Sleep-Disordered Breathing in the Acute Phase After Stroke and Neuropsychiatric Outcomes
Conditions: Stroke, Fatigue Symptom, Obstructive Sleep Apnea, Sleep Disordered Breathing (SDB)
Sponsor: Blekinge County Council Hospital

 
 
 
 
 
 
 
 
 
 
 
Sleep-Disordered Breathing in the Acute Phase after 
Stroke and Neuropsychiatric Outcomes 
 
2025-01-31 
 
 

Sleep-Disordered Breathing in the Acute Phase after Stroke and Neuropsychiatric 
Outcomes  
 
Background/Objectives  
Stroke is the second leading cause of death and a common cause of acquired disability 
worldwide, and the burden of the disease at the societal level is expected to increase in the 
coming decades (1-4). Stroke can result in various long-term consequences, both neurological 
(such as aphasia, paresis, sensory or visual disturbances, and coordination and balance 
disorders) and neuropsychiatric (such as cognitive impairment, depression, and fatigue) (5-8). 
These consequences, in turn, affect stroke survivors' physical functions, activity levels, and 
ability to participate in daily activities (9-13).  
Post-stroke fatigue is common, with prevalence estimates ranging between 25- 85%, and 40% 
of stroke survivors have reported it as one of their worst symptoms (14-16). Recent Swedish 
studies have estimated the long-term prevalence 3-5 years after stroke to be between 24-52% 
(17, 18). Post-stroke fatigue partially overlaps with post-stroke depression, but approximately 
70% of individuals with significant fatigue do not exhibit concurrent depressive symptoms 
(17). The condition is associated with poorer performance in daily activities and lower health-
related quality of life (17). Currently, there are no specific treatments for post-stroke fatigue 
(19). Due to its high prevalence and consequences, it has recently been identified as one of 
the top ten priority research questions in stroke rehabilitation by the UK National Institute for 
Health and Care Research (20).  
There are conflicting reports on whether traditional vascular risk factors such as 
hypertension, hyperlipidemia, heart disease (including atrial fibrillation), and smoking 
contribute to post-stroke fatigue (21, 22). Obesity is associated with post-stroke fatigue, and 
sleep-disordered breathing (SDB) has also emerged as a potential risk factor (23).  
Sleep-disordered breathing is prevalent after stroke, occurring in 50-70% of some populations 
(25). The dominant condition is obstructive sleep apnea syndrome (OSAS), followed by 
central sleep apnea (26). Established treatments for OSAS include continuous positive airway 
pressure (CPAP), mandibular advancement devices, surgical interventions, and weight loss 
(26), which can reduce daytime sleepiness. Research is ongoing regarding the extent to which 
treated OSAS can contribute to secondary prevention in stroke (27). Current American 
guidelines for secondary prevention provide a class 2b recommendation with moderate 
evidence for considering OSAS screening after stroke or transient ischemic attack (TIA) (28).  
The diagnosis is primarily made through overnight respiratory monitoring, with 
polysomnography being the gold standard, although it is time- and resource-intensive and 
may be cumbersome for the patient (29). Limited polygraphic examinations can also be 
conducted both in hospitals and at home (29).  
 

Research Questions:  
1. What is the 1-year prevalence of post-stroke fatigue in a hospital-based cohort in 
Blekinge?  
2. How many individuals with stroke have significant sleep-disordered breathing according 
to non-invasive measurement?  
3. What proportion of individuals with post-stroke fatigue had significant sleep-disordered 
breathing during hospitalization?  
4. Can early, non-invasive, and simple measurement of sleep-disordered breathing in 
hospitals predict a subgroup of stroke patients who will develop significant fatigue?  
5. Is there evidence that treatment goals after stroke are achieved to a lesser extent in those 
with significant fatigue?  
 
By answering these questions, our study aims to: i) Facilitate patient selection for potential 
future clinical trials, e.g., CPAP treatment for preventing/treating post-stroke fatigue. ii) 
Identify potential subgroups among individuals with post-stroke fatigue. iii) Investigate risk 
factors for post-stroke fatigue, including sleep-disordered breathing. iv) Examine whether 
fatigue leads to poorer adherence to secondary preventive treatment goals (30).  
Methodology  
The present study has been approved by the Swedish Ethical Review Authority, diary number 
2024-02659-01.  
Study participants will be prospectively identified at the Department of Medicine, Blekinge 
Hospital, Karlskrona. Inclusion and exclusion criteria are as follows:  
 
Inclusion criteria:  
• 
Age >18 years  
• 
Stroke according to WHO definition (31) (ischemic stroke, intracerebral hemorrhage, 
or subarachnoid hemorrhage)  
• 
TIA with MRI-verified lesions corresponding to symptoms  
• 
Informed consent to participate  
 
Exclusion criteria:  
• 
Traumatic stroke  
• 
Tumor-associated bleeding  
• 
Expected survival <3 months  
• 
Unconsciousness (RLS >3)  
 
Potential participants will be identified by medical staff, and informed consent will be 
obtained by a researcher.  
 

Upon obtaining consent, patients will be equipped with a Withings Sleep Analyzer and a 
Nonin WristPro 2 pulse oximeter during hospital stay days 1- 3.Withings Sleep Analyzer is 
validated to detect moderate-severe obstructive sleep apnea (32). The patient is also equipped 
with a Nonin WristPro 2 pulse oximeter with the possibility to retrospectively obtain 
registered data regarding nocturnal hypoxia (T90 – time under 90% oxygen saturation, and 
ODI – oxygen desaturation index).  
Baseline data collected include:  
• 
National Institutes of Health Stroke Scale (NIHSS) (33)  
• 
Pre-stroke modified Rankin Scale (mRS) (34)  
• 
Previous stroke history  
• 
BMI  
• 
STOP-BANG questionnaire (35)  
 
If it is not possible to obtain these data, including NIHSS, during the hospital stay, they will 
be collected later through chart review when possible. During chart review/clinical 
examination, the following will also be recorded:  
• 
Main subtype of stroke (IS, ICH, SAH)  
• 
Oxfordshire Community Stroke Project classification (OCSP) (36)  
• 
Trial of Org 10172 in acute stroke treatment (TOAST) classification (37)  
• 
Charlson Comorbidity Index (CCI) (38)  
• 
Hypertension (>140/90 mmHg at discharge or antihypertensive treatment in the last 2 
weeks)  
• 
Diabetes mellitus (previous diagnosis, fasting blood glucose >6.1 mmol/L, or non-
fasting blood glucose >11 mmol/L)  
• 
Heart disease (ischemic heart disease, previous MI, angina, PCI, CABG, heart failure, 
arrhythmias)  
• 
Hyperlipidemia (previous diagnosis, lipid-lowering treatment, total cholesterol >5 
mmol/L, LDL >3 mmol/L)  
• 
Smoking  
• 
COPD (ICD-10 J44 or described in chart)  
• 
Depression diagnosis (ICD F32-33) or antidepressant treatment  
• 
HbA1c, lipid status, blood pressure at discharge  
• 
Medications (antiplatelets, anticoagulants, antidiabetics, antihypertensives, opioids, 
sedatives, statins, antidepressants) at onset and discharge  
• 
Long-term ECG monitoring  
• 
Carotid stenosis degree on carotid ultrasound exam  
• 
Coagulation assessment, if performed  
• 
Previous stroke/recurrent stroke within 1 year  
 

Participants are subsequently invited via letter for a follow-up visit approximately 1 year after 
stroke (+3 months, but not earlier than 1 year) at the district nurse students' training clinic at 
Blekinge Institute of Technology. During this visit, the following will be recorded:  
Follow-up assessment (1 year after stroke):  
• 
Fatigue Assessment Scale (FAS) (39)  
• 
Fatigue Visual Analogue Scale (VAFS)  
• 
PHQ-9 depression scale (40)  
• 
mRS (34)  
• 
Blood pressure  
• 
Height, weight, BMI  
• 
Blood tests (HbA1c, lipid profile)  
• 
Smoking  
• 
Medication adherence  
• 
Stroke Impact Scale (41)  
• 
Ongoing BiPAP or CPAP treatment  
• 
Alcohol consumption  
 
Recruitment Calculation  
With a confidence level of 0.05, statistical power of 80%, an estimated OSAS prevalence of 
50%, and estimated significant fatigue prevalence of 30%, a total cohort of 284 participants is 
required to detect a doubled relative risk of significant fatigue with OSA. Considering a 10-
20% loss to follow-up, approximately 340 participants need to be included.  
 
Ethical Considerations  
The project involves non-invasive procedures except for blood sampling at follow-up. 
Written informed consent will be obtained.  
Data for research purposes such as apnea-hypopnea index and time under 90% blood oxygen 
saturation are collected outside of clinical praxis and do not in any way hinder concurrent 
investigation for OSA if clinically indicated. The sleep study data will be interpreted at the 1-
year follow-up and the study physicians will decide if further investigation is needed.  
 
Affiliated Researchers  
Researcher Joseph Aked is the principal investigator, with Anders Behrens and Arne 
Lindgren as co-investigators.  
 

References  
1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries 
in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of 
Disease Study 2019 Lancet. 2020;396:1204-1222. doi:10.1016/S0140-6736(20)30925-9.  
2. GBD 2016 DALYs and HALE Collaborators: Global, regional, and national disability-
adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy 
(HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global 
Burden of Disease Study 2016. Lancet 2017; 390: 1260– 1344.  
3. Feigin VL, Krishnamurthi RV, Parmar P, Norrving B, et al: Update on the global burden of 
ischemic and hemorrhagic stroke in 1990–2013: the GBD 2013 Study. Neuroepidemiology 
2015;45:161–176  
4. Wafa HA, Wolfe CDA, Emmett E, et al. Burden of Stroke in Europe: Thirty- Year 
Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years. Stroke 
2020;51:2418-2427. doi: 10.1161/STROKEAHA.120.029606. Epub 2020 Jul 10. PMID: 
32646325; PMCID: PMC7382540.  
5. Feigin VL, Barker-Collo S, Parag V, et al. Auckland Stroke Outcomes Study. Part 1: 
Gender, stroke types, ethnicity, and functional outcomes 5 years poststroke. Neurology 
2010;75:1597-1607.  
6. Barker-Collo S, Feigin VL, Parag V, et al. Auckland Stroke Outcomes Study. Part 2: 
Cognition and functional outcomes 5 years poststroke. Neurology 2010;75:1608-1616  
7. Jönsson AC, Delavaran H, Iwarsson S, et al. Functional status and patient-reported 
outcome 10 years after stroke: the Lund Stroke Register. Stroke 2014;45:1784-1790.  
8. Cumming TB, Packer M, Kramer SF, et al. The prevalence of fatigue after stroke: A 
systematic review and meta-analysis. Int J Stroke 2016;11:968-977. 
doi:10.1177/1747493016669861.  
9. Delavaran H, Jönsson AC, Lövkvist H, et al. Cognitive function in stroke survivors: A 10-
year follow-up study. Acta Neurol Scand 2017;136:187-194. doi:10.1111/ane.12709  
10. Stolwyk RJ, Mihaljcic T, Wong DK, et al. Poststroke Cognitive Impairment Negatively 
Impacts Activity and Participation Outcomes: A Systematic Review and Meta-Analysis. 
Stroke 2021;52:748-760. doi:10.1161/STROKEAHA.120.032215 11. Ayerbe L, Ayis S, 
Crichton S, et al. The natural history of depression up to 15 years after stroke: the South 
London Stroke Register. Stroke 2013;44:1105–1110. doi: 
10.1161/STROKEAHA.111.679340  
12. Christensen D, Johnsen SP, Watt T, et al. Dimensions of post-stroke fatigue: a two-year 
follow-up study. Cerebrovasc Dis 2008;26:134–141. doi: 10.1159/00013966  
13. van de Port IGL, Kwakkel G, Schepers VPM, et al. Is fatigue an independent factor 
associated with activities of daily living, instrumental activities of daily living and health-
related quality of life in chronic stroke? Cerebrovasc Dis 2007;23:40–45.  
14. Cumming TB, Packer M, Kramer SF, et al. The prevalence of fatigue after stroke: A 
systematic review and meta-analysis. Int J Stroke 2016;11:968-977. 
doi:10.1177/1747493016669861  
15. Elf M, Eriksson G, Johansson S, von Koch L, Ytterberg C (2016) Self- Reported Fatigue 
and Associated Factors Six Years after Stroke. PLOS ONE 11(8): e0161942. 
https://doi.org/10.1371/journal.pone.0161942  
16. Pedersen A, Almkvist E, Holmegaard L, Lagging C, Redfors P, Blomstrand C, Jood K et 
al (2022) Fatigue 7 years post-stroke: Predictors and correlated features. Acta Neurol Scand. 
https://doi.org/10.1111/ane.13665  
17. Aked J, Delavaran H, Wennerström F, et al. Cognition, fatigue and depression up to four 
years after first-ever stroke. Unpublished manuscript (2023).  

18. Schnitzer, L., Hansson, PO., Samuelsson, C.M. et al. Fatigue in stroke survivors: a 5-year 
follow-up of the Fall study of Gothenburg. J Neurol (2023). https://doi.org/10.1007/s00415-
023-11812-0  
19. Wu S, Kutlubaev MA, Chun HYY, et al. Interventions for post-stroke fatigue. Cochrane 
Database Syst Rev. 2015;CD007030  
20. Stroke rehabilitation and long-term care top 10 priorities. 
https://www.jla.nihr.ac.uk/priority-setting-partnerships/Stroke/stroke-rehabilitation-and-long 
term-care-top-10-priorities.htm. Accessed 4 Oct 2023.  
21. Pedersen A, Almkvist E, Holmegaard L, Lagging C, Redfors P, Blomstrand C, Jood K et 
al (2022) Fatigue 7 years post-stroke: Predictors and correlated features. Acta Neurol Scand. 
https://doi.org/10.1111/ane.13665  
22. Mahon S, Parmar P, Barker-Collo S, Krishnamurthi R, Jones K, Theadom A, Feigin V 
(2017) Determinants, prevalence, and trajectory of long-term post-stroke cognitive 
impairment: results from a 4-year follow-up of the ARCOS-IV study. Neuroepidemiology 3–
4:129–134  
23. Gu M, Xiao L, Wang J, Cai Q, Liu Y, Xu P, Liu Y et al (2021) Obesity and poststroke 
fatigue: a 2-year longitudinal study. Neurol Ther 2:955–969. https://doi.org/10.1007/s40120-
021-00276-x  
24. Kuvat N, Tanriverdi H, Armutcu F (2020) The relationship between obstructive sleep 
apnea syndrome and obesity: a new perspective on the pathogenesis in terms of organ 
crosstalk. Clin Respir J 7:595–604. https://doi.org/10.1111/crj.13175  
25. Seiler A, Camilo M, Korostovtseva L, Haynes AG, Brill AK, Horvath T, Egger M, 
Bassetti CL. Prevalence of sleep-disordered breathing after stroke and TIA: a meta-
analysis..Neurology. 2019; 92:e648–e654. doi: 10.1212/WNL.0000000000006904  
26. Stevens D, Tomazini Martins R, Mukherjee S, et al. Post-stroke sleep-disordered 
breathing – pathophysiology and therapy options. Front Surg. 2018;5:9  
27. Boulos MI, Dharmakulaseelan L, Brown DL, et al. Trials in Sleep Apnea and Stroke. 
Stroke. 2021;51:366-372  
28. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of 
Stroke in Patients with Stroke and Transient Ischemic Attack: A Guideline From the 
American Heart Association/American Stroke Association. Stroke. 2021;52:e364-e467  
29. Hedner J GL, Friberg D, Ejnell H, Harlid R, Isacsson G, Lindberg E, Midgren B, Puzio J, 
Tegelberg Å, Ulander M, Wartenberg C. Riktlinjer för utredning av misstänkt sömnapné hos 
vuxna. Nationellt Kvalitetsregister SESAR/Registercentrum Väst; 2018. 1-39  
30. Socialstyrelsen, Nationella riktlinjer for vård vid stroke 2018 Nationella riktlinjer för vård 
vid stroke – Socialstyrelsen  
31. Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st 
century: a statement for healthcare professionals from the American Heart 
Association/American Stroke Association. Stroke 2013;44:2064-2089. 
doi:10.1161/STR.0b013e318296aeca.  
32. Edouard P, Campo D, Bartet P, et al. Validation of the Withings Sleep Analyzer, an 
under-the-mattress device for the detection of moderate-severe sleep apnea syndrome. J Clin 
Sleep Med. 2021;17;1217-1227  
33. Lyden P. Using the National Institutes of Health Stroke Scale: A Cautionary Tale. Stroke. 
2017 Feb;48(2):513-519. doi: 10.1161/STROKEAHA.116.015434. Epub 2017 Jan 11. 
PMID: 28077454.  
34. Bamford, J. M., Sandercock, A. G., Warlow, C. P., Slattery, J. (1989). Interobserver 
agreement for the assessment of handicap in stroke patients (letter). Stroke, 20, 828.  
35. Hwang, M., Zhang, K., Nagappa, M., Saripella, A., Englesakis, M., & Chung, F. (2021). 
Validation of the STOP-Bang questionnaire as a screening tool for obstructive sleep apnoea 

in patients with cardiovascular risk factors: a systematic review and meta-analysis. BMJ open 
respiratory research. 8(1), e000848. https://doi.org/10.1136/bmjresp-2020-000848  
36. Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically 
identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521- 1526.  
37. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic 
stroke: definitions for use in a multicenter clinical trial. Stroke. 1993;24:35-41  
38. Hude Q, Bing L, Chantal MC, et al. Updating and Validating the Charlson Comorbidity 
Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 
Countries. American Journal of Epidemiology. 2011;173:676-682.  
39. Cumming TB, Mead G. Classifying post-stroke fatigue: Optimal cut-off on the Fatigue 
Assessment Scale. Journal of Psychosomatic Research. 2017;103:147-149  
40. Williams LS., Brizendine J, Plue L, et al. Performance of the PHQ-9 as a screening tool 
for depression after stroke. Journal of the American Heart Association. 2005;36:635-638  
41. Duncan PW, Wallace D, Lai SM, et al. The Stroke Impact Scale version 2.0: Evaluation 
of reliability, validity, and sensitivity to change. Stroke 1999;30:2131- 2140