Please wait a minute...
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (3): 275-281    DOI: 10.3785/j.issn.1008-9292.2019.06.07
    
Restless legs syndrome in ischemic stroke patients: clinical features and significance
ZHANG Lisan1,2(),SUN Yi2,WANG Tiantian3,PAN Yu2,YAO Ying2,PAN Liuqing2,XU Qinglin1,2,ZHANG Wenying1,2,XU Jiahui1,2,HU Xingyue1,*()
1. Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
2. Center for Sleep Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
3. Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Download: HTML( 5 )   PDF(0KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Objective: To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients. Methods: A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls. Results: Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (β=-133.3 mg/L, 95%CI:-200.4--0.1, P < 0.01), subcortical infarction (OR=4.05, 95%CI:1.15-14.18, P < 0.05) and female (OR=2.54, 95%CI:1.04-6.23, P < 0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%CI:2.33-6.41, P < 0.01), PHQ-9 increased by 2.17 (95%CI:0.39--3.94, P < 0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%CI:-1.79--0.15, P < 0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (OR=4.27, 95%CI:1.40-13.10, P < 0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (β=12.85, 95%CI:2.04-23.67, P < 0.05). Conclusion: RLS is common in ischemic stroke patients and has adverse influences on patients.



Key wordsBrain ischemia      Stroke/complications      Restless legs syndrome/diagnosis      Polysomnography      Depression     
Received: 08 April 2019      Published: 04 September 2019
CLC:  R743  
  R442.8  
Corresponding Authors: HU Xingyue     E-mail: zls09@zju.edu.cn;huxingyue2003@126.com
Cite this article:

ZHANG Lisan, SUN Yi, WANG Tiantian, PAN Yu, YAO Ying, PAN Liuqing, XU Qinglin, ZHANG Wenying, XU Jiahui, HU Xingyue. Restless legs syndrome in ischemic stroke patients: clinical features and significance. J Zhejiang Univ (Med Sci), 2019, 48(3): 275-281.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.06.07     OR     http://www.zjujournals.com/med/Y2019/V48/I3/275


缺血性脑卒中患者合并不宁腿综合征的特点和临床意义

目的: 研究缺血性脑卒中患者不宁腿综合征(RLS)的患病率、危险因素、临床特点以及对缺血性脑卒中的影响。方法: 收集2016年1月至2018年6月在浙江大学医学院附属邵逸夫医院神经内科住院的缺血性脑卒中患者199例。所有患者接受了多导睡眠监测。RLS采用国际RLS研究组制订的标准确诊。收集患者住院期间的临床资料进行危险因素分析。用Epworth嗜睡量表(ESS)评估患者的睡眠质量,简易智力状态检查评估患者的认知功能,患者的健康问卷(PHQ-9)评估患者的抑郁症状,采用美国国立卫生院卒中量表(NIHSS)评估患者的神经功能。选取年龄和性别匹配的原发性RLS患者,评估缺血性脑卒中合并RLS患者的多导睡眠监测特征。结果: 199例缺血性脑卒中患者中有22例存在RLS(11.1%)。广义线性模型和Logistic回归分析提示血清铁蛋白水平下降(β=-133.3 mg/L,95%CI:-200.4~-70.1,P < 0.01),皮层下梗死(OR=4.05,95%CI:1.15~14.18,P < 0.05)和女性(OR=2.54,95%CI:1.04~6.23,P < 0.05)是缺血性脑卒中合并RLS的危险因素。与不合并RLS的缺血性脑卒中患者比较,合并RLS的缺血性脑卒中患者ESS值升高4.37分(95%CI:2.33~6.41,P < 0.01),PHQ-9分值增加2.17分(95%CI:0.39~3.94,P < 0.05),中重度抑郁风险增加4.27倍(95%CI:1.40~13.10,P < 0.05),NIHSS减分值减少0.97分(95%CI:-1.79~-0.15,P < 0.05)。与原发性RLS患者相比,合并缺血性脑卒中的RLS患者伴微觉醒的周期性腿动指数增加(β=12.85,95%CI:2.04~23.67,P < 0.05)。结论: RLS在缺血性脑卒中患者中较常见,且对缺血性脑卒中患者造成不利影响,应重视筛查和治疗。


关键词: 脑缺血,  卒中/并发症,  不宁腿综合征/诊断,  多道睡眠描记术,  抑郁 
[n(%)或$\bar x \pm s$或M(IQR)]
组别 n 女性 年龄(岁) 文化程度 AHI 体质指数(kg/m2) 吸烟史 饮酒史 高血压史 糖尿病史 心房颤动史 冠心病史 卒中史 醒后卒中 进展性卒中 C反应蛋白(mg/L) NIHSS评分 糖化血红蛋白(%) 铁蛋白(mg/L) 梗死部位 同型半胱氨酸(mmol/L)
小学及以下 高中 大学及以上 皮层 皮层下 脑干 小脑
“—”无相关数据.P1值:t检验、χ2检验或秩和检验;P2值:回归分析.AHI:呼吸暂停-低通气指数;NIHSS:美国国立卫生研究院卒中量表.
合并RLS组 22 11(50.0) 65±11 10(45.5) 10(45.5) 2(9.1) 12±11 25.1±3.3 6(27.3) 2(9.1) 15(68.2) 6(27.3) 4(18.2) 3(13.6) 1(4.5) 5(22.7) 2(9.1) 3.1(4.2) 2.0(3.8) 6.5±1.8 94±68 2(9.1) 19(86.4) 1(4.5) 1(4.5) 9.7(6.4)
不合并RLS组 177 50(28.2) 61±13 61(34.5) 96(54.2) 20(11.3) 19±16 25.3±3.5 69(39.0) 43(24.3) 102(57.6) 57(32.2) 50(28.2) 17(9.6) 19(10.7) 42(23.7) 31(17.5) 2.0(4.4) 1.0(3.0) 6.4±1.4 230±154 44(24.9) 108(61.0) 16(9.0) 21(11.9) 11.0(8.8)
P1 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05 >0.05 <0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 <0.01 >0.05 <0.05 >0.05 >0.05 >0.05
ORβ值(95%CI) 2.54(1.04~6.23) 3.74(-1.94~9.42) 1.59(0.65~3.88) 0.70(0.29~1.71) 0.79(0.17~3.61) -6.98(-13.97~0.02) -0.22(-1.77~1.33) 0.59(0.22~1.57) 0.31(0.07~1.39) 1.58(0.61~4.06) 0.79(0.29~2.12) 0.56(0.18~1.75) 1.49(0.40~5.54) 0.40(0.05~3.11) 0.95(0.33~2.72) 0.47(0.10~2.12) 3.68(-0.22~7.59) 0.92(-0.40~2.23) 0.07(-0.57~0.71) -133.3(-200.4~-70.1) 0.30(0.07~1.35) 4.05(1.15~14.18) 0.48(0.06~3.80) 0.35(0.05~2.77) -1.24(-5.07~2.59)
P2 <0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 <0.01 >0.05 <0.05 >0.05 >0.05 >0.05
Tab 1 Clinical characteristics of ischemic stroke patients with and without restless legs syndrome (RLS)
[n(%)或$\bar x \pm s$]
组别 n MMSE ESS PHQ-9 中重度抑郁 NIHSS减分值
“—”无相关数据.P1值:t检验、χ2检验或秩和检验;P2值:回归分析.MMSE:简易精神状态评估量表;ESS:Epworth嗜睡量表;PHQ-9:9项健康状态问卷;NIHSS:美国国立卫生研究院卒中量表.回归分析调整了性别、梗死位置和呼吸暂停-低通气指数.
合并RLS组 22 20±5 12±5 7±5 8(36.4) 0(1.0)
不合并RLS组 177 22±5 8±4 6±4 33(18.6) 1(3.0)
P1 >0.05 <0.01 >0.05 >0.05 <0.01
ORβ值(95%CI) -1.60(-3.85, 0.65) 4.37(2.33, 6.41) 2.17(0.39, 3.94) 4.27(1.40, 13.10) -0.97(-1.79, -0.15)
P2 >0.05 <0.01 <0.05 <0.05 <0.05
Tab 2 Influences of restless legs syndrome (RLS) on cognitive function, sleep quality, post-stroke depression and rehabilitation of ischemic stroke patients
[n(%)或$\bar x \pm s$]
组别 n 女性 年龄(岁) AHI 体质指数 总PLMS指数(/h) 伴微觉醒的PLMS指数(/h) 不伴微觉醒的PLMS指数(/h)
“—”无相关数据.P1值:t检验、χ2检验或秩和检验;P2值:回归分析.AHI:呼吸暂停-低通气指数;PLMS:睡眠周期性腿动.
合并缺血性脑卒中的RLS组 10 6(60.0) 64±14 10.8±10.4 25.4±3.7 55±33 22±15 33±22
原发性RLS组 12 8(66.7) 64±9 10.6±10.9 22.9±2.9 32±27 9±11 22±20
P1 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05 >0.05
ORβ值(95%CI) 0.75(0.13~4.29) -0.03(-9.57~9.51) 0.19(-8.75~9.13) 2.46(-0.30~5.22) 23.62(-1.51~48.75) 12.85(2.04~23.67) 10.77(-6.51~28.04)
P2 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05 >0.05
Tab 3 Polysomnography features between restless legs syndrome (RLS) with ischemic stroke and primary RLS patients
[1]   MIMS K N , KIRSCH D . Sleep and stroke[J]. Sleep Med Clin, 2016, 11 (1): 39- 51
doi: 10.1016/j.jsmc.2015.10.009
[2]   OHAYON M M , O'HARA R , VITIELLO M V . Epidemiology of restless legs syndrome:a synthesis of the literature[J]. Sleep Med Rev, 2012, 16 (4): 283- 295
doi: 10.1016/j.smrv.2011.05.002
[3]   MA J F , XIN X Y , LIANG L et al. Restless legs syndrome in Chinese elderly people of an urban suburb in Shanghai:a community-based survey[J]. Parkinsonism Relat Disord, 2012, 18 (3): 294- 298
doi: 10.1016/j.parkreldis.2011.11.014
[4]   LI L H , CHEN H B , ZHANG L P et al. A community-based investigation on restless legs syndrome in a town in China[J]. Sleep Med, 2012, 13 (4): 342- 345
doi: 10.1016/j.sleep.2011.09.008
[5]   SHEN Y , LIU H , DAI T et al. Association between restless legs syndrome and hypertension:a meta-analysis of nine population-based studies[J]. Neurol Sci, 2018, 39 (2): 235- 242
doi: 10.1007/s10072-017-3182-4
[6]   LIU Y , LIU G , LI L et al. Evaluation of cardiovascular risk factors and restless legs syndrome in women and men:a preliminary population-based study in China[J]. J Clin Sleep Med, 2018, 14 (3): 445- 450
doi: 10.5664/jcsm.6996
[7]   LI X , ALLEN R P , EARLEY C J et al. Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla[J]. Sleep Med, 2016, 22:75- 82
doi: 10.1016/j.sleep.2016.05.001
[8]   EARLEY C J , KUWABARA H , WONG D F et al. Increased synaptic dopamine in the putamen in restless legs syndrome[J]. Sleep, 2013, 36 (1): 51- 57
doi: 10.5665/sleep.2300
[9]   TRENKWALDER C , ALLEN R , H?GL B et al. Restless legs syndrome associated with major diseases:A systematic review and new concept[J]. Neurology, 2016, 86 (14): 1336- 1343
doi: 10.1212/WNL.0000000000002542
[10]   ALLEN R P , PICCHIETTI D L , GARCIA-BORREGUERO D et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria:updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria-history, rationale, description, and significance[J]. Sleep Med, 2014, 15 (8): 860- 873
doi: 10.1016/j.sleep.2014.03.025
[11]   BERRY R B, BROOKS R, GAMALDO C E, et al. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, version 2.2[M]. Darien, IL, USA: American Academy of Sleep Medicine, 2015.
[12]   YEH P , WALTERS A S , TSUANG J W . Restless legs syndrome:a comprehensive overview on its epidemiology, risk factors, and treatment[J]. Sleep Breath, 2012, 16 (4): 987- 1007
doi: 10.1007/s11325-011-0606-x
[13]   TUO H , TIAN Z , MA X et al. Clinical and radiological characteristics of restless legs syndrome following acute lacunar infarction[J]. Sleep Med, 2019, 53:81- 87
doi: 10.1016/j.sleep.2018.06.004
[14]   BOULOS M I , WAN A , BLACK S E et al. Restless legs syndrome after high-risk TIA and minor stroke:association with reduced quality of life[J]. Sleep Med, 2017, 37:135- 140
doi: 10.1016/j.sleep.2017.05.020
[15]   JIMéNEZ-JIMéNEZ F J , ALONSO-NAVARRO H , GARCíA-MARTíN E et al. Genetics of restless legs syndrome:An update[J]. Sleep Med Rev, 2018, 39:108- 121
doi: 10.1016/j.smrv.2017.08.002
[16]   SHⅡNA T , SUZUKI K , OKAMURA M et al. Restless legs syndrome and its variants in acute ischemic stroke[J]. Acta Neurol Scand, 2019, 139 (3): 260- 268
doi: 10.1111/ane.13055
[17]   FULDA S , WETTER T C . Is daytime sleepiness a neglected problem in patients with restless legs syndrome?[J]. Mov Disord, 2007, 22 Suppl 18:S409- S413
[18]   SONG Y Y , HU R J , DIAO Y S et al. Effects of exercise training on restless legs syndrome, depression, sleep quality, and fatigue among hemodialysis patients:A systematic review and meta-analysis[J]. J Pain Symptom Manage, 2018, 55 (4): 1184- 1195
doi: 10.1016/j.jpainsymman.2017.12.472
[19]   KOO B B , BLACKWELL T , LEE H B et al. Restless legs syndrome and depression:effect mediation by disturbed sleep and periodic limb movements[J]. Am J Geriatr Psychiatry, 2016, 24 (11): 1105- 1116
doi: 10.1016/j.jagp.2016.04.003
[20]   ZHANG L S , HU X Y , YAO L Y et al. Prophylactic effects of duloxetine on post-stroke depression symptoms:an open single-blind trial[J]. Eur Neurol, 2013, 69 (6): 336- 343
doi: 10.1159/000345374
[21]   曾婷婷, 张力三, 杨怡 et al. 阻塞性睡眠呼吸暂停筛查量表在急性缺血性脑卒中患者中的应用评价[J]. 浙江大学学报(医学版), 2018, 47 (2): 174- 180
ZENG Tingting , ZHANG Lisan , YANG Yi et al. Screening efficiencies of obstructive sleep apnea screening scales in patients with acute ischemic stroke[J]. Journal of Zhejiang University(Medical Sciences), 2018, 47 (2): 174- 180
[1] ZHANG Congcong, LOU Min, CHEN Zhicai, CHEN Hongfang, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province . Analysis of intravenous thrombolysis time and prognosis in patients with in-hospital stroke[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 260-266.
[2] ZHONG Wansi, CHEN Zhicai, CHEN Hongfang, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, LOU Min, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province . Effects of emergency medical service on prognosis of ischemic stroke patients treated with intravenous thrombolysis[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 241-246.
[3] MA Jing, HE Wenlong, GAO Chongyang, YU Ruiyun, XUE Peng, NIU Yongchao. Glucosides of chaenomeles speciosa attenuate ischemia/reperfusion-induced brain injury by regulating NF-κB P65/TNF-α in mouse model[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 289-295.
[4] TAO Anyang, WANG Zhimin, CHEN Hongfang, XU Dongjuan, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, LOU Min, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province . Association of atrial fibrillation with hemorrhagic transformation after intravenous thrombolysis in patients with ischemic stroke[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 254-259.
[5] PAN Feihu, LOU Min, CHEN Zhicai, CHEN Hongfang, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province . Effect of different working time on the prognosis of ischemic stroke patients undergoing intravenous thrombolysis[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 267-274.
[6] CHEN Hongfang, GONG Xiaoxian, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, LOU Min, CHEN Zhicai, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province . Advanced treatment time improves outcomes of patients with ischemic stroke undergoing reperfusion therapy[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 247-253.
[7] ZHANG Jianmin. Advances in surgical treatment of ischemic cerebrovascular disease[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 233-240.
[8] LIANG Gang, NIU Yumiao, LI Yihan, Wei Anyi, DONG Jingyin, ZENG Linghui. Rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion exhibits protective effect on brain injury in rats[J]. J Zhejiang Univ (Med Sci), 2018, 47(5): 443-449.
[9] ZENG Tingting,ZHANG Lisan,YANG Yi,XIE Fei,ZHANG Dan,HU Xingyue. Screening efficiencies of obstructive sleep apnea screening scales in patients with acute ischemic stroke[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 174-180.
[10] WANG Hao,GUO Honggang,LOU Qi,SHI Qiaojuan. Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion[J]. J Zhejiang Univ (Med Sci), 2018, 47(1): 19-26.
[11] FENG Xuewen, CHEN Zhicai, ZHONG Genlong, LOU Min. Safety of tirofiban in patients with acute cerebral infarct receiving endovascular therapy[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 397-404.
[12] WANG Qingsong, ZHANG Sheng, ZHANG Meixia, CHEN Zhicai, LOU Min. Collateral score based on CT perfusion can predict the prognosis of patients with anterior circulation ischemic stroke after thrombectomy[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 377-383.
[13] ZHANG Binbin, WU Meiling, LIU Luna, ZHU Yangbin, KAI Jiejing, ZENG Linghui. Inhibiting mammalian target of rapamycin signaling pathway improves cognitive function in mice with chronic cerebral ischemia[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 405-412.
[14] ZHANG Meixia, ZHOU Ying, ZHANG Ruiting, ZHANG Sheng, LOU Min. Maximal infarct volume to benefit from intravenous thrombolysis and its relation with onset to treatment time[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 384-389.
[15] BAI Shi, SUN Yayi, WU Lijuan, WU Zhongmin, FANG Marong. Tripotolide ameliorates inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats[J]. J Zhejiang Univ (Med Sci), 2016, 45(5): 493-500.