In 1991, a small annual meeting named "International Winter Conference on Neurodegeneration (lWCN)" was established; the aim of this meeting is to review the neurodegenerative disorders and to attempt to explore how progress might be made in this field, as the neurodegenerative disorders have been emerging to be one of the major causes of morbidity and mortality in modern societies. The first meeting took place in Seefeld, Austria, in February 1992; the topics for the first IWCN were chosen to provide a broad foundation of clinical science, which included the problem of aging, classification of neurodegenerative disorders and of Alzheimer's dis natural history, pathology, and clinical neurology ease, Parkinson's disease, and amyotrophic lateral sclerosis. The fundamental pathology underlying these neurodegenerative disorders is neuronal cell death. For the understanding of pathophysiol ogy and the development of neuroprotective treatment for these dis orders, elucidation of the mechanism of neuronal cell death at the cellular and molecular level is essential. With this concept in mind, the second IWCN was held in Whistler Village in Canada in January 1993. Funding was generously provided by Schering AG, Berlin, and for the excellent organization we have to thank Ms. Ingeborg Runge.

Over the last 25 years, few topics in medicine, and none in neurology, sur- pass Parkinson's disease from the viewpOInt of progress in understanding me- chanisms and treating symptoms. Our entire concept of anatomy (the very ex- istence of a nigrostriatal pathway) and physiology (dopaminergic trans- mission) has undergrone a revolution as the result of studies on Parkinson's disease leading to (a) the recognition of dopamine depletion as a crucial bio- chemical feature, and (b) the ability to alleviate symptoms by replenishing dopamine with levodopa. From this background has emerged a subclassifica- tion of dopamine receptors into Dl and D2 types, together with the develop- ment and therapeutic application of synthetic molecules that function as agonists at dopamine receptors. The pharmacological interrelationship be- tween parkinsonism (inadequate dopamine) and chorea (excessive dopamine) has been elucidated because dopaminomimetic agents were found to alleviate parkinsonism and induce chorea, while dopamine blocking drugs induced parkinsonism and alleviated chorea. Pharmacokinetic manipulation of levo- dopa achieved by adding extracerebral decarboxylase inhibitors (carbidopa, benserazide) decreased certain side effects and resulted in efficacy being at- tained with lower dosage. Extracerebral dopamine receptor blockers have proved invaluable in decreasing the emesis of dopaminomimetics, because the dopaminoceptive chemoreceptor trigger zone is located outside the blood- brain barrier. Recently, novel routes of administration of antiparkinson drugs, such as subcutaneous infusion, have been explored in an attempt to achieve more evenly sustained blood concentrations of therapeutic agents.