ORIGINAL RESEARCH

Dystonia, 19 October 2026

Volume 5 - 2026 | https://doi.org/10.3389/dyst.2026.17246

The long-term efficacy of globus pallidus deep brain stimulation in tardive dystonia and dyskinesia

  • 1. Jean and Paul Amos Parkinson’s Disease and Movement Disorders Program, Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States

  • 2. Department of Biomedical Engineering, Georgia Tech, Atlanta, GA, United States

  • 3. Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States

Abstract

Introduction:

Tardive syndromes, including tardive dystonia (TDyst) and tardive dyskinesia (TDysk), are complications of exposure to dopamine receptor blocking agents (DRBAs) and remain common despite the use of second-generation antipsychotics. Approximately one-quarter of patients exposed to DRBAs may develop TDysk. Globus pallidus internus deep brain stimulation (GPi DBS) has emerged as a therapeutic option for medically refractory TDyst and TDysk, although data on long-term outcomes and effective stimulation sites remain limited.

Methods:

We retrospectively reviewed clinical data for 18 patients with medically refractory TDyst/TDysk, who underwent GPi DBS at a single center. Clinical outcomes were assessed preoperatively and at 11.1 ± 3.2 months, 35.9 ± 5.1 months, and 62.5 ± 7.6 months follow-up using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) in patients with TDyst, Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in patients with prominent tardive cervical dystonia, and Abnormal Involuntary Movement Scale (AIMS) in patients with TDysk. Active electrode contact locations and stimulation parameters at the last follow-up were also evaluated.

Results:

The mean duration of tardive symptoms before surgery was 9.0 ± 7.9 years. BFMDRS motor scores improved significantly after GPi DBS, decreasing from 27.5 ± 8.3 preoperatively to 9.1 ± 7.5, 5.0 ± 5.8, and 4.1 ± 7.6 at follow-up visits, respectively. Axial and extremity BFMDRS subscores showed significant improvement, whereas speech, swallowing and orofacial dystonia subscores showed numerical improvement without reaching statistical significance. TWSTRS and AIMS scores also demonstrated numerical improvement with limited statistical interpretation due to the small number of available scores.

Conclusion:

GPi DBS resulted in robust and sustained long-term improvement in medically refractory TDyst, with potential benefit in TDysk. These findings support GPi DBS as a safe and effective therapeutic option for selected patients with severe treatment-refractory tardive syndromes. Earlier surgical intervention may be considered to facilitate timely symptomatic relief and durable long-term benefit.

Introduction

Tardive syndromes including tardive dystonia (TDyst) and classical tardive dyskinesia (TDysk) are drug-induced movement disorders that are caused by dopamine receptor blocking agents (DRBAs), including antipsychotic drugs and certain antiemetics [–]. TDyst is characterized by sustained or intermittent involuntary posturing and torsional muscle contractions, most commonly involving the craniocervical region, although the trunk and limbs may also be affected []. The distribution of TDyst may be focal, segmental, multifocal, or generalized, similar to idiopathic dystonia, and symptoms often begin focally before spreading to additional body regions []. In contrast, TDysk is characterized by stereotyped, repetitive, involuntary movements, most commonly involving the oro-bucco-lingual region, followed by the upper limbs and, less commonly, the lower limbs and trunk. Both TDyst and TDysk can cause social distress and, in severe cases, significant physical disability.

One of the largest meta-analyses reported an average prevalence of TDysk of 25.3% among patients receiving DRBAs []. First-generation antipsychotics (30.0%) were associated with higher prevalence than second-generation antipsychotics (20.7%). The reported prevalence of TDyst varies widely, ranging from 0.5% to 21.6% [, –]. Tardive syndromes are generally irreversible once they develop []. In 2017, two vesicular monoamine transporter 2 (VMAT2) inhibitors were approved by the U.S. Food and Drug Administration (FDA) for the treatment of tardive dyskinesia and remain the only FDA-approved agents for this indication. Nevertheless, treatment of TDyst and TDysk remains challenging because of incomplete response, medication intolerance, limited access, and cost. Other treatments such as anticholinergics for TDyst, amantadine, benzodiazepines, and botulinum toxin injections with less evidence are often tried with limited effect [, ]; further, as TDyst and TDysk commonly co-occur, anticholinergics should be used with caution as this medication class can worsen TDysk. These therapeutic challenges have led to increasing interest in surgical interventions, including deep brain stimulation (DBS). Similar to idiopathic dystonia, the globus pallidus interna (GPi) is the most commonly targeted region, although a few reports have also described efficacy with subthalamic nucleus (STN) DBS [].

Despite apparent increasing interest in DBS for the treatment of TDyst and TDysk, this therapeutic approach remains less extensively investigated than DBS for other movement disorders, including idiopathic or genetic dystonia. Currently, DBS is considered a Level C recommendation for the treatment of TDyst and TDysk []. To date, the available studies are largely small retrospective case series and cohort studies reporting improvements in disease-specific rating scales, including Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Abnormal Involuntary Movement Scale (AIMS), ranging from 30% to 100%, with most studies reporting improvements greater than 60% [–]. The only randomized, sham-controlled DBS trial in TDyst and TDysk demonstrated a reduction in hyperkinetic movements but did not reach statistical significance, possibly because of limited statistical power and the relatively short follow-up duration of 3–6 months [].

Data on long-term clinical outcomes and effective stimulation sites remain limited, although such information is important for guiding patient selection, surgical targeting, and postoperative programming. In this study, we retrospectively evaluated long-term clinical outcomes and effective stimulation sites in patients with medically refractory TDyst and TDysk treated with GPi DBS at a single center.

Materials and methods

Participants

Eighteen adult patients (9 male, 9 female) with a diagnosis of TDyst and/or TDysk who underwent GPi DBS surgery from 2008 to 2025 at Emory University Hospital, Atlanta, GA, USA were included in this retrospective review. Demographic information, medical history, clinical rating scales, and DBS programming parameters were obtained from patient electronic medical records. The Institutional Review Board of Emory University approved this study, and written consent was waived.

Surgical procedure and DBS programming

Seventeen patients underwent bilateral GPi DBS surgery, and one patient underwent unilateral right-sided GPi DBS surgery. Quadripolar DBS electrodes were implanted using microelectrode recordings or intraoperative MRI guidance [, ]. Implanted DBS systems included commercially available DBS devices from Medtronic, Boston Scientific, and Abbott. Postoperative DBS programming was initiated approximately 4 weeks after surgery, and stimulation settings were adjusted over subsequent programming sessions as part of routine clinical care to optimize clinical benefit.

Clinical assessment

Comprehensive clinical evaluations were performed preoperatively and at postoperative follow-up visits approximately 1-year (4–16 months; short-term follow-up), 3-year (27–45 months; mid-term follow-up), and 5-year (59–79 months; long-term follow-up) after surgery. Each patient underwent pre-operative psychiatric clearance prior to DBS surgery. Two patients underwent genetic testing of which one positive result revealed a mutation consistent with ataxia telangiectasia. The clinical outcomes were measured using BFMDRS in patients with TDyst, Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in patients with prominent tardive cervical dystonia, and AIMS in patients with TDysk. Outcome measures were analyzed using available data at each time point.

DBS lead coordinates

Postoperative DBS lead localization was performed using the Image Fusion and Lead Localization modules in Brainlab Origin Data Management software (Brainlab AG, Munich, Germany). Postoperative CT images were rigidly co-registered to preoperative MRI. DBS leads were localized based on the hyperdense postoperative CT artifact. The automated lead detection in the Lead Localization module was used to identify the lead trajectory, followed by manual refinement using inline and orthogonal image views to optimize lead position. The anterior commissure (AC), posterior commissure (PC), and mid-commissural point (MCP) were manually identified on preoperative T1-weighted MRI to establish the coordinate system. AC-PC based coordinates (relative to MCP) for all 4 contact levels were recorded using the center point of each contact.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics, version 31.0.0.0 (IBM Corp., Armonk, NY, USA). Results are reported as mean ± standard deviation. Linear mixed model was utilized for BFMDRS and TWSTRS analysis due to missing patient data. AIMS evaluation was completed with analysis of variance (ANOVA). Post hoc pairwise comparisons were performed between preoperative scores and each follow-up time point with Bonferroni-adjustment for multiple comparisons. Statistical significance was set as Bonferroni-adjusted p < 0.05.

Results

Patient demographics

Detailed demographic and clinical information of the 18 patients with TDyst, TDysk, or both are shown in Table 1. Of these, nine patients were diagnosed with TDyst, two with TDysk, and seven with both. The mean age at onset of tardive symptoms was 42.0 ± 15.4 years, and the mean duration of tardive symptoms prior to surgery was 9.0 ± 7.9 years. Sixteen patients had psychiatric diagnoses. Fifteen patients had exposure to DRBAs for psychiatric indications, whereas three patients had exposure to DRBAs for nonpsychiatric indications, including promethazine in one patient and metoclopramide in two patients. Seventeen patients underwent bilateral GPi DBS surgery, and one patient had unilateral GPi DBS. One patient developed skin erosion and infection at the burr hole site that resolved without DBS lead explantation. Only on patient had both pre-operative and post-operative psychiatric scales for depression and anxiety. However, no patient had exacerbations of underlying psychiatric disorders based on chart review.

TABLE 1

PatientsSex (M/F)Age at symptom onset (yr)Tardive diagnosisDistributionSymptom duration prior to DBS (yr)Psychiatric diagnosisCausative medicationsTreatments before DBSFollow-up at final assessment (months)
1F62TDystFocal (left leg)3-PromethazineBenzodiazepine, botulinum toxin79
2F39TDystGeneralized27Depression, anxietyPerphenazineClozapine, tetrabenazine, botulinum toxin27
3M18TDystGeneralized13Bipolar disorderOlanzapine, quetiapineBenzodiazepine, botulinum toxin38
4F36TDystGeneralized3Schizophrenia, bipolar disorderLurasidoneBotulinum toxin43
5M60TDystGeneralized3PTSDAripiprazoleTrihexyphenidyl, baclofen, benzodiazepine, botulinum toxin53
6M27TDystGeneralized3Depression, anxietyProchlorperazineTrihexyphenidyl, carbidopa/levodopa, benzodiazepine, botulinum toxin60
7F47TDystGeneralized4-MetoclopramidePropranolol, trihexyphenidyl60
8F35TDystGeneralized28DepressionHaloperidol, prochlorperazineTrihexyphenidyl, botulinum toxin62
9M17TDystGeneralized10Bipolar disorderRisperidone, olanzapineBotulinum toxin66
10F-TDysk--Depression, anxietyMetoclopramideValbenazine9
11M59TDysk-8Bipolar disorderQuetiapineAmantadine, tetrabenazine, deutetrabenazine31
12M62TDyst, TDyskGeneralized8Bipolar disorderAripiprazoleValbenazine4
13F39TDyst, TDyskGeneralized6DepressionAripiprazolePropranolol, trihexyphenidyl, amantadine, benzodiazepine, deutetrabenazine, valbenazine, botulinum toxin10
14F53TDyst, TDyskGeneralized17Depression, PTSDProchlorperazine, quetiapineAmantadine, deutetrabenazine, valbenazine, botulinum toxin13
15M36TDyst, TDyskGeneralized6Autism spectrum disorderRisperidonePropranolol, benzodiazepine, tetrabenazine, deutetrabenazine, botulinum toxin35
16M20TDyst, TDyskGeneralized8Schizoaffective disorderZiprasidoneAmantadine, benzodiazepine, deutetrabenazine, valbenazine38
17F51TDyst, TDyskGeneralized5Bipolar disorderThorazine, stelazineBenzodiazepine, trihexyphenidyl, clozapine59
18M52TDyst, TDyskGeneralized5DepressionRisperidoneAmantadine, benzodiazepine61
Average SD​42.0 15.4​​9.0 7.9​​​41.6 22.5

Patient demographics.

Tardive dystonia (TDyst), tardive dyskinesia (TDysk). Post-traumatic stress disorder (PTSD).

Motor outcomes

The mean preoperative BFMDRS motor score was 27.5 ± 8.3. Compared with preoperative scores, BFMDRS motor scores improved significantly after GPi DBS (Figure 1A); 9.1 7.5 at short-term follow-up (11.1 3.2 months; p < 0.001), 5.0 5.8 at mid-term follow-up (35.9 5.1 months; p < 0.001), and 4.1 7.6 at long-term follow-up (62.5 7.6 months; p < 0.001). The corresponding mean percentage improvements from preoperative score were 64.1 30.8%, 83.8 14.1%, and 88.0 16.8%, respectively. Three patients achieved complete resolution of motor symptoms, corresponding to 100% improvement, including one patient at short-term follow-up and two patients at mid-term follow-up; this response was maintained through their last follow-up visits. Improvement varied across BFMDRS motor subscores (Figure 1B). Axial dystonia, including neck and trunk involvement, showed significant improvement at all follow-up time points. The mean axial subscore improved from 12.3 6.6 preoperatively to 3.5 3.6 at short-term follow-up (p < 0.001), 2.3 4.1 at mid-term follow-up (p < 0.001), and 1.6 3.7 at long-term follow-up (p < 0.001). Extremity dystonia also improved, with significant reductions at mid-term and long-term follow-up. The mean extremity subscore decreased from 9.1 8.2 preoperatively to 3.6 6.5 at short-term follow-up, 1.2 2.0 at mid-term follow-up (p = 0.01), and 0.3 0.8 at long-term follow-up (p = 0.02). Speech, swallowing and orofacial dystonia subscore showed numerical improvement but did not reach statistical significance, decreasing from 6.2 5.6 preoperatively to 2.0 3.0 at short-term follow-up, 1.8 2.3 at mid-term follow-up, and 2.6 4.3 at long-term follow-up.

FIGURE 1

A subset of patients with TDyst had available TWSTRS scores (Figure 2A). Although the change did not reach statistical significance, TWSTRS scores showed a sustained numerical improvement across all follow-up time points. The mean TWSTRS scores decreased from 50.3 13.6 preoperatively to 25.6 12.8 at short-term follow-up, 20.4 19.6 at mid-term follow-up, and 21.7 31.5 at long-term follow-up. TWSTRS subscores are shown in Figure 2B, with the most apparent improvements observed in the severity and disability subscores.

FIGURE 2

Among the nine patients with TDysk, four patients had available AIMS scores (Figure 3A). Although statistical significance was not reached, AIMS scores showed numerical improvement over time, decreasing from 15.8 5.4 preoperatively to 10.0 2.4 at short-term follow-up, and 5.0 at mid-term follow-up. AIMS subscores are shown in Figure 3B, with the most apparent improvement observed in the orofacial and global judgement subscores.

FIGURE 3

DBS contact locations and programming parameters

The coordinates of the active electrode contacts at the last follow-up visits were 20.6 1.9 mm lateral, 2.5 1.7 mm anterior, and 1.1 1.3 mm inferior relative to MCP. The stimulation parameters at the same timepoint are listed in Table 2. The mean stimulation amplitude was 3.8 1.0 mA, pulse width was 95.1 36.1 μs, and frequency was 119.4 38.5 Hz.

TABLE 2

PatientsLeft GPi DBSRight GPi DBS
​ConfigurationAmplitude (mA)Pulse width (μs)Frequency (Hz)ConfigurationAmplitude (mA)Pulse width (μs)Frequency (Hz)
1----M5.2120130
2M1.490130M1.690130
3M3.260130M3.360130
4M3.860130DM4.560130
5M4.7120120B3.4120120
6DM5.660100M5.890100
7M3.818060B3.121070
8B3.010060B3.310060
9DM5.112060DM4.715060
10M3.790185M3.390185
11B4.590204B4.580204
12M3.760130M3.760130
13M3.560125M2.560125
14M4.370125M4.170125
15M4.790130M4.790130
16M3.160130M4.4150130
17M3.912070M4.09070
18M2.5120130B3.390130

DBS stimulation parameters.

Monopolar configuration (M), double monopolar configuration (DM), and bipolar configuration (B). For constant-voltage DBS, system, current was calculated using the programmed voltage and therapeutic impedance.

Over time, stimulation parameters were adjusted as clinically indicated, whereas electrode configuration remained unchanged from short-term to last follow-up in all but one patient. In that patient, the configuration was changed from monopolar to double-monopolar stimulation to improve symptom control. From one to three years, the mean change in amplitude was 0.7 0.7 mA; from three to five years, the mean change amplitude was 0.5 0.5 mA. The mean change in pulse width between time intervals was less than 6.5 μs. Likewise, the mean change in frequency between time intervals was less than 10 Hz. No persistent stimulation-related adverse effects were reported.

Discussion

In this retrospective study, we evaluated the long-term clinical outcomes of GPi DBS in patients with medically refractory TDyst and TDysk. Our results demonstrate that GPi DBS provided robust and sustained improvement in TDyst, with significant reductions in BFMDRS motor scores at short-term, mid-term and long-term follow-up. The greatest improvement was observed within the first year after surgery and was maintained through 3- and 5-year follow-up among patients with available data. These findings are consistent with prior reports supporting GPi DBS as an effective treatment for refractory TDyst [, , ]. Notably, our cohort showed continued improvement from short-term to long-term follow-up, and 3 patients achieved complete resolution of motor symptoms that was maintained until their last follow-up visits. This pattern may reflect the delayed and cumulative therapeutic response to GPi stimulation previously described in dystonia []. Together, these findings support the long-term durability of GPi DBS benefit in TDyst and suggest that clinically meaningful improvement can be sustained for several years after implantation.

Although BFMDRS motor scores improved significantly at all follow-up time points, the magnitude of improvement varied across BFMDRS motor subscores. Axial dystonia improved significantly at all follow-up time points, whereas extremity dystonia showed significant improvement at mid-term and long-term follow-up. In contrast, speech, swallowing and orofacial dystonia subscores showed numerical improvement but did not reach statistical significance. This lack of statistical significance should be interpreted cautiously, as the study was likely underpowered to detect changes within individual subscores, particularly given missing follow-up data and smaller sample sizes at later time points. Previous studies have reported that DBS efficacy may vary by dystonia distribution [–], which could potentially explain the differences observed across subscores in our cohort. However, craniofacial and cervical dystonia phenotypes, including Meige syndrome and cervical dystonia, have been shown to respond to GPi DBS in large study populations [–], suggesting that nonsignificant findings in selected subscores in this cohort may reflect limited statistical power rather absence of clinical benefit.

Similarly, although BFMDRS axial subscores improved significantly at all follow-up time points, TWSTRS scores, which were available only in a subset of patients with prominent cervical TDyst, showed sustained numerical improvement without reaching statistical significance. This discrepancy may reflect several factors, including the smaller number of patients with available TWSTRS data, missing follow-up data, and differences in scale sensitivity.

AIMS scores in patients with TDysk also showed numerical improvement over time, but the small number of patients with available preoperative and postoperative AIMS scores limits interpretation and precludes definitive conclusions regarding DBS effectiveness for TDysk in this cohort. Nevertheless, the observed downward trend is consistent with prior studies reporting improvement in TDysk after GPi DBS [, , ]. Larger prospective studies are needed to better define DBS outcomes in patients with TDysk.

The coordinates of the active electrode contacts in our cohort were consistent with the GPi target region used for dystonia and aligned with previously reported GPi stimulation sites in tardive syndromes [, –]. In addition, stimulation parameters in this cohort were generally consistent with commonly used GPi DBS settings for dystonia [].

One patient developed skin erosion and infection at the burr hole site, which did not require DBS lead explantation. Otherwise, no persistent stimulation-related adverse effects were reported. This low complication rate supports the overall safety of GPi DBS in appropriately selected patients with medically refractory TDyst and TDysk. The mean duration of tardive symptoms before surgery was 9 years, with a range of 3–28 years. Given the robust and sustained improvement and low surgical complication rate observed in this cohort, earlier consideration of DBS may be reasonable in selected patients with severe, disabling, and treatment-refractory tardive syndromes.

Our study has several limitations. First, the retrospective design limited the uniformity of clinical assessments, and outcome assessments were not blinded, which may have introduced observer bias. Second, follow-up data were incomplete, particularly at later time points, which may have affected estimates of long-term treatment effect. Third, different rating scales were used depending on clinical phenotype, and not all patients had all outcome measures available. Fourth, the small number of patients with available TWSTRS and AIMS data limited statistical power for subgroup analyses.

Despite these limitations, this study adds to the growing evidence supporting GPi DBS as a safe and effective treatment for medically refractory TDyst, with sustained long-term benefit. The findings also suggest potential benefit for TDysk, although larger studies are needed to confirm this effect. Large, multicenter prospective studies with standardized outcome measures and long-term follow-up are needed to further define the efficacy, durability, and optimal stimulation parameters of DBS for tardive syndromes.

Statements

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving humans were approved by Emory University Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because the study presents no more than minimal risk of harm as the participants underwent intervention outside of the research evaluation.

Author contributions

GJ, SM, SF, and SR participated in the design, interpretation of the studies and analysis of the data and review of the manuscript; GJ, SM, PA, RT, CB, CE, LH, and ST conducted patient evaluations. SR completed statistical analysis. GJ completed figure and table creation. GJ and SR wrote the manuscript, and SM and SF were involved in the editing process. All authors contributed to the article and approved the submitted version.

Funding

The author(s) declared that financial support was not received for this work and/or its publication.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The reviewer SP declared a shared affiliation with the author(s) SF at the time of review.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

References

Summary

Keywords

globus pallidus internus, GPi deep brain stimulation, tardive dyskinesia, tardive dystonia, tardive syndromes

Citation

Je G, Miocinovic S, Huang V, Aia PG, Tripathi R, Buetefisch CM, Esper CD, Higginbotham LA, Triche S, Factor SA and Radmard S (2026) The long-term efficacy of globus pallidus deep brain stimulation in tardive dystonia and dyskinesia. Dystonia 5:17246. doi: 10.3389/dyst.2026.17246

Received

28 June 2026

Accepted

01 October 2026

Published

19 October 2026

Volume

5 - 2026

Edited by

Aasef Shaikh, Case Western Reserve University, United States

Updates

Copyright

*Correspondence: Sara Radmard,

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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