Prevalence of restless legs syndrome in patients with amyotrophic lateral sclerosis and its correlation with disease severity: A meta-analysis

doi:10.3969/j.issn.1004-583X.2023.10.002

Abstract

Abstract: Objective To evaluate the prevalence of restless legs syndrome (RLS) in patients with amyotrophic lateral sclerosis (ALS) and its correlation with disease severity. Methods Relevant articles reporting RLS in ALS patients published before December 12th 2020 were systematically searched in the Cochrane library, PubMed, Embase, Web of science, Chinese Biomedical Literature Database (CBM), CNKI, and Wanfang Data. According to the inclusion and exclusion criteria, eligible studies were selected independently by two researchers. Quality of case-control studies and cohort studies was assessed according to the Newcastle-Ottawa Scale (NOS). Data pooling and publication bias were analyzed using Revman5.3. Results A total of 6 eligible studies were included into the analysis, including 2 cohort studies and 4 case-control studies. The NOS scores of all studies were ≥6. Meta-analysis showed that the prevalence of RLS increased significantly in ALS patients(OR=8.24,95%CI =4.57-14.87). Subgroup analysis showed that the proportion of excessive daytime sleepiness (EDS) in the RLS-positive group was significantly higher than that of the RLS-negative group (OR=3.42, 95%CI =1.61-7.27, P=0.001).The ALS Functional Rating Scale-Revised (ALFRS-R) score of ALS patients in RLS-positive group was significantly lower than that of the RLS-negative group, indicating that the functional impairment was more significant in ALS patients with RLS (MD=-3.76, 95%CI =-7.16, -0.36, P=0.03). The meta-analysis showed a slight publication bias. Conclusion The prevalence of RLS in ALS patients is significantly elevated, which affects their sleep quality. The functional defect of ALS patients with RLS is more significant, which should be well concerned.

Key words: amyotrophic lateral sclerosis, sleep disorders, restless legs syndrome, meta analysis

CLC Number:

R746.4

Sun Yanan, Hao Yifeng, Li Xiaohong. Prevalence of restless legs syndrome in patients with amyotrophic lateral sclerosis and its correlation with disease severity: A meta-analysis[J]. Clinical Focus, 2023, 38(10): 878-882.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.10.002

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I10/878

Figures/Tables 7

References 19

[1]	Al-Chalabi A, Hardiman O. The epidemiology of ALS: A conspiracy of genes, environment and time, Nature reviews[J]. Nat Rev Neuro, 2013, 9(11):617-628. doi: 10.1038/nrneurol.2013.203
[2]	Al-Chalabi A, Calvo A, Chio A, et al. Analysis of amyotrophic lateral sclerosis as a multistep process: A population-based modelling study[J]. Lancet Neurol, 2014, 13(11):1108-1113. doi: S1474-4422(14)70219-4 pmid: 25300936
[3]	Ravits JM, La Spada AR. ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration[J]. Neurology, 2009, 73(10):805-811. doi: 10.1212/WNL.0b013e3181b6bbbd pmid: 19738176
[4]	Fang T, Jozsa F, Al-Chalabi A. Nonmotor Symptoms in Amyotrophic Lateral Sclerosis: A Systematic Review[J]. Int Rev Neurobiol, 2017, 134:1409-1441. doi: S0074-7742(17)30039-9 pmid: 28805578
[5]	Talarico G, Canevelli M, Tosto G, et al. Restless legs syndrome in a group of patients with Alzheimer's disease[J]. Am J Alzheimers Dis Other Demen, 2013, 28(2):165-170. doi: 10.1177/1533317512470208 URL
[6]	Trenkwalder C, Winkelmann J, Inoue Y, et al. Restless legs syndrome-current therapies and management of augmentation[J]. Nat Rev Neurol, 2015, 11(8):434-445. doi: 10.1038/nrneurol.2015.122 pmid: 26215616
[7]	Shi Y, Yu H, Ding D, et al. Prevalence and risk factors of restless legs syndrome among Chinese adults in a rural community of Shanghai in China[J]. PLoS One, 2015, 10(3):e0121215. doi: 10.1371/journal.pone.0121215 URL
[8]	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9):603-605. doi: 10.1007/s10654-010-9491-z pmid: 20652370
[9]	Limousin N, Blasco H, Corcia P, et al. The high frequency of restless legs syndrome in patients with amyotrophic lateral sclerosis[J]. Amyotroph Lateral Scler, 2011, 12(4):303-306. doi: 10.3109/17482968.2011.557736 URL
[10]	Liu S, Shen D, Tai H, et al. Restless legs syndrome in Chinese patients with sporadic amyotrophic lateral sclerosis[J]. Front Neurol, 2018, 9:735. doi: 10.3389/fneur.2018.00735 pmid: 30214425
[11]	Lo Coco D, Piccoli F, La Bella V. Restless legs syndrome in patients with amyotrophic lateral sclerosis[J]. Mov Disord, 2010, 25(15):2658-2661. doi: 10.1002/mds.v25:15 URL
[12]	Reyhani A, Benbir Senel G, Karadeniz D. Effects of Sleep-Related Disorders on the Prognosis of Amyotrophic Lateral Sclerosis[J]. Neurodegener Dis, 2019, 19(3-4):148-154. doi: 10.1159/000505575 pmid: 32114585
[13]	Sun X, Zhao X, Liu Q, et al. Study on sleep-wake disorders in patients with genetic and non-genetic amyotrophic lateral sclerosis[J]. J Neurol Neurosurg Psychiatry, 2020:jnnp-2020-324544.
[14]	Panda S, Gourie-Devi M, Sharma A. Sleep disorders in amyotrophic lateral sclerosis: A questionnaire-based study from India[J]. Neurol India, 2018, 66(3):700-708. doi: 10.4103/0028-3886.232327 pmid: 29766929
[15]	Aylor JP, Brown RH Jr, Cleveland DW. Decoding ALS: From genes to mechanism[J]. Nature, 2016, 539(7628):197-206. doi: 10.1038/nature20413
[16]	Dauvilliers Y, Winkelmann J. Restless legs syndrome: Update on pathogenesis[J]. Curr Opin Pulm Med, 2013, 19(6):594-600. doi: 10.1097/MCP.0b013e328365ab07 pmid: 24048084
[17]	Tholfsen LK, Larsen JP, Schulz J, et al. Development of excessive daytime sleepiness in early Parkinson disease[J]. Neurology, 2015, 85(2):162-168. doi: 10.1212/WNL.0000000000001737 pmid: 26085603
[18]	Baumann CR. Traumatic brain injury and disturbed sleep and wakefulness[J]. Neuromolecular Med, 2012, 14(3): 205-212. doi: 10.1007/s12017-012-8178-x URL
[19]	Sharma KR, Sheriff S, Maudsley A, et al. Diffusion tensor imaging of basal ganglia and thalamus in amyotrophic lateral sclerosis[J]. J Neuroimaging, 2013, 23(3):368-374. doi: 10.1111/j.1552-6569.2011.00679.x pmid: 22273090

纳入文献	国家	研究类型	对照组例数	ALS患者一般资料						NOS 评分
纳入文献	国家	研究类型	对照组例数	ALS 例数	男 (%)	平均年龄 (岁)	病程 (月)	延髓起病 (%)	RLS (%)	NOS 评分
Limousin^[9], 2011	法国	队列研究	未提供	69	46.38	67.1±10.0	29.9±24.6	34.78	18.84	7
Liu^[10], 2018	中国	病例对照研究	109	109	60.60	52.9±10.1	15.6±9.7	33.00	14.68	8
Lo Coco^[11], 2010	意大利	病例对照研究	100	76	57.89	58.7±12.8	26.5±13.3	22.37	25	7
Reyhani^[12], 2019	土耳其	队列研究	20	73	49.30	58.0±9.9	58.5±30	45.20	26	8
Sun^[13], 2020	中国	病例对照研究	206	204	55.88	53.5±9.9	14.6±8.9	30.00	11.30	8
Panda^[14], 2018	印度	病例对照研究	190	40	57.50	58.5±12.4	28.4±22.3	30	5	6

纳入文献	国家	研究类型	对照组例数	ALS患者一般资料						NOS 评分
纳入文献	国家	研究类型	对照组例数	ALS 例数	男 (%)	平均年龄 (岁)	病程 (月)	延髓起病 (%)	RLS (%)	NOS 评分
Limousin^[9], 2011	法国	队列研究	未提供	69	46.38	67.1±10.0	29.9±24.6	34.78	18.84	7
Liu^[10], 2018	中国	病例对照研究	109	109	60.60	52.9±10.1	15.6±9.7	33.00	14.68	8
Lo Coco^[11], 2010	意大利	病例对照研究	100	76	57.89	58.7±12.8	26.5±13.3	22.37	25	7
Reyhani^[12], 2019	土耳其	队列研究	20	73	49.30	58.0±9.9	58.5±30	45.20	26	8
Sun^[13], 2020	中国	病例对照研究	206	204	55.88	53.5±9.9	14.6±8.9	30.00	11.30	8
Panda^[14], 2018	印度	病例对照研究	190	40	57.50	58.5±12.4	28.4±22.3	30	5	6

纳入文献	组别	例数	平均年龄(岁)	病程(月)	延髓起病(%)	ALSFRS-R评分	EDS(%)
Limousin^[9], 2011	ALS/RLS+	13	72.62±6.29	44.96±36.32	30.77%	29.54±8.33	15.38%
	ALS/RLS-	56	68.59±10.27	26.37±19.82	35.71%	33.74±6.53	3.57%
Liu^[10], 2018	ALS/RLS+	16	54.81±7.32	13.2±5.9	37.50%	38.9±3.6	43.75%
	ALS/RLS-	93	52.58±10.53	16.0±10.1	32.30%	40.4±4.3	10.75%
Lo Coco^[11], 2010	ALS/RLS+	19	59.3±11.6	25.3±13.4	15.80%	26.8±7.5	36.80%
	ALS/RLS-	57	58.5±13.2	27.9±13.2	25%	33.5±8.3	22.80%

纳入文献	组别	例数	平均年龄(岁)	病程(月)	延髓起病(%)	ALSFRS-R评分	EDS(%)
Limousin^[9], 2011	ALS/RLS+	13	72.62±6.29	44.96±36.32	30.77%	29.54±8.33	15.38%
	ALS/RLS-	56	68.59±10.27	26.37±19.82	35.71%	33.74±6.53	3.57%
Liu^[10], 2018	ALS/RLS+	16	54.81±7.32	13.2±5.9	37.50%	38.9±3.6	43.75%
	ALS/RLS-	93	52.58±10.53	16.0±10.1	32.30%	40.4±4.3	10.75%
Lo Coco^[11], 2010	ALS/RLS+	19	59.3±11.6	25.3±13.4	15.80%	26.8±7.5	36.80%
	ALS/RLS-	57	58.5±13.2	27.9±13.2	25%	33.5±8.3	22.80%