[Sleep disorders associated to prion diseases].

INTRODUCTION

Description of sleep disorders associated to human prion diseases.

DEVELOPMENT

The recent advances on pathology, genetics and immunocytochemistry are an outstanding contribution to the knowledge of transmissible spongiform encephalopathies and identification of possible new variants. Despite decades of research, human prion diseases have remained enigmatic in many aspects. Among these, the intricate connection between infectivity and genetics, genotype-phenotype correlation, pathogenesis of brain damage and in some cases its proven dependence on the genotypic combination of a pathogenic mutation and a polymorphism. Regarding this subject we should take into consideration that Fatal Familial Insomnia (FFI) appears as an ideal model situation for answering some of these problems because of its distinctive clinicopathological phenotype based on a specific genotype as well as its transmissibility. This disease has recently enlarged the group of prion diseases. It is linked to a mutation at codon 178 of the prion protein gene, coupled with the methionine codon at position 129, the site of a methionine/valine polymorphism. The clinical aspects of FFI include a peculiar sleep-wake disorder and a autonomic hyperactivity associated with vegetative and hormonal circadian rhythm disregulation, besides cognitive and motor alteration, and it is related to the selective atrophy of limbic part of the thalamus. EEG conventional sleep studies and 24-hour polygraphic recordings can provide proof of early disappearance sleep spindles and the disturbances of sleep, which typify the disease. Epidemiologic, pathophysiologic, and histopathological aspects are also mentioned. Finally we remark the major neurophysiological features of Creutzfeldt-Jakob disease and Morvan's chorea.