Surgical Concepts and Long-term Outcomes of Thalamic Deep Brain Stimulation in Patients with Severe Tourette Syndrome: A Single-center Experience.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by tic movements. Deep brain stimulation (DBS) may be a treatment option for severe cases refractory to medical and behavioral therapies. In this study, we reviewed the surgical techniques used for DBS in patients with severe TS and its clinical outcomes and sought to determine the optimal surgical procedure and current issues based on our experience and the literature. A total of 14 patients, consisting of 13 men and 1 woman, who underwent centromedian thalamic DBS and were followed up for a mean duration of 2.3 ± 1.0 years, participated in this study. The mean Yale Global Tic Severity Scale severity score significantly improved from 41.4 ± 7.0 at baseline to 19.8 ± 11.4 at 6 months (P = 0.01) and 12.7 ± 6.2 at the last follow-up (P < 0.01). Moreover, the mean Yale Global Tic Severity Scale impairment score significantly improved from 47.1 ± 4.7 at baseline to 23.1 ± 11.1 at 6 months (P < 0.01) and 7.6 ± 2.9 at the last follow-up (P < 0.01). However, there were problems with continuous postoperative monitoring (three cases were lost to follow-up) and surgery-related adverse events, including one case each of lead misplacement and a delayed intracerebral hemorrhage due to severe self-injurious tics. This study aimed to highlight not only the clinical efficacy of DBS for TS but also its challenges. Clinicians should understand the three-dimensional brain anatomy so that they can perform precise surgical procedures, avoid adverse events, and achieve favorable outcomes of DBS for TS.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

[Deep Brain Stimulation for Tourette's Syndrome and Challenging for Neuropsychiatric Disease].

The efficacy of deep brain stimulation(DBS)for Tourette's syndrome is being well established. Herein, we performed DBS in 38 patients and confirmed that its efficacy was comparable with that reported internationally. Although many patients experience severe symptoms, the indications for surgery remain controversial. One reason for this is that Tourette syndrome has the potential for spontaneous remission, while DBS treatment results in the need for long-term management, which can be difficult for some patients. Furthermore, while several targets for DBS have been reported, no treatment guidelines have yet been established. The efficacy of DBS for neuropsychiatric disorders, such as obsessive-compulsive disorder, depression, and dementia, is gradually being reported. However, this use has many limitations in terms of expectations similar to those seen with Tourette's syndrome, leading to problems with expanding indications for these disorders. Indications for these disorders should be addressed in conjunction with ethical issues. It is expected that more data on this topic will be collected in the future.

Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette's syndrome: Experience and evidence.

OBJECTIVES: To evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette's syndrome (TS). METHODS: This retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. RESULTS: In total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28-74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67-25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26-23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90-15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68-52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5-87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. CONCLUSIONS: Combined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

One-year outcomes of deep brain stimulation in refractory Tourette syndrome.

AIM: Deep brain stimulation (DBS) is one option for treating refractory Tourette syndrome (TS); however, it remains unclear which preoperative factors are predictive of DBS outcomes. This study investigated the efficacy of DBS targeting the anteromedial globus pallidus internus and evaluated predisposing factors affecting the outcomes of DBS in a single center in Korea. METHOD: Twenty patients who had undergone DBS for refractory TS were reviewed retrospectively. Tic symptoms were followed up at 3-month intervals for up to 1 year after surgery. The Yale Global Tic Severity Scale was used to evaluate preoperative/postoperative tic symptoms. Scores from the Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were also evaluated. RESULTS: Patients with refractory TS achieved improvement in tic symptoms within 1 year after DBS. Initial responders who achieved a 35% reduction in Yale Global Tic Severity Scale total score within the first 3 months after DBS showed larger treatment effects during 1-year follow-up. Although no clinical or demographic factors were predictive of initial responses, patients with serious self-injurious behaviors tended to show delayed responses. CONCLUSION: This is the first study to our knowledge to report the DBS outcomes of 20 patients with TS in a single center in Asia. Our study supports the efficacy of DBS targeting anteromedial globus pallidus internus in refractory TS with no evident serious adverse events. Initial responses after DBS seem to be a predictor of long-term outcomes after surgery.

Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated With the Microlesion Effect in Tourette Syndrome.

BACKGROUND: The microlesion effect refers to the improvement of clinical symptoms after deep brain stimulation (DBS) lead placement and is suggested to indicate optimal lead placement. Very few studies have reported its implications in neuropsychiatric disorders. OBJECTIVE: To evaluate the magnitude of the microlesion effect in Tourette syndrome and the relationship between the microlesion effect and the anatomic location of implanted DBS leads. METHODS: Six male patients were included. Their median age at surgery and follow-up period were 25 years (range, 18-47) and 12 months (range, 6-24), respectively. All patients were videotaped pre- and postoperatively, and tic frequencies were counted. We also analyzed the precision of lead placement and evaluated the normative connectome associated with the microlesion area. RESULTS: The microlesion effect was observed as an improvement in tic symptoms in all patients, and the long-term clinical outcomes were favorable. The median motor tic frequency was 20.2 tics/min (range, 9.7-60) at baseline and decreased to 3.2 tics/min (1.2-11.3) in patients on postoperative day 1 ( P = .043) and to 5.7 tics/min (range, 1.9-16.6) in patients on postoperative day 7 ( P = .028). Phonic tic tended to improve immediately after surgery although the changes were not significant. Image analyses revealed that the precise position of the electrode was directed toward the anteromedial centromedian nucleus. Normative connectome analysis demonstrated connections between improvement-related areas and wide areas of the prefrontal cortex. CONCLUSION: This study shows that the microlesion effect may seem as an immediate improvement after optimal DBS lead placement in patients with Tourette syndrome.

Long-term efficacy, prognostic factors, and safety of deep brain stimulation in patients with refractory Tourette syndrome: A single center, single target, retrospective study.

BACKGROUND: To evaluate the long-term efficacy, prognostic factors, and safety of posteroventral globus pallidus internus deep brain stimulation (DBS) in patients with refractory Tourette syndrome (RTS). METHODS: This retrospective study recruited 61 patients with RTS who underwent posteroventral globus pallidus internus (GPi) DBS from January 2010 to December 2020 at the Chinese People's Liberation Army General Hospital. The Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (YBOCS), Beck Depression Inventory (BDI), Gilles de la Tourette Syndrome Quality-of-Life Scale (GTS-QOL) were used to evaluate the preoperative and postoperative clinical condition in all patients. Prognostic factors and adverse events following surgery were analyzed. RESULTS: Patient follow up was conducted for an average of 73.33 ± 28.44 months. The final postoperative YGTSS (32.39 ± 22.34 vs 76.61 ± 17.07), YBOCS (11.26 ± 5.57 vs 18.31 ± 8.55), BDI (14.36 ± 8.16 vs 24.79 ± 11.03) and GTS-QOL (39.69 ± 18.29 vs 78.08 ± 14.52) scores at the end of the follow-up period were significantly lower than those before the surgery (p < 0.05). While age and the duration of follow-up were closely related to prognosis, the disease duration and gender were not. No serious adverse events were observed and only one patient exhibited symptomatic deterioration. CONCLUSIONS: Posteroventral-GPI DBS provides long-term effectiveness, acceptable safety and can improve the quality of life in RTS patients. Moreover, DBS is more successful among younger patients and with longer treatment duration.

Improved depressive symptoms in patients with refractory Gilles de la Tourette syndrome after deep brain stimulation of posteroventral globus pallidus interna.

OBJECTIVE: Deep brain stimulation (DBS) has been used on drug-resistant Gilles de la Tourette syndrome (GTS) for more than two decades until now, but the stimulating targets are still under exploration until now. In this study, the authors reported the efficacy of the bilateral posteroventral globus pallidus interna (GPi) DBS on tic severity and neuropsychiatry symptoms of seven individuals with GTS. METHOD: Seven patients with drug-resistant GTS were enrolled in this study. The severity of these patients was evaluated with Yale Global Tics Severity Scale (YGTSS), Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning Scale (GAF). Bilateral posteroventral GPi were selected as the permanent stimulating targets. Follow-up period was at least 5 years after surgery in the enrolled patients. RESULTS: After surgery, one patient reported no improvement during the follow-up period, and a device removal surgery was performed. The other six patients reported minor to significant improvement. The overall YGTSS, YBOCS, HAMA HAMD, and GAF scores of these patients were changed positively after surgery, but only the improvement of the motor tic and HAMD scores had a statistical difference. No surgical complication was reported. CONCLUSIONS: Bilateral posteroventral GPi DBS could relieve the motor tics and depressive symptoms of the enrolled patients significantly, but the vocal tics and other psychiatric symptoms presented a progression without statistical difference during the follow-up period. The results of this study suggested that bilateral posteroventral GPi are effective targets for the motor tics in GTS patients, especially with prominent depressive symptoms.

What makes tics tick? Insights into Tourette syndrome.

This issue of Biomedical Journal provides the reader with articles concerning the latest understanding of Tourette syndrome (TS), the relation to genetic predisposition, defects in the dopaminergic system, and related comorbidities which further complications like sleep disruption. Treatment approaches for TS, attention deficit hyperactivity disorder and developmental coordination disorder are discussed. The second section of this issue offers insights into inside out integrin activation and its link to T cell activation, demonstrates how polarity in immune cells allows adoption to specialized functions, and describes the endosomal signaling of internalized T cell receptors (TCRs). The link between mutations in TCR signaling and immunodeficiencies is elucidated, as well as the interactions of thymocyte-expressed molecule involved in selection in T cell development. Additionally, we learn about a potential biomarker for colorectal cancer, screening tools for determining frailty in older adults, surgical approaches in spinal metastases, the influence of autophagy on mating behavior, and the effect of nitrite administration on SNARE proteins associated with insulin secretion. Finally, parameters for surgery in breast cancer are discussed, as well as gender and age dependent pain perception in a lysosomal storage disease, and the use of laser meridian massage in opioid use disorder. Three letters complement this issue, one concerning neuroimaging in pediatric COVID-19 patients, and two discussing the role of cancer antigen-125 and renal impairment in ovarian cancer patients.

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized, double-blinded sham-controlled periods.

BACKGROUND: There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. OBJECTIVES: In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. METHODS: We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months' assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. RESULTS: Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. CONCLUSION: Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome.

BACKGROUND: There are still no sufficient data regarding the use of deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) and no agreement on optimal target. OBJECTIVE: To compare efficacy and safety of bilateral DBS of thalamus (centromedian-ventro-oral internus, CM-Voi) versus posteroventral lateral globus pallidus internus (pvl GPi)) versus sham stimulation, and baseline in severe medically refractory GTS. METHODS: In this randomized double-blind sham stimulation-controlled trial (RCT), 10 patients (3 women, mean age = 29.4 ± 10.2 SD, range 18-47) underwent three blinded periods each lasting three months including (i) sham, (ii) pvl GPi (on-GPi), and (iii) thalamic stimulation (on-thal) followed by an open uncontrolled long-term follow-up (up to 9 years) with individually determined target and stimulation settings. RESULTS: Nine patients completed the RCT. At group level, on-GPi - but not on-thal - resulted in a significant tic reduction compared to baseline, but had no effect on premonitory urges and psychiatric comorbidities. Direct comparisons of targets resulted in inconsistent or negative (compared to sham) findings. During follow-up, we found no improvement of tics, comorbidities, and quality of life at group level, however, single patients benefitted continuously from thalamic DBS. At last follow-up 89.9 months (mean) after surgery, 50% of patients had discontinued DBS. Hardware infections occurred in 3/10 patients. CONCLUSION: Our data suggest that the initial effect of pvl GPi DBS is superior to thalamic (CM-Voi) DBS. While half of the patients discontinued treatment, single patients benefitted from thalamic DBS even after years. It is likely that outcome is influenced by various factors beyond the mere change in tic severity.

Deep brain stimulation in the management of paediatric neuropsychiatric conditions: Current evidence and future directions.

INTRODUCTION: Neurosurgery has provided an alternative option for patients with refractory psychiatric indications. Lesion procedures were the initial techniques used, but deep brain stimulation (DBS) has the advantage of relative reversibility and adjustability. This review sets out to delineate the current evidence for DBS use in psychiatric conditions, with an emphasis on the paediatric population, highlighting pitfalls and opportunities. METHODS: A systematic review of the literature was conducted on studies reporting the use of DBS in the management of psychiatric disorders. The PRISMA guidelines were employed to structure the review of the literature. Data was discussed focusing on the indications for DBS management of psychiatric conditions in the paediatric age group. RESULTS: A total of seventy-three full-text papers reported the use of DBS surgery for the management of psychiatric conditions matching the inclusion criteria. The main indications were Tourette Syndrome (GTS) (15 studies), Obsessive Compulsive Disorder (OCD) (20), Treatment Resistant Depression (TRD) (27), Eating Disorders (ED) (7) and Aggressive Behaviour and self-harm (AB) (4). Out of these, only 11 studies included patients in the paediatric age group (≤18 years-old). Among the paediatric patients, the indications for surgery included GTS, AB and ED. CONCLUSIONS: The application of deep brain stimulation for psychiatric indications has progressed at a steady pace in the adult population and at a much slower pace in the paediatric population. Future studies in children should be done in a trial setting with strict and robust criteria. A move towards personalising DBS therapy with new stimulation paradigms will provide new frontiers and possibilities in this growing field.

Deep Brain Stimulation for Refractory Tourette Syndrome: Electrode Position and Clinical Outcome.

The efficacy of deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is accepted, but whether the efficacy of DBS treatment in the Japanese population is equivalent to those reported internationally and whether adverse effects are comparable are not yet known. This study evaluated the clinical practice and outcome of DBS for TS in a Japanese institution. This study included 25 consecutive patients with refractory TS treated with thalamic centromedian-parafascicular nucleus DBS. The severity of tics was evaluated with the Yale Global Tic Severity Scale (YGTSS) before surgery, at 1 year after surgery, and at the last follow-up of 3 years or more after surgery. The occurrence of adverse events, active contact locations, and stimulation conditions were also evaluated. YGTSS tic severity score decreased by average 45.2% at 1 year, and by 56.6% at the last follow-up. The reduction was significant for all aspects of the scores including motor tics, phonic tics, and impairment. The mean coordinates of active contacts were 7.62 mm lateral to the midline, 3.28 mm posterior to the midcommissural point, and 3.41 mm above anterior commissure-posterior commissure plane. Efficacy and stimulation conditions were equivalent to international reports. The stimulation-induced side effects included dysarthria (32.0%) and paresthesia (12.0%). Device infection occurred in three patients (12.0%) as a surgical complication. The DBS device was removed because of infection in two patients. DBS is an effective treatment for refractory TS, although careful indication is necessary because of the surgical risks and unknown long-term outcome.

Effects of stereotactic radiofrequency thermocoagulation in the globus pallidus internus on refractory tic disorders.

OBJECTIVE: To investigate the effect of stereotactic radiofrequency thermocoagulation in the globus pallidus internus on refractory tic disorders. MATERIALS AND METHODS: Forty patients with refractory tic disorders were enrolled between January 2015 and July 2017 to experience stereotactic radiofrequency thermocoagulation in the globus pallidus internus. All clinical data, Yale Global Tic Severity Scale (YGTSS) scores, serum dopamine (SDA), and 5-hydroxytryptamine (5-HT) were analyzed. RESULTS: Radiofrequency thermocoagulation was successfully performed in all patients. Periprocedural complications occurred in two patients (5.0%), one with fever (2.5%) and one with a urination disorder (2.5%); both returned to normal after treatment. After 12 months of follow-ups, excellent improvement was exhibited in 18 patients (45.0%), marked improvement in 10 (25.0%), good improvement in 9 (22.5%), and invalid in 3 (7.5%), with a total efficacy rate of 92.5% (37/40). Twenty-eight patients (70%) showed excellent or marked improvement without additional treatment after surgery. YGTSS scores were significantly (p < 0.05) decreased after compared with before thermocoagulation. SDA was significantly (p < 0.05) decreased 6 months (80.78 ± 18.82 ng/ml) and 12 months (75.65 ± 15.23 ng/ml) after compared with before (125.63 ± 35.26 ng/ml) surgery, whereas 5-HT was significantly (p < 0.05) increased 6 months (58.93 ± 16.88 ng/ml) and 12 months (62.63 ± 15.21 ng/ml) after compared with before (35.62 ± 3.41 ng/ml) surgery. CONCLUSION: Stereotactic radiofrequency thermocoagulation can be safely applied in the globus pallidus internus to treat refractory tic disorders, resulting in significant tic symptom relief and a decrease in SDA but increase in 5-HT.

Lead Repositioning Guided by Both Physiology and Atlas Based Targeting in Tourette Deep Brain Stimulation.

Background: The centromedian (CM) region of the thalamus is a common target for deep brain stimulation (DBS) treatment for Tourette Syndrome (TS). However, there are currently no standard microelectrode recording or macrostimulation methods to differentiate CM thalamus from other nearby structures and nuclei. Case Report: Here we present a case of failed conventional stereotactic targeting in TS DBS. Postoperative local field potential recordings (LFPs) showed features including beta power desynchronization during voluntary movement and thalamo-cortical phase amplitude coupling at rest. These findings suggested that the DBS lead was suboptimally placed in the ventral intermediate (VIM) nucleus of the thalamus rather than the intended CM region. Due to a lack of clinical improvement in tic severity scales three months following the initial surgery, the patient underwent lead revision surgery. Slight repositioning of the DBS leads resulted in a remarkably different clinical outcome. Afterwards, LFPs revealed less beta desynchronization and disappearance of the thalamo-cortical phase amplitude coupling. Follow-up clinical visits documented improvement of the patient's global tic scores. Discussion: This case provides preliminary evidence that combining physiology with atlas based targeting may possibly enhance outcomes in some cases of Tourette DBS. A larger prospective study will be required to confirm these findings. Highlight: This report demonstrates a case of failed centromedian nucleus region deep brain stimulation (DBS). We observed suboptimal tic improvement several months following DBS surgery and subsequent lead revision improved the outcome. The neurophysiology provided an important clue suggesting the possibility of suboptimally placed DBS leads. Repeat LFPs during lead revision revealed less beta desynchronization and disappearance of the thalamo-cortical phase amplitude coupling. There was improvement in tic outcome following slight repositioning during bilateral DBS lead revision. This case provides preliminary evidence supporting the use of physiology to augment the atlas based targeting of Tourette DBS cases.

Paediatric deep brain stimulation: ethical considerations in malignant Tourette syndrome.

Gilles de la Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterised by the presence of motor and vocal tics. Patients with malignant TS experience severe disease sequelae; risking morbidity and mortality due to tics, self-harm, psychiatric comorbidities and suicide. By definition, those cases termed 'malignant' are refractory to all conventional psychiatric and pharmacological regimens. In these instances, deep brain stimulation (DBS) may be efficacious. Current 2015 guidelines recommend a 6-month period absent of suicidal ideation before DBS is offered to patients with TS. We therefore wondered whether it may be ethically justifiable to offer DBS to a minor with malignant TS. We begin with a discussion of non-maleficence and beneficence. New evidence suggests that suicide risk in young patients with TS has been underestimated. In turn, DBS may represent an invaluable opportunity for children with malignant TS to secure future safety, independence and fulfilment. Postponing treatment is associated with additional risks. Ultimately, we assert this unique risk-benefit calculus justifies offering DBS to paediatric patients with malignant TS. A multidisciplinary team of clinicians must determine whether DBS is in the best interest of their individual patients. We conclude with a suggestion for future TS-DBS guidelines regarding suicidal ideation. The importance of informed consent and assent is underscored.

Deep Brain Stimulation Results in Greater Symptomatic Improvement in Tourette Syndrome than Conservative Measures: A Meta-Analysis.

INTRODUCTION: Deep brain stimulation (DBS) has emerged as a safe and effective therapy for refractory Tourette syndrome (TS). Recent studies have identified several neural targets as effective in reducing TS symptoms with DBS, but, to our knowledge, none has compared the effectiveness of DBS with conservative therapy. METHODS: A literature review was performed to identify studies investigating adult patient outcomes reported as Yale Global Tic Severity Scale (YGTSS) scores after DBS surgery, pharmacotherapy, and psychotherapy. Data were pooled using a random-effects model of inverse variance-weighted meta-analysis (n = 168 for DBS, n = 131 for medications, and n = 154 for behavioral therapy). RESULTS: DBS resulted in a significantly greater reduction in YGTSS total score (49.9 ± 17.5%) than pharmacotherapy (22.5 ± 15.2%, p = 0.001) or psychotherapy (20.0 ± 11.3%, p < 0.001), with a complication (adverse effect) rate of 0.15/case, 1.13/case, and 0.60/case, respectively. CONCLUSION: Our data suggest that adult patients with refractory TS undergoing DBS experience greater symptomatic improvement with surprisingly low morbidity than can be obtained with pharmacotherapy or psychotherapy.

Anterior Limb of Internal Capsule and Bed Nucleus of Stria Terminalis Stimulation for Gilles de la Tourette Syndrome with Obsessive-Compulsive Disorder in Adolescence: A Case of Success.

Gilles de la Tourette syndrome (GTS) is a neurobehavioral disorder comprising motor and vocal tics. In most cases it is associated with other disorders such as obsessive-compulsive disorder (OCD). In refractory cases deep brain stimulation (DBS) is a valid treatment option. This paper describes the case of a 15-year-old adolescent with an extremely refractory GTS with associated OCD. The patient developed catatonia associated with OCD, which partially remitted after electroconvulsive therapy. At the peak of the disease the Yale Global Tic Severity Scale (YGTSS) was 100 and the patient required sedation and intubation. All medical treatment options were unsuccessful. Bilateral DBS of the anterior limb of internal capsule (ALIC)/bed nucleus of stria terminalis (BST) region was performed, using a target below the BST and a trajectory through the ALIC, with stimulation of contacts 0 and 3. Two weeks after surgery sedatives were suspended and the patient was successfully extubated. One year after surgery the patient reached a YGTSS of 19, representing an 81% improvement. OCD completely resolved. Adverse events were a superficial infection and weight gain. In conclusion, this ALIC/BST stimulation appears to have been an effective and safe treatment for GTS with OCD in this case. Young age should not be an exclusion criterion for DBS in severe GTS and OCD. Further studies should be pursued for this target.