Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disorder characterized by motor neuron cell death in the brain and spinal cord. The typical disease symptom is the rapid loss of muscle control, which eventually leads to the complete paralysis of voluntary muscles of the entire body. There is no curative treatment for amyotrophic lateral sclerosis. The rarity of the disease and the difficulties in accurate early diagnosis are the major challenges in the proper understanding of the disease and the development of curative therapy. This book brings together a team of experts, both clinicians and basic scientists, to provide a comprehensive understanding of amyotrophic lateral sclerosis, challenges, and approaches to combat this devastating disease. The clinical chapters provide excellent views of diagnosis, pathology, management, and the problem of diagnostic delay. The basic science chapters provide a comprehensive description of pathomechanisms and therapies with emphasis on dysfunctional astrocytes, impaired synaptic transmission, defective axonal transport, biomarkers, cell-based therapies, and gut microbiota. The book is primarily aimed at clinicians and basic scientists; however, it will likely be of interest to a wide audience interested in amyotrophic lateral sclerosis.

Contents

• Foreword
• Preface
• List of Contributors
• 1. Clinical Manifestation and Management of Amyotrophic Lateral Sclerosis
  Ashok Verma.
  • INTRODUCTION
  • CLINICAL FEATURES: ALS SUBTYPES BASED ON UPPER AND LOWER MOTOR NEURON INVOLVEMENT
  • PATHOLOGICAL FEATURES
  • MANAGEMENT
  • CONCLUSION
  • REFERENCES
• 2. Time to Diagnosis and Factors Affecting Diagnostic Delay in Amyotrophic Lateral Sclerosis
  Danielle Richards, John A. Morren, and Erik P. Pioro.
  • INTRODUCTION
  • DIAGNOSTIC DELAY IN NON-NEUROLOGICAL AMBULATORY MEDICINE
  • DIAGNOSTIC DELAY IN CHRONIC NEURODEGENERATIVE DISEASE
  • LENGTH OF DIAGNOSTIC DELAY IN ALS
  • PATIENT-SPECIFIC FACTORS LEADING TO DIAGNOSTIC DELAY
  • PHYSICIAN/PROVIDER-SPECIFIC FACTORS LEADING TO DIAGNOSTIC DELAY
  • ADVANTAGES OF DECREASING TIME TO DIAGNOSIS IN ALS
  • POTENTIAL DISADVANTAGES OF DECREASING TIME TO DIAGNOSIS IN ALS
  • IMPLEMENTED MEASURES FOR MINIMIZING DIAGNOSTIC DELAY IN ALS
  • PROSPECTIVE OPPORTUNITIES TO MINIMIZE DIAGNOSTIC DELAY IN ALS
  • CONCLUSION
  • REFERENCES
• 3. Astrocytes in Amyotrophic Lateral Sclerosis
  Sandra H. Vaz, Sara Pinto, Ana M. Sebastião, and Dora Brites.
  • INTRODUCTION
  • ASTROCYTIC REACTIVITY AND HETEROGENEITY
  • GLUTAMATE AND GABA TRANSPORTERS
  • DYSREGULATED AUTOCRINE/PARACRINE SIGNALING MECHANISMS
  • CONCLUSION
  • REFERENCES
• 4. Synaptic Transmission and Motoneuron Excitability Defects in Amyotrophic Lateral Sclerosis
  Frédérique Scamps, Franck Aimond, Cécile Hilaire, and Cédric Raoul.
  • INTRODUCTION
  • ELECTROPHYSIOLOGICAL PROPERTIES OF MOTONEURONS IN ALS
  • ALS-ASSOCIATED INHIBITORY TRANSMISSION DEFECTS
  • ALTERATIONS IN THE MODULATORY TRANSMISSION IN ALS
  • ALS-ASSOCIATED DEFECTS IN EXCITATORY TRANSMISSION
  • CONCLUSION
  • REFERENCES
• 5. Axonal Transport and Local Translation of mRNA in Amyotrophic Lateral Sclerosis
  Seiichi Nagano and Toshiyuki Araki.
  • INTRODUCTION
  • FUNCTION OF RNA-BINDING PROTEINS
  • PATHOLOGICAL ROLE OF RNA GRANULES
  • RIBOSOMAL PROTEIN mRNAS AS AXONAL TRANSPORT TARGETS
  • LOCAL TRANSLATION IN AXONS IN PHYSIOLOGICAL CONDITIONS AND ALS PATHOGENESIS
  • CONCLUSION
  • REFERENCES
• 6. Blood-based Biomarkers for Amyotrophic Lateral Sclerosis
  Heather M. Wilkins, Mazen M. Dimachkie, and Abdulbaki Agbas.
  • INTRODUCTION
  • POTENTIAL BIOMARKERS FOR ALS
  • CONCLUSION
  • REFERENCES
• 7. Cell-based Research and Therapy for Amyotrophic Lateral Sclerosis: Promises and Challenges
  Juliana Ferreira Vasques, Leandro Coelho Teixeira Pinheiro, Renata Guedes de Jesus Gonçalves, Rosalia Mendez-Otero, and Fernanda Gubert.
  • INTRODUCTION
  • CELL THERAPY IN ALS PRECLINICAL MODELS
  • CLINICAL TRIALS USING STEM CELLS IN ALS
  • MODELLING ALS IN VITRO WITH INDUCED PLURIPOTENT STEM CELLS
  • CONCLUSION
  • REFERENCES
• 8. Gastrointestinal Status and Microbiota Shaping in Amyotrophic Lateral Sclerosis: A New Frontier for Targeting?
  Letizia Mazzini, Fabiola De Marchi, Elena Niccolai, Jessica Mandrioli, and Amedeo Amedei.
  • INTRODUCTION
  • THE MICROBIOTA BRAIN-GUT AXIS
  • ALS AND GASTROINTESTINAL SYMPTOMS
  • METABOLIC DYSFUNCTION IN ALS
  • CHANGES IN GUT MICROBIOME COMPOSITION IN NEURODEGENERATION AND ALS
  • POSSIBLE MECHANISMS UNDERLYING THE EFFECT OF GUT MICROBIOME ON THE PATHOGENESIS OF ALS
  • EFFECTS OF MICROBIOTA-INDUCED INFLAMMATION ON THE PATHOGENESIS OF ALS
  • CLINICAL EVIDENCE THAT GUT MICROBIOME MODULATION IMPACTS ALS
  • CLINICAL CORRELATIONS AND POTENTIAL THERAPEUTIC APPROACHES
  • CONCLUSION
  • REFERENCES

Amyotrophic Lateral Sclerosis

ISBN: 978-0-6450017-7-8

DOI: https://doi.org/10.36255/exonpublications.amyotrophiclateralsclerosis.2021

Edited by

Toshiyuki Araki, MD, PhD, Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan

Published by

Exon Publications, Brisbane, Australia

Copyright© 2021 Exon Publications

Copyright of individual chapters belongs to the respective authors. The authors grant unrestricted publishing and distribution rights to the publisher. The electronic versions of the chapters are published under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). https://creativecommons.org/licenses/by-nc/4.0/. Users are allowed to share and adapt the chapters for any non-commercial purposes as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. The book in its entirety is subject to copyright by the publisher. The reproduction, modification, replication and display of the book in its entirety, in any form, by anyone, for commercial purposes are strictly prohibited without the written consent of the publisher.

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First Published in July 2021

Printed in Australia