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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 8  |  Page : 187-195

Deep Brain Stimulation for Tremor and Dystonia

Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication5-Dec-2020

Correspondence Address:
Prof. Manmohan Singh
Room No 715, C N Centre, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.302472

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 » Abstract 

Deep brain stimulation (DBS) is the most commonly used surgical treatment for drug-refractory movement disorders such as tremor and dystonia. Appropriate patient selection along with target selection is important to ensure optimal outcome without complications. This review summarizes the recent literature regarding the mechanism of action, indications, outcome, and complications of DBS in tremor and dystonia. A comparison with other modalities of surgical interventions is discussed along with a note of the recent advances in technology. Future research needs to be directed to understand the underlying etiopathogenesis of the disease and the way in which DBS modulates the intracranial abnormal networks.

Keywords: Deep brain stimulation, dystonia, neuromodulation, review, stimulation, tremor
Key Message: DBS is currently the surgical procedure of choice for selected cases of drug refractory tremor and dystonia. Technological advances in hardware and improved target localization techniques have further cemented the role of DBS as compared to other surgical techniques.

How to cite this article:
Singh M, Agrawal M. Deep Brain Stimulation for Tremor and Dystonia. Neurol India 2020;68, Suppl S2:187-95

How to cite this URL:
Singh M, Agrawal M. Deep Brain Stimulation for Tremor and Dystonia. Neurol India [serial online] 2020 [cited 2021 Sep 28];68, Suppl S2:187-95. Available from:

Surgical treatment of movement disorders initially started with the ablation of stereotactically localized intracranial targets.[1],[2] But several surgical complications were observed due to the uncontrolled irreversible lesioning of a critical brain structure.[1],[2] Technological advances led to the development of deep brain stimulation (DBS) as an alternative.[1],[2] DBS involves the delivery of current or stimulation to distinct intracranial targets via the stereotactic implantation of electrodes. It is a reversible procedure whose effects can be titrated by changing the stimulation settings. After initial positive reports in the 1990s,[3],[4] DBS has now become the surgical procedure of choice for movement disorders. FDA approval for DBS was first granted in 1997 for essential tremor and Parkinson related tremor, followed by more generalized cases of Parkinson disease (PD) in 2002 and on humanitarian grounds for dystonia in 2003.[2],[5] PD has become the most well-known indication for DBS, However, over the last two decades DBS has proven to be very effective for ET and dystonia as well.

ET is the commonest form of adult movement disorder.[6],[7],[8] It is a progressive disease which predominantly affects the distal extremities and can significantly worsen the quality of life of a patient.[6],[7],[8],[9] Pharmacotherapy in the form of propranolol and primidone have been used for treatment, but more than half of these patients derive no benefit or eventually become drug refractory.[10] Surgery offers an effective treatment alternative for such patients. Tremor related to other causes such as PD, multiple sclerosis, and dystonia has also been successfully treated.[11],[12],[13]

Dystonia causes abnormal repetitive movements and posturing of muscle groups which may be sustained.[14] A recent consensus statement classified dystonia syndromes as per clinical features (age of onset, body distribution, temporal evolution, other co-existing movement disorders, and neurological deficits) and etiology (genetic, idiopathic, or acquired/secondary).[15] The definite etiopathogenesis of dystonia is unproven. Thus there is no verified treatment of choice for dystonia.[16] Botulinum injections and medications such as trihexyphenidyl and clonazepam provide symptomatic relief only.[16] Surgical interventions like DBS target the underlying abnormal disease network and has been shown to be effective in appropriately chosen patients.[16]

 » Mechanisms of Action of DBS Top

The exact mechanism of action of DBS in movement disorders remains unknown. Several hypotheses have been proposed based on various techniques such as animal models, microdialysis, functional imaging, and computational modeling. Animal models were initially used to provide evidence for its use. PD was iatrogenically induced by injecting a toxin (MPTP - 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) which selectively damaged dopaminergic neurons in the subtahalamic nucleus. Symptoms in such animals were seen to improve by the use of high-frequency stimulation,[17] which was thought to inhibit abnormal motor activity in the basal ganglia. The applied electrical field results in the opening or closing of ionic channels, causing action potentials and the release of specific neurotransmitters.[1],[18] Constant application of the external current blocks the intrinsic activity of the target area, resulting in a phenomenon known as ‘information blockade’.[18],[19] High-frequency stimulation has also been seen to inhibit the synaptic transmission of the abnormal low-frequency oscillations seen in movement disorders.[18],[19] Recently, it has been identified that astrocytes might play an effect on neurotransmitter release and long-term synaptic plasticity to modify the effects of DBS.[18],[19],[20],[21] Movement disorders are caused due to an abnormality in the corticobasal ganglia thalamocortical loop. It is increasingly been understood that recognition and modulation of the network, which is unique to each patient, might hold the key to effective intervention.[22] DBS modulates this network in a positive fashion, the exact mechanism of which remains to be definitely proven.

 » Indications Top

Optimal patient selection is a complex process and is essential in order to ensure favorable postoperative outcomes.[23] The symptoms should be disabling as assessed by validated scoring scales (Clinical Rating Scale for Tremor – CRST[24] and Burke-Fahn-Marsden Dystonia Rating Scale – BFMDRS[25]). The patients should be drug refractory and medically fit to be able to tolerate an invasive procedure. Premorbid psychiatric conditions or cognitive dysfunction should be ruled out.[26] Fixed skeletal deformities, spasticity and myelopathy should be documented. MRI should be screened for any structural abnormality.[27]

1. Tremor:

ET predominantly affecting the distal part of the upper limbs responds best to DBS. Proximal tremor may be difficult to treat.[28] Complex tremors such as associated with multiple sclerosis and dystonia can show variable response,[10],[11],[12],[13] and thus, should be differentiated preoperatively to prognosticate patients adequately.

2. Dystonia:

Isolated and generalized idiopathic dystonia, predominantly affecting the neck, trunk, and limbs has been seen to respond best to DBS.[23],[29] It has also been effective in alleviating dystonia associated with PD, and focal dystonia such as writer's cramp, musician's dystonia, and cervical dystonia.[27],[30],[31] Outcome has been seen to be poorer with secondary dystonia.[23],[32] Specific preoperative evaluation includes the exclusion of conditions that would respond more favorably to pharmacological treatments, such as levodopa trial to rule out dopamine responsive dystonia and tests for Wilson's disease.[23],[32],[33] Genetic predictors of response to stimulation like the presence of DYT-1 gene in primary dystonia, DYT-11 in early-onset dystonia and DYT-11 gene in dystonia associated with myoclonus, should be assessed to prognosticate patients accordingly.[23],[32]

Intracranial targets

1. Tremor:

The target described for use in patients with a tremor has been the ventral intermediate nucleus (VIM) of the thalamus. The  Atlas More Details-based co-ordinates for localizing the VIM have traditionally been identified as 13–15 mm lateral and 5 mm posterior to the mid-commissural point (MCP) at the level of the line joining the anterior and posterior commissures (AC/PC line).[33] [Figure 1]
Figure 1: Schalterbrand atlas (in blue) superimposed on the patient's axial (a) and parasagittal (b) inversion recovery image. Target is marked in red. (MCP – midcommissural point, VIM – ventral intermediate nucleus)

Click here to view

Direct targeting, which is based upon the visualization of the target on each patient's individual MRI, is more commonly utilized. Studies have been undertaken to identify the exact region within the thalamus which can result in ideal outcome with no complications. Cerebello thalamic tract (CTT) in the posterior subthalamic area (PSA) were shown to have a high density of clinically relevant fibers for targeting.[34] Researchers found that leads positioned in the ventral part of VIM, i.e., the distal contacts were better as compared to the proximal contacts.[35],[36] These contacts were stimulating the CTT in the PSA. Studies comparing PSA and VIM DBS have shown the requirement of a lower stimulation amplitude for PSA DBS, a greater distal as well as proximal tremor improvement, with a comparable complication rate.[37] In a randomized double-blind trial with one year of follow-up, greater tremor and quality of life (QoL) improvement was seen with PSA as compared to VIM stimulation.[38] However, few researchers have found no clear benefit of PSA stimulation over VIM. In a retrospective study evaluating 19 patients with 38 implanted electrodes (12-VIM, 12-PSA, and 14-intermediate), authors found 63% tremor reduction in the VIM group, 47% in the PSA group and 67% in the intermediate group. No significant difference was observed in between groups.[39]

2. Dystonia:

Postero ventral lateral portion of the globus pallidus interna (GPi) is the most commonly used target site for DBS. Atlas-based co-ordinates for GPi are 19-22 mm lateral and 2 mm anterior from MCP and 4 mm ventral to AC/PC line[33] [Figure 2]. Other targets such as STN, thalamus and cerebellum have been used with varying success.[40],[41],[42] These may have a role depending upon the type of dystonia being treated. A retrospective cohort study evaluating 14 patients with GPi-DBS and 16 with STN-DBS found the former better for alleviating axial symptoms (93% vs 83% improvement in the axis sub score of BFMDRS). On the other hand, STN-DBS warranted lesser delivery of electrical energy ((124 ± 52 vs 192 ± 65 μJ) which led to lesser battery consumption.[40]
Figure 2: Schalterbrand atlas (in orange) superimposed on the patient's axial (a) and coronal (b) T2W image, depicting the GPi target on the right (blue trajectory) and left (yellow trajectory)

Click here to view

Vim-DBS has been described for patients with dystonic tremor.[41] Recently, deep anterior cerebellar lobe DBS has been used with some success in patients with cerebral palsy associated spastic dystonia.[42]


1. Tremor:

The first reports of high-frequency stimulation in six patients with essential tremor were published in a landmark study by Benabid et al.[43] Since then several studies on DBS for ET have shown favorable results.[44] A recent meta-analysis involving 1714 patients from 46 studies showed a pooled improvement in tremor scores of 61.3% at a mean follow-up of 20.0 ± 17.3 months.[45] Others have analyzed the predictors of clinical benefit and found that best outcomes are seen in older patients with greater baseline severity of disease who were unresponsive to benzodiazepine treatment.[46]

The studies reporting long-term efficacy more than two years have been compiled.[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58] [Table 1] Although favorable outcome is maintained, some loss of efficacy has been seen over time with a significant gradual increase in stimulation parameters.[55] This phenomenon has been associated with various factors, chief amongst which are the natural progression of the disease process and habituation to stimulation.[19],[59]
Table 1: Long term (>2 years) outcome after DBS for essential tremor

Click here to view

A recent study assessed the long-term outcomes with VIM-DBS in 26 patients with dystonic tremor (DT) and 97 patients with ET. They found significant improvement in rating scale scores up to 52.2% at 4-5 years of follow-up in both the cohorts. The improvements seen in activities of daily living were not sustained in the DT group, probably because of the co-existent dystonia.[11]

Tremor associated with multiple sclerosis has seen moderate improvements with DBS.[60] Dual lead DBS targeting the VIM and ventralis oralis (VO) was performed in 12 patients. A 29.6% reduction in tremor scores was noted at six months follow-up.[12]

Improvements in head and voice tremor were observed in 9/10 and 6/7 patients respectively at a mean follow-up of 10 months following bilateral DBS of the thalamus.[61] Similar significant improvement was observed in another prospective study.[62]

Limited evidence in the form of case reports and case series is also becoming available showing the efficacy of DBS in tremor due to uncommon causes like Holmes tremor, orthostatic tremor and tremor due to genetic etiology.[63] Further clarification is needed to define the selection criteria and appropriate targets.

2. Dystonia:

Class I evidence in the form of an RCT published in 2006 had 20 patients in the treatment group and an equal number in the sham group.[64] After three months of the procedure, significantly greater degree of improvement was observed in the GPi stimulation group (-15.8 points) as compared to the sham group (-1.4 points). Overall 75% in the treatment group had a favourable outcome and patients who switched over to active treatment also showed similar benefits. Dysarthria (n = 5) and infection (n = 4) at stimulator site were the most common adverse effects. Upon long-term follow-up of five years of the same cohort of patients, a sustained good outcome was seen in 30 (83%) of 36 patients at 6 months, 29 (94%) of 31 at 3 years, and 26 (81%) of 32 patients.[65]

A recent meta-analysis of 523 patients showed 65.2% improvement in BFMDRS score at a mean follow-up of 32.5 months. A 58.6% improvement in the disability score was observed as well. Higher pre-operative motor scores and younger age at surgery were found to be significant predictors of improved outcomes.[66] Similarly improvement was also reported in a meta-analysis of pediatric patients (n = 321) in which the authors co-related older age at onset of dystonia, idiopathic dystonia, inherited dystonia without neurological pathology and truncal involvement to better postoperative outcome.[67]

A retrospective analysis of outcome in three patients with DYT-6 mutation vs 23 patients with DYT-1 mutation showed better outcomes in the latter group.[68] Another comparative multicentre study in GPi-DBS showed best improvement of 60% in BFMDRS score in patients with DYT-1 mutation (9 patients), followed by 52% in the non-DYT group (38 patients). The least improvement was seen in the DYT-6 group (32% - 8 patients).[32] However at long-term follow-up (22–92 months) no significant difference in the rate of improvement between the three groups could be observed.[32] Earlier intervention, absence of fixed skeletal deformities and younger age at surgery have all been correlated to a favorable outcome, especially in DYT-1 cases.[32],[66],[69],[70],[71]

An RCT was conducted for DBS in cervical dystonia including 60 patients.[72] At 3 months, a significant reduction in dystonia severity was seen with stimulation (–5·1 points [SD 5·1], 95% CI –7·0 to –3·5) as compared to sham group (–1·3 [2·4], –2·2 to –0·4, P = 0·0024). Dysarthria was the most commonly observed side effect.

Craniocervical dystonia is also effectively treated using DBS.[73],[74] An analysis of 75 patients revealed 66.9% improvement in BFMDRS motor score and 56% improvement in disability score. No correlation was seen with the age at onset and disease duration.[73] This improvement has been sustained at long-term follow-up as seen in six patients with 53% improvement in various sub scores maintained at five years after surgery.[74] Other forms of dystonia such as blepharospasm have shown quick resolution after DBS.[75] Thalamic (ventralis oralis/ventralis intermedius) DBS has been found to be more effective than GPi DBS in treating writer's cramp.[76]

A review was published on myoclonic dystonia of the upper extremities, which combined the results of DBS in 40 patients from various case reports.[77] 93.5% of patients showed at least a 50% improvement in UMRS (myoclonus scores), while 72.7% showed at least a 50% improvement in BFMDRS. Improvements in myoclonus scores were similar for both GPi (75.7%) and VIM (70.4%), while the recovery in dystonia scores was more with GPi (60.2%), as compared to VIM (33.3%).[77]

An RCT has shown the efficacy of pallidal DBS for tardive dystonia/dyskinesia.[78] A review of the literature identified 117 patients with tardive dyskinesia.[79] At a mean follow-up of 25.6 months, 62 ± 15% improvement was seen in 51 patients reporting the Abnormal Involuntary Movement Scale, while 76 ± 21% improvement was observed in 67 cases reporting the BFMDRS.[79]

DBS used in other secondary causes of dystonia like trauma, stroke, neurodegenerative diseases has shown heterogenous results.[80],[81],[82]

Recently DBS has even been used to status dystonicus. A series of five patients with DYT-1 positive status dystonicus treated with DBS showed significant improvement in four patients. Extubation time was shorter as compared to other case reports of pharmacological treatment alone.[83],[84] In another series, surgery was performed on five patients, who all improved within 1–7 days after surgery, with no recurrence.[84]

Cognitive benefits have been observed in patients undergoing GPi DBS. In a study including 12 patients (8 – focal, 4 – generalized dystonia), with a mean follow-up of 13.1 months, statistically significant improvement was noted in working memory, executive functioning, anxiety, and depression.[85] Other studies have found that GPi-DBS has no effect on neuropsychiatric symptoms or cognition.[86] A recent systematic review of 610 patients with various types of dystonia found an improvement in physical quality of life but not so much when considering the mental QoL.[40]

 » Complications Top

Surgical complications include the risk of intracranial hemorrhage and stroke which has been seen to range from 0-4% for all DBS patients.[69],[87] In a large series of 728 patients, the incidence of asymptomatic intracerebral hemorrhage was 0.5% (4 patients), symptomatic intracranial hemorrhage was 1.1% (8 patients), intraventricular hemorrhage was 3.4% (25 patients) and infarction was 0.4% (3 patients). Seizures were seen in 2 patients (0.3%).[87] Mortality rate of 0.4% in the first 30 days following surgery has been reported, due to pneumonia, pulmonary embolism, hepatic failure and severe multiple sclerosis.[88]

Hardware-related complications such as lead breakage and implant extrusion have also been reported in up to 25% of cases.[87],[89],[90] This usually requires additional surgery to correct. These complications have been more frequently seen in dystonia as compared to PD, because of the increased risk with abnormal movements of the head and neck.[69],[90] The incidence of device infection is variable, and maybe seen in up to 10% of cases.[69],[88],[91],[92] Management usually includes explantation, although it has also been reported to have been managed with antibiotics alone.[93]

Stimulation related side effects are related to the electrodeposition and the surrounding areas which get activated by the delivered current, and are thus distinct for different targets.

GPi shares proximity to the internal capsule, which can cause motor adverse effects such as dysarthria and abnormal gait. Indeed, these are the two most common complications seen with GPi-DBS.[64],[65] The optic tract lies below the target and surgeon has to be careful not to injure it inadvertently.[33]

The VIM nucleus is an extremely small structure and cannot be clearly visualized on structural MRI.[94] It is surrounded by critical structures like the corticospinal tract (CST) and medial lemniscus (ML).[34],[95] VIM-DBS has been associated with complications related to these structures which includes dysarthria (3-18%), paraesthesia (6–36%), ataxia (3-8%) and limb weakness (4–8%).[45],[49]

 » Comparison with Other Surgical Modalities Top

For any other surgical technique to replace DBS as the procedure of choice for refractory ET, it has to prove itself as at par, if not better than DBS. Comparative studies between radiofrequency ablation (RFA) and DBS for tremor have reported better improvement in function and fewer adverse effects with DBS.[96] Long-term follow-up of patients undergoing DBS and RFA respectively has shown some decrease in efficacy with time, albeit lesser in the DBS group.[97] Ablative procedures have traditionally been shown to have significant corticobulbar adverse effects such as dysphagia, dysarthria and effects on cognition, especially with bilateral procedures.[98],[99] However, a recently published cases series comparing GPi DBS to pallidotomy showed comparable efficacy with both. Long-term hardware related complications were seen in 37.5% cases after DBS, while no surgical complications were noted with pallidotomy.[100] Drug refractory secondary dystonia has also been successfully treated with pallidotomy.[101] It has been found to be extremely cost-effective when compared to DBS.[102] Ablative procedures are the procedure of choice in resource constrained countries, on in patients with fixed contractures or thin body habitus who are otherwise unfit to undergo device implantation.[16]

Gamma knife thalamotomy (GKT) was first described in the 1990s. It's a non-invasive procedure and its efficacy has been proven in a few prospective studies.[103],[104] Some case reports on the use of GKT for dystonia have been published.[105] But the inability to monitor real time clinical response, variation in the size of the lesion produced, unpredictable radiation effects and a delay in clinical response have resulted in GKT being reserved for patients who are otherwise unfit for DBS.[106]

Another recently adopted surgical modality is MR-guided focused ultrasound (MRgFUS).[107],[108] Some of the advantages of this technique over the other available procedures include non-invasiveness, with real time control over the target and temperature at which the lesion is created, the ability to monitor patient response while creating the lesion, no hardware related complications and no need for repeat patient visits for programming.[109] In a retrospective analysis of RFA, DBS and MRgFUS for ET, outcomes and complication rates of the procedures between the three groups were not statistically different.[110] A recent study,[111] compared a trial on the use of VIM DBS for ET,[112] with the RCT done by Elias et al.[108] They found a greater percentage improvement with DBS, although the patients in DBS group had worse baseline tremor scores. The MRgFUS group had increased incidence of neurological complications as compared to the DBS group, although trajectory related complications were more in the latter.

ET and dystonia are usually progressive disorders, with most patients having bilateral symptoms with time.[14],[113] DBS has proven efficacy with bilateral implantation, while the lesioning procedures have primarily been utilized for unilateral pathology only.

 » Recent Advances and Future Direction Top

DBS hardware

Technological advances in order to increase the longevity of the implant and to improve current delivery to the target site are rapidly being made.[1],[114] The battery sizes have considerably decreased in the past decade, with contouring to facilitate easy implantation. Innovative miniature generators which may even be implanted in the skull are being designed.[1],[114] Rechargeable batteries with longer lifespan are being increasingly used. Thus physicians donot have to worry about early battery drainage while treating more severe forms of disease.[1]

Adaptive closed-loop DBS which can provide on demand stimulation after recognizing abnormal oscillations within the cortico-basal ganglia network has been developed recently.[115] The concept of segmented and directional leads has been developed in order to be able to modify the stimulation fields at the implanted site guided by individualized patient outcome and complications.[116]

Targeting techniques

Advances in hardware can only be effective as long as the target is accurate. Technological advances in MRI techniques have led to a better visualization of the targets.[117] Preliminary studies using DTI have led to delineation of the target along with the surrounding critical tracts, and have demonstrated improved outcome and reduced side effect profile as compared to traditional atlas based targeting.[95] Some limitations which need to be overcome are the standardization of DTI tracking method and software, seamless integration of the planning system with DTI, a need for specialized personnel trained in technical aspects and troubleshooting of DTI.

Computational models have been developed to aid in the positioning and programming of electrodes and predict outcomes.[118] The concept of volume of tissue activated has been developed to provide optimal coordinates for lead implantation.[119]

 » Conclusion Top

DBS is currently the surgical procedure of choice for selected cases of drug-refractory tremor and dystonia. Technological advances in hardware and improved target localization techniques have further cemented the role of DBS as compared to other surgical techniques. Further research needs to be directed to understand the underlying etiopathogenesis of the disease and the way in which DBS modulates the abnormal involved network.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

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