Disease-specific attention impairment in disorders of chronic excessive daytime sleepiness.

OBJECTIVE: Patients with chronic excessive daytime sleepiness (EDS) complain of substantial attention deficits. However, their underlying neuronal dysfunction is largely unknown. Previous studies showed similar attention performances in central disorders of hypersomnolence suggesting that EDS-related cognitive impairment is independent of its cause. The aim of the current study was to further explore attentional profiles in disorders of chronic EDS. METHODS: Ten patients with narcolepsy type 1 (NT1; age 26.7 ± 9.3 years), 14 patients with idiopathic hypersomnia (IH; age 26.7 ± 9.3 years), 14 patients with subjective EDS (sEDS; age 31.4 ± 14.3 years), ie, a mean sleep latency >8 min in the multiple sleep latency test (MSLT), and 20 healthy controls (HC; age 32.6 ± 11.3 years) performed the vigilance task and the selective attention task of the test battery SLEEP® (Vienna Test System Neuro®). We assessed mean response time (RT) and standard deviation of RT separately for the first and the second half of the vigilance task to evaluate performance changes over time (time on task effect; TOT). RESULTS: A significant interaction effect between group and TOT on the mean RT in the vigilance task suggests partly group-specific attention deficits. Combining paradigms of sustained and selective attention discriminated patients with NT1, IH, sEDS and HC. Behavioral results were unrelated to the mean sleep latency in the MSLT. CONCLUSIONS: Discriminative performance of the sustained and selective attention tasks indicate disease-specific components of attention in NT1, IH, and sEDS. Different temporal dynamics of attentional control efficiency might be one factor underlying group differences.

The Perception and Attention Functions test battery as a measure of neurocognitive impairment in patients with suspected central disorders of hypersomnolence.

The aim of the current study was to evaluate an attention test as a discriminative tool to measure neurocognitive impairment in patients with disorders of hypersomnolence. Chronic excessive daytime sleepiness is the main symptom in central disorders of hypersomnolence. For diagnostic purposes and treatment evaluation, reliable assessment of excessive daytime sleepiness is required. Thirty-six patients with central disorders of hypersomnolence were compared with 20 healthy controls. All participants performed the 'Perception and Attention Functions' (WAF) of the Vienna Test System. Patients underwent polysomnography, Multiple Sleep Latency Test and Maintenance of Wakefulness Test. Patients were divided into two groups: (i) patients who met the criteria of disorder of hypersomnolence (objective excessive daytime sleepiness); and (ii) patients with subjective excessive daytime sleepiness, i.e. with normal Multiple Sleep Latency Test results. Group 1 consisted of 23 patients with objective excessive daytime sleepiness (11 with idiopathic hypersomnia, nine with narcolepsy type 1, three with narcolepsy type 2); group 2 included 13 patients with subjective excessive daytime sleepiness. The results showed cognitive impairment in patients with objective excessive daytime sleepiness and even in patients with subjective excessive daytime sleepiness. WAF tests identified distinct attention profiles in patients with narcolepsy type 1, idiopathic hypersomnia/narcolepsy type 2, and patients with subjective excessive daytime sleepiness. WAF test measures correlated with Maintenance of Wakefulness Test and the Epworth Sleepiness Scale, but not with Multiple Sleep Latency Test and the Fatigue Severity Scale. In conclusion, the multidimensional WAF test battery detects cognitive impairment even in patients that complain of excessive daytime sleepiness but have normal Multiple Sleep Latency Test results. WAF tests offer valuable information that adds to the existing polysomnographic measures in discriminating patients with different types of chronic excessive daytime sleepiness. The results provide new insights into cognitive dysfunction underlying different types of chronic excessive daytime sleepiness.

Identification of an endocannabinoid system in the rat pars tuberalis-a possible interface in the hypothalamic-pituitary-adrenal system?

Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research. By means of immunocytochemistry, enzymes involved in EC biosynthesis, e.g., N-arachidonoyl-phosphatidylethanolamine-phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα) and enzymes involved in EC degradation, e.g., fatty acid amide hydrolase (FAAH) and cyclooxygenase-2 (COX-2), were demonstrated in PT cells of the rat. Immunoreactions (IR) for FAAH and for the cannabinoid receptor CB1 were observed in corticotrope cells of the rat adenohypophysis; these cells were identified by antibodies against proopiomelanocortin (POMC) or adrenocorticotrophic hormone (ACTH). In the outer zone of the median eminence, numerous nerve fibers and terminals displayed CB1 IR. The majority of these were also immunolabeled by an antibody against corticotropin-releasing factor (CRF). These results suggest that the EC system at the hypothalamo-hypophysial interface affects both the CRF-containing nerve fibers and the corticotrope cells in the adenohypophysis. Our data give rise to the hypothesis that, in addition to its well-known role in the reproductive axis, the PT might influence adrenal functions and, thus, the stress response and immune system.