丘脑底核脑深部刺激术治疗帕金森病的手术方法和疗效分析

目的 总结帕金森病(PD)脑深部刺激术(DBS)治疗的手术方法和效果。方法 对25例帕金森病患者进行了丘脑底核DBS治疗,其中单侧17例,双侧8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UPDRS运动评分评价刺激效果。结果 25例PD患者术后随访5～34个月,平均8.3个月。脉冲发生器开启时,在“关”状态下,UPDRS运动评分改善率50.2％;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 丘脑底核DBS是改善PD患者运动功能较为理想的治疗方法。     

双侧丘脑底核脑深部电刺激治疗帕金森病

目的 应用双侧丘脑底核脑深部电刺激（DBS）治疗难治性帕金森病（PD），并对其疗效作出评价。方法 对7例帕金森病患者采用磁共振导向立体定向及术中电生理验证方法，将刺激电极分别植入丘脑底核，采用同期或分期植入刺激发生器。术后1周用程控计算机在体外调速刺激参数，以达到最佳疗效。结果 6例患者术后均获得了显著的疗效。震颤完全消失，肌强直、步态、姿障碍以及药物所致的并发症明显,面时多巴胺类药物用量明显减少，1例曾接爱双侧丘脑腹中间核及一侧苍白球毁损后的患者只得到了轻度改善。结论 DBS法治疗中晚期PD，具有安全，副作用可逆转的优点，且可根据患者的不同状况及病情发展调节刺激参数达到最佳症状控制，完全控制震颤，明显改善肌张力障碍、步态、资势等运动障碍及药物所致的并发症，另外多巴胺类药物的用量也明显减少。     

Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with Parkinson's disease

ObjectiveTo study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinson's disease (PD) and to discuss the mechanism.MethodsA STN–DBS group (n = 27) and anti-Parkinson's medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinson's Disease Rating Scale (UPDRS-III).ResultsCompared with the preoperative and the medication control group, the UPDRS-III scores of the STN–DBS group decreased remarkably within 18 months postoperatively (P ≤ 0.001), and the SDS scores decreased notably within 6 months postoperatively (P ≤ 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P ≤ 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P ≤ 0.05), especially at 5 weeks postoperation (P ≤ 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P ≤ 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P ≤ 0.05) within 18 months postoperatively.ConclusionThe improvement in motor symptoms resulting from STN–DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients.     

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。     

双侧丘脑底核脑深部刺激术治疗帕金森病13例报告

目的 探讨双侧丘脑底核（STN）脑深部刺激术（DBS）治疗帕金森病的临床经验。方法 从2002年到2005年共完成了13例帕金森病的双侧丘脑底核DBS，根据STN解剖学定位，靶点的理论坐标值是X=11-13mm，Y=0-2mm，Z=0-4mm，通过立体定向技术在双侧丘脑底核植入刺激电极，并于锁骨下方植入脑深部电刺激器。结果 随访时间为6个月到3年，3例震颤为主病人的症状完全缓解，即震颤完全消失；僵直和运动迟缓为主要症状者的症状缓解程度达90％以上，其中以四肢肌肉僵直的效果较好，运动迟缓也有明显缓解，但是有1例病人双侧肢运动协调性差。所有患者植物神经功能症状有较明显改善，如便秘、流涎、出汗和浮肿等均有改善。结论 DBS治疗帕金森病，是帕金森病治疗的一个里程碑似的进步。它可以明显地缓解帕金森病的主要症状和体征，对运动迟缓、僵直和震颤等均有较理想的效果。     

丘脑底核脑深部电刺激治疗帕金森病的功能显像研究

目的通过单光子放射计算机断层扫描(SPECT)功能显像研究探讨丘脑底核脑深部电刺激(STN DBS)对纹状体多巴胺系统代谢的影响。方法对2只偏侧帕金森病(PD)模型猴及4例临床PD患者在施行单侧STN DBS手术前后给予SPECT检查,测定纹状体区域多巴胺转运体(DAT)及多巴胺D2受体(D2R)含量变化。结果STN DBS电刺激后2只偏侧PD模型猴及3例疗效较好的PD患者纹状体区DAT含量明显增加,2只PD模型猴D2R含量逐渐下降,4例患者D2R检测与术前无统计学意义。结论STN DBS可以明显改善PD症状,SPECT检查显示刺激侧纹状体区DAT含量升高,提示STN DBS可能改善了刺激侧纹状体区多巴胺的代谢,这可能是STN DBS的作用机制之一。     

脑深部电刺激术治疗Hallervorden-Spatz病一例及文献复习

目的 观察双侧丘脑底核脑深部电刺激术治疗1例Hallervorden-Spatz病的手术效果.方法 将脑深部刺激电极植入双侧丘脑底核,分别于术前、开机后1个月、开机后3个月,12个月时对其进行BFM及BFMDMS评分,评价治疗效果.结果 术前、开机后1个月、开机后3个月、12个月的BFMDMS评分分别为114、35、28、14分,症状改善率刺激1个月时为69%、3个月为75%、12个月为88%.持续刺激未引起任何不良反应,患者不再服用相关药物.结论 双侧丘脑底核脑深部电刺激术能够有效的改善严重的全身性肌张力障碍Hallervorden-Spatz病症状,是一种可供选择的安全有效的治疗方法.     

Deep brain stimulation of the subthalamic nucleus in PD: an analysis of the exclusion causes

OBJECTIVE: Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) represents a proper choice for the treatment of advanced Parkinson's disease (PD). A correct selection of the patients as candidates for the surgery is essential for a good outcome. In this study, we analyzed the exclusion causes of a series of PD patients hospitalized for the selection protocol. METHODS: Ninety-eight PD patients as potential candidates for the STN DBS were studied. All patients were hospitalized and underwent a clinical evaluation of the PD stage, a levodopa challenge, a MR of the brain and a neuropsychological assessment. RESULTS: The percentage of subjects considered not suitable for the surgery was 29.6%. A single cause of exclusion was present in 65.5% of not suitable patients, while multiple causes were present in 34.5%. The most frequent cause of exclusion was the finding of neuropsychological or psychic disorders (48.3%); in 37.9% of the patients, the motor disability was not severe enough to justify the surgery, while in 31%, we found relevant abnormalities at the brain MR. Three patients (10.3%) were poorly motivated for the surgery, while in three others (10.3%), we found a significant illness other than PD. CONCLUSIONS: The finding that about 30% of the PD patients potentially suitable for STN DBS presents some exclusion causes underlines the importance of a careful selection of the candidates for this surgery.     

Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be an effective treatment for the motor symptoms of Parkinson's disease. The therapeutic benefits are voltage-dependent and, in many cases, limited by the appearance of side effects, including muscle contractions. We have observed a number of clinical cases where improvements in rigidity were accompanied by a worsening of bradykinesia. Considering the anatomic position of STN and current approaches to implantation of the DBS lead, we hypothesized that this dissociation of motor symptoms arises from activation of pyramidal tract fibers in the adjacent internal capsule. The objective of this study was to assess the physiological basis for this dissociation and to test our hypothesis that the underlying etiology of this paradox is activation of fibers of the internal capsule. The effect of STN DBS at 80% of motor threshold for each of the four contacts was evaluated for its effect on rigidity, bradykinesia, and akinesia in a single primate with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Consistent with our observations in humans, this near-threshold stimulation was found to improve rigidity while bradykinesia and akinesia worsened. Worsening bradykinesia in the face of improvement of other motor signs in Parkinson's disease (PD) patients is suggestive of activation of pyramidal tract (PT) fibers during stimulation. This phenomenon may occur without overt muscle contraction and improved rigidity.     

丘脑底核脑深部电刺激治疗原发性帕金森病的不良事件

目的观察原发性帕金森病(Parkinson disease,PD)患者行丘脑底核脑深部电刺激术(deep brain stimulation of subthalamic nucleus,STN DBS)的不良事件。方法纳入行STN DBS的原发性帕金森病45例,收集患者一般临床资料,术后随访至3~9年,观察术后不良事件。结果手术相关不良事件:微毁损效应44例、囊袋积液2例、颅内出血1例、嗜睡1例;未观察到任何装置相关不良事件;刺激或疾病相关不良事件:异动症15例、步态平衡障碍12例,焦虑抑郁状态6例,构音障碍与多巴胺失调综合征各4例,智能减退2例,少数患者出现体重增加、幻觉、睁眼困难等。7例患者因共存疾病死亡。结论 STN DBS大部分不良事件可以控制,术后个体化调整参数及药物,有利于减少STN DBS不良事件。     

Effect of subthalamic nucleus deep brain stimulation on visual scanning

Objective

Deep brain stimulation (DBS) can provide insights into the workings of the basal ganglia (BG) by interfering with their function. In patients with Parkinson's disease (PD) treated with DBS of the subthalamic nucleus, we studied the effect of DBS on scanning eye movements.

Deep brain stimulation of the subthalamic nucleus reduces antiparkinsonian medication costs

This study reports a retrospective analysis of 16 patients to determine changes in medication costs associated with deep brain stimulation of the bilateral subthalamic nucleus (DBS B-STN). Antiparkinsonian medication (APMED) costs were evaluated pre- and post-operatively at 1 and 2 years, based on prescribed dosages. After treatment with DBS, patients experienced a 32% reduction in APMED costs after 1 year and a 39% reduction after 2 years. Hypothetical projections of total potential savings are presented, accounting for increasingly complex medication regimens and medication cost inflation. DBS patients may experience a significant long-term reduction in the cost of their pharmacologic treatment.     

丘脑底核脑深部电刺激治疗帕金森病临床SPECT随访

目的探讨丘脑底核脑深部电刺激(STN DBS)治疗帕金森病(PD)患者症状的改善及单光子放射计算机断层扫描(SPECT)的影像学变化。方法4例施行单侧STN DBS患者术前和给予电刺激后进行帕金森病综合评分(UPDRS)和SPECT测定。结果STN DBS术后临床症状明显改善,UPDRS运动评分缓解60%。3例改善良好的患者SPECT检查提示纹状体区域多巴胺转运体(DAT)含量较术前提高,另1例疗效欠佳的患者DAT含量降低,所有的患者多巴胺D2受体(D2R)检测与术前无明显差异。结论STN DBS可以明显改善PD患者的临床症状,SPECT检查显示刺激侧纹状体区DAT含量的升高提示STN DBS可能改善了多巴胺的代谢,而这种改善可能是STN DBS缓解PD症状的作用机制之一。     

戴立体定向仪磁共振复查在帕金森病丘脑底核脑深部刺激术中的意义

目的 ;总结帕金森病丘脑底核脑深部刺激(Subthalamic nucleus deep brain sti mulation,STN-DBS)术中戴立体定向仪磁共振复查对提高定位准确性、降低手术并发症的意义。方法 2003年~2009年共有124例帕金森病病人进行了丘脑底核DBS手术,共191侧,其中男性64例,女性60例,年龄45~80岁,平均65.5±8.7岁。术中未用微电极记录技术,但均戴立体定向仪磁共振复查,对电极触点目标位和实际位有明显误差的病人术中进行必要的调整。结果治疗效果与国内外文献报道类似,但无脑出血等手术并发症。结论术中戴立体定向仪复查磁共振既可以提高定位的准确性,又可以避免应用微电极记录可能导致的脑出血并发症、缩短手术时间。     

Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia

BackgroundSubthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters.ObjectiveHere we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia.MethodsSeven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient's pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery.ResultsPatients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments.ConclusionThis study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation.     

双侧丘脑底核脑深部电刺激对PD患者焦虑症状的短期影响

目的探讨双侧丘脑底核脑深部电刺激(STN-DBS)对帕金森病(PD)患者焦虑症状及生活质量的短期影响。方法对上海交通大学附属瑞金医院功能神经外科中心自2017年8月至2019年8月行双侧STN-DBS治疗的39例PD患者,分别于术前、术后1个月和末次随访时进行贝克焦虑自评量表(BAI)、贝克抑郁自评量表(BDI)评分,于术前和术后末次随访时进行帕金森病患者生活质量问卷-8项(PDQ-8)评分,采用统计学方法分析各节点间评分的差异,以及评分改善程度间的相关性;并进一步依据术前BAI评分将患者分为无焦虑组(n=18)、轻度焦虑组(n=10)、中度焦虑组(n=8)和重度焦虑组(n=3),以进行亚组分析。结果(1)39例患者术后1个月及末次随访时的BAI评分[14(8,20)分、9(3,14)分]均明显低于术前[16(9,27)分],术后末次随访时的BDI评分[8(6,16)分]及PDQ-8评分[3(2,6)分]均明显低于术前[15(8,21)分、9(6,13)分],差异均有统计学意义(P<0.05)。(2)相关性分析显示,术后末次随访时的BAI评分较术前的改善程度与BDI评分的改善程度呈正相关关系(rs=0.722,P=0.000),也与术前BDI评分及术前PDQ-8评分呈负相关关系(rs=-0.714,P=0.000;rs=-0.378,P=0.018)。(3)亚组分析显示,轻度焦虑组和中度焦虑组患者中,术后末次随访时的BAI评分均明显低于术前,差异均有统计学意义(P<0.05);轻度焦虑组、中度焦虑组与重度焦虑组患者的术后末次随访时的BAI评分较术前的改善程度均明显高于无焦虑组,差异均有统计学意义(P<0.05)。结论双侧STN-DBS能在短期内显著改善PD患者的焦虑症状,提高其生活质量,提示STN参与了PD患者焦虑症状的神经机制。     

Toward feedback controlled deep brain stimulation: Dynamics of glutamate release in the subthalamic nucleus in rats

Deep brain stimulation (DBS) is an effective symptomatic treatment in Parkinson's disease. High frequency stimulation (HFS) of the subthalamic nucleus elicits neurotransmitter release in multiple nuclei. Therefore, we tested the hypothesis that neurotransmitter release during HFS may be used to provide feedback control of the intensity and pattern of HFS. We studied the dynamic relationship between extracellular glutamate levels and HFS in and around the STN in anesthetized rats. We used a pseudorandom binary sequence (PRBS) of stimulation in the STN, the independent forcing function, while measuring extracellular glutamate in the same nucleus, the dependent variable. The PRBS consisted of 90 s periods during which stimulation (100 μA, 150 Hz, 10% duty cycle) was either off or on. The stimulation and extracellular glutamate levels were fitted using an autoregressive exogenous model (ARX) to determine the transfer function between HFS and the extracellular glutamate concentration in the STN. The ARX model fit the dynamics of extracellular glutamate levels well (correlation coefficients ranged from 0.74 to 0.99; n = 11). The transfer function accurately predicted extracellular glutamate levels in the STN even when the pattern of HFS was modified. We used the transfer function to develop a feedback controlled stimulation algorithm. Feedback controlled HFS maintained extracellular glutamate concentrations at any predefined level, but only intermittent HFS was required. We conclude that the transfer function between HFS and neurotransmitter levels in the brain can be used to design DBS protocols that generate specific temporal patterns of glutamate release in the STN.     

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease

Background: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. Objective: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. Methods: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. Results: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30 % at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. Conclusion: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes. Received: 4 May 2000 / Received in revised form: 31 January 2001 / Accepted: 6 February 2001     

脑深部刺激电极埋置术治疗帕金森病疗效研究

目的 探讨脑深部刺激电极埋置术治疗帕金森病的疗效及其作用机制。方法 对32例帕金森病患者应用微电极导向立体定向技术,于丘脑底核埋置体外可控性脑深部刺激电极,对其疗效和预后进行随访。结果患者术后僵硬、震颤和运动迟缓等症状明显缓解,术前、术后统一帕金森病评分量表(unified Parkinson's disease ratingscale,UPDRS)运动评分和日常生活能力(activities of daily living,ADL)评分有显著性差异(P<0.01),部分患者由药物引起的开-关现象也有明显缓解;协同服用的多巴胺类药物的用量也有不同程度的减少。所有患者术中及术后均无严重的并发症,术后随访疗效肯定。结论 丘脑底核放置深部脑刺激电极,能明显改善帕金森病患者的临床症状,提高手术的安全性,并发症少。