Correspondence of optimal stimulation and beta power varies regionally in STN DBS for Parkinson disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) for Parkinson disease (PD) normalizes neuronal hypersynchrony in the beta frequency range (13–30 Hz). The spatial correspondence of maximal beta power to the site of optimal stimulation along the DBS lead trajectory has been debated.MethodsWe determined the trajectory locations of the active contact, maximal beta power, and the dorsal border of the STN (DB-STN) in DBS patients. Beta power profiles were measured during intraoperative microelectrode recording (MER). Active contact locations were assigned during blinded, postoperative DBS programming. The DB-STN was identified both electrophysiologically during MER and anatomically on MRI. After grouping DBS trajectories into quadrants relative to the anatomic STN midpoint, we examined regional variations in the relative trajectory locations of the three entities.ResultsSTN DBS significantly improved motor performance for all 13 DBS patients, with active contacts at the DB-STN. Along trajectories passing posterior-medial to the STN midpoint, maximal beta power co-localized with active contacts at the DB-STN (difference Δ = 0.4 ± 1.6 mm, p = 0.57). By contrast, in posterior-lateral trajectories, maximal beta arose within the STN, ventral to active contacts (Δ = 1.9 ± 1.3 mm, p = 0.002). For trajectories anterior to the STN midpoint, maximal beta power co-localized with the DB-STN, while active contacts were ventral to peak beta power (p = 0.05).ConclusionOur findings indicate that co-localization of optimal stimulation and beta power varies by anatomical region in STN DBS for Parkinson disease.     

MRI verified STN stimulation site – gait improvement and clinical outcome

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson’s disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact. Methods: The active contact was visualized on peri‐operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS‐III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN. Results: Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS‐III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation. Conclusions: Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area.     

Anterior lead location predicts verbal fluency decline following STN-DBS in Parkinson's disease

IntroductionVerbal fluency (VF) decline is a well-documented cognitive effect of Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD). This decline may be associated with disruption to left-sided frontostriatal circuitry involving the anteroventral non-motor area of the STN. While recent studies have examined the impact of lead location in relation to functional STN subdivisions on VF outcomes, results have been mixed and methods have been limited by atlas-based location mapping.MethodsParticipants included 59 individuals with PD who underwent bilateral STN-DBS. Each participant's active contact location was determined in an atlas-independent fashion, relative to their individual MR-visualized STN midpoint. Multiple linear regression was used to examine lead location in each direction as a predictor of phonemic and semantic VF decline, controlling for demographic and disease variables.ResultsMore anterior lead locations relative to the STN midpoint in the left hemisphere predicted greater phonemic VF decline (B = −2.34, B SE = 1.08, β = −0.29, sr² = 0.08). Lead location was not a significant predictor of semantic VF decline.ConclusionUsing an individualized atlas-independent approach, present findings suggest that more anterior stimulation of the left STN may uniquely contribute to post-DBS VF decline. This is consistent with models in which the anterior STN represents a “non-motor” functional subdivision with connections to frontal regions, e.g., the left dorsal prefrontal cortex. Future studies should investigate the effect of DBS lead trajectory on VF outcomes.     

Flexible vs. standard subthalamic stimulation in Parkinson disease: A double-blind proof-of-concept cross-over trial

BackgroundDeep brain stimulation (DBS) of the subthalamus (STN) is effective for the treatment of cardinal motor signs of Parkinson disease (PD). Structures around the STN can suppress dyskinesia and tremor (zona incerta) and improve gait and balance (substantia nigra pars reticulata).ObjectiveIs the newer 8-contact linear lead connected to a ‘flexible’ DBS system superior to standard 4-contact stimulation in PD patients receiving STN DBS?MethodsAfter 3 months of open label programming, 10 patients were randomized to standard or flexible stimulation before crossing over to the other arm (3 months each period). Patients and assessors were blinded.ResultsA trend to improvement in Patient Global Impression of Change scores was seen with standard to flexible stimulation and worsening from flexible to standard stimulation (mean ± SD: 0.7 ± 1.2 and −0.4 ± 1.5 respectively, p = 0.152). There was a significant reduction in the number of troublesome symptoms reported prior to DBS (2.6 ± 3.3 per patient), more so with flexible stimulation (0.4 ± 0.6 vs. 1.5 ± 1.6 with standard stimulation, p = 0.001 and p = 0.034). There was no significant difference between the flexible and standard stimulation groups.ConclusionFurther studies confirming that flexible stimulation is superior to standard DBS are warranted.     

Stimulation Region Within the Globus Pallidus Does Not Affect Verbal Fluency Performance

BackgroundSubthalamic (STN) and globus pallidus (GP) deep brain stimulation (DBS) have been previously shown to be efficacious in the treatment of selected Parkinson patients with medication resistant motor fluctuations and/or tremor. Deep brain stimulation of the STN has been implicated with more cognitive and mood side effects as compared to GP DBS; however, more studies are needed to better understand possible target differences. Previously, Mikos et al. [1] reported worsening of verbal fluency depending on the stimulation location within the STN region.Objective/hypothesisThe current study applied the methods used by Mikos et al. (2011) to a different sample of Parkinson patients who underwent GP DBS. Based on differences in the size and functional somatotopy between structures (GP 412 mm³ vs. STN 167 mm³), we hypothesized that there would be a less robust relationship between volume of tissue activated, fluency performance, and stimulation contact within the GP compared to what was reported in the STN.MethodsPatient-specific DBS models were created and the volume of tissue activated within the GP was calculated. These data were correlated with patients' verbal fluency performance at dorsal, optimal, and ventral stimulation contacts.ResultsIn contrast to STN findings, there was no significant relationship between stimulation location and fluency performance in patients who received GP DBS.Conclusion(s)These results suggest that fluency may be less sensitive to stimulation location in the globus pallidus and thus there may be more flexibility in terms of DBS programming with GP DBS patients.     

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease

BackgroundParkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5–12 Hz) are important in cognition.MethodsWe tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients’ peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation.ResultsAcute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions.ConclusionHere, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.     

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.     

Effect of short and long term STN stimulation periods on parkinsonian signs

Currently, no study of subthalamic nucleus (STN) stimulation has compared continuous stimulation with a period of short‐term stimulation, which is frequently employed in the clinic and in research studies. Therefore, this study examined the effects of STN stimulation over 90 min (short) and greater than 3 months (long) on the cardinal signs of Parkinson's disease. The 90 min time period immediately followed a 12 hour withdrawal from both STN stimulation and medication. Ten PD patients who received STN stimulation were studied. Bradykinesia, rigidity, and tremor were evaluated using the UPDRS and motor control measures which included peak velocity (bradykinesia), work (rigidity), and amplitude (tremor). Results showed no difference between 90 min and greater than 3 months of STN stimulation for the UPDRS or motor control measures. This finding confirms that the treatment efficacy that is derived from a relatively short time course of stimulation generalizes to longer time periods of high frequency STN stimulation that patients experience in their daily lives. As such, it is reasonable to evaluate the effect of DBS after 90 min of stimulation in clinical trials and research studies. © 2008 Movement Disorder Society     

Rapid response of parkinsonian tremor to STN‐DBS changes: Direct modulation of oscillatory basal ganglia activity?

Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor and other cardinal symptoms in Parkinson's disease (PD), the precise mechanisms of action of DBS are still unclear. We analyzed the time course of resting tremor amplitude and frequency during discontinuation and subsequent reinitiation of STN‐DBS in nine PD patients, using a computerized three‐dimensional motion analysis combined with surface electromyography. Following discontinuation of STN‐DBS, resting tremor amplitude rapidly increased, reaching maximum amplitude after 2 min (mean ± 95%CI: 34.3 ± 13.8 mm; P < 0.01), subsequently stabilizing at a medium level. Reinitiation of stimulation after 30 min resulted in rapid, nearly complete suppression of tremor activity within 1 min (1.4 ± 1.3 mm; P < 0.01) and, furthermore, increased tremor frequency within a few seconds in seven of nine patients. These findings support the hypothesis that STN‐DBS acts by direct interference with the neurotransmission of basal ganglia networks involved in tremor. © 2009 Movement Disorder Society     

Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor

BackgroundThe subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.Methods14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.ResultsAt the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.ConclusionUnilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.     

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.     

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.     

Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson’s disease: A potential biomarker for optimal electrode placement

BackgroundDeep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson’s Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response.ObjectiveWe explored whether recovery of the H-reflex—an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD—could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation.MethodsChanges in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities.ResultsFollowing MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization.ConclusionH-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.     

Stimulation of the subthalamic nucleus in a patient with Parkinson disease and essential tremor

BACKGROUND: The preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance. OBJECTIVE: To describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET. DESIGN: Case report. PATIENT: A 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor. INTERVENTIONS: Left pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS. MAIN OUTCOME MEASURES: Control of symptoms of PD and ET. RESULTS: The left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS. CONCLUSION: Placement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.     

Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be an effective treatment for the motor symptoms of Parkinson's disease. The therapeutic benefits are voltage-dependent and, in many cases, limited by the appearance of side effects, including muscle contractions. We have observed a number of clinical cases where improvements in rigidity were accompanied by a worsening of bradykinesia. Considering the anatomic position of STN and current approaches to implantation of the DBS lead, we hypothesized that this dissociation of motor symptoms arises from activation of pyramidal tract fibers in the adjacent internal capsule. The objective of this study was to assess the physiological basis for this dissociation and to test our hypothesis that the underlying etiology of this paradox is activation of fibers of the internal capsule. The effect of STN DBS at 80% of motor threshold for each of the four contacts was evaluated for its effect on rigidity, bradykinesia, and akinesia in a single primate with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Consistent with our observations in humans, this near-threshold stimulation was found to improve rigidity while bradykinesia and akinesia worsened. Worsening bradykinesia in the face of improvement of other motor signs in Parkinson's disease (PD) patients is suggestive of activation of pyramidal tract (PT) fibers during stimulation. This phenomenon may occur without overt muscle contraction and improved rigidity.     

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients

BackgroundClosed loop deep brain stimulation (clDBS) in Parkinson's disease (PD) using subthalamic (STN) neural feedback has been shown to be efficacious only in the acute post-operative setting, using externalized leads and stimulators.ObjectiveTo determine feasibility of neural (N)clDBS using the clinical implanted neurostimulator (Activa? PC + S, FDA IDE approved) and a novel beta dual threshold algorithm in tremor and bradykinesia dominant PD patients on chronic DBS.Methods13 PD subjects (20 STNs), on open loop (ol)DBS for 22 ± 7.8 months, consented to NclDBS driven by beta (13–30 Hz) power using a dual threshold algorithm, based on patient specific therapeutic voltage windows. Tremor was assessed continuously, and bradykinesia was evaluated after 20 min of NclDBS using a repetitive wrist flexion-extension task (rWFE). Total electrical energy delivered (TEED) on NclDBS was compared to olDBS using the same active electrode.ResultsNclDBS was tolerated for 21.67 [21.10–26.15] minutes; no subject stopped early. Resting beta band power was measurable and similar between tremor and bradykinesia dominant patients. NclDBS improved bradykinesia and tremor while delivering only 56.86% of the TEED of olDBS; rWFE velocity (p = 0.003) and frequency (p < 0.001) increased; tremor was below 0.15 rad/sec for 95.4% of the trial and averaged 0.26 rad/sec when present.ConclusionThis is the first study to demonstrate that STN NclDBS is feasible, efficacious and more efficient than olDBS in tremor and bradykinesia dominant PD patients, on long-term DBS, using an implanted clinical neurostimulator and driven by beta power with a novel dual threshold algorithm, based on customized therapeutic voltage windows.     

Effective long-term subthalamic stimulation in PARK8 positive Parkinson’s disease

Whether patients with genetically defined Parkinson’s disease (PD) may be particularly eligible to benefit from deep brain stimulation of the nucleus subthalamicus (STN-DBS) is currently the subject of debate. We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.     

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。     

Kinematic optimization of deep brain stimulation across multiple motor symptoms in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms including tremor and bradykinesia (slowness of movement). Drug treatment, although capable of controlling these symptoms over a number of years, becomes less effective as the disease progresses and leads to motor complications such as drug-induced dyskinesia (involuntary abnormal movements). Deep brain stimulation (DBS) provides an alternative means of controlling motor symptoms in these patients, and while DBS has been effective in improving motor symptoms, these improvements are largely based on accurate placement of the lead and the ability of medical personnel to adequately program the DBS device following implantation. While guidelines exist for DBS programming, selection of stimulation parameters and patient outcome is greatly dependent on subjective clinical assessments and the experience of the medical personnel performing the programming. The aim of this project was to assess the feasibility of using a quantitative and objective approach to programming. Two subjects underwent standard procedures for DBS programming while wearing a small, compact motion sensor. Kinematic data were collected from subjects as they completed motor tasks to evaluate DBS efficacy. Quantitative variables characterizing tremor and bradykinesia were related to stimulation parameters. Results indicated different stimulation settings might be required for optimal improvement of different motor symptoms. A standardized method of programming DBS parameters utilizing motion analysis may provide an objective method of assessment that the programmer can use to better identify stimulation parameters to achieve optimal improvement across multiple motor symptoms.     

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.