World Stroke Organization The Paper of the Month February
01 Feb 2022A Short History of Progress in Sleep Apnea and Stroke
Title: A Short History of Progress in Sleep Apnea and Stroke
Author: Dr. Gustavo Saposnik, EiC, WSA
This article is a commentary on the following
“Sleep is that golden chain that ties health and our bodies together”
– Thomas Dekker (English dramatist, 1572-1632)
Commentary:
Sleep disorders are a prevalent medical condition in the general population. According to the American Sleep Association, 50 to 70 million of adults in the USA have a sleep disorder, half of them had obstructive sleep apnea (OSA) and 48.0% report snoring.1 The consequences of poor sleep quality include fatigue, irritability, anxiety, daytime dysfunction, slowed responses, and perpetuating mechanisms that leads to other disruptive behavior (e.g. increased caffeine, alcohol, smoking and food intake).2
Sleep disorders include insomnia, sleep apnea, rapid eye movement (REM) sleep behavior disorder, and circadian rhythm disorders. Sleep apnea is one of the most sleep disorders conditions. Obstructive sleep apnea, the most prevalent sleep apnea is manifested by a partial or complete interruption of airflow during sleep. It affects nearly 50% of patients with an ischemic stroke.3 In the present article,4 the authors provided a detailed review of the existing gaps in the diagnosis, management, and follow-up strategies of sleep apnea in stroke patients.
What have we learned about sleep apnea in patients with an ischemic stroke in the last two decades?
- The most common cause of sleep apnea is obstructive- also called Obstructive sleep apnea (OSA). It occurs when there is a change in the sleep pattern with hypopneas or apneas when the upper airway structures collapse.
- The diagnosis of OCA is based on the Apnea–hypopnea index (AHI) defined as the number of apnea and hypopnea events per hour of sleep. An AHI index greater than 15 per hour commonly measured with polysomnography.5
- Central sleep apnea after stroke is less common approximately affecting 8-12% of patients according to a meta-analysis (compared to <1% in the general population).6, 7
- Respiratory metrics (e.g. hypoxic burden and arousal index) other than the AHI may improve the accuracy in the diagnosis and outcome prediction.
- The authors report a wide range (20-86%) of the pooled prevalence of OSA depending on the population target (e.g. TIA vs post-stroke), acute vs. chronic setting and severity.3
- The most common factors associated with OSA in stroke patients (e.g. male sex, obesity,hypertension and diabetes) are similar to those reported in the general population.
- The authors proposed an algorithm for an effective screening, diagnosis and management of sleep apnea associated with stroke.
- Consequences of sleep apnea among stroke patients: The authors provided evidence regarding sleep apnea worsening stroke outcomes, the increased the incident risk of recurrent stroke, all cause mortality and an impaired functional recovery (including dementia).4, 8-10
- Respiratory (non-invasive ventilation, CPAP, or adaptative servo ventilation) and general recommendations (e.g. optimization vascular risk factors, sleep hygiene) are nicely summarized by the authors in a graph.
- Recent meta-analyses provided evidence on th benefits of CPAP functional outcomes (standardised mean differences 0.54, 95% CI 0.03–1.05).11
In summary, the present review article summarizes the advances on this topic. As highlighted by the authors several uncertainties remained. We need more sensitive metrics for the diagnosis of OSA and central sleep apnea, designing new diagnostic and therapeutic algorithms based on artificial intelligence models, and developing more cooperative approach integrating the expertise from respirologists, sleep medicine experts, stroke neurologists, academic organizations, patients with live experiences and policymakers.
References:
- Association AS. Sleep and Sleep Disorder Statistics. 2022.
- Nelson KL, Davis JE and Corbett CF. Sleep quality: An evolutionary concept analysis. Nursing forum. 2022;57:144-151.
- Bassetti CLA, Randerath W, Vignatelli L, Ferini-Strambi L, Brill AK, Bonsignore MR, Grote L, Jennum P, Leys D, Minnerup J, Nobili L, Tonia T, Morgan R, Kerry J, Riha R, McNicholas WT and Papavasileiou V. EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke. Eur J Neurol. 2020;27:1117-1136.
- Baillieul S, Dekkers M, Brill AK, Schmidt MH, Detante O, Pepin JL, Tamisier R and Bassetti CLA. Sleep apnoea and ischaemic stroke: current knowledge and future directions. Lancet Neurol. 2022;21:78-88.
- Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K and Harrod CG. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13:479-504.
- Seiler A, Camilo M, Korostovtseva L, Haynes AG, Brill AK, Horvath T, Egger M and Bassetti CL. Prevalence of sleep-disordered breathing after stroke and TIA: A meta-analysis. Neurology. 2019;92:e648-e654.
- Dong R, Dong Z, Liu H, Shi F and Du J. Prevalence, Risk Factors, Outcomes, and Treatment of Obstructive Sleep Apnea in Patients with Cerebrovascular Disease: A Systematic Review. J Stroke Cerebrovasc Dis. 2018;27:1471-1480.
- Catalan-Serra P, Campos-Rodriguez F, Reyes-Nunez N, Selma-Ferrer MJ, Navarro-Soriano C, Ballester-Canelles M, Soler-Cataluna JJ, Roman-Sanchez P, Almeida-Gonzalez CV and Martinez-Garcia MA. Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea. Stroke. 2019;50:491-494.
- Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S and Somers VK. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017;69:841-858.
- Dunietz GL, Chervin RD, Burke JF, Conceicao AS and Braley TJ. Obstructive sleep apnea treatment and dementia risk in older adults. Sleep. 2021;44.
- Brill AK, Horvath T, Seiler A, Camilo M, Haynes AG, Ott SR, Egger M and Bassetti CL. CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials. Neurology. 2018;90:e1222-e1230.
Author Interview
Prof. Claudio Bassetti
(Professor of Neurology, Chair of the Neurology Department at the Inselspital in Bern and Dean of the Medical Faculty at the University of Bern, Switzerland)
1. What did you set out to study?
The link between sleep apnoea (SA) and stroke is long known. Nevertheless, several aspects of this association, such as the prevalence, the pathophysiology, diagnostics, and therapeutic options for SA associated with stroke have been elucidated only in the last 1-2 decades. This knowledge is of relevance because SA has been shown to modulate stroke outcome, increase the risk of recurrent stroke and all-cause mortality, and worsen functional recovery.
Despite these advances, SA remains underdiagnosed and untreated in most patients, due to challenges in the detection and prediction of post-stroke SA, uncertainty as to the optimal timing for its diagnosis, and a scarcity of clear treatment guidelines.
2. Why this topic?
Sleep plays a fundamental role in maintaining health, including brain health. Sleep disturbances and brain health are linked in a bidirectional fashion where sleep disturbances act both as a risk factor and as a prodromal marker of poor brain health.
SA is globally one of the most common chronic diseases and affects more than half of stroke survivors during the acute phase after stroke. In turn, untreated SA leads to a two-fold higher risk for stroke, arguing for the inclusion of SA screening in the post-stroke work-up.
3. What were the key findings?
One key finding of this review is the importance of a clear identification of SA subtypes, i.e. obstructive and central SA, as they differ in terms of pathophysiology and treatment. In fact, we suggest that the choice of treatment should be based not solely on SA severity but requires a characterisation of the underlying endophenotypes, and the analysis of associated symptoms and comorbidities.
A second key-finding of our work is the definition, based on literature findings, of decision trees for diagnosis and treatment of SA in stroke patients.
4. Why is it important? Or how might these results impact clinical practice?
The primary aim was to raise awareness about the importance of SA in stroke patients. Today screening for SA is not a routine in most stroke units. This review will hopefully support the development of standard operating procedures for an effective management of SA associated with stroke and promote individualized treatment approaches to improve sleep quality, daytime functioning, and outcome.
5. What surprised you most?
Despite the progressing knowledge on SA associated with stroke, (even severe) SA remains often overlooked and untreated in most stroke patients.
6. What’s next for this research?
Few key-questions remain unanswered:
- At what time-point stroke survivors should be screened and treated after stroke? SA treatment reduces the risk for recurrent events, likely at whatever time treatment is started. However, SA treatment also may improve functional stroke outcome, and treatment initiation acutely after stroke may even improve stroke lesion recovery. The latter question is the main endpoint of our eSATIS study2 [NCT02554487], for which we recently completed recruitment.
- What should be screened for in stroke patients? Over the last couple of years evidence has emerged from several groups that the apnoea-hypopnea index (AHI), the standard metric for SA severity, may not reflect the actual risk conveyed by SA most accurately. In the paper we discuss the possibility that, in addition to the number of breathing events occurring in sleep, the extent of oxygen desaturations and sleep fragmentation per se may also be important. These questions are currently being addressed in an observational cohort study in Bern called Sleep Deficiency and Stroke Outcome [NCT02559739].
- What is the natural evolution of SA after stroke? Our current knowledge is based on very few polysomnographic studies, including our SAS-CARE 1 study [NCT01097967]. However, large-scale real-life data are needed. The ongoing and actively recruiting ASCENT (Apnoea, Stroke and Incident Cardiovascular Events) cohort [NCT04399200] study conducted in Grenoble will aim at addressing health trajectories of patients following a first ischemic stroke or transient ischemic attack, related to their SA status and treatment.
7. Is there anything you’d like to add?
This review exclusively focussed on SA. Although it is the most frequent and best studied sleep disorder, evidence is beginning to emerge that other sleep-wake disorders including insomnia, fatigue and excessive daxtime sleepiness/ are also frequent after stroke.3, 4
Multidisciplinary efforts are thus required to improve clinical/research pathways regarding the association of stroke and sleep-wake disturbances. We anticipate that such work will further anchor sleep medicine in care pathways and health trajectories of stroke patients.
8. References
- Baillieul S, Bailly S, Detante O, Alexandre S, Destors M, Clin R, et al. Sleep-disordered breathing and ventilatory chemosensitivity in first ischaemic stroke patients: a prospective cohort study. Thorax. 2021. 10.1136/thoraxjnl-2021-218003
- Duss SB, Brill AK, Baillieul S, Horvath T, Zubler F, Flugel D, et al. Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke). Trials. 2021;22:83. 10.1186/s13063-020-04977-w
- Hasan F, Gordon C, Wu D, Huang HC, Yuliana LT, Susatia B, et al. Dynamic Prevalence of Sleep Disorders Following Stroke or Transient Ischemic Attack: Systematic Review and Meta-Analysis. Stroke. 2021;52:655-63. 10.1161/STROKEAHA.120.029847
- Bassetti CLA, Randerath W, Vignatelli L, Ferini-Strambi L, Brill AK, Bonsignore MR, et al. EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke. Eur J Neurol. 2020;27:1117-36. 10.1111/ene.14201
Video Interview:
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