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Basic Science of Spinal Diseases
Alexander R Vaccaro, Alok D Sharan, Simon Y Tang
SECTION 1: ANATOMY AND PHYSIOLOGY OF THE INTERVERTEBRAL DISC
1:
Anatomy and Structure of the Intervertebral Disc
CASE STUDY
INTRODUCTION
The Cartilage Endplates
The Annulus Fibrosus
The Nucleus Pulposus
NUTRITION OF THE INTERVERTEBRAL DISC
THE CERVICAL, THORACIC AND LUMBAR DISCS
AREAS FOR FUTURE INVESTIGATION
2:
Biomechanics of Intervertebral Disc
CASE STUDY
INTRODUCTION AND SUMMARY
ANATOMY AND BIOMECHANICS OF THE HEALTHY IVD
INTERVERTEBRAL DISC BIOMECHANICAL CHANGES WITH DDD
CLINICAL IMPLICATIONS OF DDD AND THE ROLE OF IVD BIOMECHANICS
CONCLUSION
FUTURE QUESTIONS
3:
Vascular Anatomy of the Endplates and Nutrient Supply of the Disc
CASE STUDY
INTRODUCTION
VERTEBRAL ENDPLATE ANATOMY
ANATOMY OF THE ARTERIAL SUPPLY TO THE DISC3
VASCULAR ANATOMY AT THE ENDPLATE
NUTRIENT TRANSPORT INTO THE DISC
Transport across the Endplate
Transport through the Matrix
Nutrient Transport—Diffusion versus Convection
ASSESSING NUTRIENT SUPPLY
Animal Studies
Human Magnetic Resonance Imaging Studies
Electrode Studies
DISC MALNUTRITION
TOTAL ENDPLATE DAMAGE SCORE (TEPS)
CONCLUSION
THOUGHTS FOR FUTURE INVESTIGATION
4:
Muscular Anatomy of the Spine
CASE STUDY
INTRODUCTION1–3
EXTRINSIC MUSCLES OF THE BACK
Muscles that Link to the Shoulder Girdle or Rib Cage1–3
Muscles that Link to the Pelvic Girdle1–3
EXTRINSIC MUSCLES OF CERVICAL REGION1–3
INTRINSIC MUSCLES OF THE BACK1–3
Superficial Layer
Intermediate Layer
Deep Layer
INTRINSIC MUSCLES SPECIFIC TO CERVICAL SPINE1–3
Muscles that Indirectly Influence the Spine4
FUNCTION2,8
ARCHITECTURE OF SPINAL MUSCLES AND THEIR CLINICAL IMPLICATION2
PATHOLOGICAL VARIATIONS IN BACK MUSCLES’ STRENGTH2
MUSCLE INJURY MODEL FOR SPINAL PAIN2,12–16
SUMMARY
RESEARCH QUESTIONS FOR FUTURE
5:
Imaging of the Intervertebral Disc
CASE STUDY
INTERVERTEBRAL DISC ANATOMY
Conventional Radiography
Computed Tomography
Computed Tomography Myelography
Magnetic Resonance Imaging
CONVENTIONAL MAGNETIC RESONANCE IMAGING FINDINGS
INTRAVENOUS CONTRAST ADMINISTRATION
QUANTITATIVE MAGNETIC RESONANCE IMAGING
EMERGING TECHNOLOGIES
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
6:
Animal Models for Disc Degeneration
INTRODUCTION
MAN'S BEST FRIEND AS A SPONTANEOUS DISEASE MODEL
ANATOMY OF THE CANINE SPINE AND INTERVERTEBRAL DISC
BIOMECHANICAL PROPERTIES OF THE CANINE SPINE
CANINE INTERVERTEBRAL DISC DEGENERATION AND DISEASE
DIAGNOSTIC MODALITIES AND GRADING SYSTEMS FOR CANINE INTERVERTEBRAL DISC DEGENERATION AND DISEASE
TREATMENT OF CANINE DEGENERATIVE DISC DISEASE
WAYS TO USE THE CANINE MODEL FOR DISC DEGENERATION
QUESTIONS FOR FUTURE INVESTIGATION
7:
Animal Models of Back Pain and Sciatica
CASE STUDY
INTRODUCTION
CHARACTERISTICS AND ASSESSMENT OF ANIMAL MODELS OF LOW BACK PAIN AND SCIATICA
ANIMAL MODELS OF LOW BACK PAIN
Low Back Pain—Intervertebral Disc
Disc Puncture
Disc Puncture with Air Injection
Introduction of Complete Freund's Adjuvant into the Disc
Low Back Pain—Facet Joints
Introduction of Inflammatory Agents into the Facets
Introduction of Monosodium Iodoacetate into the Facets
Facet Crush Injury
ANIMAL MODELS OF SCIATICA
Sciatica—Mechanical Injury
Sciatic Nerve Axotomy Model
Chronic Constriction Injury Model
Partial Nerve Injury Model
Spinal Nerve Ligation Model
Chronic Compression of Dorsal Root Ganglion Model
Spared Nerve Injury Model
Sciatica—Chemical Irritation
Proinflammatory Cytokine Irritation Model
Inflammatory Stimulus Models
Sciatica—Other Models
SUMMARY
FUTURE INVESTIGATION
8:
Animal Models for Spinal Deformity and their Role in the Development of Surgical Nonfusion AIS Treatments
CASE STUDY
ADOLESCENT IDIOPATHIC SCOLIOSIS
ANIMAL MODELS FOR THE STUDY OF SPINAL DEFORMITY
HISTORICAL NONFUSION INVESTIGATIONS
PRECLINICAL NONFUSION INVESTIGATIONS
CONCLUSION
QUESTIONS
SECTION 2: PATHOPHYSIOLOGY OF THE INTERVERTEBRAL DISC
9:
Pathophysiology of Disc Degeneration
CASE STUDY
INTRODUCTION
ANATOMY OF THE INTERVERTEBRAL DISC
Components of the Intervertebral Disc
Biochemical Composition
GROWTH FACTORS
Biomechanical Principles
MECHANISMS OF DISC DEGENERATION
Homeostasis of Intervertebral Disc
Microscopic Degeneration
Macroscopic Degeneration
Vascularity
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
10:
Genetics of Disc Degeneration
CASE STUDY
INTRODUCTION
THE DIFFICULTIES OF STUDYING LUMBAR DEGENERATIVE DISC DISEASE
RISK FACTORS FOR DISC DEGENERATION
Gender and Age
Environmental Influences
Genetic Influence
Associated Genes
METHODOLOGY/FUTURE STUDIES
CONCLUSION
FURTHER INVESTIGATION
11:
The Role of Inflammation in Disc Degeneration
CASE STUDY
CLINICAL SIGNIFICANCE AND SOCIOECONOMIC IMPACT OF SPINE PAIN
CURRENT MANAGEMENT TECHNIQUES—NEED FOR BIOLOGIC THERAPEUTIC INTERVENTIONS
INFLAMMATORY-MEDIATED PAIN
ANATOMIC REGIONS OF SPINE PAIN
Intervertebral Disc
Pathogenesis of Inflammatory Cascade
Response to the Inflammatory Cascade
Targets for Biological Therapeutics in Inflammatory-Mediated Discogenic Pain
FACET JOINT
Targets of Biologic Therapies
CENTRAL AND PERIPHERAL NEURAL STRUCTURES
Peripheral Radiculopathy
Spinal Stenosis
Targets of Biological Therapies
CONCLUSION
CONCLUSION OF CASE
THREE QUESTIONS FOR FUTURE INVESTIGATION
12:
Understanding the Pathways of Pain
CASE STUDY
INTRODUCTION
PHYSIOANATOMY
Nociceptors
C-fibers and A-delta axons
Nociceptor Activation—the Molecular Basis of Pain Signal Detection
Pain Pathway
MODULATION WITHIN THE DORSAL ROOT GANGLION
DORSAL HORN OF THE SPINAL CORD
PAIN PERCEPTION
MOLECULAR BASIS OF ACUTE AND CHRONIC PAIN
Central Sensitization and the NMDA Receptor in Wind Up
INFLAMMATION AND PAIN
Inflammatory Activation of C-fibers
Inflammation-Induced Pain Potentiation
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
13:
Treatment Strategies to Regenerate the IVD
CASE STUDY
INTRODUCTION
DECREASED MATRIX PRODUCTION
CELL SENESCENCE
PROINFLAMMATORY CYTOKINE EXPRESSION
INCREASED DEGRADATIVE ENZYME PRODUCTION
STRATEGIES TO ADDRESS DECREASED DISC CELLULARITY AND METABOLIC ACTIVITY
Disc Tissue Reimplantation
Animal Studies
Human Studies
Stem Cell Implantation
Animal Studies
Human Studies
Platelet-Rich Plasma
Animal Studies
TREATMENT STRATEGIES TO ADDRESS CHANGES IN PROTEIN EXPRESSION
Protein-Based Therapy
Animal Studies
Gene Therapy
Animal Studies
Human Studies
RECONSTRUCTION USING BIOMATERIALS/HYDROGELS
Biomechanical Studies
Animal Studies
Human Studies
CONCLUSION
AREAS FOR FUTURE INVESTIGATION
SECTION 3: THE SCIENCE OF SPINAL INSTRUMENTATION
14:
Implant Properties of Spinal Instrumentation
CASE STUDY
PATIENT FACTORS IN CHOOSING IMPLANT PROPERTIES OF SPINAL INSTRUMENTATION
ANATOMY AND PHYSIOLOGY
BIOMECHANICAL CONSIDERATIONS IN CHOOSING IMPLANT PROPERTIES OF SPINAL INSTRUMENTATION
TRANSFER OF ENERGY
KINEMATICS AND KINETICS
SURGICAL CONSIDERATIONS IN CHOOSING IMPLANT PROPERTIES OF SPINAL INSTRUMENTATION
Material and Size Options
CLINICAL CONSIDERATIONS
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
15:
Biomechanics of Spinal Instrumentation
CASE STUDY
BASIC BIOMECHANICAL PRINCIPLES
Biomechanically Relevant Anatomy
Fundamental Biomechanical Principles
Deformation and Elasticity
Stability versus Instability
Implant Properties
AGING SPINE
Cervical Spondylosis and the Aging Spine
Spondylosis
Osteoporosis
Spinal Alignment
BIOMECHANICS OF INTERVENTION
Iatrogenic Spinal Destabilization
Construct Design Principles
Tension Banding
Buttressing
Neutralization
Cantilever Beam Fixation
Fixed versus Non-fixed Moment Arm Cantilevered Screws
Construct Failure
Bone–Bone Interface Failure
Biomechanics of Nonfusion Implants
Biomechanics of Nuclear Implants
Biomechanics of Total Disc Replacement
Biomechanics of Dorsal Dynamic Stabilization Devices
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
16:
Biomechanics of Cervical Spine Instrumentation
CASE STUDY
INTRODUCTION
IMPLANT CHOICE
ANTERIOR INSTRUMENTATION
Anterior Cervical Discectomy and Fusion (ACDF)
Cervical Disc Arthroplasty
Self-Contained Interbody Fusion Devices
POSTERIOR CERVICAL INSTRUMENTATION
Wiring
Laminoplasty Fixation
DORSAL RIGID FIXATION
Lateral Mass Screw Constructs
Pedicle Screw Constructs
Combined Anterior/Posterior Constructs
FUTURE INVESTIGATIONS
17:
Biomechanics of Thoracolumbar Instrumentation
CASE STUDY
INTRODUCTION
BASIC BIOMECHANICS OF THORACOLUMBAR MOTION SEGMENTS
Mechanical Characteristics of Thoracolumbar Structures
Thoracolumbar Spinal Motion
Load-sharing Mechanism of Thoracolumbar Spine Motion Segments
POSTERIOR INSTRUMENTATION
Long-segment Instrumentation
Short-segment Instrumentation
ANTERIOR INSTRUMENTATION
COMBINED ANTERIOPOSTERIOR INSTRUMENTATION
IMPLICATIONS OF OSTEOPOROSIS
AREAS FOR FUTURE INVESTIGATION
18:
Biomechanics of Lumbar Interbody Fusion
CASE STUDY
INTRODUCTION
BIOMECHANICS OF THE NATIVE INTERVERTEBRAL DISC (IVD)
BIOMECHANICS OF THE DEGENERATED IVD
BIOMECHANICS OF INTERBODY FUSION
BIOMECHANICAL CONSIDERATIONS FOR INTERBODY CAGES
Designs
Sizing
Graft Materials
EFFECT OF SURGICAL APPROACH ON CAGE BIOMECHANICS
CONCLUSION
AREAS FOR FUTURE INVESTIGATIONS
19:
Biomechanics of Motion-Preserving Implants
CASE STUDY
INTRODUCTION AND GENERAL MECHANICS
MOTION PRESERVATION
POSTERIOR DEVICES
FACET JOINT REPLACEMENT
ANTERIOR DEVICES
SUMMARY
QUESTIONS FOR FUTURE INVESTIGATION
20:
Biomechanics of Interspinous Process Devices
CASE STUDY
OVERVIEW
NORMAL SPINE ANATOMY AND KINEMATICS
CAUSES FOR LUMBAR SPINAL STENOSIS
TRADITIONAL TREATMENT OF LUMBAR SPINAL STENOSIS (LSS)
WHY INTERSPINOUS SPACERS (ISPs)?
INTERSPINOUS SPACERS (ISPs)
BIOMECHANICAL EFFECTS
Flexion and Extension
Lateral Bending
Axial Rotation
NEUROFORAMEN AND SPINAL CANAL DIMENSION
INTRADISCAL PRESSURE
SUMMARY
AREAS FOR FUTURE INVESTIGATION
21:
Biomechanics of Cement Augmentation
CASE STUDY
INTRODUCTION
CEMENT AUGMENTATION OF COMPRESSION FRACTURES
Biomechanics of Compression Fractures
VERTEBROPLASTY
KYPHOPLASTY
PEDICLE SCREW AUGMENTATION IN THE OSTEOPOROTIC SPINE
CEMENT AUGMENTATION IN SPINAL FUSION CONSTRUCTS
Lumbar Spinal Fusion
Adult Degenerative Deformity: Long Fusion Constructs
CONCLUSION
22:
Implant Design and Testing
CASE STUDY
INTRODUCTION
HISTORY AND EVOLUTION
COMPONENTS OF RIGID SYSTEMS
Screws
Cross-Links
Rods
Intervertebral Spacers/Cages
TESTING OF RIGID SYSTEMS
MOTION-SPARING OR MOTION-PRESERVING SYSTEMS
SEMIRIGID OR MOTION-STABILIZING SYSTEMS
TESTING AND EVALUATION OF ARTICULATING SYSTEMS
FATIGUE TESTING
SUMMARY
23:
Navigating the Regulatory and Reimbursement Pathways
CASE STUDY
INTRODUCTION
FOOD AND DRUG ADMINISTRATION
CLASSIFICATION OF MEDICAL DEVICES
REGULATORY SUBMISSIONS
OUTSIDE US (OUS) REGULATORY BODIES
CASE STUDY: 510(K) DEVICE
CASE STUDY: PMA DEVICE
REIMBURSEMENT PROCESS
REIMBURSEMENT DECISIONS IMPACTING THE DELIVERY OF SPINAL CARE
REIMBURSEMENT FOR NEW PROCEDURES OR DEVICES
CONCLUSION
24:
The Patent Process
CASE STUDY
INTRODUCTION
INTELLECTUAL PROPERTY TERMINOLOGY
Trade Secrets
Copyrights
Trademarks
Patent
What Can Be Patented?
Items that Cannot be Patented
The Role of a Patent
Benefits of Patent Protection
Should Every Idea Be Patented?
When Should an Idea Be Patented
Protecting the Idea
Applying for a Patent
Role of a Parent Institution
Office of Technology Transfer
Ownership of Intellectual Property
Licensing
International Patents
CONCLUSION
QUESTIONS FOR FURTHER INVESTIGATION
SECTION 4: THE SCIENCE OF SPINAL INTERVENTIONS
25:
Pharmaceutical Management of Spine Pain
CASE STUDY
INTRODUCTION
CLASSIFICATION OF PAIN
Types of Pain: Somatic vs Neuropathic
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
Mechanism of Action
ANTIDEPRESSANTS
Tricyclic Antidepressants (TCAs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Selection in the Use of Back Pain
MUSCLE RELAXANTS
BENZODIAZEPINES
OPIOIDS
MECHANISM OF ACTION
Clinical Usefulness
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
26:
Biochemistry of Epidural Steroid Injections
CASE STUDY
INTRODUCTION
PATHOPHYSIOLOGY OF RADICULAR SPINAL PAIN
RATIONALE FOR EPIDURAL INJECTIONS
MEDICATIONS USED IN EPIDURAL STEROID INJECTIONS
Corticosteroids
Anti-inflammatory (and Immunosuppressive) Effects of Corticosteroids
Genomic Effects of Corticosteroids
Nongenomic Effects of Corticosteroids
Analgesic Effects of Corticosteroids
CHOICE OF CORTICOSTEROID
Glucocorticoid Potency
Duration of Action
Particulate Size and Aggregation
Effectiveness
Benzyl Alcohol and Polyethylene Glycol
DILUENT
LOCAL ANESTHETICS
SALINE
FUTURE DEVELOPMENTS IN EPIDURAL INJECTIONS
Epidural Clonidine
Epidural Capsaicin
Epidural Tumor Necrosis Factor-α Antagonist
CONCLUSION
QUESTIONS FOR FUTURE INVESTIGATION
27:
Basic Science of Discography and Provocative Testing
CASE STUDY
DISCOGENIC PAIN
ETIOLOGY OF DISCOGENIC PAIN
Innervation of the Disc
Nociceptive Neuronal In-Growth
Neuronal Sensitization—the Cause of Discogenic Pain?
PROVOCATIVE DISCOGRAPHY
Basic Technique and Historical Clinical Application
Theory
Provocative Discography—Pressurization of Mechanonociceptors?
Lack of Clinical Predictive Diagnostic Value
Provocative Discography: More Harm than Good?
Animal Studies Using Disc Puncture as a Model for Degenerative Disc Disease
INTRADISCAL ANESTHESIA
Diagnostic Potential
CONCLUSION
QUESTIONS FOR FURTHER INVESTIGATION
28:
The Use of Stem Cells in Spine Surgery
CASE STUDY
INTRODUCTION
PHYSIOLOGY OF STEM CELLS
MESENCHYMAL STEM CELLS
USE OF STEM CELLS IN SPINAL ARTHRODESIS
CLINICAL STUDIES
GENE THERAPY
USE OF STEM CELLS IN SPINAL CORD INJURY
DISCUSSION
QUESTIONS FOR FURTHER INVESTIGATION
29:
Biology of Spinal Fusion
CASE STUDY
INTRODUCTION
BASIC SCIENCE OF SPINAL FUSION
AUTOGENOUS BONE GRAFT
ALLOGRAFT
FUTURE INVESTIGATION
30:
Bone Graft Extenders
CASE STUDY
OVERVIEW
OPTIMIZING BONE FORMATION
BIOLOGIC OSTEOINDUCTIVE AGENTS
DEMINERALIZED BONE MATRIX
CERAMIC OSTEOCONDUCTIVE AGENTS
SUMMARY
QUESTIONS FOR FUTURE INVESTIGATION
INDEX
TOC
Index
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