Sleep-disordered breathing and stroke: therapeutic approaches.

The majority of stroke patients have clinically significant obstructive sleep apnea (OSA). Also, recent evidence demonstrates that OSA serves as an independent risk factor for stroke. Treatment of OSA following stroke is associated with neurologic and functional improvements, as well as long-term reduced risk of cardiovascular events. Identification of stroke patients at risk of OSA and subsequent diagnosis and treatment is essential in stroke recovery and reducing recurrent stroke risk. Continuous positive airway pressure (CPAP), the standard modality of treating OSA, is highly effective, but is often inadequately tolerated by stroke patients. Education and medical provider support are essential in establishing CPAP use in this population. However, in cases where CPAP therapy is not feasible, it is important for clinicians to be familiar with alternative modalities in treating OSA.

Sleep-Related Eating Disorder.

Sleep-related eating disorder is a non-rapid-eye movement parasomnia typified by recurrent episodes of eating/drinking following arousals, with associated partial/complete amnesia. Adverse health consequences and quality of life impairments are common. The condition can be idiopathic but most often accompanies unrecognized/untreated comorbid sleep disorders and/or is induced by psychoactive medications. As such, management consists of addressing comorbidities and removing potentially offending medications. While a thorough clinical history is often sufficient, additional sleep testing may help identify coexisting sleep disorders and/or other phenomena that may cause arousals. Limited data suggest benefit from topiramate and other medications in idiopathic or otherwise refractory cases.

Refractory Obstructive Sleep Apnea Secondary to Vagal Nerve Stimulation.

Vagal nerve stimulator (VNS) devices are commonly used as a non-pharmacologic option for improved seizure control in patients with refractory epilepsy. However, a side effect associated with VNS device placement includes sleep-disordered breathing, which is complicated by the fact that a significant minority of patients with epilepsy have sleep-disordered breathing. We describe a patient with iatrogenically worsened refractory obstructive sleep apnea (OSA) secondary to VNS device placement, which resolved upon turning off the VNS device. This case highlights the need to screen for OSA in patients who are candidates for VNS device placement, as iatrogenic sleep-disordered breathing could place the patient at risk for adverse clinical outcomes, as well as paradoxically worsen seizure control due to poor quality sleep.

Are scoring respiratory effort-related arousals worth the effort? --A study comparing outcomes between 4 % vs 3 % hypopnea scoring rules.

STUDY OBJECTIVES: The respiratory effort-related arousal (RERA) has been combined with apneas and hypopneas into the respiratory disturbance index (RDI). RERAs are characterized by ≥ 10 s of increasing upper airway effort terminating in arousal without meeting hypopnea criteria. The recent change to hypopnea definitions now includes a ≥30 % reduction in airflow for 10 s with EITHER a 3 % oxygen desaturation OR an arousal. Consequently, many events previously categorized as RERAs will now be included in the 3 % hypopneas, likely reducing the number of events scored as RERAs. We hypothesized that the 3 % apnea-hypopnea index (3%AHI) would approximate the 4%RDI, with the number of 3 % RERAs being negligible. RESEARCH QUESTION: How does the transition from the 4 % to the 3 % hypopnea rules impact the significance of RERAs in clinical practice, and how we should relate the AHI and RDI using the different hypopnea rules? METHODS: We prospectively collected 76 consecutive polysomnography results in 4 adult age groups. We re-scored the respiratory events utilizing both the 3 % and the 4 % hypopnea rules and compared the outcomes. RESULTS: Among 76 diagnostic studies (mean age 47.5 years, males 47.4 %), the 3 % RERA index [0.8 (0.0, 3.1)] [median (Q1, Q3)] was significantly lower than the 4 % RERA index [3.5 (1.0, 7.3)]. The 3%AHI was 3.07 ± 9.23 (mean ± SD) higher than the 4%RDI (p = 0.005). The 3%AHI was 8.63 ± 8.86 higher than the 4%AHI in all age groups (p < 0.001). This was mainly due to an increased hypopnea index (+8.51 ± 9.03, p < 0.001). In patients with obstructive sleep apnea (OSA), the 3%RERA contributes 4.3 % to the 3%RDI, while the 4%RERA contributes 27.7 % to the 4%RDI. INTERPRETATIONS: Both 3%RDI and 3%AHI are higher than the 4%RDI, primarily due to identification of more hypopnea events, resulting in more patients being classified as having OSA. This change in criteria complicates the comparison of hypopnea and RERA contributions between sleep studies scored using the different hypopnea rules.

Restless Legs Syndrome and Periodic Limb Movements of Sleep: From Neurophysiology to Clinical Practice.

SUMMARY: This article summarizes restless legs syndrome (RLS), periodic limb movements of sleep, and periodic limb movement disorder. RLS is a common sleep disorder with a prevalence of 5% to 15% in the general population. RLS can present in childhood, and incidence increases with age. RLS can be idiopathic or secondary to iron deficiency, chronic renal failure, peripheral neuropathy, and medications such as antidepressants (with higher rates for mirtazapine and venlafaxine, while bupropion may reduce symptoms at least in the short term), dopamine antagonists (neuroleptic antipsychotic agents and antinausea medications), and possibly antihistamines. Management includes pharmacologic agents (dopaminergic agents, alpha-2 delta calcium channel ligands, opioids, benzodiazepines) and nonpharmacologic therapies (iron supplementation, behavioral management). Periodic limb movements of sleep are an electrophysiologic finding commonly accompanying RLS. On the other hand, most individuals with periodic limb movements of sleep do not have RLS. The clinical significance of the movements has been argued. Periodic limb movement disorder is a distinct sleep disorder that arises in individuals without RLS and is a diagnosis of exclusion.

Emergence of restless legs syndrome during opioid discontinuation.

STUDY OBJECTIVES: The development of restless legs syndrome (RLS) has been rarely reported during and following opioid withdrawal. We aimed to determine the presence and severity of RLS symptoms during and after supervised opioid tapering. METHODS: Ninety-seven adults enrolled in the Mayo Clinic Pain Rehabilitation Center who underwent supervised prescription opioid tapering were prospectively recruited. RLS presence and severity was assessed with the Cambridge-Hopkins Questionnaire 13 and International Restless Legs Syndrome Study Group Rating Severity Scale at admission, midpoint, and dismissal from the program as well as 2 weeks, 4 weeks, and 3 months after completion. Frequency and severity of RLS symptoms were compared between admission and each time point. RESULTS: Average age of the cohort was 52.6 ± 13.3 years with a morphine milligram equivalent dose for the cohort of 45.6 ± 48.3 mg. Frequency of RLS symptoms increased from 28% at admission to peak frequency of 41% at 2 weeks following discharge from the Mayo Pain Rehabilitation Clinic (P = .01), returning to near baseline frequency 3 months after opioid discontinuation. International Restless Legs Syndrome Study Group Rating Severity Scale increased from baseline and then remained relatively stable at each time point following admission. Thirty-five (36.1%) participants developed de novo symptoms of RLS during their opioid taper, with those being exposed to higher morphine milligram equivalent doses having higher risk of developing RLS. CONCLUSIONS: Moderately severe symptoms of RLS, as assessed by survey, occur commonly in individuals undergoing opioid tapering, particularly if exposed to higher doses. In many cases, symptoms appear to be self-limited, although a minority develop persistent symptoms. Our results may have implications for successful opioid tapering, but future confirmatory studies with structured clinician interview are needed to establish that these symptoms truly represent restless legs syndrome given the potential for RLS-mimicking symptoms in individuals with chronic pain syndromes. CITATION: McCarter SJ, Labott JR, Mazumder MK, et al. Emergence of restless legs syndrome during opioid discontinuation. J Clin Sleep Med. 2023;19(4):741-748.

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea.

Objective: Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA. Methods: Newly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality. Results: In cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69-0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05-1.31) and women (OR 1.26, 95% CI 1.10-1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5-8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05-1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality. Conclusion: The implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized.

Patient values and preferences regarding prognostic counseling in isolated REM sleep behavior disorder.

STUDY OBJECTIVES: Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. METHODS: One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. RESULTS: Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. CONCLUSIONS: Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients' values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

Artificial intelligence-enabled detection and assessment of Parkinson's disease using nocturnal breathing signals.

There are currently no effective biomarkers for diagnosing Parkinson's disease (PD) or tracking its progression. Here, we developed an artificial intelligence (AI) model to detect PD and track its progression from nocturnal breathing signals. The model was evaluated on a large dataset comprising 7,671 individuals, using data from several hospitals in the United States, as well as multiple public datasets. The AI model can detect PD with an area-under-the-curve of 0.90 and 0.85 on held-out and external test sets, respectively. The AI model can also estimate PD severity and progression in accordance with the Movement Disorder Society Unified Parkinson's Disease Rating Scale (R = 0.94, P = 3.6 × 10-25). The AI model uses an attention layer that allows for interpreting its predictions with respect to sleep and electroencephalogram. Moreover, the model can assess PD in the home setting in a touchless manner, by extracting breathing from radio waves that bounce off a person's body during sleep. Our study demonstrates the feasibility of objective, noninvasive, at-home assessment of PD, and also provides initial evidence that this AI model may be useful for risk assessment before clinical diagnosis.

ATS Core Curriculum 2021. Adult Sleep Medicine: Sleep Apnea.

The American Thoracic Society Sleep Core Curriculum updates clinicians on important sleep topics, presented during the annual meeting, and appearing in summary here. This year's sleep core theme is sleep-disordered breathing and its management. Topics range from pathophysiological mechanisms for the association of obstructive sleep apnea (OSA) and metabolic syndrome, surgical modalities of OSA treatment, comorbid insomnia and OSA, central sleep apnea, and sleep practices during a pandemic. OSA has been associated with metabolic syndrome, independent of the role of obesity, and the pathophysiology suggests a role for sleep fragmentation and intermittent hypoxia in observed metabolic outcomes. In specific patient populations, surgical treatment modalities for OSA have demonstrated large reductions in objective disease severity compared with no treatment and may facilitate adherence to positive airway pressure treatment. Patient-centered approaches to comorbid insomnia and sleep apnea include evaluating for both OSA and insomnia simultaneously and using shared-decision making to determine the order and timing of positive airway pressure therapy and cognitive behavioral therapy for insomnia. The pathophysiology of central sleep apnea is complex and may be due to the loss of drive to breathe or instability in the regulatory pathways that control ventilation. Pandemic-era sleep practices have evolved rapidly to balance safety and sustainability of care for patients with sleep-disordered breathing.

Specialist approaches to prognostic counseling in isolated REM sleep behavior disorder.

OBJECTIVES/BACKGROUND: Most middle-aged and older adult patients with isolated (idiopathic) REM sleep behavior disorder (RBD) eventually develop parkinsonism, dementia with Lewy bodies, or multiple system atrophy. We aimed to describe the current sleep medicine specialist approach toward RBD prognostic counseling, and to determine physician beliefs and characteristics that impact provision of counseling. PATIENTS/METHODS: We surveyed 70 sleep medicine physicians with RBD expertise for demographic information, counseling practices, and their beliefs and understandings concerning the association between RBD and synucleinopathies, among other questions. Responses were summarized by descriptive statistics. RESULTS: Among the 44 respondents (63% response rate), 41 (93.2%) regularly provided prognostic counseling for most RBD patients, but only 31.8% routinely asked about patient preferences on receiving counseling. 41.8% believed that the risk for developing overt synucleinopathy following RBD diagnosis was >80%, but only 15.9% routinely provided this detailed phenoconversion risk estimate to their patients. Most respondents were concerned that RBD prognostic counseling could adversely impact on the patient's and family's mental health. CONCLUSIONS: Most expert RBD sleep clinicians routinely counsel their patients regarding the high risk for phenoconversion to parkinsonism or dementia, yet relatively few routinely ask patients about their preferences for receiving this information, and fewer provide details concerning the known high risk estimates for developing a synucleinopathy. Future research should analyze patients' values and preferences in RBD populations to inform approaches toward shared decision making for RBD prognostic counseling.

ATS Core Curriculum 2020. Adult Sleep Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3-4-year recurring cycle of topics. These topics will be presented at the 2020 Virtual Conference. Below is the adult sleep medicine core that includes topics pertinent to sleep-disordered breathing and insomnia.

Correlation of the Epworth Sleepiness Scale and Sleep-Disordered Breathing in Men and Women.

STUDY OBJECTIVES: To compare Epworth Sleepiness Scale (ESS) scores of men and women and determine if there is a correlation with sleep-disordered breathing (SDB) based on subsequent polysomnography (PSG). METHODS: Consecutive adult patients were identified who completed ESS and PSG at Mayo Clinic in Rochester, Minnesota, between January 1, 2013, and January 31, 2015. Apnea-hypopnea index (AHI) ≥ 5 events/h was classified as presence of SDB, and increasing values represented greater severity. RESULTS: Among 6,593 patients with valid ESS scores and timely subsequent PSG, 42% were women. Mean (standard deviation [SD]) age of women was 56.2 (15.2) years; men, 58.5 (15.1) years. Mean (SD) ESS score was 9.5 (5.4) for women and 9.5 (5.3) for men. SDB was present in 83.6% of men and 68.3% of women. Mean (SD) AHI of men was 25.9 (26.7) events/h; women, 16.1 (22.4) events/h (P < .001). Each unit increase in ESS score of men was associated with a 0.51-unit increase in AHI (P < .001); women had a 0.16-unit associated increase (P = .04) (effect ratio, threefold greater for men). PSG demonstrated that women had greater sleep efficiency, less respiratory effort-related arousals, and less hypoxemia (all P < .001). Among women, ESS did not correlate with presence of SDB or mild to moderate SDB. There was a small association in women with severe SDB. CONCLUSIONS: ESS is not correlated with SDB at mild to moderate levels in women and has a smaller association than in men with severe SDB. Further work is necessary to understand sex-specific differences in patients with SDB.

Physician and patient determinants of prognostic counseling in idiopathic REM sleep-behavior disorder.

OBJECTIVES/BACKGROUND: Prognostic counseling about the risk for developing overt neurodegenerative disorders for patients with idiopathic REM sleep-behavior disorder (iRBD) and isolated REM sleep without atonia (iRSWA) is difficult, given lack of disease-modifying interventions and uncertainty in accurate prognostication for individuals. We aimed to analyze patient and physician characteristics associated with documented prognostic discussions for patients with iRBD and iRSWA. PATIENTS/METHODS: We retrospectively reviewed the medical records for 138 (112 iRBD and 26 iRSWA) patients seen at the Mayo Clinic between 2012 and 2015. We analyzed physician and patient demographics, initial complaint, and other information discussed during office visits. We then comparatively analyzed the impact of physician and patient characteristics on documented prognostic discussions using Chi Square or Fischer's exact test. RESULTS: Mean iRBD patient age was 65.0 ± 13.0, and mean iRSWA age was 58 ± 15 years. Seventy-eight (69.6%) iRBD and 22 (84.6%) iRSWA patients were men. Sixty-two (55%) iRBD and three (12%) iRSWA patients received prognostic counseling about phenoconversion risk. iRBD was a secondary complaint in 67 (59.8%). Patients over age 60 years and those having iRBD as a chief complaint more frequently received prognostic discussions than those with opposite characteristics (all p < 0.05). Patient sex and antidepressant use were not associated with counseling. Sleep neurologists disclosed prognostic information most frequently, with male more likely than female clinicians to disclose prognoses. CONCLUSIONS: Several patient and physician characteristics appear to influence documented prognostic counseling for iRBD/RSWA patients. Future studies of iRBD/RSWA patients' preferences are needed to clarify ethically appropriate physician-patient communication concerning prognosis.

Narcolepsy: Diagnosis and management.

Narcolepsy is a chronic disorder of hypersomnia that can have a significant impact on quality of life and livelihood. However, with appropriate treatment, its symptoms are manageable, and a satisfying personal, social, and professional life can still be enjoyed. Greater awareness of the disorder promotes accurate and efficient diagnosis. With ongoing research into its underlying biology, better treatments for narcolepsy will inevitably become available.

Association of vasomotor symptoms and sleep apnea risk in midlife women.

OBJECTIVE: The aim of the study was to determine the association between self-reported vasomotor symptoms (VMS) and obstructive sleep apnea (OSA) risk. METHODS: The STOP-BANG to evaluate OSA and Menopause Rating Scale (MRS) were administered to 2,935 women seen in the Women's Health Clinic at Mayo Clinic in Rochester, MN, between May 2015 and December 2016. Of these, 1,691 women were included in the analysis. Total MRS and VMS ratings were compared using logistic regression, with age, smoking, and body mass index (BMI) included as covariates between women at intermediate/high risk versus low risk for OSA. RESULTS: Total MRS scores were significantly higher in women with intermediate/high-risk OSA scores versus those with low-risk scores [mean (SD): 16.8 (8.0) vs 12.9 (7.0), P < 0.001]. Women at intermediate/high OSA risk were older, had more education, self-reported hypertension, BMI >35 kg/m, and were less likely to be married or employed. Self-reported severe/very severe VMS were significantly associated with intermediate/high risk versus low risk for OSA (26.6% vs 15.0%; P < 0.001). After adjusting for age, BMI, smoking status, and self-reported hypertension, the odds of having intermediate/high risk for OSA were 1.87 times higher for those with severe/very severe VMS compared with those with none/mild/moderate VMS (95% CI, 1.29-2.71, P < 0.001). This association persisted upon subgroup analysis based on BMI <25 kg/m (odds ratio 2.15; 95% CI, 1.12-4.16, P = 0.022). CONCLUSIONS: Self-reported severe/very severe VMS were associated with intermediate/high risk for OSA in midlife women, even in women with BMI <25 kg/m. Given the limitations of the STOP-BANG tool, OSA risk may, however, have been overestimated.

Serotnin as a possible biomarker in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a highly prevalent disease which carries substantial public health burden. Polysomnography is the standard procedure used to diagnose OSA. However cost, accessibility, technical requirements, and skilled interpretation needs constrain its widespread use and have a role in the under-diagnosis of sleep disordered breathing. There is a clinical need to develop expedient and widely accessible tools to detect this disorder., Several biochemical markers have recently been proposed as diagnostic tools in OSA. Numerous neurochemicals directly influence the activity of upper airway dilator motor neurons, which subsequently influence respiration during sleep. Serotonin (5-HT) is one such neurochemical that has a key role in ventilatory stimulation. Herein, we review the current evidence demonstrating relationships between multiple biomarkers and sleep disordered breathing and focus on relationships between OSA and 5-HT. We discuss the possibility of biomarker-driven detection technology in the future as a means of diagnosing and monitoring OSA. Finally, we explore the specific role 5-HT may have in the future in both the diagnosis and treatment of OSA.

Obstructive sleep apnea in the perioperative setting: complications and management strategies.

Obstructive sleep apnea (OSA) is frequently encountered in an undiagnosed, untreated state in perioperative patients. It increases the risk of respiratory, cardiac, and infectious complications following surgical procedures. Patients with OSA may require additional monitoring, unplanned escalations in care, and prolonged hospitalization. It is important to identify patients at risk for OSA during the preoperative assessment so that appropriate anesthesia, postsurgical monitoring, and pain control can be planned. Herein, we discuss data regarding perioperative outcomes in patients with OSA, methods to quickly identify patients at high risk for OSA, and implementation of clinical safeguards to minimize OSA-associated complications. An algorithm is provided to guide the perioperative management of patients with OSA.

Associations between Cardioembolic Stroke and Obstructive Sleep Apnea.

STUDY OBJECTIVES: To assess etiology of ischemic stroke in patients with obstructive sleep apnea (OSA) compared with controls. This information may aid in determining how OSA increases stroke risk and facilitate recurrent stroke prevention in patients with OSA. DESIGN: Retrospective, case-control study. SETTING: Academic tertiary referral center. PATIENTS: Consecutive patients who underwent polysomnography and had an ischemic stroke within 1 year were identified. Stroke subtype was determined using two validated algorithms. Polysomnographic results were used to separate patients into OSA cases and controls. Information regarding cardiovascular risks, neuroimaging, and echocardiographic data were collected. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In 53 subjects, cardioembolic (CE) strokes were more common among OSA cases than controls (72% versus 33%, P = 0.01). The majority of CE strokes occurred in those with moderate to severe OSA. Atrial fibrillation (AF) was more frequent in OSA cases (59% versus 24%, P = 0.01). The association between OSA and CE stroke remained significant after controlling for AF (P = 0.03, odds ratio 4.5). CONCLUSIONS: There appears to be a strong association between obstructive sleep apnea (OSA) and cardioembolic (CE) stroke. In patients with OSA presenting with cryptogenic stroke, high clinical suspicion for CE is warranted. This may lead to consideration of diagnostic studies to identify CE risk factors such as paroxysmal atrial fibrillation (AF). CE strokes are more common in patients with OSA even after adjusting for AF. This finding may reflect a high rate of occult paroxysmal AF in this population; alternatively, OSA may lead to CE strokes through mechanisms independent of AF.