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Nicergoline is a semisynthetic ergot derivative and has a selective alpha-1A adrenergic receptor blocking property and also other additional mechanisms of actions, both in the brain and in the periphery. It is in clinical use for over three decades in over fifty countries for conditions such as cerebral infarction, acute and chronic peripheral circulation disorders, vascular dementia, and Alzheimer's disease and has been found to be beneficial in a variety of other conditions. However, concerns about its safety have been raised, especially after the European medicines agency's (EMEA's) restriction in the use of all ergot derivatives including nicergoline. But, most of the available literature and data suggest that the adverse events with nicergoline are mild and transient. Further, none of the available treatment options for cognitive disorders afford definitive resolution of symptoms. In this backdrop, we discuss the pharmacology of nicergoline with special emphasis on the safety of this compound, especially when used in patients suffering from cognitive function disorders. [ABSTRACT FROM AUTHOR]

Effects of ABIO-08/01, a new potentially anxiolytic isoxazoline, on regional electrical brain generators were investigated by 3-dimensional EEG tomography. In a double- blind, placebo-controlled, multiple-ascending-dose study, 16 healthy males (30.2 ± 5.7 years) received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (8-day wash-out) in a randomized non-balanced design for phase-1 studies. A 3-min vigilance-controlled (V) EEG, a 4-min resting (R) EEG with eyes closed, a 1-min eyes-open (EO) EEG and psychometric tests were performed 0, 1 and 6 h after taking the drug on days 1 and 5. Low-resolution brain electromagnetic tomography (LORETA) was computed from the spectrally analyzed EEG data, and differences between drug and placebo were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux Human Brain Atlas available as a digitized MRI. An overall omnibus significance test followed by a voxel-by-voxel t test demonstrated significant regional EEG changes after ABIO-08/01 versus placebo, dependent on recording condition, dose and time. While in the EO-EEG specifically the lowest dose of ABIO-08/01 induced pronounced sedative effects (delta/theta and beta increase) 1 h after acute and slightly less so after superimposed administration, in the 6th hour a decrease in alpha and beta activity signaled less sedative and more relaxant action. In the V-EEG these changes were less pronounced, in the R-EEG partly opposite. Hemisphere-specific changes were observed, suggesting increases in LORETA power over the left temporal, parietal, superior frontal regions and decreases over the right prefrontal, temporal pole and occipital regions. These LORETA changes are discussed in the light of neuroimaging findings on anxiety and anxiolytics. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: 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® (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. [Copyright &y& Elsevier]

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 × 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 O2 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 × 7 and the Siesta database in clinical practice. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Electrical sources of auditory event-related potentials (ERPs) determined by means of low-resolution brain electromagnetic tomography (LORETA) in 48 unmedicated insomniac postmenopausal patients aged between 46 and 67 years were compared with those obtained in 48 age-matched normal female controls. Subsequently, the patients were included in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase – Climodien 2/3 [estradiol valerate (EV) 2 mg + the progestin dienogest 3 mg] was compared with EV 2 mg and placebo – followed by an open-label phase in which all of them received Climodien 2/2 (EV 2 mg + dienogest 2 mg). The double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone oddball paradigm and electrical sources of standard N1 and P2 as well as target N2 and P300 components were estimated. In both patients and controls, LORETA revealed an activation of the superior temporal gyrus [auditory cortex, Brodmann areas (BA) 41, 42, 22] for all four components. For standard P2, an additional activation was observed medially parietally in the precuneus (BA 7, 5). For target N2, also a medial frontal source (BA 9, 10, 32) was identified. Finally, for the target P300 component – in addition to the aforementioned sources – activations in the prefrontal cortex (BA 9, 10, 46, 47), the inferior parietal cortex (supramarginal gyrus, BA 40, 39) and the posterior cingulum (BA 31) were found. Thus, patients and controls did not differ in the structural processes engaged in these fundamental aspects of information processing. However, patients demonstrated significantly reduced source strength – for standard ERP components predominantly in the temporal lobe and for target components predominantly in the frontal lobe, indicating reduced energetic resources available for perceptual and cognitive demands of the discrimination task. While, as compared with placebo, estrogen alone had only minor effects on ERP source strength, Climodien generally increased the impressed current density at the ERP peak latencies, predominantly in the temporal lobe, indicating an increased stimulus-induced cortical arousal in the primary and higher-order auditory cortex. Specifically, Climodien enhanced P300 source strength in the left middle temporal gyrus and in the left superior frontal gyrus, brain regions that on the one hand have been shown to be affected by hormone therapy in positron emission tomography and functional magnetic resonance neuroimaging studies and that on the other hand are among those critical for encoding and memory processes. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of the double-blind, placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment (Climodien, Lafamme) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients, objectified by EEG mapping.Methods: In a 3-arm, 2-month parallel group design phase, patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg (Climodien 2/3) or estradiol valerate 2 mg alone or placebo. In a subsequent open-label phase, all patients received estradiol valerate 2 mg+dienogest 2 mg (Climodien 2/2). EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment.Results: As compared with placebo, Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency bands, specifically in alpha-2 activity. Moreover, a significant increase in relative alpha-2 power, a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance. In contrast, under estradiol valerate 2 mg alone, only a slight augmentation of alpha and attenuation of relative delta and beta power occurred, suggesting only a slight vigilance improvement as compared with placebo. Thus, dienogest 2 mg increased the estrogen effect, which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone (augmentation of alpha-2, attenuation of relative beta, acceleration of the dominant frequency). Moreover, Climodien 2/2 also markedly increased alpha-2 power, decreased relative beta-2 power and accelerated the alpha centroid. Finally, comparing Climodien 2/3 with Climodien 2/2, there was even a dose-efficacy relation.Conclusions: Estradiol valerate 2 mg improves vigilance slightly, thereby confirming previous findings. The additional administration of dienogest does not minimize the effect of estrogen, but on the contrary increases it, which makes the combination superior to both placebo and estradiol valerate alone. Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual, marital, occupational and social difficulties known to occur specifically in this period of life. [ABSTRACT FROM AUTHOR]

Clinical studies have demonstrated that bifemelane hydrochloride [4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride] can improve cognitive functions in patients with various types of dementia. To elucidate specific mechanisms which may underlie the clinical benefit, the effects of bifemelane were investigated by means of computerized electroencephalography (EEG), event-related potentials (P300) and psychometry. Eighteen healthy elderly subjects, aged between 60 and 73 years, were included in a double-blind, placebo-controlled crossover study. Each subject received a single dose of 150 mg bifemelane or placebo with an interval of 1 week in between. EEG and psychometric investigations were carried out before and 2, 4, 6, and 8 h after drug administration, ERP investigations only before and 3 h after drug administration. Descriptive data analysis of the EEG showed that 150 mg bifemelane accelerated the centroid of the total frequency band, induced a significant reduction of the absolute delta + theta power and increased the absolute beta power most markedly 6 h after drug intake. Topographic analyses of ERP amplitudes showed that bifemelane did not effect ERP amplitudes. While N1, P2 and N2 latencies were not changed after bifemelane, P300 latency was shortened significantly. Psychometric investigations did not show significant or consistent effects on noopsychic and thymopsychic functions. In conclusion, bifemelane affected EEG in the sense of improved vigilance. The reduction of P300 latency may be interpreted as accelerated stimulus evaluation time, therefore indicating a beneficial effect of bifemelane on cognition at this stage of information processing. [ABSTRACT FROM AUTHOR]

In a double-blind, placebo-controlled study the effects of Actovegin[sup ®] on frontal and parietal electrical P300 sources revealed by low resolution electromagnetic tomography (LORETA) were studied in age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient had, in randomized order, a treatment of 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily. Auditory ERPs were recorded before and 5 h after drug administration on day 1 (acute effect) and on day 15 (subacute and superimposed effect). Compared to age- and sex-matched normal controls, AAMI patients showed a trend towards P300 latency prolongation and a significantly reduced P300 global field power (GFP). Maximal LORETA source strength did not differ from controls. After Actovegin parietal P300 scalp amplitudes increased, while frontal and temporal amplitudes decreased as compared to placebo. This increase in hilliness, measured by the GFP, was significant. Moreover, the parietal P300 source strength increased after acute, subacute and superimposed infusion of Actovegin as compared to placebo. This may reflect improved availability of cognitive processing resources in the parietal cortex, an area that on the one hand plays an important role in fundamental aspects of attention and on the other hand has been found to be functionally impaired in dementia. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pays tribute to the late Werner Martin Herrmann, a professor of clinical psychophysiology at the Free University of Berlin, Germany.

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. [ABSTRACT FROM AUTHOR]

Objectives: Sleep bruxism (SB) is a parasomnia defined as a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. Pathophysiologically, SB is the result of biological and psychosocial influences. Treatment comprises behavioral, orthodontic and pharmacological interventions. While benzodiazepines and muscle relaxants have been reported by clinicians to reduce bruxism-related motor activity, placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate the acute effects of clonazepam (Rivotril®) as compared with placebo, utilizing polysomnography and psychometry. Method: Ten drug-free outpatients (6 females, 4 males), aged 46.5 ± 13.1 years, suffering from SB (ICD-10: F45.8; ICSD: 306.8) and having been treated by bite splints were included in the trial. Comorbidity was high: 7 patients presented nonorganic insomnia related to adjustment or anxiety disorders (5 patients) or depression (2 patients); all patients had a concomitant movement disorder (6 restless legs syndrome, 4 periodic leg movement disorder). After one adaptation night, patients received placebo and 1 mg clonazepam 1/2 hour before lights out in a single-blind, nonrandomized study design. Objective sleep quality was determined by polysomnography, subjective sleep and awakening quality by rating scales, objective awakening quality by psychometric tests. Clinical evaluation was based on the Pittsburgh Sleep Quality Index (PSQI), the Zung Depression (SDS) and Anxiety (SAS) Scales, the Quality of Life Index, the Epworth Sleepiness Scale and the International Restless Legs Syndrome Study Group (IRLSSG) Scale. Results: On admission, SB patients exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures. As compared with placebo, 1 mg clonazepam significantly improved the mean bruxism index from 9.3 to 6.3/h of sleep. Furthermore, it significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency and time awake during the total sleep period, and increased stage 2 sleep and movement time. Periodic leg movements decreased significantly, while the apnea index and apnea-hypopnea index increased marginally, but remained within normal limits. Subjective sleep quality improved as well, while in mood, performance and psychophysiology no changes were observed. Conclusion: Acute clonazepam therapy significantly improved not only the bruxism index but also objective and subjective sleep quality, with unchanged mood, performance and psychophysiological measures upon awakening, suggesting good tolerability of the drug. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Sleep and memory studies often focus on overnight rather than long‐term memory changes, traditionally associating overnight memory change (OMC) with sleep architecture and sleep patterns such as spindles. In addition, (para‐)sympathetic innervation has been associated with OMC after a daytime nap using heart rate variability (HRV). In this study we investigated overnight and long‐term performance changes for procedural memory and evaluated associations with sleep architecture, spindle activity (SpA) and HRV measures (R‐R interval [RRI], standard deviation of R‐R intervals [SDNN], as well as spectral power for low [LF] and high frequencies [HF]). All participants (N = 20, Mage = 23.40 ± 2.78 years) were trained on a mirror‐tracing task and completed a control (normal vision) and learning (mirrored vision) condition. Performance was evaluated after training (R1), after a full‐night sleep (R2) and 7 days thereafter (R3). Overnight changes (R2‐R1) indicated significantly higher accuracy after sleep, whereas a significant long‐term (R3‐R2) improvement was only observed for tracing speed. Sleep architecture measures were not associated with OMC after correcting for multiple comparisons. However, individual SpA change from the control to the learning night indicated that only "SpA enhancers" exhibited overnight improvements for accuracy and long‐term improvements for speed. HRV analyses revealed that lower SDNN and LF power was associated with better OMC for the procedural speed measure. Altogether, this study indicates that overnight improvement for procedural memory is specific for spindle enhancers, and is associated with HRV during sleep following procedural learning. [ABSTRACT FROM AUTHOR]

Objective: Obstructive sleep apnea (OSA) impacts stroke recovery and outcome negatively. Although its identification and treatment are part of the current stroke guidelines, standard management with positive airway pressure (PAP) therapy is not routinely performed and adherence rates are very low. The purpose of this study was to determine whether PAP adherence can be improved by a PAP training strategy during in-hospital rehabilitation combined with a telemedicine monitoring system after discharge.Methods: In this study, we performed a controlled trial (RCT) on standard PAP treatment (SG) as compared with proactive telemonitored PAP treatment (TG). After three months and one year, PAP adherence (min of use per day) and clinical outcome variables were compared.Results: In 33 (47.1%) out of 70 patients diagnosed with therapy-relevant OSA [70% male, 62 (5) years, body mass index (BMI) 30 (4) kg/m2, Barthel Index 90 (20), NIHSS 3 (3)] in-hospital PAP titration was performed. Subsequently, they were randomized to SG or TG. Drop-out rates after three months and after one year were 12% and 30%, respectively, with no differences between the groups. After three months, telemonitored patients used the PAP device 76 min longer per night (SG: 299 (76), TG: 375 (86) minutes per night; p = 0.017), after one year there was no significant difference.Conclusion: People with stroke and therapy-relevant OSA who accept PAP therapy should receive additional telemedicine monitoring at least for three months. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov; Unique identifier: NCT02748681. [ABSTRACT FROM AUTHOR]

Previous studies have shown abnormal electroencephalography (EEG) in Huntington's disease (HD). The aim of the present investigation was to compare quantitatively analyzed EEGs of HD patients and controls by means of low-resolution brain electromagnetic tomography (LORETA). Further aims were to delineate the sensitivity and utility of EEG LORETA in the progression of HD, and to correlate parameters of cognitive and motor impairment with neurophysiological variables. In 55 HD patients and 55 controls a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Power spectra and intracortical tomography were computed by LORETA in seven frequency bands and compared between groups. Spearman rank correlations were based on V-EEG and psychometric data. Statistical overall analysis by means of the omnibus significance test demonstrated significant ( p < 0.01) differences between HD patients and controls. LORETA theta, alpha and beta power were decreased from early to late stages of the disease. Only advanced disease stages showed a significant increase in delta power, mainly in the right orbitofrontal cortex. Correlation analyses revealed that a decrease of alpha and theta power correlated significantly with increasing cognitive and motor decline. LORETA proved to be a sensitive instrument for detecting progressive electrophysiological changes in HD. Reduced alpha power seems to be a trait marker of HD, whereas increased prefrontal delta power seems to reflect worsening of the disease. Motor function and cognitive function deteriorate together with a decrease in alpha and theta power. This data set, so far the largest in HD research, helps to elucidate remaining uncertainties about electrophysiological abnormalities in HD. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a devastating neurodegenerative disorder with prominent motor and cognitive decline. Previous studies with small sample sizes and methodological limitations have described abnormal electroencephalograms (EEG) in this cohort. The aim of the present study was to investigate objectively and quantitatively the neurophysiological basis of the disease in HD patients as compared to normal controls, utilizing EEG mapping. In 55 HD patients and 55 healthy controls, a 3-min vigilance-controlled EEG (V-EEG) was recorded during midmorning hours. Evaluation of 36 EEG variables was carried out by spectral analysis and visualized by EEG mapping techniques. To elucidate drug interference, the analysis was performed for the total group, unmedicated patients only and between treated and untreated patients. Statistical overall analysis by the omnibus significance test demonstrated significant ( p < 0.01 and p < 0.05) EEG differences between HD patients and controls. Subsequent univariate analysis revealed a general decrease in total power and absolute alpha and beta power, an increase in delta/theta power, and a slowing of the centroids of delta/theta, beta and total power. The slowing of the EEG in HD reflects a disturbed brain function in the sense of a vigilance decrement, electrophysiologically characterized by inhibited cortical areas (increased delta/theta power) and a lack of normal routine and excitatory activity (decreased alpha and beta power). The results are similar to those found in other dementing disorders. Medication did not affect the overall interpretation of the quantitative EEG analysis, but certain differences might be due to drug interaction, predominantly with antipsychotics. Spearman rank correlations revealed significant correlations between EEG mapping and cognitive and motor impairment in HD patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236). Methods: Sixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3mg/24h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings. Results: Mean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48,7.28], p <0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: −3.12 (95% CI [−5.36, −0.88], p =0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS=0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity. Conclusions: Rotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances. [Copyright &y& Elsevier]

Background: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). Methods: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21-86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. Results: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen's kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). Conclusion: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 3weeks 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±7.1min). 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

In a double-blind, placebo-controlled, multiple-ascending-dose study, the encephalotropic and psychotropic properties of ABIO-08/01, a new potentially anxiolytic and nootropic isoxazoline, were studied in 16 young healthy males. In a randomized nonbalanced phase 1 study, they received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (washout period 8 days). EEG mapping and psychometry were carried out at hours 0, 1, 6 of day 1 (acute effect) and day 5 (subacute and superimposed effects). MANOVA/ Hotelling T2 test demonstrated significant central effects of ABIO-08/01 versus placebo after acute, subacute and superimposed administration of all doses in the resting, vigilance-controlled and eyes-open EEG. Univariate analysis revealed activating patterns in the resting EEG (40 mg > 20 mg > 10 mg), and sedative patterns in the eyes-open EEG (10 mg > 20 mg > 40 mg). In the vigilance-controlled EEG, 40 mg of ABIO-08/01 induced activating patterns, whereas 10 mg induced sedative patterns. Concerning psychometry, ABIO-08/01 improved concentration (40 mg > 20 mg > 10 mg; activating effect) and deteriorated well-being (10 mg > 20 mg > 40 mg; sedative effect). Ten milligrams also improved reaction time performance and psychomotor activity. ABIO-08/01 is well-tolerated and is of interest in anxiety disorders. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Objective: To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. Methods: One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS. Results: Forty-four patients had no OSA (apnea–hypopnea index AHI<5h−1), 27 mild (5–15), 25 moderate (15–30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p =0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p =0.008), but not in the post-polysomnographic model after including respiratory variables. Conclusion: EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography. [Copyright &y& Elsevier]

Abstract: We reported earlier that overnight change in explicit memory is positively related to the change in sleep spindle activity (between a control and a learning night). However, it remained unclear whether this effect was restricted to good memory performers and whether a general association of sleep spindles and a “sleep-related learning trait” may not account for this effect. Here we now present a secondary and more detailed analysis of our randomized multicenter study. Subjects were studied over a 4-week study period (including actigraphy and daily sleep diaries), including three overnight stays in the sleep laboratory. In the course of the study, subjects completed test-batteries of memory (Wechsler-Memory-Scale-revised; WMS) and other cognitive abilities (Raven''s Advanced-Progressive-Matrices; APM) and were asked to study 160 word pairs in the evening before being tested by cued-recall. Afterwards, subjects went to bed in the laboratory with full polysomnographic montages. Additionally, subjects participated on another occasion in a non-learning control (perceptual priming) task that was counterbalanced either before or after the learning condition. Slow as well as fast spindle activities were analyzed at frontopolar and central topographies. Although it was found that spindle activity is generally (in learning as well as control nights) elevated in highly gifted subjects, spindle analyses revealed that spindle increase (control to learning night) is specifically related to explicit memory improvement overnight, independent of individual learning traits. Together these findings suggest that the spindle increase after learning is related to elaborate encoding before sleep, whereas an individual''s general learning ability is well reflected in interindividual (and trait-like) differences of absolute sleep spindle activity. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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 × 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 × 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 × 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 × 7 and demonstrated its applicability in clinical routine and sleep studies. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

One of the aims of the SIESTA project was to establish a normative database of sleep parameters for healthy and sleep-disturbed patients. Reference data for sleep parameters in non-sleep-disturbed subjects are scarce and usually refer to means and standard deviations. However, since most of the parameters do not follow a Gaussian distribution, percentiles of the distribution provide more detailed information.The present results are based on data from 198 healthy, non-sleep-disturbed subjects (104 females) in the age range of 20 to 95 years. For every subject, two consecutive nights were polysomnographically recorded in one of the eight participating clinical centres. Percentile charts were created on the basis of moving averages computed for 10 year age intervals with the presented age being the midpoint of the underlying interval. The resulting percentile curves were smoothed by a spline function. Since sample size in the oldest age groups is comparatively small, the percentile curves are restricted to the age range of 20 to 80 years.Percentile curves have been created for the parameters sleep period time (SPT), total sleep time (TST), sleep onset latency, REM sleep latency, sleep efficiency index, and percentages of NREM1, NREM2, REM sleep, SWS, and WAKE (with reference to SPT). The charts reflect the known changes of sleep parameters with age, e.g. decrease of TST and sleep efficiency with increasing age.The reference charts are intended to be a helpful tool to evaluate selected aspects of sleep quality in sleep-disturbed patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the role of EEG mapping as an objective and quantitative measure of vigilance in untreated and modafinil-treated narcoleptics, and compare it with the conventional neurophysiological method of the Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS). In 16 drug-free narcoleptics and 16 normal controls a baseline 3-min vigilance-controlled EEG (V-EEG) and a 4-min resting EEG (R-EEG) were recorded during midmorning hours. Thereafter, in a double-blind, placebo-controlled crossover design, patients were treated with a 3-week fixed titration of modafinil (200, 300, 400 mg) and placebo. EEG-mapping, MSLT and ESS measures were obtained before and at the end of the third week of therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant EEG differences between untreated patients and controls in the resting condition only (R-EEG). Subsequent univariate analysis revealed an increase in absolute and relative theta power, a decrease in alpha-2 and beta power as well as a slowing of the dominant frequency and the centroids of the alpha, beta and total power spectrum and thus objectified a vigilance decrement in narcolepsy. Modafinil 400 mg/d significantly improved vigilance as compared with placebo (p = 0.01), inducing changes opposite to the aforementioned baseline differences (key-lock principle). The MSLT and the ESS also improved under modafinil as compared with placebo, but changes were less consistent. Spearman rank correlations revealed the highest correlations between EEG mapping and the ESS, followed by those between EEG mapping and the MSLT, while the lowest correlation was found between the MSLT and the ESS. In conclusion, EEG mapping is a valuable instrument for measuring vigilance decrements in narcolepsy and their improvement under psychostimulant treatment. [ABSTRACT FROM AUTHOR]

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]Β-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. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting β-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT2A agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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 (lCD- 10: F1O.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-mm vigilance- controlled EEG (V-EEG) was obtained and analysed off-line by multi-lead BEG 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. [ABSTRACT FROM AUTHOR]

Early human pharmaco-EEG and subsequent sleep laboratory studies identified trazodone, a 5-HT[sub 2] antagonist and 5-HT reuptake inhibitor (SARI), as an antidepressant with therapeutic effects on its target symptoms depressed mood, anxiety and insomnia. On the occasion of the introduction of a controlled-release (CR) formulation (Trittico[sup ®] 150 mg retard, marketed in Austria by CSC Pharmaceuticals Handels GmbH, Vienna, Austria) in Austria in July 2000, a multi-center, open, clinical post-marketing study on the therapeutic effects, safety and target symptoms of trazodone CR in depression was carried out at 80 offices of Austrian neuropsychiatrists. 549 outpatients (63% females) of all age groups suffering from five different subtypes of depression were enrolled in the study. After a 2-week fixed dose-titration regimen up to 150 mg and a 4-week adjustment period to the optimum dose, 66% of the patients remained on 150 mg, 20% increased the dose and 11% decreased it. Only 3.7% discontinued treatment. Rating by the neuropsychiatrists based on the Clinical Global Impression showed very much to much improvement in 78.3% of the patients, and no change or a deterioration in only 3.6%. In the Hamilton Depression Scale (HAMD) a statistically significant improvement from a baseline score of 21 to a score of 14 after 2 weeks was found, and a normalization to a score of 8 after 6 weeks. Therapeutic effects were similar in the five groups suffering from different subtypes of depression and in patients with and without comedication. Self-rating by the patients based on the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) also showed a significant improvement in the 2nd and 6th week of therapy. Evaluation of the target symptoms of trazodone by ranking the most improved symptoms identified insomnia as the most improved psychopathological item in all three scales. While in the observer ratings also suicidal tendencies and weight loss were found much improved, in the self-rated Zung SDS sadness and loss of drive came second and third in the improvement ranking, in the self-rated Zung SAS anxiety and the feeling of falling apart . Tolerability was very good. In the 2nd week only 16.9% and in the 6th week only 7.6% of the patients reported side effects, mostly characterized by tiredness and rarely by nausea and vertigo. The present clinical study is in agreement with previous studies identifying trazodone as a safe and effective antidepressant, specifically regarding its target symptoms insomnia, depression and anxiety. It also confirms our own early predictions based on neurophysiological investigations concerning the mode of action of the drug. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary 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[sup ®] 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. [ABSTRACT FROM AUTHOR]

Dopaminergic agents such as ropinirole are the drugs of first choice in treating restless legs syndrome (RLS). Recently, gabapentin, a structural analogue of γ-aminobutyric acid, has also been shown to improve sensorimotor symptoms in RLS. Therefore, the tolerability and efficacy of randomized treatment with either gabapentin or ropinirole in patients with idiopathic RLS was evaluated in this 4-week open clinical trial. Patients with idiopathic RLS were treated with either 300 mg of gabapentin (n = 8) or 0.5 mg of ropinirole (n = 8) as the initial dose, and the dose was up-titrated until relief of symptoms was achieved (gabapentin mean dosage 800 ± 397 mg, range 300–1,200 mg; ropinirole mean dosage 0.78 ± 0.47 mg, range 0.25–1.50 mg). In both groups, International Restless Legs Syndrome Study Group questionnaire scores improved significantly (p ≤ 0.018), whereas the scores of the Epworth sleepiness scale remained unchanged within normal limits. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS; p < 0.03) and PLMS index (p < 0.02) in both groups. Side effects were only mild and mostly transient. After 6–10 months of follow-up, in most patients, RLS symptoms were still improved. We conclude that gabapentin and ropinirole provide a similarly well-tolerated and effective treatment of PLMS and sensorimotor symptoms in patients with idiopathic RLS.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents a study that assessed the deterioration of the noopsyche and thymopsyche in sleep laboratory-investigated patients with nonorganic insomnia as compared with healthy controls in midmorning hours. Characteristics of insomnia; Dysfunctions of the noopsyche and the thymopsyche in patients suffering from insomnia; Effects of sleep problems on daytime performance.

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 β-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 µV2 and -2.70±2.21 µV2 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... [ABSTRACT FROM AUTHOR]

Investigates the role of sleep in memory consolidation. Involvement of the hippocampal formation in memory consolidation during sleep; Electroencephalography studies during sleep; Experience-dependent changes in cerebral activation during human rapid eye movement sleep.

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 patients (mean age 50 ± 14) with nonorganic insomnia (F 51.0) related to dysthymia (F 34.1) as compared with 11 age- and sex-matched normal controls. Patients demonstrated decreased sleep efficiency and sleep stage S2 as well as increased sleep latency to S1, S2 and S3, wakefulness within the total sleep period, number of awakenings, S1 and REM sleep. There was no intergroup difference in REM latency. Subjective sleep quality and the total score of the Self-Assessment Scale for Sleep and Awakening Quality (SSA) were deteriorated as were evening and morning well-being, mood, affectivity and drowsiness. Noopsychic measures showed deteriorated numerical memory, fine motor activity and reaction time variability. In a placebo-controlled crossover design study, the acute effects of 100 mg trazodone[sup 1] , a serotonin reuptake inhibitor with a sedative action due to 5HT[sub 2] and α[sub 1] receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in slow-wave sleep (S3 + 4), a lengthening of REM latency, a decrease in REM sleep and a normalization of the periodic leg movement (PLM) index. In the morning, there was a minimal increase in somatic complaints and a decrease in critical flicker frequency and systolic blood pressure. In conclusion, our study demonstrated that dysthymia induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg trazodone, thus suggesting a key-lock principle in the treatment of nonorganic insomnia related to dysthymia with this drug.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A wide range of studies have been published over the past two decades that involve the intersection of sleep EEG, insomnia, psychiatric illness (especially depressive disorders) and psychopharmacology. Much of value has been discovered, but there have also been false starts and contradictory results. There is in fact strong evidence that insomnia is associated with medical and psychiatric illness and that the sleepiness associated with insomnia is the cause of many accidents. Thus, the direct (visits to doctors, cost of sleeping medication, complications from use of these medications) and indirect (accidents, quality of life) costs of insomnia are enormous and constitute a major public health problem in the industrialized countries. Believing that it is now timely to assess the state of this important research area, a consensus conference was convened on June 26–28, 1998, in Porto Cervo (Italy) to attempt to clarify the important issues and findings on the clinical effect of the different classes of antidepressant drugs on sleep quality in depression. The participants’ consensus on some of the main topics is presented with the hope that this discussion and analysis will contribute to productive research in this important field.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (4 females, 7 males) aged 30–55 (mean: 44±9) years with nonorganic insomnia (F 51·0) related to panic disorder (F 41·0) as compared with 11 age- and sex-matched normal controls aged 30–58 (mean: 44±9) years, utilising polysomnography (PSG) and psychometry. PSG demonstrated decreased sleep efficiency (primary target variable), total sleep time (TST) and S2 as well as increased middle and late insomnia, S1, S3+S4, snoring and PLM in patients. There were no intergroup differences in REM variables. Subjective sleep quality deteriorated, as did drive and fine motor activity in the morning, while concentration increased. Blood pressure in the evening and morning and pulse rate in the evening were elevated. These differences as compared with normals were distinct from those observed in other sleep disorders. In a subsequent acute, placebo-controlled cross-over design study, patients received alprazolam 0·5 mg (Xanor[sup ®] ;) and placebo. As compared with placebo, alprazolam induced an increase in sleep efficiency (primary target variable), TST and S2, a decrease in wakefulness during the total sleep period, S3+S4 and the oxygen desaturation and PLM indices, and improved subjective sleep quality, somatic complaints, drive, affectivity and drowsiness in the morning. There were no changes in REM variables. Thus, alprazolam induced changes that were opposite to the differences observed between patients and controls before treatment, thereby normalizing sleep and awakening quality. As observed in insomnia related to GAD and subsequent benzodiazepine therapy, the present study also points to a key-lock principle in the treatment of insomnia caused by anxiety disorders and neurophysiologically visualizes processes at the receptor level (e.g. benzodiazepine agonists versus inverse agonists). Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Recent investigations in our sleep outpatient clinic demonstrated that 30% of patients exhibited organic and 70% nonorganic sleep disorders, with 41% showing as an additional diagnosis neurotic, stress-related, and somatoform disorders, 31% affective disorders and 15% mental and behavioral disorders due to psychoactive substance use. Thus, the aim of the study was to investigate the acute effects of the imidazopyridine zolpidem on objective and subjective sleep and awakening quality in the largest of the above-mentioned groups. In this single-blind, placebo-controlled cross-over study, 15 patients (9 females and 6 males aged 51.1 + 11.3 years) diagnosed as having nonorganic insomnia (ICD–10: F 51.0) related to neurotic and stress-related disorders (F 1.1:12, F 41.2:2 and F 43.2:1) were included. Objective and subjective sleep and awakening quality measures were investigated in 3 subsequent nights in the sleep laboratory (adaptation, baseline/placebo and zolpidem 10 mg night), utilizing clinical, polysomnographic, psychometric and psychophysiological methods. The drug-free patients were matched according to age and sex with 15 normal healthy controls (age 51.2 + 11.8 years). Statistical analysis of polysomnographic variables demonstrated a significant lengthening of the total sleep period (TSP) and total sleep time (TST), an improvement in sleep efficiency and a shortening of sleep latencies after zolpidem as compared with placebo. These changes were opposite to the differences between patients and controls. Concerning sleep architecture, zolpidem increased the length of S4 and S3 + S4 as compared with placebo. Subjective sleep and awakening quality and the thymopsychic variables drive, mood, affectivity and wakefulness in the morning showed no significant changes, as a significant improvement had already occurred from the adaptation to the baseline/placebo night. Noopsychic variables (attention, concentration, attention variability, numerical memory, fine motor activity, reaction time measures) showed similar findings. Moreover, subjective sleep and awakening quality, thymopsychic and noopsychic measures during baseline/placebo recordings did not differ significantly from normative data (except for fine motor activity). Psychophysiological measures did not show any significant alterations either, except for a decrease in systolic blood pressure in the evening. Conclusion: As compared with placebo, zolpidem induced a significant improvement in objective sleep quality, mainly by increasing TSP, TST and sleep efficiency and shortening sleep latencies, thereby normalizing the disorder of initiating and maintaining sleep. Deep sleep stages S3 + S4 increased (although at baseline/placebo these stages did not differ from controls), while S1, S2 and SREM did not change significantly. Subjective sleep and awakening quality as well as thymopsychic and noopsychic performance in the morning mainly showed a placebo and ‘first- night effect’ phenomenon in these patients. Thus, the changes induced by zolpidem were somewhat different from those after classical benzodiazepines.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]