脑深部电刺激治疗运动障碍性疾病的疗效观察

目的探讨脑深部电刺激（DBS）治疗运动障碍性疾病（MD）的疗效及安全性。方法对49例运动障碍性疾病的患者进行丘脑底核（STN）、苍白球内侧部（Gpi）、丘脑腹中间核（Vim）刺激电极植入术,术前采用1.0 TMR和3.0 TMR T2加权靶点扫描,在直视下行靶点直接定位。手术前后应用统一帕金森病评分量表评分（UPDRS）及Burke Fahn-Marsden运动障碍评分（BFMs）评价临床效果。结果本组手术前帕金森病患者UPDRS：药物＂关＂状态25-80分,平均55分;药物＂开＂状态19-53分,平均34分。术后在开机的情况下UPDRS：药物＂关＂状态17-24分,平均22分,改善率60.0%;药物＂开＂状态15-24分,平均19分,改善率44.0%。4例肌张力障碍患者BFMs平均改善率55.0%。41例患者术后症状迅速改善,肌张力降低,震颤及异动症消失。结论DBS能明显改善MD患者的临床症状,改善其生活质量,且具有安全性。     

Acute effects of adaptive Deep Brain Stimulation in Parkinson’s disease

BackgroundBeta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson’s disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed.MethodsTo determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson’s Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT).ResultsMean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS.ConclusionBeta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy.     

Caregiver burden worsens in the second year after subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundCaregiver burden (CB) in Parkinson's disease (PD) does not improve in the short term after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), despite motor improvement. This may be due to increased caregiver demands after surgery or the possibility that DBS unresponsive non-motor factors, such as executive dysfunction, contribute to CB.ObjectiveTo evaluate the trajectory of CB in year 2 following bilateral STN DBS surgery for PD, and to test whether post-operative CB changes correlate with changes in executive function in a subgroup with available neuropsychological testing.MethodsThis retrospective analysis included 35 patients with PD whose caregivers completed the Caregiver Burden Inventory (CBI) at baseline and between 9 and 24 months after bilateral STN DBS. 14 of these patients had neuropsychological testing both at baseline and within 6 months of their follow up CBI assessment.ResultsCBI scores showed worsened CB from baseline to follow-up (16.4–21.5, p = 0.006). There was no correlation between change in executive function and change in CBI in the smaller subsample.ConclusionCB worsens in the 2 years after bilateral STN DBS despite improvement in motor symptoms and is not associated with change in executive dysfunction in the setting of advancing PD. These findings have implications on pre-operative counselling for patients and caregivers considering DBS for PD.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

脑深部电刺激对帕金森病患者基底节环路的影响及其作用机制

目的研究双侧丘脑底核(STN)慢性电刺激术(DBS)对晚期帕金森病(PD)患者静止期脑局部糖代谢的影响,并探讨DBS的作用机制.方法对7例进行双侧STNDBS的晚期PD患者,在术前和术后1个月电刺激条件下,分别进行18F-脱氧葡萄糖(FDG)/PET检查和UPDRS评分,并通过SPM99统计学软件进行数据分析,研究双侧STNDBS对PD患者脑内代谢的影响.结果双侧STN DBS使PD患者临床症状明显改善,同时脑局部糖代谢也发生了明显变化双侧豆状核、脑干(中脑、脑桥)、双侧顶枕部、运动前区(BA6)及扣带回的脑代谢增加;前额叶底部、海马的脑代谢减少(P＜0.05).结论双侧STN DBS可能通过兴奋STN轴突的方式,使轴突投射区域的基底节上行和下行通路代谢改善,并增加相应的额叶高级运动中枢的代谢,使PD患者临床症状改善.     

丘脑底核电刺激治疗苍白球毁损术后的帕金森病(12例报告)

目的探讨帕金森病(Parkinson's disease,PD)苍白球腹后部毁损术(posteroventral pallidotomy,PVP)后再行丘脑底核(subthalamic nucleus,STN)脑深部电刺激术(deep brain stimulation,DBS)的可行性、术中电生理学特点和治疗结果。方法应用MR和微电极记录技术进行靶点定位,对12例单侧PVP术后症状再次加重的PD患者实施STN-DBS手术,其中4例行毁损灶对侧的STN-DBS,8例行双侧STN-DBS。结果STN-DBS对本组12例PD患者症状有不同程度的改善,双侧STN-DBS的效果尤为明显,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<0．01),无明显术后并发症。术中电生理记录显示毁损灶同侧的细胞放电明显低于正常情况。结论曾行单侧PVP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,可减少药物用量。     

丘脑底核高频电刺激对大鼠纹状体多巴胺代谢影响的研究

目的研究丘脑底核(STN)高频电刺激(HFS)对大鼠纹状体多巴胺(DA)代谢的影响。方法给予正常大鼠一侧STN-HFS,应用微透析观察其对纹状体DA及其代谢产物的影响,应用免疫组化观察其对黑质DA能神经元的影响。结果微透析检测发现刺激侧纹状体DA代谢产物明显增高(P<0.05),DA水平无变化(P>0.05);免疫组化检测发现刺激组和对照组酪氨酸羟化酶(TH)阳性神经元数量无差异(损毁侧分别为24.00±6.81、23.43±5.49,P>0.05)。结论STN-HFS可能通过影响黑质-纹状体DA代谢发挥作用,STN-HFS对黑质DA能神经元可能无保护作用。     

脑深部电刺激术与毁损术治疗双侧帕金森病的疗效对照研究

目的:探讨双侧丘脑底核(STN)脑深部电刺激术(DBS)和分期双侧丘脑和(或)苍白球毁损术治疗双侧帕金森病(PD)的疗效比较。方法:2001年至2005年在该科接受双侧STN-DBS患者29例为DBS组,分期双侧丘脑或苍白球毁损术患者59例为毁损组,采用统一的PD评定量表(UPDRS),在“关”状态下对患者的日常生活活动(ADL)及运动功能进行评分(双侧DBS及第2次毁损术术前及术后1个月),计算其差值及改善率,并对并发症进行观察及评价。结果:DBS组患者ADL差值为15.93±3.98,改善率为(57.9±9.5)%,运动功能差值为29.45±5.17,改善率为(62.8±9.0)%,并发症1例。毁损组患者ADL差值为12.17±4.050,改善率为(53.8±1.2)%,运动功能差值为22.80±5.59,改善率为(59.8±1.0)%,长期及短暂并发症14例。两者术后1个月ADL及运动的UPDRS评分较术前均明显减少(P0.05),并发症比较(P=0.017)有显著性差异。结论:两种治疗方法在改善患者的临床症状方面疗效均较好,但STN-DBS减少了并发症的发生,是值得推广的治疗方法。     

Haloperidol-induced alteration in the physiological actions of group I mGlus in the subthalamic nucleus and the substantia nigra pars reticulata

Excitatory glutamatergic inputs to the subthalamic nucleus (STN), and subthalamic afferents to the substantia nigra pars reticulata (SNr) are believed to play a key role in the pathophysiology of Parkinson's disease (PD). Previously, we have shown that activation of the group I mGlus in the STN and SNr induces a direct depolarization of the neurons in these nuclei. Surprisingly, although both group I mGlus were present in the STN and SNr, mGlu5 alone mediated the DHPG-induced depolarization of the STN, and mGlu1 alone mediated the DHPG-induced depolarization of the SNr. We now report that both mGlu1 and mGlu5 are coexpressed in the same cells in both of these brain regions, and that both receptors play a role in mediating the DHPG-induced increase in intracellular calcium. Furthermore, we demonstrate that the induction of an acute PD-like state using a 16 h haloperidol treatment produces an alteration in the coupling of the group I receptors, such that post-haloperidol, DHPG-induced depolarizations are mediated by both mGlu1 and mGlu5 in the STN and SNr. Therefore, the pharmacology of the group I mGlu-mediated depolarization depends on the state of the system, and alterations in receptor coupling may be evident in pathological states such as PD.