Variable versus constant frequency deep brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial
Fumin JiaJianguo ZhangHuimin WangZhanhua LiangWeiguo LiuXuelian WangYiming LiuYi GuoZhipei LingXiaodong CaiXi WuJian WuWen LvXin XuWenbin ZhangLuming Li
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Abstract Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait (FOG), can be limited or cause further impairment. While this can be alleviated via relatively low frequency stimulation (LFS) in select patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial. Methods/Design: We propose a multicenter, double blind clinical trial involving 12 study hospitals and an established DBS team. The participants will be divided into a VFS and a constant frequency stimulation (CFS) group. The primary outcome will be changes in Stand-Walk-Sit (SWS) task scores at three months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with CFS. Discussion: This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future. Trial registration: The present protocol is registered at ClinicalTrials.gov: NCT03053726.Keywords:
Neuromodulation
Subthalamic Nucleus
Brain stimulation
Abstract To determine whether the degree to which a patient with Parkinson's disease expects therapeutic benefit from subthalamic nucleus–deep brain stimulation (STN‐DBS) influences the magnitude of his or her improved motor response, 10 patients with idiopathic Parkinson's and bilateral STN‐DBS were tested after a 12‐hour period off medication and stimulation. Four consecutive UPDRS III scores were performed in the following conditions: (a) stimulation OFF, patient aware; (b) stimulation OFF, patient blind; (c) stimulation ON, patient aware; and (d) stimulation ON, patient blind. Statistical significance ( P = 0.0001) was observed when comparing main effect ON versus OFF (mean ON: 32.55; mean OFF: 49.15). When the stimulation was OFF, patients aware of this condition had higher UPDRS motor scores than when they were blinded (mean: 50.7 vs. 47.6). With the stimulation ON, UPDRS motor scores were lower when the patients were aware of the stimulation compared with when they were blinded (mean: 30.6 vs. 34.5). The interaction between these levels was significant ( P = 0.049). This variation was important for bradykinesia and was not significant for tremor and rigidity. The authors conclude that the information about the condition of the stimulation enhanced the final clinical effect in opposite directions. The results presented support the role of expectation and placebo effects in STN‐DBS in Parkinson's disease patients. © 2006 Movement Disorder Society
Subthalamic Nucleus
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Subthalamic Nucleus
Tardive dyskinesia
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Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments. SIGNIFICANCE STATEMENT We tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait.
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We present our experience at the University of Illinois at Chicago (UIC) in deep brain stimulation (DBS) of the subthalamic nucleus (STN), describing our surgical technique, and reporting our clinical results, and morbidities. Twenty patients with advanced Parkinson's disease (PD) who underwent bilateral STN-DBS were studied. Patients were assessed preoperatively and followed up for one year using the Unified Parkinson's Disease Rating Scale (UPDRS) in "on" and "off" medication and "on" and "off" stimulation conditions. At one-year follow-up, we calculated significant improvement in all the motor aspects of PD (UPDRS III) and in activities of daily living (UPDRS II) in the "off" medication state. The "off" medication UPDRS improved by 49.3%, tremors improved by 81.6%, rigidity improved by 50.0%, and bradykinesia improved by 39.3%. The "off" medication UPDRS II scores improved by 73.8%. The Levodopa equivalent daily dose was reduced by 54.1%. The UPDRS IVa score (dyskinesia) was reduced by 65.1%. The UPDRS IVb score (motor fluctuation) was reduced by 48.6%. Deep brain stimulation of the STN improves the cardinal motor manifestations of the idiopathic PD. It also improves activities of daily living, and reduces medication-induced complications.
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Abstract A 64‐year‐old woman with Parkinson's disease who developed motor fluctuations, and both levodopa‐induced and stimulation‐induced dyskinesia, after long‐term treatment of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), underwent implantation of additional globus pallidus internus (GPi) DBS leads. Although an appropriate DBS target should be chosen, “rescue” GPi DBS can synergistically work with pre‐existing STN DBS for the treatment of dyskinesia, which might provide a “third honeymoon.”
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Deep brain stimulation (DBS) refers to a neurosurgical process in which electrical stimulation is delivered via electrodes implanted within deep brain regions. DBS has become the most established clinical therapy for patients with movement disorders, although recent studies have investigated its application in a broad range of neurological and psychiatric disorders as well. Moreover, DBS has proven effective in controlling symptoms in patients with Parkinson's disease (PD). While early DBS systems were capable of stimulation only, technological advancements have allowed for the direct assessment of dysfunctional brain activity and subsequent stimulation of the pathological circuitry. DBS can also be combined with neurochemical stimulation to address decreased concentrations of dopamine in the brain. Given that both electrical and neurochemical treatments for PD aim to rectify abnormalities in neural activity, the general term "neuromodulation" is considered more accurate and comprehensive. Recent improvements in signal detection and information processing techniques have provided further insight into PD mechanisms, which may aid in the development of personalized biomarkers and in the prediction of symptoms. In this comprehensive review, we discuss various aspects of neuromodulation in patients with PD, including basic theories, stimulation paradigms, and current challenges in the field.
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A 68-year-old man with Parkinson's disease (PD) had bilateral GPi DBS placed for management of his motor fluctuations. He developed stimulation-induced dyskinesia (SID) with left dorsal GPi stimulation.What do we know about SID in PD patients with GPi DBS? What are the potential strategies used to maximize the DBS therapeutic benefit and minimize the side effects of stimulation?Avoiding the contact implicated in SID and programming more ventral contacts, using lower voltage, frequency and pulse width and programming in bipolar configuration all appear to help minimize the SID and provide appropriate symptomatic motor control.Little is known about SID in patients with PD who had GPi DBS therapy. More studies using volume of tissue activated and diffusion tensor imaging MRI are needed to localize specific tracts in or around the GPi that may be implicated in SID.
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