Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients

The aim of the present study was to assess the efficacy and safety of chronic subthalamic nucleus deep-brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). 18 consecutive severely affected PD patients were included (mean age, SD: 56.9+/-6 years; mean disease duration: 13.5+/-4.4 years). All the patients were evaluated clinically before and 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS). Additionally, a 12 months follow-up was available in 14 patients. The target coordinates were determined by ventriculography under stereotactic conditions, followed by electrophysiology and intraoperative stimulation. After surgery, continuous monopolar stimulation was applied bilaterally in 17 patients at 2.9+/-0.4 V through 1 (n = 31) or 2 contacts (n = 3). One patient had bilateral bipolar stimulation. The mean frequency of stimulation was 140+/-16 Hz and pulse width 68+/-13 micros. Off medication, the UPDRS part III score (max = 108) was reduced by 55 % during on stimulation (score before surgery: 44.9+/-13.4 vs at 6 months: 20.2+/-10; p < 0.001). In the on medication state, no difference was noted between the preoperative and the postoperative off stimulation conditions (scores were respectively: 17.9+/-9.2 and 23+/-12.6). The severity of motor fluctuations and dyskinesias assessed by UPDRS IV was reduced by 76 % at 6 months (scores were respectively: 10.3+/-3 and 2.5+/-3; p < 0.001). Off medication, the UPDRS II or ADL score was reduced by 52.8 % during on stimulation (26.9+/-6.5 preop versus 12.7+/-7 at 6 months). The daily dose of antiparkinsonian treatment was diminished by 65.5 % (levodopa equivalent dose -- mg/D -- was 1045 +/- 435 before surgery and 360 +/- 377 at 6 months; p < 0.01). These results remained stable at 12 months for the 14 patients studied. Side effects comprised lower limb phlebitis (n = 2), pulmonary embolism (n = 1), depression (n = 6), dysarthria and freezing (n = 1), sialorrhea and drooling (n = 1), postural imbalance (n = 1), transient paresthesias and dyskinesias. This study confirms the great value of subthalamic nucleus stimulation in the treatment of intractable PD. Some adverse events such as depression may be taken into account in the inclusion criteria and also in the post-operative outcome.     

Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease

To investigate the bilateral effects of unilateral subthalamic nucleus deep brain stimulation (STN-DBS), we prospectively studied 9 consecutive advanced Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months postoperatively with and without dopaminergic medications ('on' and 'off' medication, respectively). Postoperatively, patients were assessed with and without stimulation. We found that, when compared with baseline, the 'off' medication scores of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p = 0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6 months. At 6 months after surgery, the subscore of UPDRS III of body parts contralateral to the DBS implantation had improved by 48% (p = 0.028), and the ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of levodopa was reduced by 15% at 6 months. No patient exhibited permanent side effects. These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism.     

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease

BackgroundNeuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinson's disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients.MethodsNP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales.ResultsThe number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery.ConclusionsPharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.     

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。     

Anti-cholinergics for axial symptoms in Parkinson's disease after subthalamic stimulation

Objective

We studied the effect of anti-cholinergic therapy on axial symptoms that show a tendency to worsen over time after deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD).

Patients and methods

We conducted a prospective study of 20 consecutive patients treated with the anti-cholinergic agent trihexyphenidyl after bilateral STN-DBS and assessed the effect of anti-cholinergic therapy on parkinsonism 1 month after its initiation using the Unified Parkinson's Disease Rating Scale (UPDRS).

Results

After a mean post-operative follow-up period of 22.3 months, the scores of axial symptoms on UPDRS part II (ADL score) and part III (motor score) deteriorated by 87% and 54% (baseline), respectively, compared with the pre-operative scores (P < 0.001 for both comparisons). After adding trihexyphenidyl to dopaminergic medication with stimulation, the scores of axial symptoms on UPDRS part II and part III improved from baseline by 33% and 39%, respectively (P < 0.001 for both comparisons).

Conclusions

Our findings demonstrated that the anti-cholinergic agent trihexyphenidyl shows positive effect for a patient population developing deterioration of axial symptoms after STN-DBS. The results in the present study may provide insights into the mechanism of emergence or progression of axial symptoms in patients with PD after STN-DBS.     

微电极导向核团毁损术和脑深部电刺激术治疗帕金森病的疗效分析

目的 观察微电极导向核团毁损术和脑深部电刺激术（DBS）治疗帕金森病的临床疗效。方法 对380例接受微电极导向立体定向核团毁损术和25例脑深部电刺激丘脑底核（STN—DBS）治疗的帕金森病患者进行随访和神经功能评估，分别获得术前、术后和DBS开启后1周、6个月、2年及5年的不同服药状态下统一帕金森病量表（UPDRS）评分资料，采用威尔科克森检验（Wilcoxontest），比较不同术后时间点UPDRS运动评分与术前评分的差异。结果 核团毁损术和DBS在术后1周、6个月及2年随访中均能明显改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。在5年随访时间点上仅DBS治疗组较术前比较仍显示差异性。而且DBS组患者术后左旋多巴服药的剂量较术前减少。核团毁损组总体并发症的发生率为5．8％，永久性并发症的发生率为1．2％。DBS组未发生严重并发症。结论 核团毁损术和DBS两者被证实是中晚期帕金森病安全、有效的治疗方法，能显著改善术前帕金森病患者的UPDRS运动评分，减轻左旋多巴诱发的运动波动及异动症。STN—DBS较毁损术更具有独特的可控性、安全性和长效性。     

丘脑底核电刺激术治疗原发性肌张力障碍

目的观察双侧丘脑底核(STN)脑深部电刺激(DBS)治疗原发性肌张力障碍的疗效。方法回顾性分析8例接受双侧STN-DBS的原发性肌张力障碍病人的临床资料。分别在术前和术后1、3、6个月进行Burke-Fahn-Marsden肌张力障碍评分(BFMDRS)和帕金森病综合评分量表(UPDRS),计算两项评分改善率,评价治疗效果。结果 BFMDRS和UPDRS评分的改善率:术后1个月其均值分别为47%和48%,术后3个月为69%和73%,术后6个月为75%和79%。结论 STN-DBS可有效改善原发性肌张力障碍病人的症状,术后疗效稳定。STN是DBS治疗原发性肌张力障碍的理想靶点。     

交叉电脉冲在帕金森病DBS后程控中的应用

目的 探讨交叉电脉冲（ILS）在帕金森病（PD）脑深部电刺激术（DBS）后传统刺激方式疗效不佳病人中的应用效果。方法 回顾性分析2018年2月至2021年10月丘脑底核（STN）-DBS治疗的12例PD的临床资料。12例DBS后应用传统刺激方式疗效不佳,使用ILS（时间>6个月）。使用ILS后随访6~12个月,采用统一帕金森病生活量表（UPDRS Ⅱ）评分、运动量表（UPDRS Ⅲ）评分、异动症量表（UPDRS Ⅳ-A）评分评估疗效及左旋多巴等效日剂量（LEDD）评价药物使用情况。结果 与ILS前（药物关期）相比,使用ILS后（药物关期）UPDRS-Ⅱ评分、UPDRS Ⅳ-A评分、UPDRS-Ⅲ评分总分均明显改善（P<0.05）,LEDD无明显变化（P>0.05）。结论 PD病人STN-DBS后,在传统刺激模式症状改善不佳或出现刺激副反应时,ILS可明显改善PD症状、减轻刺激相关副反应。     

Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: an ECD-SPECT study

We prospectively evaluated 20 patients with Parkinson's disease (PD) preoperatively and 12 months after subthalamic nucleus-deep brain stimulation (STN-DBS). All patients had clinical (UPDRS III) and neuropsychological evaluations as well as brain perfusion SPECT-ECD. Clinical and cognitive data were compared with 12 matched PD patients who had not undergone surgery. STN-DBS patients improved in motor symptoms and reduced medications but selectively declined in category fluency (p<0.01). No clinical and cognitive changes were found in the control group at follow-up. Worsening fluency was associated with perfusion decrements in left dorsolateral prefrontal cortex, anterior cingulate cortex and ventral caudate nucleus (p<.001).     

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1 ± 14.8 to 23.9 ± 11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n = 6), 9 months (n = 6), and 12 months (n = 4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for “off” symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.     

丘脑底核脑深部电刺激对帕金森病抑郁障碍的影响

目的探讨丘脑底核脑深部电刺激对帕金森病病人抑郁障碍的疗效及其机制。方法回顾性分析21例帕金森病合并抑郁障碍病人的临床资料,均行丘脑底核脑深部电刺激术,术前及术后3、6个月分别应用汉密尔顿抑郁量表(HAMD)评分和统一帕金森病评定量表(UPDRS)运动评分对抑郁障碍和运动功能进行临床评价并分析其相关性。结果术后UPDRS运动评分和HAMD评分均显著下降(均P0.05),但是抑郁症状的改善与运动功能的改善并没有明显的相关性(P0.05)。结论丘脑底核脑深部电刺激能够明显改善帕金森病病人的抑郁症状,其机制可能与丘脑底核受到刺激影响脑内神经递质的变化有关,术后运动功能的改善不是抑郁症状改善的主要原因。     

Chronic stimulation of the subthalamic nucleus increases daily on-time without dyskinesia in advanced Parkinson's disease

We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.     

Prognosis of high-risk patients with nonoperated symptomatic extracranial carotid tight stenosis

Forty-five patients with symptomatic (20 with transient ischemic attack, 25 with minor stroke) greater than or equal to 75% stenosis of the cervical internal carotid artery had no endarterectomy and received only medical therapy because the surgical risks (severe cardiac disease, chronic obstructive pulmonary disease, hypertension or diabetes with systemic complications, aortic aneurysm) were believed to be unacceptable. During follow-up (mean 48 months), occlusion of the internal carotid artery developed without symptoms in two patients and with symptoms in three patients. The cumulative stroke and/or death rate was 24% at 2 years and 50% at 6 years. The ipsilateral infarct rate was 10% after the first year, but decreased markedly thereafter (2.4% per year), and one third of these infarcts were probably lacunes due to hypertensive small vessel disease. Overall, stroke related to previously symptomatic internal carotid artery stenosis was not the major problem during follow-up but was largely overcome by other strokes and cardiac death.     

单侧丘脑底核电刺激治疗偏侧型帕金森病的长期疗效

目的评估单侧丘脑底核(STN)脑深部电刺激(DBS)治疗偏侧型帕金森病的长期疗效。方法回顾性分析23例偏侧型帕金森病病人的临床资料,均行单侧STN-DBS治疗,并分别于术前3~5 d、术后1年、术后5年以帕金森病统一评分量表(UPDRS)进行评估。结果术后5年,病人在刺激"关"状态下,UPDRSⅡ、Ⅲ和轴性症状评分较术前明显升高(P<0.05);而刺激"开"状态下,UPDRSⅡ、Ⅲ和轴性部分评分较同期刺激"关"状态分别降低37.37%、41.14%和26.91%。与术前比较,术后5年平均每日口服左旋多巴等效剂量降低24.92%,而异动时间和异动病残度分别增加52.63%和59.65%。本组未发生手术相关并发症,随访期间出现发声困难6例。结论对偏侧型帕金森病人,单侧STN-DBS是一种疗效持久的治疗方法。     

双侧丘脑底核电刺激对帕金森病患者生活质量影响的研究

目的对给予丘脑底核(STN)电刺激治疗的帕金森病(PD)患者进行生活质量评估,以评价治疗的有效性及不同因素对生活质量的影响。方法41例接受双侧STN深部电刺激(DBS)治疗的PD患者分别于术前及术后12个月应用统一帕金森病评定量表(UPDRS)、Hoehn和Yahr分期、Schwab和England日常生活活动量表、医院焦虑和抑郁量表(HADS)评价其临床情况;帕金森病生活质量问卷(PDQ-39)评价生活质量,并对统计结果进行配对t检验和Spearman相关性检验。结果UPDRS评分中日常生活活动、运动检查、并发症均有明显改善(P<0.001),而精神、行为和情绪无明显改善。HADS量表结果显示患者的焦虑及抑郁评分均有明显改善(P<0.001)。PDQ-39评分中运动、日常生活活动、情绪状态、身体不适、总评分等项均有明显改善(P<0.001),羞耻感也有改善(P<0.05)。相关性检验的结果提示与PDQ-39总评分变化程度成相关性的因素依次为:UPDRS运动检查“关”期(P<0.001), Schwab和England日常生活活动量表“关”期(P<0.001),UPDRS日常生活活动“关”期(P<0.01),HADS-抑郁(P< 0.05)。结论脑深部电刺激能明显改善PD患者的生活质量。     

Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease

Twenty-two patients with PD received bilateral implants for high frequency stimulation of the subthalamic nucleus. The patients were treated for more than 1 year (up to 36 months). At the last visit, the Unified Parkinson Disease Rating Scale (UPDRS) motor score without medication improved by 50.2% (p < 0.001) and the UPDRS activities of daily living score improved by 68.4% (p < 0.001). The most common long-lasting adverse events were hypophonia and dysarthria; transient events were increased sexuality and mania. The surgical procedure induced transient intraoperative psychosis in seven patients.     

Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n=11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years).     

Long-term outcome of young onset Parkinson's disease after subthalamic stimulation—A cross-sectional study

Objective

Age of onset is considered a poor prognostic factor for subthalamic deep brain stimulation (STN-DBS) outcome in the case of Parkinson's disease (PD). The goal of current study is to identify the long-term impact of STN-DBS for young onset PD (YOPD) patients.

Methods

17 YOPD patients with a mean disease onset at 32.3 years were prospectively followed up at 1, 2, 5 and 7 years after STN-DBS. Unified Parkinson's disease rating scale (UPDRS) was evaluated in 4 combinations of Med/DBS on/off.

Results

UPDRS part II–IV improved significantly 7 years after operation. While a slowly progressive worsening of levodopa response on part III, synergistic effect of medication and stimulation consistently improves motor disabilities. STN-DBS could remarkably reduce levodopa equivalent daily dose at 7 years. The morbidity rates were low. However, these patients seem to have more transient stimulation dyskinesia (47.1%) and dopamine dysregulation syndrome (11.8%) after surgery.

Conclusions

STN-DBS remains effective to improve motor disabilities over 7 years for YOPD and is a safe procedure concerning cognitive outcome and morbidity. However, stimulation dyskinesia and dopamine dysregulation syndrome deserve attention for the causal relationship between DBS surgery and behavioral outcomes.     

Does ageing influence deep brain stimulation outcomes in Parkinson's disease?

We sought to define the influence of ageing in clinical, cognitive, and quality-of-life outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We performed motor assessment (UPDRS), mood tests, cognitive, and quality of life evaluation (PDQ-39) on PD patients before surgery, and 12 and 24 months after, and we recorded adverse events. The variations of these parameters after surgery were correlated with age using regression statistical tests. Cerebral bleeding risk was evaluated by a nonparametric test. We enrolled 45 patients (mean age 60 +/- 9 years, range 40-73). No significant correlation was found between age and motor scores and PDQ-39 improvements at 12 months. At 24 months, there was a significant negative correlation between age and the improvement of three dimensions of PDQ 39 (mobility, activities of daily life, and cognition). Cognitive impairment showed no correlation, but apathy and depression were positively correlated with age. Significant statistical difference was observed between cerebral bleeding and age. STN-DBS is an effective treatment for elderly patients with advanced PD. A longer follow-up duration and a larger population seem necessary to better assess the quality of life perception in elderly patients and to determinate the real risk of hemorrage.     

Lack of motor symptoms progression in Parkinson's disease patients with long-term bilateral subthalamic deep brain stimulation

To evaluate the long-term progression of motor symptoms in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS), we retrospectively analyzed data from 50 PD patients with bilateral STN-DBS. Clinical records at baseline and at several yearly intervals were reviewed. The Unified Parkinson's Disease Rating scale (UPDRS) was performed preoperatively after withholding medications for at least 12 hr (OFF) and after taking the usual dose of levodopa. Postoperative evaluations were completed in four clinical states: OFF medications—stimulators OFF (OFF/OFF); OFF medications—stimulators ON; ON medications—stimulators OFF; and ON medications—stimulators ON. The UPDRS motor scores OFF/OFF were virtually unmodified up to 5 years when compared with preoperative OFF scores. There was no significant difference between OFF/OFF score variations from baseline in patients with shorter (<11 years) and longer PD duration at the time of surgery. No consistent deterioration from untreated baseline was noted for each UPDRS motor subscore (tremor, rigidity, bradykinesia, and axial). Untreated PD motor scores did not worsen over time in patients undergoing STN-DBS, suggesting that there is no progression of motor severity. These results could be explained either by a natural stabilization of PD motor symptoms after many years or neuroprotective properties of STN-DBS.