diagnosis of Paraneoplastic Syndromes
The Antitumor Immune Response: From Initial Observations to Immune Checkpoint Inhibitors and Immunogenetics
Antibody-Mediated Paraneoplastic Syndromes of the Peripheral Nervous System
Paraneoplastic Neurologic Syndromes Meet Antibody-Mediated Disorders of the Peripheral Nervous System
The Fast Expansion of Paraneoplastic and Autoimmune Encephalitis Mediated by Antibodies against Neuronal Surface Proteins
Autoimmune Encephalitis: Changing the Landscape of Neurology and Paraneoplastic Syndromes
Autoimmune and Paraneoplastic Encephalitis: The Impact beyond Neurology
Mechanisms of Autoimmune Encephalitis: The First Steps
The Coming of Age of Clinical Trials
References
Chapter 3 Pathogenesis and immunopathology of paraneoplastic disorders
Abstract
Introduction
High-Risk Autoantibodies
HuD (ANNA-1)
Ma1 and Ma2
Yo
Ri
Amphiphisin
CV2/CRMP5
KLHL11
Tr/DNER
SOX1
PCA2 (MAP1B)
Intermediate-Risk Autoantibodies
NMDAR
AMPAR
GABABR
mGluR5
P/Q-Type VGCC
CASPR2
Lower-Risk Antibodies
References
Section II: Paraneoplastic neurologic syndromes
Chapter 4 Epidemiology of paraneoplastic neurologic syndromes
Abstract
Introduction
Epidemiology by Organ System
Gastrointestinal
Epidemiology by Autoantibody Target
Future Directions
References
Chapter 5 Clinical approach to diagnosis of paraneoplastic neurologic syndromes
Abstract
Introduction
Clinical Approach to Diagnosis of Classical (High-Risk for Cancer) Neurologic Syndromes
Clinical Approach to Diagnosis of Intermediate-Risk for Cancer Neurologic Syndromes
Antibody Testing: Pitfalls and Limitations
Recommendations for Oncologic Screening
Author disclosures
References
Chapter 6 Overview of treatment strategies in paraneoplastic neurological syndromes
Abstract
Introduction
Tumor Treatment
Immunotherapy
Syndrome-Specific Considerations
High-Risk Clinical Syndromes
Intermediate-Risk Clinical Syndromes
References
Chapter 7 Evolution of methods to detect paraneoplastic antibodies
Abstract
Introduction
Initial Discovery
Discovery of the Antigen
Clinical Testing
Pathogenic Antibodies in the CNS
New Classification, New Targets, and Clinical Utility
Conclusions
References
Chapter 8 Paraneoplastic encephalitis
Abstract
Paraneoplastic Encephalitis
Paraneoplastic Encephalomyelitis
Limbic Encephalitis
Morvan's Syndrome
Anti-NMDA Receptor Encephalitis
Other Autoimmune Encephalitis With Possible Paraneoplastic Presentation
Antibody-Negative Autoimmune Encephalitis
Conclusion
References
Chapter 9 Autoimmune and paraneoplastic seizures
Abstract
Introduction
Pathophysiology
An Autoantibody-Driven Approach to Clinical and Investigation Features
Scoring Systems to Detect Patients With Autoimmune Seizures
Antibody Testing and Other Seizure-Related Autoimmune Syndromes
Therapies
Conclusion/Future
References
Chapter 10 Paraneoplastic cerebellar and brainstem disorders
Abstract
Introduction
Clinical Syndromes
Antibody Associations
Pathology
Pathogenesis
Differential Diagnosis
Diagnostic Evaluation
Treatment and Prognosis
Conclusion
Conflict of Interest Statement
References
Chapter 11 Paraneoplastic/autoimmune myelopathies
Abstract
Introduction
Epidemiology and Genetics
Clinical Features and Onset
Diagnostic Evaluation
Pathophysiology
Therapeutic Approach
Paraneoplastic Myelopathies and Immune Check Inhibitors
Prognosis
Future Directions
References
Chapter 12 Paraneoplastic vision loss
Abstract
Introduction
Paraneoplastic Optic Neuropathy
Collapsin Response-Mediator Protein 5 Immunoglobulin-Associated Optic Neuropathy
Paraneoplastic Autoimmune Retinopathy
Cancer-Associated Retinopathy
Melanoma-Associated Retinopathy
Bilateral Diffuse Uveal Melanocytic Proliferation
Future Directions
References
Chapter 13 Paraneoplastic movement disorders
Abstract
Introduction
Epidemiology
Phenomenology
Differential Diagnosis
Clinical Disorders
Risk Factors
Pathophysiology
Diagnostic Evaluation
Future Therapies
Future Direction
References
Chapter 14 Movement disorders associated with pediatric encephalitis
Abstract
Introduction
Historic Perspectives
Discovery of Autoantibody Biomarkers
Anti-NMDAR Encephalitis
Conclusion
References
Chapter 15 Paraneoplastic neuropathies and peripheral nerve hyperexcitability disorders
Abstract
Introduction
Cancer Diagnosis and Treatment in Paraneoplastic and Hyperexcitable Disorders
Neuroendocrine Paraneoplastic Neuropathy Modifiers
Demyelinating Paraneoplastic Neuropathies
Paraneoplastic Axonal Autoantibody Approach in Testing
Mimickers of Paraneoplastic Neuropathy
Consensus Diagnostic Criteria of Paraneoplastic Neuropathy
Classic Paraneoplastic Neuropathy Phenotypes
Axonal Paraneoplastic Antibodies with Strong Evidence Beyond ANNA-1-IgG
Antibodies with Limited Axonal Paraneoplastic Neuropathy Evidence
Summary
References
Chapter 16 Paraneoplastic autonomic neuropathies and GI dysmotility
Abstract
Introduction
Conditions Associated With Isolated Autonomic Failure
Conditions With Autonomic Failure as Part of Multifocal Neurologic Manifestations
Conclusion
References
Chapter 17 Myasthenia gravis—Pathophysiology, diagnosis, and treatment
Abstract
Introduction
Pathophysiology
Clinical Features
Diagnosis
Therapy
New or Future Treatment Options
References
Chapter 18 Lambert-Eaton myasthenic syndrome
Abstract
Introduction
Epidemiology
Pathophysiology
Tumor Association
Clinical Manifestations
Electrophysiology
Serology
Diagnosis
Treatment
Summary
Panel 1: Diagnosis
Acknowledgments
References
Chapter 19 Paraneoplastic myopathies
Abstract
Introduction
Dermatomyositis
The Antisynthetase Syndrome
Immune-Mediated Necrotizing Myopathy
Inclusion Body Myositis
Other Clinical Factors Associated With Malignancy in Patients With IIM
Cancer Screening Recommendations in Patients With IIM
Myositis in Cancer Patients Undergoing Therapy With Immune Checkpoint Inhibitors
Funding
References
Section III: Paraneoplastic autoantibodies
Chapter 20 Paraneoplastic antibodies targeting intracellular antigens
Abstract
Introduction
High-Risk Intracellular Antibodies (Association With Cancer >70%)
Intermediate-Risk Intracellular Antibodies (30%–70% Associated With Cancer)
Low-Risk Intracellular Antibodies (<30% Associated With Cancer)
Conclusions
References
Chapter 21 Antibodies to neural cell surface and synaptic proteins in paraneoplastic neurologic syndromes
Abstract
Introduction
High-Risk Antibodies Against Extracellular Targets (>70% Association With Cancer)
Intermediate-Risk Antibodies Against Extracellular Targets (30%–70% Association With Cancer)
Lower-Risk Antibodies against Extracellular Targets (<30% Association With Cancer)
Conclusions
Acknowledgments
References
Chapter 22 Optimizing the diagnostic performance of neural antibody testing for paraneoplastic and autoimmune encephalitis in clinical practice
Abstract
Introduction
Terms Relating to Neural Antibody Test Performance: Sensitivity, Specificity, Predictive Value, and Phenotype Expansion vs “Phenotype Creep”
Assays in Clinical Use for Neural Antibody Detection and Their Limitations
Panel-Based Neural Antibody Testing: The Trade-off Between Clinical Sensitivity and Specificity, and the Value of Interpretative Comments
Positive Neural Antibody Results of Uncertain Significance: Avoiding Overinterpretation in Clinical Practice
Conclusions
Acknowledgments
References
Section IV: Paraneoplastic neurological and autoantibody accompaniments of cancer
Chapter 23 Paraneoplastic autoimmune neurologic disorders associated with thymoma
Abstract
Introduction
Myasthenia Gravis
Peripheral Nerve Hyperexcitability
Autoimmune Autonomic Ganglionopathy
Autoimmune Encephalitis
Paraneoplastic Neurologic Disorders Seldom Reported With Thymoma
Concluding Remarks
Acknowledgments
References
Chapter 24 Paraneoplastic neurologic manifestations of neuroendocrine tumors
Abstract
Introduction
Immune-Mediated Paraneoplastic Neurologic Syndromes Associated With NENs
Neurologic Manifestations of Paraneoplastic Endocrine Syndromes (Humoral)
Management and Outcome
Acknowledgment
References
Chapter 25 Paraneoplastic neurologic syndrome associated with gynecologic and breast malignancies
Abstract
Introduction
Yo Paraneoplastic Cerebellar Degeneration
Other PNSs Associated With Gynecologic Malignancies
Conclusion
References
Chapter 26 Hematologic malignancies and hematopoietic stem cell transplantation
Abstract
Introduction
Lymphomas
Central Nervous System PNS in Lymphomas
Paraneoplastic Cerebellar Degeneration
Peripheral Paraneoplastic Neurologic Syndromes in Lymphomas
Other Paraneoplastic Neurologic Syndromes’ Manifestations in Lymphomas
POEMS Syndrome
Multiple Myeloma
Chronic Lymphocytic Leukemia
Myeloproliferative Neoplasms
Treatments of Paraneoplastic Neurologic Syndromes
Hematopoietic Stem-Cell Transplantation
Conclusions
References
Chapter 27 Paraneoplastic neurologic syndrome and autoantibody accompaniments of germ cell tumors
Abstract
Introduction
Pathophysiology
Germ Cell Tumors
Antibodies
Management
Conclusion
References
Section V: Neurological complications of cancer immunotherapy
Chapter 28 Neurologic manifestations of autoimmunity with immune checkpoint inhibitors
Abstract
Introduction
Epidemiology and Overview of nirAEs
General Approach to nirAEs
Overview of the nirAE Clinical Syndromes and Their Diagnosis
Treatment Considerations and Outcomes
Conclusions and Future Directions
References
Index

Bruno Giometto

- Head, Department of Neurology, Azienda Provinciale per I Servizi Sanitari (APSS) and University of Trento - Santa Chiara Hospital - 33100 TRENTO - Coordinator of a European Commission project on Paraneoplastic Neurological Syndromes (Concerted Action –PNS EURONETWORK – Fifth Framework Programme QLG1-CT-2002-01756). - Coordinator of a Specific Support Action of the European Commission on Paraneoplastic Neurological Syndromes (Sixth Framework Programme LSSM-CT-2005-518174). - Former Vice President of the Italian Neurological Society (SIN)

Affiliations and expertise

Head, Department of Neurology, Azienda Provinciale per I Servizi Sanitari (APSS) and University of Trento - Santa Chiara Hospital - 33100 TRENTO

Sean J. Pittock

Sean Pittock, M.D., is a consultant in the Department of Neurology and has a joint appointment in the Department of Laboratory Medicine and Pathology. He holds the academic rank of professor of neurology, Mayo Clinic College of Medicine. He currently serves as director of the Neuroimmunology Laboratory and is the Marilyn A. Park and Moon S. Park, M.D., Director of the Center for Multiple Sclerosis and Autoimmune Neurology. He joined the staff of Mayo Clinic in 2005.

Dr. Pittock’s research and clinical interests include autoimmune neurological disorders, paraneoplastic diseases, neuromyelitis optica and multiple sclerosis. His research focuses on the diagnosis and treatment of multiple sclerosis and autoimmune disorders that target the central and peripheral nervous systems. He founded the Autoimmune Neurology Clinic at Mayo Clinic in 2006, which has allowed the development of a unique translational practice extending the laboratory's serological findings directly from bench to bedside. He has been involved in cutting edge trials of novel immunotherapies to treat NMO and other autoimmune neurologic diseases. He has been invited to give over 100 presentations on his research and has authored over 275 journal articles, abstracts and other written publications.

He is currently the Chair of the Autoimmune Neurology Special Interest Group at the American Neurological Association and directs the educational program on Neuromyelitis Optica at the American Academy of Neurology.

Dr. Pittock serves on numerous professional societies and associations, including the Minnesota Medical Association and American Academy of Neurology, and is a committee member of the American Neurological Association.

Affiliations and expertise

Associate Professor of Neurology and Co-Director, Neuroimmunology Laboratory, Mayo Clinic, Rochester, MN, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health