Abstract

Background: Tourette syndrome (TS) is a common neurological disorder characterized by frequent and disabling motor or vocal tics. There has been widely reported variation in patient responses to deep brain stimulation (DBS) for TS treatment. However, the potentially synergistic effects of multifocal DBS placements have not been extensively explored in younger patient populations.

Case Description: Our patient is a 19-year-old male with a medical history significant for TS and comorbid psychological disorders. Despite medical treatment, the patient’s violent tics progressed from simple back extension motor tics to vigorous and aggressive behaviors. He received multiple opinions and trialed numerous pharmacological therapies without success. He was ultimately referred for neurosurgical evaluation for placement of DBS with selected targets of the bilateral nucleus accumbens (NAcc) and bilateral centromedian thalamus for lead implantation. The Yale Global Tic Severity Scale rated by the attending surgeon demonstrated a significant improvement in the patient’s baseline tics and overall quality of life from preoperatively to 56 months postoperatively. With multifocal DBS leads in place, the patient’s tics are well controlled on a low-moderate dosage of haloperidol. His emotional lability is now reported as less volatile and less extreme. He has become considerably more sociable and talkative.

Conclusion: Following DBS placement, the patient experienced substantial improvement from his preoperative violent behavior and mood lability. This case provides evidence that dual electrode DBS, in conjunction with appropriate medical management, is a safe and effective way to improve life quality in individuals struggling with debilitating TS symptoms.

Keywords: Centromedian thalamus, Deep brain stimulation, Nucleus accumbens, Tourette syndrome

INTRODUCTION

Tourette syndrome (TS) is a common neurodevelopmental disorder characterized by frequent or disabling motor and phonic tics. Symptoms generally manifest in childhood and become more noticeable between ages 12 and 17. Patients with TS have an increased risk of developmental, behavioral, and mental co-morbidities, including anxiety, obsessive compulsive disorder (OCD), depression, and attention deficit hyperactivity disorder.[ 10 ]

First described in the late 1800s, the etiology and pathophysiology of TS have not been definitively elucidated.[ 8 ]

However, both genetic and environmental influences have been shown to play a role in its development. One speculated mechanism of pathogenesis of TS includes dysregulation of the basal ganglia, involving an aberrant inhibition of the globus pallidus pars internus (GPi) and substantia nigra (SN), contributing to impairments in motor, speech, and postural control.[ 20 ] Treatment approaches are multifactorial to achieve maximum granularity in targeting motor and psychiatric elements of TS.[ 2 ] They typically focus on symptom management and may include first-line treatments such as comprehensive behavioral intervention for tics, alpha-2 and vesicle monoamine transporter 2 inhibitors, antiepileptics, and botulinum injections in cases of severe focal tics. Second-line therapy includes typical and atypical antipsychotics, while third-line therapy for medically intractable TS ultimately turns to deep brain stimulation (DBS).[ 2 ]

DBS has been used off-label to reduce tic burden in young patients experiencing debilitating tics since 1999.[ 19 ] Although it is an evolving and controversial approach for managing TS, DBS is proving to be promising for a select group of patients who are unresponsive to pharmacotherapy. It is typically considered for patients with severe and refractory symptoms who fail to respond to management with at least three different pharmacological agents.

Several studies have shown inconsistent evidence regarding the optimal anatomical brain region for stimulation in DBS for TS treatment.[ 1 ] Some find success modulating the emotional aspect of tics through the limbic system, while others focus on accounting for the nigrostriatal pathway’s role in shaping their motivational drive.[ 1 ] Stimulation of different targets may address distinct symptoms for patient specific needs.

Recent literature explores connectivity patterns in multifocal stimulation, introducing the potential for synergistic effects with multifocal DBS placements.[ 6 ] However, the common presentation of TS combined with various psychiatric disorders requires additional and serious, patient-specific consideration of stimulation interactions. Here, we present the novel and successful use of dual, bilateral electrode placements in the centromedian thalamus (cmT) and the nucleus accumbens (NAcc) for a young patient with severe TS, OCD, and other psychiatric comorbidities.

CASE PRESENTATION

A 19-year-old right-handed male with a medical history significant for TS diagnosed at age seven with severe OCD, generalized anxiety disorder, and major depressive disorder presented with tics that became progressively violent and aggressive despite years of medical treatment. Originally displaying simple back extension motor tics, the patient had begun experiencing violent behavioral outbursts such as vigorously punching his chest, banging his head into walls, and performing other outward and self-harming behaviors. With this progression in symptom severity also came the worsening of the patient’s baseline psychiatric disorders, including severe mood lability, anxiety, aggression, anger, and depression with suicidal ideation. His parents reported a sense of fear of the patient at times, with concern that he may inflict harm on his own family during episodes of severe aggression coinciding with mood lability. He received multiple opinions and tried numerous therapies without success, including multiple antipsychotics, antidepressants, topiramate, off-label guanfacine and clonidine, medical marijuana (Tetrahydrocannabinol [THC]/Cannabidiol [CBD] 76–89%), and benzodiazepines. After a thorough and detailed discussion with the patient and his family, the patient was ultimately referred for neurosurgical evaluation for placement of a DBS device.

Device implantation and programming

Following a thorough review of the existing literature, the bilateral NAcc and bilateral cmT were selected as targets for dual, bilateral lead implantation, totaling four electrode implants. The patient was taken to the OR suite, where four-point skull fixation was used for the application of the Cosman-Roberts-Wells (CRW) frame system. Appropriate coordinates were entered into the Stealth FrameLink system at 6.5 mm lateral of the anterior commissure (AC), 4.5 mm ventral to AC, and 2.5 mm rostral to the anterior border of AC. Four burr holes were created, and, with the assistance of microelectrode recordings, four leads [Medtronic, Minneapolis, MN] were introduced and placed into their final position [ Figure 1 ]. Once placed, intraoperative fluoroscopy was utilized to confirm using the CRW “bull’s eye” technique for localization.[ 12 ] Following surgery, the patient was monitored in the neurological intensive care unit for one night and was discharged the following day. In keeping with our institution’s protocol for DBS system implantation, the patient returned 1 week after surgery for placement of one DBS battery and again 3 weeks later for implantation of the second battery [ Figure 2 ].

Figure 1:

Computed tomography imaging of lead placement showing (a) sagittal, (b) coronal, and (c) axial views. Model for deep brain stimulation (DBS) leads (red) and placement showing (d) sagittal, (e) coronal, and (f) axial. Views of the terminal ends of the leads were placed on the nucleus accumbens (yellow) and centromedian thalamus within the thalamus (orange).

Figure 2:

Timeline of operative procedures for dual bilateral deep brain stimulation (DBS).

RESULTS

In the weeks following device activation, the patient was noted to have a reduction in self-injurious behaviors with no changes to the pre-existing behavioral disturbances. Throughout the following year, he returned frequently for follow-up and DBS parameter adjustments [ Table 1 ]. At 7 months postoperatively, the patient’s parents reported that he had started developing a tremor in his left arm and his behavioral disturbances returned to the preoperative baseline. Soon after, the patient tried turning off the stimulator for an evening and reported the next morning that his symptoms had worsened. The psychiatric team advised him to turn the stimulator back on, and his medication regimen was adjusted from clonazepam 0.5 mg BID to TID, with the addition of haloperidol 2 mg BID.

Table 1:

Device programming and stimulation parameter (amplitude, pulse width, frequency) timeline for dual bilateral deep brain stimulation

Following the pharmacologic regimen adjustment and over the next 4 years of clinical follow-up, the patient demonstrated significant improvement in the frequency and severity of motor tics and violent behavioral outbursts. It was noted during his most recent follow-up visit, after 56 months of postoperative follow-up and DBS acclimation, that while on a stable dose of 1mg of haloperidol BID, the patient did not exhibit any motor tics, although some residual depression, anxiety, and seizures remained, which were treated with fluoxetine 20 mg daily, clonazepam 0.5 mg TID, and hydroxyzine as needed. It should be noted that none of these remaining psychotropic therapies are medications indicated to treat TS tics. Before the operation, multiple doses of haloperidol were taken without relief of symptoms. However, with DBS in place, the patient’s tics are well controlled on a low-moderate dosage of the medication.

The Yale Global Tic Severity Scale (YGTSS) is a widely used assessment tool that measures the severity of motor and phonic tics in both children and adults.[ 5 , 20 ] It evaluates tic number, frequency, complexity, intensity, and interference, with ratings on a 6-point scale (0–5) for each domain, along with an “overall impairment” score reflecting daily life influence.[ 5 ] These scores serve as the foundation for guiding treatment and tracking tic severity over time, ensuring both reliability and validity in evaluating tic-related impairment.[ 5 ] The YGTSS was scored by the attending surgeon at baseline and 56 months postoperatively and revealed meaningful improvement in the patient’s tics and quality of life [ Figure 3 ]. This is supported by psychological and neurosurgical clinical data collected before implantation.

Figure 3:

(a-c) Yale global tic severity scale scored (May 29, 2024) 56 months postoperatively by the attending neurosurgeon shows significant improvement from baseline (September 4, 2025) symptoms.

DISCUSSION

Historically, the most targeted locations in the treatment of TS include the globus pallidus internus, thalamus, and NAcc.[ 19 ] In addition, dysfunction of cmT, implicated in habit learning and movement control, is often observed in patients with TS and comorbid OCD.[ 9 ] DBS stimulation of NAcc in a patient with TS has previously been shown to decrease tic frequency significantly.[ 7 ]

Although specific clinical correlates of each electrode placement within the cortico-striatal-thalamic pathway have not yet been fully explored, stimulation of the thalamus has previously shown the greatest reduction in tic severity. The ventral anterior/ventral lateral thalamus has shown the highest connectivity to the motor cortex, and the NAcc has shown the greatest connectivity with the amygdala in both TS patient and control data, illustrating a potential pair to target in the reduction of tic burden and to ameliorate behavioral associations with these tics.[ 6 ] As such, the median thalamus has been considered the most promising primary target to reduce tic generation through suppression of excitatory feedback, and the NAcc is preliminarily used to reduce the behavioral components, which are a frequent factor of refractory and debilitating TS in children.[ 16 ]

In patients experiencing severe and multifaceted symptoms, placement of multiple leads may be warranted to enhance the synergistic effects of stimulation and improve clinical outcomes.[ 15 ] When comparing bilateral leads to unilateral leads, key considerations include safety, effectiveness, postoperative outcomes, and patient compliance.[ 14 , 15 ] Previous studies have shown that bilateral lead placement generally yields better results than unilateral leads when treating multiple symptoms.[ 13 - 15 ] Other studies have also explored the dual target strategy in patients with TS and OCD.[ 13 ] In contrast with our case, where the focus of DBS was NAcc and cmT, another study targeted the bilateral ventral capsule/ventral striatum and posteroventral GPi structures.[ 13 ] Symptomatic improvement for TS and OCD following DBS was observed in both studies, regardless of the structure stimulated.

Given these promising results in reducing tic occurrence and severity in patients with TS and OCD, dual stimulation of the NAcc and the cmT was planned and successfully performed in our patient.

Following the procedure, the patient has experienced marked improvement in his tic severity. Although some residual tics remain, they are no longer destructive and harmful to himself and his family. These findings are further supported by the patient’s psychiatrist, who states that his condition has improved since the implantation. Before the surgical intervention, the patient had planned to move to a facility that would aid in the management of self-harming behaviors. At present, the patient experiences comparatively moderate emotional lability, has become considerably more sociable and talkative, and is even described as “gentle.” While our patient does continue to have occasional tics and remains at baseline regarding his comorbid OCD, depression, and anxiety, he continues to have a notable improvement in tic frequency, severity, violent behavioral outbursts, and self-harming behaviors that have greatly improved the patient’s quality of life.

Our patient’s relatively young age and presence of concurrent morbidities, including OCD, anxiety, and depression, make this report especially unique. Approximately three quarters of pediatric patients experience significant improvement of tic severity in early adulthood, and approximately 32% experience complete remission.[ 3 ] Considering the potential for spontaneous improvement, DBS in TS patients was recommended only for individuals aged 25 and older.[ 11 , 18 ] However, 2015 International Parkinson and Movement Disorder Society guidelines no longer consider age a strict criterion. In cases with urgent indications and refractory to pharmacotherapy, these findings have supported its recognition as a viable treatment option in patients younger than 25 years old.[ 11 , 18 ] Our patient received multiple trials of pharmacotherapy, including antipsychotics, antidepressants, topiramate, guanfacine, clonidine, medical marijuana, and benzodiazepines, with no symptomatic improvement. Cases like the one presented in this report highlight the debilitating nature of severe tics and their associated symptoms. Multiple studies report improvement in depressive and OCD symptoms following DBS in TS patients.[ 17 ] These changes are often more evident within the 1^st year following DBS and remain stable over time, regardless of follow-up. One study characterized the improvement process as a sequence, starting with the rapid alleviation of affective symptoms within seconds, followed by a reduction in anxiety within minutes. Obsessive symptoms would usually subside within days, while compulsions improved over a few weeks or several months.[ 4 ]

A tailored and multidisciplinary approach is essential to ensure comprehensive management for patients diagnosed with concurrent neurological and psychiatric conditions. Over the past two decades, advancements in functional neurosurgery have provided critical insights into the safety and potential adverse effects of DBS for TS.[ 14 , 18 ] In patients with concurrent psychiatric comorbidities, such as the one presented here, special emphasis should be placed on appropriate and consistent psychiatric care, including frequent medication reconciliation and adherence tracking, to maximize behavioral outcomes following surgery. Future studies should focus on better elucidating TS pathophysiology, integrating recent advances in neural connectomics to optimize anatomical landmarks for stimulation, optimizing the integration of postoperative psychiatric care for patients with concurrent psychiatric morbidities and investigating means of reducing adverse effects and complications associated with DBS.

CONCLUSION

When the presented patient was first diagnosed with TS at 7 years old, he suffered from progressively worsening tics and violent outbursts with comorbid OCD, anxiety, and depression. We demonstrate here that dual bilateral electrode stimulation of NAcc and cmT can be a safe and effective third-line intervention for intractable TS, evenin younger patients with severe, refractory symptoms. While this procedure was not fully curative and occasional psychomotor manifestations of TS remain, there was a substantial objective and subjective improvement in motor and cognitive manifestations of TS that greatly improved his quality of life.

Ethical approval:

The Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

Acknowledgements:

We would like to acknowledge Anna Ryan, APN for her continuous support of the patient and Vasilios Vasilopoulos for his assistance in 3D figure creation.

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