An Evaluation of DNA Methylation Levels and Sleep in Relation to Hot Flashes: A Cross-Sectional Study.

Objectives: We aimed to evaluate the DNA methylation levels in perimenopausal and postmenopausal women, measured through Long Interspersed Element-1 (LINE-1) and Alu, and the sleep parameters in relation to the presence of hot flashes (HFs). Methods: This cross-sectional study included 30 peri- or postmenopausal women aged between 45 and 55. The menopausal status was determined according to STRAW + 10 criteria and all participants had a low cardiovascular disease (CVD) risk profile determined by Framingham risk score. The sample was divided into two groups based on the presence or absence of HFs documented in their medical history during their initial visit: Group 1 (n = 15) with HFs present and Group 2 (n = 15) with HFs absent. The patients had polysomnography test and HFs were recorded both by sternal skin conductance and self-report overnight. Genomic DNA was extracted from the women's blood and methylation status was analyzed by fluorescence-based real-time quantitative PCR. The quantified value of DNA methylation of a target gene was normalized by ß-actin. The primary outcome was the variation in methylation levels of LINE-1 and Alu and sleep parameters according to the presence of HFs. Results: LINE-1 and Alu methylation levels were higher in Group 1 (HFs present), although statistically non-significant. LINE-1 methylation levels were negatively correlated with age. Sleep efficiency was statistically significantly lower for women in Group 1 (HFs present) (74.66% ± 11.16% vs. 82.63% ± 7.31%; p = 0.03). The ratio of duration of awakening to total sleep time was statistically significantly higher in Group 1 (HFs present) (22.38% ± 9.99% vs. 15.07% ± 6.93, p = 0.03). Objectively recorded hot flashes were significantly higher in Group 1 (4.00 ± 3.21 vs. 1.47 ± 1.46, p = 0.03). None of the cases in Group 2 self-reported HF despite objectively recorded HFs during the polysomnography. The rate of hot flash associated with awakening was 41.4% in the whole sample. Conclusions: Women with a history of hot flashes exhibited lower sleep efficiency and higher awakening rates. Although a history of experiencing hot flashes was associated with higher LINE-1 and Alu methylation levels, no statistical significance was found. Further studies are needed to clarify this association. This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa. Project number: TTU-2021-35629.

Distinctive sleep complaints and polysomnographic findings in antibody subgroups of autoimmune limbic encephalitis.

INTRODUCTION: Sleep disturbances are being increasingly recognized in association with autoimmune encephalitis (AIE). We investigated the prevalence of sleep-related symptoms and polysomnographic features of patients with AIE and the long-term outcomes in these patients in a multi-center, prospective study from Turkey. METHODS: We prospectively evaluated patients with definite AIE in a common database including demographics, AIE-related and sleep-related symptomatology. Maximum and latest modified Rankin scores (mRS) and Liverpool Outcome Score (LOS) were noted. RESULTS: Of 142 patients, 87 patients (61.3%) fulfilled the criteria for definite AIE (mean age, 46.8+18.8 years; 51.7% women; mean disease duration, 21.0+38.4 months). 78.9% of patients had at least one or more new onset or worsened sleep-related symptomatology: insomnia (55.3%), excessive daytime sleepiness (EDS, 28.0%), sleep apnea (18.7%), REM sleep behavior disorder (RBD, 17.3%), restless legs syndrome (10.7%) and oneiric stupor (9.3%). Sleep efficiency, N3 and REM sleep were decreased and N1 sleep was increased in patients with Ab[+] AIE. LOS points were highest in those with insomnia and sleep apnea, and lowest in those with EDS, RBD and oneiric stupor. RBD and sleep apnea were more common in anti-LG1 Ab[+] group than anti-NMDAR Ab[+] group. Index of periodic leg movements was highest in anti-LG1 Ab[+] group. Patients with EDS and oneiric stupor had more common memory problems. Maximum and latest mRS scores were positively correlated with EDS and oneiric stupor. EDS, RBD and oneiric stupor were negatively correlated with LOS points. CONCLUSION: Our study emphasizes the presence and importance of early diagnosis of sleep disturbances in AIE in regard to their deteriorative influences on disease prognosis.

Attention and executive function impairments in obstructive sleep apnea are associated with decreased sleep spindles.

INTRODUCTION: Sleep spindles play a key role in sleep-mediated cognitive processes. Cognitive functions are well-known to be affected in obstructive sleep apnea (OSA). Here, we analyzed attention and executive functions in patients with OSA and investigated the relationship between sleep spindles and cognitive abilities. METHODS: Sixty patients with OSA (18-65 years, 19 females and 41 males) and a control group (n = 41) including age-and sex-matched healthy individuals were consecutively and prospectively enrolled. All participants had a full-night polysomnography, and sleep spindles were analyzed using a semi-automated program. For the evaluation of short-term memory, attention and executive functions, Stroop test, forward and backward digit span tests were applied to all participants upon awakening following polysomnography. RESULTS: Scores of forward and backward digit span and Stroop tests were worse in OSA patients in compared to those in controls. Mean density of sleep spindles was decreased in OSA patients than those in controls (p = 0.044). A positive correlation was found between fast sleep spindle frequency and forward digit span (r = 2.222; p = 0.038) and backward digit span test scores (r = 2,157; p = 0.042) in OSA patients. In patients with moderate to severe OSA, sleep spindle density was positively correlated with forward (r = 2.323, p = 0.029) and backward (r = 2.500, p = 0.016) DSTs, and the duration of sleep spindles had positive correlation with backward DST (r = 2.452, p = 0.010). CONCLUSION: Our findings demonstrated that the disturbances in sleep spindle characteristics in OSA are associated with the cognitive impairments in attention, short-term memory, and executive functions, especially in patients with moderate to severe OSA.

Patients with restless legs syndrome exhibit reduced serum colony-stimulating factor-1, humanin-like 3 and 10 levels.

OBJECTIVE: The main pathophysiological mechanisms in restless legs syndrome (RLS) are known as genetic predisposition, brain iron deficiency, and dopaminergic dysfunction. While some genetic variants and polymorphisms were defined, the genetic basis and etiopathogenesis of RLS remain unclear. We aimed to identify new candidate genes and/or potential biomarkers associated with increased RLS risk. METHODS: Twenty-three patients with RLS, 30 patients with Parkinson's disease (PD), and 27 healthy controls were enrolled. Agilent Human 8X60K Oligo Microarray was used for the identification of gene expression levels in peripheral blood cells. Gene ontology (GO) analysis was used for functional annotation of differentially expressed genes (DEGs). Serum levels of selected DEGs were measured by ELISA for validation. RESULTS: Patients with RLS showed 30 downregulated DEGs compared to healthy controls. Two genes, MTRNR2L10 and MTRNR2L3, involved negative regulation of the execution phase of apoptosis were highlighted in GO analysis. These genes encode humanin-like 10 and 3, respectively, were encoded by these genes, and their levels, along with CSF-1, linked to neurodegeneration, were reduced in RLS patients. Humanin-like 10 and CSF-1 levels correlated with sleep efficiency and N2 sleep duration, while humanin-like 3 levels correlated with mean sleep oxygen saturation during sleep. CONCLUSION: Our study showed that several neuroprotective genes were downregulated in RLS, which may confer susceptibility to neuronal death associated with decreased sleep efficiency. Microarray results differed between RLS and PD patients, suggesting diverse pathogenetic mechanisms. CSF-1, which is involved in iron, dopamine metabolism, and blood oxygenation, appears to partake in RLS pathophysiology.

Assessment of Impact of Dietary Patterns on Obstructive Sleep Apnea Patients.

Objective Obstructive sleep apnea syndrome (OSAS) is characterized by episodic cessations of breathing due to upper airway obstruction during sleep, which may cause disturbances in dietary patterns resulting from appetite-related hormonal changes. The aim of the present study was to investigate the relationship between OSAS and nutritional and dietary patterns. Materials and Methods A total of 20 female and 53 male OSAS patients aged > 30 years were enrolled. Demographic data, as well as data on smoking and alcohol habits, were noted, anthropometric measures were made, and a questionnaire regarding chronic diseases including OSAS and four questionnaires on recent food intake frequency and content of nutrition were filled out. The content of nutrition was noted under seven categories: meat, legumes, milk and dairy products, fruits and vegetables, bread and cereals, fat and carbohydrates, and beverages. Results The severity of OSAS (assessed by the apnea-hypopnea index. AHI) was positively correlated with the body mass index (BMI), the circumferences of the waist, chest, and buttocks, and, in males, with the circumference of the neck as well. There was no correlation between the AHI and nutritional habits in terms of the frequency of meals or snacks, the scores on the Snoring, Tiredness, Observed Apnea, and High Blood Pressure-Body Mass Index, Age, Neck Circumference, and Gender (STOP-BANG) Questionnaire and the corresponding macro- and micronutrients. Worsening apnea scores led to increased intake of macronutrients of carbohydrate and protein and micronutrients of niacin and pyridoxine ( p < 0.05), and decreased intake of fat ( p < 0.05). Conclusion The present study demonstrated an association between OSAS severity and recent food intake, manifested in increased intake of carbohydrates, niacin, and pyridoxine, and decreased fat intake.

Estratificación del riesgo de fenoconversión al parkinsonismo en pacientes con trastorno de conducta del sueño REM aislado. Estudio de seguimiento en un centro de Turquía / Risk stratification for phenoconversion in patients with isolated REM sleep behavior disorder. A follow-up study from Turkey

Introducción El trastorno aislado de la conducta del sueño con movimientos oculares rápidos (iRBD) es uno de los marcadores prodrómicos más potentes de las alfa-sinucleinopatías. Nuestro objetivo fue investigar los predictores clínicos y cuan­titativos no invasivos de la fenoconversión de iRBD a parkinsonismo. Pacientes y métodos Se siguió prospectivamente a un total de 45 pacientes (57,8% hombres) durante ocho años del período de estudio. Se realizaron evaluaciones clínicas, la prueba de identificación de olores Sniffin’ Sticks, la prueba Farnsworth-Munsell 100 Hue Color Vision, el inventario de depresión de Beck y los criterios de Roma III para el estreñimiento. Se analizaron parámetros polisomnográficos, husos del sueño, análisis espectral electroencefalográfico (EEG) y variabilidad de la frecuencia cardíaca. Resultados Ocho pacientes (17,8%) mostraron fenoconversión a parkinsonismo después de una duración media de seguimiento de 3,2 ± 1 año. La odds ratio para predecir la fenoconversión fue más alta para los pacientes =60 años con anosmia y estreñimiento –44,8 (4,5-445,7); kappa = 4,291–. La disminución de la potencia del espectro EEG, junto con la edad =60 años, la anosmia y el estreñimiento, dio como resultado el índice de odds más alto –122,5 (9,7-1543,8); kappa = 3,051–. Conclusiones Es de gran importancia tener una perspectiva mundial de las tasas de fenoconversión de iRBD a neurodegeneración manifiesta, ya que los factores raciales y geográficos pueden desempeñar importantes papeles modificadores. Los biomarcadores neurofisiológicos parecen ser predictores importantes de la fenoconversión, aunque se necesita más investigación para establecer subtipos de iRBD con diferentes probabilidades de evolución hacia una sinucleinopatía manifiesta. (AU)

INTRODUCTION Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the strongest prodromal markers of alpha-synucleinopathies. We aimed to investigate non-invasive clinical and quantitative predictors of phenoconversion from iRBD to parkinsonism. PATIENTS AND METHODS We prospectively followed-up a total of 45 patients (57.8% men) for eight years. Clinical assessments, Sniffin’ Sticks Odor Identification Test, Farnsworth-Munsell 100 Hue Color Vision test, Beck Depression Inventory and Rome III Criteria for constipation were performed. Polysomnographic parameters, sleep spindles, electroencephalographic (EEG) spectral analysis, heart rate variability (HRV) were analyzed. RESULTS Eight patients (17.8%) showed phenoconversion to parkinsonism after a mean duration of 3.2 ± 1 years. Odds ratio for predicting phenoconversion was highest for patients =60 years of age with anosmia and constipation –44.8 (4.5-445.7); kappa = 4.291–. Duration, frequency or density of sleep spindles failed to demonstrate significant correlations. In EEG spectral analysis, lower alpha power in occipital region during wakefulness and REM sleep was significantly correlated with phenoconversion. Slowing in EEG spectrum power, together with age =60 years, anosmia and constipation, resulted in the highest odds ratio –122.5 (9.7-1543.8); kappa = 3.051–. CONCLUSIONS It is of great importance to have a world-wide perspective of phenoconversion rates from iRBD to overt neurodegeneration, since racial and geographical factors may play important modifying roles. Relatively younger age and shorter disease duration may also be confounding factors for lower rate in our study. Neurophysiological biomarkers seem to be important predictors of phenoconversion, though more research is needed to establish subtypes of iRBD with different probabilities of evolution to overt synucleinopathy. (AU)

Restless sleep disorder in children with epileptic and non-epileptic nocturnal attacks.

Restless sleep disorder (RSD) is an important sleep disorder characterised by the presence of frequent large muscle movements (LMM) during sleep, which may be comorbid to other conditions/diseases. In this study, we investigated the frequency and the characteristics of RSD among children who were evaluated by polysomnography (PSG) due to epileptic and non-epileptic nocturnal attacks. We analysed consecutively children younger than 18 years who were referred for PSG recording due to abnormal motor activities during sleep. The diagnosis of nocturnal events as sleep-related epilepsy was made based on the current consensus. Patients who were referred with suspicion of sleep-related epilepsy, but who were diagnosed to have non-epileptic nocturnal events and children with a definitive diagnosis of NREM sleep parasomnias were also enrolled. Sixty-two children were analysed in this study (17 children with sleep-related epilepsy, 20 children with NREM parasomnia, and 25 children with nocturnal events not otherwise classified [neNOS]). The mean number of LMM, LMM index, LMM-associated with arousal and its index were all significantly higher in children with sleep-related epilepsy. Restless sleep disorder was present in 47.1% of patients with epilepsy, 25% of patients with parasomnia, and in 20% of patients with neNOS. The mean A3 duration and the A3 index were higher in children with sleep-related epilepsy and RSD compared with those with parasomnia and restless sleep disorder. Patients with RSD had lower ferritin levels than those without RSD in all subgroups. Our study demonstrates a high prevalence of restless sleep disorder in children with sleep-related epilepsy, associated with an increased cyclic alternating pattern.

Analysis of QRS complex morphology in children and adolescents with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) leads to many cardiovascular, neurologic, metabolic, and neurocognitive consequences. Conduction deficits, deviations in electrical axis, and changes in QRS morphology reflect the impairments in cardiac muscle activity and underlie the cardiovascular complications of OSAS. Here we aimed to determine the relationship between OSAS and changes in the cardiac conduction system in children and adolescents. During the 6-month duration of the study, all children having the diagnosis of OSAS in Sleep and Disorders Unit following a full-night polysomnography (PSG) were consecutively evaluated. ECGs were performed and analyzed in the Division of Pediatric Cardiology, Department of Pediatrics. The maximum spatial vector size (QRSmax), QRS electrical axis (EA), left and right ventricular hypertrophy, and the presence of fragmented QRS (fQRS) or prolonged R or S wave were examined in detail. A total of 17 boys with OSAS and 13 healthy boys participated in the study. The mean QRSmax and the QRSmax on V5 derivative were significantly lower in the patient group compared to those in the control group (p = 0.011 and p = 0.017, respectively). EA was similar between the two groups. While none of the patients with OSAS nor the control group had left ventricular hypertrophy, only one boy with OSAS had right ventricular hypertrophy according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was significantly higher in patients with OSAS compared to healthy controls (p = 0.035), especially in children below the age of 5 years (p = 0.036).  Conclusion: This study demonstrated that male children and adolescents with OSAS have a combination of QRS complex changes characterized by low QRS voltages, and increased frequency of fragmented QRS. These findings reflect that the electrical remodeling and structural remodeling of the myocardium are considerably affected by OSAS in children and adolescents, leading to ventricular changes and intraventricular conduction problems. What is Known: • Pediatric obstructive sleep apnea syndrome (OSAS) characterized by recurrent intermittent hypoxemia, hypercapnia, and sleep fragmentation results in sympathetic nervous system activation, increased inflammation, and hypoxic endothelial dysfunction. When left untreated, OSAS leads to many cardiovascular, neurologic, metabolic and neurocognitive consequences, and also to sudden infant death syndrome in young children, probably due to the involvement of the cardiac conduction system. What is New: • This study demonstrated that mean QRSmax was significantly lower in male children and adolescents with OSAS, reflecting the structural and electrical remodeling of the myocardium, and one boy with OSAS had RVH according to ECG-derived analysis. The percentage of fQRS or notched R or S waves was much higher in boys with OSAS, especially in children below the age of five years. These finding showed that myocardium was considerably affected to impair the intraventricular conduction in younger children with OSAS.

Smoking Disturbs the Beneficial Effects of Continuous Positive Airway Pressure Therapy on Leptin Level in Obstructive Sleep Apnea.

Background: This study aimed to determine how smoking alters the effect of positive airway pressure (PAP) therapy on metabolic syndrome in obstructive sleep apnea (OSA). Methods: In this clinical trial, morphometric measures, metabolic syndrome parameters, and apnea-hypopnea index (AHI) in OSA patients were recorded and compared between active smokers and non-smokers. The mean change in metabolic syndrome parameters measured before and after 3 months of PAP therapy was determined. The study included 72 males and 43 females. Results: Morphometric values and mean AHI did not differ between active smokers and non-smokers. When the percentage of unchanged, increased, or decreased metabolic parameters measured before and after treatment was analyzed, leptin level tended to increase in active smokers with OSA after PAP therapy compared with non-smokers (P=0.034, adjusted for confounders). Conclusion: Serum leptin level was stable or decreased in non-smokers, while 40% of active smokers had increased leptin level. Therefore, smoking plays a predisposing role in leptin resistance despite PAP therapy in OSA patients.

Are We Underestimating the Central Components of the Mixed Apneas?-A Hypothesis for Revised Scoring.

PURPOSE: Apneas are classified in three categories, as obstructive, central, and mixed types. Mixed apneas are calculated together with the obstructive events in diagnosing obstructive sleep apnea syndrome (SAS). The clinical significance of mixed apneas needs to be specified. METHODS: Patients with obstructive SAS having an index of mixed apneas ≥5/hour were evaluated. A new approach was developed to score the mixed apneas, and calculated them together with either obstructive or central type of events, depending on their obstructive and central components. The relationship between the development of complex SAS and the indices of abnormal respiratory events per standard and revised scoring was evaluated. RESULTS: Ten of 56 patients (17.9%) developed complex SAS at titration polysomnography. The mean index of mixed apneas per standard scoring was significantly higher in patients who did not develop complex SAS ( P = 0.006). The use of newly developed method in scoring mixed apneas resulted that three patients (5.4%) fulfilled the diagnostic criteria for the central SAS at first-night polysomnography ( P < 0.001), and all of them had developed complex SAS at titration night requiring other modes of positive airway pressure therapy than the continuous mode ( P = 0.004). Curve estimation models showed that the change from mixed apneas to central apneas was highly significant in patients developing complex SAS ( r2 = 0.501; P = 0.022). CONCLUSIONS: Our study showed that the summation of mixed apneas with the obstructive events conventionally underestimates the central components and the diagnosis of central SAS, which are fundamental in the risk stratification of complex SAS.

Long latency trigemino-cervical reflex in restless legs syndrome.

OBJECTIVE: The trigemino-cervical complex (TCC) seems under dopaminergic inhibitory control and the abnormalities of trigemino-cervical reflex (TCR) have been reported in disorders associated with the dopaminergic system and various pain disorders. If the inhibitory response in TCC is likely dopaminergic, we hypothesized that TCR, which has never been evaluated in restless legs syndrome (RLS) patients before, would be also abnormal. METHODS: TCR was recorded from bilateral sternocleidomastoid and splenius capitis muscles in consecutive 15 drug-naive RLS patients and 16 age- and sex-matched healthy subjects. The right and left infraorbital branches of the trigeminal nerve were stimulated by percutaneous electrical stimulation separately. The presence rates, onset latencies, amplitudes, and durations of responses were measured and compared between patients with RLS and controls. RESULTS: The presence rates, onset latencies and amplitudes of TCR responses were similar between RLS patients and controls, however, the durations of responses were bilaterally longer in RLS patients compared to healthy volunteers. CONCLUSIONS: Hyperexcitability of TCR suggests defective sensory processing in the brainstem probably due to impairment of descending inhibitory dopaminergic system in RLS. The sensitization of TCC in RLS patients may also be a possible factor that might explain the association of RLS and pain disorders.

The REM-sleep-related characteristics of narcolepsy: a nation-wide multicenter study in Turkey, the REMCON study.

INTRODUCTION: Narcolepsy type 1 (NT1) is caused by hypocretin deficiency, the pathophysiology of narcolepsy type 2 (NT2) has not been delineated. Except for the hypocretin deficiency and cataplexy, all clinical and laboratory features used in the diagnosis of NT2 are identical to those used for NT1. The aim of this study was to assess the rapid eye movement (REM) sleep-related characteristics in the patients with narcolepsy; the characteristics of REM sleep in polysomnography (PSG) and multiple sleep latency test (MSLT) recordings, the quantification of REM sleep without atonia (RSWA) and atonia index, and the analysis of rapid eye movements (REMs) during REM sleep. MATERIALS AND METHODS: This study was planned by the Sleep Medicine Study Group of the Turkish Neurology Society, and conducted in 11 centers in eight cities in Turkey. The analysis of RSWA was analyzed by reviewing all REM sleep periods on nocturnal PSG and MSLT recordings per standard criteria. The total duration of the increased muscle tone during REM sleep in the chin and bilateral leg electromyography (EMG) recordings was calculated as RSWA index. The REMs index was also investigated the relation to the RSWA. RESULTS: A total of 274 patients were involved; 147 patients (53.6%) were males and 127 patients (46.4%) were females; the mean age was 29.1 ± 12.0 years. The diagnosis of NT1 was made in 166 patients (60.6%), and 108 patients (39.4%) were diagnosed as having NT2. The mean Epworth sleepiness scale score was significantly higher in patients with NT1 than the patients with NT2 (P = 0.001). The diagnosis of REM sleep behavior disorder (RBD) was made in 19.3% of the patients with NT1 versus in 2.8% of the patients with NT2 (P < 0.001). The percentage of SOREMP in PSG recordings was significantly higher in patients with NT1 (37.1%) than those with NT2 (18.9%, P = 0.001). MSLT showed that the mean sleep latency was shorter in patients with NT1 compared to those with NT2 (P < 0.001). The total duration of REMs on electrooculography recordings was also significantly higher in patients with RSWA in comparison with the patients without RSWA (P = 0.002). Total duration of REMs was significantly and positively correlated with the duration of RSWA on chin-EMG and leg-EMG recordings (P = 0.001). ROC analyses showed an RSWA index of ≥2% for the RSWA on chin-EMG with a sensitivity of 86.7% and a specificity of 71.3% (P < 0.001). The REMs index ≥20% was associated with the presence of RSWA with a sensitivity of 70.0% and a specificity of 57.1% (P = 0.008). CONCLUSIONS: In this nation-wide study, we identified for the first time that the increase in REMs density during REM sleep may be a major correlate of the RSWA. Significant positive correlations were demonstrated between the total duration of REMs on electrooculography recordings and the mean durations of RSWA in both chin and leg EMG recordings. A REMs index of >20% was demonstrated to have a moderate sensitivity and specificity in the diagnosis of RSWA. As observed in chin RSWA index, REMs index also showed a significantly high association with RBD, in comparison to RSWA per standard criteria.

Classical complement pathway factor alterations in narcolepsy.

OBJECTIVE: Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. METHODS: Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. RESULTS: C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. CONCLUSION: Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.

Polysomnographic characteristics of sleep-related bruxism: What are the determinant factors for temporomandibular disorders?

OBJECTIVE: This study aimed to evaluate the clinical and polysomnographic characteristics of sleep bruxism (SB) and delineate the determinant factors for temporomandibular disorders (TMD). METHODS: Forty-six patients were allocated into the SB group (n = 26) and control group (n = 20). The signs and symptoms of TMD were recorded using the Research Diagnostic Criteria for TMD. Patients underwent a full-night polysomnographic recording and masseter and temporal muscle electromyographic recordings. Clinical and polysomnographic data in patients with SB were analyzed in relation to TMD. RESULTS: The presence of TMJ sounds was significantly correlated with the number of bruxism bursts. Intra-articular pain in the TMJ was neither correlated with clinical nor polysomnographic parameters in patients with SB. CONCLUSION: Lower sleep efficiency in patients with SB was caused by a higher number of bruxism episodes. Morning headaches were associated with the severity of SB during rapid eye movement sleep.

Changes in sleep structure and sleep spindles are associated with the neuropsychiatric profile in paradoxical insomnia.

AIM: Sleep spindles have an important role in the pathophysiology and perception of sleep. We aimed to investigate the link between sleep spindles and microstructural architecture of sleep in regard to psychiatric characteristics in paradoxical insomnia. METHOD: A total of 40 participants (20 with paradoxical insomnia, 20 healthy controls) were included in the study. All participants were evaluated by somnologists and undergone a full-night polysomnography at sleep laboratory. In addition, psychiatric interview was made by the same psychiatrist, and questionnaires were performed to assess the dimensions of the personality such as the neuroticism or extroversion (Eysenck Personality Questionnaire, EPQR-A); to evaluate the tendency to exaggerate somatic perceptions (Somatosensory Amplification Scale, SSAS), somatic parts of dissociation (Somatoform Dissociation Questionnaire, SDQ-20), and somatization (Somatization Scale, SS); to measure participants' feelings about their health and disease anxiety (Health Anxiety Inventory, HAI-18), and the level of uncontrollable and persistent anxiety (Penn State Worry Questionnaire, PSWQ); to investigate the tendency to ruminative thinking (Ruminative Thought Style Questionnaire, RTSQ), alexithymia (Toronto Alexithymia Scale, TAS-20); and to define the presence and the severity of depressive symptoms (Beck Depression Inventory, BDI). RESULTS: The duration and frequency of the sleep spindles were similar between two groups, while the density was significantly decreased in paradoxical insomnia. The duration of sleep spindles, on the other hand, showed positive correlations with the extroversion dimension scores of EPQR-A and PSWQ scores. DISCUSSION: Sleep protective mechanisms are disturbed in paradoxical insomnia as shown by the lower density of sleep spindles. In addition, fast spindle activity is associated with the personality traits, characterized by an increase in the expression of feelings and the level of anxiety.

Contribution of brainstem circuits in pathophysiology of NREM-sleep parasomnias.

OBJECTIVE: We aimed to investigate the brainstem circuits to reveal if there was any abnormality in these circuits in clinically diagnosed patients with NREM parasomnias during wakefulness. METHODS: Twelve patients with NREM-sleep parasomnia diagnosed according to ICSD-3 criteria and a control group of 16 healthy subjects were enrolled into our study. We analyzed the auditory startle reflex (ASR), blink reflex (BR), prepulse inhibition (PPI) of BR and recovery excitability of BR. RESULTS: There was a trend for longer responses from orbicularis oculi and sternocleidomastoid muscles after auditory stimulation in the patients compared to those in the healthy subjects. The recovery percentages at 200 ms and 300 ms showed a borderline significance in the patients. No significant difference was found in the R2-PPI between the patients and healthy subjects. CONCLUSIONS: Our results suggest a mildly enhanced ASR and relatively early facilitation of BR excitability in patients with NREM-sleep parasomnia during daytime. Although our findings suggest involvement of brainstem networks in NREM-sleep parasomnia during wakefulness, it would be better to study these networks at night and during daytime to see if there is any contribution.

Peripheral blood B cell subset ratios and expression levels of B cell-associated genes are altered in benign multiple sclerosis.

The interplay between the immune system, sleep dysfunction and cognitive impairment participates in the progression of disability in multiple sclerosis (MS). Our aim was to identify molecular pathways and B cell associated with separate components of MS disability. Benign MS, non-benign MS patients and healthy controls were recruited. Patients underwent polysomnography and cognitive studies. Microarray and bioinformatics analysis performed using peripheral blood mononuclear cell samples identified B cell-associated genes with the most significantly altered expression. Expression levels of these genes were validated by real-time PCR and peripheral blood cell subsets were examined by flow cytometry. Putative correlations among clinical and laboratory parameters were investigated by correlation network analysis. Sleep and cognitive functions were equally impaired in BMS and NBMS. BMS patients showed significantly reduced memory B cell and increased regulatory B cell percentages than NBMS patients. Among genes that were selected by bioinformatics, levels of BLK, BLNK, BANK1, FCRL2, TGFB1 and KCNS3 genes were significantly different among study subgroups. Correlation network analysis showed associations among physical-cognitive disability and sleep dysfunction measures of MS versus expression levels of selected genes. BMS and NBMS differ by physical disability but not cognitive and sleep dysfunction. Different components of disability in MS are associated with peripheral blood B cell ratios and B cell related gene expression levels. Thus, it is likely that altered B cell functions participate in the progression of disability in MS.

Restless sleep disorder in children with NREM parasomnias.

STUDY OBJECTIVES: Restless sleep disorder (RSD) is a newly defined sleep disorder in the pediatric age group. Here, we investigated the frequency of RSD and the sleep characteristics in children with NREM (non-rapid eye movements) parasomnias associated with RSD. METHODS: We analyzed all patients with NREM parasomnias for the last 1 year, and investigated the clinical and polysomnographic characteristics. RESULTS: Twenty-eight children with NREM parasomnias and age- and gender-matched 20 healthy children were analyzed. The diagnosis of RSD was made in eight children with NREM parasomnias (28.6%), and none of the children had RSD in controls (p = 0.008). The most common diagnosis among children with RSD was somnambulism (six children), but not significantly (p = 0.308). Sleep efficiency was lower in children with RSD than those without RSD (p = 0.033). In cyclic alternating pattern analysis (CAP), CAP rate, durations and the indices of phases A1, A2, and A3 were significantly higher in children with NREM parasomnias in compared to controls. CAP parameters between children with or without RSD; however, were similar, except for higher index of phase A3 in children with RSD, suggesting arousal reactions accompanying RSD. CONCLUSIONS: We demonstrated that RSD was present in almost one third of the children with NREM parasomnias. Sleep quality was worse in children with NREM parasomnias and RSD. An increase in sleep instability compatible with NREM parasomnia was present, while an increased phase A3 in RSD was remarkable. RSD is associated with a worse sleep quality and increased arousals, and should be questioned in children with NREM parasomnias.

The role of pedunculopontine nucleus in isolated REM sleep behavior disorder and REM sleep without atonia.

INTRODUCTION: The aim of this study was to analyze the functions of pedunculopontine nucleus (PPN) in isolated REM sleep behavior disorder (iRBD) and REM sleep without atonia (RSWA) to investigate the role of PPN in dream-enacting motor behaviors in RBD. We evaluated the activity of PPN through the prepulse modulation (PPM) together with other brainstem reflexes to investigate the differences in changes at brainstem. METHODS: We included nine patients with isolated RSWA and 10 patients with iRBD. For diagnosis, all patients underwent polysomnography. None of the patients had parkinsonism or dementia. We also included 17 healthy participants with similar age and sex. Blink reflex (BR), PPM of BR, recovery excitability of BR, and auditory startle reflex (ASR) were recorded in all participants. RESULTS: There was a prepulse inhibition deficit in iRBD and RSWA groups compared to healthy subjects. The BR-R2 recovery at 200 ms interval was also higher in patients with iRBD and RSWA. In ASR recordings, the response probabilities were higher in the RBD group compared to RSWA and control groups. CONCLUSION: The PPM was abnormal in both iRBD and RSWA whereas ASR was enhanced in iRBD. We suggest that there are certain similarities and differences in the pathophysiologies of iRBD and RSWA.