Preface

Chapter 8 **Changes in Motor Unit Loss and Axonal Regeneration Rate in**

**Possible Different Pathogenetic Mechanisms? 227**

Chapter 9 **Eye-Gaze Input System Suitable for Use under Natural Light**

Abe Kiyohiko, Ohi Shoichi and Ohyama Minoru

Giannini and Ferdinando Sartucci

**VI** Contents

**Sporadic and Familiar Amyotrophic Lateral Sclerosis (ALS) —**

Tommaso Bocci, Elisa Giorli, Lucia Briscese, Silvia Tognazzi, Fabio

**and Its Applications Toward a Support for ALS Patients 243**

The research in amyotrophic lateral sclerosis (ALS) has dramatically increased in the last 20 years, greatly improving our understanding of the pathological mechanisms involved in the disease. The number of hypothesis on the pathogenic causes of ALS and the mechanisms of motor neuron death keeps growing. Twenty years ago there was a general agreement that ALS was a motor neuron disease. All other symptoms were secondary to the primary cause that was the death of upper and lower motor neurons. Today there are several hypotheses suggesting that dysfunction in other cell types, such as astrocytes, is the primary cause of the disease that leads to motor neuron death. Twenty years ago there were not animal mod‐ els for ALS, now there are multiple rodent and non-mammalian models of the disease.

The more accepted hypotheses for the causes of ALS are reviewed in the first chapter by Rossi and coauthors. This chapter reviews the potential pathogenic mechanism involved in the etiology of ALS providing short description of each mechanism.

The chapter by Shin and Lee reviews the cellular mechanisms found to potentially partici‐ pate in the degeneration of motor neurons in ALS. This chapter provides a cellular approach to the proposed mechanisms of motor neuron death in ALS, supporting the hypothesis that multiple molecular pathways could be involve in motor neuron death in different patients.

Diamanti and collaborators provide further support for the hypothesis of multiple molecu‐ lar mechanisms in ALS by reviewing correlations between genotype and disease presenta‐ tion. Using studies of Italian ALS patients, the authors provide evidence showing the correlation between different phenotypic presentations of ALS with known genetic causes of the disease.

The chapter by Bowerman and collaborators reviews up to day evidence of the role of neu‐ roinflammation in the pathology of ALS. The role of astrocytes and other inflammatory cells is reviewed in detail. The authors also discuss in depth the possible inflammatory mediators and molecular mechanism involved in the induction of motor neuron death.

Franco and collaborators review the highly controversial participation of oxidative stress in the pathology of ALS. The chapter focuses on the oxidative mechanisms proposed to explain the gain-of-function of ALS-linked mutant SOD.

Ferraiuolo and coauthors provide a new interpretations of the ALS literature based on the recent discovery that a plethora of new genetic mutations affecting a variety of genes are linked to ALS. The review provides an unique perspective on the strengths and weaknesses of classic and new animal models of the disease based on performance and similarities to the human disease.

The chapter by Aggarwal describes studies in at risk presymtomatic individuals carrying mutant SOD. The research uses MUNE to determine motor neurons status and the thera‐ peutic benefits of riluzole. The methods described in this chapter could provide and early diagnosis in patients carrying mutations linked to ALS allowing presymtomatic treatments.

Bocci and collaborators found by Macro-EMG, that there is a possible compensatory over‐ branching in ALS motor neurons, which provides a possible explanation for the adult onset of the disease.

Abe and collaborators provided a review of the last advances of eye-gaze systems, which allows ALS patient to communicate after almost other voluntary mobility is lost. The tech‐ nology reported here is relatively inexpensive and for those patients unable to communicate by other means could represent a significant improvement on quality of life.

> **Alvaro G. Estévez, Ph.D.** Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, USA

**Chapter 1**

**Pathophysiology of Amyotrophic Lateral Sclerosis**

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder character‐ ized by death of pyramidal neurons in the motor cortex (upper motor neurons) and motor neurons in the brain stem and central spinal cord (lower motor neurons). This results in muscle weakness, progressive motor disability, and finally death by respiratory failure or an associated infection (Shook and Pioro, 2009). There are two types of ALS familiar (fALS) and sporadic ALS (sALS). They are both clinically undistiguishale one from the other; fALS accounts for 10% of all cases being the rest of the cases sALS (Pasinelli and Brown, 2006). In the last few years, there had been an explosion of genetic studies associating ALS with several genetic mutations in genes codifying for different proteins: Cu/Zn superoxide dismutase, (SOD1), transactive response binding protein 43 (TARDBP), fused in sarcoma (FUS), and valosin containing protein (VCP). Most recently, a genetic defect was identi‐ fied with an expansion of the noncoding GGGGCC hexanucleotide repeat in the chromo‐ some 9, open reading frame 72 (C9ORF72), associated with ALS with and without

Despite of all these discoveries the etiology of ALS remains elusive. A number of potential pathogenic mechanisms have been associated with ALS including excitotoxicity, mitochon‐ drial dysfunction, apoptosis, glial activation, RNA-processing, growth factor abnormalities,

ALS is characterized by upper motor neuron (corticospinal motor neurons) and lower motor neuron (bulbospinal motor neurons) degeneration and death as well as reactive gliosis

and reproduction in any medium, provided the original work is properly cited.

© 2013 Rossi et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

etc. These potential pathogenic processes are reviewed in this chapter.

Fabian H. Rossi, Maria Clara Franco and

frontotemporal dementia (Boeve et al., 2012).

Additional information is available at the end of the chapter

Alvaro G. Estevez

**1. Introduction**

**2. Pathology**

http://dx.doi.org/10.5772/56562
