Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging.

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

Predicting the impact of CPAP on brain health: A study using the sleep EEG-derived brain age index.

OBJECTIVE: This longitudinal study investigated potential positive impact of CPAP treatment on brain health in individuals with obstructive sleep Apnea (OSA). To allow this, we aimed to employ sleep electroencephalogram (EEG)-derived brain age index (BAI) to quantify CPAP's impact on brain health and identify individually varying CPAP effects on brain aging using machine learning approaches. METHODS: We retrospectively analyzed CPAP-treated (n = 98) and untreated OSA patients (n = 88) with a minimum 12-month follow-up of polysomnography. BAI was calculated by subtracting chronological age from the predicted brain age. To investigate BAI changes before and after CPAP treatment, we compared annual ΔBAI between CPAP-treated and untreated OSA patients. To identify individually varying CPAP effectiveness and factors influencing CPAP effectiveness, machine learning approaches were employed to predict which patient displayed positive outcomes (negative annual ΔBAI) based on their baseline clinical features. RESULTS: CPAP-treated group showed lower annual ΔBAI than untreated (-0.6 ± 2.7 vs. 0.3 ± 2.6 years, p < 0.05). This BAI reduction with CPAP was reproduced independently in the Apnea, Bariatric surgery, and CPAP study cohort. Patients with more severe OSA at baseline displayed more positive annual ΔBAI (=accelerated brain aging) when untreated and displayed more negative annual ΔBAI (=decelerated brain aging) when CPAP-treated. Machine learning models achieved high accuracy (up to 86%) in predicting CPAP outcomes. INTERPRETATION: CPAP treatment can alleviate brain aging in OSA, especially in severe cases. Sleep EEG-derived BAI has potential to assess CPAP's impact on brain health. The study provides insights into CPAP's effects and underscores BAI-based predictive modeling's utility in OSA management.

Sex-specific patterns of discomfort in patients with restless legs syndrome.

STUDY OBJECTIVES: Sex differences in the prevalence of restless legs syndrome (RLS) have been reported, with a higher prevalence in women than in men. However, sex differences in clinical presentation remain unclear. We aimed to investigate the phenotypic differences in patients with RLS between sexes by comparing clinical presentations, iron status, polysomnographic parameters, and treatment. METHODS: We retrospectively evaluated 614 patients (225 men, 389 women) diagnosed with RLS. To enhance the robustness of the study, an age-matched control group of 179 men and 286 women without sleep disorders was also included. Information on demographics and sleep-related questionnaires were collected. Iron status was evaluated using blood samples, and polysomnography was performed to evaluate periodic leg movements and comorbid sleep disorders. RESULTS: Our analysis revealed no sex difference in the severity of RLS but a difference in the pattern of symptoms. Women had more frequent symptoms of pain and awakening during sleep, while men had more common motor symptoms (both self-reported symptoms and periodic leg movement on polysomnography). Women with RLS also had lower iron parameters and received more frequent iron supplementation therapy than men. In contrast to women with RLS, who presented higher sleep disturbances and depressive mood, men with RLS had a higher risk of comorbidities such as hypertension and cardiovascular disease. These sex differences were notably more pronounced than in the control group. CONCLUSIONS: This study suggests that sex differences exist in RLS phenotypes, and clinicians should consider these differences for treatment. CITATION: Kim J, Kim JR, Park HR, Joo EY. Sex-specific patterns of discomfort in patients with restless legs syndrome. J Clin Sleep Med. 2024;20(2):253-259.

White matter microstructure and connectivity changes after surgery in male adults with obstructive sleep apnea: recovery or reorganization?

Study objectives: Obstructive sleep apnea (OSA) is a prevalent clinical problem significantly affecting cognitive functions. Surgical treatment is recommended for those unable to use continuous positive airway pressure. We aimed to investigate the therapeutic effect of upper airway surgery on the white matter (WM) microstructure and brain connectivity in patients with OSA. Methods: Twenty-one male patients with moderate-to-severe OSA were recruited for multi-level upper airway surgery. Overnight polysomnography (PSG), neuropsychiatric tests, and brain MRI scans were acquired before and 6.1 ± 0.8 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group. We calculated the longitudinal changes of diffusion tensor imaging (DTI) parameters, including fractional anisotropy (ΔFA) and mean/axial/radial diffusivity (ΔMD/AD/RD). We also assessed changes in network properties based on graph theory. Results: Surgically treated patients showed improvement in PSG parameters and verbal memory after surgery. Globally, ΔFA was significantly higher and ΔRD was lower in the surgery group than in the untreated group. Especially ΔFA of the tracts involved in the limbic system was higher after surgery. In network analysis, higher Δbetweenness and lower Δclustering coefficients were observed in the surgical group than in the untreated group. Finally, the improvement of verbal memory after surgery positively correlated with ΔFA in superior thalamic radiation (p = 0.021), fronto aslant tracts (p = 0.027), and forceps minor tracts (p = 0.032). Conclusion: Surgical treatment of OSA can alleviate alterations in WM integrity and disruptions in local networks, particularly for the tracts involved in the limbic system. These findings may further explain the cognitive improvement observed after the treatment of OSA.

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.

National Estimates of Narcolepsy in Korea.

BACKGROUND AND PURPOSE: Epidemiological data on narcolepsy are rare in South Korea. We aimed to provide an overview of the burden of narcolepsy and its temporal trend in South Korea. METHODS: Patients with narcolepsy were identified by their registration in the Rare and Intractable Disease (RID) register and the Health Insurance Review and Assessment database. Individuals registered in the RID program with the code V234 were considered as having 'definite narcolepsy', while those who claimed health insurance with G47.4 as the primary diagnostic code were considered as having 'probable narcolepsy'. We estimated the annual prevalence, incidence, and medical costs of narcolepsy between 2010 and 2019. RESULTS: The prevalence of definite narcolepsy was 8.4/100,000 in 2019, peaking at 32.0/100,000 in those aged 15-19 years. The prevalence was higher in males, with a relative risk of 1.72. The prevalence has increased over the past 6 years, with an average annual growth rate (AAGR) of 12.2%. The prevalence of probable narcolepsy was 10.7/100,000 in 2019. The incidence of definite narcolepsy increased up to 1.3/100,000 in 2019 with an AAGR of 7.1%. Annual medical expenditure for definite narcolepsy gradually increased up to 4.1 billion KRW in 2019, with a compound annual growth rate of 11.9%. CONCLUSIONS: This study has provided the first nationwide estimates for narcolepsy in South Korea. The prevalence of diagnosed narcolepsy in South Korea was at the low end of the range of narcolepsy prevalence rates reported for other countries. However, the prevalence and incidence have been steadily increasing over the past decade.

Novel neuroelectrophysiological age index associated with imaging features of brain aging and sleep disorders.

Sleep architecture and microstructures alter with aging and sleep disorder-led accelerated aging. We proposed a sleep EEG based brain age prediction model using convolutional neural networks. We then associated the estimated brain age index with brain structural aging features, sleep disorders and various sleep parameters. Our model also showed a higher BAI (predicted brain age minus chronological age) is associated with cortical thinning in various functional areas. We found a higher BAI for sleep disorder groups compared to healthy sleepers, as well as significant differences in the spectral pattern of EEG among different sleep disorders (lower power in slow and ϑ waves for sleep apnea vs. higher power in ß and σ for insomnia), suggesting sleep disorder-dependent pathomechanisms of aging. Our results demonstrate that the new EEG-BAI can be a biomarker reflecting brain health in normal and various sleep disorder subjects, and may be used to assess treatment efficacy.

Does Repeated Dosing of Intravenous Ferric Carboxymaltose Alleviate Symptoms of Restless Legs Syndrome?

BACKGROUND: Several studies have reported the efficacy of intravenous (IV) iron for patients with restless legs syndrome (RLS), but little is known about the efficacy or safety of repeated IV iron treatment. The aim of this study was to evaluate the effectiveness of repeated doses of IV ferric carboxymaltose (FCM) in treating RLS symptoms. METHODS: Patients who received FCM more than twice for RLS from April 2016 to January 2020 were retrospectively reviewed. Patients who had shown positive response to initial IV FCM re-visited the clinic when their symptoms returned, and received repeated IV FCM (1000 mg). Blood iron panels were measured before initial and repeated IV FCM. We defined 'responders' as patients with a greater than 40% decrease in International Restless Legs Study Group Severity Scale (IRLS) compared with pre-treatment levels. RESULTS: A total of 42 patients, including 26 with primary RLS, 5 with gastrectomy, and 11 with anemia, completed the evaluation. Patients received IV FCM infusion 2-4 times. A total of 21 of 26 (80.8%) primary cases of RLS, 4 of 5 (80.0%) patients with a history of gastrectomy, and 9 of 11 (81.8%) patients with anemia responded to repeated FCM treatment. Serum ferritin levels of patients with primary RLS were higher before the second treatment than the baseline levels. There were no serious adverse events observed in the study. CONCLUSIONS: Repeated IV FCM for recurring symptoms is an effective treatment for primary RLS and RLS associated with iron deficiency. Serum ferritin might not be a reliable factor to monitor the sustained effects of IV iron for RLS.

Altered cerebrocerebellar functional connectivity in patients with obstructive sleep apnea and its association with cognitive function.

STUDY OBJECTIVES: Previous functional MRI studies have reported altered brain networks in patients with obstructive sleep apnea (OSA). However, the extent and pattern of abnormal connectivity were inconsistent across studies, and cerebrocerebellar connections have been rarely assessed. We investigated functional network changes in cerebral and cerebellar cortices of OSA patients. METHODS: Resting-state functional MRI, polysomnography, and neuropsychological (NP) test data were acquired from 74 OSA patients (age: 45.8 ± 10.7 years) and 33 healthy subjects (39.6 ± 9.3 years). Connectivity matrices were extracted by computing correlation coefficients from various regions of interest, and Fisher r-to-z transformations. In the functional connections that showed significant group differences, linear regression was conducted to examine the association between connectivity and clinical characteristics. RESULTS: Patients with OSA showed reduced functional connectivity (FC) in cerebrocerebellar connections linking different functional networks, and greater FC in cortical between-network connections in prefrontal regions involving the default mode network (DMN) and the control network. For OSA group, we found no correlation between FC and sleep parameters including lowest SaO2 and arousal index in the connections where significant associations were observed in healthy subjects. FC changes in DMN areas were related to reduced verbal fluency in OSA. Lower local efficiency and lower clustering coefficient of the salience network in the left cerebellum were also observed in OSA. CONCLUSIONS: OSA affects mainly the cerebrocerebellar pathway. The disruption of function in these connections are related to sleep fragmentation and hypoxia during sleep. These abnormal network functions, especially DMN, are suggested to participate in cognitive decline of OSA.

Predicting brain age based on sleep EEG and DenseNet.

We proposed a sleep EEG-based brain age prediction model which showed higher accuracy than previous models. Six-channel EEG data were acquired for 6 hours sleep. We then converted the EEG data into 2D scalograms, which were subsequently inputted to DenseNet used to predict brain age. We then evaluated the association between brain aging acceleration and sleep disorders such as insomnia and OSA.The correlation between chronological age and expected brain age through the proposed brain age prediction model was 80% and the mean absolute error was 5.4 years. The proposed model revealed brain age increases in relation to the severity of sleep disorders.In this study, we demonstrate that the brain age estimated using the proposed model can be a biomarker that reflects changes in sleep and brain health due to various sleep disorders.Clinical Relevance-Proposed brain age index can be a single index that reflects the association of various sleep disorders and serve as a tool to diagnose individuals with sleep disorders.

White matter tract-specific alterations in patients with primary restless legs syndrome.

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients' attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.

Effects of Organic Light-Emitting Diodes on Circadian Rhythm and Sleep.

OBJECTIVE: Organic light-emitting diodes (OLEDs) emit less blue light than traditional light-emitting diodes (LEDs), and we previously found that early-night OLED light exposure (LE) delays the melatonin phase by less than LED at a color temperature of 4,000 K. As a follow-up study, we investigated the effects of OLED and LED at a different color temperature (3,000 K) on melatonin profile, sleep, and vigilance. METHODS: 24 healthy subjects (27.5±5.1 years) were exposed to three light conditions [OLED, LED, and dim light (DL)] from 17:30 to 24:00, in a random order and with a 1-week interval. Saliva samples for melatonin were taken every hour from 18:00 to 24:00. Polysomnography (PSG) and a psychomotor vigilance test (PVT) were performed. RESULTS: Melatonin onset time was significantly delayed under OLED and LED compared with DL, with no significant difference between OLED and LED. The mean melatonin level at 24:00 under LED was lower than that under DL, but there was no significant difference between OLED LE and DL. The percentage of slow wave sleep (N3) in LED was significantly lower than in OLED. CONCLUSION: Exposure to light in the evening can suppress melatonin secretion late at night and disturb deep sleep, and those effects are slightly worse under LED than OLED.

Altered regional cerebral blood flow in obstructive sleep apnea is associated with sleep fragmentation and oxygen desaturation.

Altered cerebral perfusion has been reported in obstructive sleep apnea (OSA). Using dynamic susceptibility contrast MRI, we compared cerebral perfusion between male OSA patients and male healthy reference subjects and assessed correlations of perfusion abnormalities of OSA patients with sleep parameters and neuropsychological deficits at 3 T MRI, polysomnography and neuropsychological tests in 68 patients with OSA and 21 reference subjects. We found lower global and regional cerebral blood flow and cerebral blood volume, localized mainly in bilateral parietal and prefrontal cortices, as well as multiple focal cortical and deep structures related to the default mode network and attention network. In the correlation analysis between regional hypoperfusion and parameters of polysomnography, different patterns of regional hypoperfusion were distinctively associated with parameters of intermittent hypoxia and sleep fragmentation, which involved mainly parietal and orbitofrontal cortices, respectively. There was no association between brain perfusion and cognition in OSA patients in areas where significant association was observed in reference subjects, largely overlapping with nodes of the default mode network and attention network. Our results suggest that impaired cerebral perfusion in important areas of functional networks could be an important pathomechanism of neurocognitive deficits in OSA.

Complete Oculomotor Palsy after Influenza Vaccination in a Young Healthy Adult: A Case Report.

Influenza vaccines are known to have a few neurological complications, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and acute disseminated encephalomyelitis. However, oculomotor palsy caused by influenza vaccination is extremely rare. We present a case report of a 25-year-old woman without any medical history who developed complete oculomotor palsy 2 weeks after influenza vaccination. Other possible causes of oculomotor nerve palsy, such as stroke, compressive lesions, infections, and autoimmune disorders, were eliminated by blood tests, cerebrospinal fluid examination, and imaging studies. Hence, influenza vaccine was considered as the likely cause.

A Sensitive and Specific Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Quantification of Salivary Melatonin and Cortisol: Development and Comparison With Immunoassays.

Melatonin and cortisol are clinically important for diagnosing sleep and mood disorders. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of salivary melatonin and cortisol concentrations according to the Clinical and Laboratory Standards Institute guidelines. Additionally, we compared the LC-MS/MS assay with immunoassays, ELISA (Direct Salivary Melatonin Elisa EK-DSM, Bühlmann Laboratories AG, Schönenbuch, Switzerland) and electrochemiluminescence immunoassay (Cortisol II, Roche, Mannheim, Germany), using 121 saliva samples. The LC-MS/MS assay exhibited good performance in terms of linearity, precision, accuracy, limit of detection, lower limit of quantification, extraction recovery, carry-over, and matrix effect. The LC-MS/MS assay and immunoassays showed strong correlation (Pearson's r=0.910 for melatonin, r=0.955 for cortisol), but demonstrated a significant mean bias of 23.2% (range 54.0-143.7%) for melatonin and 48.9% (range 59.7-184.7%) for cortisol. Our LC-MS/MS assay provided more sensitive and reliable salivary melatonin and cortisol quantification results compared with immunoassays.

Patient characteristics predicting responses to intravenous ferric carboxymaltose treatment of restless legs syndrome.

BACKGROUND: Significant benefit of intravenous ferric carboxymaltose (FCM) treatment for restless legs syndrome (RLS) has been well-established. However, no clinical indicators predicting treatment response of RLS have been established. This study aimed to determine factors predicting outcome of clinical FCM treatment of RLS patients. METHODS: Data were retrospectively reviewed from all patients who received FCM treatment for RLS from April 2016 to April 2019. These data included: detailed history, international RLS scale score (IRLS), questionnaires, comorbidity, and previous RLS medication use. Morning fasting serum iron, ferritin, and total iron-binding capacity were measured before and at four weeks after treatment. RLS patients with possible secondary RLS were identified by reviewing the medical histories. This included patients with iron deficiency anemia, lumbosacral radiculopathy, and gastrectomy. Primary RLS included those with no indication of secondary medical factors contributing to RLS. Treatment response was assessed using the IRLS and clinical ratings at four weeks after FCM administration. Patients with a greater than 40% decrease in IRLS were classified as responders. RESULTS: The study comprised 164 patients with IRLS and clinical ratings obtained before and at four weeks after intravenous (IV) iron. Treatment responses differed considerably between diagnostic groups of RLS. Percentage responding was: 64.7% (66 of 102) for patients with primary RLS, 90.9% (10 of 11) with gastrectomy, 91.3% (21 of 23) with iron deficiency anemia and 39.3% (11 of 28) with lumbosacral radiculopathy. When responders were compared to non-responders in primary RLS patients, responders had significantly lower serum iron (80.5 ± 26.7 vs. 95.8 ± 30.5 µg/dL, p = 0.022) and percentage transferrin saturation (%TSAT) (25.4 ± 9.6 vs. 30.5 ± 10.5%, p = 0.026) in females, but not males. Logistic regression controlling for major subject variables showed that %TSAT significantly predicted response. (odds ratio [OR]: 0.955, confidence interval: 0.913-0.998, p = 0.040). CONCLUSION: Intravenous FCM in moderate to severe RLS patients is beneficial as a first-line or add-on treatment, particularly for patients with compromised peripheral iron state. Overall, lower %TSAT predicted better chance of responding to the IV iron treatment especially for females.

Effects of Evening Exposure to Light from Organic Light-Emitting Diodes on Melatonin and Sleep.

BACKGROUND AND PURPOSE: Organic light-emitting diodes (OLEDs) emit less blue light than traditional light-emitting diodes (LEDs), but the effects of OLED light exposure (LE) on melatonin and sleep have not been evaluated. METHODS: Twenty-four healthy subjects (age 26.9±5.7 years; including 18 females) with the intermediate chronotype were exposed to three different light conditions [4,000 K 150 lux OLED LE, 4,000 K 150 lux LED LE, and dim light (DL) at <10 lux] for 6.5 h from 17:30 to 24:00, in a random order and with a 1-week interval. Participants entered the unit for the experiment at 16:00, and their daylight was measured by actigraphy from 8:00 to 16:00 during each session. Saliva samples for melatonin were taken every hour from 18:00 to 24:00. Sleep was monitored by polysomnography, and vigilance was evaluated by psychomotor vigilance test upon awakening. RESULTS: Melatonin onset occurred at 21:11±01:24, 21:20±01:19, and 21:36±01:16 in the DL, OLED, and LED conditions, respectively. Melatonin onset was significantly delayed under LED LE compared to DL (p=0.007) but did not differ under OLED LE (p=0.245). Melatonin suppression, sleep parameters, and vigilance were similar among the three light conditions. The accumulated amount of daytime light in each session was negatively correlated with the melatonin onset time under the DL (rho=-0.634, p=0.002) and OLED (rho=-0.447, p=0.029) conditions, not under the LED condition (p=0.129). CONCLUSIONS: Melatonin onset under OLED LE was not significantly delayed compared to DL. Exposure to sufficient daylight may advance melatonin onset even when a subject is exposed to OLED LE in the evening.

Effect of Sleep Quality on Headache-Related Impact in Primary Headache Disorders.

BACKGROUND AND PURPOSE: Sleep disturbance is common in patients with primary headache disorders. We were interest in whether poor sleep quality affects patients directly or via increases in the frequency and severity of headaches. To that end, we investigated the direct and indirect effects of sleep quality on the headache-related impact among patients with primary headache disorders. METHODS: We analyzed migraine and tension-type headache (TTH) in patients included in the headache registry of our headache clinic from October 2015 to May 2018. We collected information on the headache frequency, severity, and psychological status. Sleep quality and headache-related impact were measured using the Pittsburgh Sleep Quality Index and Headache Impact Test-6, respectively. We performed path analyses with headache frequency and severity as covariates to determine the direct effect of sleep quality on the headache-related impact, and the indirect effects mediated by increases in the headache frequency and severity. RESULTS: This study included 915 patients: 784 with migraine and 131 with TTH. Worse sleep quality was independently associated with greater headache-related impact in both patients with migraine and those with TTH. Path analysis revealed a direct effect (ß=0.207, p<0.001) of sleep quality and an indirect effect mediated by headache frequency and severity (ß=0.067, p=0.004) on the headache-related impact in migraine. In TTH, only direct effects of sleep quality on the headache-related impact were significant (ß=0.224, p=0.004). CONCLUSIONS: We suggest that poor sleep quality can directly increase the headache-related impact in both patients with migraine and TTH as well as indirectly by increasing the headache frequency and severity in patients with migraine.

First Case of Intracranial Mycotic Aneurysm Caused by Prevotella intermedia Associated with Chronic Sinusitis in a Korean Adult.

Intracranial infection caused by anaerobic bacteria is rare, and it is difficult to identify absolute anaerobes in the clinical laboratory, especially when the bacterial load is low. Here, we report the first case of intracranial mycotic aneurysm caused by Prevotella intermedia associated with chronic sinusitis and successful identification of the bacteria by 16S rRNA sequencing from bacterial growth in broth only.

Localizing deficits in white matter tracts of patients with narcolepsy with cataplexy: tract-specific statistical analysis.

White matter alterations related to hypocretin pathway have been less evaluated in patients who have narcolepsy with cataplexy (NC), as compared to the identified exploration of gray matter and have varied among structural brain magnetic resonance imaging studies. The aim of this study was to investigate the disruption of specific white matter tracts in drug-naïve patients with NC, by using a tract-specific statistical analysis (TSSA). Forty drug-naïve NC patients with cataplexy and 42 heathy controls were enrolled in the study. All participants completed diffusion weighted imaging, polysomnography, and neuropsychological testing. At that time, we automatically identified fourteen major fiber tracts using diffusion tensor imaging techniques and analyzed the group comparison of fractional anisotropy (FA) values for each tract between the NC and controls, controlling for the participant's age and gender. The mean age of the NC patients was 26.9 years and the onset age of daytime sleepiness and cataplexy was 16.7 years and 19.9 years, respectively. Relative to the controls, the NC patients showed that there were identified decreased FA values in the bilateral inferior fronto-occipital fasciculus (IFO). The Epworth sleepiness scale was positively correlated with FA values for the left IFO and right cingulate. The REM sleep latency was positively correlated with FA values for the left IFO, cingulate, and uncinate fasciculus in patients. This TSSA study revealed disintegration of the IFO in the NC patients and suggested that disintegration of WM tracts connected to the frontal cortex contributes to clinical manifestations of narcolepsy.