Neuroinflammation

Alireza Minagar

• Publisher: Elsevier
• Year: 2010
• eBook ISBN: 9780123849144
• Topic: Medicine
• Subtopic: Immunology

Inflammation is a central mechanism in many neurological diseases, including stroke, multiple sclerosis, and brain trauma as well as meningitis and contributes to the generation of pain. We are now beginning to understand the impact of the immune system on different nervous system functions and diseases, ranging from damage through tolerance to modulation and repair.This book discusses some of the more common neuro-inflammatory diseases. Topics covered include multiple sclerosis, optic neuritis and Susac syndrome.- Comprehensive review of the latest developments in neuroinflammation- Includes contributions from leading authorities

1. Multiple Sclerosis

Pathophysiology, Clinical Features, Diagnosis, and Management

Amir-Hadi Maghzi¹²³, Aimee Borazanci⁴, Jeanie McGee⁴, J. Steven Alexander⁵, Eduardo Gonzalez-Toledo⁴⁶ and Alireza Minagar⁴

¹Isfahan Research Committee of Multiple Sclerosis (IRCOMS), Isfahan, Iran

²Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

³Neuroimmunology Unit, Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, UK

⁴Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

⁵Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

⁶Department of Radiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

Multiple sclerosis (MS) is an immune-mediated demyelinating and neurodegenerative disease of the human central nervous system, which affects young adults and is the leading cause of acquired neurologic disability in this population. The etiologic basis of MS remains elusive, blocking progress to its cure. During the past two decades our understanding of MS pathophysiology has radically changed and has led to the development of treatments for MS, which delay its natural course and the onset of disability. Currently, the guiding tenet among neurologists is early, aggressive treatment to slow disease initiation and progression. This contemporary review provides readers with a comprehensive overview of MS pathophysiology, clinical features, neuroimaging, diagnostic workup, and current treatments.

Introduction

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which largely affects young adults with certain genetic backgrounds, often following exposure to several as yet unidentified environmental antigen(s) [1] and [2]. It is believed that the interactions between environmental and genetic influences are required to trigger the massive immune response against putative CNS antigens (e.g., myelin proteins that surround axons). This progressive inflammatory process affects both gray and white matters of the brain and spinal cord and ultimately causes neurodegeneration and axonal loss, with resultant permanent disability. Inflammatory demyelination in MS slows impulse conduction or leads to complete cessation of nerve impulse transmission. Axonal loss and neurodegeneration are the fundamental mechanisms underlying brain atrophy and permanent loss of motor function. The lesions of MS can affect any region of the neuroaxis; therefore, the anatomic location of MS lesions plays a significant role in determining clinical symptoms.

Based on the clinical disease pattern, four types of MS are recognized: relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS) [3]. Interestingly, it appears that these four different forms of MS have dissimilar underlying neuropathologies, which in turn indicates that MS may represent a heterogeneous group of related diseases. The clinical course of RRMS is characterized by clear disease relapses with development of new neurologic deficits or worsening of older symptoms that last more than 24h; each relapse is typically separated from the last attack by at least 1 month of stability. Patients with relapse of MS, either with treatment with corticosteroids or spontaneously, may return to their baseline neurologic status or may recover partially, with residual neurologic deficits. Usually, during the interval between relapses there is no clinical disease progression. Clinically, RRMS is the most common form of MS; more than 85% of patients initially present with this form. SPMS is recognized by an initial RRMS that progresses to SPMS within 10–15 years. During this phase of MS, the underlying inflammatory cascade and clinical relapses decrease in severity, while the neurodegenerative process builds to become the dominant pathology. In certain ways, SPMS may be regarded as a long-term product of RRMS. Up to 15% of MS patients initially present with PPMS, which is characterized by a relentless progression with no obvious relapses; patients occasionally exhibit transient minor improvement. PRMS is characterized by progressive and devastating attacks of the disease from the beginning with acute relapses, with or without recovery. Importantly, the intervals between relapses are marked by continuous disease progression. This form of MS is the least common clinical form.

The most common form of MS, RRMS, begins with a single unifocal or multifocal demyelinating attack (known as clinically isolated syndrome [CIS]), with a complete or partial resolution of the attack. This form of MS with its dominant neuroinflammatory sequelae is clinically recognized by relapses and development of new lesions on magnetic resonance imaging (MRI) studied by CNS neuroimaging. Of course, during this process, the neurodegenerative arm of MS continuously proceeds with progressive axonal and neuronal loss to the point that the patient’s capacity to sustain any new attacks without suffering additional disability decreases. Within a few years of the onset of RRMS, the underlying neuropathology of MS involves more neurodegeneration with fewer clinical relapses, more clinical deterioration, and accumulating disability. Patients with PPMS have a progressive course from the beginning without significant evidence of inflammatory lesions on CNS neuroimaging and with no proven therapeutic response to immunomodulatory medications as compared to RRMS.

Epidemiology

The diverse worldwide epidemiology of MS provides clues to the genetic and environmental risk factors for MS. The observations from migrant studies showing that migration from high- to low-risk areas before puberty provides some protection against developing MS, and vice versa, highlight the importance of environmental factors in MS [4]. The highest incidence and prevalence of MS are more likely to be observed at the highest latitudes in both the northern and southern hemispheres. In addition, the prevalence and incidence of MS are shown to be associated with the distance from the equator [5]. This has been mostly linked to the effects of sunlight exposure and vitamin D, leading to the formulation of...

Table of contents

• Cover Image
• Table of Contents
• Front-matter
• Copyright
• Preface
• Contributors
• 1. Multiple Sclerosis
• 2. Epstein–Barr Virus and Multiple Sclerosis
• 3. Neutralizing Antibodies and Multiple Sclerosis
• 4. Animal Models of Multiple Sclerosis
• 5. Neuroimaging of Multiple Sclerosis
• 6. Role of IL-12/IL-23 in the Pathogenesis of Multiple Sclerosis
• 7. Spinal Cord Injury and its Relationship to the Development or Worsening of Clinical Multiple Sclerosis
• 8. Clinical Development and Benefit–Risk Profile of Natalizumab
• 9. Remyelination in Multiple Sclerosis
• 10. Transverse Myelitis
• 11. Neuromyelitis Optica
• 12. Optic Neuritis
• 13. Ischemic Demyelination
• 14. Inflammatory Mechanisms in Ischemic Cerebrovascular Disease
• 15. Protection Against Neuroinflammation by Promoting Co-activation of G Protein– Growth Factor Signaling and Metabolic Flexibility in the Brain
• 16. Mesenchymal Stem Cells, Inflammation, and Neurodegenerative Diseases
• 17. Inflammatory Mediators in Obstructive Sleep Apnea
• 18. The Role of Neuroinflammation in Parkinson's Disease
• 19. Neuroinflammation and Pediatric Lupus
• 20. Central Nervous System Vasculitis
• 21. Systemic Lupus Erythematosus—Vasculopathy/Vasculitis, Susac Syndrome, and Myasthenia Gravis
• 22. Inflammatory Mechanisms in Guillain–Barré Syndrome
• 23. Neurologic Manifestations of Herpes Zoster