Merritt’s Neurology

SECTION I GLOBAL BURDEN OF NEUROLOGIC DISEASE
1 Worldwide Epidemiology of Neurologic Disease
Introduction
The Classification of Disease: What is a Neurologic Disorder?
Estimating Disease Burden
Mortality
Morbidity
Life Expectancy
The Shifting Character of Neurologic Disease Over Time
The Epidemiologic Transition and the Double Burden of Disease
Disparities
Stroke
Chronic Neurological Diseases
Access to Care
Sociocultural Differences in Interpretation of Disease
Summary
2 Global Delivery of Neurologic Care
Gaps in Global Access to Neurologic Care
Components Required for Delivery of Neurologic Care
Challenges in Addressing Neurologic Disorders
Stigma Related to Neurologic Disorders
Challenges in Health-Seeking Behavior
Limited Global Access to Diagnostics and Therapeutics for Neurologic Disorders
Gaps in National Policies and Guidelines for Brain Health
Approaches and Strategies to Improve Delivery of Neurologic Care Globally
Collaborative Partnerships and Coordinated Action
Improving Access to Neurologic Care: Primary Care Workforce
Telemedicine and Information and Communication Technology
Synchronous Approaches
Asynchronous Approaches
Training Approaches to Build Capacity
Community Engagement
Programs Aimed to Raise Public Awareness
Conclusion
SECTION II APPROACH TO THE NEUROLOGIC PATIENT
3 Neurologic History Taking, Localization, and Differential Diagnosis
Introduction to Clinical Diagnostic Reasoning
Intentional Exploration of the Patient History
Identifying Localization
History of Present Neurologic Illness
Sources of Information
Approach to Taking the History
Primary Components of the History
Localization
Timing, Onset, Tempo, and Duration
Quality of Subjective Experiences
Alleviating and Aggravating Factors
Related Symptoms
Behaviors Only Observable by Others
Further Shaping the History and Differential
Age of the Patient
Gender Specificity
Technology as an Assistive Tool
Presymptomatic or Asymptomatic Genetic Variants
Neurologic Symptoms in Nonneurologic Disease
Problem-Based History
Past Medical, Psychiatric, and Surgical Histories
Neurologic Review of Systems
Social History
Travel and Occupational History
Dietary and Nutritional History
Family History
Diagnostic Synthesis
Acknowledgment
Level 1 Evidence
4 The Neurologic Examination
Introduction
Setting Goals of Examination Versus Neurologic Tests
A Top-Down Approach
Helping Your Patient Through the Neurologic Examination
Soft Versus Hard Neurologic Examination Findings
Descriptions Versus Impressions
Positioning the Patient (and Examiner)
Careful Observation and Examination Interpretation
The Patient Examination
General Medical Examination
Mental Status Examination
Determining Alertness
Language
Memory Testing
Calculation and Other Tasks of Attention and Concentration
Executive Function
Visuospatial Function
Higher Order Cognition
Key Psychiatric Examination Elements
Cranial Nerve Examination
Cranial Nerve I (Olfactory Nerve)
Cranial Nerve II (Optic Nerve)
Extraocular Movements (Cranial Nerves III [Oculomotor Nerve], IV [Trochlear Nerve], and VI [Abducens Nerve])
Cranial Nerve V (Trigeminal Nerve)
Cranial Nerve VII (Facial Nerve)
Cranial Nerve VIII (Vestibulocochlear Nerve)
The Lower Cranial Nerves Involved in Speech (IX [Glossopharyngeal Nerve], X [Vagus Nerve], and XII [Hypoglossal Nerve])
Cranial Nerve XI (Accessory Nerve)
Motor Examination
Coordination
Gait, Station, and Body Movements
Deep Tendon and Other Reflexes
Direct Muscle Percussion
Sensory Examination
Additional Neurologic Tests for Special Conditions
Dix-Hallpike Maneuver
The Head Impulse Test
Phalen and Tinel Signs
Straight Leg Raise
Additional Spinal Reflexes (Male Patients Only)
Anal sphincter Tone
Tests of Malingering
SECTION III COMMON PROBLEMS IN NEUROLOGY
5 Dizziness, Vertigo, and Hearing Loss
Introduction
Vertigo
Neuroanatomy
Diagnosis
Focused History
Focused Examination
Diagnostic Testing
Treatment
Tinnitus
Neuroanatomy
Diagnosis
Examination and Diagnostic Testing
Treatment
Hearing Loss
Diagnosis
Sudden Hearing Loss
Examination
Treatment
6 Syncope
Introduction
Epidemiology
Pathobiology
Causes of Syncope
Neurally Mediated Reflex Syncope
Cardiac Syncope
Syncope Due to Orthostatic Hypotension
Diagnosis
Differentiating Syncope from Seizure
Clinical Features of Syncope
Clinical Features of Seizures
Clinical Features of Other Spells Potentially Mistaken for Syncope
Focused Physical Examination
Diagnostic Tests
Management
Outcome
7 Seizures
Introduction
Management Strategy
Initial Diagnosis
History
Exam
Differential Diagnosis
Causes of Seizures: Provoked Seizures, Unprovoked Seizures, and Lowered Seizure Threshold
Emergent Management
Prehospital Stabilization and Treatment
Hospital Stabilization and Treatment
Initial Workup
Indications for Hospital Admission
Status Epilepticus
Second-Line Therapy
Refractory Status Epilepticus and Anesthetic (Third-Line) Treatment
Electroencephalogram Monitoring During Status Epilepticus
Level 1 Evidence
8 Pain, Numbness, and Paresthesias
Introduction
Management Strategy
Types of Sensory Symptoms
Neuropathic Pain
Neuroanatomy and Localization
Central Sensory Syndromes
Cortex
Brain Stem
Spinal Cord
Peripheral Sensory Syndromes
Nerve Roots and Dorsal Root Ganglia
Plexuses
Peripheral Nerves
Focused History
Numbness and Paresthesias
Pain
Past Medical History
Focused Exam
General Medical Examination
Neurologic Examination
Mental Status
Cranial Nerves
Motor Examination
Sensory Examination
Reflexes
Gait and Station
Diagnostic Evaluation
Serologic Tests
Neuroimaging
Lumbar Puncture
Electrodiagnostic and Quantitative Sensory Testing
Skin and Nerve Biopsy
Initial Management
Identify Potentially Serious Conditions
Symptomatic Treatment
9 Headache and Facial Pain
Introduction
General Principles
Diagnosis
History
Physical Examination
Primary Versus Secondary Headache
“Red Flags”
“Green Flags”
Primary Headache Disorders
Secondary Causes of Headache
Meningitis
Subarachnoid Hemorrhage and Intracranial Aneurysms
Brain Tumor
Subdural Hematoma
Cervical Artery Dissection
Cerebral Venous Sinus Thrombosis
Reversible Cerebral Vasoconstriction Syndrome
Giant Cell Arteritis
Spontaneous Intracranial Hypotension
Idiopathic Intracranial Hypertension
Emergency Department Evaluation and Management
Diagnostic Evaluation
Migraine Treatment in the Emergency Department
Goals of Treatment
Parenteral Therapies
Inpatient Admission
Opioids
Treatment of Other Primary Headache Disorders
Craniofacial Pain
Neuralgic Pain
Triggers
Dental Pain
Atypical Facial Pain
Facial Pain Syndromes and the Cranial Neuralgias
Level 1 Evidence
10 Visual Disturbances
Introduction
Neuroanatomy
Afferent Visual Pathway
Efferent Visual Pathway
Pupil and Eyelid Anatomy
Visual Symptom History
Defining Severity of Symptoms
Defining Type of Symptoms
Defining How the Eyes Work Together
Remainder of History
Visual Pathway Examination
Central Vision
Visual Acuity
Color
Visual Distortion
Peripheral Vision
Confrontation Visual Field Testing
Comparative Visual Field Testing
Ophthalmic Examination
External Exam
Anterior Exam
Funduscopic Exam
Ocular Motility
Examine How the Eyes Move Individually and Together
Determine Eye Alignment
Characterize Extra Eye Movements
Pupil Size and Function
Comparing Pupils to Each Other
Comparing Optic Nerves to Each Other Using the Pupil
Neurologic Exam
Ancillary Ophthalmic Testing
Fundus Photography
Optical Coherence Tomography
Perimetry
Visual Electrophysiology
Transient Visual Symptoms
Transient Ischemic Attack
Ophthalmic Causes of Transient Visual Symptoms
Optic Nerve Causes of Transient Visual Symptoms
Cerebral Causes of Transient Visual Symptoms
Transient Diplopia
Common Patterns of Afferent Pathway Disease
Ophthalmic
Optic Neuropathy
Acute Optic Neuropathies
Progressive Optic Neuropathies
Papilledema
Optic Chiasm
Optic Tract
Lateral Geniculate Nucleus
Optic Radiations
Occipital Lobe
Higher Order Visual Dysfunction
Common Patterns of Efferent Visual Pathway Dysfunction
Supranuclear Causes of Diplopia
Third Nerve Palsy
Fourth Nerve Palsy
Sixth Nerve Palsy
Multiple Cranial Neuropathies
Cavernous Sinus Syndrome
Neuromuscular Junction
Myopathies
Afferent and Efferent Dysfunction
Sellar Pathology
Orbital Apex Syndrome
High Intracranial Pressure
11 Delirium
Introduction
Causes of Delirium
Epidemiology
Pathobiology
Diagnosis
Focused History
Focused Exam
Initial Laboratory Workup
Arousal Level
Delirium Assessment
Diagnosis of Delirium After Neurologic Injury
Electroencephalogram Findings in Delirium
Delirium Versus Dementia: A Diagnostic Challenge
Management
Pharmacologic Prevention
Pharmacologic Therapy
Environmental Optimization
Conclusion
Level 1 Evidence
12 Dementia and Memory Loss
Introduction
Terminology and Classification
Dementia Versus Mild Cognitive Impairment
Dementia Versus Delirium
Dementia Versus Depression
Epidemiology
Pathobiology
Neurodegenerative Dementias
Alzheimer Disease
Lewy Body Dementia
Frontotemporal Dementias
Less Common Neurodegenerative Dementias
Vascular Dementia
Structural Causes of Dementia
Metabolic Causes of Dementia
Infectious Causes of Dementia
Dementia From Endocrine Dysfunction
Inflammatory Causes of Dementia
Diagnosis
Focused History and Differential Diagnosis
Questions to Ask
Focused Examination
Mental Status Examination
Bedside Standardized Cognitive Testing
General Neurologic Examination
Diagnostic Testing
Neuropsychological Testing
Laboratory Blood Testing
Laboratory Cerebrospinal Fluid Testing
Neurophysiologic Testing
Neuroimaging
Treatment
Outcome
Level 1 Evidence
13 Involuntary Movements
Introduction
Focused History
Focused Examination
Description of Involuntary Movements
Types of Hyperkinetic Phenomenologies
Myoclonus
Dystonia
Chorea, Athetosis, and Ballism
Tics
Stereotypies
Tremor
Akathisia
Other Hyperkinetic Movements With Variable Phenomenologic Features
Dyskinesias
Asynergia and Ataxia
Hyperekplexia
Functional Involuntary Movements
Neuroanatomy
Diagnosis
Treatment
14 Muscle Weakness, Cramps, and Stiffness
Introduction
Management Strategy
Neuroanatomy and Localization of Weakness
Central (Upper Motor Neuron) Weakness
Cortical Lesions
Subcortical Lesions
Spinal Cord Lesions
Peripheral (Lower Motor Neuron) Weakness
Brachial Plexus
Lumbosacral Plexus
Peripheral Nerves
Neuromuscular Junction
Myopathy
Focused History
Demographics and Past Medical History
Tempo of Weakness
Variability of Weakness
Distribution of Weakness
Sensory Symptoms
Pain
Stiffness and Cramps
Visual and Speech Disturbances
Respiratory Symptoms
Autonomic Disturbances
Focused Exam
Mental Status
Cranial Nerves
Motor Examination
Inspection
Adventitious Movements
Tone
Power
Sensory Examination
Reflexes
Coordination
Gait
Diagnosis and Initial Treatment
Recognition of Emergent Situations
Laboratory Testing
Imaging Studies
Lumbar Puncture
Electrodiagnostic Testing
Muscle or Nerve Biopsy
Acknowledgment
15 Gait Disorders
Introduction
Introduction to the Gait Cycle
Neural Control of Gait
Activation and Visual Guidance of Gait
Regulation of Gait
Execution of Gait
Epidemiology of Gait Disorders
Falls in the Elderly
Clinical Assessment of Stance, Gait, and Falls
History
Medications
Physical Examination
Balance and Gait Assessment
Upper Extremities
Lower Extremities
Assessment of Gait
Classification of Gait Disorders
16 Acute Stroke: The First Hour
Introduction
Phase 1: Initial Management and Imaging
Initial Survey and Vital Signs Prior to Computed Tomography
Level of Consciousness
Blood Pressure
Heart Rate
Respirations and Breathing
Temperature
Initial History
Establish Intravenous Access and Draw Admission Labs
National Institutes of Health Stroke Scale Examination
Perform Head Computed Tomography Imaging
Analysis for Hemorrhage
Analysis for Ischemic Stroke
Phase 2: Postcomputed Tomography Emergency Management
Intracerebral Hemorrhage
Diagnose and Reverse Coagulopathy and Platelet Dysfunction
Control Severe Hypertension
Treat Elevated Intracranial Pressure or Symptomatic Mass Effect
Consider External Ventricular Drain Placement or Placement of an Intracranial Pressure Monitor
Consider Emergent Surgical Hematoma Evacuation
Consider Anticonvulsant Therapy
Consider Advanced Imaging
Disposition
Acute Ischemic Stroke
Indications for Intravenous Tissue Plasminogen Activator
Contraindications to Tissue Plasminogen Activator Administration
Tissue Plasminogen Activator and Stroke Mimics
Dosage of Intravenous Tissue Plasminogen Activator
Post–Tissue Plasminogen Activator Blood Pressure Management
Aspirin
Role of Endovascular Therapy
Disposition
Level 1 Evidence
17 Acute Spinal Cord Syndromes
Introduction
Epidemiology
Pathobiology
Spinal Cord Anatomy
Motor System
Sensory System
Autonomic System
Vascular Anatomy
Syndromic Pathology
Inflammation
Ischemia
Infection
Compression
Diagnosis
Focused History
Etiology
Localization
Focused Exam
General Exam
Neurologic Exam
Imaging
Laboratory Evaluation
Management
Initial Stabilization
Spinal Stabilization
Intensive Care Unit Admission
Pulmonary Management
Cardiovascular Management
Etiology-Specific Treatment
Inflammation
Ischemia
Infection
Compression
Outcome
18 Focal Mass Lesions
Introduction
Emergent Management of Symptomatic Intracranial Mass Effect
Causes of Focal Brain Lesions
Brain Tumors
Cerebritis and Abscesses
Other Inflammatory Lesions
Focused History
Demographics
Time Course
Past Medical History
Social History
Review of Systems
Focused Exam
Diagnosis
Imaging
Lumbar Puncture and Biopsy
Initial Management
Level 1 Evidence
19 Stupor and Coma
Introduction
Definitions
Neuroanatomy
Management Strategy
Initial Resuscitation
History and General Physical Examination
Focused Neurologic Examination
Motor Responses
Respiration
Pupils
Eyelids and Eye Movements
Diagnostic Tests
Coma Presentations and Treatment
Coma from Supratentorial Herniation Syndromes
Coma from Infratentorial Structural Lesions
Coma from Metabolic or Diffuse Brain Disease
Hysteria and Catatonia
Locked-In Syndrome
Vegetative State and Minimally Conscious State
Brain Death
Future Directions
Level 1 Evidence
20 Brain Death
Introduction
The Clinical Diagnosis of Brain Death
Determine the Cause of Brain Death
Imaging Confirmation of Brain Death
Clinical Examination
Cranial Nerves
Motor Responses to Pain
Apnea Testing
Ancillary Tests to Confirm the Diagnosis of Brain Death
Brain Death in Children
Common Diagnostic Challenges and Pitfalls
Intensive Care Unit Management of the Potential Organ Donor
Ethical Issues
Conclusions
SECTION IV DIAGNOSTIC TESTS
21 Computed Tomography
Introduction
Description
Windows and Levels
Role of Computed Tomography
Head Trauma
Headache
Subarachnoid Hemorrhage
Stroke
Computed Tomography Perfusion and Angiography
Iodinated Contrast Administration
22 Magnetic Resonance Imaging
Introduction
Physics of Magnetic Resonance Imaging
Image Creation
Clinical Magnetic Resonance Imaging Systems
Magnetic Resonance Imaging Safety
Basic Sequences
T1-Weighted and T2-Weighted Imaging
Quantification of T1 and T2 Times
Diffusion-Weighted Imaging
Gradient-Recalled Echo and Susceptibility-Weighted Imaging
Gadolinium Contrast Enhancement
Magnetic Resonance Angiography and Magnetic Resonance Venography
Magnetic Resonance Imaging Artifacts
Clinical Magnetic Resonance Imaging
Cerebrovascular Disease
White Matter Disease
Brain and Spinal Cord Tumors
Transverse Myelitis
Advanced Magnetic Resonance Imaging Methods
Functional Magnetic Resonance Imaging
Diffusion Tensor Imaging
Magnetic Resonance Spectroscopy
Magnetic Resonance Perfusion Imaging
Emerging Magnetic Resonance Imaging Methods
23 Positron Emission Tomography and Single-Photon Emission Computed Tomography
Introduction
Basic Principles
Radiopharmaceuticals and Selection of Radionuclides
Detection, Acquisition, and Display of Signal
Clinical Applications
Glucose Imaging
Positron Emission Tomography Using [18F]Fluorodeoxyglucose in Epilepsy
Positron Emission Tomography Using [18F]Fluorodeoxyglucose in Dementia
Dopamine Imaging
Perfusion Imaging
Amyloid Imaging
Tau Imaging
Radiopharmaceuticals Currently in Development With Potential for Clinical Use
Synaptic Density Imaging
24 Neurovascular Ultrasound
Introduction
Extracranial Ultrasound (Duplex Ultrasound or Color Doppler)
Carotid Ultrasound Criteria for Detection of Carotid Stenosis
Assessment of Carotid Artery After Carotid Endarterectomy and Stenting
Sensitivity and Specificity of Duplex Ultrasound in Detecting Carotid Stenosis
Carotid Ultrasound of Carotid Plaque Size, Morphology, and Carotid Intima-Media Thickness
Duplex Ultrasound of the Vertebral Arteries
Multiparametric Extracranial Ultrasound
Indications for Extracranial Ultrasound Examination
Intracranial Ultrasound (Transcranial Doppler)
Indications for Transcranial Doppler Ultrasound
Sickle Cell Disease
Intracranial Stenosis and Occlusion
Sensitivity and Specificity of Transcranial Doppler in Detecting Intracranial Stenosis
Detection of Arteriovenous Malformations
Vasospasm in Subarachnoid Hemorrhage
Cerebral Microemboli Detection
Cerebral Vasomotor Reactivity Testing
Sonothrombolysis
Limitations of Transcranial Doppler
Summary
Level 1 Evidence
25 Angiography and Neuroendovascular Surgery
Introduction
History
Procedural Outline and Considerations
Preprocedural Considerations
Procedure
Postprocedural Care
Complications of Angiography
Access Site Complications
Contrast Allergy
Contrast-Induced Nephropathy
Neurologic Complications
Selected Conditions Diagnosed and Treated With Neurointerventional Procedures
Cerebral Aneurysms
Unruptured Aneurysms
Surgical Versus Endovascular Treatment
Overview of Endovascular Treatment Strategies for Aneurysms
Subarachnoid Hemorrhage
Acute Ischemic Stroke
Extracranial Carotid Artery Disease
Arteriovenous Malformations
Dural Arteriovenous Fistulas
Other Diagnostic Uses
Emerging Considerations
Chronic Subdural Hematoma
Idiopathic Intracranial Hypertension
Intracranial Stenting
Tumors
Summary
Level 1 Evidence
26 Electroencephalography and Evoked Potentials
Electroencephalography
Introduction
Normal Electroencephalography
Abnormal Electroencephalography
Epilepsy
Focal Brain Lesion or Dysfunction
Diffuse Brain Dysfunction or Injury
Long-term Monitoring
Epilepsy Monitoring Unit
Intraoperative Neuromonitoring
Critical Care Electroencephalography Monitoring
Evoked Potentials
Introduction
Somatosensory-Evoked Potentials
Visual-Evoked Potentials
Brainstem Auditory–Evoked Responses
Motor-Evoked Potentials
Magnetoencephalography
Level 1 Evidence
27 Electromyography, Nerve Conduction Studies, and Magnetic Stimulation
Introduction
Nerve Conduction Studies
Sensory and Motor Nerve Conduction Studies
Late Responses
Other Specialized Reflex Tests
Needle Electromyography
Basic Concepts
Insertional and Spontaneous Activity
Motor Unit Configuration
Recruitment and Interference Patterns
Nerve Conduction Studies and Electromyography Applications
Tests of Neuromuscular Transmission
Repetitive Nerve Stimulation
Postsynaptic Neuromuscular Junction Dysfunction
Presynaptic Neuromuscular Junction Dysfunction
Single-Fiber Electromyography
Transcranial Magnetic Stimulation
Single-Pulse Transcranial Magnetic Stimulation
Silent Period
Repetitive Transcranial Magnetic Stimulation
Acknowledgments
28 Autonomic Testing
Introduction
Selected Tests
Heart Rate Variability
Sympathetic Measures
Standing and the 30:15 Ratio
Tilt Table Studies
Tests of Sudomotor Function
Other Organ/System-Specific Tests
Use in Clinical Practice
29 Evaluation of the Special Senses (Vision, Hearing, Smell, Vestibular System)
Introduction
Vision Testing
Visual Acuity
Color Vision
Visual-Evoked Potentials
Electroretinogram
Visual Fields
Optical Coherence Tomography
Adaptive Optics
Hearing Testing
Audiogram
Brainstem Auditory-Evoked Potentials
Smell and Taste Testing
Vestibular System
Electronystagmography/Videonystagmography
Rotary Chair
Video Head Impulse Testing
Vestibular-Evoked Myogenic Potentials
Computerized Dynamic Posturography
Gait Analysis
30 Sleep Studies
Introduction
Indications for Diagnostic Sleep Testing
Polysomnography
Evoking Parasomnias
Evaluating Rapid Eye Movement Behavior Disorder
Home Sleep Apnea Test
Multiple Sleep Latency Test
Maintenance of Wakefulness Test
Evaluation of Circadian Rhythm Disturbances
Actigraphy
Biomarkers of Circadian Rhythm
Subjective Reporting of Sleep
Indications for Laboratory Testing
Narcolepsy
Restless Legs Syndrome
Imaging
31 Neuropsychological Evaluation
Strategy of Neuropsychological Testing
Test Selection
Tests Used in a Neuropsychological Evaluation
Intellectual Ability
Memory
Processing Speed
Perception
Construction
Language
Executive Function
Working Memory
Inhibition
Set Shifting
Motor and Praxis
Attention
Concept Formation and Reasoning
Personality and Emotional Status
Clinical Observation
Mental Status Testing
Diagnosis-Specific Issues
Dementia
Other Brain Disease
Epilepsy
Deep Brain Stimulation
Toxic Exposure
Medication
Psychiatric Disorders
Learning Disability
Expectations from a Neuropsychological Evaluation
How to Refer
32 Lumbar Puncture and Cerebrospinal Fluid Analysis
Introduction
Lumbar Puncture
Techniques
Ultrasound Guidance
Cerebrospinal Fluid Analysis
Cerebrospinal Fluid Pleocytosis
Hypoglycorrhachia
Cerebrospinal Fluid Findings in Inflammatory and Demyelinating Disorders
Cerebrospinal Fluid Cytology
Precaution for Patients With Hemicraniectomy
33 Brain, Muscle, Nerve, and Skin Biopsy
Introduction
Brain Biopsy
Indications
Brain Biopsy Requires an Interdisciplinary Approach
Neuropathologic Interpretation of the Brain Biopsy
Muscle Biopsy
Nerve Biopsy
Skin Biopsy
34 Intracranial Pressure and Neurocritical Care Monitoring
Introduction
Intracranial Pressure and Cerebral Perfusion Pressure Monitoring
Physiologic Principles
Intracranial Pressure
Waveforms
Cerebral Perfusion Pressure and Pressure Reactivity
Pressure Reactivity Indices
External Ventricular Drainage
Intraparenchymal Intracranial Pressure Monitors
Indications for Intracranial Pressure Monitoring
Brain Oxygenation Monitoring
Physiologic Principles
Jugular Venous Oxygen Saturation Monitoring
Brain Tissue Oxygen Pressure Monitoring
Near-Infrared Spectroscopy
Cerebral Blood Flow Monitoring
Physiologic Principles
Continuous Cerebral Blood Flow Monitoring
Thermal Diffusion Flowmetry
Cerebral Microdialysis
Physiologic Principles
Microdialysis Monitoring
Clinical Use
Continuous Electroencephalography
Seizure Detection
Titration of Therapy for Status Epilepticus
Monitoring for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
Coma Outcome
Limitations of Continuous Electroencephalography
Multimodality Monitoring Data Acquisition and Analysis
35 Genetic Testing and DNA Diagnosis
Introduction
The Process of Genetic Counseling
Obtaining the Family History
The Genetic Counseling Discussion
Genetic Phenomenology
Incomplete and Age-Dependent Penetrance
Phenotypic Variability
Polynucleotide Repeat Expansion and Anticipation
Genetic Heterogeneity
Pleiotropy
Phenocopies
Types of Genetic Tests
Microarray
Testing for Polynucleotide Repeat Disorders
Sanger Sequencing
Next-Generation Sequencing (Next-Gen)
Testing Strategy
SECTION V CEREBROVASCULAR DISEASES
36 Acute Ischemic Stroke
Introduction
Epidemiology
Pathobiology
Cerebral Blood Flow Reduction
Infarct Core and Penumbra
Completed Infarction
Etiology of Ischemic Stroke
Large Artery Atherosclerosis
Cardioembolic Stroke
Small-Vessel Infarction
Undetermined Cause of Stroke
Other Causes of Stroke
Clinical Manifestations
Middle Cerebral Artery Infarction
Anterior Cerebral Artery Infarction
Internal Carotid Artery Infarction
Border Zone Infarction
Anterior Choroidal Artery Infarction
Posterior Cerebral Artery
Vertebrobasilar Territory Infarction
Diagnosis
Symptom Recognition
Initial Hospital Evaluation
Imaging
Computed Tomography
Magnetic Resonance Imaging
Vascular Imaging
Perfusion Imaging
Acute Treatment
Intravenous Thrombolysis
Contraindications to Intravenous Thrombolysis
Complications of Thrombolysis
Hemorrhagic Conversion
Angioedema
Endovascular Therapies
Intra-arterial Thrombolysis
Mechanical Thrombectomy
Complications
Critical Care in Stroke
Clinical Syndromes
Malignant Middle Cerebral Artery Infarction
Cerebellar Infarction
Basilar Artery Occlusion
Cervical Artery Dissection
Complications of Stroke
Neurologic Deterioration
Hypertension
Infectious Complications
Venous Thromboembolism
Stroke Outcomes
Level 1 Evidence
37 Transient Ischemic Attack
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Level 1 Evidence
38 Hypoxic-Ischemic Encephalopathy
Introduction
Epidemiology
Pathobiology: Causes of Hypoxic-Ischemic Encephalopathy
Cardiac Arrest
Prolonged Hypotension
Hypoxia
Carbon Monoxide Poisoning
Cyanide Poisoning
Profound Hypoglycemia
Clinical Features
Diagnosis
Imaging
Somatosensory-Evoked Potentials
Electroencephalography
Treatment
General Concepts
Seizures
Therapeutic Hypothermia
Outcome
Level 1 Evidence
39 Intracerebral Hemorrhage
Introduction
Epidemiology
Risk Factors
Pathobiology
Clinical Manifestations
Diagnosis
Medical Management
Hemostasis and Emergency Reversal of Anticoagulation
Hemostatic Therapy for Noncoagulopathic Intracerebral Hemorrhage
Reversal Agents for Anticoagulation-Related Intracerebral Hemorrhage
Blood Pressure Control
Blood Pressure Targets
Antihypertensive Agents
Cerebral Edema and Intracranial Pressure
Seizures
Medical Support
Surgical Management
Ventricular Drainage
Craniotomy
Minimally Invasive Surgery
Secondary Prevention
Prognosis
Level 1 Evidence
40 Subarachnoid Hemorrhage
Introduction
Pathology and Epidemiology of Intracranial Aneurysms
Clinical Features
Diagnosis
Computed Tomography
Lumbar Puncture
Angiography
Laboratory Testing
Complications of Aneurysmal Subarachnoid Hemorrhage
Rebleeding
Vasospasm
Hydrocephalus
Global Cerebral Edema and Early Brain Injury
Seizures
Fluid and Electrolyte Disturbances
Neurogenic Cardiac and Pulmonary Disturbances
Fever
Anemia
Treatment
Emergency Management
Surgical Management
Endovascular Therapy
Intensive Care Management
Outcome
Other Kinds of Macroscopic Aneurysms
Fusiform or Dolichoectatic Aneurysms
Mycotic Aneurysm
Pseudoaneurysm
Vascular (Arteriovenous) Malformations
Level 1 Evidence
41 Cerebral Venous and Sinus Thrombosis
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Anticoagulation Therapy
Endovascular Therapy
Treatment of Comorbid Conditions
Treatment of Cerebral Venous Thrombosis in Children
Outcome
Level 1 Evidence
42 Vascular Malformations
Introduction
Arteriovenous Vascular Malformations
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Unruptured Arteriovenous Malformations
Ruptured Arteriovenous Malformations
Outcome
Dural Arteriovenous Fistulas
Pathobiology
Clinical Features
Diagnosis
Management and Outcome
Cavernous Malformations
Pathobiology
Diagnosis
Clinical Features
Management
Venous Malformations
Telangiectasias
Sturge-Weber Disease
Sinus Pericranii
Vascular Tumors
Hemangioblastomas
Angioblastic Meningioma and Hemangiopericytoma
Level 1 Evidence
43 Central Nervous System Vasculitis
Introduction
Primary Angiitis of the Central Nervous System
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Laboratory Findings
Imaging
Management
Outcome
AMYLOID β–RELATED ANGIITIS
Central Nervous System Vasculitis Associated With Systemic Vasculitis
Large-Vessel Vasculitis
Giant Cell (Temporal) Arteritis
Takayasu Vasculitis
Medium-Vessel Vasculitis
Polyarteritis Nodosa
Kawasaki Disease
Small-Vessel Vasculitis
The Antineutrophil Cytoplasmic Antibody–Positive Vasculitides
Immunoglobulin A Vasculitis Henoch-Schönlein Purpura
Cryoglobulinemic Vasculitis
Variable-Vessel Vasculitis
Behçet Syndrome
Cogan Syndrome
Vasculitis Associated With Systemic Disease
Miscellaneous Causes and Mimics of Central Nervous System Vasculitis
Reversible Cerebral Vasoconstriction Syndrome
Intravascular Large Cell Lymphoma
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Infectious Central Nervous System Vasculitis
Drug-Induced Central Nervous System Vasculitis
Fibromuscular Dysplasia
44 Posterior Reversible Encephalopathy Syndrome and Other Cerebrovascular Syndromes
Posterior Reversible Encephalopathy Syndrome
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Reversible Cerebral Vasoconstriction Syndrome
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Fibromuscular Dysplasia
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Moyamoya Disease
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Binswanger Disease
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Susac Syndrome
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Sneddon Syndrome
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Marantic Endocarditis
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Level 1 Evidence
45 Primary and Secondary Stroke Prevention
Introduction
Primordial Stroke Prevention
Diet
Smoking
Exercise
Primary Stroke Prevention
Hypertension
Diabetes Mellitus
Hypercholesterolemia
Atrial Fibrillation
Carotid Stenosis
Secondary Stroke Prevention
Stroke Mechanism and Evaluation
Neuroimaging
Cardiac Evaluations
Blood Work and Other Laboratory Testing
Prevention Early After Transient Ischemic Attack and Stroke
Antiplatelet Therapy
Mechanism of Action and Dosing
Impact on Outcomes
Dual Antiplatelet Therapy
Anticoagulation
Carotid Endarterectomy, Angioplasty, and Stenting
Cardiac Abnormalities
Modifiable Risk Factor Management
Hypertension
Hyperlipidemia
Diabetes Mellitus
Lifestyle Modification
Hemorrhagic Stroke
Intracerebral Hemorrhage
Hypertension
Cerebral Amyloid Angiopathy
Issues Related to Risk of Hemorrhage
Anticoagulation-Associated Hemorrhage
Management of Atrial Fibrillation in Patients at High Risk for Intracerebral Hemorrhage
Hemorrhage Related to Anticoagulation
Arteriovenous Malformations
Aneurysmal Subarachnoid Hemorrhage
Stroke Rehabilitation
Level 1 Evidence
SECTION VI NEUROTRAUMA
46 Concussion and Chronic Traumatic Encephalopathy
Concussion
Introduction
Definition
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Chronic Traumatic Encephalopathy
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
47 Traumatic Brain Injury
Epidemiology
Pathobiology
Skull Fractures
Cerebral Concussion and Axonal-Shearing Injury
Brain Swelling and Cerebral Edema
Parenchymal Contusion and Hemorrhage
Subdural Hematoma
Epidural Hematoma
Traumatic Subarachnoid Hemorrhage
Initial Assessment and Stabilization
Cardiopulmonary Resuscitation
Initial Neurologic Assessment and Stabilization
History
Radiography and Imaging
Secondary Neurologic Evaluation
Management
Admission to the Hospital
Low-risk Group
Moderate-risk Group
High-risk Group
Surgical Intervention
Intracranial Pressure Management
Intensive Care Unit Management of Severe Head Injury
Serial Neurologic Evaluation
Airway and Ventilation
Blood Pressure Management
Fluid Management
Nutrition
Analgosedation
Temperature Management
Anticonvulsants
Intensive Insulin Therapy
Steroids
Deep Vein Thrombosis Prophylaxis
Gastric Stress Ulcer Prophylaxis
Antibiotics
Acute Complications of Head Injury
Cerebrospinal Fluid Fistula
Carotid-Cavernous Fistula
Traumatic Arterial Dissection and Vascular Injuries
Cranial Nerve Injury
Infections
Outcomes
Postconcussion Syndrome
Seizures and Posttraumatic Epilepsy
Posttraumatic Movement Disorders
Pediatric Trauma Brain Injury
Missile-Related Cerebral Blast Injury
Level 1 Evidence
48 Traumatic Spinal Cord Injury
Introduction
Etiology and Epidemiology
Mechanism of Injury
Pathobiology
Gross Pathology
Histopathology
Immediate Phase (Initial 1-2 H)
Acute Phase (Hours to 1-2 D)
Intermediate Phase (Days to Weeks)
Late Phase (Weeks to Months/Years)
Diagnosis, Neurologic Assessment, and Classification
Clinical Evaluation
Imaging Studies
Risk Stratification
Cervical X-Rays
Cervical Computed Tomography
Neurologic Assessment and Classification
Brown-Séquard Syndrome
Central Cord Syndrome
Anterior Cord Syndrome
Posterior Cord Syndrome
Conus Medullaris and Cauda Equina Syndromes
Acute Medical Management
General Trauma Care
Steroids
Autonomic Dysfunction and Blood Pressure Management
Critical Care
Surgical Treatment
Chronic Medical Management
Pain
Autonomic Dysreflexia
Coronary Artery Disease
Pulmonary Disease
Genitourinary Complications
Gastrointestinal Dysfunction
Abnormal Bone Metabolism
Spasticity
Psychiatric Complications
Conclusion
Level 1 Evidence
49 Traumatic Cranial and Peripheral Nerve Injury
Introduction
Anatomy and Physiology
Mechanisms of Injury
Injury Classification
Repair and Regeneration
Clinical Features
Cranial Nerve Lesions
Cranial Nerve I: The Olfactory Nerve
Cranial Nerve II: The Optic Nerve
Cranial Nerve III, IV, VI: the Oculomotor, Trochlear, and Abducens Nerves
Cranial Nerve V: The Trigeminal Nerve
Cranial Nerve VII: The Facial Nerve
Cranial Nerve IX: The Glossopharyngeal Nerve
Cranial Nerve X: The Vagus Nerve
Cranial Nerve XI: The Spinal Accessory Nerve
Cranial Nerve XII: The Hypoglossal Nerve
Upper Extremity Nerve Lesions
Brachial Plexus Injuries
Proximal Nerve Injuries
Median Nerve
Radial Nerve
Ulnar Nerve
Axillary Nerve
Lower Extremity Nerve Lesions
Lumbosacral Plexus
Obturator Nerve
Iliohypogastric Nerve
Ilioinguinal Nerve
Genitofemoral Nerve
Lateral Femoral Cutaneous Nerve
Femoral Nerve
Sciatic Nerve
Common Peroneal Nerve
Tibial Nerve
Diagnosis
Electrodiagnostic Findings in Peripheral Nerve Injury
Neurapraxia
Axonotmesis
Neurotmesis
Timing of Studies
Role in Surgical Planning
Treatment
Indications for Early Operative Management
Surgical Techniques
Neurolysis
Split Repair
End-to-End Neurorrhaphy
Graft Repair
Nerve Transfer
Tendon Transfer
Outcomes
SECTION VII DEMENTIA
50 Mild Cognitive Impairment
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Testing
Neuropsychological Testing
Laboratory Testing and Neuroimaging
Biomarker-Based Assessments
Treatment
Outcomes
Level 1 Evidence
51 Alzheimer Disease
Introduction
Epidemiology
Genetic Basis of Alzheimer Disease
Pathobiology
Diagnosis
Clinical Features
Diagnostic Testing
Neuropsychological Testing
Laboratory Testing and Neuroimaging
Biomarker-Based Assessments
Management
Outcome
Level 1 Evidence
52 Frontotemporal Dementia
Introduction
Epidemiology
Pathobiology
Genetics
Clinical Manifestations
Behavioral Variant
Primary Progressive Aphasia
Diagnosis
Management
Outcome
Level 1 Evidence
53 Lewy Body Dementias
Introduction
Epidemiology
Pathobiology
Neuropathology
Lewy Bodies
Lewy Neurites
Alzheimer Pathology
Spongiform Change/Microvacuolation
Distinction Between Dementia With Lewy Bodies and Parkinson Disease Dementia
Neurotransmitter Systems
Genetic Risk Factors
APOE
SNCA
GBAL
Clinical Manifestations
Cognitive Impairment
Psychiatric Symptoms
Parkinsonism
Sleep Disorders
Autonomic Dysfunction
Fluctuating Attention and Concentration
Diagnosis
Prodromal Dementia With Lewy Bodies
Diagnostic Testing and Evaluation
Neuropsychological Testing
Neuroimaging
Autonomic Testing
Differential Diagnosis
Treatment
Cognitive Symptoms
Motor Symptoms
Psychosis
Other Features
Mood Disorders
Sleep
Dysautonomia
Lifestyle
Future Directions
Outcome
Level 1 Evidence
54 Vascular Dementia and Cognitive Impairment
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Prevention and Treatment of Stroke
Cognitive and Behavioral Symptoms
Outcome
Level 1 Evidence
55 Prion Diseases
Introduction
History and Nomenclature
Pathobiology
Prion Protein Properties
Prion Protein Functions
Prion Protein Pathogenicity
Sporadic Creutzfeldt-Jakob Disease
Epidemiology
Clinical Presentation
Molecular Classification
Diagnosis
Genetic Prion Disease
Familial Creutzfeldt-Jakob Disease
Gerstmann-Sträussler-Scheinker Disease
Fatal Familial Insomnia
Octapeptide Repeat Insertions
Acquired Prion Disease
Variant Creutzfeldt-Jakob Disease
Iatrogenic Creutzfeldt-Jakob Disease
Management and Outcomes
Symptomatic Treatments
Investigational Treatments
Level 1 Evidence
SECTION VIII HEADACHE AND PAIN SYNDROMES
56 Primary and Secondary Headache Disorders
Anatomy and Physiology of Headache
Clinical Evaluation of Headache Disorders
Secondary Headache
Primary Headache Disorders
Migraine
Epidemiology
Pathophysiology
Diagnosis and Clinical Features
Treatment of Migraine
Trigger and Lifestyle Approaches to Management
Acute Therapies
Preventive Treatments for Migraine
Tension-Type Headache
Clinical Features
Pathophysiology
Treatment
Trigeminal Autonomic Cephalalgias
Cluster Headache
Clinical Features
Pathophysiology
Treatment
Paroxysmal Hemicrania
Sunct/Suna
Clinical Features
Treatment
Hemicrania Continua
Other Primary Headaches
Primary Cough Headache
Primary Exertional Headache
Primary Headache Associated With Sexual Activity
Cold-Stimulus Headache
External Pressure Headache
Primary Stabbing Headache
Nummular Headache
Hypnic Headache
New Daily Persistent Headache
Posttraumatic Headache
Level 1 Evidence
57 Facial Pain Disorders and Painful Cranial Neuralgias
Introduction
Facial Pain Due to Disorders of Sinuses, Nose, and Ears
Rhinosinusitis
Epidemiology and Pathobiology
Diagnosis
Management and Outcome
Facial Pain Attributed to Disorders of Intranasal Mucosal Contact Points
Epidemiology and Pathobiology
Diagnosis
Management and Outcome
Otalgia Attributed to Disorder of Ears and Referred Pain
Epidemiology and Pathobiology
Diagnosis
Facial Pain Due to Temporomandibular Disorders and Disorders of the Teeth or Mouth
Temporomandibular Disorders
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Treatment and Outcome
Cranial Neuralgias
Trigeminal Neuralgia
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Treatment and Outcome
Glossopharyngeal Neuralgia
Nervus Intermedius Neuralgia
Occipital Neuralgia
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Treatment and Outcome
Idiopathic Facial Pain
Burning Mouth Syndrome
Persistent Idiopathic Facial Pain
Primary Headache Disorders Presenting as Facial Pain
Level 1 Evidence
58 Complex Regional Pain Syndrome
Introduction
Epidemiology
Clinical Features and Pathology
Pathobiology
Diagnostic Criteria
Clinical Diagnostic Criteria
Research Diagnostic Criteria
Management
Physical Therapies
Nonopioid Pharmacotherapy
Opioid Treatment
Topical Creams
Continuous Infusion Therapy
Intravenous Therapies and Intravenous Regional Blockade
Sympathetic Blocks and Sympathectomy
Neuromodulation
Pain Prevention
Future Research
Conclusions
59 Neuropathic Pain
Introduction
Epidemiology
Pathobiology
Normal Processing of Nociceptive Pain
Transduction and Transmission
Modulation and Perception
Mechanisms Underlying Neuropathic Pain
Peripheral Sensitization
Central Sensitization
Diagnosis
Management
General Principles
Pharmacologic Treatments
Gabapentinoids
Serotonin-Norepinephrine Reuptake Inhibitors and Tricyclic Antidepressants
Sodium Channel Antagonists
Antiepileptics
Capsaicin
Opioids and Other Controlled Substances
Other Pharmacologic Agents
Cognitive Behavioral and Physical Therapy
Procedural Interventions
Outcome
Level 1 Evidence
SECTION IX EPILEPSY AND PAROXYSMAL DISORDERS
60 Classification of Seizures and Epilepsy
Introduction
Epidemiology
Gene Mutations in Epilepsy
Classifications of Seizures and Epilepsy
Classification of Seizures
Focal Seizures
Generalized Seizures
Unknown Onset Seizures
Classification of Epilepsies
Generalized Epilepsy
Focal Epilepsy
Epilepsy Syndromes
Idiopathic Generalized Epilepsy Syndromes
Selected Focal Epilepsy Syndromes
Lennox-Gastaut Syndrome (A Type of Combined Focal and Generalized Epilepsy Syndrome)
Infantile Spasms (West Syndrome)
Post-traumatic Seizures
Epilepsia Partialis Continua
Level 1 Evidence
61 Management of Epilepsy
Introduction
Acute Symptomatic Seizures
The Single Seizure
Initial Diagnostic Evaluation
History and Examination
Electroencephalography
Brain Imaging
Other Laboratory Tests
Long-Term Monitoring
Medical Treatment
Antiepileptic Drugs
Selection of Antiepileptic Drugs
Adverse Effects of Antiepileptic Drugs
Dose-Related Adverse Effects
Idiosyncratic Reactions
Antiepileptic Drug Pharmacology
Specific Drugs
Use of Generic Equivalents
Discontinuing Antiepileptic Drugs
Reproductive Health Issues
Bone Health
Surgical Treatment
Resective Procedures
Anterior Temporal Lobe Resection
Lesionectomy
Nonlesional Cortical Resections
Corpus Callosotomy
Hemispherectomy
Preoperative Evaluation
Neurostimulation in Drug-Resistant Epilepsy
Vagus Nerve Stimulation
Deep Brain Stimulation
Responsive Neurostimulation
Psychosocial and Psychiatric Issues
Compliance
Psychogenic Seizures
Level 1 Evidence
62 Ménière Syndrome, Benign Paroxysmal Positional Vertigo, and Vestibular Neuritis
Introduction
Ménière Disease
Definitions
Diagnosis
Medical Treatment
Surgical Management
Conservative Procedures
Destructive Procedures Labyrinthectomy
Other Treatment Methods
Intratympanic and Oral Corticosteroids
Intratympanic Gentamicin
Meniett Device
Streptomycin
Benign Paroxysmal Positional Vertigo
Vestibular Neuritis
Conclusion
Level 1 Evidence
63 Transient Global Amnesia
Introduction
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment
SECTION X CENTRAL NERVOUS SYSTEM INFECTIONS
64 Acute Bacterial Meningitis
Introduction
Etiology
Pathobiology
Clinical Manifestations
Diagnosis
Differential Diagnosis
Cerebrospinal Fluid Analysis for the Differential Diagnosis
Treatment
Complications
Level 1 Evidence
65 Brain, Spinal, and Epidural Abscess and Other Parameningeal Infections
Brain Abscess
Epidemiology
Source of Infection in Brain Abscess
Causative Organisms of Brain Abscess
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Subdural Empyema
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Spinal Epidural Abscess
Epidemiology and Pathobiology
Clinical Manifestations
Diagnostic Testing
Management
Outcome
Malignant Otitis Externa
Epidemiology and Pathobiology
Clinical Manifestations
Diagnosis
Management and Outcome
Osteomyelitis of the Skull Base
Epidemiology and Pathobiology
Clinical Manifestations
Diagnosis
Management and Outcome
66 Other Bacterial Central Nervous System Infections and Toxins
Introduction
Rickettsial Infections
Spotted Fever Rickettsiosis
Epidemiology
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Ehrlichiosis and Anaplasmosis
Epidemiology
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Scrub Typhus
Clinical Manifestations
Diagnosis
Treatment and Outcome
Typhus Group Rickettsiae
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Zoonotic Infections
Q Fever
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Brucellosis
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Leptospirosis
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Cat-Scratch Disease
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Anthrax
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Diseases of Human-To-Human Transmission
Whipple Disease
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Mycoplasma pneumoniae
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Toxins
Diphtheria
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Botulism
Pathophysiology
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
Tetanus
Pathophysiology
Epidemiology
Clinical Manifestations
Diagnosis
Treatment and Outcome
67 Chronic Meningitis
Introduction
General Diagnostic Approach
Fungal Meningitis
Cryptococcal Meningitis
Epidemiology and Pathobiology
Clinical Features
Diagnosis
Treatment Update
Outcomes
Coccidioidomycosis
Epidemiology and Pathobiology
Clinical Features
Diagnosis
Treatment
Outcomes
Blastomycosis and Histoplasmosis
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Aspergillosis
Epidemiology and Pathobiology
Clinical Features
Diagnosis
Treatment
Tuberculosis
Epidemiology and Pathobiology
Clinical Features
Diagnosis
Treatment
Neurosyphilis
Epidemiology and Pathobiology
Clinical Features
Diagnosis
Treatment
Lyme Disease
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Hypothesis-Free Investigations
Level 1 Evidence
68 Parasitic Infections
Introduction
Parasitic Neurologic Diseases
Cerebral Malaria
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Methods
Management
Trypanosomiasis
African Trypanosomiasis
American Trypanosomiasis
Amebic Meningoencephalitis
Neurocysticercosis
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Methods
Management
Larva Migrans and Eosinophilic Meningitis
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Methods
Management
Outcome
Schistosomiasis (Bilharzia)
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Manifestations
Diagnostic Methods
Management and Outcome
Level 1 Evidence
69 Viral Infections
Introduction
Picornavirus
Enteroviruses
Poliomyelitis
Enterovirus D68
Enteroviruses 70 and 71
Coxsackievirus and Echoviruses
Arboviruses
Flaviviruses
Dengue
Tick-Borne Encephalitis Virus
Japanese Encephalitis Virus
West Nile Virus
Murray Valley Encephalitis Virus
St. Louis Encephalitis Virus
Powassan Virus
Bunyaviruses
Lacrosse Virus
Jamestown Canyon Virus
Togaviruses
Alphavirus (Equine Encephalitis)
Rubivirus
Coronaviruses: Severe Acute Respiratory Syndrome Virus
Epidemiology
Neurologic Clinical Features Associated With COVID-19
Cerebrospinal Fluid Analyses and Neuroradiographic Imaging in COVID-19
Histopathologic Findings Associated With COVID-19
Orthomyxoviruses: Influenza Virus
Paramyxoviruses
Henipaviruses
Measles Encephalitis
Subacute Sclerosing Panencephalitis
Rhabdovirus: Rabies
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Arenaviruses
Lymphocytic Choriomeningitis Virus
Clinical Manifestations
Diagnosis and Treatment
Adenovirus
Herpesviruses
Herpes Simplex Virus 1 and 2
Herpes Simplex Virus Encephalitis
Neonatal Herpes Simplex Virus 2 Encephalitis
Benign Recurrent Lymphocytic Meningitis
Varicella-Zoster Virus
Herpes Zoster
Epstein-Barr Virus
Cytomegalovirus
Clinical Manifestations
Diagnosis and Treatment
Human Herpesvirus 6
John Cunningham Virus
Pathobiology
Clinical Features
Diagnosis
Treatment and Prognosis
Level 1 Evidence
70 Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS)
Introduction
Classification of HIV Disease
Epidemiology
Epidemiology of HIV Infection in Adults
Epidemiology of HIV Infection in Children
Etiology
Pathobiology
Primary HIV Infection
Progression to AIDs
Impact of Antiretroviral Therapy
Central Nervous System Pathogenesis
Diagnosis
Initial Diagnostic Approach
Neurological HIV-Related Syndromes
HIV Associated Neurocognitive Disorder
Stroke
Seizures
Leukoencephalopathy
Movement Disorders
Myelopathy
Motor Neuron Disease
Peripheral Neuropathy
Myopathy
Opportunistic Infections
Neoplasms
Nutritional and Metabolic Consequences
Management
Adverse Neurologic Effects of Drug Treatment for HIV Infection
Precautions for Clinical and Laboratory Services
Outcomes
SECTION XI DEMYELINATING AND INFLAMMATORY DISEASES
71 Multiple Sclerosis and Related CNS Neuroimmune Diseases
Introduction
Multiple Sclerosis
Introduction
Epidemiology
Pathobiology
Immunobiology
Pathology
Genetic Risk Factors
Environmental Influences
Diagnosis
Disease Course
Clinical Manifestations
Diagnostic Criteria
Imaging
Biomarkers
Differential Diagnosis
Management
Treatment of Acute Exacerbations
Disease-Modifying Drugs
Symptom Management
Pregnancy and Breastfeeding
Vaccination
Pediatric Multiple Sclerosis
Outcomes
Neuromyelitis Optica Spectrum Disorder
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Manifestations
Radiologic Manifestations
Biomarkers
Management
Outcomes
Anti–Myelin Oligodendrocyte Glycoprotein Syndromes
Epidemiology
Pathobiology
Diagnosis
Clinical Manifestations
Diagnostic Criteria
Biomarkers
Management
Level 1 Evidence
72 Transverse Myelitis
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Presentation
Magnetic Resonance Imaging
Cerebrospinal Fluid
Biomarkers of Transverse Myelitis
Other Investigations
Management
Outcome
Level 1 Evidence
73 Neuromyelitis Optica Spectrum Disorder
Introduction
Epidemiology
Worldwide Distribution/Ethnicity
Sex
Familial Occurrence
Risk Factors
Pathobiology
AQP4-IgG– and MOG-IgG–Mediated Immunopathology
T-cell Activation, Helper T Cell 17 Polarization, B-cell Recognition, and “Upstream” Pathogenesis
Diagnosis
Characteristic Symptoms and Diagnostic Criteria
Serologic Testing and Cerebrospinal Fluid
Red Flags, Comorbid Conditions, and Differential Diagnosis
Neuromyelitis Optica Spectrum Disorder Versus Multiple Sclerosis
AQP4-IgG– Versus MOG-IgG–Associated NMOSD
Management
Acute Attacks
Maintenance Therapy for Neuromyelitis Optica Spectrum Disorder
Maintenance for Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Disease
Outcomes
Mortality in Neuromyelitis Optica Spectrum Disorder
Disability in Neuromyelitis Optica Spectrum Disorder
Level 1 Evidence
74 Autoimmune Encephalitis and Meningitis
Introduction
Epidemiology
Pathobiology
Immunobiology
Immunopathology
Diagnosis
Clinical Manifestations
Autoimmune Meningitis
Autoimmune Encephalitis: General Features
Classical Encephalitis Syndromes
Clinically Restricted Forms
Nonlimbic Encephalitis: Serologically Defined Entities
Neural IgG Seronegative Autoimmune Encephalopathy
Imaging
MRI Brain Imaging
Positron Emission Tomography
Electroencephalography
Antibody Testing
Cancer Workup
Management
Acute Therapy
Chronic Therapy
Predictive Scores
Outcome
75 Neurosarcoidosis
Introduction
Epidemiology
Pathobiology
Clinical Manifestations
Cranial Nerves
Meninges
Brain Parenchyma
Spinal Cord
Diagnosis
Magnetic Resonance Imaging Findings
Cerebrospinal Fluid Findings
Peripheral Nervous System and Muscle Presentations
Management
Outcomes
SECTION XII MOVEMENT DISORDERS
76 Essential Tremor
Introduction
Epidemiology
Etiology
Pathobiology
Clinical Manifestations
Introduction
Tremor
Other Motor Features
Nonmotor Features
Natural History
Associated Morbidity and Mortality
Diagnosis
Treatment
Outcome
Level 1 Evidence
77 Tics and Tourette Syndrome
Introduction
Epidemiology
Pathobiology
Neurobiology
Motor Circuits
Neurotransmitters
Genetics
Immune System
Clinical Manifestations
Diagnosis
DSM-5 Tic Disorder Diagnoses
Scales
Coexisting Conditions
Attention Deficit Hyperactivity Disorder
Obsessive-Compulsive Behaviors and Obsessive-Compulsive Disorder
Anxiety and Depression
Other Psychopathologies
Academic Issues
Sleep Disorders
Management
Initial Management
Behavioral Treatment for Tics
Habit Reversal Training
Comprehensive Behavioral Intervention for Tics
Exposure Response Prevention
Complementary and Alternative Medications
Pharmacotherapy
Tier 1 Medications
Tier 2 Medications
Other Medications
Neuromodulation
Noninvasive Neuromodulation
Invasive Neuromodulation
Outcome
Conclusion
Level 1 Evidence
78 Restless Legs Syndrome
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Level 1 Evidence
79 The Dystonias
Introduction
Defining Features of Dystonia
Discrimination of Dystonia from Related Disorders
Additional Relevant Terminology
Classification of Dystonia Subtypes
Axis I: Clinical Manifestations
Axis II: Etiologies
Epidemiology
Isolated Dystonia Syndromes
Other Syndromes With Dystonia
Pathobiology
Anatomic Underpinnings of Dystonia
Physiologic Underpinnings of Dystonia
Muscle Activity
Neuronal Physiology
Network Physiology
Developmental or Degenerative Processes
Etiologies for Dystonia
Idiopathic Dystonias
Acquired Dystonias
Inherited Dystonias
Diagnosis
Approach to Clinical Evaluation
Diagnostic Imaging
Routine Laboratory Investigations
Genetic Testing
Management
Counseling
Oral Medications
Drugs Targeting Acetylcholine Pathways
Drugs Targeting Dopamine Pathways
Drugs Targeting γ-Aminobutyric Acid Pathways
Miscellaneous Drugs
Special Populations
Botulinum Neurotoxins
Applications
Contraindications and Side Effects
Surgical Treatments
Deep Brain Stimulation
Procedures Involving Focal Ablation
Procedures Involving Peripheral Nerve or Muscle
Physical and Occupational Therapy
Outcomes
Acknowledgments
80 Hemifacial Spasm
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Medication
Botulinum toxin injections
Surgery
Outcome
Medication
Botulinum toxin injections
Surgery
Level 1 Evidence
81 Myoclonus
Introduction
General Considerations
Epidemiology
Phenomenologic Characterization of Myoclonus
Cortical Myoclonus
Pathobiology
Clinical Manifestations
Diagnosis
Subcortical Including Brainstem Myoclonus
Pathobiology
Clinical Manifestations
Diagnosis
Spinal Myoclonus
Pathobiology
Clinical Manifestations
Diagnosis
Peripheral Myoclonus
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
82 Hereditary and Acquired Ataxias
Introduction
Neuroanatomy of the Cerebellum
Cerebellar Neurophysiology
Cerebellar Circuits
Control of Movement by the Cerebellum
Epidemiology
Clinical Approach to Cerebellar Ataxia
Signs and Symptoms of Ataxia
Neurologic Examination
Laboratory Testing
Neuroimaging
Other Diagnostic Tests
Acquired Ataxia
Cerebellar Stroke
Paraneoplastic and Autoimmune Ataxia
Classic Paraneoplastic Cerebellar Ataxia
Cerebellar Ataxias Resulting from Ion Channel Antibodies
Ataxia Due to Other Accessible/Cell-Surface Antigens
Gluten Ataxia
Neurosarcoidosis
Inherited Ataxias
Spinocerebellar Ataxia
Introduction
Genetic Testing
Autosomal Recessive Ataxia
Cerebellar Ataxia With Predominant Sensory Neuropathy (Friedreich Ataxia)
Cerebellar Ataxia with Sensorimotor Axonal Neuropathy
Cerebellar Ataxia Without Neuropathy
Other Inherited Ataxias
X-Linked Ataxia
Mitochondrial Ataxia
Episodic Ataxia
Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome
Degenerative Ataxia
Multiple System Atrophy
Idiopathic Late-Onset Cerebellar Ataxia
Psychogenic Ataxia
Management and Future Developments
83 Tardive Dyskinesia and Other Neuroleptic-Induced Syndromes
Introduction
Epidemiology
Pathobiology
Diagnosis
Acute Dystonic Reaction
Acute Akathisia
Drug-Induced Parkinsonism
Neuroleptic Malignant Syndrome
Tardive Dyskinesia Syndromes
Withdrawal Emergent Syndrome
Classic Tardive Dyskinesia
Tardive Dystonia
Tardive Akathisia
Other Tardive Syndromes
Management
Acute Dystonic Reaction
Acute Akathisia
Drug-Induced Parkinsonism
Neuroleptic Malignant Syndrome
Tardive Dyskinesia Syndromes
Outcome
Level 1 Evidence
84 Choreas
Introduction
Epidemiology
Pathobiology
Causes of Chorea
Autoimmune Choreas
Sydenham Disease
Systemic Lupus Erythematosus
Antiphospholipid Antibody Syndrome
Chorea due to Other Autoantibodies
Structural and Vascular Chorea and Ballism
Genetic Causes of Chorea
Autosomal Recessive
X Linked
Autosomal Dominant
Other Choreas
Diagnosis
Management
Outcome
Level 1 Evidence
85 Huntington Disease
Introduction
Epidemiology
Pathobiology
Genetics
Neuropathology
Neurochemistry
Diagnosis
Differential Diagnosis
Clinical Manifestations
Motor Signs
Cognitive Impairment
Behavioral Signs
Measures of Disease Progression
Clinical Progression Composite Measures
Structural and Molecular Imaging
Fluid Biomarkers
Management
Treatment of Movement Disorder
Antidopaminergic Agents for Chorea
Antiglutamatergic Therapy for Chorea
Treatment of Dystonia
Treatment of Voluntary Motor Impairment (Gait and Swallowing)
Treatment of Weight Loss
Treatment of Cognitive Impairment
Treatment of Psychiatric Symptoms
Disease-Modifying Therapies
Improving Mitochondrial Function and Reducing Oxidative Stress
Immune Modulation
mHTT Huntingtin-Lowering Strategies
Nonpharmacologic Treatments
Outcome
Level 1 Evidence
86 Parkinson Disease
Introduction
Epidemiology
Pathobiology
Pathology
Etiology
Genetics
Pathogenesis
Clinical Manifestations
Signs and Symptoms
Tremor
Bradykinesia
Rigidity
Postural Instability
Dystonia
Speaking and Swallowing
Freezing
Parkinson Mimics
Clinical Course
Non-Motor Manifestations
Differential Diagnosis
Overview of Parkinson Disease Treatment
Levodopa
Levodopa-Induced Dyskinesias
Levodopa and Adjunctive Therapies
COMT Inhibitors
MAO-B Inhibitors
Amantadine
Anticholinergic (Antimuscarinic) Drugs
Dopaminergic Agonists
Adenosine A2A Antagonists
Treating the Nonmotor Problems of Parkinson Disease
Mental and Behavioral Complications
Other Non-Motor Symptoms
Surgical Therapy
Outcome
Level 1 Evidence
87 Parkinson-Plus Syndromes
Introduction
Parkinson-Plus Syndromes
Progressive Supranuclear Palsy
History
Pathobiology
Symptoms and Signs
Multiple System Atrophy
History
Pathobiology
Symptoms and Signs
Corticobasal Degeneration
History
Pathobiology
Symptoms and Signs
Epidemiology
Diagnosis
Treatment
Other Parkinson-Like Syndromes
Drug/Toxin-Induced Parkinsonism
Dopamine Receptor–Blocking Drugs
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine
Other Drugs Besides Dopamine Receptor Blockers and 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine
Lytico-Bodig (Parkinson-Dementia-Amyotrophic Lateral Sclerosis Complex of Guam)
Hemiparkinsonism-Hemiatrophy Syndrome
Normal Pressure Hydrocephalus
Parkinson-Dementia Syndromes
Postencephalitic Parkinsonism
Vascular Parkinsonism
SECTION XIII NEUROMUSCULAR DISEASES
88 Amyotrophic Lateral Sclerosis and Motor Neuron Diseases
Introduction
Amyotrophic Lateral Sclerosis
Epidemiology
Pathobiology
Genetics
Neuropathology
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Clinical Manifestations
Diagnosis
Amyotrophic Lateral Sclerosis Diagnostic Criteria
Motor Neuron Disease Variants
Progressive Muscular Atrophy
Primary Lateral Sclerosis
Progressive Bulbar Palsy
Monomelic Muscular Atrophy
Bibrachial Amyotrophy
Diagnostic Testing
Electrodiagnostic Testing
Neuroimaging
Lab Testing
Muscle Biopsy
Differential Diagnoses
Multifocal Motor Neuropathy
Myasthenia Gravis
Spinal Stenosis
Myopathy
Postpolio Syndrome
Benign Fasciculations
Spinobulbar Muscular Atrophy (Kennedy Disease)
Management
Pharmacotherapy
Multidisciplinary Supportive Care
Outcome
Level 1 Evidence
89 Bell's Palsy and Cranial Neuropathies
Introduction
The Olfactory Nerve (Cranial Nerve 1)
The Trigeminal Nerve (Cranial Nerve V)
Trigeminal Neuralgia
Epidemiology and Pathobiology
Diagnosis
Management and Outcome
The Facial Nerve (Cranial Nerve VII)
Bell’s Palsy
Epidemiology and Pathobiology
Diagnosis
Treatment and Outcome
Ramsay Hunt Syndrome
Other Causes of Facial Nerve Injury
The Glossopharyngeal Nerve (Cranial Nerve IX)
Glossopharyngeal Neuralgia
The Vagus Nerve (Cranial Nerve X)
The Spinal Accessory Nerve (Cranial Nerve XI)
The Hypoglossal Nerve (Cranial Nerve XII)
Level 1 Evidence
90 Mononeuropathies and Compression Neuropathies
Approach to Peripheral Nerve Disorders
Epidemiology
Clinical Features
Etiology and Diagnosis
Outcome
The Spinal Roots and Brachial Plexus
Trunk and Root Injury
Upper Radicular Syndrome
Middle Radicular Syndrome
Lower Radicular Syndrome (Klumpke Palsy)
Cord Injury
Diffuse Plexus Injury
Thoracic Outlet Syndrome
Pathology
Clinical Features
Diagnosis and Treatment
The Spinal Roots and Lumbar and Sacral Plexuses
The Lumbar Plexus
The Sacral Plexus
Radiation Plexopathy
The Proximal Nerves of the Arm
The Axillary Nerve
The Long Thoracic Nerve
The Brachial Cutaneous and Antebrachial Cutaneous Nerves
The Suprascapular Nerve
The Peripheral Nerves
The Radial Nerve
The Median Nerve
The Ulnar Nerve
The Musculocutaneous Nerve
The Nerves of the Leg
The Obturator Nerve
The Iliohypogastric Nerve
The Ilioinguinal Nerve
The Genitofemoral Nerve
The Lateral Femoral Cutaneous Nerve of the Thigh
The Femoral Nerve
The Sciatic Nerve
The Common Fibular Nerve
The Tibial Nerve
Mononeuropathies in Diabetes Mellitus
91 Acquired Peripheral Neuropathies
Approach to Peripheral Nerve Disorders
Epidemiology
Clinical Features
Etiology and Diagnosis
Treatment
Outcome
Specific Acquired Polyneuropathies
Guillain-Barré Syndrome
Epidemiology
Pathobiology
Clinical Features
Diagnosis and Differential Diagnosis
Treatment
Outcome
Chronic Inflammatory Demyelinating Polyneuropathy
Multifocal Motor Neuropathy
Sensory Neuronopathy and Neuropathy
Idiopathic Autonomic Neuropathy
Vasculitic and Cryoglobulinemic Neuropathies
Neuropathies Associated With Myeloma and Nonmalignant Immunoglobulin G or Immunoglobulin A Monoclonal Gammopathies
Neuropathies Associated With Immunoglobulin M Monoclonal Antibodies That React With Peripheral Nerve Glycoconjugate Antigens
Progressive Inflammatory Neuropathy (Among Swine Slaughterhouse Workers)
Amyloid Neuropathy
Neuropathy Associated With Carcinoma (Paraneoplastic Neuropathy)
Hypothyroid Neuropathy
Acromegalic Neuropathy
Hyperthyroid Neuropathy
Celiac Neuropathy
Uremic Neuropathy
Neuropathy Associated With Hepatic Disease
Neuropathies Associated With Infection
Neuropathy of Leprosy
Diphtheritic Neuropathy
HIV-Related Neuropathies
Neuropathy of Herpes Zoster
Lyme Neuropathy
Sarcoid Neuropathy
Polyneuropathy Associated With Dietary States
Critical Illness Polyneuropathy
Neuropathies Caused by Heavy Metals
Arsenic
Lead
Mercury
Thallium
Other Chemicals
Neuropathies Caused by Therapeutic Drugs
Alcoholic Neuropathy
Diabetic Neuropathy
Generalized Polyneuropathies
Idiopathic Neuropathy
Level 1 Evidence
92 Inherited Peripheral Neuropathies
Introduction
Epidemiology
Pathobiology
Clinical Presentation
Diagnosis
Genetic Testing
Age of Onset and Progression
Associated Symptoms and Signs
Neurophysiologic Pattern
Inheritance Pattern
At-Risk Populations
Management
Gene Therapy
Normalization of Gene Dosage
Neurotrophic Support
Reduction of Neurotoxic Aggregates/Misfolded Proteins
Targeting Transport Defects
Cellular Reprogramming and High-Throughput Therapeutic Screening
Outcome
93 Myasthenia Gravis and Other Disorders of the Neuromuscular Junction
Introduction
Myasthenia Gravis
Epidemiology
Pathobiology
Autoimmune Antibodies
T Cell Autoimmunity
New Insights
Diagnosis
Clinical Features
Laboratory Testing and Electrophysiologic Testing
Management
Acetylcholinesterase Inhibitors
Glucocorticoids
Steroid-Sparing Agents
Plasma Exchange and Intravenous Immunoglobulins
Other Immunomodulatory Treatments
Thymectomy
Myasthenic Crisis
Vaccination in Myasthenia Gravis
Pregnancy and Myasthenia Gravis
Outcome
Congenital Myasthenic Syndromes
Neonatal Myasthenia Gravis
Congenital Myasthenic Syndromes
Presynaptic Congenital Myasthenic Syndromes
Synaptic Basal Lamina-Associated Syndromes
Defects in the Acetylcholine Receptor
Defects in Postsynaptic Membrane
Defects in Glycosylation
Other Congenital Myasthenic Syndromes
Treatment of Congenital Myasthenic Syndromes
Drug-Induced Myasthenia Gravis
Penicillamine
Immune Checkpoint Inhibitors
Medications Which may Exacerbate Myasthenia Gravis
Lambert-Eaton Myasthenic Syndrome
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Electrodiagnosis and Laboratory Testing
Management
Botulism
Epidemiology and Pathobiology
Diagnosis
Clinical Features
Laboratory and Electrodiagnostic Testing
Management
Acknowledgment
Level 1 Evidence
94 Inflammatory and Autoimmune Myopathies
Introduction
Dermatomyositis
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Antisynthetase Syndrome and Overlap Myositis
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Sporadic Inclusion Body Myositis
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Immune-Mediated Necrotizing Myopathy
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Polymyositis
Muscle Pathology
Dermatomyositis
Antisynthetase Syndrome
Polymyositis and Inclusion Body Myositis
Immune-Mediated (Autoimmune) Necrotizing Myopathy
Level 1 Evidence
95 Critical Illness Myopathy and Neuropathy
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Manifestations
Laboratory Testing and Electrophysiology
Muscle Biopsy
Management
Outcome
Level 1 Evidence
96 Endocrine and Toxic Myopathies
Introduction
Endocrine Myopathies
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Testing
Management
Outcome
Toxic Myopathies
Epidemiology
Pathobiology
Diagnosis
Clinical Features
Diagnostic Testing
Management
Outcome
97 Periodic Paralysis and Other Channelopathies
Introduction
Hypokalemic Periodic Paralysis
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Management and Outcome
Hyperkalemic Periodic Paralysis
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Management and Outcome
Andersen-Tawil Syndrome
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Management and Outcome
Nondystrophic Myotonias
Epidemiology and Pathobiology
Clinical Manifestations and Diagnosis
Management and Outcome
Acknowledgment
Level 1 Evidence
98 Stiff Person Syndrome and Peripheral Nerve and Muscle Hyperexcitability
Introduction
Stiff Person Syndrome
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Laboratory Data
Electrophysiology
Imaging
Treatment and Outcomes
Other Central Nervous System Disorders of Muscle Stiffness
Peripheral Nerve and Muscle Hyperexcitability
Acquired Neuromyotonia (Isaac Syndrome)
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment
Tetany
Neuroleptic Malignant Syndrome and Malignant Hyperthermia
Muscle Cramps
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment
Outcome
Level 1 Evidence
99 Metabolic and Mitochondrial Myopathies in Adults
Introduction
Epidemiology
Pathobiology
Diagnosis
Disorders of Glycogen Metabolism (Glycogenoses)
Disorders of Lipid Metabolism
Mitochondrial Diseases
Approach to Diagnostic Testing
Management
Outcome
Level 1 Evidence
SECTION XIV NEUROONCOLOGY
100 Gliomas
Introduction
Epidemiology
Pathobiology
Molecular Features of Gliomas
Diagnosis
Management
Surgery
Radiation Therapy
Chemotherapy
Outcome
Astrocytomas
Pilocytic Astrocytoma
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Diffuse Astrocytoma
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Anaplastic Astrocytoma and Glioblastoma
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Oligodendrogliomas
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Management of WHO Grade II Diffuse Oligodendrogliomas
Management of WHO Grade III Anaplastic Oligodendrogliomas
Outcome
Level 1 Evidence
101 Metastatic Tumors
Introduction
Overview of Metastatic Tumors
Epidemiology
Pathobiology
Diagnosis
History and Physical Examination
Laboratory Studies
Imaging
Tissue Diagnosis
Management
Corticosteroids and Antiepileptics
Surgery
Radiation Therapy
Chemotherapy
Brain Metastasis
Epidemiology and Clinical Manifestations
Diagnosis
Management
Focal Treatment
Whole Brain Radiation Therapy in Addition to Focal Treatment
Reirradiation
Chemotherapy, Targeted Therapy, and Immunotherapy
Epidural Spinal Column Metastasis
Epidemiology and Clinical Manifestations
Diagnosis
Management
Leptomeningeal Metastasis
Epidemiology and Clinical Presentation
Diagnosis
Management
Conclusions
Level 1 Evidence
102 Meningiomas
Introduction
Meningiomas
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment
Surgery
Radiotherapy
Chemotherapy
Outcomes
World Health Organization Grade I Meningioma
World Health Organization Grade II Meningioma
World Health Organization Grade III Meningioma
Incidental Meningioma
Other Dural Diseases
Hemangiopericytomas
Dural Metastases
Hypertrophic Pachymeningitis
103 Primary Central Nervous System Lymphoma
Introduction
Epidemiology
Pathobiology
Clinical Features and Diagnosis
Treatment
Newly Diagnosed Primary Central Nervous System Lymphoma
Treatment of Primary Central Nervous System Lymphoma in Elderly Patients
Relapsed and Refractory Primary Central Nervous System Lymphoma
Neurotoxicity
Outcome
Level 1 Evidence
104 Tumors of the Pituitary Gland
Introduction
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Radiographic Features
Endocrine Evaluation
Differential Diagnosis
Management
Surgery
Radiation Therapy
Recurrent Tumors
Outcome
Surgery
Radiation Therapy
Medical Therapy
105 Pineal Region Tumors
Introduction
Epidemiology
Pathobiology
Histologic Subtypes
Germ Cell Tumors
Pineal Cell Tumors
Gliomas
Meningiomas
Metastasis and Other Miscellaneous Tumors
Pineal Cysts
Clinical Features
Diagnosis
Management
Management of Hydrocephalus
Surgery
Postoperative Staging
Radiotherapy
Chemotherapy
Outcome
106 Acoustic Neuroma and Other Skull Base Tumors
Vestibular Schwannoma (Acoustic Neuroma)
Epidemiology
Pathobiology
Diagnosis
Management and Outcomes
Observation/Expectant Management
Stereotactic Radiosurgery
Surgical Resection
Chemotherapy
Malignant Tumors of the Skull and Skull Base
Metastasis to the Skull Base
Epidemiology
Diagnosis
Management and Outcomes
Extension of Malignant Tumors to the Skull Base
Primary Malignant Tumors of the Skull and Skull Base
Chondrosarcoma
Chordoma
Osteogenic Sarcoma
Soft-Tissue Sarcoma
Glomus Jugulare Tumors
Benign Tumors of the Skull
Osteoma
Chondroma
Hemangioma
Dermoid and Epidermoid Tumors
Neoplastic-Like Lesions of the Skull
Hyperostosis
Fibrous Dysplasia
Paget Disease (Osteitis Deformans)
Mucocele
Miscellaneous
107 Spinal Tumors
Introduction
Epidemiology
Pathobiology
Clinical Features
Extramedullary Tumors
Extradural (Epidural) Tumors
Epidural Spinal Cord Metastasis
Intradural Extramedullary Tumors
Intramedullary Tumors
Primary Intramedullary Tumors
Intramedullary Metastases
Regional Syndromes
Foramen Magnum Tumors
Cervical Tumors
Thoracic Tumors
Lumbar Tumors
Tumors of the Conus and Cauda Equina
Diagnosis
Radiography
Cerebrospinal Fluid
Management
Intradural Extramedullary Tumors
Intramedullary Tumors
Epidural Disease from Metastatic Cancer
Outcome
Level 1 Evidence
108 Paraneoplastic Syndromes
Introduction
Epidemiology
Pathobiology
Clinical Manifestations
Encephalitis
Epilepsy
Myelitis
Cerebellar Ataxia
Neuropathies
Sensory Neuronopathy
Sensory-Motor Neuropathies
Autonomic Neuropathies
Motor Neuropathies
Peripheral Hyperexcitability
Neuromuscular Junction Disorders
Myopathy
Movement Disorders
Paraneoplastic Disorders Affecting the Eyes
Management
Diagnosis
Treatment
Outcomes
Level 1 Evidence
109 Complications of Cancer Therapy
Introduction
Neurologic Complications of Radiotherapy
Introduction
Pathobiology
Clinical Manifestation, Epidemiology, and Diagnosis
Acute Encephalopathy
Pseudoprogression or Worsening of Preexisting Symptoms
Focal Radionecrosis
Leukoencephalopathy and Cognitive Impairment
Radiation-Induced Myelopathy
Cranial Neuropathies
Brachial and Lumbosacral Plexopathies
Indirect Radiation-Induced Complications to Nervous System
Management and Outcome
Neurologic Complications of Chemotherapy
Introduction
Pathobiology
Clinical Manifestations, Epidemiology, and Diagnosis
Acute or Subacute Encephalopathy
Acute Cerebellar Syndrome
Posterior Reversible Encephalopathy Syndrome
Chronic Leukoencephalopathy
Peripheral Neuropathy
Management and Outcome
Neurologic Complications of Biologic Agents
Monoclonal Antibodies
Small Molecule Inhibitors
Neurologic Complications of Immunotherapy
Introduction, Epidemiology, and Pathobiology
Clinical Manifestations and Diagnosis
Management and Outcome
Neurologic Complications of Hematopoietic Stem Cell Transplantation
Introduction and Epidemiology
Pathobiology, Clinical Manifestations, and Diagnosis
Management and Outcome
Conclusion
Level 1 Evidence
SECTION XV HYDROCEPHALUS AND CEREBRAL EDEMA
110 Hydrocephalus
Introduction
Classification
Cerebrospinal Fluid Diversion Systems
Acute Obstructive Hydrocephalus
Epidemiology
Pathobiology
Stroke and Intraventricular Hemorrhage
Tumor Related (Ball and Valve)
Clinical Features
Diagnosis
Treatment and Outcomes
Congenital Obstructive Hydrocephalus
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment and Outcomes
Communicating Hydrocephalus
Normal-Pressure Hydrocephalus
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Treatment and Outcomes
Low-Pressure Hydrocephalus
Epidemiology
Pathobiology
Clinical Diagnosis
Treatment and Outcome
External Hydrocephalus
General Complications After Shunt Placement
Level 1 Evidence
111 Brain Edema and Increased Intracranial Pressure
Introduction
Brain Edema
Pathobiology
Vasogenic Edema
Cytotoxic Edema
Osmotic Edema
Interstitial (Hydrocephalic) Edema
Selected Causes of Brain Edema
Cerebral Infarction
Intracerebral Hemorrhage
Subarachnoid Hemorrhage
Venous Infarction
Cardiac Arrest
Traumatic Brain Injury
Brain Tumors
Fulminant Hepatic Encephalopathy
Reye Syndrome
Brain Abscess
Viral Encephalitis
Meningitis
Posterior Reversible Encephalopathy Syndrome
High-Altitude Cerebral Edema
Postendarterectomy Hyperperfusion Syndrome
Intracranial Pressure Management
General Approach
Tiered Approach to Intracranial Pressure Management in a Monitored Patient
Advanced Treatment Options for Medically Refractory Intracranial Pressure
Salvage Interventions for Super-Refractory Intracranial Pressure
Specific Treatments for Brain Edema
Glucocorticoids
Mannitol
Hypertonic Saline
Idiopathic Intracranial Hypertension
Causes of Idiopathic Intracranial Hypertension
Endocrine and Metabolic Disorders
Drugs and Toxins
Hematologic and Connective Tissue Disorders
Pulmonary Encephalopathy
Spinal Cord Diseases
Pathobiology
Clinical Features
Diagnosis
Treatment
Level 1 Evidence
112 Spontaneous Intracranial Hypotension
Introduction
Spontaneous Intracranial Hypotension
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
General Management
Outcomes
Postcraniotomy Brain Sagging
Clinical Features
Diagnosis
Management
SECTION XVI SPINAL CORD DISORDERS
113 Intervertebral Disk Disease and Radiculopathy
Introduction
Epidemiology
Pathophysiology
Intervertebral Disk Disease
Clinical Features
Radicular Pain and Lumbar Disk Disease
Thoracic Disk Rupture
Cervical Disk Disease
Myelopathy
Diagnosis
Initial Management and Evaluation
Considerations in the Cervical Spine
Other Diagnostic Considerations
Imaging and Electrodiagnostic Studies
Magnetic Resonance Imaging
Myelography and X-ray
Electromyography and Nerve Conduction Studies
Treatment
Expert Referral
Lumbar Diskectomy
Cervical Diskectomy
Summary
Level 1 Evidence
114 Cervical and Lumbar Spinal Stenosis
Introduction
Epidemiology
Pathobiology
Spondylosis
Congenital Stenosis
Myelopathy
Pain
Diagnosis
Clinical Manifestations
Cervical Stenosis
Lumbar Stenosis
Physical Examination
Radiographic Studies
Plain Radiography
Computed Tomography and Computed Tomography Myelography
Magnetic Resonance Imaging
Additional Tests
Management
Cervical Stenosis
Lumbar Stenosis
Outcomes
Level 1 Evidence
115 Acquired and Hereditary Myelopathies
Introduction
Syringomyelia
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Neoplastic Myelopathy
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Infectious Myelopathy
Viral Myelitis
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Human T-cell Lymphotropic Virus-Associated Myelopathy (Tropical Spastic Paraparesis)
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Inflammatory Myelopathy
Clinical Features
Diagnosis
Management
Outcome
Vascular Myelopathy
Spinal Cord Infarction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Spinal Arteriovenous Malformations and Fistulas
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Toxic/Metabolic Causes of Myelopathy
Myelopathy due to Radiation or Chemotherapy
Nitrous Oxide Toxicity
Hepatic Myelopathy
Genetic Causes of Myelopathy
Hereditary Spastic Paraplegia
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Outcome
Level 1 Evidence
SECTION XVII AUTONOMIC AND SLEEP DISTURBANCES
116 Autonomic Failure, Autonomic Neuropathy, and Orthostatic Intolerance
Introduction
Epidemiology
Acute and Subacute Autonomic Disorders
Paraneoplastic Autonomic Neuropathy
Orthostatic Intolerance
Chronic Neurogenic Orthostatic Hypotension and Autonomic Neuropathy
Parkinsonian Syndromes and Pure Autonomic Failure
Chronic Autonomic Neuropathies
Diagnosis and Management of Autonomic Disorders
Hereditary Sensory and Autonomic Neuropathy and Familial Dysautonomia
Familial Dysautonomia (Riley-Day Syndrome)
Clinical Manifestations
Diagnosis
Biochemical and Pathologic Data
Treatment
Outcome
Other Hereditary Autonomic Disorders
Acknowledgment
117 Paroxysmal Sympathetic Hyperactivity After Acute Brain Injury
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Manifestations
Diagnostic Criteria
Management
Outcome
118 Sleep Disorders
Introduction
Physiology of Normal Sleep
Neuroanatomy and Neurochemistry of Sleep
Specific Disorders of Sleep
Insomnia
Diagnosis
Management
The Hypersomnias
Narcolepsy
Kleine-Levin Syndrome
Sleep-Related Breathing Disorders
Snoring
Sleep Apnea
Hypoventilatory and Hypoxemic Disorders
Catathrenia
Sleep-Related Movement Disorders
Restless Legs Syndrome and Periodic Limb Movement Disorder
Sleep-Onset Movements
Sleep-Related Movements
Circadian Rhythm Disorders
Delayed Sleep Phase
Advanced Sleep Phase
Nonentrained and Irregular Sleep Phase
Nocturnal Behaviors
Parasomnias
Non–Rapid Eye Movement Parasomnias
Rapid Eye Movement Parasomnias
Conclusion
Level 1 Evidence
SECTION XVIII SYSTEMIC ORGAN FUNCTION AND THE NERVOUS SYSTEM
119 Heart-Brain Interactions
Introduction
Cerebral Complications of Cardiac Procedures
Epidemiology
Pathobiology
Diagnosis
Management
Prevention
Acute Ischemic Stroke
Intracranial Hemorrhage
Outcome
Cardiovascular Complications of Neurologic Injury
Neurogenic Stunned Myocardium
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment and Outcome
Paroxysmal Sympathetic Storming
Epidemiology
Clinical Features
Diagnosis
Management
Outcome
Level 1 Evidence
120 Sepsis-Associated Encephalopathy
Introduction
Epidemiology
Pathobiology
Brain Signaling
Neuroinflammation and Glial Cell Activation
Astrocytes and Blood-Brain Barrier Dysfunction
Ischemic Processes
Neurotransmitter Dysfunction
Diagnosis
Clinical Features
Brain Imaging
Continuous Electroencephalogram Monitoring
Management
Outcome
Impact of Sepsis-Associated Encephalopathy on Survival
Impact on Sepsis-Associated Encephalopathy on Long-term Outcome
Societal Cost of Sepsis-Associated Encephalopathy
Conclusion
Level 1 Evidence
121 Respiratory Support for Neurologic Diseases
Introduction
Epidemiology
Pathobiology
Pulmonary Gas Exchange
Respiratory Failure
Effects of Respiratory Compromise on Neurologic Injury
Diagnosis
Examination
Pulmonary Function Testing
Blood Gas Analysis and Monitoring
Management of Respiratory Failure
Noninvasive Positive Pressure Ventilation
Endotracheal Intubation and Mechanical Ventilation
Manipulation of Ventilation: Effects on Intracranial Pressure and Cerebral Blood Flow
Prevention of Ventilator-Associated Pneumonia
Weaning from Mechanical Ventilation
Tracheostomy
Long-Term Ventilation
Outcomes
Level 1 Evidence
122 Endocrine Diseases and the Brain
Introduction
Pituitary Disorders
Hypopituitarism
Epidemiology
Pathobiology
Clinical Features, Diagnosis, and Treatment
Hyperpituitarism
Epidemiology
Pathobiology
Clinical Features, Diagnosis, and Treatment
Pituitary Tumors
Pituitary Adenomas
Other Pituitary Tumors
Other Pituitary Disorders
Pituitary Apoplexy
Empty Sella
Thyroid Disease
Hypothyroidism
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Hyperthyroidism
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Diabetes Mellitus
Epidemiology
Etiology
Clinical Features
Neurologic Complications
Diagnosis
Management
Adrenal Disease
Adrenal Insufficiency
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Hyperadrenalism
Cushing Syndrome
Hyperaldosteronism
Pheochromocytoma
Parathyroid Disease
Hypoparathyroidism
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
Hyperparathyroidism
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Management
123 Hematologic Diseases and the Brain
Red Blood Cell Disorders
Anemia
Anemia and Transfusion in Hospitalized and Critically Ill Neurologic Patients
Sickle Cell Disease
Polycythemia
Polycythemia Vera
White Blood Cell Disorders
Malignancies of Lymphoid Cells
Lymphoma, Lymphoblastic Leukemia, and Posttransplant Lymphoproliferative Disorders
Plasma Cell Malignancies
Acute Myeloid Leukemia
Hematopoietic Cell Transplantation
Epidemiology
Pathobiology
Clinical Manifestations, Diagnosis, and Treatment
Platelet Disorders
Thrombocytopenia
Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome
Heparin-Induced Thrombocytopenia
Impaired Platelet Function
Thrombocytosis
Essential Thrombocythemia
Coagulation Disturbances
Normal Coagulation
Impaired Coagulation
Warfarin-Induced Intracranial Hemorrhage
Reversal of Novel Oral Anticoagulants
Bleeding Associated With Thrombolytic Therapy
Bleeding Associated With Unfractionated or Low Molecular Weight Heparin
Hypercoagulable States
Familial Thrombophilia
Antiphospholipid Antibody Syndrome
Level 1 Evidence
124 Hepatic Disease and the Brain
Introduction
Cirrhosis and Hepatic Encephalopathy
Epidemiology
Pathobiology
Clinical Features
Cirrhosis
Minimal Hepatic Encephalopathy
Overt Hepatic Encephalopathy
Hepatic Myelopathy
Persistent Hepatic Encephalopathy
Diagnosis
Minimal Hepatic Encephalopathy
Overt Hepatic Encephalopathy
Treatment
Minimal Hepatic Encephalopathy
Overt Hepatic Encephalopathy
Outcome
Acute Liver Failure and Cerebral Edema
Epidemiology
Pathobiology
Multiple Organ Failure
Encephalopathy and Cerebral Edema
Clinical Features
Diagnosis
Treatment
General Management
High-Volume Plasma Exchange
Intracranial Pressure and Transcranial Doppler Monitoring
Intracranial Pressure Management
Seizures
Ammonia Clearance
Artificial Liver Support Systems
Transplantation
Outcome
Level 1 Evidence
125 Renal Disease, Electrolyte Disorders, and the Nervous System
Introduction
Uremic Encephalopathy
Pathobiology
Diagnosis
Treatment
Dialysis Disequilibrium Syndrome
Dialysis Dementia
Cerebrovascular Disease
Restless Legs Syndrome
Peripheral Neuropathy
Pathobiology
Diagnosis
Management
Myopathy
Neurologic Complications of Renal Transplantation
Posterior Reversible Encephalopathy Syndrome
Primary Central Nervous System Lymphoma
Opportunistic Infections
Hyponatremia
Clinical Features
Diagnosis
Management
Acute Symptomatic Hyponatremia
Chronic Hyponatremia
Osmotic Demyelination Syndrome
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Prevention and Treatment
Outcome
126 Gastric and Genitourinary Function and the Brain
Introduction
Neuroanatomy
Gastrointestinal Manifestations of Neurologic Disease
Dysphagia
Esophageal Dysmotility
Gastroparesis
Stress Gastric Ulcer
Bowel Dysmotility
Incontinence
Urinary Manifestations of Neurologic Disease
Voiding Dysfunction
Storage Dysfunction
Sexual Manifestations of Neurologic Disease
Female Sexual Dysfunction
Male Sexual Dysfunction
Neurologic Disorders and the Gastrointestinal and Genitourinary Systems
Peripheral Neuropathy
Spinal Cord Injury
Multiple Sclerosis
Parkinsonism
Cortical and Subcortical Disease
Neurologic Consequences of Primary Gastrointestinal Disease
The Microbiome-Gut-Brain Axis and Neurologic Disease
Level 1 Evidence
127 Bone Diseases and the Central Nervous System
Paget Disease
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Fibrous Dysplasia
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Achondroplasia
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Ankylosing Spondylitis
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Atlantoaxial Dislocation
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Fractures and Secondary Osteoporosis: Neurologic Causes
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Level 1 Evidence
128 Malnutrition, Malabsorption, and Vitamin Deficiencies
Introduction
Causes of Nutritional Deficiencies
Vitamin Deficiency and Excess Syndromes
Vitamin B12 (Cobalamin) Deficiency
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Vitamin B1 (Thiamine) Deficiency
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Vitamin B6 (Pyridoxine) Deficiency or Excess
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Vitamin B9 (Folic Acid) Deficiency
Vitamin B3 (Niacin) Deficiency
Vitamin A Deficiency or Toxicity
Vitamin D Deficiency
Vitamin E Deficiency
Mineral Deficiency and Excess Syndromes
Copper Deficiency and Toxicity
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Wilson Disease
Other Mineral Deficiencies and Toxicities
Neurologic Complications of Bariatric Surgery
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Neurologic Complications of Gluten-Related Disorders
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
129 Neurologic Disease During Pregnancy
Introduction
Biology of Pregnancy
Epilepsy
Epidemiology
Seizure Control and Monitoring Antiseizure Medication Concentrations
Teratogenicity
Effects of Antiseizure Medications on Cognition
Management of Epilepsy During Pregnancy
Breastfeeding
Preeclampsia and Eclampsia
Epidemiology
Clinical Features
Diagnosis
Treatment
Stroke
Epidemiology
Ischemic Stroke
Cerebral Venous Thrombosis
Diagnosis
Treatment
Intravenous Thrombolysis
Mechanical Thrombectomy
Unfractionated and Low Molecular Weight Heparin
Cerebral Hemorrhage
Epidemiology
Diagnosis and Treatment
Multiple Sclerosis
Epidemiology
Clinical Features
Pathobiology
Treatment
Migraine
Epidemiology
Clinical Features
Pathobiology
Diagnosis
Treatment
Neoplasms
Epidemiology
Clinical Features and Diagnosis
Treatment
Neuropathies
Carpal Tunnel Syndrome
Bell Palsy
Meralgia Paresthetica
Myasthenia Gravis
Epidemiology
Clinical Features
Treatment
Movement Disorders
Restless Legs Syndrome
Chorea Gravidarum
Parkinsonism and Idiopathic Parkinson Disease
Level 1 Evidence
130 Neurologic Complications of Organ Transplantation
Introduction
General Considerations
Central Nervous System Infections
Encephalopathy and Delirium
Drug Toxicity
Organ-Specific Complications
Lung Transplantation
Cardiac Transplantation
Liver Transplantation
Intestinal Transplantation
Long-Term Effects of Immunosuppression
Conclusions
SECTION XIX NEUROLOGIC TOXIDROMES
131 Alcoholism
Introduction
Acute Ethanol Syndromes
Intoxication
Ethanol-Drug Interactions
Ethanol Withdrawal
Clinical Manifestations
Pathobiology
Management
Chronic Ethanol Syndromes
Wernicke-Korsakoff Syndrome
Clinical Manifestations
Pathobiology
Management and Outcome
Alcoholic Cerebellar Degeneration
Alcoholic Polyneuropathy
Alcoholic Amblyopia
Pellagra
Alcoholic Liver Disease
Hypoglycemia
Alcoholic Ketoacidosis
Infection in Alcoholics
Trauma in Alcoholics
Alcohol and Cancer
Alcohol and Stroke
Alcoholic Myopathy
Central Pontine Myelinolysis and Marchiafava-Bignami Disease
Alcoholic Dementia
Fetal Alcohol Spectrum Disorders
Treatment of Chronic Alcoholism
132 Drug Intoxication and Withdrawal
Introduction
Drugs of Dependence
Opioids
Psychostimulants
Sedatives
Marijuana
Hallucinogens
Inhalants
Phencyclidine
Anticholinergics
Complications of Drug Toxidromes
Trauma
Infection
Seizures
Stroke
Altered Mentation
Fetal Effects
Miscellaneous Effects
133 Neurotoxicology
Introduction
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Outcome
Common Neurotoxidromes
Anticholinergic Toxicity
Clinical Features
Treatment
Sympathomimetic Toxicity and Acute Excited State
Clinical Features
Diagnosis
Treatment
Cholinergic Toxicity: Organophosphates and Carbamates
Epidemiology
Pathobiology
Clinical Features
Diagnosis
Treatment
Outcome
Neuroleptic Malignant Syndrome
Clinical Features
Diagnosis
Treatment
Outcome
Serotonin Syndrome
Pathobiology
Diagnosis
Management
Carbon Monoxide Poisoning
Clinical Features
Diagnosis
Treatment
Malignant Hyperthermia
Strychnine Poisoning
Methanol (Methyl Alcohol)
Volatile Organic Compounds
Nitrous Oxide Myelopathy
Heavy Metals
Lead
Mercury
Arsenic
Thallium
Manganese
Aluminum
Plant, Animal, and Marine Neurotoxins
Acknowledgment
134 Radiation Injury
Introduction
Epidemiology
Pathobiology
Diagnosis
Acute Radiation Sickness
Cerebral Edema and Early Delayed Leukoencephalopathy
Radiation Necrosis
Myelopathy
Radiation-Induced Vasculopathy and SMART Syndrome
Neuropathy and Plexopathy
Optic Neuropathy and Ocular Neuromyotonia
Neuroendocrine Dysfunction
Neurocognitive Effects
Management
Outcome
Level 1 Evidence
135 Electrical and Lightning Injury
Introduction
Epidemiology
Pathobiology
Electrical Injuries
Lightning Strikes
Clinical Features
Diagnosis
Management
Outcome
136 Decompression Illness
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Level 1 Evidence
SECTION XX PEDIATRIC NEUROLOGY
137 Neonatal Neurology
Introduction
Germinal Matrix-Intraventricular Hemorrhage
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Prevention
Therapeutic Intervention
Outcome
Perinatal Asphyxia/Hypoxic-Ischemic Encephalopathy
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Neonatal Seizures
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Stroke and Sinus Venous Thrombosis
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Periventricular Leukomalacia
Epidemiology
Pathobiology
Clinical Manifestations
Diagnosis
Management
Outcome
Level 1 Evidence
138 Nervous System Formation and Malformation
Overview
Formation of Neuroectoderm
Neural Tube Closure
Primary Neurulation
Specific Neural Tube Defects
Encephaloceles
Meckel Syndrome
Embryonic Nervous System Segmentation
Transcriptional Factors and Homeobox Genes
Septo-Optic Dysplasia
Ventral Induction
Normal Prosencephalon Division
Disorders of Ventral Induction
Holoprosencephaly
Neuronal and Glial Proliferation
Normal Cell Proliferation
Disorders of Neuronal and Glial Proliferation
Microcephaly
Megalencephaly and Hemimegalencephaly
Neuronal Differentiation
Normal Differentiation
Neuronal Migration
Normal Migration
Cortical Neuronal Migration Disorders
Lissencephaly
Kallmann Syndrome
Zellweger Syndrome
Polymicrogyria
Congenital Bilateral Perisylvian Syndrome
Heterotopias
Cortical Dysgenesis
Posterior Fossa Formation and Malformation
Joubert, Meckel-Gruber, and Other Ciliopathies
Rhombencephalosynapsis
Dandy-Walker
Process Outgrowth and Synapse Formation
Corpus Callosum
Normal Synapse Formation
Disorders of Process Outgrowth
Conclusions
139 Inherited Metabolic Diseases
Introduction
Small Molecule Disorders
Glucose Transporter Type 1 Deficiency Syndrome
Clinical Syndrome
Laboratory Data
Molecular Genetics and Pathogenesis
Diagnosis
Management
Hyperammonemia
Neonatal Hyperammonemia
Hyperammonemia in Older Children and Adults
Valproate-Associated Hyperammonemia
Disorders of Amino Acid Metabolism
Phenylketonuria
Other Amino Acid Disorders
Organic Acidurias
Disorders of Purine and Pyrimidine Metabolism
Introduction
Lesch-Nyhan Syndrome
Other Purine Disorders
Porphyrias
Disorders of Metal Metabolism
Disorders of Copper Metabolism
Disorders of Iron Metabolism
Disorders Associated With Acanthocytosis
Large Molecule Disorders
Lysosomal and Associated Large Molecule Disorders
Lipidoses
Mucopolysaccharidoses
Mucolipidoses
Neuronal Ceroid Lipofuscinoses
Leukodystrophies
Disorders of Carbohydrate Metabolism
Glycogen Storage Diseases
Peroxisomal Diseases: Adrenoleukodystrophy, Zellweger Syndrome, and Refsum Disease
Zellweger Spectrum Disorder
Adrenoleukodystrophy
Refsum Disease
140 Chromosomal Disorders and Disorders of DNA
Introduction
Chromosomal Disorders
Genomic Imprinting
Autism Spectrum Disorder and Genomic Imprinting
Intellectual Disability Associated With Subtelomeric Chromosomal Deletion
Chromosomal Microarray
Array Comparative Genomic Hybridization
Disorders of DNA Maintenance, Transcription, and Translation
DNA Maintenance and Transcription
DNA Translation and Modification
Cell Cycle Control
Specific Disorders
141 The Floppy Infant
Introduction
Central Hypotonia
Vascular Causes
Structural Causes
Metabolic Causes
Systemic Causes
Chromosomal Disorders
Spinal Cord
Peripheral Hypotonia
Anterior Horn Cell Disorders
Brachial Plexus Palsy
Peripheral Neuropathy
Demyelinating Neuropathies
Axonal Neuropathies
Mixed Axonal and Demyelinating Neuropathy
Neuromuscular Junction Disorders
Muscle Disorders
142 Disorders of Motor and Cognitive Development
Introduction
Disorders of Motor Development
Approach to the Child With Motor Delay
Cerebral Palsy
Spastic Diplegia
Spastic Quadriplegia
Spastic Hemiparesis
Dyskinetic Cerebral Palsy
Ataxic Cerebral Palsy
Management of Cerebral Palsy
Developmental Coordination Disorder
Disorders of Higher Cerebral Functions
Approach to the Child With Language, Cognitive, or Academic Delays
Developmental Language Disorders
Intellectual Disability
Learning Disabilities
Dyslexia
Nonverbal Learning Disabilities
Dyscalculia
Attention Deficit Hyperactivity Disorder
Level 1 Evidence
143 Autism Spectrum Disorders
Introduction
Epidemiology
Pathobiology
Genetics
Neuropathology
Diagnosis
Evaluation
Neurologic Examination
Cognition and Language
Medical and Psychiatric Comorbidities
Epilepsy
Neurodiagnostic Testing
Management
Outcome
144 Mitochondrial Encephalomyopathies
Introduction
Epidemiology
Pathobiology
Pathobiology of mtDNA Mutations: Mitochondrial Genetics Versus Mendelian Inheritance
Mendelian Inheritance
Direct Hits Mutations
Indirect Hits Mutations
Defects of Mitochondrial Ribonucleic Acid (mtRNA) Translation
Defects of the Inner Mitochondrial Membrane Lipid Milieu
Defects of Mitochondrial Dynamics
Defects of Mitochondrial DNA Maintenance
Disorders of Mitochondrial Protein Importation
Diagnosis
Mitochondrial DNA-Related Diseases
Mendelian Inheritance
Defects of the Inner Mitochondrial Membrane Lipid Milieu
Defects of Mitochondrial Translation
Defects of Mitochondrial Dynamics
Defects of Mitochondrial DNA Maintenance
Mitochondrial DNA Depletion Syndromes
Syndromes due to Multiple Mitochondrial DNA Deletions
Coexistence of Mitochondrial DNA Depletion and Mitochondrial DNA Multiple Deletions
Diagnostic Workup
Laboratory
Neuroradiology
Exercise Physiology
Pathology
Skeletal Muscle
Neuropathology
Biochemical Findings
Management
Mitochondrial Transfer
Shifting Heteroplasmy
Enhancement of Oxidative Phosphorylation Function
Elimination of Noxious Compounds
Small Molecule Therapies
Alteration of Mitochondrial Dynamics
145 Neurocutaneous Syndromes
Introduction
Neurofibromatosis
Introduction
Epidemiology
Molecular Genetics and Pathogenesis
Neuropathology
Symptoms and Signs
Cutaneous Manifestations
Ocular Findings
Neurologic Symptoms
Skeletal and Limb Manifestations
Miscellaneous Manifestations
Diagnosis
Laboratory Data
Management
Tuberous Sclerosis Complex
Introduction
Epidemiology
Genetics
Pathology and Pathogenesis
Symptoms and Signs
Cutaneous Findings
Neurologic Findings
Ophthalmic Findings
Visceral and Skeletal Findings
Laboratory Data
Diagnosis
Course and Prognosis
Management
Encephalotrigeminal Angiomatosis
Introduction
Epidemiology
Genetics
Neuropathology
Symptoms and Signs
Cutaneous Manifestations
Neurologic Manifestations
Ophthalmologic Manifestations
Laboratory Data
Diagnosis
Management
Incontinentia Pigmenti
Introduction
Genetics
Neuropathology
Cutaneous Findings
Neurologic, Ophthalmic, and Other Symptoms
Laboratory Data
Management
Incontinentia Pigmenti Achromians (Hypomelanosis of Ito)
Introduction
Epidemiology and Genetics
Pathogenesis and Pathology
Clinical Manifestations
Diagnosis and Laboratory Data
Management
146 Spinal Muscular Atrophies of Childhood
Introduction
Epidemiology
Clinical Characteristics
Type I Spinal Muscular Atrophy
Type II Spinal Muscular Atrophy
Type III Spinal Muscular Atrophy
Outliers
Other “Spinal Muscular Atrophies”
Genetics
The SMN Gene
Newborn Screening
Pathobiology
Management
Agents That Upregulate SMN2 Gene Expression and Promote Exon 7 Inclusion
Small Molecules
Other Approaches
Antisense Oligonucleotides
Gene Therapy
Care of the Patient With Spinal Muscular Atrophy
Summary
Level 1 Evidence
147 Muscular Dystrophies and Congenital Myopathies
Introduction
Definitions
Muscular Dystrophy Classification
Congenital Myopathy Classification
Laboratory Diagnosis
Congenital Muscular Dystrophies
Definitions
Epidemiology
Diagnosis
Merosin-Deficient Congenital Muscular Dystrophy
COL6-Related Dystrophies
Dystroglycanopathies
Management
Dystrophinopathies
Definitions
Epidemiology
Duchenne and Becker Muscular Dystrophies
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Intermediate Phenotype
Manifesting Carriers
Diagnosis
Molecular Genetics
Management
Scapuloperoneal Myopathies
Emery-Dreifuss Muscular Dystrophy
LMNA-Related Myopathies
Facioscapulohumeral Muscular Dystrophy
Definition
Molecular Genetics
Clinical Manifestations
Associated Disorders
Differential Diagnosis
Laboratory Studies
Management
Myotonic Muscular Dystrophy and Proximal Myotonic Myopathy
Definitions
Epidemiology
Diagnosis
Clinical Features
Electrodiagnostic Features
Other Clinical Features
Genetics
Myotonia Variants
Congenital Myotonic Dystrophy
Proximal Myotonic Myopathy
Management
Limb-Girdle Muscular Dystrophy
Definition
Epidemiology
Diagnosis
Clinical Manifestations
Autosomal Recessive Limb-Girdle Muscular Dystrophy
Lgmdr1/Lgmdd4 (Lgmd2a)
Lgmdr2 (Lgmd2b)
Lgmdr3-6 (Sarcoglycanopathies) (Lgmd2c-F)
Lgmdr9
Lgmdr12
Other Recessive Limb-Girdle Muscular Dystrophies
Autosomal Dominant Limb-Girdle Muscular Dystrophy
Limb-Girdle Muscular Dystrophy 1A
Limb-Girdle Muscular Dystrophy 1B
Limb-Girdle Muscular Dystrophy 1C
Limb Girdle Muscular Dystrophy 1D
Limb-Girdle Muscular Dystrophy D2
Limb-Girdle Muscular Dystrophy 1G Through Limb-Girdle Muscular Dystrophy 1H
Differential Diagnosis
Management
Oculopharyngeal Muscular Dystrophy
Other Rare Dystrophies
Distal Myopathies (Distal Muscular Dystrophies)
Nondystrophic Myopathies—Congenital Myopathies
Definitions
Epidemiology
Diagnosis
X-Linked Myotubular Myopathy
Other Centronuclear Myopathies
Nemaline Myopathy
Core Myopathies—RYR1-Related Myopathies
Core Myopathies—SELENON-Related Myopathy
TTNopathies
Management
Outcomes
Level 1 Evidence
148 Seizures and Epilepsies in Neonates and Children
Introduction
Age-Dependent Seizures Not Traditionally Diagnosed As Epilepsy
Neonatal Seizures
Febrile Seizures
Age-Dependent Epilepsies and Epilepsy Syndromes in Neonates and Children
Benign Epilepsies in Neonates and Infants
Benign Familial Neonatal Epilepsy
Benign Familial Neonatal-Infantile Epilepsy
Benign Familial Infantile Epilepsy
Epileptic Encephalopathy Syndromes in Neonates and Infants
Ohtahara Syndrome and Early Myoclonic Encephalopathy
West Syndrome
Genetic Developmental and Epileptic Encephalopathies in Neonates and Infants
KCNQ2 Encephalopathy
STXBP1 Encephalopathy
GNAO1 Encephalopathy
ARX Disorders
SCN2A Encephalopathies
CDKL5 Encephalopathy
Epilepsy of Infancy With Migrating Focal Seizures
SCN8A Encephalopathy
Genetic Epilepsy With Febrile Seizures Plus
Dravet Syndrome
PCDH19 Girls Clustering Epilepsy
Toddler-Onset Epilepsy Syndromes
Lennox-Gastaut Syndrome
Epilepsy With Myoclonic-Atonic Seizures
Landau-Kleffner Syndrome and Continuous Spikes and Waves During Slow Sleep
Idiopathic Focal Epilepsies of Childhood
Childhood Epilepsy With Centrotemporal Spikes
Panayiotopoulos Syndrome
Gastaut Syndrome
Idiopathic Generalized Epilepsies of Childhood
Childhood Absence Epilepsy
Jeavons Syndrome
Epilepsy with Myoclonic Absences
Juvenile Myoclonic Epilepsy
Juvenile Absence Epilepsy
Epilepsy with Generalized Tonic-Clonic Seizures Alone
Rasmussen Encephalitis
Inborn Errors of Metabolism Causing Seizures and Epilepsy in Neonates and Children
Pyridoxine-dependent Epilepsy
Glut1 Deficiency Syndrome
Progressive Myoclonic Epilepsies
Epilepsies Associated With Brain Malformations
Cortical Dysgenesis
Focal Cortical Dysplasia
Tuberous Sclerosis Complex
Hemimegalencephaly and Dysplastic Megalencephaly
Periventricular Nodular Heterotopias
Lissencephaly
Hypothalamic Hamartomas
Sturge-Weber Syndrome
Level 1 Evidence
149 Pediatric Stroke
Introduction
Perinatal Stroke
Epidemiology
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Pathobiology
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Clinical Features
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Diagnosis and Imaging
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Management
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Outcome
Perinatal Arterial Ischemic Stroke
Perinatal Cerebral Sinovenous Thrombosis
Perinatal Intracranial Hemorrhage
Epidemiology
Childhood Arterial Ischemic Stroke
Childhood Cerebral Sinovenous Thrombosis
Childhood Intracranial Hemorrhage
Pathobiology
Childhood Arterial Ischemic Stroke
Childhood Cerebral Sinovenous Thrombosis
Childhood Intracranial Hemorrhage
Diagnosis
Childhood Arterial Ischemic Stroke
Childhood Cerebral Sinovenous Thrombosis
Childhood Intracranial Hemorrhage
Management
Childhood Arterial Ischemic Stroke
Childhood Cerebral Sinovenous Thrombosis
Childhood Intracranial Hemorrhage
Outcome
Childhood Arterial Ischemic Stroke
Childhood Cerebral Sinovenous Thrombosis
Childhood Intracranial Hemorrhage
Sickle Cell Anemia
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Neurologic Deficits
Recurrence
Mortality
Genetics of Stroke in Children
Disorders with Abnormal Angiogenesis
Disorders of Vessel Wall Stenosis
Connective Tissue Disorders
Thrombophilic Disorders
Genetic or Metabolic Stroke or Stroke-like Episodes
Level 1 Evidence
150 Brain Tumors in Children
Introduction
Epidemiology
Incidence
Histologies
Risk Factors
Survival
Pathobiology
Sonic Hedgehog, Wnt Signaling, Cerebellar Development, and Medulloblastoma
Astrocytes, Growth Factors, Tumor Suppressors, and Astrocytoma
Ependymal Cells, RELA Fusions, and Ependymoma
Integrated Classification of Central Nervous System Tumors
Clinical Features
Symptoms
Diagnosis
Treatment
Surgery
Radiation Therapy
Chemotherapy
Specific Types of Pediatric Central Nervous System Tumors
Congenital Tumors
Craniopharyngioma
Epidermoid Cysts
Teratoma and Chordoma
Choroid Plexus Tumors
Colloid Cysts
Ganglioglioma and Related Glioneuronal Tumors
Dysplastic Gangliocytoma
Dysembryoplastic Neuroepithelial Tumor
Schwannoma (Neurilemmoma)
Astrocytoma
Low-Grade Astrocytoma
High-Grade Astrocytoma
Brainstem Glioma
Spinal Cord Astrocytoma
Oligodendroglioma
Medulloblastoma and Embryonal Tumors
Medulloblastoma
Nonmedulloblastoma Embryonal Tumors
Pineoblastoma and Trilateral Retinoblastoma
Atypical Teratoid/Rhabdoid Tumor
Ependymoma and Other Tumors
Ependymoma
Central Nervous System Germ Cell Tumors
Central Nervous System Lymphoma
Meningioma and Mesenchymal Tumors
Malignant Melanoma
Late Effects of Treatment and Quality of Life
Radiation Effects
Endocrine Dysfunction
Cardiovascular and Pulmonary Effects
Neurologic Sequelae
Secondary Malignancies
151 Pediatric Brain Injury and Shaken Baby Syndrome
Introduction
Epidemiology
Pathobiology
Primary Brain Injury
Secondary Brain Injury
Macroscopic Secondary Injury
Microscopic Secondary Injury
Diagnosis and Management
Minor Traumatic Brain Injury
Indications for Head Computed Tomography Imaging in Minor Traumatic Brain Injury
Severe Traumatic Brain Injury
Intracranial Pressure in Children
Hypothermia Following Severe Traumatic Brain Injury
Seizure Prophylaxis
Repeat Imaging
Decompressive Craniectomy
Outcome
Level 1 Evidence
152 Human Immunodeficiency Virus, Fetal Alcohol Syndrome, and Drug Effects
Pediatric Aids and Human Immunodeficiency Virus Infection
Introduction
Epidemiology
Pathobiology
Clinical Manifestations
Human Immunodeficiency Virus Encephalopathy
Primary Central Nervous System Lymphoma
Stroke
Opportunistic Central Nervous System Infection
Less Common Manifestations
Diagnostic Testing
Human Immunodeficiency Virus Testing
Neuroimaging
Cerebrospinal Fluid
Management
Antiretroviral Therapy
Outcome
Fetal Alcohol Spectrum Disorders
Introduction
Epidemiology
Pathobiology
Diagnosis
Partial Fetal Alcohol Syndrome
Alcohol-Related Neurodevelopmental Disorder
Alcohol-Related Birth Defects and Other Outcomes
Postnatal Alcohol Exposure
Alcohol Withdrawal Syndrome
Management and Outcome
Prenatal and Perinatal Effects of Substance Abuse
Cocaine
Neurobehavior
Strokes
Seizures
Malformations
Neurodevelopmental Impact
Cocaine Exposure in Childhood
Withdrawal Symptoms
Opiates
Withdrawal Symptoms
Level 1 Evidence
SECTION XXI PSYCHIATRY AND NEUROLOGY
153 Psychosis
Introduction
Schizophrenia and Other Psychotic Disorders
Epidemiology
Pathobiology
Diagnosis
Management and Outcome
Antipsychotic Medication
Nonpharmacologic Treatment
Other Causes of Psychosis
Conclusion
Level 1 Evidence
154 Mood Disorders
Introduction
Epidemiology
Pathobiology
Pathophysiology of Major Depressive Disorder
Pathophysiology of Bipolar Disorder
Clinical Manifestations
Depressive Disorders
Bipolar Disorders
Seasonal Affective Disorder
Diagnosis
Differential Diagnosis
Differential Diagnosis With Neurologic Disorders
Differential Diagnosis With Other Psychiatric Disorders
Treatment
Treatment of Depressive Disorders
Treatment of Bipolar Disorders
Treatment of Mood Disorders Comorbid With Neurologic Disorders
Outcome
Level 1 Evidence
155 Anxiety Disorders, Posttraumatic Stress Disorder, and Obsessive-Compulsive Disorder
Introduction
Epidemiology
Pathobiology
Diagnosis
Clinical Features Across Anxiety Disorders
Panic Disorder and Agoraphobia
Social Anxiety Disorder (Social Phobia)
Posttraumatic Stress Disorder and Acute Stress Disorder
Obsessive-Compulsive Disorder
Generalized Anxiety Disorder
Specific Phobias
Separation Anxiety Disorder
Selective Mutism
Anxiety and Neurologic Disease: Comorbidity and Differential Diagnosis
Management
General Approaches to Anxiety Disorders
Panic Disorder and Agoraphobia
Social Anxiety Disorder
Posttraumatic Stress Disorder and Acute Stress Disorder
Obsessive-Compulsive Disorder
Generalized Anxiety Disorder
Specific Phobias
Separation Anxiety Disorder and Selective Mutism
Treatment of Anxiety Disorders Comorbid With Neurologic Disorders
Outcome
Level 1 Evidence
156 Somatic Symptom Disorders
Introduction
Somatic Symptom Disorders in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)
Somatic Symptom Disorder
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Illness Anxiety Disorder
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Conversion Disorder (Functional Neurologic Symptom Disorder)
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Factitious Disorder
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Psychological Factors Affecting Other Medical Conditions
Introduction
Epidemiology
Pathobiology
Diagnosis
Management
Outcome
Conclusions
Level 1 Evidence
SECTION XXII RECOVERY AND END-OF-LIFE CARE
157 Neurologic Rehabilitation
Introduction
Compensation and Recovery
Neuroplasticity and Recovery
Injury-Induced Plasticity
Activity-Dependent Plasticity
Levels of Care
The Disciplines
Physician
Rehabilitation Nursing
Physical Therapy
Occupational Therapy
Speech, Language, and Cognitive Therapy
Psychology and Neuropsychology
Social Work
Recreational Therapy
Specialized Neurologic and Medical Management
Dysphagia
Bladder and Bowel Dysfunction
Medical Care
Level 1 Evidence
158 End-of-Life and Palliative Care in Neurology
Introduction
Disease Trajectories
Palliative Care
Advance Directives and Care Planning
Orders for Life-Sustaining Treatment
Informed Consent and Decision Making
End-of-Life Care
Life-Sustaining Therapies
Ineffective, Inappropriate, and Futile Therapies
Withholding and Withdrawing
Death, Dying, and Hospice Care
Refusal of Therapy, Physician-Assisted Suicide, and Euthanasia
Other Neurologic Issues With Death
Conclusion
Index