Periodic Limb Movements In Sleep Research Articles

Heart Rate Variability and Interoception in Periodic Limb Movements in Sleep: Interference with Psychiatric Disorders?

Periodic limb movements in sleep (PLMS) are a prevalent disorder characterized by rhythmic, involuntary movements of the lower limbs, such as dorsiflexion of the ankle and extension of the big toe, occurring in periodic intervals during sleep. These movements are often linked to disrupted autonomic nervous system (ANS) activity and altered interoception. Interoception involves perceiving internal bodily states, like heartbeat, breathing, hunger, and temperature, and plays a crucial role in maintaining homeostasis and the mind-body connection. This review explores the complex relationships between PLMS, heart rate variability (HRV), ANS dysregulation, and their impact on psychiatric disorders. By synthesizing the existing literature, it provides insights into how ANS dysregulation and altered interoceptive processes, alongside PLMS, contribute to psychiatric conditions. The review highlights the potential for integrated diagnostic and therapeutic approaches and presents a cause-and-effect model illustrating the mutual influence of psychiatric disorders, ANS dysregulation, PLMS, and interoception.

The Validation of the SOMNOwatch™ Actigraphy System for Periodic Limb Movements in Sleep Assessment.

There is a growing body of evidence regarding the clinical significance of PLMS, and this movement disorder is of concern in both clinical and scientific contexts. Leg actigraphy is a convenient and promising method for screening periodic limb movements in sleep (PLMSs). This study aims to demonstrate the reliability of the SOMNOwatch™ actigraph for detecting periodic limb movements in sleep. Twenty-eight patients, referred to a sleep laboratory for various sleep problems, underwent nocturnal polysomnography with simultaneous one-sided actigraphy using the SOMNOwatch™ actigraph. Recordings of leg movements obtained from both methods were manually scored, calculating the periodic limb movement index (PLMI). The agreement between the methods was assessed through correlation analysis and event-by-event comparison. The correlation between the PLMI derived from PSG and SOMNOwatch™ was high and statistically significant (r = 0.98, p < 0.0001). The SOMNOwatch™ demonstrated a sensitivity of 86.7% and a specificity of 92.3% in detecting PLMS. Similarly, for detecting patients with a PLMI equal to or greater than 15, the sensitivity was 85.7%, and the specificity was 95.2%.

Long-term mortality risk in obstructive sleep apnea: the critical role of oxygen desaturation index.

Mortality predictors in obstructive sleep apnea (OSA) patients yet to be comprehensively understood, especially within large cohorts undergoing long-term follow-up. We aimed to determine the independent predictors of mortality in OSA patients. In our retrospective cohort study, 3,541 patients were included and survival data was obtained from electronic medical records. Demographic characteristics, anthropometric measurements, comorbidities, laboratory tests, and polysomnography parameters were analyzed for the survived and deceased patient groups. Univariate and multivariate Cox regression analyses were performed to determine independent predictors of all-cause mortality in patients followed for at least 5 years. Among all patients, 2,551 (72%) patients were male, with a mean age of 49.7 years. 231 (6.5%) patients had died. Deceased patients were significantly older and had higher waist-to-hip ratio and Epworth Sleepiness Scale (p < 0.001, p < 0.001, p = 0.003). OSA (nonpositional and not-rapid eye movement-related), periodic limb movements in sleep and Comorbidities of Sleep Apnea Score ≥ 1 were found to be associated with increased mortality (p < 0.001). Systemic immune-inflammation index was also significantly higher in the deceased group (p < 0.001). Higher oxygen desaturation index (ODI) and apnea-hypopnea index (AHI) were associated with increased mortality (p < 0.001). Due to the high correlation between ODI and AHI, two separate multivariate Cox regression models were created. While AHI lost its significance in the multivariate analysis, ODI remained significantly higher in the deceased patient group (HR = 1.007, 1.001-1.013, p = 0.01). ODI, as the only polysomnography parameter, emerged as an independent predictor of mortality in OSA patients.

Wearable-Based Integrated System for In-Home Monitoring and Analysis of Nocturnal Enuresis.

Nocturnal enuresis (NE) is involuntary bedwetting during sleep, typically appearing in young children. Despite the potential benefits of the long-term home monitoring of NE patients for research and treatment enhancement, this area remains underexplored. To address this, we propose NEcare, an in-home monitoring system that utilizes wearable devices and machine learning techniques. NEcare collects sensor data from an electrocardiogram, body impedance (BI), a three-axis accelerometer, and a three-axis gyroscope to examine bladder volume (BV), heart rate (HR), and periodic limb movements in sleep (PLMS). Additionally, it analyzes the collected NE patient data and supports NE moment estimation using heuristic rules and deep learning techniques. To demonstrate the feasibility of in-home monitoring for NE patients using our wearable system, we used our datasets from 30 in-hospital patients and 4 in-home patients. The results show that NEcare captures expected trends associated with NE occurrences, including BV increase, HR increase, and PLMS appearance. In addition, we studied the machine learning-based NE moment estimation, which could help relieve the burdens of NE patients and their families. Finally, we address the limitations and outline future research directions for the development of wearable systems for NE patients.

A Historical Overview of the Role of Benzodiazepines including Clonazepam in the Treatment of Adult Restless Legs Syndrome and Periodic Limb Movements in Sleep.

Benzodiazepines are frequently used as therapy in Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep. The order of benefit is Sleep>RLS>PLMS and arousals > PLMS. For clonazepam dosages of 0.5 mg-2.0 mg/day are most frequently employed. Benzodiazepines exert their therapeutic effect through GABA-ergic mechanisms.

Effect of series of periodic limb movements in sleep on blood pressure, heart rate and high frequency heart rate variability.

The phenomenon known as periodic limb movements in sleep (PLMS) has been linked to a change in autonomic nervous system (ANS) activity and its effect on circulatory regulation. Autonomic dysfunction or dysregulation in patients with PLMS has been described in some domains; however, any relationship between heart rate variability (HRV) and PLMS has not been clearly established. HRV analysis is a recognised, non-invasive research method that describes the influence of the ANS on heart rate (HR). The aim of our study was to further investigate the dysregulation of autonomic HR control in patients with PLMS. We undertook a retrospective analysis of the polysomnographic (PSG), demographic and medical data of five patients with a total number of 1,348 PLMS. We analysed HR, HRV HF, systolic blood pressure (SBP), and diastolic blood pressure (DBP) for 10 heartbeats before the series of PLMS and 10 consecutive heartbeats as beat-to-beat measurements. The presented method of using successive, short, 10 RR interval segments refers to the time-frequency measurement, which is very clear and useful for presenting changes in the calculated parameters over time and thereby illustrating their dynamics. This method allowed us to assess dynamic changes in HRV HF during successive PLMS series. Statistical analysis was performed using IBM SPSS Statistics (v. 28.0.0.0). The Kruskal-Wallis test was performed to find statistically significant changes from baseline. No statistically significant changes in HR, SBP, or DBP were found in our group, although an increase in the value of the HRV HF was noted, suggesting an increase in intracardiac parasympathetic activity during the subsequent series of PLMS. Our study indicates an increase in parasympathetic activity during the appearance of successive PLMS, which, with the simultaneous lack of changes in HR, may suggest an increase in sympathetic activity, and therefore the appearance of so-called 'autonomic co-activation' resulting in the possibility of life-threatening cardiac events. Our findings add to the literature information regarding HRV in PLMS, and highlight the need for further studies to elucidate the effects of these conditions on the ANS, and on cardiovascular health.

Periodic limb movements in sleep: evolving role of autonomic nervous system.

Periodic limb movements in sleep: evolving role of autonomic nervous system.

0808 Nighttime Distribution of Periodic Limb Movements of Sleep After Surgical OSA Treatment in Pediatric Population

0808 Nighttime Distribution of Periodic Limb Movements of Sleep After Surgical OSA Treatment in Pediatric Population

Elevated periodic limb movement index is associated with hypoxemia in children with early onset scoliosis.

Patients with early onset scoliosis are at high risk of sleep disordered breathing, sleep disruption, and adverse consequences of poor sleep. In this study, we aim to assess the prevalence of periodic limb movements of sleep in a cohort of children with early onset scoliosis and identify factors that correlate with the presence of periodic limb movements. This is a retrospective chart review of 40 patients with EOS (ages 1-17years) who underwent a PSG from 2003 through 2019. Data collected included age, sex, and polysomnography parameters. Descriptive statistics were used: independent T test and Pearson correlation. The average age was 9.6years (SD 5.2); 22 were female. Eleven patients (27.5%) had elevated periodic limb movement index (PLMI) (≥ 5). Those with PLMI ≥ 5 had arousal index of 15.4 (SD 7.2) and those with normal PLMI having an arousal index of 9.4 (SD 4.9); this reached statistical significance (p < 0.05). Those with elevated PLMI spent 4.9 (SD 8.3) minutes with saturations below 88%, while those with normal PLMI spent 1.0 (SD 1.8); this was statistically significant. There was a moderate positive correlation between arousal index, hypoxemia, and PLMI. The study suggests that children with early onset scoliosis have higher frequency of periodic limb movements during sleep, and these may be correlated with increased arousal and with hypoxemia.

Clinical and Polysomnographic Characteristics of Patients With Periodic Limb Movements During Sleep and Insomnia

Objectives: Periodic limb movements of sleep (PLMS) is known to accompany restless legs syndrome, and studies on PLMS are limited. Moreover, the relationship between insomnia and PLMS is underrecognized. This study aimed to investigate the polysomnography (PSG) data, questionnaires, and iron-related laboratory data of patients with insomnia and were confirmed PLMS.Methods: Between April 2015 and May 2022, 423 patients with insomnia as the primary symptom who were diagnosed with PLMS based on overnight PSG were included and divided into three groups based on their PLM index (PLMI). The participants’ demographics, insomnia-related questionnaires, PSG findings, and iron-related laboratory findings were used in the analysis.Results: The severe PLMS group (PLMI &gt;50) were mostly males, had more individuals taking sleeping pills, and had higher body mass index than the mild PLMS group (PLMI 5–25). Significant differences were not found in questionnaire about insomnia and sleep quality. In PSG, the severe PLMS group showed shorter total sleep time and low spontaneous arousal index than the mild to moderate PLMS groups. Moreover, more patients in the severe PLMS group showed arrhythmia than the mild PLMS group. Ferritin and transferrin saturation results had no significant difference between the three groups.Conclusions: PLMS did not affect the severity of insomnia and fatigue. The results shown in PSG may be influenced by age or sleeping pills intake. Arrhythmia was higher in the severe PLMS group. More studies on the causal relationship between PLM and cardiac diseases are needed.

First uninterrupted sleep periodin children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy.

The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. We conducted a post hoc analysis of a prospective study in 30 treatment-naïve children with enuresis who underwent avideo-polysomnographyand a 24-h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep(PLMS), and arousal indexes and their correlations with the urinary parameters. Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow-up and evaluation of therapeutic strategies for enuresis.

Restless legs syndrome, periodic limb movements of sleep, and subclinical cardiovascular disease.

The online version contains supplementary material available at 10.1007/s41105-023-00497-7.

Periodic Limb Movements of Sleep: A Survey on Polysomnographic Characteristics of Patients with Obstructive Sleep Apnea

Background and Objective: Periodic limb movements of sleep (PLMS) and obstructive sleep apnea (OSA) are two common sleep disorders that frequently co-occur in one subject. In this study, we evaluated the polysomnographic (PSG) features of patients with OSA with and without PLMS.&#x0D; Materials and Methods: Patients with OSA diagnosed by PSG who referred to our sleep clinic over 2 years were studied for PLMS during a standard diagnostic sleep study. PSG features including apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and sleep quality were evaluated and compared between patients with OSA with and without PLMS.&#x0D; Results: We evaluated 122 patients with OSA, of whom 17 had comorbid PLMS. Mean sleep quality was significantly lower in patients with PLMS compared to those without PLMS (P &lt; 0.05). There was no significant difference in terms of mean age, gender, arousal index (AI), ODI, and apnea/hypopnea between the two groups.&#x0D; Conclusion: Patients with OSA with PLMS comorbidity have remarkably lower sleep quality and this finding is independent of the severity of arousals or respiratory events. Proper evaluation, diagnosis, and treatment of PLMS comorbidity in patients with OSA might improve treatment response.

The clinical characteristics of Parkinson's disease patients with concomitant periodic limb movements in sleep

The current study aimed to investigate the clinical characteristics of Parkinson's disease (PD) patients with concomitant periodic limb movements in sleep (PLMS). The clinical data of 36 PD patients who underwent polysomnography (PSG) in Beijing Tiantan Hospital from October 2018 to July 2022 were collected. Unified Parkinson's Disease Rating Scale 3.0 and Hoehn & Yahr (H-Y) stage were used to evaluate the disease severity. Patients were divided into two groups: the PLMS+group periodic limb movements in sleep index [(PLMSI)≥15 times/h] and the PLMS-group (PLMSI<15 times/h), using the PLMSI 15 times/h as the cut-off value. The clinical characteristics between the two groups were compared. There were 15 patients (42%) in the PLMS+group and 21 patients (58%) in the PLMS-group, among which 12 patients (12/15) in the PLMS+group and 9 patients (42.9%) in the PLMS-group had rapid eye movement sleep behavior disorder (RBD). The rate of RBD in PLMS+group was higher than that in PLMS-group (P<0.05). There was statistically significant difference in the blood folate level between the PLMS-group and PLMS+group [6.20 (5.14, 11.70) ng/ml vs 4.41 (3.07, 5.64) ng/ml] (P<0.01). Folate deficiency was more common in the PLMS+group, while no statistically significant differences were found in homocysteine and ferritin levels (both P>0.05). Four patients in the PLMS+group had falling experience, while 14.3% (3/21) patients in the PLMS-group had falling experience. Patients in the PLMS+group were more likely to fall. The PLMS+group had higher arousal index according to PSG [PLMS-group: 11.90 (9.10, 15.80) times/h; PLMS+group: 21.50 (19.35, 29.90) times/h] (P<0.05). No statistically significant differences in other sleep parameters were detected between the two groups (all P>0.05). Meanwhile, the apnea-hypopnea index (AHI) in both groups was higher than normal (<5 times/h), of which the PLMS-group was 9.80 (4.70, 22.20) times/h and the PLMS+group was 8.20 (1.70, 11.15) times/h, indicating that PD patients were more likely to experience sleep apnea and hypopnea. PD patients with PLMS had lower folate level, higher risk for falls, higher sleep arousal index, more sleep fragmentation, and higher prevalence of RBD.

0705 Restless sleep disorder and periodic limb movement disorder in children with history of prematurity

Abstract Introduction Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency, including restless legs syndrome and periodic limb movements of sleep (PLMS). In this study we assess the prevalence of restless sleep disorder and PLMS in children with history of prematurity. Methods Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity, from July 2021 to July 2022 at Seattle Children's Hospital. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery were included. Results During the study, 2,577 sleep studies were conducted, 162 were in children with history of prematurity (6%): 25 were split or titration studies (14%), 29 children had syndromes (Down, Prader Willi, Wiedmann Beckmann, Achondroplasia), 4 tracheostomy studies, 6 in infants aged &amp;lt; 12 months and 6 were post airway intervention. Ninety-two diagnostic studies were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; 18% had PLMS index &amp;gt;5/hour, 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). Altogether, children with RSD and those with PLMS had restless sleep as an indication for the sleep study in 70% of cases while snoring was the indication in only 26.7% of them. Conclusion We have previously reported that in the Seattle Children's Hospital Sleep Center the prevalence of RSD is 7.7% and that of PLMS is 9.3%; in this new analysis we found a higher frequency of RSD and elevated PLMS in children with history of prematurity. Premature children are higher risk of iron deficiency, among other complications and comorbidities. These new results confirm the previous reports of increased PLMS and add new knowledge on the prevalence of RSD in these children Support (if any)

0794 Effect of Surgical OSA Treatment on Periodic Limb Movements of Sleep in Pediatric Patients

Abstract Introduction The relationship between obstructive sleep apnea (OSA) and periodic limb movements of sleep (PLMS) is not completely understood, especially among pediatric patients. Previous research describes varied changes in PLMS following OSA treatment, including increased, decreased, or unchanged PLMS frequency. This study aimed to evaluate the effect of surgical OSA treatment on the periodic limb movement index (PLMI) in pediatric patients with OSA and significant PLMS. Methods Retrospective chart review was performed to identify pediatric patients who had polysomnography demonstrating significant PLMS (PLMI ≥ 5/hour) and OSA (obstructive apnea-hypopnea index (OAHI) ≥ 1.5/hour) that was treated with upper airway surgery. Patients aged 1-18 years were included if significant PLMS was present on either pre-treatment or post-treatment polysomnograms between 1/1/2010 and 7/31/2022. Patients were evaluated for changes in PLMI and OAHI between a pre- and post-treatment polysomnogram, each obtained within 12 months of OSA treatment. Patients with inadequate sleep time (&amp;lt; 2 hours) were excluded. Data are reported as mean ± standard deviation and results from mixed effect linear models. Results Medical record review identified 198 patients. The average age was 5.3±3.8 years (range 1.1-16.9 years) at pre-treatment polysomnogram, including 129 (65.2%) male patients. Adenotonsillectomy was the most common OSA treatment (n=136). For the whole group, the OAHI decreased from 12.3±15.3 to 5.3±8.1/hour and the PLMI increased from 5.5±8.5 to 7.0±8.7/hour after treatment, for an average PLMI increase of 1.5/hour (SE=0.7, p=0.04). Sub-group analysis of patients with decreased OAHI following treatment (n=152) showed an average PLMI increase of 2.3/hour (SE=0.8, p=0.004), while patients with increased OAHI following treatment (n=44) did not show a significant change in PLMI. There were 74 patients (37.4%) who developed significant PLMS following treatment and 36 patients (18.2%) with significant PLMS before and after treatment. Conclusion Effective OSA treatment led to increased PLMI among a majority of children, highlighting the potential for unmasking of PLMS in some pediatric patients with OSA. Furthermore, over one third of patients developed polysomnographic criteria for significant PLMS after OSA management. This may suggest a sub-group of children with OSA who have a PLMD phenotype that may not become apparent until appropriate OSA treatment. Support (if any)

1022 Two Teenagers with New Onset Insomnia post COVID

Abstract Introduction Sleep disturbances are increasingly seen in COVID-19 infection. Multiple reports have described the onset of insomnia, excessive daytime sleepiness, and fatigue in patients with both acute COVID infection and long COVID syndrome. Most of these are limited to adults. We report the cases of 2 teenagers with new onset chronic insomnia post COVID-19 infection. Report of case(s) The first patient is a 14-year-old male who presented with sleep onset and sleep maintenance insomnia, excessive daytime sleepiness, difficulty concentrating, fatigue, and chronic cough, with onset five months prior presentation to the sleep clinic. He developed these symptoms after testing positive for COVID-19. He had significant impairment with multiple school absences and tardies for which he required accommodation. He completed a 2-week actigraphy test which showed prolonged sleep latencies and insufficient sleep. He was scheduled for polysomnography (PSG) followed by a multiple sleep latency test (MSLT) but could not proceed to MSLT due to insufficient sleep the night before. The PSG did not reveal either obstructive sleep apnea or periodic limb movements of sleep. His laboratory testing was significant for a low ferritin level of 21. He was referred for IV iron infusion due to intolerance for oral iron. He was started on melatonin without benefit. He was offered clonidine and trazodone but declined. The second patient, a 17-year-old male, presented with insomnia of 3 months duration which started after an acute COVID infection. In addition to insomnia, he had comorbid mood symptoms. He went from being engaged in school and work to being unmotivated and listless. His actigraphy testing revealed he was having sufficient sleep on several days during which he reported not getting any sleep. He failed trials of multiple medications including melatonin, trazodone, hydroxyzine, and gabapentin. He also denied benefit with CBT-I. Conclusion These case reports link COVID 19 and chronic insomnia in pediatric patients. While it is yet unclear whether the development of sleep disturbances post COVID is as a result of an intrinsic characteristic of the COVID-19 virus or the biopsychosocial effects of the pandemic, it is important to develop and implement targeted interventions focused on recognizing and treating insomnia early. Support (if any)

Why the worsening at rest and worsening at night criteria for Restless Legs Syndrome are listed separately: review of the circadian literature on RLS and suggestions for future directions.

The field of circadian research on Restless Legs Syndrome (RLS) and periodic limb movements (PLMs) is reviewed in general. RLS has five obligatory criteria for diagnosis: (1) an urge to move the legs often accompanied by uncomfortable leg sensations; (2) symptoms are worse at rest, i.e., lying or sitting; (3) there is a least partial and temporary relief of symptoms by activity, e.g., walking or stretching or bending the legs; (4) symptoms are worse later in the day or at night; and (5) mimics of RLS such as leg cramps and positional discomfort should be excluded by history and physical. In addition, RLS is frequently accompanied by PLMs, either periodic limb movements of sleep (PLMS) as determined by polysomnography or periodic limb movements while awake (PLMW) as determined by the suggested immobilization test (SIT). Since the criteria for RLS were based upon clinical experience only, an early question after the development of the criteria was whether criteria 2 and 4 were the same or different phenomena. In other words, were RLS patients worse at night only because they were lying down, and were RLS patients worse lying down only because it was night? Early circadian studies performed during recumbency at different times of the day suggest that the uncomfortable sensations, PLMS, and PLMW as well as voluntary movement in response to leg discomfort follow a similar circadian pattern with worsening at night independent of body position and independent of sleep timing or duration. Other studies demonstrated that RLS patients get worse when sitting or lying down independent of the time of day. These studies as a whole suggest that the worsening at rest and the worsening at night criteria for RLS are related but separate phenomena and that criteria 2 and 4 for RLS should be kept separate based upon the circadian studies, as had been the case previously based upon clinical grounds alone. To more fully prove the circadian rhythmicity of RLS, studies should be conducted to see if bright light shifts the signs and symptoms of RLS to a different circadian time in concert with circadian markers.

Periodic limb movements in sleep are associated with hippocampal atrophy in stroke-free community-dwelling older adults.

Journal Article Accepted manuscript Periodic limb movements in sleep are associated with hippocampal atrophy in stroke-free community-dwelling older adults Get access Oscar H Del Brutto, Oscar H Del Brutto School of Medicine and Research Center, Universidad Espíritu Santo – Ecuador, Samborondón, Ecuador Corresponding author: Oscar H. Del Brutto, MD. Urbanización Toscana, Apt 3H, Km 4.5 vía Puntilla-Samborondón, 092301, Samborondón – Ecuador. Email: oscardelbrutto@hotmail.com https://orcid.org/0000-0003-1917-8805 Search for other works by this author on: Oxford Academic Google Scholar Robertino M Mera, Robertino M Mera Biostatistics/Epidemiology, Freenome, Inc., South San Francisco, CA, USA Search for other works by this author on: Oxford Academic Google Scholar Denisse A Rumbea, Denisse A Rumbea School of Medicine and Research Center, Universidad Espíritu Santo – Ecuador, Samborondón, Ecuador Search for other works by this author on: Oxford Academic Google Scholar Pablo R Castillo Pablo R Castillo Sleep Disorders Center, Mayo Clinic College of Medicine, Jacksonville, Florida, USA https://orcid.org/0000-0002-0423-1354 Search for other works by this author on: Oxford Academic Google Scholar Sleep, zsad088, https://doi.org/10.1093/sleep/zsad088 Published: 30 March 2023 Article history Received: 15 December 2022 Published: 30 March 2023

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

Many cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk. 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? 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. 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. 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. ClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www. gov.