RICERCA ITALIANA     

Ultradian rhythms of wakefullness and sleep structure alterations in narcolepsy: relationship between neutophysiological, cognitive, neurometabolic and genetic aspects.

Università degli Studi di Bologna

Abstract

Sleep disorders are frequent and excessive daytime sleepiness represents a common complain encountered in the clinical practice. The increasing interest on this field is mostly due to their association with significant morbidity. Despite recent progresses in the understanding the pathophysiological mechanisms and phenotypic expressions of narcolepsy, a well defined sleep disorders presenting with excessive daytime sleepiness, a number of aspects still need to be clarified. The present proposal aims to contribute to the understanding of pathophysiological basis and of the related neuropsychological deficits of narcolepsy. In particular, the proposed study, involving five Italian Research Units leaders in their specific field of interest, display a highly interdisciplinary and integrated approach by encompassing genetics, neurophysiology, neuro-imaging and neuro-psycology and will comprehensively evaluate multiple genetic determinants of the complex phenotypic expression in narcolepsy.
The specific scientific and technological objectives are:
* to characterise clinically and by polysomnography (PSG) 100 narcoleptic patients.
* to identify, by using a candidate gene approach, predisposing genetic factors which may contribute to excessive sleepiness, and other clinical, PSG, neurochemical, neuroimaging, and neuropsychological features in patients with narcolepsy.
* to identify by exploring the main cognitive functions the relationships between >>>

Principal Investigator

Giuseppe PLAZZI Università degli Studi di BOLOGNA

Research Objectives

The aim of this study is to identify and relate the clinical, neurophysiological, cognitive, brain metabolic, subtle structural, activation and genetic findings in order to contribute to the identification of the multiple determinants of the complex phenotypic expression in narcolepsy. One hundred patients with narcolepsy (range 18(70 years) will be enrolled in this study by one Research Unit. The diagnosis will be based on clinical and laboratory criteria. Patients with Narcolepsy with at least two sleep onset REM-sleep episodes upon the multiple sleep latency test (MSLT), and excessive diurnal sleepiness, reflected by a mean sleep latency at the MSLT of 5 min or less. Patients with Narcolepsy with cataplexy with at least two sleep onset REM-sleep episodes upon the multiple sleep latency test (MSLT), cataplexy and excessive diurnal sleepiness, reflected by a mean sleep latency at the MSLT of 5 min or less. They all must carry the human leukocyte antigen (HLA) DQB1*0602. All narcoleptic patients will undergo to a 48-hour free running polygraphic recording, spending two consecutive nights in the sleep lab, followed by MSLT. Data will stored in electronic format for off-line analysis. The aim of the study of the Research Unit I is to analyse the REM and NREM sleep pattern of a large population of narcoleptic patients, focusing not only on the conventional sleep parameters, but also on the sleep "microstructure" by mean of the analysis of the cycling alternating pattern (CAP) >>>

Timescale

24 months

National and international background

Narcolepsy is a disabling underdiagnosed neurological disease affecting 0.02-0.06% individuals and characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. Cataplexy, a sudden muscle tone loss brought on by emotions, is a clinical feature almost exclusive to narcolepsy that occurs in around 60% of patients. Typical features in narcolepsy are represented by sleep onset REM periods (SOREMPs) during daytime, as revealed by the multi-sleep latency test (MSLT), SOREMPs and reduced sleep efficiency revealed by nocturnal polysomnography. Under the term Narcolepsy the International Classification of Sleep Disorders encloses two separate clinical entities: Narcolepsy and Narcolepsy with cataplexy. Both are chronic disabling neurological diseases accounting for REM sleep abnormalities with characteristic REM sleep onset periods. While the latter is considered a model disease, characterized by a homogeneous phenotype, Narcolepsy without cataplexy still represents a less defined clinical entity. The sleep structure changes found in narcoleptic patients were reduced REM latency and sleep efficiency, and increased wake after sleep onset (WASO) and stage 1 NREM sleep in DQB1*0602-positive subject, not only in comparison to control subjects but also in comparison to DQB1*0602-negative narcoleptics (1). Other features shared by all narcoleptic patients are reduced sleep stage 2 and slow-wave sleep and increased >>>