Differences in factors associated with insomnia symptoms between patients with epilepsy with and without depressive symptoms.

OBJECTIVE: To determine if insomnia-related factors differ depending on the presence of depression in patients with epilepsy. METHODS: This cross-sectional multicenter study collected data on depressive symptoms, insomnia symptoms, and excessive daytime sleepiness, which were defined as a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10, an Insomnia Severity Index (ISI) score of ≥ 15, and an Epworth Sleepiness Scale (ESS) of ≥ 11, respectively. Further, uncontrolled seizures were defined as one or more seizures per month during antiseizure medications treatment. A stepwise logistic regression analysis was conducted, with a logistic regression with interaction terms performed to identify differences in insomnia-related factors depending on depressive symptoms. RESULTS: Of 282 adults with epilepsy (men, 58 %; mean age, 40.4 ± 13.9 years), a PHQ-9 score ≥ 10, an ISI score ≥ 15, an ESS score ≥ 11 were noted in 23.4 % (n = 66), 20.2 % (n = 57), and 12.8 % (n = 36), respectively. More patients with depressive symptoms had an ISI score ≥ 15 (56.1 % vs. 9.3 %; p < 0.001) than those without. In multiple logistic regression, uncontrolled seizures (odds ratio [OR], 4.896; p < 0.01), daytime sleepiness (OR, 5.369; p < 0.05), and a history of psychiatric disorders (OR, 3.971; p < 0.05) were identified as significant factors that were more likely to be associated with an ISI score ≥ 15; however, this was only true in patients without depressive symptoms. In contrast, use of perampanel (OR, 0.282; p < 0.05) was less likely associated, while female sex (OR, 3.178; p < 0.05) was more likely associated with an ISI score ≥ 15 only in patients with depressive symptoms. CONCLUSIONS: Insomnia-related factors in patients with epilepsy may differ between patients with and without depression. Our findings of different insomnia-related factors based on the presence of depression may facilitate the management of patients with epilepsy.

qEEG as Biomarker for Alzheimer's Disease: Investigating Relative PSD Difference and Coherence Analysis.

Purpose: Electroencephalography (EEG) is a non-intrusive technique that provides comprehensive insights into the electrical activities of the brain's cerebral cortex. The brain signals obtained from EEGs can be used as a neuropsychological biomarker to detect different stages of Alzheimer's disease (AD) through quantitative EEG (qEEG) analysis. This paper investigates the difference in the abnormalities of resting state EEG (rEEG) signals between eyes-open (EOR) and eyes-closed (ECR) in AD by analyzing 19-scalp electrode EEG signals and making a comparison with healthy controls (HC). Participants and Methods: The rEEG data from 534 subjects (ages 40-90) consisting of 269 HC and 265 AD subjects in South Korea were used in this study. The qEEG for EOR and ECR states were performed separately for HC and AD subjects to measure the relative power spectrum density (PSD) and coherence with functional connectivity to evaluate abnormalities. The rEEG data were preprocessed and analyzed using EEGlab and Brainstorm toolboxes in MATLAB R2021a software, and statistical analyses were carried out using ANOVA. Results: Based on the Welch method, the relative PSD of the EEG EOR and ECR states difference in the AD group showed a significant increase in the delta frequency band of 19 EEG channels, particularly in the frontal, parietal, and temporal, than the HC groups. The delta power band on the source level was increased for the AD group and decreased for the HC group. In contrast, the source activities of alpha, beta, and gamma frequency bands were significantly reduced in the AD group, with a high decrease in the beta frequency band in all brain areas. Furthermore, the coherence of rEEG among different EEG electrodes was analyzed in the beta frequency band. It showed that pair-wise coherence between different brain areas in the AD group is remarkably increased in the ECR state and decreased after subtracting out the EOR state. Conclusion: The findings suggest that examining PSD and functional connectivity through coherence analysis could serve as a promising and comprehensive approach to differentiate individuals with AD from normal, which may benefit our understanding of the disease.

CNN for a Regression Machine Learning Algorithm for Predicting Cognitive Impairment Using qEEG.

Purpose: Electroencephalogram (EEG) signals give detailed information on the electrical brain activities occurring in the cerebral cortex. They are used to study brain-related disorders such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). Brain signals obtained using an EEG machine can be a neurophysiological biomarker for early diagnosis of dementia through quantitative EEG (qEEG) analysis. This paper proposes a machine learning methodology to detect MCI and AD from qEEG time-frequency (TF) images of the subjects in an eyes-closed resting state (ECR). Participants and Methods: The dataset consisted of 16,910 TF images from 890 subjects: 269 healthy controls (HC), 356 MCI, and 265 AD. First, EEG signals were transformed into TF images using a Fast Fourier Transform (FFT) containing different event-rated changes of frequency sub-bands preprocessed from the EEGlab toolbox in the MATLAB R2021a environment software. The preprocessed TF images were applied in a convolutional neural network (CNN) with adjusted parameters. For classification, the computed image features were concatenated with age data and went through the feed-forward neural network (FNN). Results: The trained models', HC vs MCI, HC vs AD, and HC vs CASE (MCI + AD), performance metrics were evaluated based on the test dataset of the subjects. The accuracy, sensitivity, and specificity were evaluated: HC vs MCI was 83%, 93%, and 73%, HC vs AD was 81%, 80%, and 83%, and HC vs CASE (MCI + AD) was 88%, 80%, and 90%, respectively. Conclusion: The proposed models trained with TF images and age can be used to assist clinicians as a biomarker in detecting cognitively impaired subjects at an early stage in clinical sectors.

Sleep and Circadian Rhythm in Relation to COVID-19 and COVID-19 Vaccination-National Sleep Survey of South Korea 2022.

BACKGROUND: Currently, information on sleep and circadian patterns in relation to COVID-19 or vaccination remains limited. We aimed to investigate sleep and circadian patterns according to history of COVID-19 and COVID-19 vaccination side effects. METHODS: We used data from the National Sleep Survey of South Korea 2022, a nationwide cross-sectional population-based survey regarding sleep-wake behaviors and sleep problems among Korean adults. Analysis of covariance (ANCOVA) and logistic regression analyses were performed to explore the different sleep and circadian patterns according to the history of COVID-19 or self-reported side effects of the COVID-19 vaccination. RESULTS: The ANCOVA showed that individuals with a history of COVID-19 presented a later chronotype than individuals without a history of COVID-19. Individuals who had experienced vaccine-related side effects had a shorter sleep duration, poorer sleep efficiency, and worse insomnia severity. Multivariable logistic regression analysis showed a later chronotype related to COVID-19. A short sleep duration, poorer sleep efficiency, and worse insomnia severity were associated with self-reported side effects of the COVID-19 vaccination. CONCLUSIONS: Individuals who recovered from COVID-19 had a later chronotype than those without a history of COVID-19. Individuals who had experienced vaccine-related side effects presented with poorer sleep than those without side effects.

The eveningness chronotype is associated with nightmare distress and dream recall: a cross-sectional study.

Dreaming may be affected by sleep behavior; however, evidence of the effect of chronotypes on dreaming is limited. We investigated sleep patterns, dream recall, and nightmare distress according to chronotypes. This cross-sectional study retrospectively enrolled adult participants (age > 18 years) who visited a sleep laboratory between 2016 and 2021 and underwent standard polysomnography (PSG) and completed a self-reported questionnaire. Patients with major sleep disorders were excluded. Chronotypes and dreaming components were assessed using the Korean version of the morningness-eveningness questionnaire and a nine-item dreaming questionnaire (nightmare distress and dream recall), respectively. Among healthy participants without major sleep disorders, the eveningness chronotype correlated with better dream recall than the morningness and intermediate chronotypes. Participants with the eveningness chronotype were younger and more likely to be unmarried than those with the other chronotypes. No significant chronotype-based difference was observed in the subjective measurements of sleep quality, insomnia, daytime sleepiness, depression, and anxiety or in respiration and movement events on PSG. In multivariate linear regression analysis, the chronotypes were independently related to nightmare distress (b = - 0.296; p = 0.002) and dream recall (b = - 0.334; p = 0.002). The apnea-hypopnea index was associated with nightmare distress (b = - 0.209; p = 0.029) and dream recall (b = - 0.189; p = 0.044). Depression was positively correlated with nightmare distress (b = 0.450; p = 0.002). Dream recall was best in the eveningness group among healthy adults. Greater eveningness was associated with higher nightmare distress and better dream recall. Further research is needed to understand the role of chronotypes in dreaming.

Comparisons of impulsivity among patients with different subtypes of epilepsy.

PURPOSE: This study assessed whether patients with epilepsy have a higher level of impulsivity than healthy controls, and compared impulsivity among patients with different subtypes of epilepsy. METHODS: The multicenter study included 108 subjects with epilepsy and 56 healthy volunteers. Subjects were evaluated by the Barratt Impulsiveness Scale-11 (BIS-11) and Patient Health Questionnaire-9, with BIS-11 scores analyzed as both dichotomized and continuous variables. High impulsivity was defined as a total BIS-11 score ≥ 67. RESULTS: Of the 108 subjects with epilepsy, 36 had idiopathic generalized epilepsy (IGE), 47 had temporal lobe epilepsy (TLE), and 25 had frontal lobe epilepsy (FLE). A significantly higher percentage of subjects with epilepsy (22.2%) than controls (1.8%) had BIS-11 scores ≥ 67 (p = 0.001), although mean BIS-11 scores were similar in subjects with epilepsy (59.5 ± 10.0) and controls (58.8 ± 4.6). Higher percentages of subjects with IGE and FLE had BIS-11 scores ≥ 67 than subjects with TLE and controls. Mean total BIS-11 scores did not differ between controls and subjects with IGE and FLE, but were lower in subjects with TLE than in controls. Differences in impulsivity among controls and subjects with epilepsy subtypes varied depending on BIS-11 subscale. CONCLUSIONS: Patients with epilepsy, particularly IGE and FLE, were more likely to have high impulsivity scores, defined by a certain cutoff on the BIS-11, than controls and subjects with TLE. However, mean impulsivity scores did not differ among controls and subjects with IGE and FLE. Dichotomizing BIS-11 scores may be necessary to avoid false negative results in subjects with epilepsy.

Increased pulsatility index of the basilar artery is a risk factor for neurological deterioration after stroke: a case control study.

BACKGROUND: Higher pulsatility of the middle cerebral artery (MCA) is known to be associated with stroke progression. We investigated whether pulsatility index (PI) of the basilar artery (BA) can predict neurological deterioration (ND) after acute cerebral infarction. METHODS: A total of 708 consecutive patients with acute ischemic stroke who had undergone transcranial Doppler (TCD) ultrasonography were included. ND was defined as an increase in the National Institutes of Health Stroke Scale scores by two or more points after admission. The patients were categorized into quartiles according to BA PI. Multivariable logistic regression analysis was performed to examine whether BA PI is independently associated with ND. RESULTS: BA PI was well correlated with the right (n = 474, r2 = 0.573, P < 0.001) by Pearson correlation analysis although MCA PI could not be measured from right MCA (n = 234, 33.05%) and left MCA (n = 252, 35.59%) by TCD owing to insufficient temporal bone window. Multivariable logistic regression analysis including age, sex, cerebral atherosclerosis burden, National Institutes of Health Stroke Scale at admission, and the proportion of patients with current smoking status, hypertension, diabetes mellitus, atrial fibrillation revealed that the higher BA PI (odds ratio, 3.28; confidence interval, 1.07-10.17; P = 0.038) was independently associated with ND. CONCLUSIONS: BA PI, which would be identified regardless of temporal window, could predict ND among acute stroke patients.

Quantitative electroencephalography changes in patients with mild cognitive impairment after choline alphoscerate administration.

There is limited evidence on the effectiveness of choline alphoscerate for mild cognitive impairment (MCI) in studies using neuropsychological markers. The aim of this study was to evaluate the spectral change at a source level using quantitative electroencephalography (qEEG) as a biomarker for cognitive function after choline alphoscerate administration to patients with MCI. This study used the qEEG data of patients with MCI who visited the Department of Neurology of the Chung-Ang University Hospital between April 2017 and December 2018. Resting-state EEG studies were performed on 33 patients with MCI at baseline and compared with those of the 18 normal controls selected from the community. After baseline qEEG, choline alphoscerate 400 mg was administered twice daily for 2 months to the patients with MCI. Follow-up qEEG was performed in 20 subjects. Baseline qEEG of patients with MCI was compared to qEEG after choline alphoscerate administration. We found that the MCI group exhibited a decreased alpha power compared to that of the control group. Patients with MCI treated with choline alphoscerate exhibited a decrease in the theta and delta power of the parietal and temporal lobe and an increase in the alpha power spectrum of the occipital lobes. We also identified the trend of default mode network enhancement after choline alphoscerate administration. Our results suggest that choline alphoscerate may have a positive effect in patients with MCI and support the usefulness of qEEG for monitoring the therapeutic effect of nootropics.

Aggression is more strongly associated with suicidality, independent of depression, than emotional instability and impulsivity in people with epilepsy.

PURPOSE: We evaluated the relative contributions of emotional instability, impulsivity, and aggression to the presence of suicide risk in people with epilepsy after adjusting for depressive symptoms. METHODS: This was a cross-sectional study that used the short form of the Affective Lability Scale (ALS-18), the Barratt Impulsiveness Scale Version 11 (BIS-11), the Brief Aggression Questionnaire (BAQ), and the Patient Health Questionnaire-9 (PHQ-9). Suicidality was assessed using the Mini International Neuropsychiatric Interview (MINI), and the presence of suicide risk was defined as a MINI suicidality score ≥1. Stepwise logistic regression and mediation analyses using a two-stage regression method were performed. RESULTS: Of the 171 subjects (63.2% men) included, suicide risk was present in 38 subjects (22.2%). The stepwise logistic regression analysis identified four variables that were independently associated with suicide risk: higher PHQ-9 score, higher BAQ score, longer duration of epilepsy, and unemployment. The univariate analysis showed that ALS-18 and BIS-11 scores were significantly associated with suicide risk; however, they were backward eliminated from the logistic model according to the criterion of p > 0.1. The mediating effects of ALS-18 and BIS-11 scores on suicide risk via PHQ-9 scores (but not BAQ scores) were significant, with the proportion mediated 61.5% and 54.0% of the total effect, respectively. CONCLUSIONS: Alongside depressive symptoms, aggression may be a more useful concept than emotional instability and impulsivity for identifying suicidal risk in people with epilepsy.

Analysis of microRNA signatures in ischemic stroke thrombus.

BACKGROUND: We investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism. METHODS: This study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at -70℃ after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA. RESULTS: In total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients. CONCLUSIONS: The microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived.

Is Functional Connectivity after a First Unprovoked Seizure Different Based on Subsequent Seizures and Future Diagnosis of Epilepsy?

Background and Purpose: There are no highly sensitive biomarkers for epilepsy to date. Recently, promising results regarding functional connectivity analysis have been obtained, which may improve epilepsy diagnosis even in the absence of visible abnormality in electroencephalography. We aimed to investigate the differences in functional connectivity after a first unprovoked seizure between patients diagnosed with epilepsy within 1 year due to subsequent seizures and those who were not. Methods: We compared quantitative electroencephalography power spectra and functional connectivity between 12 patients who were diagnosed with epilepsy (two or more unprovoked seizures) within 1 year and 17 controls (those not diagnosed within 1 year) using iSyncBrain® (iMediSync Inc., Suwon, Korea; https://isyncbrain.com/). In the source-level analysis, the current distribution across the brain was assessed using the standardized low-resolution brain electromagnetic tomography technique, to compare relative power values in 68 regions of interest and connectivity (the imaginary part of coherency) between regions of interest. Results: In the epilepsy group, quantitative electroencephalography showed lower alpha2 band power in left frontal, central, superior temporal, and parietal regions and higher beta2 power in both frontal, central, temporal, occipital, and left parietal regions compared with the control group. Additionally, epilepsy patients had significantly lower connectivity in alpha2 and beta2 bands than the controls. Conclusions: Patients experiencing their first unprovoked seizure presented different brain function according to whether they have subsequent seizures and future epilepsy. Our results propose the potential clinical ability to diagnose epilepsy after the first unprovoked seizure in the absence of interictal epileptiform discharges.

Impulsivity in persons with epilepsy: Association with seizure severity and suicide risk.

PURPOSE: Clinical research regarding impulsivity in patients with epilepsy is limited. The present study investigated the associations between impulsivity and seizure-related factors or suicidality in patients with epilepsy, independent of depression and anxiety. METHODS: The multicenter study included 146 subjects (63% men). We utilized the Barratt Impulsiveness Scale-11 (BIS-11), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and suicidality module of the Mini International Neuropsychiatric Interview (MINI). Stepwise regression analyses and an analysis of covariance with interaction terms were performed. RESULTS: The mean BIS-11 score was 59.3 (SD = 10.7). Psychiatric pathologies, including suicidality, were reported in relatively large proportions of patients, including PHQ-9 score ≥ 10 in 29 (19.9%) patients, GAD-7 score ≥ 7 in 35 (24.0%) patients, and MINI suicidality score ≥ 6 in 15 (10.3%) patients. Stepwise linear regression revealed that BIS-11 score was positively associated with the PHQ-9 scores (p < 0.001), antiseizure medication polytherapy (p < 0.001), use of lamotrigine (p = 0.009), and recurrence of generalized or focal to bilateral tonic clonic seizures (p = 0.010). The coefficient of determination for the model was 0.397. Generalized or focal to bilateral tonic clonic seizure recurrence tended to be positively associated with total BIS-11 scores in men but not in women. In subscale analyses, somewhat different variables were associated with different BIS-11subscales. A trend for a positive association between BIS-11 score and suicidality was found (p = 0.066). CONCLUSIONS: This study identified a positive association between clinical seizure severity and impulsivity, and found that this association tended to be sex-specific, occurring only in males. Impulsivity could potentially be weakly associated with suicidality in patients with epilepsy.

Insomnia moderates the association between recurrent seizures and emotional instability in persons with epilepsy.

PURPOSE: We investigated the moderating effect of sleep disturbance on the association between seizure recurrence and emotional instability in patients with epilepsy, independent of psychological distress. METHODS: This was a cross-sectional study. Patients completed the short form of the Affective Lability Scale (ALS-18), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). A stepwise linear regression analysis and an analysis of covariance with an interaction term were performed. RESULTS: A total of 171 subjects (63.2% men) were included. The mean ALS-18 score was 15.6 ±â€¯11.3. An ISI ≥ 15, PHQ-9 ≥ 10, and GAD-7 ≥ 7 were noted in 20.5%, 18.1%, and 23.4% of subjects, respectively. A stepwise linear regression analysis found that recurrent seizures in the last year, an ISI ≥ 15, a GAD-7 ≥ 7, and use of levetiracetam were significant and independent factors that were positively associated with higher ALS-18 scores. The coefficient of determination for the model was 0.331. The interaction between recurrent seizures and an ISI ≥ 15 had a significant effect on the ALS-18 scores (F = 6.812, p = 0.010, partial eta2 = 0.040). An ISI ≥ 15 was associated with ALS-18 scores in patients without seizure recurrence (p < 0.001). This association almost reached significance (p = 0.084) in those with recurrent seizures. In contrast, the presence of recurrent seizures was associated with ALS-18 scores in patients with an ISI < 15 (p < 0.001), but not in those with an ISI ≥ 15 (p = 0.360). CONCLUSIONS: The significant interaction between insomnia and seizure status may have an effect on emotional instability. These findings have clinical implications in the development of potential interventions for emotional instability in patients with epilepsy.

Sex differences in seizure effects on social anxiety in persons with epilepsy.

PURPOSE: We investigated sex differences in the effect of seizures on social anxiety in persons with epilepsy. METHOD: In this cross-sectional multicenter study, social anxiety was measured using the short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). SPS-6 scores ≥ 9 and SIAS-6 scores ≥ 12 were considered to indicate social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9, Stigma Scale-Revised, and Family Adaptation-Partnership-Growth-Affection-Resolve scale were also completed. A logistic regression analysis with an interaction term was used to analyze the data. RESULTS: Out of 285 participants, a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12 were noted in 62 (21.8%) and 36 (12.6%) of participants, respectively. There was no difference in the prevalence of social anxiety between men and women. Intractable seizures and lack of seizure freedom were associated with a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12, but statistical significance was lost in the adjusted models. However, intractable seizures and lack of seizure freedom significantly interacted with sex for a SPS-6 score ≥ 9 (p = 0.018) and a SIAS-6 score ≥ 12 (p = 0.048) in both the separate and adjusted models. Specifically, intractable seizures tended to be positively associated with SPS-6 scores ≥ 9 than non-intractable seizures in men only (odds ratio = 2.602, p = 0.068), whereas lack of seizure freedom tended to be negatively associated with SIAS-6 scores ≥ 12 than seizure freedom in women only (odds ratio = 4.804, p = 0.053). CONCLUSION: We found significant sex differences in seizure effects on social anxiety. Intractable seizures were associated with social phobia in men, whereas lack of seizure freedom in the last year was associated with social interaction anxiety in women.

Survey on Antiepileptic Drug Therapy in Patients with Drug Resistant Epilepsy.

BACKGROUND AND PURPOSE: Individualized anti-epileptic drug (AED) selection in patient with epilepsy is crucial. However, there is no unified opinion in treating patients with drug resistant epilepsy (DRE). This survey aimed to make a consolidate consensus with epileptologists' perspectives of the treatment for Korean DRE patients by survey responses. METHODS: The survey was conducted with Korean epilepsy experts who have experience prescribing AEDs via e-mail. Survey questionnaires consisted of six items regarding prescription patterns and practical questions in treating patients with DRE in Korea. The research period was from February 2021 to March 2021. RESULTS: The survey response rate was 83.3% (90/108). Most (77.8%) of the responders are neurologists. The proportion of patients whose seizures were not controlled by the second AED was 26.9%. The proportion of patients who had taken five or more AEDs is 13.9%, and those who are currently taking five or more AEDs are 7.3%, of which 54.5% and 37.9% reported positive effects on additional AED, respectively. The majority (91.1%) of respondents answered that the mechanism of action was the top priority factor when adding AED. Regarding data priority, responders considered that expert opinion should have the top priority, followed by clinical experiences, reimbursement guidelines and clinical evidence. Responders gave 64.9 points (range from 0 to 100) about overall satisfaction on reimbursement system of Health Insurance Review and Assessment Service for AED. CONCLUSIONS: This study on AED therapy for DRE patients is the first nationwide trial in Korean epilepsy experts. In five drug failure, the top priorities on AED selection are mechanism of action and expert opinion. These findings might help to achieve consensus and recognize the insight on optimal therapy of AED in DRE.

Obstructive sleep apnea in airline pilots during daytime sleep following overnight flights.

To identify the vulnerability of recovery sleep, this study investigated the occurrence of obstructive sleep apnea during daytime sleep following overnight flights in healthy airline pilots. We conducted daytime polysomnography following a long-haul night-time flight in 103 pilots. The following variables were assessed: apnea-hypopnea index, respiratory disturbance index and oxygen desaturation index. Moderate-to-severe obstructive sleep apnea was defined as an apnea-hypopnea index ≥15. Seventy-three pilots (70.9%) with no known history of obstructive sleep apnea presented with moderate-to-severe obstructive sleep apnea. Pilots showed high mean apnea-hypopnea, respiratory disturbance and oxygen desaturation indices. The body mass index, Berlin questionnaire score and cumulative flight time contributed to these indices, with both body mass index and cumulative flight time remaining significant at an apnea-hypopnea index ≥15. We found that pilots are vulnerable to obstructive sleep apnea during daytime sleep after night-time flights, which may deteriorate their health, increase fatigue and impair overall flight safety. Further research is needed to ensure flight safety, as daytime recovery sleep is unavoidable for night-time flight pilots. The pilots' normal and recovery sleep patterns should both be studied to develop an effective sleep management protocol.

Association of Bone Mineral Density to Cerebral Small Vessel Disease Burden.

OBJECTIVE: To test the hypothesis that bone mineral loss is mechanistically related to cerebral small vessel disease (SVD), we investigated the relationship between bone mineral density and the prevalence and intensity of SVD among patients with stroke. METHODS: We analyzed data of 1,190 consecutive patients with stroke who were >50 years of age and underwent both brain MRI and dual-energy x-ray absorptiometry from the stroke registry of Chung-Ang University Hospital in Seoul, Korea. The patients were categorized into 3 groups according to their bone mineral density (normal, osteopenia, and osteoporosis). White matter hyperintensities, silent lacunes, cerebral microbleeds, and extensive perivascular space were assessed from brain MRI. Multinomial logistic regression model was used to examine the association between osteoporosis and total SVD score. We also recruited 70 patients with stroke to study serum bone turnover markers and microRNAs related to both cerebral atherosclerosis and bone metabolism to understand bone and brain interaction. RESULTS: Osteoporosis was determined among 284 patients (23.9%), and 450 patients (37.8%) had osteopenia. As bone mineral density decreased, total SVD score and the incidence of every SVD phenotype increased except strictly lobar cerebral microbleeds. Multinomial logistic regression analysis showed that osteoporosis was independently associated with severe SVD burden. The levels of microRNA-378f were significantly increased among the patients with osteoporosis and maximal total SVD score and positively correlated with parathyroid hormone and osteocalcin. CONCLUSIONS: These findings suggest a pathophysiologic link between bone mineral loss and hypertensive cerebral arteriolar degeneration, possibly mediated by circulating microRNA.

Real-world prescribing trends of valproate in women with epilepsy in Korea.

Avoiding valproate is recommended in women of childbearing age due to possible teratogenicity and infertility. We aimed to examine the recent trend of valproate prescriptions in Korea to review the adequacy of anticonvulsant prescriptions in women with epilepsy (WWE). Oral valproate utilization was assessed using nationwide and unselected data from the Korean National Health Insurance Service from 2009 to 2017. The temporal trends of the proportions of valproate prescriptions were analyzed using the Poisson regression model and expressed as average annual percentage change (AAPC). Among the WWE of childbearing age, valproate was prescribed in 37.0% overall and 29.4% as initial prescription in 2017. The proportion of valproate utilization showed a decreasing trend in overall prescription (AAPC = -1.10%) and initial prescription (AAPC = -2.63%). However, the proportion was static over time in the initial monotherapy group (AAPC = -0. 53%), while it was significantly decreasing in the initial polytherapy group (AAPC = -8.25%). A noticeable proportion of WWE was still being prescribed valproate in Korea. In particular, the use of valproate for initial monotherapy has not decreased over the past nine years. This result calls not only for reinforcement of education regarding anticonvulsant selection but also for monitoring the actual prescription.

Differences between memory encoding and retrieval failure in mild cognitive impairment: results from quantitative electroencephalography and magnetic resonance volumetry.

BACKGROUND: The memory impairments in mild cognitive impairment (MCI) can be classified into encoding (EF) and retrieval (RF) failure, which can be affected by underlying pathomechanism. We explored the differences structurally and functionally. METHODS: We compared quantitative electroencephalography (qEEG) power spectra and connectivity between 87 MCI patients with EF and 78 MCI with RF using iSyncBrain® (iMediSync Inc., Republic of Korea) ( https://isyncbrain.com/ ). Voxel-based morphometric analysis of the gray matter (GM) in the MCI groups and 71 cognitive normal controls was also done using the Computational Anatomy Toolbox 12 ( http://www.neuro.uni-jena.de/cat/ ). RESULTS: qEEG showed higher frontal theta and lower beta2 band power, and higher theta connectivity in the EF. There was no statistically significant difference in GM volume between the EF and RF. However, when compared to normal control, GM volume reductions due to EF in the left thalamus and bilateral hippocampi and reductions due to RF in the left thalamus, right superior frontal lobe, right superior temporal lobe, and right middle cingulum were observed (p < 0.05, family-wise error correction). CONCLUSIONS: MCI differs functionally and structurally according to their specific memory impairments. The EF findings are structurally and functionally more consistent with the prodromal Alzheimer's disease stage than the RF findings. Since this study is a cross-sectional study, prospective follow-up studies are needed to investigate whether different types of memory impairments can predict the underlying pathology of amnestic MCI. Additionally, insufficient sample size may lead to ambiguous statistical findings in direct comparisons, and a larger patient cohort could more robustly identify differences in GM volume reductions between the EF and the RF group.

Association between arterial stiffness and the presence of cerebral small vessel disease markers.

OBJECTIVE: We investigated the effect of arterial stiffness on the severity of enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) at different brain locations. METHODS: A total of 854 stroke patients underwent both brachial-ankle pulse wave velocity (baPWV) measurement and brain MRI. The extent of EPVS was separately rated at the levels of the basal ganglia (BG) and centrum semiovale (CS). The CMBs were categorized as strictly lobar CMB and deep CMB. The patients were categorized according to baPWV quartiles, and multivariable logistic regressions were performed to evaluate whether the baPWV increment was independently associated with each cerebral SVD marker at different locations. The odds ratio (OR) with 95% confidence interval (CI) was derived on the reference of the first quartile. RESULTS: Severe EPVSs at BG and CS were detected in 243 (28.5%) and 353 patients (41.3%), respectively. The increment of baPWV quartiles was associated with both severe BG EPVS burden (Q4: OR = 2.58, CI = 1.45-4.60) and severe CS EPVS burden (Q4: OR = 2.06, CI = 1.24-3.42). Deep CMBs were found in 259 patients (30.3%), and strictly lobar CMBs were found in 170 patients (19.9%). Multivariable logistic regression model revealed deep CMB was independently associated with the baPWV increment (Q4: OR = 2.52, CI = 1.62-3.94). However, strictly lobar CMB had a neutral relationship with baPWV. CONCLUSION: Increased arterial stiffness is consistently associated with the presence of deep CMB and severe EPVS burden at the BG and CS, suggesting a common pathophysiologic mechanism.