Lifestyle factors associated with symptoms suggestive of restless legs syndrome in Korean adolescents.

OBJECTIVE: Restless legs syndrome (RLS) is a common sleep disorder among adolescents. This study aimed to investigate the lifestyle factors and sleep disturbances associated with the symptoms suggestive of RLS in Korean adolescents. METHODS: In this cross-sectional study, we investigated a total of 25,789 adolescents (mean age, 15.8 ± 1.7 years; male, 48.5 %). The presence of symptoms suggestive of RLS was assessed with a single question about RLS in the Global Sleep Assessment Questionnaire. We performed multiple logistic regression analysis to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of lifestyle factors and sleep disturbances that were independently associated with adolescent RLS. RESULTS: The prevalence of RLS-suggestive symptoms was 5.1 % among adolescents. After adjustment, lifestyle factors associated with symptoms suggestive of RLS were occasional alcohol consumption (OR, 1.245; 95 % CI, 1.006-1.540) and proneness to Internet addiction (OR, 1.027; 95 % CI, 1.021-1.033). Bedtime behaviors associated with RLS-suggestive symptoms were sleeping with a doll or pet (OR, 1.194; 95 % CI, 1.032-1.381) and sleeping with a TV or radio on (OR, 1.366; 95 % CI, 1.156-1.614). Male sex, frequent snoring and witnessed apnea, perceived sleep insufficiency, excessive daytime sleepiness were also associated with RLS-suggestive symptoms in adolescents. CONCLUSIONS: Adolescents with symptoms suggestive of RLS were associated with different lifestyle factors compared to adults with RLS. Further research is needed to determine the clinical implications of lifestyle factors in adolescent RLS.

Risk of encephalitis and meningitis after COVID-19 vaccination in South Korea: a self-controlled case series analysis.

BACKGROUND: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. METHODS: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1-28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. RESULTS: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91-1.16). CONCLUSIONS: Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies and eventually phenoconverts to overt neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Associations of baseline resting-state electroencephalography (EEG) with phenoconversion have been reported. In this study, we aimed to develop machine learning models to predict phenoconversion time and subtype using baseline EEG features in patients with iRBD. METHODS: At baseline, resting-state EEG and neurological assessments were performed on patients with iRBD. Calculated EEG features included spectral power, weighted phase lag index, and Shannon entropy. Three models were used for survival prediction, and four models were used for α-synucleinopathy subtype prediction. The models were externally validated using data from a different institution. RESULTS: A total of 236 iRBD patients were followed up for up to 8 years (mean 3.5 years), and 31 patients converted to α-synucleinopathies (16 PD, 9 DLB, 6 MSA). The best model for survival prediction was the random survival forest model with an integrated Brier score of 0.114 and a concordance index of 0.775. The K-nearest neighbor model was the best model for subtype prediction with an area under the receiver operating characteristic curve of 0.901. Slowing of the EEG was an important feature for both models. CONCLUSIONS: Machine learning models using baseline EEG features can be used to predict phenoconversion time and its subtype in patients with iRBD. Further research including large sample data from many countries is needed to make a more robust model.

Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study.

INTRODUCTION: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia. METHODS: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing. RESULTS: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes. DISCUSSION: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion. HIGHLIGHTS: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion.

Fatigue or excessive daytime sleepiness: which is more closely related to depression?

OBJECTIVE/BACKGROUND: This study investigated fatigue and excessive daytime sleepiness to determine which was more closely related to depression in the general population. PATIENTS/METHODS: Participants were investigated across 15 South Korean districts. Excessive daytime sleepiness, fatigue, and depression were evaluated using the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Patient Health Questionnaire-9 (PHQ-9), respectively. Depression was defined as PHQ-9 ≥ 10. The authors classified the combination of excessive daytime sleepiness and fatigue as excessive daytime sleepiness with fatigue (E+F+, ESS ≥ 11, FSS ≥ 36), fatigue without excessive daytime sleepiness (E-F+, ESS < 11, FSS ≥ 36), excessive daytime sleepiness without fatigue (E+F-, ESS ≥ 11, FSS < 36), and no fatigue and excessive daytime sleepiness (E-F-, ESS < 11, FSS < 36). RESULTS: Among 2,493 participants (1,257 women), mean age was 47.9 ± 0.3 years. The prevalence of depression, fatigue, and excessive daytime sleepiness was 8.4% (n = 210), 30.8% (n = 767), and 15.3% (n = 382), respectively. The frequency of the four categories with depression (vs. controls) was as follows.: E+F+ (n = 67, 31.9% vs. 7.3%) (P < 0.001), E-F+ (n = 71, 33.8% vs. 20.3%) (P < 0.001), E+F-( n = 16, 7.6% vs. 5.8%) (P = 0.294), and E-F- (n = 56, 26.7% vs. 66.6%) (P < 0.001). After adjusting for covariates, depression was associated with E+F+ (odds ratio, OR 8.804, 95% confidence interval (CI) 5.818-13.132), E-F+ (OR 3.942, 95% CI 2.704-5.747), E+F- (OR 2.812, 95% CI 1.542-5.131), and E-F- (reference). Additionally, we performed logistic regression according to two categories. There was no significant difference in the association of depression between E+F- (reference) and E-F+ (OR 1.399, 95% CI 0.760-2.575). CONCLUSION: Although fatigue and excessive daytime sleepiness were associated with depression regardless of the presence of each other, we could not clarify which was more closely related to depression.

Otogenic Enterobacter cloacae meningitis complicated with pneumocephalus.

Pneumocephalus refers to a pathologic collection of gas within the cranial cavity and is mostly caused by head trauma and neurosurgical procedures. Spontaneous nontraumatic pneumocephalus is a very rare condition. We herein report an unusual case of community-acquired bacterial meningitis with a combination of acute otitis media, Enterobacter cloacae, and nontraumatic pneumocephalus. A 75-year-old woman presented with fever, mental change, and neck stiffness. Brain imaging demonstrated pneumocephalus and fluid collection in the left mastoid air cells. E. cloacae was isolated from both blood and otorrhea cultures, and the patient was successfully treated with intravenous ceftazidime for 3 weeks. Although E. cloacae is a very rare cause of community-acquired bacterial meningitis in adults, it should be considered as a possible pathogen in otogenic meningitis complicated with pneumocephalus.

Quantitative Network Comparisons of REM Sleep Without Atonia Across the α-Synucleinopathy Spectrum: A Systematic Review.

Purpose: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by REM sleep without atonia (RWA) and is regarded as the prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). RWA is also associated with neurodegeneration driven by α-synucleinopathy. However, the level of RWA across the α-synucleinopathy spectrum remains elusive. We aimed to rate the percentage of RWA across the α-synucleinopathy spectrum, encompassing prodromal and overt phenotypes. Methods: A systematic search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases. We included cohort, cross-sectional, and case-control studies comparing the RWA percentage during REM sleep evaluated by tonic chin activity (RWA%-T) or by phasic chin activity (RWA%-P) across the α-synucleinopathy spectrum. Bayesian network meta-analysis was used to combine both direct and indirect evidence regarding the group differences in the RWA%-T and RWA%-P. The surface under the cumulative ranking curve was used to estimate the ranked probability. Results: Fifteen articles met the inclusion criteria. The investigations included 204 iRBD, 295 PD with RBD (PDwtRBD), 187 PD without RBD (PDwoRBD), 42 MSAwtRBD, 9 DLBwtRBD patients, and 246 controls. MSAwtRBD ranked first in RWA%-T, whereas iRBD ranked first in RWA%-P. RWA% in PDwoRBD patients was comparable to that in the controls and was lower than that in PDwtRBD patients. Conclusion: Overt phenotypes such as MSAwtRBD and PDwtRBD ranked high in RWA%-T, whereas iRBD, a prodromal type, ranked highest in RWA%-P. Taken together, our data suggest that the percentage of neurodegeneration in RBD patients may be associated with RWA%-T rather than RWA%-P. Prospero Registration Number: CRD42021276445.

Quantitative measurement of motor activity during sleep in isolated REM sleep behavior disorder patients using actigraphy before and after treatment with clonazepam.

STUDY OBJECTIVES: We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures. RESULTS: Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered "much or very much improved" on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman's rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements). CONCLUSIONS: Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

STUDY OBJECTIVES: The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). METHODS: We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RESULTS: RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). CONCLUSIONS: Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.

Characterization of attentional event-related potential from REM sleep behavior disorder patients based on explainable machine learning.

BACKGROUND AND OBJECTIVE: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of neurodegeneration and is associated with cortical dysfunction. The purpose of this study was to investigate the spatiotemporal characteristics of cortical activities underlying impaired visuospatial attention in iRBD patients using an explainable machine-learning approach. METHODS: An algorithm based on a convolutional neural network (CNN) was devised to discriminate cortical current source activities of iRBD patients due to single-trial event-related potentials (ERPs), from those of normal controls. The ERPs from 16 iRBD patients and 19 age- and sex-matched normal controls were recorded while the subjects were performing visuospatial attentional task, and converted to two-dimensional images representing current source densities on flattened cortical surface. The CNN classifier was trained based on overall data, and then, a transfer learning approach was applied for the fine-tuning to each patient. RESULTS: The trained classifier yielded high classification accuracy. The critical features for the classification were determined by layer-wise relevance propagation, so that the spatiotemporal characteristics of cortical activities that were most relevant to cognitive impairment in iRBD were revealed. CONCLUSIONS: These results suggest that the recognized dysfunction in visuospatial attention of iRBD patients originates from neural activity impairment in relevant cortical regions and may contribute to the development of useful iRBD biomarkers based on neural activity.

Emotional and Environmental Factors Aggravating Dream Enactment Behaviors in Patients with Isolated REM Sleep Behavior Disorder.

Objective: To identify emotional and environmental factors that aggravate dream enactment behaviors (DEBs) in isolated rapid eye movement (REM) sleep behavior disorder (iRBD). Methods: In this cross-sectional study, a total of 96 polysomnography-confirmed iRBD patients (mean age, 68.5 years; men, 68%) and their caregivers completed questionnaires regarding potential aggravating factors related to DEBs, including emotion/feelings (stress, anger, anxiety, depressive mood, fatigue, pain), food (alcohol, caffeine, overeating in the evening, fasting/hunger), activities and sleep patterns (strenuous exercise, sex before bed, conflict/fighting, sleep deprivation, oversleeping, sleeping away from home, watching TV before bed), weather/environmental factors (cloudy or rainy weather, heat, cold, noise) and medication (skipping medication, taking hypnotics). Results: The patients reported that stress (61%) was the most aggravating factor for DEBs, followed by anxiety (56%), anger (51%), fatigue (49%), and watching TV before bed (46%). Similarly, the caregivers reported that these factors were most relevant to the aggravation of DEBs in the patients, although some factors were ranked differently. In the subgroup analyses, aggravating factors for DEBs did not differ by RBD symptom severity. Interestingly, the proportion of patients experiencing DEB aggravation by stress, anxiety and depressive mood was significantly higher in women than in men. Furthermore, depressed patients reported that stress and cloudy or rainy weather made DEBs worse than nondepressed patients. Conclusion: Our results suggest that DEBs in iRBD patients may be mainly aggravated by emotional factors. These negative effects appeared to be more prominent in female and depressed patients.

Association of Nucleus Basalis of Meynert Functional Connectivity and Cognition in Idiopathic Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND AND PURPOSE: Cognitive impairments are common in isolated rapid-eye-movement sleep behavior disorder (iRBD), in which the cholinergic system may play an important role. This study aimed to characterize the cortical cholinergic activity using resting-state functional connectivity (FC) of the nucleus basalis of Meynert (NBM) according to the cognitive status of iRBD patients. METHODS: In this cross-sectional study, 33 patients with polysomnography-confirmed iRBD and 20 controls underwent neuropsychological evaluations and resting-state functional magnetic resonance imaging. Thirteen of the iRBD patients had mild cognitive impairment (iRBD-MCI), and the others were age-matched patients with normal cognition (iRBD-NC). The seed-to-voxel NBM-cortical FC was compared among the patients with iRBD-MCI, patients with iRBD-NC, and controls. Correlations between average values of significant clusters and cognitive function scores were calculated in the patients with iRBD. RESULTS: There were group differences in the FC of the NBM with the left lateral occipital cortex and lingual gyrus (adjusted for age, sex, and education level). The strength of FC was lower in the iRBD-MCI group than in the iRBD-NC and control groups (each post-hoc p<0.001). The average NBM-lateral occipital cortex FC was positively correlated with the memory-domain score in iRBD patients. CONCLUSIONS: The results obtained in this study support that cortical cholinergic activity is impaired in iRBD patients with MCI. FC between NBM and posterior regions may play a central role in the cognitive function of these patients.

White matter tract-specific microstructural disruption is associated with depressive symptoms in isolated RBD.

OBJECTIVE: White matter (WM) tract-specific changes may precede gray matter loss in isolated rapid eye movement sleep behavior disorder (iRBD). We aimed to evaluate tract-specific WM changes using tract-specific statistical analysis (TSSA) and their correlation with clinical variables in iRBD patients. METHODS: This was a cross-sectional single-center study of 50 polysomnography-confirmed iRBD patients and 20 age- and sex-matched controls. We used TSSA to identify tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in fourteen major fiber tracts and analyzed between-group differences in these values. Correlations between FA or MD values and clinical variables, including RBD symptom severity, depression and cognition, were evaluated. RESULTS: Patients with iRBD showed lower FA in the right anterior thalamic radiation (ATR) and higher MD in the bilateral ATR and right inferior fronto-occipital fasciculus (IF-OF) than controls after adjusting for age, sex, and years of education. MD values in the IF-OF positively correlated with scores on the Korean version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-KR, p = 0.042) and the Korean version of the geriatric depression scale (GDS-K, p = 0.002) in iRBD patients. Only GDS-K scores independently correlated with IF-OF MD values after adjusting for RBDQ-KR scores (adjusted p = 0.026). CONCLUSION: This study suggests WM microstructural disruption in the bilateral ATR and right IF-OF in patients with iRBD and that alterations in the IF-OF may contribute to depressive symptoms.

Comparison of rapid eye movement without atonia quantification methods to diagnose rapid eye movement sleep behavior disorder: a systematic review.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep without atonia (RWA) is essential for diagnosing REM sleep behavior disorder (RBD). Manual and automatic quantifications of RWA that use different criteria have been validated. This study compared the RWA quantification methods for diagnosing RBD. METHODS: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were systemically searched for studies published from inception to December 2021. The inclusion criteria were cohort, cross-sectional, and case-control studies assessing the sensitivity and specificity of RWA quantification methods. Pooled estimates of the sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were determined. Risk of bias and certainty of evidence was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and the Grading of Recommendations, Assessment, Development, and Evaluations framework, respectively. RESULTS: Fourteen articles including 402 patients with RBD met the inclusion criteria. Manual methods evaluating any chin and phasic flexor digitorum superficialis (FDS) activity had the highest DOR (138.8, 95% CI = 21.8% to 881.7%) and AUC (0.9686). The automatic REM atonia index (RAI) showed similar or higher sensitivity (89.1%, 95% CI = 84.6% to 92.7%) but a lower specificity (73.5%), DOR (43.1), and AUC (0.9369) than the manual techniques. CONCLUSIONS: In this meta-analysis, manual RWA quantification that employed chin or phasic FDS activity had the best RBD diagnostic performance. The automatic RAI method may be useful for screening patients with RBD. The results should be interpreted carefully because of the high risk of bias in patient selection and significant heterogeneity among the studies. PROSPERO REGISTRATION NUMBER: CRD42021276445.

Association between Self-Perceived Periodic Limb Movement during Sleep and Excessive Daytime Sleepiness Depend on Restless Leg Symptoms in Korean Adolescents.

Although periodic limb movement during sleep (PLMS) and restless legs syndrome (RLS) are common in children and adolescents, they are relatively overlooked as a target of treatment. PLMS has been evaluated as having a lower clinical significance than RLS. This study examined the relationship of socio-behavioral factors of PLMS in Korean adolescents and checked whether PLMS is associated with excessive daytime sleepiness (EDS), depending on whether restless legs symptoms accompany it. In a cross-sectional study, 25,789 adolescents between 12 and 18 years of age (15.76 ± 1.73 years; female 51.49%) were evaluated using an online survey. Various self-report questionnaires were used to assess PLMS and RLS symptoms, EDS, sleep habits, and various socio-behavioral factors. The prevalence of self-perceived PLMS and restless legs symptoms were 903 (3.50%) and 1311 (5.08%), respectively. Of the 1311 participants, 399 had self-perceived PLMS. The odds ratios (ORs) for self-perceived PLMS in participants with restless legs symptoms were: males (OR = 1.528; 95% CI: 1.145-2.040), usually/always experienced apnea apnea (OR, 3.006; 95% CI, 1.954-4.624), increased proneness to Internet addiction (OR = 1.013; 95% CI: 1.001-1.025), sometimes/often consuming coffee (OR = 1.312; 95% CI: 1.015-1.695), EDS (OR = 0.826; 95% CI: 0.488-1.398), and perceived insufficient sleep (OR = 1.143; 95% CI: 0.835-1.565). The male gender, witness apnea, consuming coffee, and being prone to Internet addiction were identified as factors significantly associated with self-perceived PLMS in participants with restless legs symptoms. However, EDS and insufficient sleep were associated with self-perceived PLMS in the absence of restless legs symptoms.

Isolated rapid eye movement sleep behavior disorder combined with obstructive sleep apnea: response to treatment and its associated factors.

OBJECTIVE/BACKGROUND: When isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is combined with obstructive sleep apnea (OSA), the pattern of temporal association between REM without atonia (RWA) and apnea-hypopnea events may be related to improvements in RBD symptoms after positive airway pressure (PAP) treatment. We evaluated the frequency of improvement in RBD symptoms after PAP and the relationship of the degree of co-occurrence between RWA and apnea-hypopnea events to RBD symptom improvement after PAP treatment. PATIENTS/METHODS: In an institutional cohort with sleep disorders, 31 patients with video-polysomnography confirmed iRBD and concomitant OSA with an apnea-hypopnea index (AHI) of ≥15/h who received PAP treatment were included. Along with gross video-polysomnography parameters such as AHI and electromyography activity index during REM sleep, a mini-epoch-based parameter apnea-hypopnea-electromyography activity ratio (AH EMG activity ratio) was used to evaluate the co-occurrence between RWA and apnea-hypopnea events. Improvement in RBD symptoms after PAP treatment was designated as a clinical global impression-improvement (CGI-I) score of 0-3 at three-month. RESULTS: Twenty-three (74.2%) patients exhibited improvement in RBD symptoms after PAP treatment. No patient was taking an antidepressant medication. An AH EMG activity ratio of ≥15% (Odds ratio [OR] 10.146, 95% CI 1.302-79.032, P = 0.027) was significantly associated with clinical improvement after PAP treatment in a regression model adjusted for age, sex, AHI, and electromyography activity index during REM. CONCLUSIONS: Treatment of concomitant OSA with PAP can improve symptoms of iRBD. Respiratory events that co-occur with RWA may predict improvement in RBD symptoms after PAP treatment.

Clinical significance of Epstein-Barr virus polymerase chain reaction in cerebrospinal fluid.

Purpose: Epstein-Barr virus (EBV) is implicated in various neurological conditions. However, the relationship between EBV DNA in cerebrospinal fluid (CSF) and central nervous system (CNS) infection is unclear. We evaluated the clinical manifestation of patients with EBV DNA detected in CSF. Methods: We reviewed the medical records of patients admitted to Seoul National University Hospital from January 2000 to March 2021 who underwent EBV polymerase chain reaction (PCR) tests in CSF. The subjects were divided into positive and negative groups depending on the presence of EBV DNA, and further clinical information was obtained from positive patients. Results: CSF EBV PCR tests were performed in 807 patients, and 57 (7.1%) tested positive. Pleocytosis was common (81.1%) in CSF samples with EBV DNA detected, and the proportion was significantly higher than that in samples that were EBV PCR negative (44.5%, p < 0.0001). Among 57 patients with EBV DNA detected in CSF, 51 (89.5%) were diagnosed with CNS infection or inflammatory disorders. Of the 51 patients, 31 (60.8%) had possible etiologies other than EBV. Follow-up evaluation was conducted in 19 of 20 patients, and 63.2% showed a favorable outcome. Conclusion: Positive EBV PCR in CSF is mostly nonspecific and should be interpreted with caution. A comprehensive workup is needed to identify other etiologies before considering EBV as the sole culprit.

Fatigue is associated with depression independent of excessive daytime sleepiness in the general population.

PURPOSE: This study aimed to investigate sleep problems and comorbid conditions associated with fatigue in the general population. METHODS: The data were obtained from a nationwide cross-sectional survey conducted in 2018. The Fatigue Severity Scale was used to assess fatigue. We examined sleep habits, such as workday sleep duration, chronotype, and free-day catch-up sleep, excessive daytime sleepiness (EDS), depression, and other comorbid conditions. We conducted multiple logistic regression analysis with the presence of fatigue as a dependent variable. RESULTS: Of 2,493 adults aged 19 to 92 years, 50% men, mean age was 47.9 ± 16.4 years. The average workday sleep duration was 7.1 ± 1.1 h, and the prevalence of fatigue was 31%. After adjusting for potential confounders, fatigue was associated with EDS (odds ratio [OR] 3.751, 95% confidence interval [CI] 2.928-4.805), depression (OR 3.736, 95% CI 2.701-5.169), perceived insufficient sleep (OR 1.516, 95% CI 1.249-1.839), free-day catch-up sleep (OR 1.123, 95% CI 1.020-1.235), less alcohol intake (OR 0.570, 95% CI 0.432-0.752), and physical inactivity (OR 0.737, 95% CI 0.573-0.948). On subgroup analysis, fatigue was additionally associated with short workday sleep duration (OR 0.899, 95% CI 0.810-0.997) in individuals without EDS. However, among those with EDS, only depression (OR 2.842, 95% CI 1.511-5.343) and less alcohol intake (OR 0.476, 95% CI 0.247-0.915) were associated with fatigue. CONCLUSION: Fatigue was significantly associated with depression independent of EDS. Further research is warranted to better understand the pathophysiological relationship between fatigue, depression, and sleep.