Brain, Vol. 123, No. 11, 2361-2363,
November 2000
© 2000 Oxford University Press
Book reviews |
AMYOTROPHIC LATERAL SCLEROSIS.
Edited by Robert H. Brown Jr, Vincent Meininger and Michael Swash.1999. London: Martin Dunitz Publishers. Price £75. Pp. 479. ISBN 1-85317-421-1.
Department of Neurology, Royal Preston Hospital, Preston, UK
Any author or editor contemplating a new volume on motor neurone disease (MND) enters an increasingly competitive field. All recent works reviewing this rapidly expanding area of neurology stake their claim in different ways, generally with success. Some try to achieve this by reducing the numbers of contributors to the minimum, thus ensuring relative uniformity of style; others, as in this case, use a multi-author approach. This is a way of trying to ensure that the chapters are written by experts, but it can lead to a patchiness of style. Each strategy has its potential advantages and disadvantages. Such is the pace of development in this area of research that a delay in publication resulting from a late-submitted chapter can mean that the main body of the volume becomes outdated by the time it is published. This is an increasing area of concern with the increasing trend towards electronic publishing. Contrasts in approach also exist within this volume: while a number of chapters are written by a single author, others are the work of multiple authors, in one case as many as 13! There is also a considerable variation in chapter length. Some topics such as excitotoxicity and oxidant stress are discussed in more than one chapter. Although this might lead to a risk of repetition it does not detract from the overall usefulness of the book. Indeed, the presence of different views on the same topic within the same volume can serve to enhance understanding and increase the value to the reader. Several authors exercise their minds on the selective vulnerability of the motor neurone. These contributions give tantalising insights into potential pathogenetic mechanisms in MND. It is not surprising that superoxide dismutase 1 (SOD1) gene mutations frequently enter the discussion. Several authors offer opinions on possible links between these mutations and disease causation. These discussions contribute hugely to the strength of this volume. Many are highly insightful.
The importance of the clinical perspective is strongly emphasized. The need to keep the diagnosis of MND under constant critical review during follow-up is given particular emphasis, advice that is not only vital in patients with a working diagnosis of MND but also very sound advice for many other chronic neurological disorders. The specific diagnostic and clinical issues that can arise in patients with suspected familial MND are discussed in detail.
There are comprehensive reviews of geographical variants, including the Madras disease and Pacific Rim variants as they occur in the Kii peninsula of Japan, Guam and the Irian Jaya of New Guinea. Exogenous neurotoxins and MND variants as they occur on the Pacific Island of Guam and elsewhere around the Pacific Rim are described, along with a review of the possible role of aluminium and Cycad in these clinical entities. For those practising outside these areas the importance of detecting potentially treatable MND mimic syndromes such as multifocal motor neuropathy is stressed.
The coverage of molecular pathology is very strong. The section relating inclusion bodies seen in patients with MND with those encountered in other neurodegenerative diseases is also particularly illuminating. The interface between MND, MND mimic syndromes and other motor neurone diseases such as spinal muscular atrophy are exhaustively discussed. The issue of the selective vulnerability of motor neurones is not only reviewed in a chapter on biochemical pathology but also raised in several other chapters. Excitotoxic hypotheses of MND are also discussed by several contributors along with the possible role of glutamate transporter proteins.
The review of neurotrophins examines the evidence which suggests that they might promote motor neurone survival in vivo or in vitro, as well as the evidence that has accrued from randomized controlled clinical trials investigating these drugs as putative treatments for MND. Several authors evaluate evidence pointing towards oxidant stress as a major influence in the pathogenesis of MND.
Pathology bridges the link between basic science and clinical practice. The upper motor neurone remains the great unmeasurable in MND and potential electrophysiological approaches to the objective evaluation of upper motor function are discussed. The use of orthodox EMG and nerve conduction studies is also reinforced along with detailed coverage of quantitative techniques. This section interfaces with thoughts on the potential contribution of electrophysiological techniques to MND clinical trial methodology. The role of the cortical motor neurone in MND pathogenesis is discussed in relation to findings from MR spectroscopy, PET and cortical magnetic stimulation studies. The role of cortical magnetic stimulation studies is developed further in a subsequent chapter followed by a discussion of the role of imaging investigations in patients suspected of suffering from MND. The importance of these in excluding MND mimic syndromes that may have neurosurgical connotations is stressed. This section is particularly well illustrated and contains valuable material for all clinical neuroscientists.
The text moves into a further discussion of potential pathogenetic mechanisms. The issue of oxidant stress is again raised in the context of both sporadic and familial MND. The unanswered question of the link between SOD1 mutations and the pathogenesis of the disease phenotype is discussed at length. The leads into a debate on the interface between oxidant stress and excitotoxicity. While both are currently front runners as potential pathogenetic mechanisms in MND it is important to remember that these hypotheses are not necessarily mutually exclusive.
The finding of SOD1 gene mutations in some kindreds with familial MND has clearly been a landmark in the study of MND: such has been the significance of this finding that no-one would now question the reality of familial MND as a clinical entity. Yet there was a time when the existence of familial MND as a specific clinical entity was doubted: intrafamilial aggregation of ALS was attributed by some to common environmental exposure. Nonetheless, the genetics versus environment debate continues, and this is discussed within the text. A very useful list of 73 of the described SOD1 mutations is given, along with an equally useful summary of non-SOD1 candidate genes. Contrasts with genetic markers in other motor neurone diseases, including hereditary spastic paraparesis, spinal muscular atrophy and Kennedy's syndrome, are also discussed along with comments regarding the absence of genetic markers in Guamian MND. The potential importance of transgenic animal models in developing experimental neuroprotective strategies is debated.
Considerable emphasis is placed on the difficulty in accessing the site of pathology, i.e. the anterior horn cell for experimental research aimed at leading us closer to a knowledge of potential pathogenetic mechanisms in MND. Immunological aspects, including calcium channel antibodies, are discussed along with thoughts on the possible importance of the glia. This leads into a very useful review of the potential importance of apoptosis.
Science evolves into clinical management and the importance of securing an adequate disease specific quality of life rating scale is stressed. There is a very thorough summary of the scales that have been used in the study of MND. There is a critical review of the pitfalls of the inappropriate use of quality of life rating scales. There is a very useful review of previous clinical trials, which includes a valuable overview of some of less commonly known drugs which have been evaluated as putative disease modifying therapies in MND such as cyclophosphamide, cyclosporine and azathioprine. The previous SPECIALS trial of branch chain amino acids remains a matter of concern. This was a landmark trial that has never been published in a peer-reviewed journal. It has generally come to be assumed that this was a negative trial. The importance of publishing negative trials is stressed.
The section on general management issues as well as symptomatic and disease modifying treatment is outstanding. There is an authoritative chapter on the moral and ethical issues associated with euthanasia and physician-assisted suicide. The discussion of terminal care emphasizes the importance of non-pharmacological issues including the management of dysphagia and ventilatory difficulties. These symptoms present major challenges in palliative care. The volume concludes with a section contributed by the voluntary sector. This provides a most valuable and contrasting perspective that gives salutary insights into a perspective from outside the health service.
This volume is a major contribution. It is strongly recommended to those wishing to gain an authoritative overview of the state of the art in MND. Established MND researchers will probably want a copy for their own use and this reviewer would strongly suggest that it should also be widely available within departments of neurology. It is an excellent starting point for the neurological trainee who wishes to consider a research project in a topic related to MND. It is very likely that they will find a contribution which gives them an entrée into their proposed area of study and point them in the direction of the important references.
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