高频rTMS治疗帕金森病伴白天过度嗜睡的临床疗效及与弥散张量成像的相关性研究

Clinical efficacy of high frequency rTMS combined with selegilan hydrochloride in the treatment of PD with excessive daytime sleepiness sleep disorder and its correlation with DTI

目的:观察高频重复经颅磁刺激联合盐酸司来吉兰治疗帕金森病(PD)伴白天过度嗜睡型(EDS)睡眠障碍的临床疗效以及与弥散张量成像的相关性。方法:选择PD伴EDS患者88例随机分为对照组和观察组各44例。2组均采用动态调整的基础药物配合盐酸司来吉兰治疗,观察组加用重复经颅磁刺激(rTMS),对照组采用假刺激,2组共干预12周。观察2组干预前后的磁共振弥散张量成像(DTI)的各向异性分数(FA)变化(感兴趣区域为黑质、红核、壳核、中脑被盖、脑桥被盖);比较干预前、干预3、6及12周以及治疗结束后3个月的左旋多巴(LD)总药物剂量及Epworth嗜睡量表(ESS)、39项帕金森病生活质量问卷(PDQ-39)、PD统一评分量表(UPDRS)评分。结果:观察组在干预6及12周以及干预结束后3个月的LD总剂量均低于治疗前和对照组(P<0.05);分组和时间对剂量存在交互效应(F交互=18.459,P=0.015);在ESS方面,观察组在干预6及12周以及干预结束后3个月的ESS均低于对照组;分组和时间对ESS存在交互效应(F交互=8.466,P=0.028);在PDQ-39方面,观察组在干预3、6及12周以及干预结束后3个月的评分均低于对照组(P<0.05);分组和时间对PDQ-39存在交互效应(F交互=11.474,P=0.021)。在UPDRS方面,观察组在干预6及12周以及干预结束后3个月的UPDRSⅠ、UPDRSⅡ和UPDRSⅣ评分明显低于对照组(P=0.031、0.021、0.039);DTI方面,干预后观察组在中脑被盖、脑桥被盖的FA高于对照组(P<0.05)。相关性分析显示,治疗后观察组LD总剂量、ESS评分、PDQ-39评分以及UPDRS(Ⅰ和Ⅱ)评分下降与中脑被盖FA值上升呈负相关(P<0.05);而LD总剂量与UPDRSⅠ评分下降及脑桥被盖FA值上升呈负相关(P<0.05)。结论:重复经颅磁刺激联合盐酸司来吉兰干预PD伴EDS,其近远期疗效显著;患者生活质量和相关非运动症状得到有效改善,考虑与DTI成像在脑桥被盖和中脑被盖的FA上升有关。

Objective:To observe the clinical efficacy of high frequency repetitive transcranial magnetic stimulation(rTMS)combined with selegiline hydrochloride in the treatment of Parkinson’s disease(PD)with excessive daytime sleepiness(EDS)sleep disorder and its correlation with diffusion tensor imaging(TDI).Methods:A total of PD 88 patients with EDS treated in our hospital from August 2017 to July 2020 were selected as the research objects.They were randomly divided into control group and observation group.Both groups were treated with dynamically adjusted basic drugs combined with selegilan hydrochloride,and the control group was treated with pseudomagnetic stimulation.The observation group was treated with real rTMS.The two groups were intervened for 12 weeks.The changes of fractional anisotropy(FA)of DTI before and after intervention were observed in the two groups(the areas of interest contained substantia nigra,red nucleus,putamen,mesencephalic tegmentum and pontine tegmentum).The total dose of left DOPA(LD),Epworth Sleepiness Scale(ESS),39 item questionnaire(PDQ-39)and Unified Parkinson’s Disease Rating Scale(UPDRS)were observed before intervention,and 6 weeks,12 weeks and 3 months after treatment.Results:The total dose of LD in the observation group at 6th week,12th week and 3rd month after the intervention was lower than that before treatment and the control group(P<0.05);Grouping and time had interactive effects on dose(F=18.459,P=0.015).In terms of DTI indexes,the FA of midbrain tegmentum and pontine tegmentum in the observation group after intervention was higher than that in the control gro-up,and the difference was statistically significant(P<0.05).The ESS score in the observation group was lower than that in the control group at 3rd week,6th week,12th week and 3rd month after the intervention;Grouping and time had interaction effects on ESS score(f interaction=8.466,P=0.028).The PDQ-39 score in the observation group was lower than that in the control group at 3rd week,6th week,12th week and 3rd month after the intervention(P<0.05);Grouping and time had interaction effects on PDQ-39(f interaction=11.474,P=0.021).The scores of UPDRS,UPDRSⅠ,UPDRSⅡand UPDRSⅣin the observation group were significantly lower than those in the control group at 6th week,12th week and 3rd month after the intervention(P=0.031,0.021,0.039).Correlation analysis showed that the decrease of LD total dose,ESS score,PDQ-39 score and UPDRS(ⅠandⅡ)score in the observation group after treatment was negatively correlated with the increase of FA value of midbrain tegmental.The decrease of total LD dose and UPDRS I score was negatively correlated with the increase of pontine tegmental FA value(P<0.05).Conclusion:The rTMS combined with selegilan hydrochloride has significant short-term and long-term effects on PD with EDS;The effective improvement of patients’quality of life and related non motor symptoms is considered to be related to the increase of FA in pontine tegmentum and midbrain tegmentum by DTI.