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.

脑深部电刺激猴帕金森病模型的建立

目的通过猴偏侧帕金森病（Parkinson disease,PD）模型丘脑底核（subthalamic nucleus,STN）脑深部电刺激（deep brain stimulation,DBS）系统的植入,对脑深部电刺激动物模型的制备进行了探讨.方法2只猴偏侧PD模型,按照猴脑立体定向图谱,在右侧STN植入脑深部刺激电极,并同期皮下植入脉冲发生器.术后行头颅X线平片和MRI检查,给予慢性高频电刺激,观察运动症状改善.结果2只偏侧猴PD模型成功的同期植入DBS系统,术后的症状观察和阿朴吗啡（apomorphine,APO）诱发旋转实验,证实STN慢性高频电刺激有效地缓解了猴PD样症状.结论通过立体定向技术同期将DBS系统植入动物体内,可以有效的建立DBS动物模型,为DBS在神经疾病的应用研究提供了良好的实验模型.     

Image-based biophysical modeling predicts cortical potentials evoked with subthalamic deep brain stimulation

BackgroundSubthalamic deep brain stimulation (DBS) is an effective surgical treatment for Parkinson’s disease and continues to advance technologically with an enormous parameter space. As such, in-silico DBS modeling systems have become common tools for research and development, but their underlying methods have yet to be standardized and validated.ObjectiveEvaluate the accuracy of patient-specific estimates of neural pathway activations in the subthalamic region against intracranial, cortical evoked potential (EP) recordings.MethodsPathway activations were modeled in eleven patients using the latest advances in connectomic modeling of subthalamic DBS, focusing on the hyperdirect pathway (HDP) and corticospinal/bulbar tract (CSBT) for their relevance in human research studies. Correlations between pathway activations and respective EP amplitudes were quantified.ResultsGood model performance required accurate lead localization and image fusions, as well as appropriate selection of fiber diameter in the biophysical model. While optimal model parameters varied across patients, good performance could be achieved using a global set of parameters that explained 60% and 73% of electrophysiologic activations of CSBT and HDP, respectively. Moreover, restricted models fit to only EP amplitudes of eight standard (monopolar and bipolar) electrode configurations were able to extrapolate variation in EP amplitudes across other directional electrode configurations and stimulation parameters, with no significant reduction in model performance across the cohort.ConclusionsOur findings demonstrate that connectomic models of DBS with sufficient anatomical and electrical details can predict recruitment dynamics of white matter. These results will help to define connectomic modeling standards for preoperative surgical targeting and postoperative patient programming applications.     

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。     

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。     

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。     

Neuronal oscillations predict deep brain stimulation outcome in Parkinson's disease

BackgroundNeuronal oscillations are linked to symptoms of Parkinson's disease. This relation can be exploited for optimizing deep brain stimulation (DBS), e.g. by informing a device or human about the optimal location, time and intensity of stimulation. Whether oscillations predict individual DBS outcome is not clear so far.ObjectiveTo predict motor symptom improvement from subthalamic power and subthalamo-cortical coherence.MethodsWe applied machine learning techniques to simultaneously recorded magnetoencephalography and local field potential data from 36 patients with Parkinson's disease. Gradient-boosted tree learning was applied in combination with feature importance analysis to generate and understand out-of-sample predictions.ResultsA few features sufficed for making accurate predictions. A model operating on five coherence features, for example, achieved correlations of r > 0.8 between actual and predicted outcomes. Coherence comprised more information in less features than subthalamic power, although in general their information content was comparable. Both signals predicted akinesia/rigidity reduction best. The most important local feature was subthalamic high-beta power (20–35 Hz). The most important connectivity features were subthalamo-parietal coherence in the very high frequency band (>200 Hz) and subthalamo-parietal coherence in low-gamma band (36–60 Hz). Successful prediction was not due to the model inferring distance to target or symptom severity from neuronal oscillations.ConclusionThis study demonstrates for the first time that neuronal oscillations are predictive of DBS outcome. Coherence between subthalamic and parietal oscillations are particularly informative. These results highlight the clinical relevance of inter-areal synchrony in basal ganglia-cortex loops and might facilitate further improvements of DBS in the future.     

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.     

丘脑底核脑深部电刺激术治疗帕金森病早期语音声学研究

目的 探讨丘脑底核（STN）脑深部电刺激术（DBS）治疗帕金森病（PD）患者构音障碍的早期疗效.方法 回顾性纳入南京医科大学附属脑科医院神经外科2017年5月至11月行STN-DBS治疗的10例PD患者（PD组）,同时纳入健康志愿者10名（健康对照组）.对未服药状态下的10例PD患者,分别于术后1个月未开机、开机后1个月和开机后3个月,在相对安静的房间录制语音,应用Praat软件分析语音信号并提取3个基频参数,分别为基频均值、基频范围和基频标准差.同时对健康对照组受试者进行语音信号采集和分析.结果 PD患者术后1个月未开机时,语音的基频范围[PD组为（15.5 ±4.8） St、健康对照组为（22.5 ±5.6） St,t=-2.962,P=0.008]和基频标准差[PD组为（2.4±0.7）St、健康对照组为（3.7±0.8）St,t=-4.017,P=0.001]均显著小于健康对照组.PD患者开机后1个月时,语音的3个基频参数与术后1个月未开机时的差异均无统计学意义（均P＞0.05）;开机后3个月时,语音的基频范围[开机后3个月为（19.2 ±3.8）St、术后1个月未开机为（15.5 ±4.8）St,P=0.017]和基频标准差[开机后3个月为（3.2±0.8）St、术后1个月未开机为（2.4±0.7）St,P=0.001]均显著高于术后1个月未开机时,且与健康对照组间3个基频参数的差异均无统计学意义（均P＞0.05）.结论 STN-DBS治疗早期能改善PD患者语音语调单一的特征,缓解患者喉部肌肉及声带僵硬情况.     

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。     

丘脑底核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

目的评价丘脑底核脑深部电刺激术联合药物治疗帕金森病的有效性和安全性。方法以subthalamic nucleus、deep brain stimulation、DBS、STN、Parkinson disease、random等英文检索词,计算机检索1980年1月1日-2016年10月1日美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane图书馆等数据库收录的关于丘脑底核脑深部电刺激术联合药物治疗帕金森病的随机对照临床试验,采用Jadad量表、Cochrane系统评价手册和Rev Man 5.2统计软件进行文献质量评价和Meta分析。结果共获得3245篇文献,经剔除重复和不符合纳入标准者,最终纳入6项高质量(Jadad评分≥4分)临床试验共958例帕金森病患者。Meta分析显示:与单纯药物治疗相比,丘脑底核脑深部电刺激术联合药物治疗可以显著降低帕金森病患者服药(SMD=-0.570,95%CI:-0.710~-0.430;P=0.000)和未服药(SMD=-1.170,95%CI:-1.500~-0.850;P=0.000)状态下统一帕金森病评价量表第三部分(UPDRSⅢ)评分,以及UPDRSⅠ评分(SMD=-0.150,95%CI:-0.290~-0.010;P=0.030)和39项帕金森病调查表评分(SMD=-0.510,95%CI:-0.660~-0.370;P=0.000);但增加严重不良事件(RD=0.140,95%CI:0.090~0.190;P=0.000)和构音障碍不良事件(RD=0.070,95%CI:0.010~0.120;P=0.020)发生率,而减少运动障碍不良事件发生率(RR=0.450,95%CI:0.330~0.620;P=0.000)。结论丘脑底核脑深部电刺激术联合药物治疗能够显著改善帕金森病患者运动功能、精神状态和生活质量,但术后发生严重不良事件和构音障碍不良事件的风险增加,应引起临床医师的重视。     

偏侧猴PD模型STN慢性高频电刺激对脑内多巴胺系统的影响

目的探讨丘脑底核(STN)慢性高频电刺激对猴偏侧帕金森病(PD)模型脑内多巴胺(DA)系统的影响。方法采用单侧颈内动脉注入1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)建立猴偏侧PD模型2只,体内植入脑深部电刺激(DBS)系统,行右侧STN慢性高频电刺激。在电刺激前后不同时间点采用微透析技术检测纹状体区细胞外液的多巴胺(DA)及其代谢产物高香草酸(HVA)含量,腰穿取脑脊液标本测量脑脊液中DA、HVA含量,单光子放射计算机断层扫描(SPECT)检测脑内纹状体区巴胺转运体(DAT)及多巴胺D2受体(D2R)的变化。结果猴偏侧PD模型在给予单侧STN慢性高频电刺激后纹状体区DA、HVA明显增高。SPECT显示在有效刺激后纹状体区DAT特异性摄取率增高,D2R特异性摄取率下降。脑脊液中多巴胺及其代谢产物的含量与术前相比无明显差异。结论通过微透析检测提示在给予STN有效慢性高频电刺激后提高了纹状体区DA及其代谢产物的升高,DAT特异性摄取率增高,D2R特异性摄取率下降提示纹状体区的代谢活性有明显升高,这可能是STN-DBS治疗帕金森病的重要机制之一。     

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。     

丘脑底核电刺激治疗继发性肌张力障碍

目的 探讨丘脑底核（STN）的脑深部电剌激（DBS）治疗继发性肌张力障碍的可行性、适应证和并发症。方法 5例行双侧STN—DBS，1例行单侧STN—DBS。结果 术中利用微电极记录的电信号获得STN的准确靶点定位，电刺激后患者肌张力有不同程度下降，但扭转改善不明显。随访半年至3年，6例患者中，药物引起的迟发性肌张力障碍及外伤性肌张力障碍的患者疗效理想，BFMDRS评分改善均在90％以上，且随着随访时间的延长，效果持续不断改善；其余4例患者疗效不佳，4例均肌张力略有改善，其中1例扭转略改善，1例语言及步态略有改善。手术后患者均无明显合并症，但1例术后16个月发现左侧电极折断，后取出。结论 DBS治疗迟发性和外伤性继发性肌张力障碍效果理想，而对于缺氧或脑基底节区弥漫性损害的继发性肌张力障碍效果不佳；STN可以成为治疗本病的理想靶点；术中应根据电生理记录结果和肌张力的轻度改善作为靶点定位的指标；手术无明显合并症。     

Evoked potentials reveal neural circuits engaged by human deep brain stimulation

BackgroundDeep brain stimulation (DBS) is an effective therapy for reducing the motor symptoms of Parkinson’s disease, but the mechanisms of action of DBS and neural correlates of symptoms remain unknown.ObjectiveTo use the neural response to DBS to reveal connectivity of neural circuits and interactions between groups of neurons as potential mechanisms for DBS.MethodsWe recorded activity evoked by DBS of the subthalamic nucleus (STN) in humans with Parkinson’s disease. In follow up experiments we also simultaneously recorded activity in the contralateral STN or the ipsilateral globus pallidus from both internal (GPi) and external (GPe) segments.ResultsDBS local evoked potentials (DLEPs) were stereotyped across subjects, and a biophysical model of reciprocal connections between the STN and the GPe recreated DLEPs. Simultaneous STN and GP recordings during STN DBS demonstrate that DBS evoked potentials were present throughout the basal ganglia and confirmed that DLEPs arose from the reciprocal connections between the STN and GPe. The shape and amplitude of the DLEPs were dependent on the frequency and duration of DBS and were correlated with resting beta band oscillations. In the frequency domain, DLEPs appeared as a 350 Hz high frequency oscillation (HFO) independent of the frequency of DBS.ConclusionsDBS evoked potentials suggest that the intrinsic dynamics of the STN and GP are highly interlinked and may provide a promising new biomarker for adaptive DBS.     

Effect of bilateral subthalamic deep brain stimulation on diphasic dyskinesia

OBJECTIVES: The goal of this study was to assess the effect of bilateral subthalamic deep brain stimulation (STN DBS) on levodopa-induced diphasic dyskinesia in patients with Parkinson disease (PD). PATIENTS AND METHODS: Six PD patients with diphasic dyskinesia were included in this study. Prior to surgery, the duration and severity of dyskinesia were determined in each patient, along with the Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Bilateral STN electrode implantation was performed during a single operation. RESULTS: The median duration of the follow-up period was 21.5 months (range 14-24 months). STN DBS had a beneficial effect on diphasic dyskinesia in all patients. At the last follow-up, 3 patients had no dyskinesia and 1 had only a small amount of peak-dose dyskinesia. One patient showed a reduction in the duration of diphasic dyskinesia, despite a lack of reduction in the total duration of dyskinesia. In the last patient, although the total duration of dyskinesia increased, the pattern of dyskinesia changed from severe painful disabling dyskinesia to the less severe peak-dose type of dyskinesia. There were no intraoperative or postoperative surgical complications. CONCLUSIONS: Bilateral STN DBS is good at reducing diphasic dyskinesia, and it can be a good therapeutic option for patients with diphasic dyskinesia.