Thalamic Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome

Inclusion Criteria:

1. Males and females who are >=15 years of age. There is no strict age cutoff at the
upper limit of inclusion, however subjects may meet the exclusion criteria based on
medical contraindications to deep brain stimulation surgery (Points 3. and 6. under
the Exclusion Criteria). For subjects in the age range of 15-24 years, an additional
Ethics Committee consultation will be obtained prior to offering the subject the
required screening visit. This is based on the revised screening criteria now proposed
by Shrock, Mink, et al. on studies investigating DBS in TS. Additionally, for subjects
in the age range of 15-20, a caregiver will be required to be present for all study
visits.

2. Subject has a diagnosis of TS as determined by a review of medical records, discussion
with referring psychiatrist as well as the DSM-IV criteria and videotaped assessment.
This will include an assessment to determine the presence of psychogenic tics,
embellishment, factitious symptoms, personality disorders and malingering.

3. Subject determined to be treatment-resistant for at least one year prior to the
Screening Visit as demonstrated by clinical evidence (determined by review of medical
records and discussion with referring psychiatrist or neurologist) of persistent
functionally impairing tics that have not responded to treatment with a minimum of
three adequate regimens of medication including two failed trials of at least one
typical neuroleptic and one atypical neuroleptic medication, along with one failed
trial of a first tier medication as defined as follows:

1. Adequate trials of one non-neuroleptic medication including drugs from the
following (first tier) list: clonidine, guanfacine, topiramate, baclofen,
levetiracetam, and clonazepam. Trial failure is defined as demonstrated lack of
efficacy or severe side effects.

2. Two adequate trials of at least one typical neuroleptic medication (pimozide,
fluphenazine, haloperidol) and at least one atypical neuroleptic (risperidone,
aripiprazole, ziprasidone, olanzapine, quetiapine). Trial failure is defined as
demonstrated lack of efficacy or severe side effects.

4. A mandatory trial of behavioral interventions in an attempt to reduce the severity of
the tics or comorbid symptoms must also be completed by the subject before offering
participation in this trial. This may include habit reversal therapies, stress
reduction therapies, or other behavioral therapies under investigation for tic
suppression.

5. Subject has both significant vocal and motor tics with a tic subscale score of at
least 35 on the YGTSS (Yale Global Tic Severity Scale) at all three Baseline Visits
prior to undergoing surgery. For subjects with predominantly vocal tics (and minimal
motor) causing significant problems this score requirement will be reduced to 18,
similarly for subjects with predominantly motor tics (and minimal vocal) causing
significant problems the required score will be 18. A portion of the study team,
including the surgeon and two neurologists, will determine by consensus which category
the subject falls into and whether the tics are a significant problem.

6. All other aspects of the subject's care must be optimized during the preceding 6
months before admission to the study. This includes treatment for comorbid medical,
neurological, and psychiatric disorders. Additionally, it includes psychological
interventions for any ongoing psychosocial problems the subject may have during the
preceding 6 months before study admission.

7. Subject must be ambulatory.

8. Females who are postmenopausal, physically incapable of childbearing, or practicing an
acceptable method of birth control. Acceptable methods of birth control include
surgical sterilization, hormonal contraceptives, or double-barrier methods (condom or
diaphragm with a spermicidal agent or intrauterine device [IUD]). If practicing an
acceptable method of birth control, a negative urine pregnancy test result has been
obtained at baseline Visits 1 and 3.

9. Subject is determined by an independent psychiatrist with expertise in capacity
assessments to have decision-making capacity to provide informed consent.

10. Subject is able to read English, understand and cooperate with study procedures, and
has signed a written informed consent form prior to any study procedures.

Exclusion Criteria:

1. Subject has a positive urine drug screen at any of the three Baseline Visits.

2. Subject had major surgery within three months prior to Baseline Visit 1 or has other
surgery planned during the proposed study period.

3. Subject is determined by medical consultant to have medical contraindications to
undergoing surgery.

4. Subject is pregnant or breast-feeding.

5. Subject has a history of alcohol or drug abuse within the past 6 months and/or
dependence within the past year.

6. Subject has a medical illness/condition, and/or abnormal diagnostic finding that would
interfere with the completion of the study, confound the results of the study, or pose
risk to the patient.

7. Subject has an untreated or uncontrolled Axis I disorder or other major psychiatric
disorder including major depression, bipolar disorder, or schizophrenia as determined
by the screening psychiatrist.

8. Subject has either a current or past history of suicidal plan and/or intent.

9. Subject has a tic disorder or other movement disorder attributable to another medical,
neurological, or psychiatric disorder other than Tourette Syndrome.

10. Subject has a drug-induced tic disorder.

11. Subject has significant psychosocial factors that might increase the risk of the DBS
procedure or complicate recovery and outcome assessments. (Examples include - history
of noncompliance with previous medical and psychosocial treatments, multiple failed
medication treatments of inadequate dose or duration, a history of multiple other
surgical procedures with poor outcome, unexplained medical history gaps, or pending
lawsuits or other legal action.)

12. Subject has metal in the head or any other type of implanted stimulator (i.e. cardiac
pacemaker, deep brain stimulator for a different disease, spinal cord stimulator,
cochlear implant, vagus nerve stimulator, etc.).

13. Subject has participated in another investigational drug trial or therapeutic trial
within 30 days of Baseline Visit 1.

14. Subject has a diagnosis of intellectual disability with documented IQ<70.

15. Subject has a neurological condition, or a history of traumatic brain injury
associated with loss of consciousness of > 1 hour and/or
intracranial/epidural/subdural bleeding.