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The aim of the present placebo-controlled sleep laboratory study was to compare the acute effects of gabapentin (GBT) and ropinirole (ROP) in restless legs syndrome (RLS). In a parallel-group design, 40 RLS patients received 300 mg GBT and another 40 patients 0.5 mg ROP as compared with placebo. Polysomnographic and psychometric measures were obtained in three sleep laboratory nights (screening/placebo/drug). Statistics included a Wilcoxon test for differences between drug and placebo and a U test for inter-group differences. Sleep efficiency and latency were found significantly improved after GBT, while they remained unchanged after ROP, with significant inter-drug differences. Sleep architecture showed oppositional changes after the two drugs: While GBT decreased S1, increased slow-wave sleep and SREM and shortened REM latency, ROP increased S2, decreased slow-wave sleep and SREM and increased REM latency. Periodic leg movements (PLM) showed a significantly greater decrease after ROP (-73%) than after GBT (-35%). Subjective sleep quality improved significantly only after GBT; mental performance improved after both drugs with no inter-drug differences. In conclusion, the dopamine agonist ROP showed acute therapeutic efficacy with regard to PLM measures only, whereas GBT had a less pronounced effect on these measures, but improved objective and subjective sleep and awakening quality as compared with both placebo and ROP. Differential acute drug effects may serve as prognostic indicators of therapeutic response of individual patients.

The pathogenesis, pathophysiology, and pharmacotherapy of sleep bruxism (SB) are still not fully understood. We investigated symptomatology, objective and subjective sleep and awakening quality of middle-aged bruxers compared with controls and acute effects of clonazepam 1 mg compared with placebo by polysomnography and psychometry. Twenty-one drug-free bruxers spent 3 nights in the sleep lab, 21 age- and sex-matched controls 2 nights. Clinically, bruxers exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures, polysomnographically impaired sleep maintenance, increased movement time, stage shift index, periodic leg movements (PLM) and arousals and psychometrically deteriorated subjective sleep and awakening quality, evening/morning well-being, drive, mood, drowsiness, attention variability, memory, and fine motor activity. As compared with placebo, clonazepam significantly decreased the SB index in all patients (mean: -42 +/- 15%). Sleep efficiency, maintenance, latency, awakenings and nocturnal wake time, the stage shift index, S1, PLM, the arousal index, subjective sleep and awakening quality, and fine motor activity improved.

Background and Purpose: Recent neuroimaging studies in narcolepsy discovered significant gray matter loss in the right prefrontal and frontomesial cortex, a critical region for executive processing. In the present study, event-related potential (ERP) low-resolution brain electromagnetic tomography (LORETA) was used to investigate cognition before and after modafinil as compared with placebo., Patients and Methods: In a double-blind, placebo-controlled cross-over design, 15 patients were treated with a 3-week fixed titration scheme of modafinil and placebo. The Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT) and auditory ERPs (odd-ball paradigm) were obtained before and after the 3 weeks of therapy. Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components., Results: The ESS score improved significantly from 15.4 (+/- 4.0) under placebo to 10.2 (+/- 4.1) under 400mg modafinil (p=0.004). In the MWT, latency to sleep increased nonsignificantly after modafinil treatment (11.9+/-6.9 versus 13.3+/-7.1 min). In the ERP, N2 and P300 latencies were shortened significantly. While ERP amplitudes showed only minor changes, LORETA revealed increased source strengths: for N1 in the left auditory cortex and for P300 in the medial and right dorsolateral prefrontal cortex., Conclusion: LORETA revealed that modafinil improved information processing speed and increased energetic resources in prefrontal cortical regions, which is in agreement with other neuroimaging studies.

Interrater variability of sleep stage scorings has an essential impact not only on the reading of polysomnographic sleep studies (PSGs) for clinical trials but also on the evaluation of patients' sleep. With the introduction of a new standard for sleep stage scorings (AASM standard) there is a need for studies on interrater reliability (IRR). The SIESTA database resulting from an EU-funded project provides a large number of studies (n = 72; 56 healthy controls and 16 subjects with different sleep disorders, mean age +/- SD: 57.7 +/- 18.7, 34 females) for which scorings according to both standards (AASM and R&K) were done. Differences in IRR were analysed at two levels: (1) based on quantitative sleep parameter by means of intraclass correlations; and (2) based on an epoch-by-epoch comparison by means of Cohen's kappa and Fleiss' kappa. The overall agreement was for the AASM standard 82.0% (Cohen's kappa = 0.76) and for the R&K standard 80.6% (Cohen's kappa = 0.68). Agreements increased from R&K to AASM for all sleep stages, except N2. The results of this study underline that the modification of the scoring rules improve IRR as a result of the integration of occipital, central and frontal leads on the one hand, but decline IRR on the other hand specifically for N2, due to the new rule that cortical arousals with or without concurrent increase in submental electromyogram are critical events for the end of N2.

Aim: Pupillometry is a non-invasive measurement technique based on the pupillary response to specific sensoric, mental and emotional variables. After topical application of a cholinergic antagonist (tropicamide) an increased pupillary dilatation response in Alzheimers s disease patients was described ("receptor test"). The aim of the present study was to evaluate the usefulness of the 0.01% tropicamide receptor test in differentiating types of dementia., Method: 425 patients (159 men, 266 women, mean age 75 years) of the Memory Clinic of the SMZ Ost Vienna, Austria were included in the study. 195 patients suffered from a dementia in Alzheimer's disease with late onset (ICD-10: F00.1), 42 from dementia in Alzheimer's disease with early onset (F00.0), 71 from vascular dementia (F01), 34 from Lewy-Body dementia (F03) and 83 from mixed dementia (F00.2). All patients were investigated by means of a computer-assisted pupillometer. The pupillary diameter of the left eye was measured 4 times (baseline=0 minutes, after 20, 40 and 60 minutes). 4 minutes after baseline one drop of 0.01% tropicamide solution was installed onto the left eye of the patients., Results: At baseline the pupillary diameter was largest in Lewy-Body dementia, smallest in vascular dementia. Significant differences were observed between vascular dementia and early-onset dementia in Alzheimer's disease as well as between Lewy-Body dementia and all other dementia syndromes (except dementia in Alzheimer's disease with early onset). The 0.01% tropicamide receptor test made it possible to differentiate early-onset dementia in Alzheimer's disease from vascular and mixed dementia., Conclusion: Utilizing pupillometry in combination with the 0.01% tropicamide receptor test allows to discriminate between different dementia types of, as demonstrated in our study.

Objective: Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography., Methods: In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF)., Results: In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity., Conclusions: Narcoleptic patients showed prolonged information processing, as indexed by N2 and P300 latencies and decreased energetic resources for cognitive processing., Significance: Electrophysiological aberrations in brain areas related to the 'executive attention network' and the 'limbic system' may contribute to a deterioration in mental performance and mood at the behavioral level.

Early pharmacological studies in animals demonstrated that ABIO-08/01, a new isoxazoline, exerted anxiolytic and anticonvulsant, but also cognition-enhancing properties. Thus, the aim of the present double-blind, placebo-controlled multiple-ascending-dose study was to investigate the effect of the new compound on event-related potentials (ERPs). In a randomized ascending-dose design for phase-1 studies, 16 young healthy male subjects aged 30.2 +/- 5.7 years received three ascending drug doses (10, 20, and 40 mg) and placebo for 7 days, with a washout period of 8 days in between. Auditory ERPs were recorded pre-dose and 2 h post-dose on days 1 (acute effect) and 5 (subacute and absolute superimposed effect). Descriptive statistics with one confirmatory statement on P300 latency demonstrated a significant shortening after acute, subacute, and superimposed administration of 40 mg ABIO-08/01. While ERP amplitudes showed only minor effects, low-resolution brain electromagnetic tomography (LORETA) demonstrated that ABIO-08/01 promotes more efficient information processing by reallocating perceptual and cognitive ERP resources. Thus, our ERP studies confirm early pharmacological findings in animals of a cognition-enhancing effect of ABIO-08/01, which is interesting in the context of the anxiolytic mode of action of the compound as its CNS effects are quite different from those of anxiolytic sedatives, such as benzodiazepines., (2008 John Wiley & Sons, Ltd.)

Background: In a pilot placebo-controlled study, low dosages of 0.5-2mg/24h rotigotine showed a dose-dependent beneficial effect in restless legs syndrome (RLS) patients., Methods: Efficacy and safety of the dopamine agonist rotigotine, formulated as a once-daily transdermal system (patch), was investigated for five fixed dosages and compared to placebo in patients with idiopathic RLS in a double-blind, randomized, parallel-group, multicenter, six-week dose-finding trial. Primary efficacy measure was the total score of the International RLS Severity Scale (IRLS); in addition, the RLS-6 scales and the Clinical Global Impressions (CGI) were administered., Results: Of 371 enrolled patients, 341 patients (mean age 58+/-10years, 67% females) were randomized. The IRLS total score improved between baseline and end of the six-week treatment period by -10.6 (0.5mg/24h rotigotine; patch area 2.5cm2), -15.1 (1mg/24h; 5cm2), -15.7 (2mg/24h; 10cm2), -17.5 (3mg/24h; 15cm2), and -14.8 (4mg/24h, 20cm2) as compared to placebo (-9.2). The hierarchical statistical test procedure demonstrated superiority of rotigotine over placebo for 4mg/24h, 3mg/24h, 2mg/24h, and 1mg/24h, with p-values of 0.0013, <0.0001, 0.0003, and 0.0004, respectively. Only the 0.5mg/24h dose was not different compared to placebo (p=0.2338). The CGI and the RLS-6 severity items supported the efficacy of the rotigotine doses beyond 0.5mg/24h. The most frequent side effects were application site reactions and nausea and tended to be more frequent with higher doses., Conclusions: This dose-finding trial identified the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h. The lowest dose was ineffective and, with the highest dose, no additional benefit was observed.

Unlabelled: Patients with somatoform pain often complain of sleep disorders, but sleep disorders are not an integrated part of the diagnosis of this disorder. Restless legs syndrome is associated with painful symptoms and sleep disturbances. The aim of our study was to evaluate the prevalence of restless legs syndrome (RLS) in somatoform pain disorder., Method: In this study 100 consecutive patients (mean age: 46.4; SD: 11.4; women: 58) diagnosed with somatoform pain disorder (SPD) were clinically investigated for the occurrence of RLS at the behavioral medicine clinic for pain outpatients in the department of psychiatry within the Medical University of Vienna. The pain parameters of SPD were assessed using a pain questionnaire and visual analogue scales (VAS). The severity of RLS was established using the questionnaire of the International Restless Legs Syndrome Study Group (IRLSSG)., Results: The prevalence of restless legs syndrome found in somatoform pain disorder was 42%. Interrupted sleep was found in 83.3% in somatoform pain disorder with comorbid RLS and in 64.1% in somatoform pain disorder without RLS. Patients with continuous somatoform pain had a significant higher occurrence of RLS (Sample: 55%; with RLS: 71.4% and without RLS: 43.1%). The pain parameters increased parallel to the severity of RLS. Additionally, RLS was associated with higher psychosocial disability in family life., Conclusions: The prevalence of RLS is high in our sample of patients with somatoform pain disorder. There seems to be a difference in pain profile between patients with and without RLS. RLS may increase the pain level and prolong pain in somatoform pain disorder. RLS should be considered when a somatoform pain disorder is diagnosed.

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.

Traditionally, auscultation is applied to the diagnosis of either respiratory disturbances by respiratory sounds or cardiac disturbances by cardiac sounds. In addition, for sleep apnea syndrome diagnosis, snoring sounds are also monitored. The present study was aimed at synchronous detection of all three sound components (cardiac, respiratory, and snoring) from a single spot. The sounds were analyzed with respect to the cardiorespiratory activity, and to the detection and classification of apneas. Sound signals from 30 subjects including 10 apnea patients were detected by means of a microphone connected to a chestpiece which was applied to the heart region. The complex nature of the signal was investigated using time, spectral, and statistical approaches, in connection with self-defined time-based and event-based characteristics. The results show that the obstruction is accompanied by an increase of statistically relevant spectral components in the range of 300 to 2000 Hz, however, not within the range up to 300 Hz. Signal properties are discussed with respect to different breathing types, as well as to the presence and the type of apneas. Principal component analysis of the event-based characteristics shows significant properties of the sound signal with respect to different types of apneas and different patient groups, respectively. The analysis reflects apneas with an obstructive segment and those with a central segment. In addition, aiming for an optimum detection of all three sound components, alternative regions on the thorax and on the neck were investigated on two subjects. The results suggest that the right thorax region in the seventh intercostal space and the neck are optimal regions. It is concluded that for patient assessment, extensive acoustic analysis offers a reduction in the number of required sensor components, especially with respect to compact home monitoring of apneas.

Objective: Although epidemiological and clinical studies suggest that hormone replacement therapy (HRT) may protect against cognitive disorders and neurodegenerative diseases, the relation between estrogen and cognition in postmenopausal women remains controversial., Methods: In a double-blind placebo-controlled, parallel group design study the effects of HRT with the estrogen-progestogen combination Presomen 1.25 compositum((R)) (1.25mg equine conjugated estrogens administered for 21 days plus the progestogen 5mg medrogeston given for 11 days) on event-related potentials (ERPs) in postmenopausal patients with age-related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were investigated. After a pre-drug comparison with age-matched normal postmenopausal controls, 48 psychotropic drug-free patients aged 60 +/- 6 years were randomized to receive either placebo or verum for 4 months. ERPs were recorded before as well as on the 91-92 days of the study, which thus fell into the estrogen phase of the treatment during the fourth cycle., Results: At baseline, patients showed a lengthening of P300 latency and an attenuation of P300 amplitudes as compared with normal controls. After HRT with Presomen, a significant shortening of P300 latency as compared with placebo was observed., Conclusions: The baseline P300 differences suggest that in the patient group the aging process was advanced, while after HRT with Presomen a significant improvement and normalization of information processing as indexed by P300 was observed.

To date, the only standard for the classification of sleep-EEG recordings that has found worldwide acceptance are the rules published in 1968 by Rechtschaffen and Kales. Even though several attempts have been made to automate the classification process, so far no method has been published that has proven its validity in a study including a sufficiently large number of controls and patients of all adult age ranges. The present paper describes the development and optimization of an automatic classification system that is based on one central EEG channel, two EOG channels and one chin EMG channel. It adheres to the decision rules for visual scoring as closely as possible and includes a structured quality control procedure by a human expert. The final system (Somnolyzer 24 x 7) consists of a raw data quality check, a feature extraction algorithm (density and intensity of sleep/wake-related patterns such as sleep spindles, delta waves, SEMs and REMs), a feature matrix plausibility check, a classifier designed as an expert system, a rule-based smoothing procedure for the start and the end of stages REM, and finally a statistical comparison to age- and sex-matched normal healthy controls (Siesta Spot Report). The expert system considers different prior probabilities of stage changes depending on the preceding sleep stage, the occurrence of a movement arousal and the position of the epoch within the NREM/REM sleep cycles. Moreover, results obtained with and without using the chin EMG signal are combined. The Siesta polysomnographic database (590 recordings in both normal healthy subjects aged 20-95 years and patients suffering from organic or nonorganic sleep disorders) was split into two halves, which were randomly assigned to a training and a validation set, respectively. The final validation revealed an overall epoch-by-epoch agreement of 80% (Cohen's kappa: 0.72) between the Somnolyzer 24 x 7 and the human expert scoring, as compared with an inter-rater reliability of 77% (Cohen's kappa: 0.68) between two human experts scoring the same dataset. Two Somnolyzer 24 x 7 analyses (including a structured quality control by two human experts) revealed an inter-rater reliability close to 1 (Cohen's kappa: 0.991), which confirmed that the variability induced by the quality control procedure, whereby approximately 1% of the epochs (in 9.5% of the recordings) are changed, can definitely be neglected. Thus, the validation study proved the high reliability and validity of the Somnolyzer 24 x 7 and demonstrated its applicability in clinical routine and sleep studies.

Patients with chronic pain often suffer from sleep disturbances, specifically decreased deep sleep, and thus may get into a vicious circle which maintains their pain condition. Utilizing polysomnography and psychometry, objective and subjective sleep and awakening quality was investigated in 11 patients with nonorganic insomnia (F51.0) related to somatoform pain disorder (SPD; F45.4) as compared with age- and sex-matched healthy controls of the Siesta normative database. Patients demonstrated a markedly deteriorated Pittsburgh Sleep Quality Index, a decreased Quality of Life Index, slightly increased self-reported anxiety (Zung SAS) and depression scores (Zung SDS), as well as an increased Epworth Sleepiness Scale and International Restless Legs Syndrome Scale score. Subjective sleep and awakening quality was markedly reduced, while somatic complaints were increased. Polysomnographic evaluation by a recently developed automatic sleep classifier (Somnolyzer 24 x 7) based on the rules of Rechtschaffen and Kales demonstrated reduced slow-wave sleep (SWS), the target variable in the present study, a decreased stage shift index, increased SWS latency and stage 4 sleep (S4) latency and an increased frequency of shifts from S2 to wakefulness (W) in patients as compared with controls. Minimal oxygen saturation was found decreased, periodic leg movements (PLMs) were increased. In the morning, patients showed deteriorated well-being, drive, mood and wakefulness. There were no significant noopsychic or psychophysiological differences between patients and controls (except for a reduced numerical memory and a slightly increased morning diastolic blood pressure in patients). Subsequent evaluation of the acute effects of 100 mg of a controlled-release formulation of trazodone (Trittico retard) in the patients demonstrated an increase in the target variable SWS, accompanied by a reduction in the number of awakenings and stage shifts. It normalized the frequency of shifts from S2 to W and reduced the frequency of shifts from W to S1, from S1 to S2, as well as from any stage to S1 and S2. Trazodone, however, also significantly reduced the total sleep period and S2 and increased the latency to S1. Moreover, the drug increased the reduced minimal O(2 )saturation, reduced the arousal index and the PLMs-in-wake index and normalized the increased morning diastolic blood pressure. In conclusion, our study demonstrated that SPD induced significant changes in subjective and objective sleep and awakening quality, which were partially mitigated by trazodone therapy. The data on the target variable SWS support our hypothesis of a key-lock principle in the diagnosis and drug treatment of sleep disorders. Our study provided the first evidence on the usefulness of the Somnolyzer 24 x 7 and the Siesta database in clinical practice.

Objectives: Along with spindles, K-complexes are well known hallmarks of stage 2 (S2) sleep. However, little is known about their quantity in S2 sleep of patients with Parkinson's disease (PD)., Setting: Sleep laboratory, Department of Neurology, University of Vienna, Austria., Patients and Methods: Whole-night polysomnography (PSG) was performed in twelve treated PD patients and ten healthy controls without history of sleep complaints. The quantity of spontaneous K-complexes, K-alpha-complexes, and sleep spindles in one hour S2 sleep, distributed in four epochs of 15 minutes all through the night, were visually selected and analysed. The quantity and the temporal course of these phasic events were compared with the quantity in age-matched healthy controls. Nine of the twelve PD patients underwent [123I]beta-CIT SPECT for calculating dopamine transporter binding in the striatum and serotonin transporter density in the thalamus-hypothalamus region., Results: There was no difference between the quantity of K-complexes, K-alpha-complexes, and sleep spindles in PD patients and in the healthy control group. K-complexes but not sleep spindles decreased over the night in both groups. The number of sleep spindles did not correlate with the dopamine transporter binding in the striatum or the serotonin binding in the thalamic/hypothalamic region., Conclusion: K-complexes and sleep spindles are not reduced and do not seem to be related to the degree of dopaminergic degeneration in treated PD patients.

The aim of the study was to investigate abnormalities of event-related potentials (ERPs) in social phobia patients indicating deficits in speed and amount of perceptual and cognitive resources as well as relationships between ERPs and cognitive functioning. ERPs were recorded from 19 EEG leads in a two-tone oddball paradigm in medication-free patients with DSM-IV social phobia (n=25) and in age- and sex-matched healthy controls (HC). Neuropsychological test performance was administered. Compared with the HC group, patients with social phobia showed reductions in N1 at temporal leads, N2 and P300 amplitudes, predominantly centroparietally, and longer P300 latencies. The observed P300 latency prolongation was associated with reduced Non-Verbal Learning Test (NVLT) but not the Wisconsin Card Sorting Test (WCST) scores. The reduction in N1 amplitude indicates an impairment in perceptual processing. The reduced P300 amplitudes may reflect reduced cognitive resources for the evaluation of relevant information. The increased P300 latency, indicating longer stimulus evaluation time, was correlated to deficits in learning processes as measured by the Non-Verbal Learning Test but not to executive function as measured by the Wisconsin Card Sorting Test. It may therefore be concluded that social phobia patients show deficits in cognitive information processing as reflected by ERPs.

Recent studies have suggested an information-processing bias in social phobia (SP). Little is known about the electrophysiological correlates of anxiety in SP. The aim of the present study was to investigate the quantitative electroencephalogram (EEG) in 25 drug-free patients with SP as compared with age- and sex-matched normal controls and to correlate anxiety and depressive symptoms with EEG data. EEG was recorded under vigilance-controlled and resting conditions. The Spielberger State and Trait Anxiety Scale (STAI) and the Beck Depression Inventory (BDI) were administered to assess anxiety and depression levels. Multivariate analysis of variance revealed significant differences between patients and controls, specifically frontopolarly and right centrally. Statistical analysis demonstrated a decrease in absolute and relative delta, theta power, alpha-adjacent slow-beta and fast beta power and an increase in absolute and relative intermediate beta power, as well as an acceleration of the total centroid and a slowing in beta centroid and its variability. Trait anxiety and depression scores correlated positively with the dominant alpha frequency and the alpha centroid, and negatively with absolute theta and slow alpha power as well as with the centroid of the delta/theta frequency band. In conclusion, EEG mapping in patients with SP revealed significant differences from normal controls suggesting a hyperarousal as a pathogenetic factor of anxiety.

Aims: Early clinical electroencephalographers reported that low-voltage fast desynchronized patterns were frequently seen in chronic alcoholism, suggesting hyperarousal of the central nervous system (CNS). The aim of the present study was to investigate the brain function of drug-free, detoxified alcoholics, and compare this with that of normal controls, utilizing computerized quantitative EEG analysis and subsequent EEG mapping. Moreover, differences between patients relapsing or abstaining during 6 months of relapse prevention therapy, pharmacologically supported by either flupentixol decanoate 10 mg or placebo i.m. every 2 weeks, were determined., Methods: 22 drug-free, detoxified patients (15 men, seven women) aged between 27 and 58 (mean 41.5 +/- 8.1) years, diagnosed as alcohol-dependent (ICD-10: F10.23) were included in the study. They were subdivided into abstainers (n = 11) and relapsers (n = 11), and matched with normal healthy controls according to age (mean 41.5 +/- 8.4 years) and sex. A 3-min vigilance-controlled EEG (V-EEG) was obtained and analysed off-line by multi-lead EEG power spectral analysis and subsequent mapping methods., Results: The drug-free, detoxified, alcohol-dependent patients showed, as compared with controls, aberrant brain function characterized by a decrease in delta and slow alpha and an increase in beta activity as well as an acceleration of the total centroid. These findings were more pronounced in relapsing than in abstaining patients. After 6 months of treatment, abstaining patients showed an increase in slow activity, a decrease in fast alpha, an acceleration of the delta/theta centroid and a deceleration of the alpha centroid, reflecting a normalization of brain function., Conclusion: EEG maps of alcohol-dependent patients differ significantly from those of normal controls and patients suffering from other mental disorders and thus EEG mapping may be used for diagnostic purposes. Moreover, the quantitative EEG may also be of prognostic value as relapsing patients differ from abstaining ones, since they show a significantly more pronounced hyperarousal of the CNS.

Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea-hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.

Objective: The purpose of this study of 100 patients suffering from sleep-disorders was to determine correlations between their subjective health-related quality of life (HRQoL) and objective variables in sleep initiation and maintenance, sleep architecture, objective quality of awakening, psychophysiological parameters and subjective quality of sleep and awakening., Methods: Objective measurements were obtained from overnight diagnostic polysomnography. Subjective HRQoL was determined from the Quality of Life Index (QLI, Mezzich and Cohen) completed prior to the adaptation night. Other measurements included subjective and objective quality of sleep and awakening (psychometry) the evening before and morning after polysomnographic investigations., Results: 63% of the patients were suffering from nonorganic and 37% from organic sleep disorders (SDs). Within the first group, nonorganic insomnia predominated; within the second, sleep apnea. Subjective HRQoL correlated well with subjective sleep and awakening quality, especially in nonorganic SDs. There were only a few correlations of objective measurements with subjective HRQoL: in the total group of SD patients HRQoL correlated with sleep stage S2, and in nonorganic SDs with attention scores and psychophysiological measurements (mainly the pulse rate in the evening and morning)., Conclusion: Our findings suggest only a weak relationship between objective sleep variables and subjective HRQoL in both organic and nonorganic SDs. However, we found various significant correlations of HRQoL with subjective measurements of sleep, especially in nonorganic SDs.

Subjective health-related quality of life (HRQoL) was investigated in 100 patients with disturbed sleep (39 women aged 52 +/- 13 years and 61 men aged 53 +/- 10 years) referred to the sleep laboratory and compared with HRQoL in 100 normal healthy adults. Measurements included the Quality of Life Index (QLI) (Mezzich and Cohen), and objective (polysomnographic) and subjective (psychometric) quality of sleep and awakening. Statistical analysis (Mann-Whitney U-test) showed HRQoL to be significantly reduced in sleep disorders (SDs), with a more pronounced reduction in nonorganic than in organic SDs. Patients with nonorganic hypersomnia were more disturbed than those with nonorganic insomnia. Within organic SDs, patients with apnea were more disturbed than those with obstructive snoring. Out of ten elementary HRQoL components, seven were disturbed in SDs: physical well-being, psychological well-being, self-care and independent functioning, occupational functioning, interpersonal functioning, personal fulfillment, and overall quality of life. No differences between patients and normal healthy subjects where found in the components social support, community and services support or spiritual fulfillment. Patients suffering from nonorganic SDs had significantly worse scores in physical and psychological well-being and overall quality of life than those with organic SDs. Patients with both SDs and additional diagnoses of affective disorders had more profoundly reduced HRQoL than those with anxiety disorders. Follow-up of 51 patients (31 with nonorganic SDs and 20 with organic SDs) one year after sleep laboratory investigation and subsequent treatment found significantly improved HRQoL compared with pre-treatment. Moreover, patients diagnosed and treated in the sleep laboratory showed lower re-hospitalization rats.

The influence of a combined estrogen-progestin regimen (Climodien, Lafamme) on auditory event-related potentials (ERPs) was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3=estradiol valerate 2 mg+the progestin dienogest 3 mg, EV=estradiol valerate 2 mg, and placebo), followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg+dienogest 2 mg). Both the double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone odd-ball paradigm in 49 patients aged between 46 and 67 yr with the diagnosis of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1). Climodien reduced standard N1 and target P300 latencies as compared to placebo, while EV did not affect N1 latency but similarly reduced P300 latency. Climodien increased N1, P2 and P300 amplitudes dose-dependently, predominantly at frontal leads. Estrogen alone had only minor effects on ERP amplitudes. The shortening of standard N1 latency and enhancement of N1 and P2 amplitudes indicates a positive effect of Climodien on perceptual processing, most likely due to vigilance improvements also observed in EEG mapping. Concerning target P300, it seems that estradiol is responsible for the improvement in stimulus evaluation time, as reflected by the shortening of the peak latency, while dienogest seems to account for the improvement in cognitive information processing capacity, whereby 3 mg induced a more pronounced augmentation of P300 amplitudes than 2 mg. Based on the spatial distribution of this increase, it can be speculated that Climodien mainly affects the more frontally distributed P3a subcomponent, which is associated with attention and orientation. Furthermore, the observed changes in ERP-components are consistent with recent studies showing significant positive effects of hormone replacement therapy on cholinergic functions. Thus, Climodien seems to be of interest in preventing cognitive decline and treating cognitive disorders in postmenopausal women. Indeed, there is increasing evidence of beneficial effects of estrogen in dementia. Our present findings suggest that the estrogen effects may be augmented by dienogest.

Background: S-Adenosyl-L-methionine (SAMe, or ademetionine) is a naturally occurring molecule used as both a nutraceutical and a pharmaceutical to treat depression., Objective: The central mode of action of SAMe was investigated in 20 healthy volunteers by mapping of electroencephalograms (EEGs) and event-related potentials (ERPs) and low-resolution brain electromagnetic tomography (LORETA)., Design: In an acute and subacute, double-blind, placebo-controlled, crossover study, subjects received in random order infusions of 800 mg SAMe and placebo for 7 d, with a washout period of 3 wk between the 2 treatment periods. EEG recordings were made 0, 1, 3, and 6 h after and ERP recordings were made 0 and 1 h after the drug infusions on days 1 and 7., Results: Multivariate analyses of variance and Hotelling T2 tests showed significant acute and subacute encephalotropic effects of SAMe compared with placebo. Acute pharmaco-EEG changes were typical of classic antidepressants of the thymoleptic type; subacute alterations were typical of cognition enhancers. Regarding ERPs, standard N1 and P2 latencies were shortened, and target P300 latencies were lengthened. N1 amplitudes increased after subacute treatment, and temporooccipital P300 amplitudes increased after the acute dose. Similar changes were described for antidepressants. LORETA showed that the N2 source strength increased in both the left and the right temporal lobes, whereas the P300 source strength increased in the dorsolateral prefrontal regions and decreased in the ventral limbic regions., Conclusion: EEG-ERP mapping identified SAMe as an antidepressant. LORETA targeted brain regions crucial in the therapeutic efficacy of antidepressants.

In the treatment of snoring (SN) and sleep-related breathing disorders (SRBD), mandibular advancement devices (MAD) are of increasing importance. Their mode of action is based on the advancement of the mandible, thereby increasing various upper airway dimensions and thus airway patency and airflow during sleep. The aim of the present study was to investigate efficacy and tolerability of an individually fitted MAD on 11 patients (10 males, 1 female), mean age 57 years, using sleep laboratory methods in 3 subsequent nights (adaptation-, baseline-, treatment night). The MAD consists of 2 separate parts that attach to both dental arches. On occlusion the upper maxillary part with a protruding cone meets an inclined plane of the lower mandibulary part, thereby forcing the mandible to advance. 10 patients (6 with obstructive sleep apnea, 3 with obstructive hypopnea and 1 primary snorer) tolerated the MAD well; one patient (primary snorer) removed the MAD after 1 hour. Regarding the target variable, the snoring index (SI), confirmatory statistics demonstrated a significant improvement from 108 to 53/h sleep, though normalisation could not be achieved. Descriptive data analysis showed significant improvement of the apnea-hypopnea index (AHI) from 15 to 5.5/h and of the oxygen desaturation index (O2-DI) from 21 to 13/h sleep. Arousal variables and periodic leg movement index (PLMI) improved as well. Objective sleep efficiency and subjective sleep- and awakening quality remained unchanged. Thus, besides the good therapeutic efficacy (the medians of improvement of the SI, AI, AHI, O2-DI and PLMI were 37, 48, 53, 51 and 29%, respectively), acute acceptance of the MAD was also satisfactory. Last but not least our present study showed once more the necessity of an adaptation night, as from the first to the second sleep laboratory night respiratory indices deteriorated significantly.

Objective: Together with spindles, K-complexes are well known hallmarks of stage 2 sleep (S2). However, little is known about their topographical distribution in comparison to delta-waves and to K-complexes superimposed by spindles., Patients and Methods: In this study, the topographical distribution of spontaneous K-complexes and delta-waves in S2 and delta-waves in stage 4 sleep (S4) in 10 healthy young adults (aged 20 to 35 years, 7 female) was investigated. K-complexes with and without spindles in S2, delta-waves with and without spindles in S2, and delta-waves in S4 distributed all over the night were visually selected. EEG power maps and statistical parametric maps were calculated., Results: Absolute delta power of S2 K-complexes appeared to be significantly higher than of S2 delta-waves and delta power of S4 delta-waves was higher than of S2 delta-waves. In K-complexes and delta-waves, power was found to be highest over medio-frontal regions in the delta frequency band (0.5-4.0 Hz) with a second maximum occipitally in delta-waves, no matter whether superimposed by a spindle or not., Conclusion: K-complexes and delta-waves in S2 differ in topographical distribution. Even though in S2 delta-waves have less power, they have a similar topographical distribution in S2 and S4, supporting the hypothesis that delta-waves in S2 further develop towards delta-waves in slow wave sleep. The delta frequency components of K-complexes and delta-waves are unaffected by spindles.

Restless legs syndrome (RLS) is a sensorimotor movement and sleep disorder with a high prevalence. While the sleep disturbance due to RLS has been studied quite well polysomnographically, little is known about the electrophysiological function during daytime. The aim of the present study was to investigate the diurnal quantitative EEG and clinical symptomatology in 33 drug-free RLS patients as compared with age- and sex-matched normal controls. Investigations comprised brain mapping of the vigilance-controlled EEG as well as completion of the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Quality of Life Index, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale for evaluation of clinical symptomatology. Statistical analysis demonstrated an increase in absolute delta and absolute and relative alpha-2 power, a decrease in absolute and relative alpha-1 power, an acceleration of the dominant frequency and the alpha centroid, and a slowing of the delta/theta centroid, as well as a non-significant attenuation in total power. These findings are characteristic of dissociated vigilance changes described in depression. Indeed, RLS patients demonstrated significantly higher depression and anxiety scores, lower quality of life and deteriorated sleep quality. The score of the Epworth Sleepiness Scale was not elevated, in contrast to the increased daytime sleepiness observed in other highly prevalent organic sleep disorders (e.g. sleep apnea). In conclusion, daytime EEG mapping revealed neurophysiological correlates of depression in RLS, which was confirmed by self-ratings at the symptomatological level.

Aims: Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and beta-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity., Methods: Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg(-1) body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS)., Results: Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for total power and theta power, respectively. Relative power decreased in the delta (-1.20+/-1.31% after 120 min at P3) and theta (-3.30+/-2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00+/-0.88% after 90 min at P3) and beta-4 (0.30+/-0.24% after 90 min at P3) subbands. Finally, an increase was also seen for the centroid of the total activity and its deviation. EEG modifications began as early as 15-30 min, reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4-6 h after administration., Conclusions: The central effects of ayahuasca could be objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of previously reported subjective effects. The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system.

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (five females, six males) aged 35-75 years (mean age 54.1 +/- 11.4) suffering from nonorganic insomnia (F 51.0) related to a depressive episode (F 32) or recurrent depressive disorder (F 33). as compared with 11 age- and sex-matched normal controls (five females, six males) aged 36-75 years (mean age 53.0 +/- 13.5). PSG demonstrated decreased sleep efficiency, total sleep time (TST), total sleep period (TSP) and sleep stage S2, as well as increased wakefulness during TSP, early morning awakening, sleep latency to S1, S2, S3 and sleep stage S1 in depressed patients. Subjective sleep quality and the total score of the Self-Assessment of Sleep and Awakening Quality Scale (SSA) were deteriorated as were morning and evening well being, drive, mood and fine motor activity right. Evening and morning blood pressure, the O2 desaturation index and periodic leg movement (PLM) index were increased. In a subsequent acute, placebo-controlled cross-over design study, the acute effects of 100 mg of trazodone, a serotonin reuptake inhibitor with a sedative action due to 5-HT2 and alpha1 receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in sleep efficiency (primary target variable), TST, TSP and SWS (S3 + S4), as well as a decrease in wakefulness during the TSP, early morning awakening and S2. There was no change in rapid eye movement (REM) sleep with the exception of an increase in the REM duration in minutes. Trazodone also caused an improvement in subjective sleep quality, affectivity, numerical memory and somatic complaints. All respiratory variables remained within normal limits. Critical flicker frequency and moming diastolic blood pressure were decreased. The present study demonstrated that depression induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg of trazodone, thus suggesting a key-lock principle in the treatment of depression.