Main description:

Neurologic Complications of Cancer reviews the impact of cancer on the nervous system. It examines the diagnosis and management of neurological complications of specific types of cancer, as well as the side effects of oncological treatments. Updated with approximately 30% new material it includes new diagnostic techniques and treatments.

Contents:

INTRODUCTION
RATIONALE for NEURO-ONCOLOGY
Neurologic complications are common
Neurologic complications are increasing
Neurologic complications are serious
Diagnosis is difficult
Treatment helps
Research is essential
Biologic relationship of nervous system to cancer
CLASSIFICATION OF NEURO- ONCOLOGIC DISORDERS
Metastases
Nonmetastatic complications
Vascular disorders
Infections
Metabolic and Nutritional disorders
Side Effects of Cancer Treatment
"Remote Effects"-Paraneoplastic Syndromes
APPROACH TO THE PATIENT
Patient with known cancer
Patient without known cancer
EVALUATING THE PATIENT
Relevant scales
2: Pathophysiology Of Nervous System Metastases
INTRODUCTION
PATHOPHYSIOLOGY OF THE METASTATIC PROCESS
Transformation and Growth
Vascularization (Angiogenesis)
Invasion
Intravasation (blood vessels, lymph channels)
Circulation
Arrest 1st capillary bed e.g. lung, liver, bone
Passage to arterial circulation
Arrest final capillary bed
Tumor Emboli
Extravasation
Dormancy
Growth in CNS
CLINICAL CONSIDERATIONS RELEVANT TO NERVOUS SYSTEM METASTASIS
Tumor Size and lymph node involvement
Properties of Metastases
Differences between a Primary Tumor and Its Metastasis
Site of Metastases
Hemodynamic hypothesis-relevance to nervous system metastases
Seed and soil hypothesis- relevance to nervous system metastases
Subtypes
Timing of Metastases
The Cascade Process
PATHOPHYSIOLOGIC FACTORS RELEVANT TO SPREAD AND GROWTH OF CANCER TO SPECIFIC NEURAL STRUCTURES
Brain
Spinal Cord
Vertebral metastases
Foraminal invasion
Epidural metastases
Consequences of spinal cord compression
Leptomeninges
Cranial and Peripheral Nerves
3: Blood-Nervous System Barrier Dysfunction: Pathophysiology And Treatment
INTRODUCTION
ANATOMY AND PHYSIOLOGY
Blood-Brain Barrier
Blood-Peripheral Nerve Barrier
Blood-Cerebrospinal Fluid Barrier
DISRUPTION OF BLOOD-CENTRAL NERVOUS SYSTEM BARRIERS
Brain Edema
Other Sources of Disruption
Other Substances Causing Blood-Brain Barrier Breakdown
CONSEQUENCES OF BLOOD-BRAIN BARRIER DISRUPTION: INCREASED INTRACRANIAL
PRESSURE, PLATEAU WAVES, AND CEREBRAL HERNIATION
Treatment of Cerebral Herniation
TRANSPORT OF CHEMOTHERAPEUTIC DRUGS ACROSS THE BLOOD-BRAIN BARRIER
RESTORATION OF BLOOD-CENTRAL NERVOUS SYSTEM BARRIERS
Lowering Intracranial Pressure
Corticosteroids
Brain metastases
Spinal cord compression
Corticosteroids for other neurologic complications of cancer
Corticosteroid taper
Mechanisms of corticosteroid action on blood-brain barrier
4: Supportive Care and Its Complications
INTRODUCTION
EDEMA/GLUCOCORTICOIDS
Salutary effects of corticosteroids
Unwanted side effects of corticosteroids
MYOPATHY
BEHAVIORAL/COGNITIVE SIDE-EFFECTS
INSOMNIA
HYPERGLYCEMIA
BONE DISORDERS
LIPOMATOSIS
VISUAL PROBLEMS
GASTROINTESTINAL DISORDERS
Ulceration
Bowel Perforation
Pneumatosis Cystoides Intestinalis
Colonic Ileus
Constipation/Diarrhea
OTHER SIDE-EFFECTS
DRUG INTERACTIONS
CORTICOSTEROID WITHDRAWL
SEIZURES/ANTICONVULSANTS
Incidence and Epidemiology
Therapy
STATUS EPILEPTICUS
PROPHYLATIC ANTICONVULSANTS
UNTOWARD EFFECTS of ANTICONVULSANTS
Drug interactions
Side-effects
VENOUS THROMBOSIS/ANTICOAGULANTS
PAIN/ANALGESIA
Other Sources of Disruption
Other Substances Causing Blood-Brain Barrier Breakdown
CONSEQUENCES OF BLOOD-BRAIN BARRIER DISRUPTION: INCREASED INTRACRANIAL
PRESSURE, PLATEAU WAVES, AND CEREBRAL HERNIATION
Treatment of Cerebral Herniation
TRANSPORT OF CHEMOTHERAPEUTIC DRUGS ACROSS THE BLOOD-BRAIN BARRIER
RESTORATION OF BLOOD-CENTRAL NERVOUS SYSTEM BARRIERS
Lowering Intracranial Pressure
Corticosteroids
Brain metastases
Spinal cord compression
Corticosteroids for other neurologic complications of cancer
Corticosteroid taper
Mechanisms of corticosteroid action on blood-brain barrier
4: Supportive Care and Its Complications
INTRODUCTION
EDEMA/GLUCOCORTICOIDS
Salutary effects of corticosteroids
Unwanted side effects of corticosteroids
MYOPATHY
BEHAVIORAL/COGNITIVE SIDE-EFFECTS
INSOMNIA
HYPERGLYCEMIA
BONE DISORDERS
LIPOMATOSIS
VISUAL PROBLEMS
GASTROINTESTINAL DISORDERS
Ulceration
Bowel Perforation
Pneumatosis Cystoides Intestinalis
Colonic Ileus
Constipation/Diarrhea
OTHER SIDE-EFFECTS
DRUG INTERACTIONS
CORTICOSTEROID WITHDRAWL
SEIZURES/ANTICONVULSANTS
Incidence and Epidemiology
Therapy
STATUS EPILEPTICUS
PROPHYLATIC ANTICONVULSANTS
UNTOWARD EFFECTS of ANTICONVULSANTS
Drug interactions
Side-effects
VENOUS THROMBOSIS/ANTICOAGULANTS
PAIN/ANALGESIA
PSYCHOLOGICAL DISTRESS/PSYCHTROPIC AGENTS
FATIGUE
NAUSEA, VOMITING/ ANTI-EMETIC AGENTS
INFECTION/ANTIBIOTICS
INTENSIVE CARE/ COMMON AGENTS
5: INTRACRANIAL METASTASES
GENERAL PRINCIPLES
INTRODUCTIONCLASSIFICATION
INCIDENCE
BRAIN METASTASES (PARENCHYMAL)
Source
Pathophysiology of Neurologic Symptoms and Signs
Pathology
Clinical Findings
Symptoms and Signs
Headache
Focal weakness
Cognitive/behavioral impairment
Seizures
Other symptoms
Presenting signs
Onset of symptoms
Laboratory findings
MRI
Biopsy
Other tests
Differential diagnosis
Approach to patient without known cancer
Treatment
Symptomatic treatment
Corticosteroids
Radiation Therapy
WBRT
Radiosurgery
Interstitial radiation
Prophylactic radiation
Re-irradiation
Surgery
Chemotherapy
Prognosis
SPECIFIC TUMORS
Small-cell lung cancer
Non-small-cell lung cancer
Breast
Melanoma
Renal
Colon
Testes
Gynocologic
Sarcomas
Hematologic
Unknown primary
LESS COMMON SITES of INTRACRANIAL METASTASES
Calvarium
Dura
Pineal
Choroid
Pituitary
6: SPINAL METASTASES
INTRODUCTION
EPIDURAL METASTASES
Frequency
Biology of epidural metastases
Pathophysiology of symptoms and signs
Pathology
Clinical findings
Pain
Local pain
Mechanical instability
Radicular pain
Referred and funicular pain
Weakness
Upper motor neuron weakness
Lower motor neuron weakness
Sensory loss
Lhermitte sign
Autonomic dysfunction
Ataxia
Unusual symptoms and signs
Laboratory examination
Plain x-rays
Radionuclide bone scans
CT
Positron emission tomography
MRI
Myelography
Differential diagnosis
Epidural hemorrhage
Epidural abscess
Herniated disk
Other epidural masses
Treatment
Corticosteroids
Hyperosmolar agents
Hormonal and chemotherapeutic agents
Radiation therapy
Principles
Prognosis
Radiosurgery
Re-irradiation
Back braces and bed rest
Surgery
Indications for surgery
Decision-making and epidural spinal cord compression
Specific tumors
Prostate cancer
Breast cancer
Lymphoma/myeloma
Lung cancer
Other cancers
INTRADURAL and INTRAMEDULLARY METASTASES
Diagnosis
Treatment
7: Leptomeningeal Metastases
INTRODUCTION
FREQUENCY
BIOLOGY OF LEPTOMENINGEAL METASTASES
PATHOPHYSIOLOGY OF SIGNS AND SYMPTOMS
Hydrocephalus
Parenchymal Invasion
Ischemia
Metabolic Competition
Immune Responses
Inflammation
Blood-Cerebrospinal Fluid Barrier Disruption
CLINICAL FINDINGS
Cerebral (Brain) Symptoms and Signs
Headache
Gait difficulty
Cognitive dysfunction
Episodic loss of consciousness
Other cerebral complaints
Neurologic signs
Cranial Nerve Symptoms and Signs
Spinal Symptoms and Signs
LABORATORY TESTS
Magnetic Resonance Scanning
Lumbar Puncture
CSF pressure
Cell count
Protein concentration
Glucose concentration
Cytologic examination
Immunocytochemistry
Flow Cytometry
Biochemical/molecular Markers
Other Diagnostic Tests
Myelography
Cerebral arteriography
Electroencephalography
Electromyography
Meningeal biopsy
Positron emission tomography
CSF flow
DIFFERENTIAL DIAGNOSIS
DIAGNOSTIC APPROACH
TREATMENT
Radiation Therapy
Chemotherapy
Route of administration
Chemotherapeutic agents
Intrathecal agents
Systematically administered agents
Complications
Surgery
Complications
PROGNOSIS
8: Cancer Involving Cranial, Peripheral Nerves And Muscles
INTRODUCTION
FREQUENCY
CRANIAL NERVES
Clinical Findings
Olfactory nerve
Optic nerve
Ocular motor nerves
Ocular motor syndromes
Trigeminal nerve
Gasserian ganglion syndrome
Numb chin syndrome
Other sites
Facial nerve
Glosspharyngeal/Vagus nerves
Jugular foramen syndrome
Syncope
Facial pain
Spinal accessory nerve
Hypoglossal nerve
Occipital condyle syndrome
Diagnosis and Treatment
SPINAL ROOTS
NERVE PLEXUSES
Cervical Plexus
Brachial Plexus
Clinical findings
Laboratory tests
Course
Differential diagnosis
Treatment
Lumbosacral plexus
Lumbar plexus
Clinical findings
Laboratory tests
Differential diagnosis
Treatment
Sacral Plexus
Clinical findings
Laboratory tests
Differential diagnosis
Treatment
PERIPHERAL NERVES
Mononeuropathies
Clinical findings
Differential diagnosis
Polyneuropathy
MUSCLES
9: Vascular Disorders
INTRODUCTION
FREQUENCY
PATHOPHYSIOLOGY OF CEREBROVASCULAR DISEASE
Hypocoagulation
Hypercoagulation
CENTRAL NERVOUS SYSTEM HEMORRHAGE
Hemorrhage into Brain Metastases
Clinical findings
Diagnosis
Differential diagnosis
Treatment
Subdural Hemorrhage
Clinical findings
Diagnosis
Treatment
Coagulopathic Hemorrhage
Intracerebral Hemorrhage
Clinical Findings
Treatment
Spinal Hemorrhage
Leukostasis
Hyperviscosity
Hypertension
CENTRAL NERVOUS SYSTEM INFARCTION
Atherosclerosis
Disseminated Intravascular Coagulation
Pathology
Incidence
Clinical Findings
Laboratory Tests
Differential Diagnosis
Treatment
Arterial Occlusion by Extrinsic Tumor
Clinical Findings
Cerebral Emboli
Nonbacterial Thrombotic Endocarditis
Clinical Findings
Laboratory Tests
Pathology
Treatment
Septic Arterial Occlusions
Clinical Findings
Pathology
Treatment
Tumor Emboli
Thrombotic Microangiopathy
Cerebral Vasculitis
Intravascular Lymphoma)
Thrombocytosis
VENOUS OCCLUSION
Compressive Venous Sinus Occlusion
Clinical Findings
Differential Diagnosis
Treatment
Venous Sinus Thrombosis
Clinical Findings
Treatment
Prognosis and Sequelae
Tumor Emboli
OTHER DISORDERS
Systemic Thrombophlebitis
Episodic Neurologic Dysfunction in Patients with Hodgkin's Disease
Systemic Hypotension
Air embolism
APPROACH TO THE PATIENT
10: Central Nervous System Infections
INTRODUCTION
PATHOPHYSIOLOGY OF CENTRAL NERVOUS SYSTEM INFECTION
Host Defenses
Physical barriers
Immunologic defenses
Multiple defects
Infection Sites within the Central Nervous System
Meningitis
Cerebritis and brain abscess
Meningoencephalitis
CLINICAL FINDINGS
Signs and Symptoms
Meningitis
General physical examination
Neurologic examination
Diagnosis
Lumbar puncture
CSF evaluation
Imaging
Meningoencephalitis
Brain Abscess
Vascular Lesions
APPROACH TO THE PATIENT
SPECIFIC ORGANISMS CAUSING CENTRAL NERVOUS SYSTEM INFECTION IN PATIENTS WITH CANCER
T-Lymphocyte and Mononuclear Phagocyte Defects
Bacteria
Listeria
Nocardia
Fungi
Viruses
Varicella-Zoster
Varicella
Reye's syndrome
Zoster
Complications
Post-herpetic neuralgia
Paralysis
Myelitis
Urinary retention
Encephalitis
Cerebral vasculitis
Multifocal encephalopathy
Diagnosis
Herpes Simplex Progressive multifocal leukoencephalopathy
Cytomegalovirus
Other viruses
Parasites
Toxoplasma
Strongyloides
Eosinophilic meningitis
Neutrophil Defects
Enteric bacteria
Fungi
Aspergillus
Zygomycetes
Candida
Splenectomy or B-Cell Abnormalities
Bacteria
Streptococcus Pneumonia
Cerebrospinal Fluid-Surface Communication
Bacteria
Parasites
Other Infections
Infectious endocarditis
"Malignant" external otitis
11: Delirium And Metabolic And Nutritional Complications of Cancer
INTRODUCTION
DELIRIUM ASSOCIATED WITH CANCER
Definitions
Incidence
Pathophysiology
Clinical findings
Diagnosis
Causes of delirium
METABOLIC BRAIN DISEASE IN PATIENTS WITH CANCER
Incidence
Clinical Signs
Laboratory Tests
Differential Diagnosis
Treatment
SPECIFIC METABOLIC CAUSES of DELIRIUM
Postoperative delirium
Drugs
Substrate deprivation
Hypoxia
Ischemia
Hypoglycemia
Hyperglycemia
Sepsis
Critical illness weakness
Electrolyte imbalance
Hypercalcemia
Hypocalcemia
Hyponatremia
Hypernatremia
Hypomagnesemia
Hypophosphatemia
Endocrine and other organ dysfunction
Adrenal dysfunction
Adrenal failure
Adrenal excess
Hyper/hypo-thyroidism
Organ failure
Tumor lysis
Lactic acidosis
NUTRITIONAL DISORDERS ASSOCIATED WITH CANCER
Malnutrition and Cachexia
Disorders of Nutrient Deprivation Associated with Cancer
Wernicke-Korsakoff syndrome
Vitamin B12/Folate deficiency
Carcinoid syndrome
12: Side Effects Of Chemotherapy
INTRODUCTION
CLINICAL FINDINGS AND DIAGNOSIS
Peripheral Nervous System
Diffuse neuropathy
Focal neuropathy
Central Nervous System
Acute encephalopathy
Chronic encephalopathy
Other neurologic disorders
Non-neurologic toxicity
SPECIFIC AGENTS
Cytotoxic Agents
Alkylating Agents
Platinum-based agents
Cisplatin
Peripheral neuropathy
Cranial nerve neuropathy
Lhermitte's sign
Muscles
Hearing/vestibular
Visual/ocular toxicity
Encephalopathy
Nitrosoureas
Mustards
Ifosfamide
Cyclophosphamide
Melphalan
Chlorambucil
Other alkylating agents
Busulfan
Dacarbazine (DTIC)/ Temozolomide
Nitrogen mustard (Mechlorethamine)
Procarbazine
Mitotane
Altretamine (Hexamethylmelamine)
Thiotepa
Antineoplastic Antibiotics
Anthracyclines
Doxorubicin
Idarubicin, epirubicin,daunorubicin
Mitoxantrone
Other antibiotics
Bleomycin
Mitomycin C
Dactinomycin (Actinomycin D)
Antimetabolites
Antifolates
Methotrexate (MTX)
Aseptic meningitis
Encephalomyelopathy
Transverse myelopathy
Acute/subacute encephalopathy
Chronic encephalopathy
Pathophysiology
Pemetrexed
Cytidine analogs
Cytarabine (cytosine arabinoside, ara-C)
5-azacytidine/decitabine
Gemcitabine
Fluorinated pyridmidines
5-fluorouracil
Capecitabine
Pentostatin
Purines and other antimetabolites
Adenosine analogs
Fludarabine
Cladribine
Pentostatin
Guanine analogs
Hydroxyurea
Plant Alkaloids
Vinca alkaloids
Vincristine
Vindesine, vinblastine, vinorelbine
Podophyllins
Etoposide
Teniposide
Taxanes
Paclitaxel, docetaxel
Other tubulin binding agents
Estramustine
Epothilones
Miscellaneous Cytotoxic Agents
L-Asparaginase
Amsacrine
Suramin
Camptothecins
Thalidomide
Combination Chemotherapy
Anti-neoplastic Hormones
Anti-estogens
Anti-androgens
Biologic Agents
Antibodies
Cellular therapies
Vaccines
Cytokines
Interleukins
Interferons
Immune enhancers
Immunosuppressive agents
Growth factors
Erythropoietin
Granulocyte stimulating factors
Interleukin-11
Keratinocyte growth factor
Small molecules
Imatinib
Gefitinib
Sunitnib
Sorafenib
Lapatinib
Tipifarnib
Bortezomib
Differentiation agents
All-trans-retinoic acid/arsenic trioxide
Hematopoietic stem cell transplantation
Adjuvant agents
Amifostine
Allopurinol
Zoledronic acid
13: SIDE Effects Of Radiation Therapy
INTRODUCTION
BIOLOGY OF RADIATION DAMAGE
Ionization
Fractionation
Mechanisms of nervous system damage
The Linear-Quadratic Concept
DIAGNOSIS OF RADIATION-INDUCED NEUROTOXICITY
Direct radiation damage to the nervous system
Brain
Acute encephalopathy
Early-delayed encephalopathy
Neurologic deterioration
Radiation somnolence syndrome
Focal encephalopathy
Pathogenesis
Late-delayed encephalopathy
Radiation necrosis
Cerebral atrophy
Post-irradiation "migraine"
Treatment
Spinal Cord
Acute myelopathy
Early-delayed myelopathy
Late-delayed myelopathy
Progressive myelopathy
Lower motor neuron syndrome
Spinal hemorrhage
Peripheral nervous system
Cranial nerves
Olfactory nerve
Optic nerve
Ocular motor nerves
Trigeminal nerve
Facial nerve
Acoustic/Vestibular nerve
Lower cranial nerves
Peripheral Nerves
Brachial plexus
Acute brachial plexopathy
Early-delayed plexopathy
Late-delayed plexopathy
Acute ischemic plexopathy
Lumbosacral plexopathy
Sacral plexopathy
Muscle
Trismus
Dropped head syndrome
Indirect radiation damage to the nervous system
Radiogenic Tumors
Radiation-Induced Vasculopathy
Endocrine Dysfunction
Combination Radiation and Drugs
TREATMENT
14: Neurotoxicity Of Surgical And Diagnostic Procedures
INTRODUCTION
DISORDERS RESULTING from ANESTHESIA
General Anesthesia
CNS Complications
Postoperative delirium/ Cognitive Dysfunction
Peripheral Nerve Complications
Regional anesthesia
Intubation
SURGERY
Craniotomy
Vascular lesions
Infections
Seizures
Aseptic Meningitis
Pneumocephalus
Decompression Optic Neuropathy
Headache
Cerebellar Mutism
Craniectomy Defect/CSF leak
Electrolyte/other disorders
Skull base surgery
Spinal Surgery
Head and Neck Surgery
Breast Surgery
Thoracotomy
Abdominal/Pelvic surgery
Extremity Surgery
DIAGNOSTIC PROCEDURES
Computed Tomography
Lumbar Puncture
Cerebral Herniation
Intracranial Hypotension
Spinal Herniation
Spinal Hemorrhage
Meningitis
Arterial/venous catheters
Epidural/intrathecal catheters
15: Paraneoplastic Syndromes
INTRODUCTION
GENERAL CONSIDERATIONS
Classification
Frequency
Importance
Pathogenesis
Diagnosis
Clinical approach
Prognosis
Treatment
SPECIFIC SYNDROMES
Paraneoplastic Cerebellar Degeneration
Diagnosis
Pathogenesis
Pathology
Treatment
Subacute Sensory Neuronopathy/Encephalomyelitis
Hippocampus (Limbic Encephalitis)
Hypothalamus
Brainstem
Cerebellum
Spinal cord
Dorsal root ganglia
Autonomic system
Antibodies
Treatment
Opsoclonus/Myoclonus
Spinal Cord Syndromes
Myelitis
Necrotizing myelopathy
Motor neurons syndromes
Stiff- person syndrome
Cranial Nerves
Retinopathy
Carcinoma Associated Retinopathy (CAR)
Melanoma associated retinopathy
Optic neuropathy
Peripheral Nerve Syndromes
Sensory neuropathy
Sensorimotor neuropathy
Motor neuropathy
Autonomic neuropathy
Plasma cell dyscrasias
Vasculitic neuropathy
Neuromuscular Junction Syndromes
Lambert-Eaton myasthenic syndrome
Myasthenia gravis
Neuromyotonia
Muscle Syndromes
Inflammatory myopathies
Necrotizing myopathy