Book contents
- Frontmatter
- Contents
- Foreword
- Preface
- Acknowledgements
- Abbreviations
- 1 Epidemiological considerations
- 2 The clinical spectrum of ALS
- 3 The pathology of ALS
- 4 Pathogenic mechanisms in ALS
- 5 The role of clinical neurophysiology in ALS
- 6 The application of imaging techniques
- 7 ALS therapy, therapeutic trials, and neuroprotection
- 8 The overlap syndromes
- References
- Index
4 - Pathogenic mechanisms in ALS
Published online by Cambridge University Press: 25 March 2010
- Frontmatter
- Contents
- Foreword
- Preface
- Acknowledgements
- Abbreviations
- 1 Epidemiological considerations
- 2 The clinical spectrum of ALS
- 3 The pathology of ALS
- 4 Pathogenic mechanisms in ALS
- 5 The role of clinical neurophysiology in ALS
- 6 The application of imaging techniques
- 7 ALS therapy, therapeutic trials, and neuroprotection
- 8 The overlap syndromes
- References
- Index
Summary
Introduction
Despite the rapid proliferation of reports describing pathophysiological mechanisms in ALS, the cause of this disorder is still unknown. As for other diseases, it is important to distinguish between initiating factors for ALS (e.g. a genetic basis in familial disease), secondary effects induced by the disease (e.g. depletion of amino acid contents in brain and spinal cord) and effects produced in the late or terminal stages of ALS (e.g. agonal effects). Any review of the pathogenesis of ALS must also be mindful of the many promising leads in this area that have proved to be fruitless. Furthermore, the data reported in some studies related to ALS (for instance measurement of cerebrospinal fluid glutamate levels) are sometimes so inconsistent that it is impossible to draw firm conclusions.
Our view is that ALS is a heterogeneous disease in which a variety of relatively distinct initiating factors such as Cu/Zn–SOD1 mutations or abnormal glutamate metabolism lead to common clinical manifestations. The view that ALS is a multifactorial disease does not mean that different initiating factors cannot share similar pathophysiological mechanisms for motoneuron death. In fact, we expect that some, or perhaps all, of the initiating stimuli will trigger a common cascade of ‘downstream’ processes, ultimately resulting in neuronal dysfunction. For instance, it appears likely that mutations in the Cu/Zn–SOD1 gene are involved in some cases of FALS. This view is supported by recent work showing some relation between the specific mutation and the clinical course of the disease.
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- Amyotrophic Lateral SclerosisA Synthesis of Research and Clinical Practice, pp. 106 - 143Publisher: Cambridge University PressPrint publication year: 1998