Table of Contents

Contents

SECTION 1 OVERVIEW

1. HISTORY
DEFINITIONS
CLASSIFICATION
HISTORY
Pathogenesis
EPIDEMIOLOGY
IMPORTANCE

2. CLINICAL FINDINGS, TREATMENT AND PROGNOSIS
INTRODUCTION
CLINICAL APPROACH
The Patient without Known Cancer The Patient with Known Cancer
CLUES TO DIAGNOSIS
Clinical Findings Laboratory Investigation
PATHOLOGY
TREATMENT
Plasma Exchange (Plasmapheresis) Intravenous Immunoglobulin
Rituximab Cyclophosphamide Corticosteroids Human Chorionic Gonadotropin Recommendations
PROGNOSIS

3. PATHOGENESIS
INTRODUCTION
HISTORICAL VIEWS
Toxic Substances Competition for Essential Substrate Bullet Opportunistic Infection Immune Mediated
CURRENT CONCEPTS OF PATHOGENESIS
Unresolved Questions Conclusions
ANIMAL MODELS

SECTION 2 CLINICAL SYNDROMES

4. BRAIN (CEREBRUM)
INTRODUCTION
CEREBRAL CORTEX
WHITE MATTER DEMYELINATION
BLOOD VESSELS (VASCULITIS)
HIPPOCAMPUS/LYMBIC ENCEPHALITIS
Clinical Findings Laboratory Findings Differential Diagnosis Pathology Pathogenesis Treatment
HYPOTHALAMUS
BASAL GANGLIA/THALAMUS
COGNITIVE/BEHAVIORAL ABNORMALITIES
Depression
ENCEPHALOMYELITIS

5. BRAIN (CEREBELLUM AND BRAINSTEM)
INTRODUCTION
BRAINSTEM
Opsoclonus/Myoclonus Brainstem Encephalitis
CEREBELLUM
Clinical Findings Laboratory Findings Pathology Pathophysiology Diagnosis Trea tment Prognosis

6. SPINAL CORD
INTRODUCTION
TRANSVERSE MYELOPATHY
Inflammatory Myelopathy/Myelitis Necrotizing Myelopathy Demyelinating Myelopathy Bullet Neuromyelitis Optica Inflammatory Myelitis
FOCAL MYELOPATHY
Focal Demyelinating Myelopathy Motor Neuron Disease (ALS) Stiff Person Syndrome
MOVEMENT DISORDERS
Myoclonus

7. CRANIAL NERVES
TASTE AND SMELL
VISUAL DISTURBANCES
Carcinoma Associated Retinopathy (CAR) Melanoma Associated Retinopathy (MAR) BDUMP Optic Neuropathy Uveitis/Vitreitis Oculomotor Neuropathy Proptosis
TRIGEMINAL NEUROPATHY
ACOUSTIC/VESTIBULAR NEUROPATHY
OTHER CRANIAL NERVES

8. DORSAL ROOT GANGLIA AND PERIPHERAL NERVES
INTRODUCTION
DORSAL ROOT GANGLION (PSN)
Clinical Features Pathology/Pathogenesis Bullet Diagnosis Treatment
PERIPHERAL NERVE SYNDROMES
Sensory Neuropathy Sensorimotor Neuropathy Guillain-Barré Syndrome Motor Neuropathy Autonomic Neuropathy Bullet Paraproteinemias Leukemia/Lymphoma Vasculitic Neuropathy Focal Neuropathies

9. NEUROMUSCULAR JUNCTION AND MUSCLE
INTRODUCTION
NEUROMUSCULAR JUNCTION
Lambert-Eaton Myasthenic Syndrome Myasthenia Gravis Peripheral Nerve Hyperexcitability
MUSCLE
Inflammatory Myopathies (Myositis)Necrotizing Myopathy Polymyalgia Rheumatica Bullet Myotonia

10. SYSTEMIC SYNDROMES (WITH NEUROLOGIC IMPLICATIONS)
INTRODUCTION
ENDOCRINE SYNDROMES
Cushing Syndrome Hypercalcemia SIADH Hypoglycaemia Hyperthyroidism
RHEUMATOLOGIC SYNDROMES
Arthropathy Fasciitis
AUTOIMMUNE SYNDROMES
Lupus Scleroderma Raynaud's Syndrome Digital Ischemia Still Disease
RHEUMATIC VASCULITIDES
OTHER RHEUMATIC DISORDERS
Complex Regional Pain Syndrome Erythromelalgia
PANNICULITIS
DERMATOLOGIC SYNDROMES
Skin Hair/Nail Disorders Cutaneous Vascular Disorders Oral
BONE DISORDERS
Osteomalacia
SYSTEMIC DISORDERS
Cachexia Fever Vasculopathy Other Organ Disorders

SECTION 3 ANTIBODIES

11. NUCLEAR/NUCLEOLAR ANTIBODIES
ANTI-HU
Antibody Antigen Gene Anti-Hu Syndrome
ANTI-RI
Antibody Antigen Gene Animal Models Clinical Findings Treatment/Prognosis
ANTI-MA (MA-1/MA-2)
Antibodies Antigen Gene Clinical Findings Treatment/Prognosis
ANNA-3
Anti-Zic
SOX (ANTI GLIAL NUCLEAR ANTIBODY)
Antibody Antigen

12. CYTOPLASMIC ANTIBODIES
INTRODUCTION
ANTI-YO
Antibody Antigen/gene Clinical Findings Pathology Pathogenesis Treatment/Prognosis
ANTI TR
Antibody Antigen/Gene Clinical Findings Pathogenesis/Treatment
ANTI CRMP 5 (CV2)
Antibody Antigen/Gene Clinical Findings
ANTI-PCA2
Antibody Antigen/Gene Clinical Findings/Treatment/Prognosis
ANTI KINASE ANTIBODIES
Anti Protein Kinase C Gamma (PKC Gamma) Anti-BR Serine/Theroine Kinase 2 Anti-adenylate Kinase 5
ANTI-UBIQUITIN CONJUGATING ENZYME (UBE2E1)
ANTI-NB

13. SYNAPTIC/CHANNEL ANTIBODIES
INTRODUCTION
INTRACELLULAR SYNAPTIC ANTIBODIES
Anti Amphiphysin Antibodies Anti-Glutamic Acid Decarboxylase Antibodies Anti-Gephrin Antibodies Anti-Synaptotagmin Antibodies Anti-Synaptophysin Antibodies
SYNAPTIC RECEPTOR ANTIBODIES
Anti-GABA Receptor Antibodies Anti-glutamate Receptor Antibodies Other Glutamate Receptor Antibodies Anti-glycine Receptor Antibodies Anti-ganglionic Acetylcholine Receptor Antibodies
ION CHANNEL ANTIBODIES
Anti-P/Q Voltage Gated Calcium Channel Antibodies Anti-voltage Gated Potassium Antibodies (Anti-VGKC)
ANTI-ACETYLCHOLINE RECEPTOR AND OTHER POST SYNAPTIC RECEPTOR ANTIBODIES
Anti-acetylcholine Receptor Anti-muscle Antibodies Anti-neuronal Surface Antibodies

14. ANTI-RETINAL/OPTIC NERVE ANTIBODIES
INTRODUCTION
CARCINOMA ASSOCIATED RETINOPATHY
Anti Recoverin Antibodies Anti-alpha-Enolase Antibodies Anti-alpha-Transducin Antibodies Other Antibodies
ISOLATED CONED DYSFUNCTION
MELANOMA ASSOCIATED RETINOPATHY ANTIBODIES
Interphotoreceptor Retinoid Binding Protein
BILATERAL DIFFUSE MELANOCYTIC PROLIFERATION

SECTION 4 CANCERS

15. THORACIC CANCERS
INTRODUCTION
LUNG CANCER
Small Cell Lung Cancer Carcinoid Non-small Cell Lung Cancer
THYMUS CANCER (THYMOMA)
Paraneoplastic Syndromes Antibodies

16. BREAST/GYNECOLOGIC/TESTICULAR CANCER
INTRODUCTION
GYNECOLOGIC CANCERS
BREAST CANCER
TESTICULAR CANCER

17. HEMATOLOGIC CANCERS/MISCELLANEOUS SOLID TUMORS
INTRODUCTION
LEUKEMIA/LYMPHOMA
Neurologic Paraneoplastic Syndromes Nonneurologic Paraneoplastic Syndromes
MELANOMA
URINARY TRACT CANCERS
Renal Cancers Prostate Cancer Bladder Cancer
GASTROINTESTINAL CANCERS
Colon Cancer Pancreatic/Hepatic Cancer Gastric/Esophageal Cancer
HEAD AND NECK CANCER
SARCOMAS

Index

About the Author

Dr. Darnell studied neurology as Chief Resident with Dr. Fred Plum at The New York Hospital, Cornell, and then, beginning in 1990 and continuing through the present time, with Dr. Jerome Posner at Memorial Sloan-Kettering Cancer Center. Dr. Darnell is currently the Heilbrunn Cancer Professor and Senior Physician at The Rockefeller University and an Investigator with the Howard Hughes Medical Institute, and is an Affiliate Attending Neurologist at Memorial
Sloan-Kettering Cancer Center. He is a past recipient of the Derek Denny-Brown Young Neurological Scholar Award, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, and a member of
the Institute of Medicine.

Dr. Posner did a Neurology residency at the University of Washington under Dr. Fred Plum. Before coming to Memorial Sloan-Kettering cancer Center in 1967, Dr. Posner was attending neurologist at King County Hospital in Seattle Washington and at The New York Hospital, Cornell. Dr. Posner currently holds the George C. Cotzias of Neuro-Oncology at Memorial Sloan-Kettering cancer Center and was recently in only clinical research professor ship from the American Cancer Society. He is an attending
neurologist at Memorial Hospital and a Professor of Neurology and Neuroscience Cornell Medical College. He was the first chair of the department of neurology at Memorial Sloan-Kettering cancer Center.
He is a member of the Institute of medicine.

Reviews

"In a field such as paraneoplastic syndromes that is changing constantly, Drs Posner and Darnell have written a book to stay. Divided in 17 chapters covering historical aspects, individual syndromes, type of immune responses, and specific cancers the authors describe in a detail only possible from physicians with extensive experience, all paraneoplastic neurological and non-neurological syndromes known to date. There are abundant and excellent vignettes,
tables, and pictures. Given that any part of the nervous system and any organ may be affected by these disorders, this is a book that any physician should read and keep on the bookshelf." --Josep Dalmau,
MD, PhD, ICREA Research Professor, IDIBAPS/Hospital Clinic, University of Barcelona, Spain, and adjunct Professor of Neurology, University of Pennsylvania, Philadelphia, PA
"Paraneoplastic Syndromes is another wonderful volume in the distinguished Contemporary Neurology Series by Robert Darnell and Jerry Posner...This book may be read as a single unit, or it may be used as a complete resource for selective referencing. The illustrations and figures are of high quality and descriptive. This book will be useful for students, residents, and the experienced practitioner who is looking for a definitive book on
this topic. It is written to help the clinician with understanding the pathophysiology and diagnosis of this baffling disease syndrome. Moreover, basic scientists and neuroanatomists will appreciate the care that has
been placed into the analysis of the anatomical pathophysiology of this disease." -- Thomas Chen, MD, PhD, Director, USC Neuro-oncology, Departments of Neurosurgery and Pathology, Los Angeles, CA
"Dr. Posner and Dr. Darnell's Paraneoplastic Syndromes is a comprehensive and accessible review by two of the world's experts of an area of medicine that bridges the fields of neurology, oncology, and immunology. Despite the potential complexity of these disorders, the thoughtful organization and clarity of presentation of this volume, with sections organized by specific clinical syndromes, antibodies, and cancer types, makes this an essential
reference both clinicians and scientists with an interest in paraneoplastic syndromes." --Howard Colman, MD, PhD, Director of Medical Neuro-Oncology, Department of Neurosurgery and Huntsman Cancer Institute, University
of Utah School of Medicine, Salt Lake City, UT