Sleep modelled as a continuous and dynamic process predicts healthy ageing better than traditional sleep scoring.

BACKGROUND: In current clinical practice, sleep is manually scored in discrete stages of 30-s duration. We hypothesize that modelling sleep automatically as continuous and dynamic process predicts healthy ageing better than traditional scoring. METHODS: Sleep electroencephalography of 15 young healthy subjects (aged ≤40 years) was used to train the modelling method. Each 3-s sleep mini-epoch was modelled as a probabilistic combination of wakefulness, light and deep sleep. For 79 healthy sleepers (aged 20-77 years), 15 sleep features were derived from manual traditional scoring (manual features), 7 from the automatic modelling (automatic features) and 24 from a combination of automatic modelling with traditional scoring (combined features). Age was predicted with seven multiple linear regression models with i) manual, ii) automatic, iii) combined, iv) manual + automatic, v) manual + combined, vi) automatic + combined, and vii) manual + automatic + combined sleep features. Using the same seven sleep feature groups, two support vector machine and one random forest classifiers were used to discriminate younger (aged <47 years) from older subjects with fivefold cross-validation. Adjusted coefficients of determination (adj-R2) and average validation accuracy (ACC) were used to compare the linear models and the classifiers. RESULTS: The linear model and the classifiers using only manual features achieved the lowest values of adjusted coefficient of determination and classification validation accuracy (adj-R2 = 0.295, ACC = 63.00% ± 16.22%) compared to the ones using automatic (adj-R2 = 0.354, ACC = 65.83% ± 9.39%), combined (adj-R2 = 0.321, ACC = 63.42% ± 8.78%), manual + automatic (adj-R2 = 0.416, ACC = 67.00% ± 8.60%), manual + combined (adj-R2 = 0.355, ACC = 72.17% ± 12.90%), automatic + combined (adj-R2 = 0.448, ACC = 65.92% ± 7.97%), and manual + automatic + combined sleep features (adj-R2 = 0.464, ACC = 70.92% ± 10.33%). CONCLUSIONS: Continuous and dynamic sleep modelling captures healthy ageing better than traditional sleep scoring.

Effects of singing bowl exposure on Karolinska sleepiness scale and pupillographic sleepiness test: A randomised crossover study.

BACKGROUND: The aim of this study was to investigate the effects on subjective and objective sleepiness of a stay above a large struck singing bowl compared to a relaxation period in a silent singing bowl. METHODS: Fifty-eight healthy subjects were recruited for the study, 48 participated on two days, one week apart, during the same timeslot. The Karolinska sleepiness scale was used to evaluate current subjective sleepiness, and the relative pupillary unrest index to assess objective sleepiness. In this randomized cross-over study, the intervention consisted of a 20-minute stay in a hammock while the singing bowl, positioned beneath, was struck seven times. The controlled comparator was a 20-minute stay in the same hammock above the singing bowl, but without being struck. After these two interventions subjective and objective sleepiness were re-evaluated. RESULTS: The mean relative pupillary unrest index values after relaxation in the struck and silent singing bowl groups were 0.74 and respectively 0.71 (p = 0.460). The median Karolinska sleepiness scale value after relaxation with the struck singing bowl was 3 compared with 4 (p = 0.041) for the silent singing bowl. DISCUSSION: This study evaluated the influence of a struck singing bowl on sleepiness during daytime. Subjective sleepiness was significantly lower after relaxation above a struck singing bowl. After gender stratification, the difference was still significant in women. Objective sleepiness was not different in both groups. Finally, we can only speculate if women may be more susceptible to subjective improvements in case of sleepiness and show another perception of relaxation in a struck singing bowl compared to men.

Multimodal Magnetic Resonance Imaging reveals alterations of sensorimotor circuits in restless legs syndrome.

STUDY OBJECTIVES: Integrated information on brain microstructural integrity and iron storage and its impact on the morphometric profile is not available in restless legs syndrome (RLS). We applied multimodal magnetic resonance imaging (MRI) including diffusion tensor imaging, the transverse relaxation rate (R2*), a marker for iron storage, as well as gray and white matter volume measures to characterize RLS-related MRI signal distribution patterns and to analyze their associations with clinical parameters. METHODS: Eighty-seven patients with RLS (mean age 51, range 20-72 years; disease duration, mean 13 years, range 1-46 years, of those untreated n = 30) and 87 healthy control subjects, individually matched for age and gender, were investigated with multimodal 3T MRI. RESULTS: Volume of the white matter compartment adjacent to the post- and precentral cortex and fractional anisotropy (FA) of the frontopontine tract were both significantly reduced in RLS compared to healthy controls, and these alterations were associated with disease duration (r = 0.25, p = 0.025 and r = 0.23, p = 0.037, respectively). Corresponding gray matter volume increases of the right primary motor cortex in RLS (p < 0.001) were negatively correlated with the right FA signal of the frontopontine tract (r = -0.22; p < 0.05). Iron content evaluated with R2* was reduced in the putamen as well as in temporal and occipital compartments of the RLS cohort compared to the control group (p < 0.01). CONCLUSIONS: Multimodal MRI identified progressing white matter decline of key somatosensory circuits that may underlie the perception of sensory leg discomfort. Increases of gray matter volume of the premotor cortex are likely to be a consequence of functional neuronal reorganization.

Association of mitochondrial iron deficiency and dysfunction with idiopathic restless legs syndrome.

BACKGROUND: Restless legs syndrome is a sensorimotor neurological disorder of the limbs that impairs quality of life and disturbs sleep. However, there has been progress in understanding the disease involving the dopaminergic system as well as iron metabolism. The exact pathophysiological mechanisms of restless legs syndrome remain elusive. We tried to elucidate the underlying mechanisms in iron metabolism in restless legs syndrome subjects on a systemic, cellular, and mitochondrial level. METHODS: We conducted a study prospectively recruiting 168 restless legs syndrome patients and 119 age-matched healthy controls focusing on iron metabolism using human monocytes as surrogates. RESULTS: Evaluation of systemic iron metabolism parameters in the circulation showed no significant difference between patients and controls. We observed a significant reduction in mRNA levels of heme oxygenase 1 and mitochondrial iron genes like mitoferrin 1 and 2 in monocytes isolated from restless legs syndrome patients, indicating mitochondrial iron deficiency. Interestingly, we also observed reduced expression of iron regulatory protein 2 along with impaired activity of mitochondrial aconitase and reduced mitochondrial superoxide formation in restless legs syndrome subjects. Along this line, patients had reduced mitochondrial respiratory capacity that improved in restless legs syndrome subjects under treatment with dopaminergic drugs compared with untreated patients. CONCLUSIONS: Our data suggest that restless legs syndrome is linked to mitochondrial iron deficiency and associated impairment of mitochondrial function. This is partly corrected by treatment with dopaminergic drugs compared with untreated patients, which may be linked to an effect of dopamine on cellular iron homeostasis. © 2018 International Parkinson and Movement Disorder Society.

Screening for idiopathic REM sleep behavior disorder: usefulness of actigraphy.

Study Objectives: To evaluate the utility of multimodal low-cost approaches including actigraphy, a wrist-worn device monitoring rest/activity cycles, in identifying patients with idiopathic REM sleep behavior disorder (iRBD). Methods: Seventy patients diagnosed with sleep disorders causing different motor manifestations during sleep (iRBD, sleep apnea, restless legs syndrome) and 20 subjects without any relevant motor manifestation during sleep, underwent video-polysomnography (vPSG) and 2 week actigraphy, completed six validated RBD screening questionnaires, and sleep apps use was assessed. Actigraphy was analyzed automatically, and visually by seven blinded sleep medicine experts who rated as "no," "possible," and "probable" RBD. Results: Quantitative actigraphy analysis distinguished patients from controls, but not between patients with different types of motor activity during sleep. Visual actigraphy rating by blinded experts in sleep medicine using pattern recognition identified vPSG confirmed iRBD with 85%-95% sensitivity, 79%-91% specificity, 81%-91% accuracy, 57.7% ± 11.3% positive predictive value, 95.1% ± 3.3% negative predictive value, 6.8 ± 2.2 positive likelihood ratio, 0.14 ± 0.05 negative likelihood ratio and 0.874-0.933 area under the ROC curve (AUC). AUC of the best performing questionnaire was 0.868. Few patients used sleep apps; therefore, their potential utility in the evaluated patients' groups is limited. Conclusions: Visual analysis of actigraphy using pattern recognition can identify subjects with iRBD, and is able to distinguish iRBD from other motor activities during sleep, even when patients are not aware of the disease in contrast to questionnaires. Therefore, actigraphy can be a reliable screening instrument for RBD potentially useful in the general population.

Dream Content in Patients With Sleep Apnea: A Prospective Sleep Laboratory Study.

STUDY OBJECTIVES: Few studies have addressed dreaming in patients with sleep apnea. We hypothesized that respiratory events and subsequent oxygen desaturation act as an important physiological trigger and may thus influence dream content in patients with a sleep-related breathing disorder. METHODS: Seventy-six patients (28 women, mean age 54 years, range 20-82) who underwent polysomnography because of suspected sleep apnea participated in this study. Dream reports and dream questionnaires were collected immediately after first morning awakening, at 5:30 AM, at the sleep laboratory. Dream content analysis with respect to possible respiratory-related content was performed. Patients were stratified into primary snoring, mild, moderate, and severe sleep apnea groups. RESULTS: In 63 patients sleep apnea was diagnosed (mild n = 31, 49.2%, moderate n = 13, 20.6%, severe n = 19, 30.2%), and 13 subjects in whom a sleep-related breathing disorder was not confirmed were included as a control group with primary snoring. There was no significant difference in respiratory-related dream topics between patients and controls. Also, no influence of respiratory parameters measured during polysomnography on dream content was detectable. CONCLUSIONS: We failed to detect a difference in dream content between patients with sleep apnea and controls. Further studies are required to determine whether these results indicate that the incorporation of respiratory events into dreams is absent in patients with sleep apnea or represents a bias due to the collection of dream content in the early morning hours.

CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1.

Introduction: Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease. Methods: We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay. Orexin/hcrt-specific T-cell reactivity was also determined by cytokine (interferon gamma and granulocyte-macrophage colony-stimulating factor) analysis. Individuals were considered as responders if the cell division index of CD3+CD4+ T cells and both stimulation indices of cytokine secretion exceeded the cutoff 3. Additionally, T-cell reactivity to orexin/hcrt had to be confirmed by showing reactivity to single peptides present in different peptide pools. Results: Using these criteria, 3/15 patients (20%) and 0/13 controls (0%) showed orexin/hcrt-specific CD4+ T-cell proliferation (p = .2262). The heterogeneous reactivity pattern did not allow the identification of a preferential target epitope. Conclusions: A significant role of orexin/hcrt-specific T cells in narcolepsy type 1 patients could not be confirmed in this study. Further studies are needed to assess the exact role of CD4+ T cells and possible target antigens in narcolepsy type 1 patients.

Not Only Sleepwalking But NREM Parasomnia Irrespective of the Type Is Associated with HLA DQB1*05:01.

STUDY OBJECTIVES: Despite the high prevalence and clinical relevance of NREM parasomnias, data on supportive genetic markers are scarce, and mainly refer to sleepwalking only. METHODS: We retrospectively analyzed clinical, polysomnographic, and HLA findings of 74 adults (37 men) with NREM parasomnia gathered from four neurological sleep centers. Parasomniac events were classified according to ICSD-2 criteria. HLA DQB1 genotyping was compared to regional-matched reference allele-frequencies. RESULTS: Fifty-six patients had more than 2 different parasomnia type: 11 sleepwalking, 4 sleep terrors, 3 confusional arousals only. Parasomniac events were documented during video-polysomnography (V-PSG) in 70% (49/70) of subjects (71.4% confusional arousals, 8.2% sleep terrors, 4.1% sleepwalking, 16.3% ≥ 2 NREM parasomnia types). Violent behavior during V-PSG occurred in 8.5% (6/71). NREM parasomnia onset was reported after the age of 30 years in 6.8% (5/74). The HLA DQB1*05:01 allele was present in 41% (29/71) compared to 24.2% in the regional-matched reference allele group (p < 0.05). This haplotype prevalence did not differ within the NREM parasomnia type. Epworth Sleepiness Score was 10 or higher in 28.6%. CONCLUSIONS: This is a large polysomnography-based case series of patients with NREM parasomnia. In patients with suspected sleepwalking or sleep terrors, polysomnography is highly useful in detecting arousals from NREM sleep as a marker of NREM parasomnia. We confirmed previous findings by demonstrating a high prevalence of the HLA DQB1*05:01 genotype for different types of NREM parasomnias. Our findings therefore support a common genetic background, and corroborate the importance of video-polysomnography in the work-up of parasomnia.

Oxygen desaturation during night sleep affects decision-making in patients with obstructive sleep apnea.

This study assessed decision-making and its associations with executive functions and sleep-related factors in patients with obstructive sleep apnea. Thirty patients with untreated obstructive sleep apnea and 20 healthy age- and education-matched controls performed the Iowa Gambling Task, a decision-making task under initial ambiguity, as well as an extensive neuropsychological test battery. Patients, but not controls, also underwent a detailed polysomnographic assessment. Results of group analyses showed that patients performed at the same level of controls on the Iowa Gambling Task. However, the proportion of risky performers was significantly higher in the patient group than in the control group. Decision-making did not correlate with executive functions and subjective ratings of sleepiness, whereas there was a significant positive correlation between advantageous performance on the Iowa Gambling Task and percentage of N2 sleep, minimal oxygen saturation, average oxygen saturation and time spent below 90% oxygen saturation level. Also, the minimal oxygen saturation accounted for 27% of variance in decision-making. In conclusion, this study shows that a subgroup of patients with obstructive sleep apnea may be at risk of disadvantageous decision-making under ambiguity. Among the sleep-related factors, oxygen saturation is a significant predictor of advantageous decision-making.

Natural course of restless legs syndrome/Willis-Ekbom disease: long-term observation of a large clinical cohort.

OBJECTIVE: Although restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is a common neurological disorder, data on the long-term course and management of the disease are scarce. The aim of the current study was to extend the knowledge on the long-term clinical course and treatment outcome of RLS/WED. METHODS: In this retrospective analysis, we performed a chart review of consecutive visits of 160 patients with definite RLS/WED from the RLS/WED database of the Innsbruck Medical University. RESULTS: A total of 160 patients (58.8% female, aged 58.9 years, range 21.5-86.8 years) met inclusion criteria of two or more visits during a follow-up of at least five years. The duration of the observational period was 8.1 ± 2.9 years. During the observational period, the percentage of treated patients increased (first vs last visit: 67.5% vs 77.5%). Of the patients, 59.4% had one or more switches of medication. Overall the RLS/WED severity, evaluated using a combined severity score (CSS) ranging from 1 to 5, decreased between the first and last visits (median [range], first visit: 3 [1-5] vs last visit 2.5 [1-5]; p <0.001). Symptoms improved in 55.0% of patients, worsened in 10.6%, and remained unchanged in 34.4% during the observational period. Augmentation of RLS/WED occurred in 42 patients (13/42 as the presenting cause; 29/42 occurring during treatment after 4.1 years). The annual rate of augmentation for subjects on dopaminergic medication was 8.1%. CONCLUSIONS: Our data suggest that, with the possibility of regular treatment adjustments, RLS/WED remains treatable in the majority of patients over years. Nevertheless, in this study, despite the overall decreased severity, RLS symptoms remained unchanged or worsened in 45% of the patients during the observational period.

Long-Term Follow-up Investigation of Isolated Rapid Eye Movement Sleep Without Atonia Without Rapid Eye Movement Sleep Behavior Disorder: A Pilot Study.

STUDY OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a harbinger of synuclein-mediated neurodegenerative diseases. It is unknown if this also applies to isolated REM sleep without atonia (RWA). We performed a long-term follow-up investigation of subjects with isolated RWA. METHODS: Participants were recruited from 50 subjects with isolated RWA who were identified at the sleep laboratory of the Department of Neurology at the Medical University of Innsbruck between 2003 and 2005. Eligible subjects underwent follow-up clinical examination, polysomnography, and assessment of neurodegenerative biomarkers (cognitive impairment, finger speed deficit, impaired color vision, olfactory dysfunction, orthostatic hypotension, and substantia nigra hyperechogenicity). RESULTS: After a mean of 8.6 ± 0.9 y, 1 of 14 participating subjects (7.3%) progressed to RBD. Ten of 14 RWA subjects (71.4%) were positive for at least one neurodegenerative biomarker. Substantia nigra hyperechogenicity and presence of mild cognitive impairment were both present in 4 of 14 subjects with isolated RWA. Electromyographic activity measures increased significantly from baseline to follow-up polysomnography ("any" mentalis and both anterior tibialis muscles: 32.5 ± 9.4 versus 52.2 ± 16.6%; p = 0.004). CONCLUSION: This study provides first evidence that isolated RWA is an early biomarker of synuclein-mediated neurodegeneration. These results will have to be replicated in larger studies with longer observational periods. If confirmed, these disease findings have implications for defining at-risk cohorts for Parkinson disease.

A Prospective Video-Polysomnographic Analysis of Movements during Physiological Sleep in 100 Healthy Sleepers.

STUDY OBJECTIVES: Video-polysomnography (v-PSG) is the gold standard for the diagnosis of sleep disorders. Quantitative assessment of type and distribution of physiological movements during sleep for the differentiation between physiological and pathological motor activity is lacking. We performed a systematic and detailed analysis of movements during physiological sleep using v-PSG technology. DESIGN: Prospective v-PSG investigation. SETTING: Academic referral center sleep laboratory. PARTICIPANTS: One hundred healthy sleepers aged 19-77 years recruited from a representative population sample after a two-step screening. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All subjects underwent v-PSG. In all cases where electromyographic activity > 100 msec duration was visible during sleep in the mentalis, submentalis, flexor digitorum superficialis, or anterior tibialis muscles, the time-synchronized video was analyzed. Visible movements were classified according to movement type and topography, and movement rates were computed for the different sleep stages. A total of 9,790 movements (median 10.2/h, IQR 4.6-16.2) were analyzed: 99.7% were elementary, 0.3% complex. Movement indices were higher in men than women (men: median 13/h, interquartile range 7.1-29.3, women: median 7.9/h, interquartile range 3.4-14.5; P = 0.006). The majority of movements involved the extremities (87.9%) and were classified as focal (53.3%), distal (79.6%), and unilateral (71.5%); 15.3% of movements were associated with arousals. REM-related movements (median 0.8 sec, IQR 0.5-1.2) were shorter than NREM-related movements (median 1.1 sec, IQR 0.8-1.6; P = 0.001). Moreover, REM-related movements were predominantly myocloniform (86.6%), whereas NREM-related movements were more often non-myocloniform (59.1%, P < 0.001). CONCLUSION: Minor movements are frequent during physiological sleep, and are associated with low arousal rates. REM-related movements were predominantly myocloniform and shorter than NREM movements, indicating different influences on motor control during both sleep states.

Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD.

OBJECTIVE: The aim of the present study was to determine the predictive value of olfactory dysfunction for the early development of a synuclein-mediated neurodegenerative disease in subjects with idiopathic REM sleep behavior disorder (iRBD) over an observational period of 5 years. METHODS: Thirty-four patients with polysomnography-confirmed iRBD underwent olfactory testing using the entire Sniffin' Sticks test assessing odor identification, odor discrimination, and olfactory threshold. Patients with iRBD were prospectively followed up over a period of 4.9 ± 0.3 years (mean ± SD). The diagnosis of neurodegenerative diseases was based on current clinical diagnostic criteria. RESULTS: After 2.4 ± 1.7 years (mean ± SD), 9 patients (26.5%) with iRBD developed a Lewy body disease (6 Parkinson disease and 3 dementia with Lewy bodies). The entire Sniffin' Sticks test and the identification subtest had the same overall diagnostic accuracy of 82.4% (95% confidence interval: 66.1%-92.0%) in predicting conversion. The relative risk for a Lewy body disease in the lowest tertile of olfactory function was 7.3 (95% confidence interval: 1.8-29.6) compared with the top 2 tertiles. CONCLUSIONS: Assessment of olfactory function, particularly odor identification, may help to predict the development of a Lewy body disease in patients with iRBD over a relatively short time period and thus to identify patients suitable for future disease modification trials.

Subjective deficits of attention, cognition and depression in patients with narcolepsy.

OBJECTIVE: Patients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood. PATIENTS/METHODS: A total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory. RESULTS: Patients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits. CONCLUSION: The present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments.

Sleep and Respiration in 100 Healthy Caucasian Sleepers--A Polysomnographic Study According to American Academy of Sleep Medicine Standards.

STUDY OBJECTIVES: Despite differences between American Academy of Sleep Medicine (AASM) and Rechtschaffen and Kales scoring criteria, normative values following the current AASM criteria are lacking. We investigated sleep and respiratory variables in healthy adults over the lifespan, and established polysomnographic normative values according to current standards. DESIGN: Prospective polysomnographic investigation. SETTING: Academic referral hospital sleep laboratory. PARTICIPANTS: One hundred healthy sleepers aged 19-77 y were selected from a representative population sample by a two-step screening. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All subjects underwent one full-night polysomnography. Sleep and arousals were scored according to AASM standards. Respiration was scored according to AASM 2007 and 2012 criteria in order to compare both methods. Percentile curves showed age-related differences in sleep architecture: a decrease was found for sleep efficiency [≤ 30 y: 87.0 (71.9-94.1)% versus > 60 y: 79.7 (44.5-90.9)%], total sleep time [≤ 30 y: 413.5 (345.6-451.9) min versus > 60 y: 378.3 (216.0-440.0) min], the percentages of N3 [≤ 30 y 20.7 (15.2-37.5)% versus > 60 y: 14.9 (2.4-35.6)%] and rapid eye movement sleep [≤ 30 y 15.5 (7.5-23.6)% versus. > 60 y: 10.3 (1.9-21.9)%], whereas the percentage of wake time after sleep onset increased with age [≤ 30 y 6.0 (1.9-22.8)% versus > 60 y: 15.2 (6.3-48.7)%]. The apnea-hypopnea index (AHI) was higher when applying the AASM 2012 criteria [AHI AASM 2007 0.7 (0.0-21.5)/h versus 2012: 1.7 (0.0-25)/h; P < 0.001]. Eight percent of subjects had an AHI > 15/h. CONCLUSIONS: This study provides normative data on sleep macrostructure, microstructure, and respiration in adults following AASM standards. Furthermore, we demonstrated that respiration scoring according to AASM 2012 results in higher AHIs, and challenge the use of age-independent respiratory cutoff values.

Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder.

Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm(2) vs. 0.19 ± 0.07 cm(2) ; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time.

Validation of an integrated software for the detection of rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES AND DESIGN: Rapid eye movement sleep without atonia (RWA) is the polysomnographic hallmark of REM sleep behavior disorder (RBD). To partially overcome the disadvantages of manual RWA scoring, which is time consuming but essential for the accurate diagnosis of RBD, we aimed to validate software specifically developed and integrated with polysomnography for RWA detection against the gold standard of manual RWA quantification. SETTING: Academic referral center sleep laboratory. PARTICIPANTS: Polysomnographic recordings of 20 patients with RBD and 60 healthy volunteers were analyzed. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Motor activity during REM sleep was quantified manually and computer assisted (with and without artifact detection) according to Sleep Innsbruck Barcelona (SINBAR) criteria for the mentalis ("any," phasic, tonic electromyographic [EMG] activity) and the flexor digitorum superficialis (FDS) muscle (phasic EMG activity). Computer-derived indices (with and without artifact correction) for "any," phasic, tonic mentalis EMG activity, phasic FDS EMG activity, and the SINBAR index ("any" mentalis + phasic FDS) correlated well with the manually derived indices (all Spearman rhos 0.66-0.98). In contrast with computerized scoring alone, computerized scoring plus manual artifact correction (median duration 5.4 min) led to a significant reduction of false positives for "any" mentalis (40%), phasic mentalis (40.6%), and the SINBAR index (41.2%). Quantification of tonic mentalis and phasic FDS EMG activity was not influenced by artifact correction. CONCLUSION: The computer algorithm used here appears to be a promising tool for REM sleep behavior disorder detection in both research and clinical routine. A short check for plausibility of automatic detection should be a basic prerequisite for this and all other available computer algorithms.

Is there a polysomnographic signature of augmentation in restless legs syndrome?

OBJECTIVE: Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients. METHODS: Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT). RESULTS: Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P <0.05). However, augmented patients scored highest on RLS severity scales (P <0.05) and were the only group with a substantial number of PLM during the SIT. CONCLUSION: This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness.