The Neurologic Involvement In Systemic Autoimmune Diseases

Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. Advances in the diagnosis, laboratory investigations, and management of these conditions has placed an increasing burden on the practicing clinician to correctly assess and treat these patients. This volume of the Handbook of the Systemic Autoimmune Diseases will help the clinician and researcher better understand the current concepts of nervous system involvement from systemic autoimmune disorders, recognize current approaches to diagnosis and treatment, current controversies, and areas that need significant research efforts. It is believed that providing this approach in a single volume will facilitate its use as a frequent resource for all those caring for or investigating these patients and their diseases. Each chapter follows a consistent outline to provide the reader with important and useful information in an easy-to-navigate manner and is also liberally referenced to provide more primary source material for further consideration. The standardized approach to each chapter will allow the reader to be able to compare and contrast more efficiently the neurological complications of the autoimmune diseases discussed.

Autoimmune Neurology presents the latest information on autoimmune neurologic disease, the immune response to the body where organs run wild, causing the immune system to attack itself. Autoimmunity is a main element in numerous nervous system diseases and can target any structure within the central or peripheral nervous system. Over the past 20 years, significant advances in our understanding of the pathophysiology of autoimmune disorders, including the use of biomarkers has led to new diagnosis and treatment options. Neurologic conditions associated with autoimmune reactions include dementia, neuromuscular disease, epilepsy, sleep disorders, diabetes, and other common neurologic disorders and disease. This current tutorial-reference will be a must-have title for clinical neurologists, research neurologists, neuroscientists, and any medical professional working with autoimmune disease and disorders. Includes comprehensive coverage of autoimmune neurology Details the latest techniques for the study, diagnosis, and treatment of diseases and disorders, including dementia, neuromuscular disease, epilepsy, and sleep disorders Presents a focused reference for clinical practitioners and the clinical neurology and neurology research communities

Systemic disorders with possible involvement of the nervous system include a variety of diseases with presumed inflammatory and autoimmune pathomechanisms, among them Behçet disease, sarcoidosis, systemic lupus erythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögren syndrome. This disease group encompasses systemic inflammatory disorders with a genetically defined dysregulation of the innate immune system as well as systemic autoimmune disorders characterized by alterations of the adaptive immunity such as autoantibodies and autoreactive T cells. Although more commonly diagnosed in adults, all of these diseases can manifest in childhood and some as early as infancy. Neurological involvement may represent the initial manifestation, and nearly every neurological symptom can be caused by inflammatory/autoimmune diseases. In a child with (sub)acute onset of otherwise unexplained neurological findings, consideration of inflammatory/autoimmune disorders may be of crucial therapeutic and prognostic importance. In the absence of disease-specific clinical features, the initial diagnostic workup is broad. Basic blood tests include inflammatory markers and autoantibodies. Cerebral magnetic resonance imaging and a lumbar puncture with measurement of opening pressure as well as cerebrospinal fluid analysis are indicated in most patients with central nervous system (CNS) involvement. Skin, muscle, or organ biopsies (e.g., renal) may provide additional information. Especially in patients with isolated CNS involvement, a brain biopsy may be indicated. Timely recognition and treatment of CNS inflammation may improve or even reverse clinical symptoms and prevent secondary brain injury.

This comprehensive, up-to-date book is designed to make recent developments in neuroimmunology accessible to medical professionals in the field. The field of neuroimmunology is complex and rapidly evolving, especially with the current improvements in targeted biologic therapies. This resource concisely offers clear explanations of these scientific and clinical advancements. Divided into five parts, the book begins with an in-depth introduction to neuroimmunology and the principles of immunotherapy. Section two consists of eight chapters devoted to multiple sclerosis, including discussions on the clinical features of the disease as well as symptom management and diagnosis. Subsequent chapters then dive into other central nervous system inflammatory disorders such as neuromyelitis optica, autoimmune encephalopathies, and immunological aspects of cancer. Following this are two chapters that examine distinct aspects of autoimmune disorders of the peripheral nervous system. Finally, the book closes with a review on the neurologic manifestations, diagnostic approaches and treatments of the various systemic rheumatic diseases. Following its successful predecessor edition, Clinical Neuroimmunology: Multiple Sclerosis and Related Disorders, Second Edition is positioned to be an invaluable asset to neurologists, residents and fellows, internists, and general practitioners who treat patients with neurologic disorders and other systemic autoimmune diseases.

This detailed, practical textbook focuses on immune mediated disorders of the nervous system with particular focus on systemic autoimmune disorders. Divided into three sections, the first discusses the neuroanatomical and pathophysiologic basis of immune mediated disorders of the nervous system. Following this are 25 chapters devoted to individual clinical conditions. To conclude, the final section explains what is known about the mechanisms of immunomodulatory treatments and practical points about monitoring patients on these treatments. Neurorheumatology: A Comprehensive Guide to Immune Mediated Disorders of the Nervous System bridges the gaps among different branches of medicine and is an indispensable resource for rheumatologists and neurologists looking to develop a firm understanding of these dynamic disorders

Autoimmune diseases of the central nervous system (CNS) are a group of complex and disabling disorders characterized by the immune system mistakenly attacking the CNS. During the last 2 decades, we have witnessed a rapidly evolving spectrum of CNS autoimmune diseases, which has become a research hotspot in neurology. These include CNS inflammatory demyelinating diseases such as multiple sclerosis and neuromyelitis optical spectrum disorders, paraneoplastic, and other autoimmune encephalomyelitis and CNS involvement in systemic autoimmune diseases. Recently, although remarkable discoveries have accumulated more understanding of the autoimmune basis behind the physiopathologic mechanism, the exact pathogenic processes are still unclear. Patients may present with a variety of manifestations, posing a great challenge to diagnosis and management. The determination of biomarkers plays a significant role in CNS autoimmune diseases. Biomarkers can reflect the presence, nature, and intensity of certain immune responses triggered by both genetic and environmental processes, and bear great importance in guiding clinical diagnosis, estimating disease risk or prognosis, evaluating disease severity, and monitoring progression or response to therapy. For instance, the detection of disease-specific antibodies can contribute to the accurate diagnosis and precise treatment. Moreover, identifying the diverse biomarkers could further help to achieve the ultimate goal of personalized medicine.

The book covers the immunological and clinical aspects of immune-mediated diseases of the central and peripheral nervous system, excluding multiple sclerosis. It includes paraneoplastic neurological disorders, and discusses the immune mechanisms in the growing number of recognised paraneoplastic conditions. It not only provides an overview of the field but also discusses the possible role of immunity in other neurological disorders such as epilepsy. Chapters are written by scientists and clinicians directly involved in each specific area, who have summarized the current understanding of neuroimmunology, with emphasis on the underlying abormalities of the immune responses, the different clinical expression of the diseases and the important use of immunotherapies in treatment. Figures and tables are included in each chapter.

The scope of this contributed volume is to provide an overview of the latest translational research in the field of lupus pathogenesis, with particular emphasis on how these discoveries progress in parallel with therapeutic drug development. Systemic lupus erythematosus (SLE) is a multifaceted disease with a number of well-defined immune pathways that are dysregulated, resulting in an immune-mediated chronic inflammatory injury at target organs. As knowledge of these pathways evolves to provide opportunities for targeted drug therapy and lays the foundation for personalized medicine, clinicians and researchers need to keep up with the ever-expanding medical literature. This book will critically appraise the current understanding of important immunological pathways that contribute to the pathogenesis of lupus. We will review the role of interferons as part of the innate immune defects that perpetuate the loss of self-tolerance in SLE. B cell hyperactivity, as a defining hallmark of SLE, and different strategies of B cell targeted therapy will be discussed. The role of co-stimulation or immune checkpoint molecules in activating B and T cells will be reviewed, as well as other cytokines that serve in the amplification loop promoting a more proinflammatory Th1 or Th17 responses. Intracellular targets, such as signaling molecules in the JAK/STAT pathway, or a variety of kinases and proteasomes, can cause a cascading downstream effect of transcriptional responses that are important in SLE. Immune homeostasis can also be restored by bolstering the naturally occurring anti-inflammatory mechanisms. Glucocorticoid, as a potent natural anti-inflammatory hormone, can mediate its effects by recruiting histone deacetylase that serve to repress gene transcription. Glucocorticoid-induced leucine zipper is a gene upregulated by glucocorticoid that can be a potential target for development of anti-inflammatory strategy. Finally, T regulatory cells can be utilized to help restore to immune tolerance and are amongst the latest focus of therapeutic development in SLE.