Our knowledge of cerebellar functions has increased exponentially during the last two decades. Powerful new neuroimaging techniques and the spectacular development of molecular biology are probably the most striking examples of developments that have completely changed the field.

We started the project that led to this book because we were convinced that the time was ripe for an updated, comprehensive text attempting to summarize this new knowledge and present it in a coherent, systematic fashion. In preparing this book, our aim was to present the current perspective on the functional roles of the cerebellum as well as on the clinical and pathophysiological aspects of cerebellar diseases. We wanted to provide a comprehensive review of the major advances of these last years.

The Cerebellum and its Disorders is divided into nine parts, each giving an overview of a particular area. In each chapter the latest discoveries are presented in the context of their clinical relevance. In Part I, the fundamental aspects of cerebellar structure and functions are covered. This part serves as the basis for those that follow. Part II addresses the main models of cerebellar function that have been proposed so far. Part III includes an overview of cerebellar symptoms and their pathophysiology, including the emerging concepts on the cognitive roles of the cerebellum and their clinical implications. Part IV addresses the broad spectrum of sporadic cerebellar disorders. Part V deals with the effect of toxic agents on the cerebellum. Part VI covers the growing area of cerebellar grafts. Part VII summarizes the neuropathology of cerebellar disorders. Parts VIII and IX are dedicated to the genetics of dominant and recessive cerebellar ataxias, respectively.

Introduction

In 1863, Nicholaus Friedreich, Professor of Medicine in Heidelberg, Germany, wrote three articles about a ‘degenerative atrophy of the posterior columns of the spinal cord’ causing progressive ataxia, sensory loss, and muscle weakness (Friedreich, 1863a, 1863b, 1863c). It could strike several siblings with normal, unaffected parents. Friedreich reported additional cases in 1876 and 1877. Charcot suspected for some time that Friedreich had described a form of tabes, but eventually he recognized that it was a new disease entity. Brousse (1882) was the first to use the name ‘Friedreich ataxia.’ After a few years, Ladame (1890) reported more than 100 cases. In the years that followed, more and more descriptions of inherited degenerative diseases causing ataxia were published. Many of these cases were noted to have some characteristics resembling Friedreich's ataxia, eventually blurring the definition of the disease (Bell and Carmichael, 1939). Only in the late 1970s did landmark studies establish the autosomal recessive pattern of inheritance (Geoffroy et al., 1976; Harding, 1981; Harding and Zilkha, 1981) and define rigorous diagnostic criteria (Geoffroy et al., 1976; Harding, 1981). It was realized that the disease shows variability in the clinical picture, sometimes with atypical presentations coexisting in the same family with typical cases (Winter et al., 1981; Filla et al., 1990, 1991; Muller-Felber et al., 1993). Specific variants, such as the so-called Acadian ataxia (Barbeau et al., 1984; Richter et al., 1996), were recognized in some ethnic groups.