Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: Long‐term observation

Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long‐term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on‐period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long‐term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures. © 2008 Movement Disorder Society     

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。     

Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery

Before the introduction of high frequency stimulation of the subthalamic nucleus (STN), many disabled tremor dominant parkinsonian patients underwent lesioning or chronic electrical stimulation of the thalamus. We studied the effects of STN stimulation in patients with previous ventral intermediate nucleus (VIM) surgery whose motor state worsened. Fifteen parkinsonian patients were included in this study: nine with unilateral and two with bilateral VIM stimulation, three with unilateral thalamotomy, and one with both unilateral thalamotomy and contralateral VIM stimulation. The clinical evaluation consisted of a formal motor assessment using the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests encompassing a 50 point frontal scale, the Mattis Dementia Rating Scale, and the Beck Depression Inventory. The first surgical procedure was performed a mean (SD) of 8 (5) years after the onset of disease. STN implantation was carried out 10 (4) years later, and duration of follow up after beginning STN stimulation was 24 (20) months. The UPDRS motor score, tremor score, difficulties in performance of activities of daily living, and levodopa equivalent daily dose significantly decreased after STN stimulation. Neither axial symptoms nor neuropsychological status significantly worsened after the implantation of the STN electrodes. The parkinsonian motor state is greatly improved by bilateral STN stimulation even in patients with previous thalamic surgery, and STN stimulation is more effective than VIM stimulation in tremor dominant parkinsonian patients.     

双侧丘脑底核脑深部刺激术治疗帕金森病13例报告

目的 探讨双侧丘脑底核（STN）脑深部刺激术（DBS）治疗帕金森病的临床经验。方法 从2002年到2005年共完成了13例帕金森病的双侧丘脑底核DBS，根据STN解剖学定位，靶点的理论坐标值是X=11-13mm，Y=0-2mm，Z=0-4mm，通过立体定向技术在双侧丘脑底核植入刺激电极，并于锁骨下方植入脑深部电刺激器。结果 随访时间为6个月到3年，3例震颤为主病人的症状完全缓解，即震颤完全消失；僵直和运动迟缓为主要症状者的症状缓解程度达90％以上，其中以四肢肌肉僵直的效果较好，运动迟缓也有明显缓解，但是有1例病人双侧肢运动协调性差。所有患者植物神经功能症状有较明显改善，如便秘、流涎、出汗和浮肿等均有改善。结论 DBS治疗帕金森病，是帕金森病治疗的一个里程碑似的进步。它可以明显地缓解帕金森病的主要症状和体征，对运动迟缓、僵直和震颤等均有较理想的效果。     

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

OBJECTIVE: To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). METHODS: The efficacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "off" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). RESULTS: Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION: These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.     

Different effects of unilateral versus bilateral subthalamic nucleus stimulation on walking and reaching in Parkinson's disease.

The purpose of this study was to determine the effects of unilateral versus bilateral subthalamic nucleus (STN) stimulation on quantitative measures of walking and reaching in Parkinson's disease (PD). We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 6 people with PD who had bilateral STN stimulators implanted for at least 6 months and withheld their anti-parkinson medication for at least 8 hours. Subjects were studied with both stimulators off, one on, and both on. Kinematic data were collected as subjects walked, reached to a target, and were rated using the UPDRS motor subscale. STN stimulation improved walking speed and stride length, with the greatest benefit from bilateral stimulation. Reaching speed was improved by unilateral STN stimulation alone, with no additive effect of bilateral stimulation. UPDRS motor subscale ratings paralleled the kinematic findings. STN stimulation did not restore PD subjects' movements to the level of age-matched controls. Overall, these results provide further evidence that the basal ganglia pathways involved in control of walking and reaching may be distinct. We speculate that basal ganglia may influence walking through bilateral pedunculopontine projections and reaching through ipsilateral thalamocortical projections. Our findings also suggest that maximal improvement of walking requires bilateral rather than unilateral STN stimulation.     

Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease

Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8-35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60-90 Hz band, if present (seven sides, on medication). Levodopa-induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8-35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency-specific. Our results support a link between levodopa-induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.     

Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease

CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating parkinsonian symptoms even to the extent to permit levodopa withdrawal. OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN: Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS: Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were evaluated in off-medication and on-medication conditions. Dopaminergic drug dosages were reduced after surgery, aiming for complete withdrawal. Six months after surgery, patients were reeavaluated in off- and on-medication conditions, with the stimulation turned on and off. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the off-medication condition improved by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by 65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All results reached significance (P<.001). Stimulation of the STN achieved antiparkinsonian effect similar to that of treatment with levodopa. No life-threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation safely improves all parkinsonian symptoms, decreases or eliminates the need for levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal of levodopa is feasible with this technique and the overall motor effect of STN stimulation is quantitatively comparable to that obtained with levodopa.     

Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease.

OBJECTIVE: To reduce antiparkinsonian medication in parkinsonian patients with bilateral high frequency subthalamic nucleus (STN) stimulation. BACKGROUND: Parkinsonian syndromes are characterized by hyperactivity of the STN. Preliminary data indicate that functional inactivation of the STN may reduce the requirement for dopaminergic therapy in PD. METHODS: Bilateral quadripolar leads were implanted stereotactically in the STN of seven patients with advanced PD (mean age, 57.4 years; mean disease duration, 15.4 years). High-frequency stimulation was applied for 24 hours a day. Following implantation, antiparkinsonian medication was reduced to the minimum possible and stimulation was gradually increased. The patients were evaluated in the practically defined "off" and "on" conditions using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England scale. The average follow-up was 16.3+/-7.6 months. A battery of neuropsychological tests was applied before and 9 months after the implant. RESULTS: Parkinsonian features improved in all patients--the greatest change seen in rigidity, then tremor, followed by bradykinesia. Compared with the presurgical condition, off-drug UPDRS motor scores improved by 41.9% on the last visit (p = 0.0002), UPDRS activities of daily living (ADL) scores improved by 52.2% (p = 0.0002), and the Schwab & England scale score improved by 213% (p = 0.0002). The levodopa-equivalent daily dose was reduced by 65%. Night sleep improved in all patients due to increased mobility at night, and in five patients insomnia was resolved. All patients gained weight after surgery and their appetite increased. The mean weight gain at the last follow-up was 13% compared with before surgery. During the last visit, the stimulation amplitude was 2.9+/-0.5 V and the total energy delivered per patient averaged 2.7+/-1.4 W x10(-6). The results of patient self-assessment scales indicated a marked improvement in five patients and a moderate improvement in the other two. The neuropsychological data showed no changes. Side effects were mild and tolerable. In all cases, a tradeoff between the optimal voltage and the severity of side effects made it possible to control parkinsonian signs effectively. The most marked side effects directly related to STN stimulation consisted of ballistic or choreic dyskinesias of the neck and the limbs elicited by contralateral STN stimulation above a given threshold voltage, which varied depending on the individual. CONCLUSIONS: Parkinsonian signs can be controlled by bilateral high-frequency STN stimulation. The procedure is well tolerated. On-state dyskinesias were greatly reduced, probably due to the reduction of total antiparkinsonian medication. Bilateral high-frequency STN stimulation compensated for drug reduction and elicited dyskinesias, which differ from those observed following dopaminergic medication. ADL improved significantly, suggesting that some motor tasks performed during everyday chores, and that are not taken into account in the UPDRS motor score, also improved.     

Treatment of advanced Parkinson's disease by subthalamotomy: one-year results.

We studied effects on parkinsonian features at 6 and 12 months in 12 patients who underwent unilateral ablation of subthalamic nucleus (STN). Microelectrode mapping was used, and a lesion was created in the STN using thermal coagulation and confirmed with magnetic resonance imaging. At 6 months postoperatively, improvements were seen in several areas: 1) Unified Parkinson's Disease Rating Scales II and III (UPDRS II and III) scores, 30% in off period, 38% in on period; 2) Schwab and England Scale (S&E) score, 21%; and 3) on dyskinesia, 85%. Contralateral rigidity, bradykinesia, UPDRS II and III scores, and S&E scores remained improved at 12 months. Daily dosage of levodopa requirement was reduced by 42%. Axial motor features, gait, postural stability, off period tremor, and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. Complications include 3 cases of hemiballism, of whom 2 patients recovered spontaneously but 1 died from aspiration pneumonia. One patient had asymptomatic hematoma, and 2 suffered transient postural asymmetries. We conclude that unilateral subthalamotomy results in moderate improvement in all aspects of parkinsonian features, allows reduction in the dose of levodopa required, and ameliorates drug-induced complications throughout 12-month assessments.     

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson's disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on ('stim-on') or off ('stim-off'). METHODS: After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores. RESULTS: After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor. CONCLUSION: Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.     

Deep brain stimulation for the treatment of Parkinson's disease: subthalamic nucleus versus globus pallidus internus

OBJECTIVES: Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinson's disease who have side effects from drugs. Which is the best target-globus pallidus internus (GPi) or subthalamic nucleus (STN)-is still a matter of discussion. The aim of this prospective study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinson's disease. PATIENTS AND METHODS: Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinson's disease. Presurgery and 3, 6, and 12 months postsurgery patients were scored according to the CAPIT protocol. RESULTS: Stimulation of the STN increased best Schwab and England scale score significantly from 62 before surgery to 81 at 12 months after surgery; GPi stimulation did not have an effect on the Schwab and England scale. Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication. Whereas STN stimulation increased the unified Parkinson's disease rating scale (UPDRS) motor score, GPi stimulation did not have a significant effect. Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively. CONCLUSION: Stimulation of the GPi reduces medication side effects, which leads to a better drug tolerance. There was no direct improvement of bradykinesia or tremor by GPi stimulation. Stimulation of the STN ameliorated all parkinsonian symptoms. Daily drug intake was reduced by STN stimulation. The STN is the target of choice for treating patients with severe Parkinson's disease who have side effects from drugs.     

Impact of Subthalamic Nucleus Stimulation on Young‐Onset Parkinson's Disease

Objective. To clarify the efficacy of subthalamic nucleus (STN) stimulation in young‐onset Parkinson's disease (PD), we compared the effects of STN stimulation on the motor symptoms between young‐onset PD (YOPD) and late‐onset PD (LOPD). Methods. We analyzed the effects of STN stimulation on motor function and motor fluctuations in 15 patients with YOPD, and 113 patients with LOPD who underwent STN stimulation during the same period. The Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated during the on‐period and off‐period, which are defined as the times at which the motor symptoms are the best and worst during the daily active time with sustaining anti‐parkinsonian drugs. The dyskinesia severity rating scale (DSRS) also was employed to assess the severity of peak‐dose dyskinesia. We analyzed the changes in levodopa equivalent daily dose (LED), motor fluctuations, DSRS, and UPDRS part 3 score after STN stimulation, and compared the changes in each score between the two groups (YOPD vs. LOPD). Results. The LED was reduced, and the on‐off motor fluctuation index, dyskinesia rating scale score (on‐period), and UPDRS part 3 score (on‐ and off‐periods) were improved in both the YOPD and LOPD groups. The improvement rates of the UPDRS part 3 scores in both the on‐ and off‐periods in the YOPD group were superior to those in the LOPD group. The results of multivariate logistic regression analysis demonstrated that YOPD itself is the best responder to STN stimulation. Conclusions. STN stimulation can reduce the LED and improve motor fluctuations in patients with YOPD. The effects of STN stimulation on the motor symptoms of YOPD patients are superior to those in LOPD. The present findings suggest that YOPD patients suffering from several problems related to pharmacological therapy are probably good candidates for STN stimulation.     

Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease

Objective To assess the long-term efficacy and safety of chronic bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD). Methods 36 consecutive patients with idiopathic Parkinson’s disease treated with bilateral stimulation of the STN were studied. Parkinsonian status was assessed preoperatively and at 1 and 3 years postoperatively using the Unified Parkinson’s Disease Rating Scale (UPDRS) and neuropsychological evaluation in on and off-medication / on and off stimulation conditions. Results At 3 years follow-up, STN stimulation reduced the UPDRS motor score by 54.2 % compared to baseline in the off-medication conditions. Tremor, rigidity, bradykinesia, postural stability, and gait improved by 72.2 %, 62.4 %, 56.8 %, 40.5 % and 45.3 %, respectively. UPDRS part II scores were reduced by 41.4 %. The overall dopaminergic drugs dose was reduced by 48.6 % after surgery and four patients were no longer taking antiparkinsonian medication at three years. However, axial dopa-unresponsive signs worsened in some patients. The most frequent transient adverse event consisted in mood disorders in 23 patients. Conclusions Our data demonstrate that: 1) bilateral STN stimulation is relatively safe, improves the motor symptoms and drug-related motor complications of PD, and reduces the daily dosage of medication; 2) this benefit is sustained over time despite the occurrence of axial doparesistant signs in some patients.     

Neurosurgery for Parkinson's disease

Medical therapy for Parkinson's disease (PD) often becomes inadequate over several years. Disability increases despite maximal medical management and many patients develop motor fluctuations and dyskinesia. In addition, medications provide good control of tremor in only 50% of cases. In appropriately selected cases, surgical therapies for PD provide benefit for medically refractory symptoms. Recent advances have provided a greater array of surgical options. Unilateral thalamotomy and thalamic stimulation are considered safe and effective procedures to treat contralateral tremor. Pallidotomy and pallidal stimulation primarily reduce contralateral dyskinesia, with lesser effects on bradykinesia and rigidity. Studies indicate that subthalamic nucleus (STN) stimulation improves "off" period function, decreases "off" time, and lessens dyskinesia. Fetal cell transplantation remains experimental, and studies are underway to evaluate the safety and efficacy of porcine fetal cell and human retinal pigment epithelial cell transplantation. This chapter reviews the history of surgical procedures for PD, describes current procedures, and offers a look into the future of neurosurgical options for PD.     

Effect of bilateral subthalamic nucleus stimulation on parkinsonian gait

Clinical reports show that bilateral subthalamic nucleus (STN) stimulation is effective in improving parkinsonian gait. Quantitative analysis of the efficacy of STN stimulation on gait is of interest and can be carried out using a commercially available stride analyser. Ten parkinsonian patients (5 men, 5 women) with a mean age of 55.8, SD 9.6 years were included in our study. They had a mean duration of Parkinson's disease (PD) of 13.3, SD 4.5 years and a motor examination score (part III of the Unified Parkinson's Disease Rating Scale) (UPDRS) of 43, SD 13 in off-stimulation off-drug condition. All the patients had bilateral chronic STN stimulation which had started from 3 to 36 months before the study. Patients were evaluated in off-drug and on-drug conditions both with and without stimulation. We analysed the principal gait measures: velocity, cadence, stride length, gait cycle, duration of single and double limb support. The clinical parkinsonian signs were evaluated with the part III of the UPDRS. In the off-drug condition, STN stimulation significantly (p < 0.05) improved velocity and stride length. The effect was similar to that of levodopa. When STN stimulation was switched on at the best of the levodopa induced effect, no further improvement was observed. The UPDRS motor score was significantly (p < 0.001) decreased after both stimulation and levodopa. In conclusion, STN stimulation is effective on parkinsonian gait.     

脑深部电刺激治疗帕金森病的程控

目的探讨丘脑底核脑深部电刺激术治疗帕金森病(PD)的手术方法和脉冲发生器程控调节。方法自2000年1月～2004年2月用脑深部电刺激丘脑底核(STN)治疗帕金森病61例,其中单侧30例,双侧31例。采用磁共振扫描结合微电极记录技术进行靶点定位。术后用帕金森病评定量表(UPDRS)运动评分评价刺激效果。结果61例PD患者术后随访6～36个月,平均11．3个月。脉冲发生器开启时,在“关”状态下,UPDRS运动评分改善率45．2％;在“开”状态下,UPDRS运动评分改善率20．7％,未发现任何并发症。结论脑深部刺激(DBS)能有效控制帕金森病患者的症状,手术并发症少,术后可根据患者的症状调节参数,丘脑底核(STN)已成为治疗帕金森病的最佳靶点。     

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson’s disease

Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat Parkinson’s disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory and electrode to treat patients with tremor-dominant PD, yet outcome data for this procedure remains sparse. Our objective is to determine the safety and efficacy of combination STN-VIM DBS. We conducted a single-center retrospective case series of all patients who underwent combined STN-VIM DBS. Demographic, perioperative, and outcome data, including Unified Parkinson Disease Rating Scale-III (UPDRS) and tremor scores (OFF-medication), and levodopa equivalent daily dose (LEDD), were collected and analyzed. Nineteen patients underwent this procedure. Patients were 89% male and 11% female, with a mean age of 63.6 years. Mean preoperative UPDRS was 24.1, and LEDD was 811.8. At a mean follow-up of 33.8 months, UPDRS and LEDD decreased by an average of 9.2 (38.2%) and 326.3 (40.2%), respectively. Tremor scores decreased by 4.9 (59.0%), and 58% were able to decrease total medication burden. One patient developed transient left-sided weakness, yielding a complication rate of 5.3%. Combined targeting of STN and VIM thalamus via a single frontal trajectory for tremor-dominant Parkinson’s Disease results in similar UPDRS outcomes to STN DBS and improved control of tremor symptoms. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.     

Changes in Glucose Metabolism in Cerebral Cortex and Cerebellum Correlate With Tremor and Rigidity Control by Subthalamic Nucleus Stimulation in Parkinson's Disease: A Positron Emission Tomography Study

Objective. Employing [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control.     

丘脑底核电刺激治疗帕金森病的临床应用

目的探讨丘脑底核(STN)脑深部电刺激术(DBS)治疗帕金森病(PD)的手术方法和脉冲发生器的程控调节。方法行STN DBS治疗PD61例,其中单侧30例,双侧31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。结果术后随访6～36个月,平均11.3个月。脉冲发生器开启时,在“关”状态下,UPDRS运动评分改善率5.2%;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STN DBS能有效控制PD症状,手术并发症少,术后可调节参数,已成为治疗PD的重要手术方法。