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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.

 

 

Last Updated on Friday, June 16, 2017 08:16 AM