Brain, Vol. 124, No. 11, 2336-2338,
November 2001
© 2001 Oxford University Press
Book reviews |
HANDBOOK OF ATAXIA DISORDERS.
Edited by Thomas Klockgether. 1999. New York: Marcel Dekker. Price US$215. Pp. 689. ISBN 0-82470-381-2.
Section of Neurology, Department of Medicine, University Hospital of Wales, Cardiff, UK
This is Volume 51 of the Marcel Dekker (http://www.dekker.com) handbook series `Neurological Disease and Therapy', which attempts to collate the increasing contributions from recent molecular advances of the ataxic disorders. The pace of these advances can create disadvantages in a book of this kind, with an inevitable lag between compilation and publication. It has contributions from a number of respected authors in the field, but with a European and particularly German dominance.
There are 32 chapters, organized within seven themed sections, although three sections have only one chapter each. In general the book is well constructed with comprehensive summaries and generates some interesting points of discussion. The first two chapters of the Introduction examine the architectural and functional aspects of the cerebellar system. Chapter 1 deals with the complex organization of the cerebellum and its connections, and efforts are made to integrate this complexity with clinical classification. The attempt to summarize the complex physiology of the cerebellar afferent and efferent fibres seems a little brief and is placed before the details of embryology. The second chapter provides a competent and understandable picture of the normal functions of the cerebellar system and some helpful insights into the pathophysiological basis for the cerebellar syndrome.
Chapter 3 deals with historical aspects of ataxia research as well as the long-running controversies in the ataxia field: its nosology and disease classification. The influence of recent advances in the past decade of molecular analyses is aptly collated in this chapter. The Introduction is closed with Chapter 4, written by the editor, on rational routes in the clinical approach to patients presenting with ataxia as a predominant feature. It is of interest that the three suggested diagnostic steps rely heavily on historical points (age of onset, possible mode of inheritance and associated symptoms) following decisions on focal or diffuse cerebellar disease and recognition of established subgroup phenotypes, raising the issue of whether clinical neurology has made any recent advances or whether we simply rely more heavily on laboratories. The discussions on these diagnostic steps are coherent and clear in style, and will provide a useful guide to clinicians dealing with such patients.
Section two, comprising only Chapter 5, entitled `Developmental disorders: cerebellar malformations' is well illustrated, particularly with neuroimaging, a feature that is lacking in other parts of this book. Relatively rare conditions are discussed in adequate length, and congenital dysgenesis is well covered. There is an awareness of the difficulty of clinical identification of these disorders in early life and the extent of the influence of imaging technologies on diagnosis. Despite such technology, many of these disorders have genetic bases to them about which little is known.
Section three takes on the main diagnoses in the ataxias: autosomal recessive ataxias, mitochondrial disorders, autosomal dominant ataxias and transmissible spongiform encephalopathies. The reader is immediately aware of the limitations involved in elaborating aspects of epidemiology, neuropathology and the management of these distinctive disorders, with some exceptions. Nevertheless, attempts are made towards a rational analysis that is well supported by clinical experience. A strength of all the chapters in this section is the molecular pathogenesis (even though many issues are still unclear) and the thorough description of clinical features of various groups of disorders. Undoubtedly these positive features make the book worth consulting when standard neurology textbooks fail to satisfy.
The majority of the chapters spanning this 689-page book (Chapters 6–15), are on recessively inherited ataxias. Beginning with useful discussions on a disorder that was first described by Nicolaus Friedreich (1825–1882) in Chapter 6, similarly interesting issues are considered with Madame Louis Barr (1941), and ataxia telangiectasia in Chapter 7. Interestingly, attempts are made to move from the commonly encountered one or two paragraph discussion on the management issues, and to shed some light on what can be done to alleviate the disability, as well as looking forward to future therapeutic approaches with our increasing knowledge of the disorder at molecular level. Chapter 8 deals with early-onset cerebellar ataxia (EOCA) with retained tendon reflexes, nosology coined by Harding (1981), which is recognized for being distinct, clinically and genetically, from Friedreich's ataxia. Despite some limitations, due to a degree of uncertainty about this disorder, the authors have presented a wide differential diagnosis which supplements their recognition that only a small proportion of these patients are identified with laboratory testing.
Chapters 9–13 introduce the reader to ataxia associated with metabolic disorders, the majority of which are, not surprisingly, of autosomal recessive inheritance. These include abetalipoproteinaemia, ataxia with isolated vitamin E deficiency, Refsum's disease, cerebrotendinous xanthomatosis and ataxias associated with rare metabolic disorders. Chapters 14 and 15 cover infantile-onset spinocerebellar ataxia and autosomal recessive spastic ataxia of Charlevoix–Saguenay, respectively. Perhaps because of the single racial heritage known for both conditions (the former with a Finnish family and the latter with Charlevoix French ancestors), the respective authors have the advantages of being able to produce a more detailed account of the neuropathology that is lacking sometimes in other chapters.
Section four has only one chapter to it, attending to a variety of mitochondrial disorders. Following the discovery of an abnormal mitochondrial genome in 1988 and the link of defective mitochondrial respiratory chain with ataxias, there has been increasing detection of deletions (single or multiple) and point mutations for various mitochondropathies. Despite the absence of any epidemiological data, some credit should be given to the author for the accounts of the other essential clinical aspects of these disorders, which are sometimes overlooked.
Autosomal dominant ataxias are discussed in Section five, consisting of nine chapters (Chapters 17–25). The absence of any Japanese contributor becomes apparent from the omission of DRPLA as a subject heading. With the amount of information now known about this disorder, and its prevalence in Japan, it would seem appropriate for some more detailed attention in this handbook. The terms used for distinctive disorders in this section relate to the clinical classification proposed by Harding (1983), which remains useful despite the increasingly used mutation-based classification. The coherent chapter styles in this section are useful and allow easy comparison. There are some useful insights into possible pathophysiological mechanisms. Chapter 26 discusses the transmissible spongiform encephalopathies (TSE) or, simply, prion diseases. This group of progressive, chronic, disabling and fatal disorders remains poorly understood.
The final theme is covered in Section seven and comprises Chapters 27–32, which look into the non-hereditary ataxias. The title of Chapter 27 (Idiopathic cerebellar degeneration) is rather misleading since the main theme is multiple system atrophy (MSA), and it seems probable that only 15% of the idiopathic late-onset cerebellar ataxia cases actually progress to develop the clinical features of MSA. Certainly this group of disorders poses a considerable diagnostic challenge to most neurologists since the diagnosis is often only confirmed at autopsy. Frequent references are made to the consensus published in 1999 (Journal of Neurological Sciences) for the diagnosis of MSA in the discussions of the clinical features, presumably in an attempt to assist the reader in trying to distinguish idiopathic late-onset cerebellar ataxia from MSA clinically at presentation. With the importance of glial cytoplasmic inclusions, there appears to be a certain lack of neuropathological discussion, in which case there is a considerable pathological overlap between MSA and other degenerative late-onset ataxias in sharing the features of olivopontocerebellar atrophy (OPCA). Nonetheless, the discussion of recent advances in using the supplementary tests is promising and fulfils one of the aims of the handbook.
Chapter 28 discusses the features related to alcoholic cerebellar degeneration as well as other toxic causes such as heavy metals, drugs and solvents. As the exact mechanisms for such degeneration are unknown, the chapter is a rather quick read, hastily reaching its comprehensive references list. In Chapter 29 (Paraneoplastic cerebellar degeneration), it is shown that recent molecular advances have greatly influenced the detection of auto-antibodies among cancer patients. However, these antibodies have not been shown to cause cerebellar degeneration, and some studies suggest immunopathogenesis mediated by cytotoxic T cells to be the culprit. Despite this, it is recognized that the absence of these anti-neuronal antibodies does not rule out paraneoplastic cerebellar involvement. The variable responses to treatment strategies are also mentioned. The following chapter deals with cerebellar encephalitis including gluten ataxia (a term proposed by one of the authors recently), infective causes of cerebellar encephalitis, Miller–Fisher syndrome and the controversial link between cerebellar ataxia and anti-glutamic acid decarboxylase antibodies. Equally interesting are the final chapters, where there are organized discussions on ataxia related to acquired vitamin deficiencies or endocrine disorders and heat-induced cerebellar insult, respectively. Both chapters give adequate discussions of these distinctive disorders, with also some insights to their management.
This is another book that deserves to make its way to any neurology library bookshelf. Despite some sense of urgency to complete the book, resulting in a rather unattractive layout with one or two omissions, it provides a comprehensive summary of the ataxias useful for neurologists of all grades, as well as clinicians in related disciplines, to aid in understanding this heterogeneous group of disorders. With the knowledge that many of these patients and their families still face unmet needs, our current increasing understanding of the aetiology and pathogenesis will, in the near future, permit us to identify more therapeutic avenues as well as setting up improved designs of clinical trials and more effective management plans. Last but not least, it should be remembered that any attempt to compile such a book on ataxia is difficult at best, as the information gathered about the ataxias has rapidly expanded with new advances that have transformed the attitudes towards degenerative cerebellar ataxias.
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