帕金森病人GPi、Vim及STN的电生理特征研究

目的：探讨帕金森病（PD）患者的苍白球内侧部（GPi)，丘脑腹外侧中间核（Vim)及丘脑底核（STN）的电生理特性，方法：用立体定向毁损术治疗54例PD手术中，应用美国FHC公司生产的微电极记录系统，记录GPi,Vim和STN不同部位的电活动。结果PD病人的丘脑内和基底节不同结构部位怕电话动频率，幅度，放电 背景噪声均有显著差异，Vim中可记录到与震颤同步的高频放电，GPi，STN可记录到一致稳定的放电活动。结论：利用GPi,Vim和STN不同部位的电活动特性，可以为立体定向治疗PD手术中的精确定位，提高疗效，降低并发症提供参考依据。     

运动障碍病的神经电生理基础

目的探讨运动障碍病的细胞学病理生理基础,提高手术治疗的有效率和安全性.方法回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术.包括帕金森性病(PD)、原发性震颤(ET)、扭转痉挛和痉挛性斜颈等.手术的靶点包括苍白球腹后部(PVP),丘脑底核(STN)和丘脑腹外侧核(VL).术中应用微电极和肌电(EMG)记录技术,采集GPi,STN和VL神经元和肢体肌电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系,并进行相关性检验.结果PD性震颤在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床.原发性震颤在丘脑腹中间核(Vim)获取的放电频率,也有临床指导意义.扭转痉挛和痉挛性斜颈扭转痉挛和痉挛性斜颈患者的神经元簇放电无明显规则可寻.结论识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义.     

运用障碍病的神经电生理基础

目的：探讨运动障碍病的细胞学病理生理基础。提高手术治疗的有效率和安全性。方法：回顾过去3年的工作,1200例运动障碍病患者接受了微电极导向的立体定向神经外科手术,包括帕金森性病（PD）、原发性震颤（ET）、扭转痉挛和痉挛性斜颈等。手术的靶点包括苍白球腹后部（PVP）,丘脑底核（STN）和丘脑腹外侧核（VL）。术中应用微电极和肌电（EMG）记录技术,采集GPi,STN和VL神经元和肢体肌电活动,术后应用分析软件甄别单细胞及其电活动特点,分析其与临床症状的关系。并进行相关性检验。结果：PD性震颤：在GPi,STN、VL获得相关神经元簇放电频率是不一致,可指导临床,原发性震颤;在丘脑腹中间核（Vim)获取的放电频率,也有临床指导意义。扭转痉挛和痉挛性伤痛颈：扭转痉挛和痉挛性伤痛颈患者的神经元簇放电无明显规则可寻,结论：识别和确定GPi、STN和VL细胞电活动特点及其分布,对于指导立体定向手术的功能定位,提高运动障碍病手术治疗的疗效和降低手术并发症具有重要的意义。     

帕金森性震颤和与震颤相关的电活动

目的对PD患者行STN和GPi切开术术中应用微电极记录技术采集神经元的电活动,术后分析其与震颤的关系和特点,为手术选择最佳的毁损位置提供客观的电生理指标.方法40个PD患者,其中21例PD患者接受了立体定向GPi切开术和19例PD患者接受立体定向STN切开术.病人要求清醒合作且处于“关”状态.术中应用微电极和肌电(EMG)记录技术,采集GPi和STN神经元和手术对侧肢体震颤的生物电活动.术后应用分析软件甄别单细胞及其电活动特点,分析其与震颤症状的关系,并进行相关性检验.结果在21个针道共记录到184 GPi个神经元单位,其簇状放电的节律与肢体震颤的节律高度一致(4～6Hz),R2=0.78(P＜0.01).在20个针道共记录到161个STN神经元单位,其放电频率在42～88Hz之间.STN的簇状放电的节律与肢体震颤的节律一致(4～6Hz),R2=0.64(P＜0.01).毁损这些震颤细胞导致震颤症状的消失.结论震颤型PD患者的GPi和STN存在与肢体震颤节律一致的震颤细胞,且震颤和震颤细胞有着内在的关系.对于指导手术毁损的部位和范围提供了可靠的依据.     

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.     

立体定向射频颅内靶点毁损治疗帕金森病

目的总结立体定向射频毁损丘脑腹中间核(Vim)和苍白球内侧部(GPi)治疗帕金森病的经验。方法对28例帕金森病病人行MRI、CT定位,微电极引导,配合术中测量阻抗和电刺激确定Vim、GPi靶点,以80℃、90s毁损。结果术后89.3%的病人即刻症状消除,10.7%症状减轻。手术后帕金森病统一量表(UPDRS)评分显著性下降(P <0.01)。随访3～48个月,复发率10.7%。结论立体定向射频毁损Vim、GPi治疗帕金森病有效率高;准确定位是手术成功的关键因素。     

帕金森病患者丘脑腹外侧核团神经元振荡活动特点

目的 探讨帕金森病(PD)患者丘脑腹外侧核团(Vop/Vim)神经元振荡活动与PD症状的关系.方法 23例PD患者在接受立体定向丘脑毁损术时应用微电极和肌电记录技术采集细胞和肢体电活动.单细胞和峰间隔分析鉴别细胞放电频率和模式;功率谱分析神经元振荡活动与症状的关系.PD综合评分量表(UPDRS)进行疗效评估.结果 114个振荡活动神经元中78％伴有震颤节律,并与肢体震颤相关;22％伴有β节律.发现震颤节律振荡活动神经元主要分布在Vim,β节律振荡活动神经元主要分布在Vop (P ＜0.05).结论 Vim是改善震颤的最佳靶点.β节律振荡活动神经元与僵直、运动不相关,提示Vop可以改善PD僵直和迟缓.     

深部电刺激脑内靶点在帕金森病中的应用

本综述脑深部电剌激(DBS)治疗帕金森病常用靶点的临床应用，目前常用靶点包括丘脑腹中间核(Vim)，苍白球内侧(GHi)和丘脑底核(STN)，根据病人症状可选择不同靶点。Vim DBS对单纯震颤的帕金森病有显疗效，GPi DBS和STN DBS适用于既有震颤和僵硬的帕金森病病人，又适用于运动迟缓和异动症病人，术后可逐渐减少服用多巴胺的剂量。目前认为STN DBS缓解震颤和僵硬疗效要优于GPi和Vim DBS，研究表明STN DBS具有一定的神经保护作用，它抑制了STN的过度兴奋，使谷氨酸的释放减少，降低对投射区域的神经毒性作用，减少了多巴胺能神经元的变性，延缓帕金森病的进展，可作为DBS治疗帕金森病的首选靶点。     

不同靶点脑深部电刺激治疗帕金森病患者的疗效 特点

帕金森病（PD）严重影响着中老年患者的生活质量,目前PD患者行脑深部电刺激术（DBS） 的常用靶点包括丘脑腹中间核（Vim）、丘脑底核（STN）、苍白球内侧核（GPi）和桥脑脚核（PPN）,由于Vim对 PD患者症状的改善局限于震颤,目前已被STN和GPi靶点所替代,这两个靶点解决了PD患者的震颤、僵 硬、运动迟缓以及异动症的症状,近十几年来,PPN靶点的应用解决了PD患者步态失调和姿势不稳等中 轴症状,现根据不同靶点DBS后PD患者症状改善情况进行综述。     

内苍白球震颤细胞的电活动与帕金森性震颤

目的 探讨帕金森病（PD）特征性震颤与内苍白球（GPi）神经元电活动的关系，指导手术靶点的精确定位。方法 10例PD患者接受了立体定向苍白球腹后部毁损术，术中应用微电极和肌电（EMG）记录技术，采集GPi神经元和肢体震颤的生物电活动。术后应用分析软件甄别单细胞及其电活动特点，分析其与震颤症状的关系，并进行相关性检验。结果 在GPi共记录到了112个神经元，有57个（51％）震颤细胞，且主要分布在视束上方4－6mm，其簇状放电的节律与肢体震颤的节律高度一致（4－6Hz），R^2＝0.71（P＜0.01）。毁损震颤细胞导致震颤症状的消失。结论 震颤型PD患者的GPi存在电活动与肢体震颤节律一致的震颤细胞，该细胞的发现和定位，对于指导手术毁损的部位和范围具有重要意义。     

脑深部电刺激对帕金森病二次手术的临床应用价值

目的探讨帕金森病(Parkinson'sdisease,PD)毁损术后再行脑深部电刺激术(deepbrainstimulation,DBS)的可行性、靶点选择、术中电生理学特点和治疗结果。方法应用MRI和微电极记录技术进行靶点定位,对13例毁损术后的PD患者行DBS手术,其中7例曾行单侧苍白球毁损术(posteroventralpallidotomy,PVP),5例曾行单侧丘脑毁损术,1例曾行双侧丘脑及左侧苍白球毁损术。DBS的靶点包括单侧丘脑底核(subthalamicnucleus,STN)6例,单侧丘脑腹中间核(ventralintermediatnucleus,Vim)1例,双侧STN4例,一侧STN及对侧苍白球(globuspallidusinternus,Gpi)2例。结果DBS对毁损术后的PD患者症状有不同程度的改善,其中单侧毁损术后行双侧DBS效果最明显。术后3个月的UPDRS运动及ADL评分较术前明显减少(P<0.05或0.01),美多巴的用量明显减少(P<0.05),无新的手术合并症。结论曾行毁损术的PD患者如面临二次手术,可以选择DBS手术,以双侧STN的DBS效果最好,并可减少药物用量,不加重原有的术后并发症。     

Deep brain stimulation in the management of Parkinson's disease

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease and other movement disorders. This surgical technique is applied to three brain targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internus (Gpi) and the subthalamic nucleus (STN). Vim DBS improves contralateral parkinsonian tremor. STN and GPi DBS improve contralateral bradykinesia, rigidity, parkinsonian tremor and also levodopa-induced dyskinesia. There is little comparative data between bilateral STN and bilateral GPi procedures but the improvement with bilateral STN DBS seems more pronounced than with bilateral GPi DBS. Moreover, only STN BDS allows a significant decrease of antiparkinsonian medication. The other advantage of STN over GPi DBS is the lower consumption of current. The DBS procedure contrary to ablative surgery has the unique advantage of reversibility and adjustability over time. Patients with no behavioral, mood and cognitive impairments benefit the most from bilateral STN DBS. The stimulation-induced adverse effects related to DBS are reversible and adjustable. More specific adverse effects related do hardware are: disconnection, lead breaking, erosion or infection. The disadvantage of DBS is a relatively high cost. The setting of stimulation parameters to achieve the best clinical result may be very time-consuming. Most authors agree that DBS is a safer and more favorable procedure than ablative surgery.     

脑深部电刺激治疗帕金森病和特发性震颤的近期和远期疗效

自1987年以后,脑深部电刺激(deep brain stimulation,DBS)成为治疗难治性帕金森病和特发性震颤的主要外科手段。刺激的靶点最先为丘脑腹侧中间核(nucleus ventero-intermedius,Vim)。由于Vim DBS只能缓解震颤,而对于帕金森病的其他核心症状以及多巴长期应用后的不良反应,如运动波动和异动症疗效不显著,1990年后治疗PD的靶点转移到丘脑底核(subthalamic nucleus,STN)和苍白球内侧部(interal globus pallidus,GPi),上述问题在这两个靶点得到显著改善。Vim DBS仍然为治疗特发性震颤的位点。本文就这3个靶点的持续电刺激在治疗帕金森病和特发性震颤的近期和远期疗效等进行评述。     

神经导航下猴苍白球区电生理特性的实验研究

目的探讨猴苍白球区（Gp）电生理的特性.方法运用Brainlab神经导航系统通过微电极技术记录猴Gp不同部位的电活动.结果微电极可在Gp的不同部位记录到不同特征的电活动.苍白球外侧部（Gpe）背侧可测到低频的电活动,Gpe腹侧可测到高频的电活动;苍白球内侧部（Gpi）可测到高频、高幅的电活动.结论猴Gp不同部位电活动的频率、幅度、放电方式均有统计学意义,利用Gp不同部位的电生理特性可以帮助立体定向手术中的精确定位.     

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.     

丘脑底核与苍白球内侧部电刺激术治疗帕金森病疗效的Meta分析

目的 系统评价脑深部电刺激术（DBS）作用丘脑底核（STN）与苍白球内侧部（GPi）治疗帕金森病（PD）的疗效。方法 计算机检索2015年6月之前在PubMed、Cochrane Library、Embase、CNKI及VIP等数据库中DBS作用STN或GPi治疗PD的随机临床对照研究,按纳入排除标准进行资料的筛选和提取,利用RevMan 5.3软件进行Meta分析。结果 纳入7个研究共613例患者,其中STN组331例,GPi组282例。Meta分析显示,STN-DBS与GPi-DBS治疗后,患者运动症状改善效果（SMD=0.36;95% CI为-0.07~0.78;P=0.10）及生活质量改善（SMD=-0.20,95%CI为-0.78~0.39;P=0.51）相似,且术后3年均效果稳定。STN组较GPi组能明显减少术后药物用量（SMD=0.37;95% CI为0.19~0.55;P<0.0001）;gpi组抑郁发生率较stn组明显减少（rr ci为="" 1.28~2.27;p="0.0003）。结论 STN-DBS与GPi-DBS治疗PD后,患者运动症状改善效果与生活质量改善效果相似,STN -DBS能有效减少术后用药量,GPi-DBS术后抑郁发生率更低。     

Parkinson's disease: deep brain stimulation

The effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal pallidum (GPi) on the parkinsonian triad and on levodopa-induced dyskinesias are very similar. The antiakinetic effect of STN DBS seems to be slightly better. On the contrary to pallidal DBS, stimulation of the STN allows to reduce dopaminergic treatment by more than 50p.100 on average. Moreover, the current drain is smaller in STN. Thus, the STN is a low budget target compared to the GPi. STN DBS seems to be as effective on PD tremor as stimulation of the classic thalamic target, the ventral intermediate nucleus (Vim), whereas Vim stimulation has no effect on akinesia and very little on levodopa-induced dyskinesias. Thus, the STN has become the main target nucleus for DBS in PD, which is most often performed bilaterally in one surgical procedure. There is a good correlation of the preoperative response to levodopa and postoperative effects of bilateral STN DBS and this defines the patient population. Given the large patient population, simple guidelines for patient selection are developed. The referring physician can preselect patients based mainly on age (less than 70), absence of dementia and presence of severe disability related to motor fluctuations or dyskinesias. It is the responsibility of the operating centre to determine the levodopa response, to confirm the diagnosis, to rule out contraindications and to make sure that the medical treatment cannot be further optimised. Severe surgical complications with permanent sequels are relatively rare, about 1p.100 per implanted side. The patient selection, the precision of the surgery and the quality of the postoperative follow-up are the three main determinants of success.     

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。     

Stereotactic neurosurgery for movement disorders

Stereotactic neurosurgery for the treatment of movement disorders focuses primarily on the treatment of Parkinson's disease (PD), essential tremor (ET), and dystonia. The surgical targets in use are the subthalamic nucleus (STN) and the globus pallidus internus (GPi) for PD, GPi for dystonia, and ventralis intermedius (Vim) nucleus of the thalamus for ET. Following target selection, procedures include the generation of lesions or the placement of deep brain stimulating electrodes in the selected target. Additionally, transplantation has been used in the treatment of PD. The indications, outcomes, and risks of the various procedures are reviewed.     

Deep brain stimulation therapy for involuntary movements]

During the last decade, it has become clear that deep brain stimulation (DBS) therapy provides a dramatic improvement in the symptoms of movement disorders. We have experienced DBS in 110 patients with various types of involuntary movements, and confirmed the benefits of stimulation of the thalamic nucleus ventralis intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN) in these patients. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait disturbance are often induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. DBS of the Vim also provides excellent control of post-stroke involuntary movements, including hemiballism and hemichoreoathetosis. Dystonia in young patients is controlled effectively by DBS of GPi. Ablative procedures for control of involuntary movement disorders, such as thalamotomy and pallidotomy, always carry a risk associated with creating additional lesions in an already damaged brain. In contrast, there is not such a risk in DBS therapy. This modality of therapy is an important option in treating involuntary movements.