Deep Brain Stimulation for Movement Disorders

Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low—generally ≤ 5% at experienced, large-volume centers. It has been used widely in essential tremor, Parkinson’s disease, and dystonia when medical treatment becomes ineffective, intolerable owing to side effects, or causes motor complications. Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson’s disease), and globus pallidus (Parkinson’s disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of “closed loop” stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.     

脑深部电刺激治疗运动障碍性疾病的疗效观察

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

Deep brain stimulation of the Vim nucleus of the thalamus in the treatment of parkinsonian tremor

Deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (Vim) has been recently introduced by Benabid and his colleagues as a new surgical procedure in the treatment of tremor-dominant Parkinson's disease (PD). The advantage of DBS Vim over lesioning (thalamotomy) is its reversibility and adjustability with the same clinical effect, but without the need to make a destructive thalamic lesion. In this procedure high-frequency stimulation is employed to simulate a thalamic lesion using an implanted electrode connected to a subcutaneously placed neuropacemaker. Four patients with tremor-dominant PD were included in the study. There were 3 men and one women. Three stimulators were implanted in the left and one in the right cerebral hemisphere. The patients were evaluated using clinical scales, before and up to 24 months after surgery. Adverse effects associated with chronic Vim stimulation were mild and reversible. Chronic thalamic stimulation is effective for drug-resistance parkinsonian tremor suppression, with few adverse side-effects. The method results in a significant improvement of function.     

The effect of deep brain stimulation on quality of life in movement disorders

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.     

Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson’s Disease

Deep brain stimulation (DBS) is effective for Parkinson’s disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS).     

Deep brain stimulation in movement disorders

Deep brain stimulation (DBS) is used for advanced and medically intractable patients with Parkinson's disease (PD), essential tremor (ET), and dystonia who meet strict criteria after a detailed motor, cognitive, and psychiatric evaluation. The potential targets are the ventral intermediate nucleus (VIM) of the thalamus for tremor, the globus pallidus interna (GPI) and the subthalamic nucleus (STN) for PD, and GPI for dystonia. The optimal target for PD has not been determined yet, although STN DBS has been performed more frequently in recent years. The mechanism of DBS effect is believed to be associated with disruption of pathological network activity in the cortico-basal ganglia-thalamic circuits by affecting the firing rates and bursting patterns of neurons and synchronized oscillatory activity of neuronal networks. Good candidates should be free of dementia, major psychiatric disorders, structural brain lesions, and important general medical problems. Although the risk for complications with DBS is less than with lesioning techniques, there is still a small risk for major complications associated with surgery. Bilateral procedures are more likely to cause problems with speech, cognition, and gait.     

Deep brain stimulation for dystonia.

Within the past few years, there has been a renaissance of functional neurosurgery for the treatment of dystonic movement disorders. In particular, deep brain stimulation (DBS) has widened the spectrum of therapeutical options for patients with otherwise intractable dystonia. It has been introduced only with a delay after DBS became an accepted treatment for advanced Parkinson' disease (PD). In this overview, the authors summarize the current status of its clinical application in dystonia. Deep brain stimulation for dystonia has been developed from radiofrequency lesioning, but it has replaced the latter largely in most centers. The main target used for primary dystonia is the posteroventral globus pallidus internus (GPi), and its efficacy has been shown in generalized dystonia, segmental dystonia, and complex cervical dystonia. The optimal target for secondary dystonias is still unclear, but some patients appear to benefit more from thalamic stimulation. The improvement of dystonia with chronic DBS frequently is delayed, in particular concerning tonic dystonic postures. Because more energy is needed for stimulation than in other movement disorders such as PD, more frequent battery replacements are necessary, which results in relatively higher costs for chronic DBS. The study of intraoperative microelectrode recordings and of local field potentials by the implanted DBS electrodes has yielded new insights in the pathophysiology of dystonia. Larger studies are underway presently to validate the observations being made.     

Postoperative rehabilitation after deep brain stimulation surgery for movement disorders

Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy for a set of neurological and psychiatric conditions and especially movement disorders such as Parkinson’s disease, essential tremor and dystonia. Recent developments have improved the DBS technology. However, no unequivocal algorithms for an optimized postoperative care exist so far. The aim of this review is to provide a synopsis of the current clinical practice and to propose guidelines for postoperative and rehabilitative care of patients who undergo DBS. A standardized work-up in the DBS centers adapted to each patient’s clinical state and needs is important, including a meticulous evaluation of clinical improvement and residual symptoms with a definition of goals for neurorehabilitation. Efficient and complete information transfer to subsequent caregivers is essential. A coordinated therapy within a multidisciplinary team (trained in movement disorders and DBS) is needed to achieve the long-range maximal efficiency. An optimized postoperative framework might ultimately lead to more effective results of DBS.     

Closed-loop cortical neuromodulation in Parkinson’s disease: An alternative to deep brain stimulation?

Deep brain stimulation (DBS) is usually performed to treat advanced Parkinson’s disease (PD) patients with electrodes permanently implanted in basal ganglia while the stimulator delivers electrical impulses continuously and independently of any feedback (open-loop stimulation). Conversely, in closed-loop stimulation, electrical stimulation is delivered as a function of neuronal activities recorded and analyzed online. There is an emerging development of closed-loop DBS in the treatment of PD and a growing discussion about proposing cortical stimulation rather than DBS for this purpose. Why does it make sense to “close the loop” to treat parkinsonian symptoms? Could closed-loop stimulation applied to the cortex become a valuable therapeutic strategy for PD? Can mathematical modeling contribute to the development of this technique? We review the various evidences in favor of the use of closed-loop cortical stimulation for the treatment of advanced PD, as an emerging technique which might offer substantial clinical benefits for PD patients.     

Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non-Parkinson’s disease parkinsonian syndrome

Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is a useful treatment in patients with tremor-dominant Parkinson’s disease (PD). Efficacy to alleviate rigidity remains controversial. We report a 65-year-old right-handed man with persistent severe rigidity and bradykinesia on the right side despite daily administration of levodopa/carbidopa (600/60 mg). His right-hand tremor was continuous at rest and present at action. His antiparkinsonian medications appeared ineffective and he reported difficulties with writing and eating. Repeated ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy studies demonstrated a non-PD pattern. He underwent the stereotactic implantation of a DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous unipolar stimulation with a pulse generator implanted in a subclavian pocket. This improved the tremor and the rigidity and bradykinesia of his right hand. Postoperative image analysis revealed the likelihood of simultaneous stimulation of the Vim and the nucleus ventralis oralis posterior. Our findings suggest thalamic stimulation as a therapeutic option for drug-resistant rigidity (and tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at the globus pallidus internus or subthalamic nucleus.     

脑深部电刺激治疗帕金森病和特发性震颤的近期和远期疗效

自1987年以后,脑深部电刺激(deep brain stimulation,DBS)成为治疗难治性帕金森病和特发性震颤的主要外科手段。刺激的靶点最先为丘脑腹侧中间核(nucleus ventero-intermedius,Vim)。由于Vim DBS只能缓解震颤,而对于帕金森病的其他核心症状以及多巴长期应用后的不良反应,如运动波动和异动症疗效不显著,1990年后治疗PD的靶点转移到丘脑底核(subthalamic nucleus,STN)和苍白球内侧部(interal globus pallidus,GPi),上述问题在这两个靶点得到显著改善。Vim DBS仍然为治疗特发性震颤的位点。本文就这3个靶点的持续电刺激在治疗帕金森病和特发性震颤的近期和远期疗效等进行评述。     

Twiddler’s syndrome in a patient with a deep brain stimulation device for generalized dystonia

Deep brain stimulation (DBS) is the technique of neurostimulation of deep brain structures for the treatment of conditions such as essential tremor, dystonia, Parkinson’s disease and chronic pain syndromes. The procedure uses implanted deep brain stimulation electrodes connected to extension leads and an implantable pulse generator (IPG). Hardware failure related to the DBS procedure is not infrequent, and includes electrode migration and disconnection. We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed. Radiographs showed multiple twisting of the extension leads with disconnection from the brain electrodes and a diagnosis of Twiddler’s syndrome was made. Twiddler’s syndrome was first described in patients with cardiac pacemakers. Patients with mental disability, elderly and obese patients are at increased risk. Twiddler’s syndrome should be suspected whenever there is a failure of the DBS device to relieve symptoms previously responsive to stimulation. Surgical correction is usually required.     

Seventy years of pallidotomy for movement disorders

The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid‐1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa‐induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience. © 2017 International Parkinson and Movement Disorder Society     

Long-term suppression of extrapyramidal motor symptoms with deep brain stimulation (DBS)

Deep Brain Stimulation (DBS) was investigated for the treatment of extrapyramidal motor symptoms. Both tremor and rigidity as well as akinesia are known to be permanently suppressed by applying a high-frequency current to different basal ganglia nuclei. Chronic DBS was performed in 113 patients using stereotactically implanted quadripolar electrodes in the ventrolateral thalamus (n = 43), the globus pallidus internus (n = 15), or the subthalamic nucleus (n = 55). Subcutaneous implantation of the generator occurred during a second procedure following correct positioning of the electrodes and confirmation of effectiveness by external stimulation. Patients were followed up using standardized rating scales before and after surgery. Deep Brain Stimulation significantly suppresses extrapyramidal symptoms such as tremor (p < 0.001), rigidity (p < 0.001), dyskinesia (p < 0.01), akinesia, and dystonia (p < 0.05). Permanent side effects were avoided by changing the stimulation parameters. Severe complications occurred in only two patients (n = 2, 1.8 %). DBS is a safe and effective long-term treatment for tremor, rigidity, dyskinesia, akinesia and dystonia.     

脑深部电刺激治疗运动障碍性疾病

目的探讨脑深部电刺激(DBS)对帕金森病(PD)和肌张力障碍(dystonia)等运动障碍性疾病的治疗作用及手术方法。方法应用3.0TMRI和微电极导向技术及手术计划系统进行靶点定位,对40例PD病人和3例继发性肌张力障碍病人进行双侧丘脑底核(STN)电极植入。结果PD病人的主要症状有显著改善,服药量也明显减少,术前和术后UPDRS评分有显著差异;3例继发性肌张力障碍病人症状均有不同程度的改善,如以UDRS和BFMS作为评价指标,其中1例药物引起的迟发性肌张力障碍病人症状改善达90%以上;术后无严重及永久并发症。结论首次证实STN-DBS对继发性肌张力障碍是一种有效的治疗方法,双侧STN-DBS是外科治疗PD的首选方法,DBS对运动障碍性疾病的治疗已显示出良好的前景。     

Deep Brain Stimulation in Movement Disorders: From Experimental Surgery to Evidence‐Based Therapy

Deep brain stimulation (DBS) of 3 different targets is the most important therapeutic innovation of the past 30 years for patients with fluctuating Parkinson's disease (PD), disabling dystonia, tremors, and refractory Gilles de la Tourette syndrome. When compared with medical treatment alone, controlled studies have shown better motor, nonmotor, and particularly quality‐of‐life outcomes with large effect sizes for advanced complicated PD that cannot be improved with medication, and also for PD patients with only early fluctuations. Class 1 studies have also shown superiority over medical treatment for generalized, segmental, and botulinum‐toxin refractory focal cervical dystonia. Long‐term efficacy is established for all indications with open studies. For tremors, open studies have shown that DBS is remarkably effective on PD and essential tremor, but efficacy on severe essential tremor and cerebellar tremors is limited by a tendency for tolerance/habituation, including concerns about long‐term efficacy. Open studies of disabling Gilles de la Tourette syndrome show an improvement in tics. New developments hold a promise for further improvement. New hardware with directional stimulation and new stimulation paradigms are further areas of research. The targets of DBS are refined with new imaging processing that will help to diversify the surgical targets. New indications are being explored. Closed‐loop DBS using brain or peripheral sensor signals have shown favorable clinical short‐term results. Long‐term data are lacking, and it is hoped that similar approaches for other movement or behavioral disorders may be developed. Exciting new developments carry the hope for a more pathophysiology‐based approach for DBS for various brain circuit disorders. © 2019 International Parkinson and Movement Disorder Society     

Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders

The centre median-parafascicular (CM-Pf) complex of the thalamus is considered to be a possible target for deep brain stimulation (DBS) in patients with movement disorders. In a prospective study on the effect of CM-Pf DBS versus somatosensory thalamic DBS on chronic neuropathic pain, three of 12 patients had additional movement disorders. Bifocal quadripolar electrodes were implanted by computed tomography guided stereotactic surgery under local anaesthesia contralaterally to the side of the pain for test stimulation. Two of the three patients with movement disorders had permanent implantation of CM-Pf electrodes. During test stimulation of the left CM-Pf complex for several days, a 67 year old woman received no benefit with respect to the neuropathic pain, but the choreoathetotic movements of her right foot ceased. As the pain syndrome was not improved, she decided not to have permanent implantation. A 74 year old man with postzoster neuralgia and allodynia enjoyed excellent relief from his pain with chronic CM-Pf DBS. In addition, improvement in the tremor at rest was noted. A 72 year old man had sustained reduction in his stump dyskinesias. Further evaluation of the possible role of the "forgotten" central and medial thalamic nuclei in the treatment of movement disorders may be warranted.     

Advances in neurostimulation for movement disorders

In just 12 years since its introduction, deep brain stimulation (DBS) has become well established as a safe and effective therapy in the treatment of medically refractory movement disorders. Ventralis intermedius (Vim) DBS has virtually replaced thalamotomy in the routine clinical treatment of essential tremor, affording relief to thousands of patients who previously would not have undergone surgery, and there is increasing usage of Vim DBS in other tremors of intention (e.g., multiple sclerosis). Subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS have revolutionized the treatment of advanced stage Parkinson's disease, improving all cardinal disease features and increasing 'on' time without dyskinesias. Finally, DBS of various sub-cortical structures is being developed and tested in other less prevalent movement disorders such as dystonia. Future developments in this rapidly advancing area will no doubt include widening indications for this relatively safe surgical procedure, elucidation of the mechanisms of action of electrical stimulation, and technological advancements improving effectiveness and convenience.     

运动障碍病脑深部电刺激手术的并发症分析

目的分析运动障碍病脑深部电刺激(DBS)手术的并发症,探讨其原因及预防和治疗措施。方法给615例运动障碍病患者进行了1008根DBS手术,行单侧DBS手术的患者222例,双侧手术者393例。其中帕金森病患者566例,原发性震颤患者18例,肌张力障碍患者11例,痉挛性斜颈患者7例,抽动症患者9例,Meige综合征2例,其他2例。回顾性分析与手术操作或硬件故障相关的并发症。结果 615例患者术后随访1~3年,出现手术操作或硬件相关并发症的患者45例;其中出血4例,植入脉冲发生器(IPG)周围皮下积液10例,感染10例,电极位置不好9例,电极断裂10例,急性水肿1例,IPG不适重新植入1例。结论手术操作中诸多技术环节与术后并发症有关联。手术者经验的提高,可以明显减少手术并发症的发生。     

Increased risk of lead fracture and migration in dystonia compared with other movement disorders following deep brain stimulation.

Deep brain stimulation (DBS) therapy is a continually expanding field in the functional neurosurgical treatment of movement disorders. However, the occurrence of adverse events related to implanted hardware cannot be overlooked. We report on a specific feature noted in our experience of DBS-related complications. From 1998 until present we have found an overall rate of 5.3% of DBS electrode lead dysfunction (out of 133 patients) in our series (slipped leads 2.3%, lead fracture 3.8%). Interestingly, all of these failures occurred in dystonia patients (18.4% of all dystonia patients and 9.2% of all electrodes). We postulate on mechanisms that may explain why these complications predominate in this group of patients.