Subthalamic prelemniscal radiation stimulation for the treatment of Parkinson's disease: electrophysiological characterization of the area

Previous reports have provided evidence of a reticulo-thalamic system, extending from the mesencephalic reticular formation (MRF) to the ventrolateral thalamus (VL), involved in the production of tremor. In humans, a funnel of fibers in the posterior subthalamus named the prelemniscal radiations (Raprl) has been described as an exquisite target to treat tremor in cases of Parkinson's disease.In the present study, a group of 14 patients suffering from Parkinson's disease, with prominent unilateral tremor and rigidity, were implanted with tetrapolar depth brain stimulation (DBS) electrodes in Raprl to perform chronic electrical stimulation (ES) for the treatment of patient symptoms. Electrodes were left externalized to corroborate their placement throughout MRI studies and also to perform the following electrophysiological battery: (a) recording of somatosensory-evoked responses (SEP) through different electrode contacts and scalp by means of a paradigm to study the attention process; (b) evoking scalp EEG responses by stimulation with low (3 cps, 6 cps) and high (60-120 cps) frequencies with stimuli delivered through different electrode contacts, and (c) studying recovery cycle (RC) potentials in the Raprl while the upper MRF was being stimulated and, conversely, the RC in MRF while Raprl was being stimulated, before and after subacute Raprl stimulation. Thereafter, the electrodes were internalized and connected to a pulse generator (IPG) to carry on chronic ES, while the effects of stimulation were determined through a quantitative evaluation that measured phasic and tonic muscular activity with EMG recordings during different motor tasks.Results indicate the following: (a) that late, but not early, SEP components were recorded in Raprl and modulated in different attentive conditions; (b) that bilateral recruiting responses and spike and wave complexes were elicited by Raprl through low-frequency stimulation, while bilateral positive DC shifts induced by high-frequency stimulation were recorded, similar to those obtained in animals from MRF, and (c) that Raprl-ES induced RC inhibition at Raprl, but Raprl ES did not change MRF-RC. Long-term Raprl-ES induced a significant decrease in tremor and rigidity.It was concluded that Raprl represents a subthalamic circuit electrophysiologically related to MRF in the genesis of tremor and rigidity and in the process of selective attention. Raprl-ES induced a significant improvement in tremor and rigidity by causing inhibition of the stimulated area.     

Subthalamic deep brain stimulation for Parkinson＇s disease： correlation of active contacts and electrophysiologically mapped subthalamic nucleus

Background Subthalamic deep brain stimulation （STN-DBS） has been shown to be effective in the treatment of Parkinson＇s disease. The site for permanent stimulation is still in debate. This study aimed to assess the position of active contacts in relation to the subthalamic nucleus. Methods We reviewed the location of 40 electrodes in 34 patients who underwent STN-DBS. The position of electrode was evaluated by postoperative magnetic resonance imaging （MRI）. The position of active contacts was compared with the subthalamic nucleus （STN） determined by intraoperative electrophysiological mapping and postoperative MRI. Results The average position of the 40 active contacts was （11.7±1.2） mm lateral, （0.6±1.3） mm anterior, and （0.7±1.4） mm vertical to the midcommissural point. The dorsal margin of the STN was （11.6±1.1） mm lateral, （0.2±1.1） mm anterior, and （1.3±1.1） mm vertical to the midcommissural point. When compared with the dorsal margin of the STN, the active contacts were located more dorsally （P=0.033） and anteriorly （P=-0.012）, no significant difference was found in the lateral direction （P=0.107）. When compared with the position of the STN, 26 （65%） of active contacts were located in the region dorsal to the STN, only 13 （32.5%） were located in the upper two-thirds portion of STN. Conclusions The site for permanent stimulation appears to be in the subthalamic region dorsal to the STN, close to the dorsal margin of the STN. Besides the dorsal portion of the STN, other structures such as fields of Forel H and zona incerta may also be involved in the therapeutic benefit of deep brain stimulation.     

丘脑底核深部电刺激治疗帕金森病

目的:探讨脑深部电刺激(deep brain stimulaiton,DBS)丘脑底核(the subthalamic nucleus,STN)对帕金森病(Parkinson's disease,PD)的治疗机制、方法和疗效.方法:PD患者30例,应用CT和微电极导向立体定向技术将刺激电极植入丘脑底核,术前1 wk及术后1 mo采用UPDRS和Webster评分,随访6～12 mo.结果:脑深部电刺激治疗患者30例,术后肢体僵直、震颤、运动迟缓等症状较术前明显好转,UPDRS运动功能及日常生活评分和Webster评分较术前均有降低(P<0.05),口服药物剂量明显减少(P<0.05).结论:脑深部电刺激可使帕金森病患者症状全面改善,同时可通过调节刺激参数达到长期治疗效果,减少药物用量,是安全有效的治疗方法.     

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease

OBJECTIVE: To evaluate the effects of bilateral deep brain stimulation in the subthalamic nucleus for symptomatic relief of advanced idiopathic Parkinson's disease. DESIGN: Prospective cohort study. SETTING: Patients were assessed and received medical treatment at the Kingston Centre, Southern Health, Melbourne. Surgery took place at Melbourne Neuroscience Centre, The Royal Melbourne Hospital. Both are tertiary public institutions. SUBJECTS: 14 patients with Parkinson's disease with intact cognition and difficult to manage motor symptoms who were referred to Kingston Centre between 1996 and 2000 and were eligible for surgical intervention. INTERVENTIONS: All patients were assessed both after 12 hours' withdrawal from and while taking their levodopa medication on two occasions before surgery. Further assessments were carried out one, three, six and 12 months after surgery. MAIN OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale motor exam and gait parameters, such as stride length and velocity, were compared at six months after surgery with neither stimulation nor medication, with stimulation only, with medication only, and with stimulation and medication. RESULTS: Stimulators were explanted in one patient after intracranial haemorrhage and relocated to the thalamus in a second. Extraneous factors prevented two patients from attending at six-month follow-up. Motor performance improved significantly with stimulation alone in the 10 remaining patients. Further significant gains were seen with stimulation and medication combined, with an apparent reduction in side-effects such as dyskinesia. CONCLUSIONS: Bilateral deep brain stimulation of the subthalamic nucleus significantly improves motor performance in advanced Parkinson's disease, despite a rather high complication rate.     

帕金森病模型大鼠丘脑底核神经元电生理活动的研究

目的：建立6-羟多巴胺（6-OHDA）诱导的帕金森病（Parkinson＇s disease,PD）大鼠模型,研究丘脑底核（subthalamicnucleus,STN）神经元电生理活动的改变,探讨PD的病理生理学机制。方法：采用立体定向技术将6-0HDA两点法注入大鼠左侧黑质致密部（substantia nigra pars compacta,SNc）建立帕金森病大鼠模型,对诱发成功的大鼠模型和对照组均采用玻璃微电极细胞外记录法记录STN神经元放电。结果：分别观察和分析了对照组大鼠STN中的20个神经元和PD组大鼠STN中的37个神经元。两组神经元的放电频率无显著差异（P〉0．05）。但PD组大鼠STN神经元中爆发放电的神经元多于对照组,而不规则放电的神经元少于对照组（P〈0．05）。结论：PD状态下STN神经元放电频率与对照组无显著差异,但放电形式发生了改变,爆发放电的神经元显著增多,说明STN神经元的活动增强。     

电刺激小脑顶核对帕金森病合并抑郁患者的治疗作用

目的探讨电刺激小脑顶核（FNS）对帕金森患者的运动症状及抑郁症状的影响。方法将105例伴随抑郁症状的帕金森病（PD）患者随机分为FNS＋美多巴组（药物＋刺激组）、单纯刺激组（刺激组）、单纯美多巴组（药物组）,每组35例。根据分组,对需要刺激的患者予以FNS治疗,每次通电30min,每日治疗1次,连续治疗30d。需要服药的患者仍按常规服用美多巴。所有患者治疗期间美多巴用量不变。于治疗前、后予以改良Webster评分及汉密尔顿抑郁分级量表（HAMD）评分。结果 FNS治疗后,药物＋刺激组患者运动症状有所改善,抑郁症状有所减轻,Webster和HAMD评分均减少,其差异具有统计学意义（P〈0.05）;单纯刺激组运动症状改善不明显,但抑郁症状有所减轻,其差异具有统计学意义（P〈0.05）;单纯药物组则无明显改变。结论电刺激小脑顶核作为康复疗法,在改善帕金森病患者运动症状和抑郁症状方面均有疗效,是一种行之有效的疗法,适用于PD患者的康复治疗。     

脑深部电极刺激术治疗帕金森病患者围手术期护理

目的:观察脑深部刺激治疗帕金森患者并发症与护理。方法:对17例帕金森患者,行双侧脑深部刺激器(deep brain stimulator,)植入术。手术采用磁共振扫描结合微电极记录技术进行靶点定位,刺激靶点为丘脑底核,对患者围手术期进行并发症的观察与护理。结果:17例患者术后切口愈合良好,肢体震颤僵直缓解,行动迟缓明显改善,无严重并发症。术后随访无异常不适,生活质量明显提高。结论:围手术期严密观察病情,对患者进行针对性的心理护理,加强患者肢体的功能锻炼,并给予正确的出院指导,对患者康复有重要意义。     

手术治疗帕金森病的进展和若干概念

帕金森病 (Parkinson’sdisease ,PD)的手术治疗经历了半个多世纪的发展 ,于九十年代初复兴 ,苍白球腹后部取代丘脑腹外侧核成为原发性PD的最佳治疗靶点。微电极导向的苍白球切开术不仅能改善以震颤、僵直和导动症为代表的PD运动增多症 ,还能改善以行动迟缓、步僵和“关”状态为代表的PD运动减少症。苍白球和丘脑手术的结合适用于合并顽固性震颤的PD患者。双侧苍白球切开术似乎并不存在类似于双侧丘脑手术的严重并发症 ,如构音障碍和严重的认知障碍 ,但明显增加语音低下和吞咽困难的风险。     

Parkinson's disease

The management of the elderly patient with idiopathic Parkinson's disease requires great attention to detail. Treatment should only be considered when the daily activities of life are affected. Medication should be commenced cautiously. Regular review is essential and co-ordination with other members of the multidisciplinary team is vital.     

原发性帕金森病的双侧丘脑底核电刺激治疗

目的评价对原发性帕金森病,实施双侧丘脑底核脑深部电刺激(DBS)治疗的疗效.方法对6例帕金森病患者采用磁共振导向立体定向方法,将刺激电极分别植入双侧丘脑底核,同期植入刺激发生器.术后1个月用程控仪在体外调整刺激参数,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、姿势障碍以及药物所致的并发症明显改善,同时多巴胺类药物用量明显减少.结论 DBD治疗PD,具有安全,可逆转、疗效显著等优点,因观察时间短,长期疗效有待进一步观察.     

丘脑底核电刺激改善帕金森病症状的电生理基础

目的探讨丘脑底核（STN）细胞电活动、脑深部刺激（DBS）电极触点位置与帕金森病（PD）症状改善的关系。方法19例PD患者在接受STNDBS治疗的同时采集细胞电活动和肢体EMG。应用单细胞分析、相关性检验探讨不同放电模式细胞活动与症状的关系,PD综合量表进行术前和术后疗效评估。结果在278个STN神经元中发现与震颤相关（12．6％）的放电活动多分布在STN上部,而紧张性（32．7％）和不规则（54．7％）放电活动多分布在STN下部,进一步比较STN上下部各类细胞的分布均有统计学意义（P〈0．05）。对DBS刺激触点的疗效分析发现,上部触点对震颤改善显著,而下部触点对僵直和迟缓的改善明显。结论STN不同放电模式神经元与PD症状有内在联系。     

丘脑底核深部脑电刺激术对帕金森病患者神经心理功能的影响

目的:探讨帕金森(PD)患者丘脑底核深部脑电刺激术(STN-DBS)后神经心理功能的变化特征。方法:共纳入2014年12月到2016年3月武汉大学中南医院诊断的42例PD患者,分为手术组(接受STN-DBS,同时服用抗PD药物)和对照组(仅服用抗PD药物)。在基线期和6月随访期,服用抗PD药物和电刺激的状态下,收集一般人口学信息,并用统一帕金森评分量表、艾森布鲁克认知检测-修订版、Hoehn-Yahr分期、Schwab-England日常生活能力、汉密尔顿焦虑和抑郁量表对患者的精神、日常生活能力、运动症状、药物并发症、定向力和注意力、记忆、语言流畅性、语言、视空间、疾病分期、焦虑和抑郁进行评测。用配对t检验或Wilcoxon符号秩和检验比较基线和随访期资料,用独立样本t检验或Mann-Whitney U检验比较手术组和对照组资料。结果:手术组PD患者术后总体认知功能未见明显变化,语言流畅性显著下降(P=0.022)。与对照组相比,手术组PD患者运动能力(P=0.000)、日常生活能力(P=0.047)、抑郁(P=0.009)和焦虑(P=0.003)症状显著改善,服用抗帕金森药物减少(P=0.000)。结论:STN-DBS对PD患者认知功能总体安全,可改善患者日常生活能力、抑郁、焦虑和运动等症状。本前瞻性研究可为中晚期PD患者接受STN-DBS治疗提供一定的指导意义。     

底丘脑核中MPEP对治疗早期帕金森病模型大鼠运动行为的影响

目的：：探讨底丘脑核(STN)中代谢型谷氨酸受体5(mGluR5)拮抗剂 MPEP 对部分损毁的帕金森病(PD)模型大鼠运动行为的影响及神经保护作用。方法：将大鼠随机分为假手术组(n=12)、损毁+生理盐水组(n=12)、损毁+MPEP 组(n=12)。采用行为学和神经化学检测方法,观察3组大鼠在旷场实验中的自发运动能力和斜板实验中的停留角度,以及纹状体中多巴胺(DA)含量。结果：与假手术组大鼠相比较,损毁+生理盐水组大鼠的水平运动能力(P<0.001)、垂直运动能力(P<0.001)和斜板停留角度(P<0.001)均明显降低,而损毁+MPEP组大鼠均恢复至假手术组水平(P>0.05)。神经化学检测结果显示,与假手术组大鼠相比较,损毁+生理盐水组大鼠纹状体DA含量降低了56.3%(P<0.001),而损毁+MPEP组大鼠与假手术组大鼠无明显差异(P>0.05),且与损毁+生理盐水组比较明显升高(P<0.001)。结论：慢性STN局部应用MPEP对早期PD模型大鼠的运动行为和神经元具有保护作用。