Effect of Sleep Phase Related Obstructive Sleep Apnea on Sleep Structure and Prognosis of Acute Ischemic Stroke Patients

doi:10.3969/j.issn.1673-5765.2019.04.004

Abstract

Abstract:

Objective To investigate the effect of REM and non-rapid eye movement (NREM) sleep related OSA on sleep structure and prognosis of acute ischemic stroke (AIS) patients. Methods Data of consecutive AIS patients with PSG examination in the Second Affiliated Hospital of Soochow University from Feburary 2011 to August 2018 were resepectively colleted.Collected data included the general information, emotion and cognition assessment, sleep scales, MRI and PSG findings, the NIHSS scores at 48 hours after admission and at discharge, and mRS scores at discharge and 3 months. According to overall AHI, AHI during REM (REM-AHI) and during NREM (NREM-AHI), they were divided into AIS group, AIS+REM-related OSA group and AIS+NREM-related OSA group. Univariate and multivariate analyses were used to analyze the effect of sleep phase related OSA on sleep architecture and prognosis of AIS patients. Results A total of 110 eligible patients were enrolled in this study, with 30 (27.3%) in AIS group,15 (13.6%) in AHI+REM-related OSA group and 65 (59.1%) in AHI+NREM-related OSA group. BMI was more higher in AIS+NREM-related OSA group than that in AIS group. The lesions of AIS group were mostly located in telencephalon, while the lesions of AIS+REM-related OSA group were located in brain stem, telencephalon and diencephalon. The time and proportion of NREM 1 were higher and the time and proportion of slow wave sleep (SWS) were shorter in AIS+NREMrelated OSA group than that in AIS group.Microarousal index, respiratory related microarousal index, spontaneous microarousal index were higher in AIS+NREM-related OSA group than that in AIS+REM-related OSA group. There was no difference in mRS score at 3 months.Logistic analysis results revealed that high NIHSS score on admission, the low level of education and high BMI were independent risk factors of poor prognosis of AIS patients. Conclusions Sleep structure of AIS can be disturbed by NREM-related OSA, with sleep characteristics of longer NREM1, shorter deep sleep (NREM 3 and 4) and fragmentation. These changes may result in worse prognosis of AIS.

Key words: Ischemic stroke; Obstructive sleep apnea; Rapid eye movement sleep; Non rapid eye movement sleep; Prognosis

摘要：

目的探讨REM期与非快动眼睡眠（non-rapid eye movement，NREM）期相关OSA对急性脑梗死（acute ischemic stroke，AIS）患者睡眠结构及预后的影响。方法回顾性收集2011年2月-2018年8月于苏州大学附属第二医院就诊且完成PSG的AIS患者，收集的数据包括一般资料，情绪、认知、睡眠量表评估，MRI 、PSG检查，出院时功能恢复情况（应用NI HSS 量表和mRS量表评估）及3个月预后（应用mRS量表评估）。根据总睡眠期、REM期和NREM期睡眠AHI，将患者分为单纯脑梗死组、脑梗死合并REM期相关OSA组和脑梗死合并NREM期相关OSA组，对3组一般资料、临床量表评分、睡眠数据及预后情况进行单因素和多因素分析，观察睡眠不同时相OSA对患者睡眠结构及预后的影响。结果最终纳入110例患者，其中单纯脑梗死组30例（27.3%），脑梗死合并REM期相关OSA组15例（13.6%），脑梗死合并NREM期相关OSA组65例（59.1%）。脑梗死合并NREM期相关OSA组BMI高于单纯脑梗死组。脑梗死组病灶部位多位于大脑半球，脑梗死合并REM期相关OSA组病灶依次位于脑干、大脑半球、间脑。与单纯脑梗死组相比，脑梗死合并NREM期相关OSA组NREM1期睡眠时间及比例高，慢波睡眠时间及比例低。与脑梗死合并REM期相关OSA组相比较，脑梗死合并NREM期相关OSA组微觉醒指数、呼吸相关微觉醒指数、自发相关微觉醒指数高，上述差异均具有统计学意义。各组间3个月后mRS评分差异无统计学意义。Logistic回归分析提示入院时高NIHSS评分、低受教育水平、高BMI是脑梗死患者预后不良的独立危险因素。结论 NREM期相关OSA会改变脑梗死患者的睡眠结构，使其浅睡眠1期延长，深睡眠（NREM 3期和4期）缩短，睡眠片段化，此种改变可能会导致脑梗死患者预后更差。

关键词: 脑梗死; 睡眠呼吸暂停; 快动眼睡眠; 非快动眼睡眠; 预后

CHEN Qin, LI Jie, MAO Cheng-Jie, SHEN Yun, FU Xiang, LIU Yu-Lu, LIU Chun-Feng. Effect of Sleep Phase Related Obstructive Sleep Apnea on Sleep Structure and Prognosis of Acute Ischemic Stroke Patients[J]. Chinese Journal of Stroke, 2019, 14(04): 317-326.

陈沁，李洁，毛成洁，沈赟，傅翔，刘昱璐，刘春风. 睡眠时相相关阻塞性睡眠呼吸暂停对急性脑梗死患者睡眠结构及预后的影响[J]. 中国卒中杂志, 2019, 14(04): 317-326.

References

[1] JOHNSON K G，JOHNSON D C. Frequency of

sleep apnea in stroke and tia patients：A metaanalysis[

J]. J Clin Sleep Med，2010，6（2）：131-137.

[2] ARZT M，YOUNG T，FINN L，et al. Association

of sleep-disordered breathing and the occurrence

of stroke[J]. Am J Respir Crit Care Med，2005，172

（11）：1447-1451.

[3] REDLINE S，YENOKYAN G，GOTTLIEB D J，et

al. Obstructive sleep apnea-hypopnea and incident

stroke：the sleep heart health study[J]. Am J Respir

Crit Care Med，2010，182（2）：269-277.

[4] YAGGI H K，CONCATO J，KERNAN W N，et al.

Obstructive sleep apnea as a risk factor for stroke

and death[J]. N Engl J Med，2005，353（19）：2034-

2041.

[5] 许亚男，李洁，黄隽英，等. 阻塞性睡眠呼吸暂停对

急性脑梗死患者睡眠结构的影响[J]. 中华医学杂志，

2017，97（12）：920-924.

[6] YÖN M ?，KÖKTÜRK O. Is NREM-predominant

obstructive sleep apnea syndrome a different clinical

entity?[J]. Turk J Med Sci，2018，48（5）：967-972.

[7] IBER C，ANCOLI-ISRAEL S，CHESSON A，et

al. The AASM Manual for the Scoring of Sleep

and Associated Events：Rules，Terminology and

Technical Specification[M]. 1st ed. West Chester，

Illinois：American Academy of Sleep Medicine. 2007：

1-58.

[8] HABA-RUBIO J，JANSSENS J P，ROCHAT T，et

al. Rapid eye movement-related disordered breathing：

Clinical and polysomnographic features[J]. Chest，

2005，128（5）：3350-3357.

[9] CHAN W，COUTTS S B，HANLY P. Sleep apnea

in patients with transient ischemic attack and minor

stroke：Opportunity for risk reduction of recurrent

stroke?[J]. Stroke，2010，41（12）：2973-2975.

[10] GASANOV R L. Structure of nocturnal sleep in

patients with various locations of stroke[J]. Zh

Nevrol Psikhiatr Im S S Korsakova，2001，（Suppl 3）：

32-34.

[11] LI Q，ZHAO X，GONG D H，et al. Sleep disorders

of acute thalamic stroke and its influence on plasma

il-17[J]. J Biol Regul Homeost Agents，2017，31（3）：

745-751.

[12] FALUDI B，TOTH M，PUSCH G，et al. Dynamic

changes in sleep-related breathing abnormalities in

bilateral paramedian mesencephalon and thalamus

stroke：a follow-up case study[J]. Sleep Breath，2016，

20（1）：237-242.

[13] PACE M，CAMILO M R，SEILER A，et al. Rapid

eye movements sleep as a predictor of functional

outcome after stroke：a translational study[J/OL].

Sleep，2018，41（10）. https：//doi.org/10.1093/sleep/

zsy138.

[14] PICCHIONI D，PIXA M L，FUKUNAGA M，et al.

Decreased connectivity between the thalamus and

the neocortex during human nonrapid eye movement

sleep[J]. Sleep，2014，37（2）：387-397.

[15] HIMANEN S L，MARTIKKALA L，SULKAMO S，

et al. Prolonged partial obstruction during sleep is a

NREM phenomenon[J/OL]. Respir Physiol Neurobiol，

2018，255：43-49. https：//doi.org/10.1016/

j.resp.2018.05.009.

[16] CAVALCANTI P，CAMPOS T，ARAUJO

J. Actigraphic analysis of the sleep-wake cycle

and physical activity level in patients with stroke：

implications for clinical practice[J]. Chronobiol Int，

2012，29（9）：1267-1272.

[17] LIM A S，YU L，SCHNEIDER J A，et al. Sleep

fragmentation，cerebral arteriolosclerosis，and brain

infarct pathology in community-dwelling older

people[J]. Stroke，2016，47（2）：516-518.

[18] GAO B，CAM E，JAEGER H，et al. Sleep disruption

aggravates focal cerebral ischemia in the rat[J]. Sleep，

2010，33（7）：879-887.

[19] ZUNZUNEGUI C，GAO B，CAM E，et al. Sleep

disturbance impairs stroke recovery in the rat[J].

Sleep，2011，34（9）：1261-1269.

[20] MOLDOVAN M，CONSTANTINESCU A O，

BALSEANU A，et al. Sleep deprivation attenuates

experimental stroke severity in rats[J]. Exp Neurol，

2010，222（1）：135-143.

[21] CAM E，GAO B，IMBACH L，et al. Sleep

deprivation before stroke is neuroprotective：a preischemic

conditioning related to sleep rebound[J/

OL]. Exp Neurol，2013，247：673-679. https：//doi.

org/10.1016/j.expneurol.2013.03.003.

[22] WEIL Z M，NORMAN G J，KARELINA K，et al.

Sleep deprivation attenuates inflammatory responses

and ischemic cell death[J]. Exp Neurol，2009，218

（1）：129-136.

[23] HSU J C，LEE Y S，CHANG C N，et al. Sleep

deprivation prior to transient global cerebral

ischemia attenuates glial reaction in the rat

hippocampal formation[J]. Brain Res，2003，984（1-

2）：170-181.

[24] STAHL S M，YAGGI H K，TAYLOR S，et al.

Infarct location and sleep apnea：evaluating the

potential association in acute ischemic stroke[J].

Sleep Med，2015，16（10）：1198-1203.

[25] WEBER F，CHUNG S，BEIER K T，et al. Control

of REM sleep by ventral medulla GABAergic

neurons[J]. Nature，2015，526（7573）：435-438.

[26] HAYASHI Y，KASHIWAGI M，YASUDA K，et al.

Cells of a common developmental origin regulate

REM/non-REM sleep and wakefulness in mice[J].

Science，2015，350（6263）：957-961.

[27] Arens R，Marcus C L. Pathophysiology of upper

airway obstruction：a developmental perspective[J].

Sleep，2004，27（5）：997-1019.

[28] DEFLANDRE E，GERDOM A，LAMARQUE C，

et al. Understanding pathophysiological concepts

leading to obstructive apnea[J]. Obes Surg，2018，28

（8）：2560-2571.

[29] NAJI M，KOMAROV M，KRISHNAN G P，et al.

Computational model of brain-stem circuit for statedependent

control of hypoglossal motoneurons[J]. J

Neurophysiol，2018，120（1）：296-305.

[30] CAMPOS-RODRÍGUEZ F，FERNÁNDEZPALACÍN

A，REYES-NÚÑEZ N，et al. Clinical

and polysomnographic features of rapid-eyemovement-

specific sleep-disordered breathing[J].

Arch Bronconeumol，2009，45（7）：330-334.

[31] VARGA A W，MOKHLESI B. REM obstructive

sleep apnea：risk for adverse health outcomes and

novel treatments[J/OL]. Sleep Breath，2018. https：//

doi.org/10.1007/s11325-018-1727-2.

[32] MCHUTCHISON C A，BACKHOUSE E V，Cvoro

V，et al. Education，socioeconomic status，and

intelligence in childhood and stroke risk in later

life：a meta-analysis[J]. Epidemiology，2017，28（4）：

608-618.

[33] SALEHI S，TAHAN N，BAGHEBAN A A，et

al. Quality of life within three months after

stroke：a study in the city of arak，iran[J/OL]. J

Natl Med Assoc，2019. https：//doi.org/10.1016/

j.jnma.2019.03.007.

[34] OHLSSON C，BYGDELL M，SONDÉN A，et al.

BMI increase through puberty and adolescence is

associated with risk of adult stroke[J]. Neurology，

2017，89（4）：363-369.

[35] TULSULKAR J，NADA S E，SLOTTERBECK B

D，et al. Obesity and hyperglycemia lead to impaired

post-ischemic recovery after permanent ischemia

in mice[J]. Obesity（Silver Spring），2016，24（2）：

417-423.

[36] RIST P M，CAPISTRANT B D，MAYEDA E R，

et al. Physical activity，but not body mass index，

predicts less disability before and after stroke[J].

Neurology，2017，88（18）：1718-1726.

[37] HUANG K，LIU F，HAN X，et al. Association of

BMI with total mortality and recurrent stroke among

stroke patients：a meta-analysis of cohort studies[J/

OL]. Atherosclerosis，2016，253：94-101. https：//doi.

org/10.1016/j.atherosclerosis.2016.08.042.

[38] RODRIGUEZ-CASTRO E，RODRIGUEZ-YANEZ

M，ARIAS-RIVAS S，et al. Obesity paradox in

ischemic stroke：clinical and molecular insights[J].

Transl Stroke Res，2019. https：//doi.org/10.1007/

s12975-019-00695-x.