Foundations of Neurology – serie

The evaluation of the efficacy and safety of a clinical tool, be it a diagnostic technique, a preventive methodology, or a therapeutic intervention, is an im­ portant responsibility of physicians. The history of medicine is characterized by the authoritarianisms of teachers and of organizations giving way to the clinical experience of physicians; authoritarian dictum was replaced by case report and then by case series. As physicians learned to substitute the analysis of data for the inconsistencies of dictums and anecdotes, the problems of the case series as an investigative tool became more evident: patient selection criteria, measurements of outcome, significance of results, and extrapolation of conclusions to the community of patients. In response to these issues, the methodology of the controlled clinical trial has evolved and with it the instru­ ments of study design and of biostatistics as aids to study design and data analysis. The medical - surgical armamentarium has evolved from being dependent solely upon the observations and conclusions of a skilled clinician to being constructed upon the systematic collection and evaluation of data by a team of skilled clinicians and their statistical colleagues: this is the controlled clinical trial. During the past two decades, the evaluation of clinical approaches to pre­ vention and therapy has become particularly important to clinicians concerned with nervous system dysfunction. There has been and continues to be an explosion of information from the basic neurosciences and from the applica­ tion of biotechnology to the nervous system.

This book encompasses basic and clinical reports on the cerebellum and its primary atrophic disorders, the cerebellar degenerations. Rapid progress has been made in undestanding the organization and function of the cerebellum at the neuronal, synaptic, and molecular level. Of particular importance has been the identification of the chemical transmitters utilized by the cer­ ebellar cellular systems. More than any other brain region, the cerebellum utilizes amino acids as its main excitatory and inhibitory neurotransmitters. Excitatory amino acid transmitters, in addition to serving neuronal com­ munication, may also mediate trophic and toxic effects, and as such, they may playa role in neurodegenerative processes. The cerebellar degenerations were among the first human disorders with primary system atrophy to be studied clinically and pathologically. This field of clinical cerebellar sciences, no longer confined to the previously known descriptive level, is now advancing rapidly, propelled by rapid advances in neuroimaging, immunology, and molecular biology. The advent of CT, MRI, and PET has in recent years permitted the study of central nervous system alterations in living patients, thus contributing substantially to the accuracy of the diagnosis and the classification of these disorders. The nosology of cerebellar degenerations, which has been the subject of much debate for over a century, is presently a dynamic field, with new entities being recognized and old "classic ataxias" being redefined in the light of new genetic evidence.

The evaluation of the efficacy and safety of a clinical tool, be it a diagnostic technique, a preventive methodology, or a therapeutic intervention, is an im­ portant responsibility of physicians. The history of medicine is characterized by the authoritarianisms of teachers and of organizations giving way to the clinical experience of physicians; authoritarian dictum was replaced by case report and then by case series. As physicians learned to substitute the analysis of data for the inconsistencies of dictums and anecdotes, the problems of the case series as an investigative tool became more evident: patient selection criteria, measurements of outcome, significance of results, and extrapolation of conclusions to the community of patients. In response to these issues, the methodology of the controlled clinical trial has evolved and with it the instru­ ments of study design and of biostatistics as aids to study design and data analysis. The medical - surgical armamentarium has evolved from being dependent solely upon the observations and conclusions of a skilled clinician to being constructed upon the systematic collection and evaluation of data by a team of skilled clinicians and their statistical colleagues: this is the controlled clinical trial. During the past two decades, the evaluation of clinical approaches to pre­ vention and therapy has become particularly important to clinicians concerned with nervous system dysfunction. There has been and continues to be an explosion of information from the basic neurosciences and from the applica­ tion of biotechnology to the nervous system.