Deep brain stimulation in dystonia

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.     

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.     

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 in the management of Parkinson's disease

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease and other movement disorders. This surgical technique is applied to three brain targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internus (Gpi) and the subthalamic nucleus (STN). Vim DBS improves contralateral parkinsonian tremor. STN and GPi DBS improve contralateral bradykinesia, rigidity, parkinsonian tremor and also levodopa-induced dyskinesia. There is little comparative data between bilateral STN and bilateral GPi procedures but the improvement with bilateral STN DBS seems more pronounced than with bilateral GPi DBS. Moreover, only STN BDS allows a significant decrease of antiparkinsonian medication. The other advantage of STN over GPi DBS is the lower consumption of current. The DBS procedure contrary to ablative surgery has the unique advantage of reversibility and adjustability over time. Patients with no behavioral, mood and cognitive impairments benefit the most from bilateral STN DBS. The stimulation-induced adverse effects related to DBS are reversible and adjustable. More specific adverse effects related do hardware are: disconnection, lead breaking, erosion or infection. The disadvantage of DBS is a relatively high cost. The setting of stimulation parameters to achieve the best clinical result may be very time-consuming. Most authors agree that DBS is a safer and more favorable procedure than ablative surgery.     

Long‐Term Follow‐Up Study of Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Cervical Dystonia

Objectives. Medically refractory cervical dystonia has recently been treated using deep brain stimulation (DBS), targeting the subthalamic nucleus (STN). There has been limited literature regarding short‐term outcomes and no literature regarding long‐term outcomes for refractory cervical dystonia following DBS of the STN. Materials and Methods. Two patients with medically refractory cervical dystonia underwent STN DBS. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and immediately postoperatively as well as just prior to turning on the stimulators and subsequently at 24–48 hours, six months, one, two, and three years after stimulation. Microrecordings were used to identify the STN and substantia nigra reticulata (SNr). Results. Significant immediate and sustained long‐term improvements were seen in motor, disability, pain, and total TWSTRS scores. In one patient, only unilateral stimulation was required. The STN and SNr were easily identified as having activity similar to off‐state Parkinson's patients. Conclusions. DBS therapy for cervical dystonia utilizing the STN as the surgical target may be novel and may be an alternative target to the globus pallidus internus as supported by this first long‐term outcome report. Further studies need to be performed to confirm these conclusions.     

Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review

Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40–50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy.     

Deep brain stimulation in the treatment of movement disorders]

The introduction of deep brain stimulation (DBS) was a historical step forward for the treatment of advanced and medically intractable movement disorders that include Parkinson's disease, dystonias, essential tremor, and Holmes' tremor. DBS is able to modulate the target region electrically in a reversible and adjustable fashion in contrast to an irreversible and destructive lesioning procedure. In the treatment of movement disorders, the potential targets are the thalamic ventral intermediate nucleus (Vim), globus pallidus internus (GPi), subthalamic nucleus (STN), pedunculopontine nucleus (PPN), and thalamic Vo-complex nucleus. With the development of DBS technology and stereotactic neurosurgical techniques, its therapeutic efficacy has been increased while reducing surgical complications. DBS has become an established therapy for disabling movement disorders and is currently being used to treat neuropsychiatric disorders.     

Surgery for Dystonia and Tremor

Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia. Essential tremor is quite amenable to DBS, though the response of other forms of postural and kinetic tremor is not nearly as robust or consistent based on available evidence. Regarding targeting, DBS lead placement in the globus pallidus internus has shown marked efficacy in dystonia reduction. The subthalamic nucleus is an emerging target, and increasing evidence suggests that this may be a viable target in dystonia as well. The ventralis intermedius nucleus of the thalamus is the preferred target for essential tremor, though targeting the subthalamic zone/caudal zona incerta has shown promise and may emerge as another option in essential tremor and possibly other tremor disorders. In the carefully selected patient, DBS and lesioning procedures are relatively safe and effective for the management of dystonia and tremor.     

Deep brain stimulation therapy for involuntary movements]

During the last decade, it has become clear that deep brain stimulation (DBS) therapy provides a dramatic improvement in the symptoms of movement disorders. We have experienced DBS in 110 patients with various types of involuntary movements, and confirmed the benefits of stimulation of the thalamic nucleus ventralis intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN) in these patients. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait disturbance are often induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. DBS of the Vim also provides excellent control of post-stroke involuntary movements, including hemiballism and hemichoreoathetosis. Dystonia in young patients is controlled effectively by DBS of GPi. Ablative procedures for control of involuntary movement disorders, such as thalamotomy and pallidotomy, always carry a risk associated with creating additional lesions in an already damaged brain. In contrast, there is not such a risk in DBS therapy. This modality of therapy is an important option in treating involuntary movements.     

Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson's disease.

We investigated the control of movement in 12 patients with Parkinson's disease (PD) after they received surgically implanted high-frequency stimulating electrodes in the subthalamic nucleus (STN). The experiment studied ankle strength, movement velocity, and the associated electromyographic patterns in PD patients, six of whom had tremor at the ankle. The patients were studied off treatment, ON STN deep brain stimulation (DBS), on medication, and on medication plus STN DBS. Twelve matched control subjects were also examined. Medication alone and STN DBS alone increased patients' ankle strength, ankle velocity, agonist muscle burst amplitude, and agonist burst duration, while reducing the number of agonist bursts during movement. These findings were similar for PD patients with and without tremor. The combination of medication plus STN DBS normalized maximal strength at the ankle joint, but ankle movement velocity and electromyographic patterns were not normalized. The findings are the first to demonstrate that STN DBS and medication increase strength and movement velocity at the ankle joint.     

Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson’s disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission. Received in revised form: 27 April 2006     

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).     

Gait disturbance and deep brain stimulation

Gait disturbance, one of the axial symptoms, is caused by various disorders, including basal ganglia disease. Deep brain stimulation (DBS) has widened the spectrum of therapeutic options for patients with gait disturbance due to Parkinson disease and dystonia. In gait disturbance caused by basal ganglia disease, the main targets of DBS are the subthalamic nucleus (STN) and globus pallidus internus (GPi). STN DBS is more than GPi DBS effective for treating levodopa-responsive parkinsonian symptoms, including gait disturbance. GPi DBS is effective for the treatment of primary segmental or generalized dystonia. The pedunculopontine tegmental nucleus (PPN), which is involved in locomotion, is one of the new targets for treating gait disturbance in Parkinson disease. We review DBS in the treatment of gait disturbance due to Parkinson disease and dystonia.     

Painful cervical dystonia triggered by the extension wire of a deep brain stimulator

Deep brain stimulation (DBS) can be complicated by adverse events, which are generally classified as surgical-hardware or stimulation-related. Here we report the onset of a painful cervical dystonia probably triggered by the extension wire of a subthalamic nucleus (STN)–DBS device in a woman suffering from advanced Parkinson’s disease (PD). Two months after implantation of the STN–DBS device, our patient developed a painful cervical dystonia, which was not responsive to neurostimulation or to medication. No sign of infections or fibrosis was detected. A patch test with the components of the device was performed, revealing no hypersensibility. The patient was referred back to surgery to reposition the pulse generator in the contralateral subclavian region. A deeper channeling of the wire extensions produced a complete remission of the painful dystonia.     

脑深部电刺激治疗运动障碍病276例病例分析

目的 分析276例运动障碍病(MD)的脑深部电刺激(DBS)治疗效果和经验.方法 276例MD患者接受421侧DBS植入手术治疗.其中含帕金森病(PD)232例,原发性震颤(ET)7例,肌张力障碍(DT)25例,抽动秽语综合征(TS)5例,Meige综合征等其他病例7例.结果 PD患者UPDRS运动功能评分(关状态)平均改善率45.6%.手术后非运动症状(NMS)出现频数明显下降的是:疼痛、感觉异常、失眠、多梦、不安腿、体质量下降.ET患者双上肢震颤完全停止(单侧DBS手术者除外).DT患者BFM改善率22.0%～95.8%,个体间差异较大.TS患者YGTSS综合评分改善率43.2%.强迫症状明显减轻.结论 DBS是有肯定疗效的MD治疗手段,但许多问题值得探讨.DBS可以使PD患者一部分NMS症状和TS患者强迫症状得到改善,对于情感障碍的治疗有借鉴意义.DBS对于原发性DT有较好的疗效,但对于继发性和不同分布特点的DT,缺乏预实验确定手术适应证,也没有对照研究确定最佳DBS靶点.     

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.     

Deep brain stimulation for camptocormia in dystonia and Parkinson’s disease

Camptocormia, or “bent spine syndrome”, may occur in various movement disorders such as primary dystonia or idiopathic Parkinson’s disease (PD). Although deep brain stimulation (DBS) is an established treatment in refractory primary dystonia and advanced PD, few data are available on the effect of DBS on camptocormia comparing these two conditions. Seven patients (4 with dystonia, 3 with PD; mean age 60.3 years at surgery, range 39–73 years) with camptocormia were included in the study. Five patients underwent bilateral GPi DBS and two patients underwent bilateral STN DBS guided by CT-stereotactic surgery and microelectrode recording. Pre- and postoperative motor assessment included the BFM in the dystonia patients and the UPDRS in the PD patients. Severity of camptocormia was assessed by the BFM subscore for the trunk at the last available follow-up at a mean of 17.3 months (range 9–36 months). There were no surgical complications. In the four patients with dystonia there was a mean improvement of 53% in the BFM motor score (range 41–79%) and of 63% (range 50–67%) in the BFM subscore for the trunk at the last available follow-up (mean 14.3 months, range 9–18 months). In the three patients with camptocormia in PD who underwent bilateral STN DBS (2 patients) or pallidal DBS (1 patient), the PD symptoms improved markedly (mean improvement in the UPDRS motor subscore stimulation on/medication off 55%, range 49–61%), but there was no or only mild improvement of camptocormia in the two patients who underwent STN DBS, and only moderate improvement in the patient with GPi DBS at the last available follow-up (mean 21 months, range 12–36 months). GPi DBS is an effective treatment for camptocormia in dystonia. The response of camptocormia to chronic STN or GPi DBS in PD is more heterogenous. The latter may be due to a variety of causes and needs further clarification.     

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 and medication for parkinsonian tremor during secondary tasks.

This study examined the efficacy of subthalamic nucleus (STN), deep brain stimulation (DBS), and medication for resting tremor during performance of secondary tasks. Hand tremor was recorded using accelerometry and electromyography (EMG) from 10 patients with Parkinson's disease (PD) and ten matched control subjects. The PD subjects were examined off treatment, on STN DBS, on medication, and on STN DBS plus medication. In the first experiment, tremor was recorded in a quiet condition and during a cognitive task designed to enhance tremor. In the second experiment, tremor was recorded in a quiet condition and during isometric finger flexion (motor task) with the contralateral limb at 5% of the maximal voluntary contraction (MVC) that was designed to suppress tremor. Results showed that: (1) STN DBS and medication reduced tremor during a cognitive task that exacerbated tremor, (2) STN DBS normalized tremor frequency in both the quiet and cognitive task conditions, whereas tremor amplitude was only normalized in the quiet condition, (3) a secondary motor task reduced tremor in a similar manner to STN DBS. These findings demonstrate that STN DBS still suppresses tremor in the presence of a cognitive task. Furthermore, a secondary motor task of the opposite limb suppresses tremor to levels comparable to STN DBS.     

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.