Website Edition: October/November 2009

Update on DBS for Tourette Syndrome

Irene A.C. Malaty, Michael S. Okun
University of Florida, Department of Neurology

University of Florida Center for Movement Disorders & Neurorestoration


The demonstration in the 1960's that symptoms of Tourette syndrome (TS) could be effectively treated with haloperidol helped to revolutionize the understanding of the disease and shift the conceptualization from a purely psychological (or "psychogenic") problem to one of a more organic etiology. Since that time, the arsenal for pharmacologic treatment has expanded, but has unfortunately remained unsatisfactory for some medically-refractory patients. The advancements in deep brain stimulation (DBS) surgery for movement disorders such as Parkinson disease and dystonia coupled with the scattered historical reports of lesion therapies for TS have led to a growing interest in exploring the role of DBS for addressing the most severe medically and behaviorally resistant patients.

History of Surgery for TS

Tourette syndrome is felt to be a disease of corticostriatothalamocortical loops. Historical attempts at neurosurgical intervention for medically-refractory Tourette syndrome have included lesions of frontal, limbic, thalamic, infrathalamic, and cerebellar targets. These have all been utilized as a means to disrupt the abnormal communication in these abnormally firing circuits. Temel and Visser-Vandewalle have reviewed in detail the isolated historical reports of treatment from 1960 to 2003 (Temel and Visser-Vandewalle 2004). Conclusions from isolated procedures however are limited by lack of standardized outcome reporting and a lack of true knowledge of the target localization.

Small patient series in TS surgery have included Hassler and Dieckmann's work. They initially reported a series of three patients treated with intralaminar and medial thalamic nuclei ablation, leading to 70-100% tic remission. In their series there were only minor complications related to concentration and memory, and these improved with time. Notably, the target confirmation was limited to the anatomical expertise of the surgeon, and 11-13 coagulations were performed in each patient, such that the technical procedure itself therefore may not have been limited to the intended target (Hassler and Dieckmann 1970).

Babel et al summarized the long-term follow-up of 17 patients treated between 1970 and 1998 with infrathalamic and/or thalamic lesions in zona incerta (ZI) and ventrolateral/lamella medialis (VL/PM) thalamotomy. Eleven patients were followed for an average of 7 years (3.5-17), and 6 were lost to long-term follow-up. A significant reduction in motor and vocal tics as assessed by a tic severity rating scale (P<0.001) was found in both immediate and long-term assessments, and all patients except for two felt satisfied with surgical outcomes. Sixty-eight percent of patients had transient complications. One of six patients treated unilaterally had a permanent (Babel, Warnke et al. 2001) complication, and two of five treated bilaterally and followed long-term had disabling complications. Complications included mild hemiparesis and hemiballism.

Additional procedures have historically included prefrontal leukotomy (Kulisevsky, Berthier et al. 1995), limbic leukotomy (Robertson, Doran et al. 1990), cingulotomy with or without hypothalamotomy (Kurlan, Kersun et al. 1990; Baer, Rauch et al. 1994), the infrathalamic target of zona incerta with or without red nucleus (Leckman, de Lotbiniere et al. 1993; Babel, Warnke et al. 2001), the medial and intralaminar thalamic nuclei (Hassler and Dieckmann 1970), and dentatotomy (Nadvornik, Sramka et al. 1972) (Neimat, Patil et al. 2006).

Targets and trials

In the last decade, multiple targets have been investigated for DBS as a surgical approach for improving medication-refractory Tourette syndrome.

1.) Target: Thalamus

The first case of DBS for TS was reported by Visser-Vandewalle and colleagues in 1999, targeting the intralaminar thalamic nuclei and employing a trajectory which recapitulated the technique of Hassler and Dieckman, including the centromedian and ventral oral internal thalamic nuclei as well as the substantia paraventricularis (Vandewalle, van der Linden et al. 1999). This case was followed by reports of two additional surgeries in the same target, and there was a 72-90% tic reduction overall. Adverse effects included fatigue and change in sexual function (Visser-Vandewalle, Temel et al. 2003).

Bajwa et al reported a 48yo man with malignant TS who had developed progressive left-sided weakness from spinal cord trauma due to whiplash (violent head jerking) tics. He was also implanted in the centromedian, substantia periventricularis, and ventro-oralis internis, and experienced tic reduction of 66% in the Yale Global Tic Severity Scale (YGTSS) at 24months post-operatively. The patient also had improvement on self-assessment, as well as obsessive-compulsive and mood symptoms (Bajwa, de Lotbiniere et al. 2007). Maciunas et al. reported a randomized, double blind trial of bilateral thalamic DBS in 5 patients with TS. Outcomes were assessed with each unilateral lead, both leads, or with both leads off. Motor and vocal tic counts improved with bilateral stimulation by 40% and 21%, respectively, at 3months. Unilateral stimulation was not found to be effective. As a secondary outcome, there was a 44% improvement at 3months in YGTSS total score. This measure did not reach statistical significance for all patients, but three of the patients had improvement on all outcome measures (Maciunas, Maddux et al. 2007).

Servello et al. reported the largest series of 18 patients (age 17-47 years) with TS who underwent bilateral centromedian parafascicular (CM-Pf) and ventralis oralis (Vo) complex thalamus stimulation and who were subsequently followed for 3-18months. All patients experienced improvement of tics, but to varying degrees, with motor tics tending to respond to a greater degree than vocal tics. "On/off" and sham conditions were employed in a subset (9) of the patients using a blinded rater to confirm stimulation effects. Premonitory urges, obsessive-compulsive symptoms, anxiety, and self-injurious behaviors were also reported to improve. Only 2 patients experienced surgical adverse effects, which included a failure of the scalp incision to heal due to compulsive touching, and an abdominal hematoma related to the pulse generator (Servello, Porta et al. 2008).

2.) Target: Globus pallidus, internal segment (GPi)

The first long-term report of a case of bilateral GPi DBS was reported by Diederich et al in 2005, with 73% reduction in tic frequency per minute, and progressive benefit that was sustained at 14 months post-operatively. The YGTSS improved from 83 before surgery to 44 at 14 months post-operatively. A 48 hour period off stimulation led to return of tics. A permanent side effect of left-sided bradykinesia occurred. (Diederich, Kalteis et al. 2005).

Ackermans et al, reported a 27 year old man with one year follow-up who had improvement in both tic counts and obsessive compulsive symptoms following bilateral GPi DBS (Ackermans, Temel et al. 2006).

Shahed et al described a 16 year old boy with intractable TS who had bilateral GPi DBS, resulting in 63% improvement in YGTSS and 85% improvement in tic symptoms on self report (Shahed, Poysky et al. 2007).

3.) Target: Anterior limb internal capsule/ nucleus accumbens

Flaherty et al. reported a 37 year old woman with severe tics who had a 25% reduction at 18months after anterior limb internal capsule/nucleus accumbens (ALIC/NA) DBS implantation. Stimulation dorsal or ventral to the active contact resulted in hypomania or depressive symptoms, respectively (Flaherty, Williams et al. 2005).

Zabek, et al reported abatement of motor and vocal tics with compulsions and self-injurious behavior sustained at 28 months of follow-up after unilateral right-sided nucleus accumbens DBS (Zabek, Sobstyl et al. 2008).

Kuhn and colleauges reported the case of a 26 year old male with TS complicated by self-injurious behavior and obsessive compulsive disorder (SIB and OCD) implanted in nucleus accumbens. The patient had 41% improvement in YGTSS and 50% reduction Rush Video-based Tic Rating Scale (RVTRS) at 2.5 years, as well as improvement in OCD (YBOCS 25 preoperatively, 12 at last follow-up) (Kuhn, Lenartz et al. 2007).

Neuner et al. recently reported the 3 year outcome of a 38 year old man implanted for severe TS and OCD. In addition to tics and self-injurious behavior, he had the compulsion to break glass and had broken the windshield of his car on multiple occasions. YGTSS improved from 100 before surgery to 54 at 3 months post-operatively, and to 56 at 36 months of followup. Interestingly, the urge to break glass abated, and he lost the urge to smoke. The Yale-Brown Obsessive Compulsive Scale (YBOCS) dropped from 32 before surgery to 14 at 36 months of followup (Neuner, Podoll et al. 2009).

4.) Multiple targets

Visser-Vandewalle et. al reported a patient implanted in both medial thalamus and the internal segment of the globus pallidus. Stimulation at each lead was individually assessed, and the former led to 80% tic reduction, compared to 95% reduction with the latter. Benefit was maintained at 6months follow-up.

Houeto et al also reported a 36-year-old woman with childhood-onset of GTS with coprolalia, tics, and self-injurious behavior implanted bilaterally with both centromedian-parafasicular complex of thalamus and GPi DBS. Double-blind assessment of tic frequency was conducted for stimulation at one or both of the targets, and with sham stimulation. Tic reduction was documented by the Yale Global Tic Severity Scale (YGTSS) and Rush video based tic scale (RVBTS) and was 65% and 77% for thalamic and 65% and 67% for pallidal stimulation, respectively. Sham stimulation led to full return of tics and self-injurious behavior, and stimulating at both targets bilaterally led to 70% reduction in tics (Houeto, Karachi et al. 2005).

Servello et al. reported outcomes from "rescue" lead implantation for two patients with persistent, disabling OCD following VO/CM-Pf DBS who were then implanted in ALIC/NA. Also, two subsequent patients were implanted de novo in ALIC/NA plus VO/CM-PF, or ALIC/NA alone based on prominence of obsessive-compulsive symptoms. Although all patients had some improvement in tics and OCD symptoms, the magnitude of improvements in mood and OCD were not as robust as the authors had hoped, relative to prior benefit reports in primary OCD patients (Servello, Sassi et al. 2009).

Important Questions For Moving Forward with DBS for Tourette Syndrome:

When and who? Patient selection and timing

Given the natural history of significant abatement or resolution of TS symptoms in the majority of patients by late adolescence or early adulthood, the appropriate timing of intervention and patient selection will need to be defined. Certainly, adequate therapeutic trials with regard to variety, dose, and duration of medical therapy will be mandatory. The use of behavioral therapies such as habit reversal will need more attention.

Will complex patients require more than one target?

Future trials will help elucidate whether particular therapeutic targets may offer greater benefit for different symptoms of TS. Perhaps motor symptoms may require one target, and obsessive compulsive symptoms another. Combination therapy may be required for management of the most complex patients.


The Tourette Syndrome Study Group, through the Tourette Syndrome Association, gathered experts in the fields of TS and DBS to review current knowledge and guide future directions in research by producing guidelines for the safe, informed participation of appropriate subjects, based on the current understanding of TS (Mink, Walkup et al. 2006).

Guidelines ultimately proposed included:

Inclusion Criteria Exclusion Criteria
>/= 25yo Secondary tics
Severe impairment Medical, psychiatric, or neurological contraindication to participate in DBS
Treatment refractory to conventional therapy including behavioral Ongoing psychological treatment needs
Active treatment for >6mo before DBS Psychosocial factors that may obstruct participation
Active involvement in psychological treatment Unwilling to participate in needed psychological interventions

As we move forward in navigating this new and exciting avenue in the care of the refractory TS patient, detailed outcome reporting will be essential. There is a clear need for double blind, sham controlled trials with adequate power and long-term follow-up (Okun, Fernandez et al. 2008). Comprehensive evaluation of the cognitive and behavioral stretches of the disease, both before and after surgery, are needed to elucidate the impact on motor and non-motor aspects of TS. Imaging studies for target confirmation and reporting of both positive and negative outcomes, as well as effective programming parameters will be critical. Recently two centers in the United States have FDA approval to perform DBS for TS (University of Florida and Case Western), and many other countries are performing the surgery worldwide.

Ackermans, L., Y. Temel, et al. (2006). "Deep brain stimulation in Tourette's syndrome: two targets?" Mov Disord 21(5): 709-13.

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette's syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS.

Babel, T. B., P. C. Warnke, et al. (2001). "Immediate and long term outcome after infrathalamic and thalamic lesioning for intractable Tourette's syndrome." J Neurol Neurosurg Psychiatry 70(5): 666-71.

OBJECTIVE: The surgical treatment of intractable Tourette's syndrome is controversial. Experience with 17 consecutive patients treated between 1970 and 1998 is reviewed and the efficacy and safety of surgical treatment is assessed. METHODS: These patients were retrospectively reclassified into subtypes according to the protocol of the Tourette's Syndrome Study Group. One patient was excluded from the study. Ventriculography based stereotactic zona incerta (ZI) and ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all patients. The preoperative, postoperative, and late tic severities were assessed by the tic severity rating scale. The median follow up of 11 patients (65%) was 7 years (range 3.5-17 years) and six patients were lost to long term follow up. RESULTS: Median age was 23 years (range 11-40) at the time of surgery. Median duration of illness was 14 years (range 3-33). The mean preoperative motor and vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66), respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry of symptoms provide an effective control of tic severity (p motor and vocal<0.001). In attenuation of contralateral symptoms, a second surgical intervention in the relevant side could reduce tic severity sufficiently (p motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients. Only one permanent complication was registered in six patients followed up after unilateral surgery. Two out of five patients followed up after bilateral surgery had disabling side effects of surgery. CONCLUSIONS: ZI and VL/LM lesioning provide a significant long term reduction of tic severity in intractable Tourette's syndrome. Adequate selection of the side of first intervention might prevent the patient from increased risk of bilateral surgery.

Baer, L., S. L. Rauch, et al. (1994). "Cingulotomy in a case of concomitant obsessive-compulsive disorder and Tourette's syndrome." Arch Gen Psychiatry 51(1): 73-4.

Bajwa, R. J., A. J. de Lotbiniere, et al. (2007). "Deep brain stimulation in Tourette's syndrome."Mov Disord22(9): 1346-50.

A 48-year-old man with severe, lifelong Tourette's syndrome (TS) characterized by forceful self-injurious motor tics and obsessive-compulsive disorder was treated with bilateral deep brain stimulation (DBS). The decision to treat was based on his progressive neurological impairment (left sided weakness secondary to spinal cord injury) because of his relentless, violent head jerks. Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis internus). DBS resulted in a substantial reduction of tics. These data show that bilateral DBS of the thalamus can have a good effect on severe tics in adult patients suffering from intractable TS.

Diederich, N. J., K. Kalteis, et al. (2005). "Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report."Mov Disord 20(11): 1496-9.

The usefulness of deep brain stimulation (DBS) of thalamic nuclei in Gilles de la Tourette syndrome (GTS) has recently been advocated. We report on a 14-month follow-up study of a patient with intractable GTS in whom bilateral DBS of the internal globus pallidus was carried out. Tic frequency per minute decreased by 73% in the postoperative phase and in particular the vocal tics became less intense. Pronation/ supination bradykinesia of the left extremities was a well-tolerated, permanent side effect. Pallidal DBS could become a valuable rescue therapy for otherwise intractable GTS.

Flaherty, A. W., Z. M. Williams, et al. (2005). "Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report." Neurosurgery 57(4 Suppl): E403; discussion E403.

OBJECTIVE AND IMPORTANCE: Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. CLINICAL PRESENTATION: We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. INTERVENTION: We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. CONCLUSION: Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome.

Hassler, R. and G. Dieckmann (1970). "[Stereotaxic treatment of tics and inarticulate cries or coprolalia considered as motor obsessional phenomena in Gilles de la Tourette's disease]." Rev Neurol (Paris) 123(2): 89-100.

Houeto, J. L., C. Karachi, et al. (2005). "Tourette's syndrome and deep brain stimulation." J Neurol Neurosurg Psychiatry 76(7): 992-5.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

Kuhn, J., D. Lenartz, et al. (2007). "Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome." J Neurol 254(7): 963-5.

Kulisevsky, J., M. L. Berthier, et al. (1995). "Longitudinal evolution of prefrontal leucotomy in Tourette's syndrome."Mov Disord 10(3): 345-8.

We report the case of a 69-year-old man with severe Tourette's syndrome (TS) who underwent a bilateral prefrontal leucotomy at the age of 29 years to alleviate coprolalia, copropraxia, and obsessive-compulsive disorder. No improvement was observed during the 5 years after the leucotomy. Tics and associated behavioral abnormalities disappeared thereafter, to recur at age 67. Long-term follow-up of single cases can help to estimate the role of neurosurgery in the treatment of TS.

Kurlan, R., J. Kersun, et al. (1990). "Neurosurgical treatment of severe obsessive-compulsive disorder associated with Tourette's syndrome."Mov Disord 5(2): 152-5.

We describe two patients with Gilles de la Tourette's syndrome (TS) and disabling obsessive-compulsive and ritualistic behaviors who underwent bilateral radiofrequency anterior cingulotomy. Both achieved a limited but sustained improvement in behavioral symptoms and overall functional abilities. Our observations indicate involvement of limbic structures in this disorder. The procedure should be considered for patients with TS complicated by resistant obsessive-compulsive disorder.

Leckman, J. F., A. J. de Lotbiniere, et al. (1993). "Severe disturbances in speech, swallowing, and gait following stereotactic infrathalamic lesions in Gilles de la Tourette's syndrome." Neurology 43(5): 890-4.

A 40-year-old man with severe Gilles de la Tourette's syndrome characterized by forceful self-injurious motor tics, coprolalia, and obsessive-compulsive disorder had bilateral anterior cingulotomies and bilateral infrathalamic lesions placed stereotactically during two neurosurgical procedures. During the second procedure, the patient acutely developed a marked dysarthria. Postoperatively, he manifested a severe gait disturbance with postural instability, bradykinesia, axial rigidity, micrographia, and a profound swallowing disorder. MRI showed asymmetric (left > right) low-density areas in an infrathalamic region as well as low-density areas bilaterally in the anterior cingulate gyri. Although the patient's tic and obsessive-compulsive symptoms improved, the self-injurious motor tics along with other motor and phonic tics have recurred. The patient's speech remains largely unintelligible 8 months following the last surgical procedure, and the other neurologic deficits remain unchanged.

Maciunas, R. J., B. N. Maddux, et al. (2007). "Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome." J Neurosurg 107(5): 1004-14.

OBJECT: The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. METHODS: Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. RESULTS: In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. CONCLUSIONS: Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

Mink, J. W., J. Walkup, et al. (2006). "Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome."Mov Disord 21(11): 1831-8.

In response to recent publicity regarding the potential use of deep brain stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the Tourette Syndrome Association convened a group of TS and DBS experts to develop recommendations to guide the early use and potential clinical trials of DBS for TS and other tic disorders. The goals of these recommendations are to ensure that all surgical candidates are (1) fully informed about the risks, benefits, and alternative treatments available; (2) receive a comprehensive evaluation before surgery to ensure that DBS is clearly the appropriate clinical treatment choice; and (3) that early clinical experience will be documented publicly to facilitate rational decision-making for both clinical care and future clinical trials.

Nadvornik, P., M. Sramka, et al. (1972). "Experiences with dentatotomy." Confin Neurol 34(5): 320-4.

Neimat, J. S., P. G. Patil, et al. (2006). "Novel surgical therapies for Tourette syndrome." J Child Neurol 21(8): 715-8.

Tourette syndrome is a common neurologic disorder with close ties to obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The majority of patients improve spontaneously as they near adulthood. Most others are effectively treated with pharmacologic agents, although these therapies fail for an unfortunate few. For patients debilitated by the disease despite medical therapy, surgery can become an important option.

Neuner, I., K. Podoll, et al. (2009). "Deep brain stimulation in the nucleus accumbens for intractable Tourette's syndrome: follow-up report of 36 months." Biol Psychiatry 65(4): e5-6.

Okun, M. S., H. H. Fernandez, et al. (2008). "Avoiding deep brain stimulation failures in Tourette syndrome." J Neurol Neurosurg Psychiatry 79(2): 111-2.

Robertson, M., M. Doran, et al. (1990). "The treatment of Gilles de la Tourette syndrome by limbic leucotomy." J Neurol Neurosurg Psychiatry 53(8): 691-4.

A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy.

Servello, D., M. Porta, et al. (2008). "Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation." J Neurol Neurosurg Psychiatry 79(2): 136-42.

BACKGROUND: There have been several reports of successful deep brain stimulation (DBS) for the treatment of severe Gilles de la Tourette syndrome (GTS). METHOD: 18 cases of GTS who were resistant to at least 6 months of standard and innovative treatments, as well as to psychobehavioural techniques, underwent DBS. DBS was placed bilaterally in the centromedian-parafascicular (CM-Pfc) and ventralis oralis complex of the thalamus. Patients were evaluated after surgery, with immediate and formal assessments at least every 3 months, including "on-off" and "sham off" in the first nine patients. RESULTS: All patients responded well to DBS, although to differing degrees. The duration of follow-up assessments ranged from 3 to 18 months. The comorbid symptoms of obsessive-compulsive behaviour, obsessive-compulsive disorder, self-injurious behaviours, anxiety and premonitory sensations decreased after treatment with DBS. There were no serious permanent adverse effects. CONCLUSIONS: DBS is a useful and safe treatment for severe GTS. The results of ours and previous DBS reports suggest that the CM-Pfc and ventralis oralis complex of the thalamus may be a good DBS target for GTS.

Servello, D., M. Sassi, et al. (2009). "De novo and rescue DBS leads for refractory Tourette syndrome patients with severe comorbid OCD: a multiple case report." J Neurol 256(9): 1533-9.

Invasive treatment for Gilles de la Tourette syndrome has shown interesting results in a number of published reports; it seems to be evolving into a promising therapeutic procedure for those patients demonstrating disabling clinical pictures who are refractory to conservative treatments. There are important issues concerning the stimulated brain target, with different nuclei currently under investigation. Our group asked in this pilot study whether Tourette syndrome could be treated by tailoring specific brain targets for specific symptoms. Deep brain stimulation for Tourette syndrome may thus in the future be tailored and patient specific, utilizing specific target regions for individual clinical manifestations. In our early experience we did not adequately address non-motor clinical symptoms as we only used a thalamic target. More recently in an obsessive compulsive disease cohort we have had success in using the anterior limb of the internal capsule and nucleus accumbens region as targets for stimulation. We therefore explored the option of a "rescue" procedure for our Tourette patients with persistent obsessive-compulsive disorder following ventralis oralis/centromedianus-parafascicularis (Vo/CM-Pf) deep brain stimulation. Following two cases where rescue anterior limb of internal capsule/nucleus accumbens leads were employed, we performed two additional procedures (anterior limb of the internal capsule plus ventralis oralis/centromedianus-parafascicularis and anterior limb of the internal capsule alone) with some mild improvement of comorbid obsessive-compulsive disorder, although the number of observations in this case series was low. Overall, the effects observed with using the anterior limb of the internal capsule either alone or as a rescue were less than expected. In this report we detail our experience with this approach.

Shahed, J., J. Poysky, et al. (2007). "GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities." Neurology 68(2): 159-60.

Temel, Y. and V. Visser-Vandewalle (2004). "Surgery in Tourette syndrome."Mov Disord 19(1): 3-14.

Tourette syndrome (TS) is a neuropsychiatric disorder with onset in early childhood. It is characterized by tics and often accompanied by disturbances in behavior, such as obsessive-compulsive disorder (OCD). In most cases, the disorder is self-limited or can be treated by medication or behavioral therapy. In a small percentage, however, symptoms are intractable to any conservative treatment. Since 1955, various attempts have been made to treat these patients through neurosurgical procedures. The target sites have been diverse and include the frontal lobe (prefrontal lobotomy and bimedial frontal leucotomy), the limbic system (limbic leucotomy and anterior cingulotomy), the thalamus, and the cerebellum. Combined approaches have also been tried such as anterior cingulotomies plus infrathalamic lesions. The results have often been unsatisfactory or major side effects have occurred, such as hemiplegia or dystonia. Our review of the literature from 1960 until 2003 revealed 21 reports and 3 descriptions in textbooks covering about 65 patients in total who had undergone ablative procedures for intractable TS, the first being reported in 1962. In 1999, deep brain stimulation (DBS) was introduced as a new approach for intractable TS. To date, 3 patients have been reported who underwent bilateral thalamic stimulation, with promising results on tics and obsessive-compulsive symptoms.

Vandewalle, V., C. van der Linden, et al. (1999). "Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus." Lancet 353(9154): 724.

Visser-Vandewalle, V., Y. Temel, et al. (2003). "Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases." J Neurosurg 99(6): 1094-100.

Based on the results of thalamotomies described by Hassler in 1970, the authors performed bilateral thalamic high-frequency stimulation (HFS) in three patients with intractable Tourette syndrome (TS). In this report they describe the long-term effects. Three male patients (42, 28, and 45 years of age) had manifested motor and vocal tics since early childhood. The diagnosis of TS was made according to the criteria of the Tourette Syndrome Classification Study Group. Any drug or alternative treatment had been either ineffective or only temporarily effective in all three patients. There was no serious comorbidity. The target for stimulation was chosen at the level of the centromedian nucleus, substantia periventricularis, and nucleus ventrooralis internus. After 2 weeks of test stimulation, the pulse generators were implanted. After a follow-up period of 5 years in the patient in Case 1, 1 year in the patient in Case 2, and 8 months in the patient in Case 3, all major motor and vocal tics had disappeared and no serious complications had occurred. When stimulation was applied at the voltage necessary to achieve an optimal result on the tics, a slight sedative effect was noted in all three patients. In the patients in Cases 1 and 3 there were stimulation-induced changes in sexual behavior. Chronic thalamic HFS may be an effective and safe treatment for medically intractable TS in adult patients. Unwanted stimulation-induced side effects may occur.

Zabek, M., M. Sobstyl, et al. (2008). "Deep brain stimulation of the right nucleus accumbens in a patient with Tourette syndrome. Case report." Neurol Neurochir Pol 42(6): 554-9.

We describe the effects of unilateral right-sided nucleus accumbens (NA) stimulation in a patient with intractable Gilles de la Tourette syndrome (GTS) with associated compulsions and self-injurious behaviour. Pharmacological and behavioural therapies had completely failed to control the patient's tics and compulsions. The electrode (Model 3389 Medtronic, Minneapolis, MN) was implanted in the right NA. At 28-month follow-up, deep brain stimulation (DBS) of the right NA effectively alleviated tics and compulsions with patient's self-injurious behaviour. We suggest that this approach can be an effective treatment option for GTS with intractable motor and vocal tics with associated compulsions with self-injurious behaviour.