Purpose of ReviewClinical presentation of central hypersomnolence disorders, including narcolepsy type 1 and 2 and idiopathic hypersomnia, is often similar, and determining the correct diagnosis... Show morePurpose of ReviewClinical presentation of central hypersomnolence disorders, including narcolepsy type 1 and 2 and idiopathic hypersomnia, is often similar, and determining the correct diagnosis remains challenging. Neuroimaging techniques have provided valuable insights into the pathophysiology of narcolepsy and idiopathic hypersomnia. Here, we review current structural and functional brain imaging findings in central hypersomnolence disorders and discuss the future perspectives of neuroimaging in these sleep disorders.Recent FindingsMost studies have focused on narcolepsy type 1 (or narcolepsy with cataplexy), showing inconsistent but extensive structural differences in the hypothalamus and its normally widespread projections. Functional studies have mainly focused on resting-state or emotion regulation in narcolepsy type 1 and have revealed disturbed activity in limbic and mesolimbic structures in relation to cataplexy. Finally, recent studies suggest a disruption of the default-mode network in patients with idiopathic hypersomnia.SummaryMost neuroimaging studies to date have been conducted in small samples, while narcolepsy type 2 (or narcolepsy without cataplexy) and idiopathic hypersomnia remain relatively understudied. Larger studies with consistent clinical phenotyping should be the focus of future investigations. In addition, multi-modal imaging methods will be crucial to resolve previous inconsistencies and identify reliable objective biomarkers that could aid in understanding the pathophysiology and potentially support the diagnostic process. Show less
Kallweit, U.; Bassetti, C.L.A.; Oberholzer, M.; Fronczek, R.; Beguin, M.; Strub, M.; Lammers, G.J. 2018
Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble... Show moreSleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons. The total number of hypocretin-1 immunoreactive neurons was quantified in postmortem hypothalami of AD patients (n = 10) and matched controls (n = 10). In addition, the hypocretin-1 concentration was measured in postmortem ventricular cerebrospinal fluid of 24 AD patients and 25 controls (including the patients and controls in which the hypothalamic cell counts were performed). The number of hypocretin-1 immunoreactive neurons was significantly decreased by 40% in AD patients (median [25th–75th percentiles]); AD 12,935 neurons (9972–19,051); controls 21,002 neurons (16,439–25,765); p = 0.049). Lower cerebrospinal fluid (CSF) hypocretin-1 levels were found in AD patients compared with controls (AD: 275 pg/mL [197–317]; controls: 320 pg/mL [262–363]; p = 0.038). Two AD patients with documented excessive daytime sleepiness showed the lowest CSF hypocretin-1 concentrations (55 pg/mL and 76 pg/mL). We conclude that the hypocretin system is affected in advanced AD. This is reflected in a 40% decreased cell number, and 14% lower CSF hypocretin-1 levels. Show less
The first part deals with the hypothalamic hypocretin system in disorders that are accompanied by narcolepsy-like sleep disturbances, i.e. Prader-Willi Syndrome, Parkinson__s Disease and Huntington... Show moreThe first part deals with the hypothalamic hypocretin system in disorders that are accompanied by narcolepsy-like sleep disturbances, i.e. Prader-Willi Syndrome, Parkinson__s Disease and Huntington__s Disease. To determine whether the hypocretin system is affected in these disorders, the total number of hypocretin neurons was determined using quantitative techniques in post-mortem human hypothalami. The reason why hypocretin neurons disappear in narcolepsy is still a mystery. A putative autoimmune aetiology has been hypothesized, but a screening for autoantibodies and a n=1 trial with intravenous immunoglobulins yielded no unequivocal results in favor of this hypothesis. In the second part, the consequences of hypocretin deficiency in narcoleptic patients are explored, focussing on vigilance, metabolism and the autonomic nervous system and skin temperature regulation. The ability of a specific neuropsychological test to measure vigilance as a severity indicator for narcolepsy is explored. Two possible causes for the obesity commonly seen in narcolepsy are a decreased basal metabolic rate and a changed autonomic tone. To assess the influence of hypocretin deficiency on skin temperature regulation, thermoregulatory profiles of the proximal and distal skin of narcoleptic subjects were compared to profiles of healthy controls during a daytime sleep registration. Show less
