The relationship between the morningness-eveningness questionnaire and incident cancer: A historical clinical cohort study.

OBJECTIVE: We conducted a retrospective cohort study to explore the relationship between chronotype measured by the total Morningness-Eveningness Questionnaire (MEQ) score and incident cancer. METHODS: We used clinical and provincial health administrative data on consecutive adults who underwent a Level 1 Polysomnography (PSG) and completed the MEQ between 2010 and 2015 in an academic hospital (Ontario, Canada) and were cancer-free at baseline. Cancer status was derived from the Ontario Cancer Registry. Individuals were followed until death or March 31, 2020. We used multivariable Cox cause-specific regressions to address the research objective. RESULTS: Of 3,004 individuals, 1,781 were analyzed: a median age of 54 years (IQR: 40-64) and 838 (47.1%) men. The median total MEQ score was 63 (IQR: 55-69); 61 (3.4%) were classified as evening (≤41), 536 (30.1%) as intermediate (42-58), and 1,184 (66.5%) as morning chronotypes (≥59). Over a median of 7 years (IQR: 5-8), 120 (6.7%) developed cancer. A U-shape relationship was found between the total MEQ score and an increased hazard of incident cancer, controlling for PSG measures of sleep apnea severity and sleep architecture, demographics, and comorbidities. Compared to the median of 63.0, a total MEQ score greater or less than the median was associated with an increased hazard of incident cancer, with the largest effect for those with a total score ≥76 (e.g., HR of a MEQ total score of 78 vs. 63: 2.01, 95% CI: 1.09-3.71). CONCLUSION: The U-shaped curve may reflect deviations from a standard circadian tendency, which may stress biological systems and influence malignancy risk.

Obstructive sleep apnea in those with idiopathic intracranial hypertension undergoing diagnostic in-laboratory polysomnography.

RATIONALE: The association of obstructive sleep apnea (OSA) with idiopathic intracranial hypertension (IIH) remains unclear, and few studies have used objective in-laboratory polysomnography (PSG) data. Thus, we used PSG data to examine the: 1) association between OSA, and its severity, with IIH and 2) sex differences in OSA severity in those with and without IIH. METHODS: We retrospectively analyzed diagnostic PSG data from January 2015 to August 2023 for patients who were diagnosed with IIH by a neuro-ophthalmologist using the modified Dandy criteria. We selected three age, sex, and body mass index (BMI) matched controls for each IIH patient. We examined potential associations of IIH with OSA using regression. Sex differences were analyzed using ANOVA. RESULTS: Of 3482 patients who underwent PSG, we analyzed 78 IIH patients (16 males) and 234 matched controls (48 males). Five (6.4 %) IIH and 39 (16.7 %) control patients had OSA, defined as AHI≥15. After adjusting for age, sex, BMI, and comorbidities, IIH was negatively associated with the presence of OSA (OR 0.29, 95%CI 0.10-0.87, p = 0.03). However, models that adjusted for acetazolamide use, with or without comorbidities, showed no significant relationship with OSA (OR 0.31, p = 0.20). Males with IIH had a significantly higher age (p = 0.020), OSA severity (p = 0.032), and arousal index (p = 0.046) compared to females with IIH. CONCLUSIONS: IIH treated with acetazolamide was not an independent risk factor for OSA presence or severity. The presence of IIH treated with acetazolamide likely does not warrant routine screening for OSA, but related risk factors may identify appropriate patients.

Machine-learning assisted swallowing assessment: a deep learning-based quality improvement tool to screen for post-stroke dysphagia.

Introduction: Post-stroke dysphagia is common and associated with significant morbidity and mortality, rendering bedside screening of significant clinical importance. Using voice as a biomarker coupled with deep learning has the potential to improve patient access to screening and mitigate the subjectivity associated with detecting voice change, a component of several validated screening protocols. Methods: In this single-center study, we developed a proof-of-concept model for automated dysphagia screening and evaluated the performance of this model on training and testing cohorts. Patients were admitted to a comprehensive stroke center, where primary English speakers could follow commands without significant aphasia and participated on a rolling basis. The primary outcome was classification either as a pass or fail equivalent using a dysphagia screening test as a label. Voice data was recorded from patients who spoke a standardized set of vowels, words, and sentences from the National Institute of Health Stroke Scale. Seventy patients were recruited and 68 were included in the analysis, with 40 in training and 28 in testing cohorts, respectively. Speech from patients was segmented into 1,579 audio clips, from which 6,655 Mel-spectrogram images were computed and used as inputs for deep-learning models (DenseNet and ConvNext, separately and together). Clip-level and participant-level swallowing status predictions were obtained through a voting method. Results: The models demonstrated clip-level dysphagia screening sensitivity of 71% and specificity of 77% (F1 = 0.73, AUC = 0.80 [95% CI: 0.78-0.82]). At the participant level, the sensitivity and specificity were 89 and 79%, respectively (F1 = 0.81, AUC = 0.91 [95% CI: 0.77-1.05]). Discussion: This study is the first to demonstrate the feasibility of applying deep learning to classify vocalizations to detect post-stroke dysphagia. Our findings suggest potential for enhancing dysphagia screening in clinical settings. https://github.com/UofTNeurology/masa-open-source.

Strengthening oropharyngeal muscles as an approach to treat post-stroke obstructive sleep apnea: A feasibility randomised controlled trial.

This study aimed to determine the feasibility of a randomised controlled trial (RCT) evaluating oropharyngeal exercise (OPE) intervention as an alternative therapy for obstructive sleep apnea (OSA) in patients with stroke or transient ischaemic attack (TIA). Despite the high prevalence of OSA in this population, the standard therapy, continuous positive airway pressure (CPAP), is often poorly tolerated. Thirty stroke/TIA patients with OSA unable to tolerate CPAP were randomly assigned to an oropharyngeal exercise or sham exercise protocol. They performed exercises for 6 weeks, 5 days per week, 30 minutes twice per day. Feasibility was ascertained by the proportion of enrolled patients who completed more than 80% of the OPE regimen. Isometric tongue pressures, apnea-hypopnea index (AHI), oxygen desaturation index (ODI), daytime sleepiness, and quality of life (QOL) outcomes were collected at baseline, post-training (6-week follow-up), and retention (10-week follow-up) to document preliminary efficacy. Adherence to study exercises was excellent, with 83% of participants completing more than 80% of the exercises. The isometric tongue pressures were observed to improve in the oropharyngeal exercise group (compared with the sham group), along with a decrease in OSA severity (measured by the AHI and ODI), reduced daytime sleepiness, and enhanced quality of life outcomes following the exercise programme. Only the effects on posterior isometric tongue pressure and daytime sleepiness remained significantly different between groups at the retention session. In conclusion, an RCT evaluating the efficacy of oropharyngeal exercises on post-stroke/TIA OSA is feasible and our preliminary results suggest a clinically meaningful effect.

Sex Differences in Obstructive Sleep Apnea after Stroke.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is prevalent after stroke and associated with recurrent stroke, prolonged hospitalization, and decreased functional recovery. Sex differences in post-stroke OSA remain underexplored. The objective of this study was to evaluate sex differences in functional outcomes, stroke and OSA severity, and clinical manifestations of OSA in stroke patients with OSA. METHODS: We retrospectively evaluated data from three previously conducted studies. Study patients had an imaging-confirmed stroke and had been found to have OSA (apnea-hypopnea index [AHI] ≥ 5) on either in-laboratory polysomnography or home sleep apnea testing performed within 1 year of their stroke. Linear regression models were used to evaluate study outcomes. RESULTS: In total, 171 participants with post-stroke OSA (117 males [68.4%] and 54 females [31.6%]) were included. Female sex was an independent predictor for greater functional impairment (ß = 0.37, 95% CI 0.029-0.71, p = 0.03), increased stroke severity (ß = 1.009, 95% CI 0.032-1.99, p = 0.04), and greater post-stroke depressive symptoms (ß = 3.73, 95% CI 0.16-7.29, p = 0.04). Female sex was associated with lower OSA severity, as measured by the AHI (ß = -5.93, 95% CI -11.21- -0.66). Sex was not an independent predictor of specific symptoms of OSA such as daytime sleepiness, snoring, tiredness, and observed apneas. CONCLUSION: Females with post-stroke OSA had poorer functional outcomes and more severe strokes compared to males, despite having lower OSA severity. Females with post-stroke OSA also exhibited more depressive symptoms. Understanding sex differences in patients with post-stroke OSA will likely facilitate better recognition of OSA and potentially improve clinical outcomes.

Normal multiple sleep latency test values in adults: A systematic review and meta-analysis.

Sleep latency is a measure of time it takes to enter sleep. Very short sleep latencies are indicative of excessive daytime sleepiness and pathological sleep conditions such as narcolepsy. The normal range of mean sleep latency calculated from the multiple sleep latency test in healthy adults is not well-established. We provide a review of normative mean sleep latency values on the multiple sleep latency test by synthesizing data from 110 healthy adult cohorts. We also examine the impact of demographic variables such as age, sex, body mass index, sleep architecture and sleep-disordered breathing as well as methodological variables such as sleep onset definitions and multiple sleep latency test protocols. The average mean sleep latency was 11.7 min (95% CI: 10.8-12.6; 95% PI: 5.2-18.2) for cohorts evaluated using the earlier definition of sleep onset and 11.8 min (95% CI: 10.7-12.8; 95% PI: 7.2-16.3) for those evaluated using the later definition. There were no significant associations between mean sleep latency and demographic or methodological variables. A negative association of -0.29 per one unit increase (95% CI: -0.55 to -0.04) was found between mean sleep latency and apnea-hypopnea index on prior night polysomnography. Establishing updated ranges for mean sleep latency among healthy adults may guide clinical decision-making surrounding sleep pathologies and inform future research into the associations between patient variables, daytime sleepiness, and sleep pathologies.

Impact of sleep chronotype on in-laboratory polysomnography parameters.

Morningness-eveningness preference, also known as chronotype, is the tendency for a person to sleep during certain hours of the day and is broadly categorised into morning and evening types. In-laboratory polysomnography (iPSG) is the gold-standard to assess sleep, however, an individual's chronotype is not accounted for in current protocols, which may confound collected sleep data. The objective of our study was to assess if chronotype had an association with sleep physiology. Patients who completed the diagnostic iPSG and the Morningness-Eveningness Questionnaire (MEQ), which categorises patients into morning type, neither or evening type, were assessed. Multivariable linear regression models were used to assess if chronotype was associated with sleep quality, duration, and physiology during iPSG. The study sample included 2612 patients (mean age of 53.6 years, 48% male) recruited during 2010-2015. Morning type, compared with neither type, was significantly associated with an increase in total sleep time and rapid eye movement (REM) sleep, and a decrease in sleep onset latency and the arousal index. Evening type, compared with neither type, was significantly associated with a decrease in total sleep time, sleep efficiency, and REM sleep, and an increase in sleep onset latency and wake after sleep onset. Additionally, iPSG lights out time was significantly different between the different chronotypes. Overall, a morningness chronotype was associated with favourable sleep quality and duration while an eveningness chronotype was associated with reduced sleep quality. Our study quantifies the association of chronotype with iPSG metrics and suggests that laboratory protocols should consider chronotype in their evaluations.

Men Are at Higher Risk of Screening Positive for Vascular Cognitive Impairment Compared to Women after Stroke and Transient Ischemic Attack.

While women have greater incidence of dementia, men have higher prevalence of vascular risk factors. This study examined sex differences in risk of screening positive for cognitive impairment after stroke. Ischemic stroke/TIA patients (N = 5969) participated in this prospective, multi-centered study, which screened for cognitive impairment using a validated brief screen. Men showed a higher risk of screening positive for cognitive impairment after adjusting for age, education, stroke severity, and vascular risk factors, suggesting that other factors may be contributing to increased risk among men (OR = 1.34, CI 95% [1.16, 1.55], p < 0.001). The effect of sex on cognitive impairment after stroke warrants further attention.

Language discordance as a marker of disparities in cerebrovascular risk and stroke outcomes: A multi-center Canadian study.

Background: Differences in ischemic stroke outcomes occur in those with limited English proficiency. These health disparities might arise when a patient's spoken language is discordant from the primary language utilized by the health system. Language concordance is an understudied concept. We examined whether language concordance is associated with differences in vascular risk or post-stroke functional outcomes, depression, obstructive sleep apnea and cognitive impairment. Methods: This was a multi-center observational cross-sectional cohort study. Patients with ischemic stroke/transient ischemic attack (TIA) were consecutively recruited across eight regional stroke centers in Ontario, Canada (2012 - 2018). Participants were language concordant (LC) if they spoke English as their native language, ESL if they used English as a second language, or language discordant (LD) if non-English speaking and requiring translation. Results: 8156 screened patients. 6,556 met inclusion criteria: 5067 LC, 1207 ESL and 282 LD. Compared to LC patients: (i) ESL had increased odds of diabetes (OR = 1.28, p = 0.002), dyslipidemia (OR = 1.20, p = 0.007), and hypertension (OR = 1.37, p<0.001) (ii) LD speaking patients had an increased odds of having dyslipidemia (OR = 1.35, p = 0.034), hypertension (OR = 1.37, p<0.001), and worse functional outcome (OR = 1.66, p<0.0001). ESL (OR = 1.88, p<0.0001) and LD (OR = 1.71, p<0.0001) patients were more likely to have lower cognitive scores. No associations were noted with obstructive sleep apnea (OSA) or depression. Conclusions: Measuring language concordance in stroke/TIA reveals differences in neurovascular risk and functional outcome among patients with limited proficiency in the primary language of their health system. Lower cognitive scores must be interpreted with caution as they may be influenced by translation and/or greater vascular risk. Language concordance is a simple, readily available marker to identify those at risk of worse functional outcome. Stroke systems and practitioners must now study why these differences exist and devise adaptive care models, treatments and education strategies to mitigate barriers influenced by language discordance.

Polysomnographic Assessment of Sleep Disturbances in Cancer Development: A Historical Multicenter Clinical Cohort Study.

BACKGROUND: Many cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk. RESEARCH QUESTION: What is the association between polysomnographic measures of sleep disturbances and incident cancer, and what is the validity of cluster analysis in identifying polysomnography phenotypes? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study using linked clinical and provincial health administrative data on consecutive adults free of cancer at baseline with polysomnography data collected between 1994 and 2017 in four academic hospitals in Ontario, Canada. Cancer status was derived from registry records. Polysomnography phenotypes were identified by k-means cluster analysis. A combination of validation statistics and distinguishing polysomnographic features was used to select clusters. Cox cause-specific regressions were used to assess the relationship between identified clusters and incident cancer. RESULTS: Among 29,907 individuals, 2,514 (8.4%) received a diagnosis of cancer over a median of 8.0 years (interquartile range, 4.2-13.5 years). Five clusters were identified: mild (mildly abnormal polysomnography findings), poor sleep, severe OSA or sleep fragmentation, severe desaturations, and periodic limb movements of sleep (PLMS). The associations between cancer and all clusters compared with the mild cluster were significant while controlling for clinic and year of polysomnography. When additionally controlling for age and sex, the effect remained significant only for PLMS (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.06-1.50) and severe desaturations (aHR, 1.32; 95% CI, 1.04-1.66). Further controlling for confounders, the effect remained significant for PLMS, but was attenuated for severe desaturations. INTERPRETATION: In a large cohort, we confirmed the importance of polysomnographic phenotypes and highlighted the role that PLMS and oxygenation desaturation may play in cancer. Using this study's findings, we also developed an Excel (Microsoft) spreadsheet (polysomnography cluster classifier) that can be used to validate the identified clusters on new data or to identify which cluster a patient belongs to. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www. CLINICALTRIALS: gov.

Laxatives are Associated with Poorer Polysomnography-derived Sleep Quality.

OBJECTIVE: To characterize 1) the relationship between laxative use and objective sleep metrics, and 2) the relationship between laxative use and self-reported insomnia symptoms in a convenience sample of middle-aged/elderly patients who completed in-laboratory polysomnography. METHODS: We cross-sectionally analyzed first-night diagnostic in-laboratory polysomnography data for 2946 patients over the age of 40 (mean age 60.5 years; 48.3% male). Laxative use and medical comorbidities were obtained through self-reported questionnaires. Patient insomnia symptoms were based on self-report. Associations between laxative use and objective sleep continuity were analyzed using multivariable linear regression models. Associations between laxative use and insomnia were assessed using multivariable logistic regression models. RESULTS: After adjusting for age, sex, body mass index, total recording time, and relevant comorbidities, laxative users had a 7.1% lower sleep efficiency (p < 0.001), 25.5-minute higher wake after sleep onset (p < 0.001), and a 29.4-minute lower total sleep time (p < 0.001) than patients not using laxatives. Laxative users were found to be at greater odds of reporting insomnia symptoms (OR = 1.7, p = 0.024) than patients not using laxatives. CONCLUSION: Laxative use is associated with impairments in objective sleep continuity. Patients using laxatives were also at greater odds of reporting insomnia symptoms.

Factors Associated With Sleep Disturbance Amongst Youth With Bipolar Disorder.

Background: While sleep disturbances and their impact on functioning are well-established in adults with bipolar disorder (BD), little is known about this topic in youth. Objective: This study investigates the prevalence and correlates of sleep disturbance among youth with BD. Methods: The study included 103 youth (72 BD, 31 healthy controls [HC]), ages 14-20 years. Study measures included a semi-structured diagnostic interview and the Pittsburgh Sleep Quality Index (PSQI). PSQI yields a global score and 7 subscale scores. Analyses examined between group differences in PSQI scores, and correlates of PSQI within BD. Results: BD youth had significantly higher (worse) global sleep scores, and higher scores on 5/7 subscales (quality, latency, disturbance, sleep medication use, daytime dysfunction). In univariate analyses, poorer sleep quality was associated with higher lifetime and current depression severity, mixed mood state, self-reported affective lability, and borderline personality traits. Lifetime lithium treatment and euthymic mood state were associated with better sleep scores. In multivariate analyses, greater current depression severity and self-reported affective lability were most robustly associated with poor sleep quality. Conclusions: Converging with data from adults, present findings indicate greater sleep disturbance among youth with BD versus HC. Also convergent with adults with BD, mood disturbance, whether depression severity or emotional lability, comprised the predominant correlates of sleep disturbance among youth with BD. Future research is warranted to better understand the temporal association between sleep disturbance and its correlates in youth with BD. Relatedly, interventions that address both mood and sleep disturbances may help improve overall functioning.

Contexte: Bien que les perturbations du sommeil et leur effet sur le fonctionnement soient bien établies chez les adultes souffrant du trouble bipolaire (TB). Nous en savons peu à ce sujet chez les jeunes. Objectif: La présente étude investigue la prévalence et les corrélats de la perturbation du sommeil chez les jeunes souffrant du TB. Méthodes: L'étude comprenait 103 jeunes (72 TB, 31 témoins en santé [TS]), âgés de 14 à 20 ans. Les mesures de l'étude étaient notamment une entrevue diagnostique semi-structurée et l'Index de Qualité du Sommeil de Pittsburgh (IQSP). L'IQSP donne un score global et 7 scores de sous-échelles. Les analyses ont examiné entre les différences de groupes dans les scores IQSP, et les corrélats d'IQSP dans le TB. Résultats: Les jeunes souffrant de TB avaient des scores de sommeil globaux significativement plus élevés (pires), et des scores plus élevés à 5/7 sous-échelles (qualité, latence, perturbation, utilisation de médicament pour dormir, dysfonction diurne). Dans les analyses univariées, la mauvaise qualité du sommeil était associée à la gravité de la dépression de durée de vie et actuelle, à l'état de l'humeur mixte, à la labilité affective auto-déclarée, et aux traits de la personnalité limite. Le traitement au lithium de durée de vie et l'état de l'humeur euthymique étaient associés avec de meilleurs scores de sommeil. Dans les analyses multivariées, une plus grande gravité de la dépression actuelle et de la labilité affective auto-déclarée étaient très robustement associées à une mauvaise qualité du sommeil. Conclusions: Convergeant avec les données des adultes, les résultats actuels indiquent une plus grande perturbation du sommeil chez les jeunes souffrant du TB contre les TS. Convergeant également avec les adultes souffrant de TB, la perturbation de l'humeur, que ce soit par la gravité de la dépression ou la labilité émotionnelle, comprenait les corrélats prédominants de la perturbation du sommeil chez les jeunes souffrant de TB. La future recherche est justifiée pour mieux comprendre l'association temporelle entre la perturbation du sommeil et ses corrélats chez les jeunes souffrant du TB. Étant liées, les interventions qui abordent l'humeur et les perturbations du sommeil peuvent aider à améliorer le fonctionnement général.

Relationship between gastroesophageal reflux disease and objective sleep quality.

STUDY OBJECTIVES: To objectively characterize (1) the relationship between gastroesophageal reflux disease (GERD) and sleep quality, and (2) the influence of sleep position on this relationship, using in-laboratory polysomnography. METHODS: We retrospectively analyzed first-night diagnostic in-laboratory polysomnography data for 3411 patients (median age 55 years; 48% male). Medication use and medical condition data were obtained through self-reported questionnaires. Associations between sleep quality and the presence of GERD, and the influence of sleep position on these associations, were analyzed using multivariable linear regression models. RESULTS: After adjusting for age, sex, body mass index, and relevant comorbidities, GERD was associated with a 3.0% decrease in sleep efficiency, 8.8-minute increase in wake after sleep onset, 24.4-minute increase in rapid eye movement (REM) latency, 13.4-minute decrease in total sleep time, 1.4% decrease in %REM sleep, and 1.5% increase in %N3 sleep. Having both GERD and the majority of sleep on the right side was associated with an 8.6% decrease in sleep efficiency, 27.5-minute increase in wake after sleep onset, 35.6-minute decrease in total sleep time, 2.1% decrease in %REM sleep, and 3.5% increase in %N3 sleep. Having both GERD and the majority of sleep on the left side was associated with an 8.7-minute increase in sleep onset latency. CONCLUSIONS: GERD is associated with an impairment in objective sleep quality. These associations were more pronounced in right-sided sleep and mostly ameliorated in left-sided sleep. Physicians should recognize the potential for poor sleep quality in patients with GERD and the effect of body position on this relationship. CITATION: Gurges P, Murray BJ, Boulos MI. Relationship between gastroesophageal reflux disease and objective sleep quality. J Clin Sleep Med. 2022;18(12):2731-2738.

Incidental Findings Among Youth Participating in Multimodal Imaging Research: Characteristics of Findings and Description of a Management Approach.

Research imaging in healthy and clinical youth populations yields incidental findings that require a management strategy. Our primary objective was to document the frequency and nature of incidental findings within a research group integrating multiple imaging modalities. A second objective was to describe the evolution of an approach to handling incidental findings. A case example was included to display the intricacies of some of these scenarios. Youth, ages 13-20 years, with bipolar disorder, familial risk for bipolar disorder, or healthy controls, obtained one or a combination of neuroimaging, cardio-thoracic imaging, retinal imaging, and carotid imaging. All images were systematically reviewed for incidental findings. Overall, of 223 participants (n = 102 healthy controls), 59% (n = 131) had a brain magnetic resonance imaging (MRI) incidental finding and 27% (n = 60) had at least one incidental brain finding requiring non-urgent follow-up. In addition, of 109 participants with chest/cardiac MRI and carotid ultrasound, 3% (n = 3) had chest findings, 2% (n = 2) had cardiac findings, and 1% (n = 1) had a carotid finding. Of 165 youth with retinal imaging, 1% (n = 2) had incidental findings. While the vast majority of these incidental findings were of a non-serious, non-urgent nature, there were noteworthy exceptions. Imaging research groups need a system that emphasizes the value of clinical review of research images and one that is collaborative and responsive in order to inform follow-up plans. Rating systems that have been developed and used in neuroimaging for the classification of incidental findings can be adapted for use in areas other than the brain. Regardless of severity, incidental findings may raise anxiety in youth participants and their parents. The optimal threshold is one that balances transparency with utility.

Sleep Quality in Neuromyelitis Optica Spectrum Disorder: A Systematic Review.

Background: This review summarizes the literature on sleep quality in neuromyelitis optica spectrum disorder (NMOSD) and discusses these findings in the context of current knowledge of sleep physiology. Methods: A literature search was performed using Ovid MEDLINE, Embase, and Scopus from inception to September 3, 2020. All included studies reported at least 1 measure of sleep quality in individuals with NMOSD. Pittsburgh Sleep Quality Index (PSQI) scores of individuals from 4 studies were compared with those from a data set of controls. Results: Thirteen studies (1041 individuals with NMOSD) were included in the review. Disturbed sleep was demonstrated across subjective metrics based on patient surveys and objective metrics such as polysomnography. An estimated 70% of individuals with NMOSD can be classified as poor sleepers. Standardized mean difference between PSQI scores of 183 individuals with NMOSD and those of 9284 controls was 0.72 (95% CI, 0.57-0.86; P < .001). Decreased sleep quality was significantly associated with decreased quality of life and increased anxiety, depression, and disability status. Sleep disturbances in NMOSD were similar in severity to those in multiple sclerosis. Conclusions: Sleep disturbances are a major contributor to NMOSD disease burden and may arise from the disruption of sleep circuitry, in addition to physical and psychological complications. Multiple processes involved in sleep regulation may be affected, such as, but not limited to, neural circadian circuit disruption, direct effects of inflammation, aminergic projecting system abnormalities, glymphatic system impairment, and development of sleep disorders such as restless legs syndrome/sleep apnea. A better understanding of these mechanisms is necessary for developing effective therapies for NMOSD-associated sleep disturbances.

Association of Periodic Limb Movements With Medication Classes: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: To investigate the association between various medication classes and the periodic limb movement index (PLMI) in a clinical cohort of adults who completed in-laboratory polysomnography. METHODS: A single, diagnostic, overnight, in-laboratory polysomnogram was completed for 3,488 patients consecutively referred from 2010 to 2015 to determine PLMI. Medication use and medical comorbidities were collected through patient questionnaires. Associations between medication classes and PLMI were ascertained using multivariable ordinal logistic regression models. RESULTS: The median age of the cohort was 56.0 years (48.2% male). After adjusting for age, sex, body mass index, relevant comorbidities, and sleep measures, the use of selective serotonin reuptake inhibitors (SSRIs) (odds ratio [OR] 1.52) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (OR 1.99) was associated with increased PLMI. Conversely, gabapentinoids (OR 0.71), stimulants (OR 0.52), benzodiazepines (OR 0.79), and dopamine agonists (OR 0.38) were associated with decreased PLMI. A non-statistically significant trend for decreased PLMI with neuroleptic use was observed. No significant associations were found between PLMI and the use of antihypertensives, statins, tricyclic antidepressants, bupropion, anticoagulants, antiplatelets, modafinil, and antihistamines. DISCUSSION: The use of SSRIs and SNRIs was associated with elevated PLMI while the use of gabapentinoids, stimulants, benzodiazepines, and dopamine agonists was associated with decreased PLMI. These results can assist physicians in managing periodic limb movements in sleep (PLMS) and invite further research into the relationship between PLMS and medications with the modulating effects of dose, formulation type, and time of administration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that SSRIs and SNRIs are associated with elevated PLMI while gabapentinoids, stimulants, benzodiazepines, and dopamine agonists are associated with decreased PLMI.