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.

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.

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.

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.

A cross-sectional study on restless legs syndrome (RLS) in polycythemia vera (PV): is iron deficiency the only culprit?

INTRODUCTION: In polycythemia vera (PV) patients undergoing phlebotomy, iron deficiency (ID) may develop. ID has been linked to restless legs syndrome (RLS), and in one study, 29.6% of PV patients had RLS. We aimed to evaluate the frequency of RLS in PV and to evaluate factors that might play a role in RLS development among PV and essential thrombocythemia (ET) patients. METHODS: We consecutively included PV cases as the patient group, and ET and ID patients and healthy subjects (HSs) were included as controls. Those with conditions that could lead to RLS were excluded. All subjects were questioned according to the diagnostic criteria of the International Restless Legs Syndrome Study Group. RESULTS: Twenty-seven PV, 23 ET, and 22 ID patients and 23 HSs were included. RLS was detected in 25.9%, 34.8%, and 45.5% of PV, ET, and ID patients, respectively. None of the HSs had RLS. In univariate analysis, interferon-α and anagrelide use, magnesium levels, and the Leeds assessment of neuropathic symptoms and signs (LANSS) scores had a significant impact on RLS in PV and ET patients (p = 0.014, p = 0.032, p = 0.036, and p = 0.003, respectively). CONCLUSION: RLS was more common among PV and ET patients than HSs, which was irrespective to the iron status. RLS was more frequent in ET patients than that observed in PV cases, indicating that ID may not be the only causative factor for RLS development in PV. Further prospective studies are needed to determine the prevalence and risk factors of RLS developing in PV and ET.

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.

Neutrophil­to­lymphocyte ratio as a marker of inflammation in restless legs syndrome during pregnancy.

PURPOSE: The pregnancy is accepted as an independent risk factor for restless legs syndrome/Willis-Ekbom disease (RLS/WED). The neutrophil-to-lymphocyte ratio (NLR) was recently reported in the pathophysiology of RLS/WED. In this report, we investigated the relationship between the presence of RLS/WED and the levels of NLR in pregnancy. METHODS: We included 268 pregnant women attending routine prenatal visits; 148 women had RLS/WED, and 120 women without RLS/WED were the control group. A pre-formed questionnaire was administered to all participants regarding demographic characteristics, habitual behaviors, detailed medical history and questions about RLS/WED including disease duration, severity, and family history. Laboratory investigations were performed in all participants regarding the complete blood count, NLR, fasting blood glucose, blood urea nitrogen, creatinine, ferritin, and total iron binding capacity. RESULTS: NLR was significantly higher in pregnant women with RLS/WED as compared to those without it (3.9±0.9 versus 3.5±1.1, p=0.039). Smoking was also significantly more common in pregnant women with RLS/WED (p=0.022). NLR significantly increased as the gestational period progressed, even after the adjustments for age, BMI, and smoking (p=0.035). Higher NLR in pregnant women with RLS/WED was especially prominent in the 3rd trimester, although the difference was not significant. CONCLUSION: These results may suggest that an increased inflammation demonstrated by the increased NLR, may, in part, play a role in higher prevalence of RLS/WED in pregnancy, especially in late gestational weeks (Tab. 2, Fig. 1, Ref. 34). Text in PDF www.elis.sk Keywords: neutrophil-to-lymphocyte ratio, restless legs syndrome/Willis-Ekbom disease, pregnancy, inflammation.

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.

Evaluating Pain Management Practices for Cancer Patients among Health Professionals: A Global Survey.

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients' reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large.

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.

Quality of life and burden in family caregivers of patients with advanced cancer receiving specialized palliative care.

Background: The caregivers of advanced cancer patients face many physical, psychological, social, and economic problems. In this study, the quality of life and burden in the primary family caregiver of patients with advanced cancer receiving inpatient palliative care were investigated. Methods: A total of 200 patients with advanced cancer hospitalized at palliative care center and primary caregivers were included. Functional capacities of patients were evaluated with Karnofsky Performance Scale and need of care with Katz index. The Turkish version of World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF TR) was used to assess the quality of life of caregivers. Results: The median Karnofsky Performance score of patients was found to be 30% and Katz Index score to be 2. The mean WHOQOL-BREF TR domain scores of family caregivers were 48.96 (Standard deviation (SD) =12.67) for physical health, 59.21 (SD=14.09) for psychological status, 56.83 (SD=20.91) for social relations, and 55.67 (SD=14.13) for environmental domain. Scores of psychological and environmental subscales were lower in women caregivers. The environmental subscale showed a significant difference in terms of education. The score of social relations subscale of the care giving spouse was lower than caregiving children and siblings. The score of environmental subscale of caregivers with insufficient income was found to be lower than caregivers with sufficient income. Karnofsky Performance and Katz Index scores and subscales of WHOQOL-BREF TR did not reveal any significant relation. Conclusion: This study showed that all subscales of quality of life are impaired in caregivers of advanced cancer patients, physical health being the most prominent.

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.

Acute-Onset Hemiparkinsonism Secondary to Subacute-Chronic Subdural Hematoma.

Subdural hematomas constitute rare causes of secondary Parkinsonism in elderly. Subacute or chronic subdural hematomas occur in the elderly following minor head trauma or even without a remarkable history of trauma. A 69-year-old woman admitted with a rapidly progressive acute-onset hemiparkinsonism on the left side of her body. She denied any precipitating event before the onset of her symptoms, and her medical history was unremarkable. The anti-Parkinsonian therapy showed no benefit, but gradually worsening of the symptoms was observed. Her brain magnetic resonance imaging revealed a large subacute-chronic subdural hematoma on the right side with a mass effect on the basal ganglia structures, contralateral to her symptomatology. On thorough questioning, she confessed to having fallen out of the bed at night almost four weeks ago, three-weeks before the onset of her symptomatology. She had no complications associated with this fall and merely remembered this event. She denied any history of rapid eye movements (REM) sleep behavior disorder. The anti-Parkinsonian treatment was discontinued; the subdural hematoma was evacuated via burr hole drainage surgery. Her symptoms disappeared instantly after the surgery, with a normal neurologic examination one week after the surgery.

Restless legs syndrome in pediatric onset multiple sclerosis.

BACKGROUND: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) was shown to have a high prevalence among adults with multiple sclerosis (MS). OBJECTIVE: We aimed to investigate the prevalence of RLS/WED and to define the disease characteristics in young patients with pediatric onset multiple sclerosis (POMS) METHOD: 50 patients with POMS were questioned for the presence of RLS/WED. The demographic, clinical and laboratory data were compared between POMS patients with and without RLS/WED, including the total number of clinical and/or radiological MS attacks, interval between first two attacks, EDSS, number of the hyperintense and/or contrast-enhancing lesions, localization of demyelinating lesions, IgG index in cerebrospinal fluid, oligoclonal band, serum ferritin, C-reactive protein, ratio of neutrophil to lymphocyte count, and 25­hydroxy vitaminD. RESULTS: Eleven patients (22%) had RLS/WED - mostly of moderate in severity (54.5%). Mean EDSS score was significantly higher in POMS patients with RLS/WED than those without (p = 0.003). The Ig G index was almost two times higher in POMS patients with RLS/WED, but it failed to reach to the statistically significant level (p = 0.073). CONCLUSION: Our study demonstrated high prevalence of RLS/WED in young patients with POMS. Higher EDSS scores in patients with POMS and RLS/WED indicates disease-related factors in the emergence of RLS/WED.