Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson's Disease.
Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson's Disease.
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DOI：
10.1371/journal.pone.0138462
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuwabara S
中科院分区：
文献类型：
--
作者：
Yamamoto T;Uchiyama T;Higuchi Y;Asahina M;Hirano S;Yamanaka Y;Kuwabara S
虽然丘脑底核脑深部电刺激（STN-DBS）对晚期帕金森病（PD）患者有效，但其生理机制尚不清楚。由于STN-DBS对运动症状通过L-3，4-二羟基苯丙氨酸（L-DOPA）治疗显著缓解的PD患者有效，因此术前较高的儿茶酚胺水平可能与术后较好的临床结局相关。我们的目的是检查术前儿茶酚胺水平与丘脑底核脑深部电刺激术后临床结局之间的相关性。STN-DBS在对多巴胺能药物反应良好的患者中的有效性表明多巴胺能系统和STN-DBS之间存在因果关系。我们还研究了丘脑底核刺激后如何调节儿茶酚胺水平。共入组了25例PD患者（平均年龄66.2 ± 6.7岁，平均病程11.6 ± 3.7年）。术前平均左旋多巴等效剂量为1032 ± 34.6 mg。在手术前口服抗帕金森病药物后1小时测量脑脊液和血浆儿茶酚胺水平。在手术前后获得了平均统一帕金森病评定量表评分（PDRS）和帕金森病问卷-39（PDQ-39）。在25例患者中，11例患者在随访时的刺激期间口服抗帕金森病药物后1小时收集术后脑脊液和血浆。术后平均左旋多巴等效剂量显著降低，运动功能和生活质量改善。术前儿茶酚胺水平与术后运动评分和生活质量基本呈负相关，提示术前较高的儿茶酚胺水平与STN-DBS术后较好的预后有关。术前血浆左旋多巴水平与术后3个月非手术期的FDIRS- III评分呈显著负相关。术前脑脊液中DOPAC和5-HT水平与术后1年非手术期STN-DBS评分呈显著负相关，术前脑脊液高香草酸水平与术后3个月手术期STN-DBS评分呈显著负相关。在PDQ-39 SI（汇总指数）中，术前血浆多巴胺（DA）水平与STN-DBS后1年的术后PDQ-39 SI呈显著负相关，表明术前较高的血浆DA水平导致STN-DBS后1年的生活质量（QOL）较好。逐步多元线性回归研究显示，术前较高的血浆HVA水平对术后运动症状有负面影响（即，术前脑脊液L-DOPA水平升高对术后运动症状和QOL有积极影响（术后L-DOPA和PDQ-39 SI评分降低）。尽管左旋多巴等效剂量显著降低，但11例患者术后儿茶酚胺水平未显著降低。出乎意料的是，STN-DBS后CSF HVA水平从0.00089±0.0003 ng/μ l显著升高至0.002±0.0008 ng/μl。术前儿茶酚胺水平可能影响术后运动症状和生活质量。尽管左旋多巴等效剂量显著降低，但术后儿茶酚胺水平未显著降低。
Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation. In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients. Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with postoperative UPDRS- III score in off phase three months after STN-DBS. The preoperative cerebrospinal fluid (CSF) 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) levels had significantly negative correlations with postoperative UPDRS- III score in off phase one year after STN-DBS and the preoperative CSF homovanilic acid (HVA) levels had significant negative correlations with postoperative UPDRS- III score in on phase three months after STN-DBS. In PDQ-39 SI (summary index), preoperative plasma dopamine (DA) level had significantly negative correlations with postoperative PDQ-39 SI one year after STN-DBS suggesting that higher preoperative plasma DA level resulted in better quality of life (QOL) one year after STN-DBS. The stepwise multiple linear regression study revealed that higher preoperative plasma HVA levels had negative influence on the postoperative motor symptoms (i.e., increase in the score of UPDRS), whereas higher preoperative CSF L-DOPA levels had positive influence on the postoperative motor symptoms and QOL (decrease in the score of UPDRS and PDQ-39 SI) The catecholamine levels were not significantly reduced postoperatively in 11 patients despite the significant reduction in levodopa equivalent doses. Unexpectedly, CSF HVA levels significantly increased from 0.00089±0.0003 ng/μl to 0.002±0.0008 ng/μl after STN-DBS. The preoperative catecholamine levels might affect the postoperative motor symptoms and quality of life. The catecholamine levels were not significantly reduced postoperatively despite the significant reduction in levodopa equivalent doses.