Deep Brain Stimulation in Tourette Syndrome

Table Summarizing Clinical Research Studies

Studies used in this table were either double-blinded crossover trials and/or prospective trials or case series.

First Author (Year)	Study Title	Country Funder(s)	Intervention  Tested	Study Size	Inclusion Criteria, Patient Demographics	Trial Type	Findings +/-
Investigational Brain Stimulation Target: Centromedian Nucleus (CMT) / Parafasicular Complex (Pf) / Ventral Oral Nucleus (Voa) / Substantia Paraventricularis (Spv) of the Thalamus
Okun (2013)	A Trial of Scheduled Deep Brain Stimulation for Tourette Syndrome: Moving Away From Continuous Deep Brain Stimulation Paradigms	United States --- • National Institutes of  Health	Condition after Bilateral CMT Stimulation vs Condition without Stimulation  vs Condition before Implantation	5	• Adults (≥25 years old) • Severe disabling Tourette syndrome • No response to at least 4 drugs • No untreated mood disorder or psychosis • No severe medical conditions • No recent illicit drug use • No prior neurosurgical intervention • No neurological disorder	Double Blinded Crossover Study followed by a Prospective Cohort Study Approved by the Institutional Review Board Length: 6 months	• Significant improvement seen at 6 months (average of 18.6% improvement • Improvement delayed in patients randomized to group with delayed stimulation • Immediate effect of scheduled stimulation was found to be comparable to the immediate effect of continuous stimulation Major Adverse Events:    • None
Porta (2012)	Deep brain stimulation for treatment of refractory Tourette syndrome: long-term follow-up	Italy --- • Italian Tourette Syndrome Association • National Hospital Research Development Fund	Condition after Bilateral CM-Pf-Voa  vs Condition before Implantation	18	• Patients ages 17-47 • Severe disabling Tourette syndrome • No response to at least 6 months medical treatment with at least 2 drugs • No severe medical conditions	Prospective Cohort Study Approved by the Institutional Ethical Standards Committee Length: ≥ 5 years	• Significant improvement seen at 36 months (average of 35.5% improvement) • 50% patients had at least a 35% improvement in their OCD score • Improvement in concurrent depression (average of 27.0% improvement) • Improvement in concurrent anxiety (average of 56.0% improvement) • Improvement in overall daily function (average of 32.0% improvement) Major Adverse Events:    • Intracranial hemorrhage (1/8)    • Discontinued stimulation due to lack of adequate therapeutic effects (2/8)
Savica (2012)	Deep Brain Stimulation in Tourette syndrome: A Description of 3 Patients With Excellent Outcome	United States --- • National Institutes of Health	Condition after Bilateral CMT-Pf Stimulation  vs Condition before Implantation	3	• Patients ages 17-35 • Severe Tourette syndrome • No response to at least 5 drugs • No response to behavioral therapy • Stable ADHD	Case Series Approved by the Institutional Review Board Length: 12 months	• Significant improvement seen at 12 months (average of 70% improvement) • Some immediate improvement of tics • Concurrent psychiatric symptoms remained stable or slightly improved Major Adverse Events:    • None
Ackermans (2010)	Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome	Belgium The Netherlands --- none mentioned	Condition after Bilateral CM-Vca-Spv  vs Condition without Stimulation vs Condition before Implantation	6	• Adults (≥25 years old) • Severe Tourette syndrome • No response to 3 month trials of at least 3 different medications • No response to 10 sessions of behavioral therapy • No psychiatric disorder • No current substance use • No structural brain abnormalities	Double Blinded Randomized Crossover Study Approved by the Institutional Ethics Committee Length: 12 months (3 month crossover)	• Blinded phase demonstrated significant improvement only in patients receiving stimulation (average of 37% more than those without stimulation) • Significant improvement seen at 12 months (average 49.2% improvement) • No effect on cognition • No significant improvement in concurrent ADHD, OCD,  Anxiety, or Depression Major Adverse Eventts:    • Brain hemorrhage (1/6)    • Infection (1/6)    • Decreased energy level (6/6)    • Blurry or double vision (6/6)
Visser-Vandewalle (2003)	Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases	Belgium The Netherlands --- none mentioned	Condition after Bilateral CMT-Pf Stimulation  vs Condition before Implantation	3	• Patients ages 28-45 • Severe Tourette syndrome • No response to multiple medications • No response to behavioral therapy • No severe medical conditions	Case Series Approved by the Institutional Ethics Committee Length: 26.7± 28.9 months (range 8-60 months)	• Significant reduction in tics after long-term follow-up (average of 82%) Major Adverse Events:    • None Side Effects:    • Decreased energy level (3/3)    • Increase Sexual Drive (1/3)
Investigational Brain Stimulation Target: Globus Pallidus pars interna (GPi)
Cannon (2012)	Deep brain stimulation of anteromedial globus pallidus interna for severe Tourette's syndrome	Australia --- • •Medtronic, Inc. • New South Wales Institute of Psychiatry Training Fellowship • National Health and Medical Research Council of Australia Program	Condition after Bilateral GPi Stimulation  vs Condition before Implantation	11	• Adults (≥18 years old) • Severe Disabling Tourette syndrome • No response to at least 3 drugs • No response to behavioral therapy	Prospective Cohort Study Approved by the Institutional Review Boad Length: ≥3 months	• Significant improvement seen at 3 months (average of 49.6% improvement) • 54.5% had at least 50% improvement in their tic severity score • 92% reported improvement within 3 days of surgery •Significant improvement in concurrent Depression (average of 60.2% improvement) •Significant improvement in concurrent OCD (average of 56.9% improvement) Major Adverse Events:    • Worsening tics (1/11)    • Worsening Depression or Anxiety (2/11)    • Hardware malfunction (3/11)    • Infection (1/11)
Multiple Stimulation Locations
Welter (2008)	Internal pallidal and thalamic stimulation in patients with Tourette syndrome	France --- • National Institute of Health and Medical Research (INSERM) • University of Pierre and Marie Curie (Paris VI)  • Assistance-Publique-Hôpitaux de Paris	Condition after Bilateral Gpi Stimulation vs Condition after Bilateral CM-Pf Stimulation vs Condition after Bilateral Stimulation of Gpi & CM-Pf vs Condition without Stimulation	3	• Adults (≥18 years old) • Severe Disabling Tourette syndrome • No response to at least 6 months medical treatment • No cognitive deficits • No psychosis	Controlled Double Blinded Randomized Crossover Study Approved by INSERM and Institutional Ethics Committee Length: 37.7± 20.4 months	•The most significant improvement was seen with Gpi stimulation (average of 78.3% improvement) • Significant improvement was seen with CM-Pf stimulation (average of 44.7% improvement) • Significant improvement was seen with stimulation of both (average of 59.7%) • In 2 patients, turning off stimulation resulted in return of symptoms nearly to baseline levels • No negative effect on cognition • Decrease in Depression and Anxiety with CM-Pf stimulation Major Adverse Events:    • Decreased energy level (3/3)    • Numbness of face/arm (3/3)    • Nausea/Vertigo (2/3)   • Decreased libido (1/3)

Compiled during 2012-2013 by International Neuromodulation Society member Chengyuan Wu, MD, MSBmE, Thomas Jefferson University Hospital, Department of Neurosurgery and second-year medical student Lekhaj Daggubati, Drexel University School of Medicine

Please note: This information should not be used as a substitute for medical treatment and advice. Always consult a medical professional about any health-related questions or concerns.