Hypersomniac Patients Research Articles

Single sessions of transcranial direct current stimulation and transcranial random noise stimulation exert no effect on sleepiness in patients with narcolepsy and idiopathic hypersomnia.

Hypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia. A sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS). There were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness. We could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.

Electroencephalographic Markers of Idiopathic Hypersomnia: Where We are and Where We are Going

Idiopathic hypersomnia is a poorly defined nosological entity and has important phenotype heterogeneity. Moreover, diagnosing idiopathic hypersomnia is challenging as patients can report significant symptoms but may not meet diagnostic criteria on standard objective tests. Advanced analyses of electroencephalographic (EEG) activity could provide objective markers of idiopathic hypersomnia and explain part of its pathophysiology and heterogeneity. In fact, the EEG signal recorded during wakefulness and sleep not only captures sleep macroarchitecture but also homeostatic sleep process efficiency, strength of neural synchrony during sleep, sleep consolidation, and changes in cognitive processes. In this review, we will present current and potential markers of idiopathic hypersomnia, with a focus on sleep propensity. We will also discuss EEG changes occurring in sleep deprivation conditions and recovery nights, as well as those observed in other central hypersomnolence conditions, namely narcolepsy type-1 and type-2. Among EEG markers studied in sleep deprivation and narcolepsy are those derived from sleep macroarchitecture (sleep consolidation, sleep stage proportion, sleep-stage transitions, sleep onset in rapid-eye movement sleep) and microarchitecture (slow-wave activity, spindles), spectral analysis of the waking electroencephalographic signal, and cognitive event–related potentials. To date, no clear objective EEG markers of idiopathic hypersomnia exist, as studies were generally performed on small samples, used heterogeneous protocols (including changes of diagnostic criteria that occurred over time), and most of them focused on more traditional macroarchitecture sleep analyses. Based on studies of sleep deprivation and narcolepsy, further studies are needed to understand the EEG signal in idiopathic hypersomnia. Future studies should take advantage of the richness and the complexity of the EEG signal and verify whether subgroups of hypersomniac patients exist.

Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans.

Socio-professional handicap and accidental risk in patients with hypersomnias of central origin

Narcolepsy and idiopathic hypersomnia profoundly affect quality of life, education and work. Young patients are very handicapped by unexpected sleep episodes during lessons. Professionals frequently complain about sleepiness at work. Motor discomfort (i.e., cataplectic attacks) surprisingly is less handicapping in narcoleptics than sleepiness but only a few studies clearly assess the problem. Quality of life is also largely impaired in its physical and emotional dimensions. Sleepiness is the major factor explaining a decrease of quality of life and unexpectedly cataplectic attacks have little impact on patients. Another potential problem for these patients is the risk of accidents at work or when driving. Narcoleptic and hypersomniac patients have a higher risk of accidents than apneic or insomniac subjects. But, confounding factors such as duration of driving, number of cataplectic attacks or even objective level of alertness are not always entered in the analytic models mainly because of small samples of patients. Unlike in apneic patients, the effect of treatment on accidental risk has not been studied in narcoleptics or in hypersomniacs. Epidemiological data are needed to improve knowledge concerning these areas. Clinical trials assessing the impact of treatment on driving and work are also urgently needed. Finally, medical treatment does not seem to be completely efficient and physicians should pay more attention to the education, work, life and social environment of their patients.

Daytime sleepiness in hypersomniac patients, epileptic patients, and in healthy subjects

We evaluated daytime sleepiness in 26 hypersomniac patients, 100 epileptic patients, and 267 healthy subjects using the Epworth sleepiness scale (ESS). The ESS score was higher in hypersomniac patients, and no difference was found between epileptic patients and healthy subjects. The score had a weak correlation with the number and amount of anti-epileptic drugs used by epileptic patients. The patients with symptomatic epilepsy and who had a high seizure frequency reported a high daytime sleepiness. The ESS score showed a weak-positive correlation with the apnea-hypopnea index and a strong-negative correlation with the average and lowest O2 saturation during all-night non-rapid eye movement sleep in patients with obstructive sleep apnea syndrome. The ESS is a valid and convenient measure for evaluating daytime sleepiness in epileptic patients.

Increased REM density in narcolepsy-cataplexy and the polysymptomatic form of idiopathic hypersomnia.

The present work is focused on REM sleep density in patients with primary hypersomnia in comparison with non-hypersomnia subjects. 28 unmedicated patients with narcolepsy-cataplexy (NC) and 10 unmedicated patients suffering from the polysymptomatic form of idiopathic hypersomnia (IH) and their age- and sex-matched controls were included in the study. The clinical diagnosis was confirmed by MSLT and nocturnal PSG, HLA typing was performed in a respective group of narcoleptic patients. Polygraphical recordings were visually scored with particular regard to the two most characteristic phasic features of REM sleep: the number of rapid eye movements (REMs) and chin muscle twitches (Tws) per minute. These events were evaluated according to recognized criteria; a closer look was taken at both their frequency and their distribution across all the nocturnal REM periods (REMPs). The following main differences between hypersomniac patients (of both groups examined) and healthy controls were found in terms of phasic activity: (I) REM density (expressed in REMs/min and Tws/min in each REM period) was significantly increased in the hypersomniac patients in comparison with the controls. (p>0.05).(II) The intra-night phasic activity distribution was found rising more conspicuously in the hypersomniacs than in the controls.

Association Between HLA Antigens and Different Types of Hypersomnia

<h3>To the Editor.—</h3> A close association has been reported between HLA antigens and narcolepsy.^1-3Over the past two years we compared various types of hypersomnia in 56 patients. Thirty-four narcoleptics and 13 patients with idiopathic central nervous system hypersomnia, all unrelated and white, were included in the statistics (Table). These patients were diagnosed on the basis of a clinical interview and polygraphic recordings of at least five daytime naps. Polygraphic recordings were scored blind with regard to the results of HLA determinations. All narcoleptics exhibited excessive daytime sleepiness, cataplexy, and sleep-onset rapid eye movement periods during nap recordings. All idiopathic hypersomniacs had severe excessive daytime sleepiness without cataplexy and short sleep latencies but no sleep-onset rapid eye movement periods during naprecordings. Sleep apnea and nocturnal myoclonus were ruled out in all idiopathic hypersomniac patients by two all-night polygraphic recordings. Fifty-four HLA antigens of loci A, B, C, and

Monoamine Interactions in Narcolepsy and Hypersomnia: A Preliminary Report

Principal component analysis was performed on data obtained for the concentrations of 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, homovanillic acid, and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid from a group of normal volunteers (n = 40), hypersomniac patients (n = 13), and narcoleptic patients (n = 8). All four compounds were shown to be highly intercorrelated in the normal volunteers. In the hypersomniac patients, 3-methoxy-4-hydroxyphenylethylene glycol did not appear to be correlated with the other three compounds. In the narcoleptic patients, homovanillic acid and 3,4-dihydroxyphenylacetic acid appeared not to be correlated with the other two metabolites. The results provide tentative support for a neurochemical distinction between narcolepsy and hypersomnia and suggest that attention should be given to a possible malfunction of the dopamine system in narcolepsy and norepinephrine in hypersomnia.

An Alternative to the Multiple Sleep Latency Test for Determining Sleepiness in Narcolepsy and Hypersomnia: Polygraphic Score of Sleepiness

This article describes a quantitative assessment of pathological diurnal sleepiness in three groups of patients with excessive daytime sleepiness: narcoleptic patients, idiopathic hypersomniac patients, hypersomniac patients with sleep apnea syndrome. We analyzed polygraphic diurnal recordings of 45 min duration obtained under standardized conditions. We called the percentage of total sleep time during the 45-min recording the polygraphic index of sleepiness. The polygraphic score of sleepiness is determined by the latencies and total durations of the individual sleep stages. Because deeper sleep stages correspond to more pronounced sleepiness than do superficial sleep stages, we introduced coefficients for each sleep stage. We present a formula for calculating a score in a single figure that gives a good indication of the patient's sleepiness and makes inter- and intraindividual comparison possible. Separate REM and NREM sleep scores are also given.

Nocturnal sleep of narcoleptic patients: revisited.

Narcoleptic patients were compared to idiopathic hypersomniac patients and REM hypersomnia patients with regard to nocturnal sleep disruption. Results showed specificity of the narcoleptic sleep pattern and a possible correlation between REM fragmentation and cataplexy. Patients with and without periodic movements in sleep (PMS) were compared and no difference was found in their nocturnal sleep pattern, suggesting that PMS is not the major determinant of sleep disruption previously described in narcoleptic patients. Finally, nocturnal sleep disruption was treated with gamma-hydroxybutyrate (GHB) and results further indicate a possible link between REM fragmentation and cataplexy.

HLA antigens in narcolepsy and idiopathic central nervous system hypersomnolence.

Several studies have shown familial incidence of narcolepsy and idiopathic central nervous system (CNS) hypersomnia. HLA antigen studies performed in mongoloid and caucasoid narcoleptic patients on the A, B, and C loci have yielded conflicting results. The aim of this study is to document a possible association between the HLA system, including the DR locus and excessive daytime somnolence. Thirty-one narcoleptic patients and 10 idiopathic hypersomniac patients were selected and typed for 54 HLA antigens. A family with narcoleptic members in 3 generations was also studied. HLA-DR2 was found in 100% of narcoleptic patients. The frequency of HLA-A3 and B7, which are in linkage disequilibrium with DR2 was also increased in this group. Idiopathic hypersomniac patients showed an increase of HLA-Cw2, DR5, and B27, three antigens known to be in linkage disequilibrium. In the family study, narcoleptic patients were also HLA-DR2; moreover, 3 subjects, one of whom was narcoleptic, were HLA-DR2 as a result of recombination (i.e., genetic crossing-over). These results locate the hypothetic gene associated with narcolepsy more precisely, and indicate that narcolepsy and idiopathic CNS hypersomnolence are two different entities.

Paroxysmal awakenings from sleep associated with excessive daytime somnolence: a form of nocturnal epilepsy.

We describe 14 hypersomniac patients whose polysomnographic recordings revealed abnormal EEG patterns consisting of paroxysmal epileptic discharges during stages 2 and 3 of NREM sleep, associated with arousals, fragmentation of sleep, and reduction in sleep efficiency, particularly REM sleep. Three patients who received anticonvulsants showed clinical and polysomnographic documented improvement in sleep patterns. These patients probably had a unique form of nocturnal epilepsy-related sleep disorder, manifested by paroxysmal wakenings from sleep.

Lateral differences in amplitudes of the auditory middle latency response : I. Kadobayashi, A. Toyoshima, M. Kohga and N. Kato (Kyoto, Japan)

Narcolepsy and idiopathic hypersomnia profoundly affect quality of life, education and work. Young patients are very handicapped by unexpected sleep episodes during lessons. Professionals frequently complain about sleepiness at work. Motor discomfort (i.e., cataplectic attacks) surprisingly is less handicapping in narcoleptics than sleepiness but only a few studies clearly assess the problem.Quality of life is also largely impaired in its physical and emotional dimensions. Sleepiness is the major factor explaining a decrease of quality of life and unexpectedly cataplectic attacks have little impact on patients.Another potential problem for these patients is the risk of accidents at work or when driving. Narcoleptic and hypersomniac patients have a higher risk of accidents than apneic or insomniac subjects. But, confounding factors such as duration of driving, number of cataplectic attacks or even objective level of alertness are not always entered in the analytic models mainly because of small samples of patients. Unlike in apneic patients, the effect of treatment on accidental risk has not been studied in narcoleptics or in hypersomniacs.Epidemiological data are needed to improve knowledge concerning these areas.Clinical trials assessing the impact of treatment on driving and work are also urgently needed. Finally, medical treatment does not seem to be completely efficient and physicians should pay more attention to the education, work, life and social environment of their patients.

Sodium gamma-hydroxybutyrate in the treatment of essential hypersomnia

Five non-narcoleptic hypersomniac patients were given GHB (3.10 to 4.5 g per os) at night. Four patients reported a persistent improvement of their daytime sleepiness as a result of this treatment. Nocturnal polygraphic recordings were performed in all patients before and after GHB. The durations of sleep and of waking times were reduced after GHB while there was an increase of stages 3 and 4 during the first third of the night. It is possible that the increase in delta wave sleep early in the night is responsible for a re-establishment of a normal distribution of subsequent sleep stages and thus produces a more recuperative sleep.

Sleep respiratory arrhythmias in control subjects, narcoleptics and non-cataplectic hypersomniacs

Normal subjects may present central-type apneas or periodic respiration during sleep (stages I and II and paradoxical sleep). The importance of these respiratory disorders increases with age. Hypersomniac patients can manifest either similar or more significant sleep respiratory disorders than normal subjects. The presence of cataplexy or obesity does not permit the prediction of the existence of respiratory arrhythmias or of their type. Sleep respiratory arrhythmias of central type are not likely to cause hypersomnia; however, an aggravating role may be played by obstructive apneas.

The human tongue during sleep: Electromyographic activity of the genioglossus muscle

The bilateral genioglossi muscles of the tongue, by virtue of their protrusive action, play an important role in the mechanics of maintaining an open air passage in the oropharyngeal region. Electromyographic studies of the genioglossus muscle during sleep were conducted in six healthy human volunteers. The principal results are the following: In quiet waking and in quiet sleep (stages I–IV), the genioglossal EMG is characterized by continuous discharges with substantially augmented activity during inspiration. When the subject enters REM sleep, the tonic genioglossal activity almost ceases except for small bursts during the inspiratory phase of respiration. During REM sleep, genioglossal motor units may become inactive for periods of up to 90 sec. However, these silent periods are regularly interrupted by three to six vigorous inspiratory genioglossal bursts. Genioglossal EMG with substantially augmented discharges during inspiration are best recorded from indwelling electrodes placed close to the origin of the muscle. During snoring, the genioglossal activity related to certain phases of the respiratory cycle is vastly increased. The results are discussed in context with problems encountered in hypersomniac patients with the sleep apnea syndrome.