Neurosurg Focus 17 (1):E2, 2004, Click here to return to Table of Contents Deep brain stimulation in the treatment of dyskinesia and dystonia HIROKI TODA, M.D., PH.D., CLEMENT HAMANI, M.D., PH.D., AND ANDRES LOZANO, M.D., PH.D., F.R.C.S.(C) Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Ontario, Cananda Deep brain stimulation (DBS) has become a mainstay of treatment for patients with movement disorders. This modality is directed at modulating pathological activity within basal ganglia output structures by stimulating some of their nuclei, such as the subthalamic nucleus (STN) and the globus pallidus internus (GPi), without making permanent lesions. With the accumulation of experience, indications for the use of DBS have become clearer and the effective- ness and limitations of this form of therapy in different clinical conditions have been better appreciated. In this review the authors discuss the efficacy of DBS in the treatment of dystonia and levodopa-induced dyskinesias. The use of DBS of the STN and GPi is very effective for the treatment of movement disorders induced by levodopa. The relative ben- efits of using the GPi as opposed to the STN as a target are still being investigated. Bilateral GPi stimulation is gain- ing importance in the therapeutic armamentarium for the treatment of dystonia. The DYT1 forms of generalized dys- tonia and cervical dystonias respond to DBS better than secondary dystonia does. Discrimination between the diverse forms of dystonia and a better understanding of the pathophysiological features of this condition will serve as a plat- form for improved outcomes. KEY WORDS • dystonia • dyskinesia • Parkinson disease • deep brain stimulation • stereotactic neurosurgery Long-term electrical stimulation is being used increas- movements that are caused by long-term medication treat- ingly in patients with movement disorders whose disabil- ment and disease progression. Both lesioning and high- ity continues despite medical treatment. Because of its frequency stimulation in the GPi and STN can be effective effectiveness and potential reversibility, in many regions in the treatment of these abnormal movements. of the world DBS has gradually replaced lesioning proce- Stimulation of the STN. The improvement in dyskine- dures for the treatment of PD, dystonia, and essential sias after DBS of the STN is probably related to two tremor. With the accumulation of experience, the indica- mechanisms: the first is the reduction in medication that tions for DBS have become clearer and the effectiveness often occurs after surgery and the second is a direct anti- and limitations of this form of therapy are being better dyskinetic effect. The mean levodopa-equivalent dose appreciated. Although DBS has multiple applications, we intake used preoperatively is reduced by 50 to 60% after will limit this discussion to DBS for dyskinesias induced DBS of STN.5,24,29,30,52,56,62,66,77,80 Along with this reduction in by levodopa therapy and for dystonia. medications, Unified PD Rating Scale Part IV (complica- tions of therapy) scores improve by 70 to 95% after 6 months in patients treated with STN stimulation.5,66,80 The USE OF DBS FOR LEVODOPA-INDUCED duration of dyskinesias is reduced by 70 to 85% after DBS DYSKINESIAS of the STN and there are significant improvements in both disability (by 58–93%), and motor fluctuations (by Dyskinesias induced by long-term levodopa therapy 5,16,24,29,30,33,48,52,56,62,70,75 represent one of the major limitations in the treatment 45–61%). The improvement in dyski- nesias is sustained at 5 years after surgery of the STN for of patients with PD. These involuntary choreiform and 30 dystonic drug-induced movements constitute a common DBS. problem for which the incidence is as high as 80% after 5 Stimulation of the GPi. Stimulation of the GPi has a years of treatment.58 Most patients with PD who have dys- strong, direct effect on reducing or eliminating levodopa- kinesias become significantly disabled by these abnormal induced dyskinesias that is independent of any reduction in medications after surgery.16–18,31,79 There is a 65 to 75% reduction in dyskinesia scores, and the duration of these symptoms throughout the day improves by 65 to 70% at 3 16,17,31,79 Abbreviations used in this paper: DBS = deep brain stimulation; to 6 months after pallidal DBS. The 50% reduction GP = globus pallidus; GPe = GP externus; GPi = GP internus; in dyskinesia scores remained at 3 years after pallidal PD = Parkinson disease; STN = subthalamic nucleus. DBS.18 Neurosurg. Focus / Volume 17 / July, 2004 9 Unauthenticated | Downloaded 09/30/21 03:05 PM UTC H. Toda, C. Hamani, and A. Lozano The relationship between the location of the stimulating musculature that lead to twisting and abnormal postures of 36 electrode’s contacts in the GP and the clinical effect of the neck. Dopamine D5 receptor dysfunction has been DBS is somewhat complex and controversial. The best implicated in this disorder.8,57 Compared with DYT1 and location within the GP for the treatment of dyskinesias idiopathic cervical dystonia, the responses of non-DYT1 seems to be the ventral portion of the GPi. Some groups primary dystonias and secondary dystonias to surgery are have reported that stimulation of the GPe and the dorsal variable.1,7,13,15,19,27,34,36,37,47,59,71,83 Nonetheless, several pa- border of the GPi improves akinesia and worsens dyski- tients with a variety of non-DYT1 dystonias and sec- nesias.6,17,31 The results of GPi stimulation can be op- ondary dystonias, such as those seen in Hallervorden– timized by adjusting the device’s parameters and careful- Spatz syndrome,73,80 have benefited from GPi lesioning or ly choosing among the multiple contacts on the DBS DBS.28,35,44,64,69,74,81 electrode within the GPi. Use of Stereotactic Surgery for Dystonia. The surgical Targets for the treatment of dyskinesias and PD. The treatment of dystonia has a long history, beginning in the issue of whether the GPi or the STN is a better target for 1950s. In the past, the most common target for ablation the treatment of advanced PD and levodopa-induced was the thalamus. In one of the largest series of patients dyskinesias is still debated.16,32,36,40,77 The GP is a larger with dystonia who were treated with thalamotomies, structure and there is more heterogeneity in its response to Cooper14 reported an overall improvement in 70% of surgical interventions.4 This is probably related to varia- cases. Nevertheless, his procedures varied in location tions in the position of the stimulating electrode contacts within targets, by number of lesions, number of repeated in the pallidal complex.22,45 In contrast, the STN is smaller procedures, methods of ablation, and targeted nuclei, in- and appears to provide more consistent results.46 In the cluding the nuclei ventralis oralis anterior, ventralis oralis only prospective randomized study published so far, posterior, and ventralis intermedius, and centromedian, Burchiel, et al.,10 have shown that after 1 year dyskinesias the pulvinar, and portions of the nucleus ventralis postero- were improved by 67% with DBS of the STN and by 47% lateralis. Studies in which patients with dystonia were fur- with DBS of the GPi. This difference was not statistically ther subdivided according to type have shown that thala- significant because the study was underpowered; it in- motomies improved the dystonic symptoms in 25 to 80% cluded only 10 patients. A multicenter prospective non- of patients with generalized dystonia, in 33 to 62% of randomized cross-over study showed that dyskinesia those with focal/segmental dystonia, in 35 to 60% of scores improved by 58% with DBS of the STN and by patients with primary dystonia, and in 34 to 63% of those 66% with DBS of the GPi at 6 months.16 The time spent in with secondary dystonia.2,11,21,63,65,84 The nuclei ventralis the “on” condition with dyskinesias was reduced by 69% intermedius,2,65 ventralis oralis posterior,65 and the transi- with DBS of the STN and by 65% with DBS of the GPi at tional nucleus ventralis oralis anterior/posterior,11,84 were 6 months. Randomized double-blinded trials will be nec- the most common targets chosen for ablation. The major essary to evaluate the relative effectiveness of each of limitation of thalamotomies, particularly when they were these approaches in the treatment of levodopa-induced performed bilaterally, was the high incidence of compli- abnormal movements. cations including speech problems, motor weakness, and pseudobulbar palsy.2,11, 21,63,65,84 Even though in some of the older studies the GPi has also been reported as a target,14,23 USE OF DBS FOR DYSTONIA pallidal procedures for the treatment of dystonias have only recently regained attention.26,47 Dystonia Types. Dystonia is a syndrome of sustained Stimulation of the GPi. Patients with dystonia who muscle contractions that produces twisting and repetitive have significant disability and whose condition is resistant movements and abnormal postures.20 Various forms of to pharmacotherapy are considered to be surgical candi- dystonia have been described, most of which are refrac- dates. The main advantages of pallidal stimulation over tory to medical therapies. In this context, DBS has been pallidotomy are reversibility and the ability to adjust the used to treat several of these conditions but its efficacy desired parameters of stimulation. These characteristics varies according to the type of dystonia. may be important in younger patients or patients with sec- The common form of inherited generalized primary ondary dystonia in whom structural lesions already exist dystonia is the DYT1 form (Oppenheim dystonia).