丘脑底核脑深部电刺激治疗帕金森病合并抑郁障碍的长期疗效

目的研究丘脑底核（STN）脑深部电刺激（DBS）治疗帕金森病（PD）合并抑郁障碍的长期疗效并探讨其神经机制。方法对15例合并抑郁障碍的PD患者实施STN脑深部电极植入，术后3个月、6个月和12个月进行随访和临床评价。结果术后运动功能症状如肢体僵硬、震颤、运动迟缓和姿势平衡障碍改善良好，停药后PD分级量表运动评分显著下降（P〈0．01）。术后抑郁障碍症状如焦虑、绝望和激越症状改善良好，停药后汉密尔顿抑郁量表评分显著下降（P〈0．05）。结论STN-DBS能显著改善PD的抑郁障碍症状，STN在PD抑郁障碍神经机制中起重要作用。     

脑深部电刺激术联合药物治疗帕金森病有效性和安全性的meta分析

目的评价脑深部电刺激术联合药物治疗帕金森病的有效性及安全性。方法检索在2018年9月之前于Pub Med、EMBASE、Cochrane Library、CNKI文献数据库中DBS治疗帕金森病的临床研究。按纳入标准和排除标准进行资料筛选和提取,利用Rev Man 5. 3软件进行数据分析。结果纳入11个研究共274名帕金森患者。Meta分析显示:5年单纯DBS治疗与术后5年基线差异有统计学意义(P 0. 01),运动症状较术后基线改善,UPDRS-III(SMD=-21. 31,95%CI:-25. 18～-17. 44);术后5年单纯DBS治疗与药物联合DBS治疗差异有统计学意义(P 0. 01),运动症状UPDRSIII (SMD=-7. 26,95%CI:-9. 02～-5. 02)、生活质量UPDRS-II (SMD=-4. 2,95%CI:-6. 02～-2. 82)较单纯手术治疗有改善;术前术后LEDD (SMD=453. 76,95%CI:394. 31～513. 21)差异有统计学意义(P 0. 01)。DBS副作用发生率较低,脑出血发生率4. 4%,感染6例(2. 2%);癫痫3例(1. 1%)。结论脑深部电刺激术在术后5年无论是单纯手术治疗或手术联合药物治疗均能改善患者的运动症状及生活质量,较术前明显降低了左旋多巴类药物的用量,且副作用少,安全性高。     

丘脑底核脑深部电刺激治疗帕金森病抑郁障碍的初步临床研究

目的研究丘脑底核(STN)脑深部电刺激(DBS)治疗帕金森病(PD)抑郁障碍的短期疗效。方法对15例合并抑郁障碍的帕金森病患者丘脑底核进行电极植入,术后3个月进行PD分级量表(UPDRS)运动评分和汉密尔顿抑郁量表(HAMD17)评分,与术前1个月的评价对照。结果术后15例运动功能症状如肢体僵硬、震颤、运动迟缓和姿势平衡障碍改善良好,停药后UPDRS运动评分下降显著(P<0.01)。术后HAMD17总分下降显著(P<0.01),抑郁障碍改善显进2例(HAMD17减分率≥50%),进步7例(HAMD17减分率≥25%)。术后焦虑/躯体化、阻滞、睡眠障碍和体重因子分均显著低于术前(P<0.01),认知障碍因子分与术前无显著性差异(P>0.05)。结论STNDBS可明显改善帕金森病抑郁障碍症状,对焦虑/躯体化和阻滞等症状尤其显著。     

丘脑底核深部电刺激对帕金森病患者抑郁及焦虑的影响

目的探讨丘脑底核(STN)深部电刺激(DBS)手术对帕金森病(PD)患者抑郁及焦虑的影响。方法41例接受STNDBS治疗的PD患者进行神经心理评估,分别于术前1周及术后12个月应用HY分期、统一PD评定量表运动检查部分(UPDRSⅢ)、医院焦虑和抑郁量表(HADS)及PD生活质量问卷(PDQ39)评价其病情、运动状况、情绪及生活质量,并进行统计学分析。结果术后患者UPDRSⅢ、HADS及PDQ39评分较术前极显著改善(均P<0.001),HY分期在“开”及“关”状态均明显改善(P<0.05,P<0.001);Spearman相关性检验提示HADS抑郁评分与PDQ39中情绪状态、羞耻感及总评分变化正相关(r分别为0.35、0.37、0.34,均P<0.05),与HY分期、UPDRSⅢ不相关。HADS焦虑评分与其均不相关。结论STNDBS能改善PD患者的情绪,特别是抑郁状态,进而改善其生活质量。     

丘脑底核脑深部电刺激对帕金森病抑郁障碍的影响

目的探讨丘脑底核脑深部电刺激对帕金森病病人抑郁障碍的疗效及其机制。方法回顾性分析21例帕金森病合并抑郁障碍病人的临床资料,均行丘脑底核脑深部电刺激术,术前及术后3、6个月分别应用汉密尔顿抑郁量表(HAMD)评分和统一帕金森病评定量表(UPDRS)运动评分对抑郁障碍和运动功能进行临床评价并分析其相关性。结果术后UPDRS运动评分和HAMD评分均显著下降(均P0.05),但是抑郁症状的改善与运动功能的改善并没有明显的相关性(P0.05)。结论丘脑底核脑深部电刺激能够明显改善帕金森病病人的抑郁症状,其机制可能与丘脑底核受到刺激影响脑内神经递质的变化有关,术后运动功能的改善不是抑郁症状改善的主要原因。     

丘脑底核电刺激治疗帕金森病

目的 探讨脑深部电刺激（DBS）对原发帕金森病（PD）的治疗作用及手术方法。方法 应用微电极导向技术和手术计划系统进行靶点定位，对20例PD病人的丘脑底核（STN）进行电极植入，术后至少6个月的评价和随访。结果 15例单侧和5例双侧STN的DBS术后病人肢体僵直、震颤和运动迟缓等症状改善明显，术前术后UPDRS运动评分和日常生活能力评分均有显著下降（P＜0.01），服药量也有不同程度的减少，无严重及永久并发症。结论 STN的DBS手术治疗PD，对症状改善非常全面，可通过参数调整达到最佳治疗效果。服药量明显减少，是一种安全、有效的治疗方法。     

丘脑底核电刺激术治疗帕金森病的疗效观察

目的 探讨丘脑底核（STN）行脑深部电刺激术（DBS）治疗帕金森病（PD）的疗效。方法 回顾性分析2016年1月至2017年9月收治的64例PD的临床资料,均采用STN-DBS治疗。术后均随访3个月,使用统一帕金森病评定量表（UPDRS-Ⅲ）评分评估疗效。结果 64例手术顺利完成,平均用时（4.39±1.01）h。共置入128根刺激电极,术后CT计算移位距离为0~1.89 mm,平均（0.91±0.42）mm。术前检测64例改善率在37.20%~82.54%,平均（55.36±5.62）%。术后抗PD药物的左旋多巴等效剂量明显低于术前（P<0.05）;术后开机状态下UPDRS-Ⅲ评分明显低于术前（P<0.05）。术后出现颅内积气29例、颅内出血2例、延伸导线移位3例、情绪改变、构音障碍2例、异动9例,末次随访时均完全改善或症状消失。结论 STN-DBS治疗PD,能有效改善病人运动功能,减少抗PD药物的使用,但围术期并发症风险高,临床应重视操作技巧。     

脑深部电刺激治疗帕金森病的长期随访研究

目的长期随访一组采用双侧脑深部电刺激(DBS)丘脑底核(STN)的帕金森(PD)病人,为临床研究提供参考。方法 195例PD病人在我院接受了双侧STN-DBS手术。术中采用微电极记录STN的外放电信号,刺激电极测试病人症状改善情况及副反应阈值。分别在术前术后1年、3年和5年采用UPDRS评分评估PD病人开/关两种状态下的症状改善程度。结果术前对照,PD病人术后5年关状态运动评分改善率为60.3%;日常生活评分的改善率为54.2%。语言是运动评分中唯一没有改善的症状。异动症除外,术后1年开状态下运动评分没有显著改善。第1年和第5年开状态下运动迟缓、姿势障碍和步僵症状较术前均有加重。术后第5年异动症较术前明显改善。结论 PD病人双侧STN-DBS术后长期随访结果表明,关状态下运动评分和开状态下异动症均明显改善。术后第1年和第5年比较,行动迟缓、语言、姿势异常、步僵和认知功能的障碍均有加重。     

单侧丘脑底核电刺激治疗偏侧型帕金森病的长期疗效

目的评估单侧丘脑底核(STN)脑深部电刺激(DBS)治疗偏侧型帕金森病的长期疗效。方法回顾性分析23例偏侧型帕金森病病人的临床资料,均行单侧STN-DBS治疗,并分别于术前3~5 d、术后1年、术后5年以帕金森病统一评分量表(UPDRS)进行评估。结果术后5年,病人在刺激"关"状态下,UPDRSⅡ、Ⅲ和轴性症状评分较术前明显升高(P<0.05);而刺激"开"状态下,UPDRSⅡ、Ⅲ和轴性部分评分较同期刺激"关"状态分别降低37.37%、41.14%和26.91%。与术前比较,术后5年平均每日口服左旋多巴等效剂量降低24.92%,而异动时间和异动病残度分别增加52.63%和59.65%。本组未发生手术相关并发症,随访期间出现发声困难6例。结论对偏侧型帕金森病人,单侧STN-DBS是一种疗效持久的治疗方法。     

丘脑底核电刺激术治疗帕金森病的疗效

目的评估丘脑底核脑深部电刺激(STN-DBS)对帕金森病的临床疗效。方法回顾性分析应用STN-DBS手术治疗的32例帕金森病病人的临床资料,在术前、术后3个月分别采用统一帕金森病评定量表(UPDRS)、抑郁自评量表(SDS)和症状自评量表(SCL-90)进行随访评估、心理状况问卷调查和分析。结果脉冲发生器开启后,32例病人的UPDRS日常活动和运动功能在"关"状态,平均改善率为51.7%和60.9%;在"开"状态下,平均改善率21.4%和22.3%。20例病人术前SDS评分50分,其SCL-90的抑郁、焦虑、躯体化、人际敏感、敌对、恐怖和偏执7个因子显著高于中国常模(P0.05)。术前与术后SCL-90抑郁、躯体化、恐怖、焦虑、精神病性因子有显著性差异(P0.05),人际敏感、偏执、敌对和强迫等因子无显著性差异(P0.05)。结论 STN-DBS可以改善帕金森病病人的运动功能,提高日常生活能力,还可以明显改善帕金森病伴抑郁病人的心理状况,是安全有效的治疗方法。     

帕金森病患者丘脑底核电极植入术中位置判断和调整

目的探讨帕金森病患者脑深部刺激术（DBS）中丘脑底核（STN）电极植入位置准确性判断和调整。方法对137例帕金森病（PD）患者进行了丘脑底核DBS治疗,其中单侧68例,双侧69例。采用磁共振扫描,图像直接定位和坐标值定位相结合的方法计算靶点坐标,微电极记录细胞外放电。术中采用微毁损效应,观察刺激效果和副作用,X线透视和带立体定向头架MRI复查。结果绝大部分患者都能观察到电极植入的微毁损效应、电刺激效果和刺激副作用,术中X线透视和带立体定向头架MRI复查能观察到电极实际位置,并进行必要的调整。结论通过微毁损效应、电刺激效果和刺激副作用观察以及术中影像学检查能及时纠正电极位置偏差,减少二次手术,从而提高PD患者的DBS疗效。     

脑深部电刺激治疗帕金森病的程控

目的探讨丘脑底核脑深部电刺激术治疗帕金森病(PD)的手术方法和脉冲发生器程控调节。方法自2000年1月～2004年2月用脑深部电刺激丘脑底核(STN)治疗帕金森病61例,其中单侧30例,双侧31例。采用磁共振扫描结合微电极记录技术进行靶点定位。术后用帕金森病评定量表(UPDRS)运动评分评价刺激效果。结果61例PD患者术后随访6～36个月,平均11．3个月。脉冲发生器开启时,在“关”状态下,UPDRS运动评分改善率45．2％;在“开”状态下,UPDRS运动评分改善率20．7％,未发现任何并发症。结论脑深部刺激(DBS)能有效控制帕金森病患者的症状,手术并发症少,术后可根据患者的症状调节参数,丘脑底核(STN)已成为治疗帕金森病的最佳靶点。     

Side-effects of subthalamic stimulation in Parkinson's disease: clinical evolution and predictive factors

Chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) is an alternative treatment for disabling forms of Parkinson's disease when on–off fluctuations and levodopa-induced dyskinesias compromise patients' quality of life. The aim of this study was to assess the evolution of side-effects during the first year of follow-up and search for clinical predictive factors accounting for their occurrence. We compared the frequency of side-effects at 3 and 12 months after surgery in a cohort of 44 patients. The off-medication scores of Unified Parkinson's Disease Rating Scale (UPDRS) II, III, axial symptoms, disease duration and age at surgery were retained for correlation analysis. Dysarthria/hypophonia, weight gain and postural instability were the most frequent chronic side-effects. Whereas dysarthria/hypophonia remained stable over time, weight gain and postural instability increased during the first year post-op. High axial and UPDRS II scores at surgery were predictive of dysarthria/hypophonia. Age and axial score at surgery were positively correlated with postural instability. Despite the occurrence of side-effects, the benefit/side-effects ratio of STN stimulation was largely positive during the first year of follow-up. Age, intensity of axial symptoms and UDPRS II off-medication score before surgery are predictive factors of dysarthria/hypophonia and postural instability after surgery.     

Subthalamic deep brain stimulation and impulse control in Parkinson's disease

Background and purpose:  Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson ' s disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy.
Methods:  In a cross-sectional evaluation, 53 consecutively eligible patients were assessed for impulsivity with the Barratt Impulsiveness Scale, for impulse control disorders (ICDs) using the Minnesota Impulsive Disorders Interview, and for obsessive–compulsive symptoms using the Maudsley Obsessional-Compulsive Inventory.
Results:  Independent samples t -tests revealed that compulsivity scores were not different between DBS patients and patients without DBS. However, impulsivity scores were significantly higher in DBS patients. Additionally, ICDs were observed in 3 of 16 (19%) DBS patients and in 3 of 37 (8%) medically treated patients. No association was found between the use of dopamine agonists and impulsivity in DBS patients.
Conclusions:  Our data suggest that screening for impulsivity and ICDs should be performed prior to DBS, and that patients should be monitored for these problems during follow-up. Prospective trials are needed to confirm the findings of this exploratory study and to elucidate the reasons of a possible induction of impulsivity by STN DBS.     

帕金森病丘脑底核脑深部电刺激术后的长期随访研究

目的 研究丘脑底核脑深部电刺激(STN-DBS)术治疗帕金森病(PD)的长期临床效果.方法 对采用STN-DBS术治疗的75例PD患者进行术后长期随访.对患者手术前抗PD药物“关”与“开”状态进行统一帕金森病评定量表(UPDRS)评估;术后第1、3、5和10年,在STN-DBS持续治疗下对患者药物“关”与“开”状态进行...     

Chronic deep brain stimulation of the subthalamic nucleus in a monkey model of hemiparkinsonian Dynamic alterations of extracellular fluid dopamine levels in corpus striatum

BACKGROUND： Although experimental studies have utilized high-frequency stimulation in animal models, few reports have focused on long-term subthalamic nucleus deep brain stimulation （STN DBS） in Parkinson＇s disease （PD） animal models. OBJECTIVE： The present study simulated long-term DBS system and utilized microdialysis technology to study the influence of STN DBS on levels of extracellular dopamine （DA） and its metabolites, homovanillic acid （HVA） and dihydroxy phenyl acetic acid, in the corpus striatum of a hemiparkinsonian monkey model. DESIGN, TIME AND SETTING： A controlled animal study was performed at the Neurosurgery Laboratory, Changhai Hospital of the Second Military Medical University of Chinese PLA between January 2004 and December 2007. MATERIALS： 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyrindinewas （MPTP） purchased from Sigma, USA. Type-3389 DBS electrode and type-7246 pulse generator were provided by Medtronic, USA. METHODS： Hemiparkinsonism was induced in 2 male, adult Rhesus Macaque monkeys through unilateral internal carotid artery infusion of MPTP. Following model establishment, stimulation electrodes were implanted in the right STN, and chronic high-frequency stimulation （60 μs pulse width, 130 Hz frequency, and 1.5 2.0 V pressure） was performed. MAIN OUTCOME MEASURES： Prior to, and 2 hours, 8 hours, 1 week, 1 month, and 2 months after DBS, samples were collected from the caudate nucleus and putamen using microdialysis technology Extracellular levels of DA and its metabolites were measured using high-performance liquid chromatography and electrochemical detection （HPLC-ECD） methods. RESULTS： At 8 hours, 1 week, 1 month, and 2 months after DBS, DA levels in the putamen and caudate nucleus were increased on the electrode-implanted side by 39%, 91%, 111%, and 114% and 31%, 91%, 106%, and 102%, respectively. The DA turnover rate （HVA/DA） was increased in the putamen and caudate nucleus by 186% and 91%, respectively, at 8 hours after DBS, while there was no significant difference at 1 week, 1 month, and 2 months after DBS. CONCLUSION： Effective, chronic, high frequency DBS increased extracellular DA levels in the corpus striatum, which could be one of mechanisms involved in the effects of STN DBS.     

多通道微电极记录在帕金森病脑深部电刺激定位中的作用

目的丘脑底核(STN)是帕金森病(PD)脑深部电刺激(DBS)治疗的主要靶点,使用多通道微电极记录可以准确地发现STN的感觉运动区,提高治疗精准度,提高DBS治疗效果;但多通道微电极记录的方法和风险目前介绍的比较少。现通过10例帕金森病STN-DBS手术中应用多通道微电极记录的方法,探讨多通道微电极记录的精准定位作用与风险。方法 2012年10月至2013年5月10例帕金森病患者在STNDBS手术中,应用多通道微电极记录(4~5个通道),同步使用评分法记录,结合宏电极刺激结果,选择最终置入刺激电极的通道,比较术前预设的放置靶点与最终放置靶点的不同,测量通道的长度。结果不同的通道显示了不同的神经元放电模式以及其放电的强度与长度。比较最后电极植入通道与术前的预设中心靶点显示:左侧STN:放置中心位置6例,非中心4例,其中前方2例,外侧1例,内侧1例;右侧STN:中心位置5例,非中心5例,其中外侧4例,内侧1例,STN感觉运动区的通道长度:左侧STN感觉运动区信号长度为(4.85±1)mm(3~6 mm),右侧STN感觉运动区信号长度为(4.83±0.7)mm(4~6 mm)。10例患者手术中未见出血并发症。结论 10例患者中选择预设靶点即中心靶点的比例只有50%~60%,有40%~50%的患者最终放置植入电极的位置与预设的靶点不同。多通道微电极记录可以覆盖整个STN,通过记录其电信号并分析比较,可以准确显示出STN的运动区域,选择最佳的通道植入电极,提高DBS治疗的效果;未见明显的出血并发症。因此多通道微电极记录是DBS手术中一种可以提高精准定位,同时也非常安全有效监测的方法。     

New electrophysiological mapping combined with MRI in parkinsonian's subthalamic region

The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson's disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel's field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2-mm anterior track. We calculated off-line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on-line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2–ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.     

人用DBS系统在脑深部电刺激猴模型构建中的应用

目的探讨人用脑深部电刺激(DBS)系统在构建猴脑深部电刺激模型中的应用。方法 4只偏侧帕金森病(PD)猴模型,按照猴脑立体定向图谱,在右侧丘脑底核(STN)植入脑深部刺激电极(Medtronic 3389),其中刺激组2只猴同期皮下植入Medtronic 7495型连接导线和Soletra TM7426型脉冲发生器,术后一周给予慢性高频电刺激。另2只偏侧PD模型猴仅在右侧STN植入电极,不植入脉冲发生器,作为对照组。连续观察12个月,进行运动障碍评分观察和阿朴吗啡(APO)诱发旋转实验。结果术后影像学观察电极前端均位于STN核范围内;刺激组同期植入脉冲发生器给予慢性高频电刺激,猴偏侧帕金森样症状明显改善,有效高频电刺激可以立即停止APO所诱发的旋转,而对照组在观察期内症状无明显缓解。结论人用DBS系统通过立体定向技术植入猴脑内特定靶点,可以有效的建立DBS动物模型,为DBS在神经系统疾病中的应用研究提供了良好的实验模型。