丘脑底核电刺激对大鼠黑质网状部及苍白球细胞外神经递质的影响

目的 通过电刺激正常及癫痫大鼠丘脑底核(STN),研究黑质网状部(SNr)及苍白球(GP)细胞外液中谷氨酸(Glu)、γ-氨基丁酸(GABA)的变化,探讨电刺激治疗癫痫的机制.方法 正常大鼠和癫痫大鼠各加只,将刺激电极植入一侧STN,分别用130 Hz和260 Hz进行刺激,同时在同侧的SNr和GP收集细胞外液,用高压液相色谱法检测其Glu和GABA的含量.结果 癫痫大鼠SNr的GABA基础值明显高于正常大鼠.电刺激使两组SNr的GABA明显升高.130 Hz和260 Hz刺激明显增高两组GP和SNr的Glu含量,但130 Hz的更显著.结论 SNr细胞外GABA升高在STN电刺激治疗中起重要作用.电刺激增加了GP细胞的活动,STN电刺激治疗癫痫机制不能单纯解释为"功能的毁损".     

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。     

高频电刺激丘脑底核对偏侧帕金森病猴模型苍白球内侧部神经元放电的影响

目的 探讨深部电刺激丘脑底核(STN)治疗帕金森病(PD)的可能作用机制. 方法 通过在模型猴单侧大脑注入1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备偏侧PD模型,随后在立体定向技术下参照猴脑立体定向图谱,将记录的玻璃微电极和刺激电极分别插入苍白球内侧部(Gpi)和STN内,通过单细胞胞外记录法记录并分析神经元刺激前和刺激时的放电改变情况. 结果 PD猴未注药侧GPi神经元自发放电较规则,放电频率为(44.38±13.66)锋电位/s;注药侧GPi神经元放电频率为(50.57±15.53)锋电位/s,较未注药侧稍快但差异无统计学意义(P＞0.05).刺激过程中GPi神经元存在4种反应:部分抑制、完全抑制、兴奋和无变化,多数神经元表现为受到抑制,注药侧更为明显,平均抑制率为56.29％±29.66％,高于未注药侧的36.03％±35.25％,差异有统计学意义(P＜0.05). 结论 深部电刺激术治疗PD的作用机制为通过高频刺激对STN神经元异常兴奋性的调控,改变相关的联系核团如GPi或黑质网状部(SNr)的异常功能状态,最终使基底节运动环路正常控制功能重新恢复,进而改善PD症状.     

双侧丘脑底核电刺激对帕金森病患者抑郁状况的影响

目的 探讨双侧丘脑底核脑深部电刺激对帕金森病患者抑郁状况的影响.方法 设置STN-DBS组及药物治疗对照组,配对人组,有效病例27对.两组患者均只服用左旋多巴制剂且剂量前后无显著变化,均未服用抗抑郁药物.前后共6次分别评估其抑郁及运动状况.结果 与术前及药物治疗组相比,STN-DBS组术后运动功能改善,抑郁状况短期内(3～6个月)改善;STN-DBS组术后运动评分与抑郁评分短期内(5周～6个月)相关,双侧电压均值与其抑郁评分均相关;STN-DBS组术后电压均值对抑郁评分的标准回归方程及回归系数均显著,运动评分对抑郁评分的标准回归方程及同归系数在短期内(5周～3个月)显著.结论 STN-DBS对PD患者运动障碍症状的改善在短期内可改善其抑郁状况,但长期效应不明显.在STN-DBS治疗电压值范围内,双侧电压均值越高,PD患者的抑郁状况越严重.     

丘脑底核电刺激治疗帕金森病的临床应用

目的探讨丘脑底核(STN)脑深部电刺激术(DBS)治疗帕金森病(PD)的手术方法和脉冲发生器的程控调节。方法行STN DBS治疗PD61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UPDRS运动评分评价刺激效果。结果术后随访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5.2%;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STN DBS能有效控制PD症状,手术并发症少,术后可调节参数,已成为治疗PD的重要手术方法。     

丘脑底核电刺激治疗帕金森病的临床应用

目的探讨脑深部电刺激术治疗帕金森病的手术方法和脉冲发生器程控调节。方法自2000年1月至2005年10月用脑深部电刺激丘脑底核治疗帕金森病126例,其中单侧46例,双侧80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82例帕金森病患者术后随访6～60个月,平均11.8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25.7%,未发现任何并发症。结论脑深部电刺激丘脑底核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。     

高频脑深部电刺激对帕金森病模型大鼠丘脑底核神经元放电的影响

目的观察高频电刺激丘脑底核对帕金森病大鼠丘脑底核神经元放电的影响。方法应用6-羟基多巴胺制备偏侧帕金森病大鼠模型,在其丘脑底核区插入刺激电极进行高频电刺激,采用细胞外单位记录的方法记录刺激前和刺激过程中丘脑底核神经元的放电。结果电刺激前对照组和帕金森组丘脑底核神经元放电频率无显著差异,而放电形式不同,对照组大部分丘脑底核神经元表现为规则或不规则放电,帕金森组丘脑底核神经元以爆发放电为主;高频电刺激两组大鼠丘脑底核神经元后,两组丘脑底核神经元放电都主要表现为部分抑制或完全抑制。结论爆发式放电增多可能是帕金森发病潜在的电生理基础。高频电刺激丘脑底核可抑制丘脑底核的异常放电活动,这可能是脑深部电刺激治疗帕金森病的可能机制之一。     

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。     

丘脑底核电刺激对猴偏侧帕金森病纹状体神经递质的影响

目的 探讨应用微透析技术在慢性STN—DBS对纹状体细胞外液多巴胺及代谢产物的影响。方法 选择已经成功安装脑深部刺激电极的偏侧PD猕猴模型2只，分别在打开脉冲发生器前、后的不同时间点取样（开机后8h、1周、1个月、2个月）。应用高效液相电化学方法检测开机前后的尾状核和壳核细胞外液的多巴胺（DA）及其代谢产物含量。结果 电极侧壳核和尾状核的DA在开机后8h、1周、1个月、2个月相应地分别较各自开机前的DA含量增高了39％、91％、111％、114％和31％、91％、106％、102％（P〈0．05）。电极侧壳核和尾状核HVA／DA在开机后8h分别较各自开机前增高了186％和91％（P〈0．05），而开机后1周、1个月、2个月HVA／DA较开机前无明显变化（P〉0．05）。电极侧的多巴胺周转率在开机后的各时间点均显著低于非电极侧（P〈0．01）。结论 STN—DBS可有效的改善猴偏侧PD模型的症状，应用微透析取样技术结合高效液相色谱测，定法发现在给予有效电刺激后可增加刺激侧纹状体细胞外液的多巴胺及其代谢产物含量。为STN—DBS治疗帕金森病提供理论依据。     

Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation

BackgroundDeep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized.ObjectiveThe objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr).MethodsTwo microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD). Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode.ResultsInhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .013). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation but not in SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003).InterpretationPersistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.     

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。     

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.     

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。     

The effect of electrical stimulation of the subthalamic nucleus on seizures is frequency dependent

PURPOSE: Animal studies and anecdotal human case reports have indicated that the subthalamic nucleus (STN) may be a site of anticonvulsant action. METHODS: We tested the hypothesis that continuous electrical stimulation of the STN inhibits seizures acutely. We determined the effects of three stimulation frequencies, 130 Hz, 260 Hz, and 800 Hz, on generalized clonic and tonic-clonic flurothyl seizures. Adult male rats were implanted with concentric bipolar stimulating electrodes in the STN bilaterally. After recovery, rats underwent flurothyl seizures to compare the effects of each stimulation frequency on seizure threshold. Rats were tested 4 times, twice in the stimulated condition, and twice in the unstimulated condition. The order of trials was random, except that stimulation trials alternated with control trials. Flurothyl seizure thresholds under each stimulation condition were compared with control values from the same animal. RESULTS: Bilateral stimulation of the STN at 130 Hz produced a significant increase in the seizure threshold for clonic flurothyl seizures, whereas stimulation at 260 Hz did not appear to have any effect on seizures. STN stimulation at 800 Hz significantly lowered seizure threshold for tonic-clonic seizures. CONCLUSIONS: We conclude that electrical stimulation of the STN can be anticonvulsant, but the effects appear to depend on the stimulation frequency and the type of seizure.     

丘脑底核脑深部电极刺激术治疗Meige综合征

目的 观察双侧丘脑底核-脑深部电刺激术( STN - DBS)治疗3例Meige综合征患者的术后长期疗效.方法 3例Meige综合征患者接受双侧脑深部电极刺激术,术中微电极记录确定准确靶点定位,术后进行参数程控.术后1、3、6、12、24个月及最后一次复诊时进行随访,采用BFMDRS评价治疗效果,观察参数变化.结果 3例患者术后症状均得到明显改善,术后1个月时3例患者BFMDRS总评分、运动评分及功能障碍评分均有下降,术后3-6个月3例患者BFMDRS总评分、运动评分及功能障碍评分改善最明显,改善率达到90％以上,6个月后疗效稳定.结论 STN- DBS治疗3例Meige综合征患者效果理想,可以成为治疗Meige综合征的一种选择.     

Subthalamic nucleus lesion regularizes firing patterns in globus pallidus and substantia nigra pars reticulata neurons in rats

Subthalamic nucleus lesion altered the statistical properties of the firing patterns of globus pallidus and substantia nigra pars reticulata neurons recorded in urethane anesthetized rats by increasing the proportion of cells in both structures that fired with a very highly regular pattern (from 25%to 50%). In all cases, the most regularly firing neurons fired at a higher mean rate than did more slowly firing neurons. In contrast, globus pallidus lesion shifted the pattern of substantia nigra neurons towards more irregular firing and induced a bursty pattern in two neurons.     

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.     

丘脑底核毁损术对帕金森病大鼠脚内核和黑质网状部的影响

目的 :观察毁损丘脑底核 (STN)对帕金森病 (PD)大鼠脚内核 (EP)及黑质网状部 (SNr)γ -氨基丁酸(GABA)能系统的影响。方法 :将 6 0只Wistar大鼠随机分为 6组 ,每组 10只。对照组采用 6 -OHDA立体定向注入大鼠右侧前脑内侧束 (MFB)和中脑被盖腹侧区 (VTA) ,制成偏侧PD模型。实验组分为第Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ组 ,分别于 6 -OHDA注射前 7d、注射后 1h、2h、3d、7d5个不同时间点 ,局部注射海人藻酸 (KA)破坏STN。 4周后处死大鼠 ,采用免疫组化染色方法 ,定量测量各组大鼠SNr区和EP区的GABA免疫反应阳性区面积和免疫反应强度。实验数据采用方差分析和t检验统计学处理。结果 :GABA免疫组化显示Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ实验组的注射侧EP面积分别为正常侧的 72 9%、83 7%、79 7%、88 1%、90 1%。对照组注射侧为正常侧面积的 139 1% (P <0 0 5、0 0 1)。各实验组注射侧EP的GABA免疫反应强度 (积分光密度 )均较正常侧减少 ,对照组注射侧较正常侧积分光密度增加 (P <0 0 5 ,P <0 0 1)。Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ实验组的注射侧SNr面积分别为正常侧的 90 6 %、86 9%、87 3%、80 5 %、80 4%。对照组注射侧面积为正常侧的 10 8 1% (P <0 0 5、0 0 1) ,各实验组注射侧SNr的GABA免疫反应强度均较正常侧减少 ,对照组注射