Brain Stimulation for the Treatment of Tourette Syndrome

DBS is a surgical procedure that seeks to change the brain's electrical signalling by means
of applied electrical current. To this end, a wire with tiny stimulating electrodes is
implanted into one or both sides of the brain. An electrode is a small piece of metal used to
take an electric current to or from a power source. These electrodes are connected under the
skin on the scalp to a small electrical unit called an INS (implantable neurostimulator),
which is similar to a heart pacemaker. The device sends out electrical impulses that appear
to change the normal flow of electricity in the brain.

The wires which house the electrodes will be implanted on both sides of the brain oriented
towards the centromedian thalamus-parafascicular complex. This region of the brain has to
date the greats number of documented cases revealing significant improvements in motor tics.

This region of the brain will also provide a target where physiological changes related to
motor tics are likely to be discovered.

The device we propose for this study has several features that make it more suitable for use
in the TS population than other devices. It is self-contained in the skull and brain, and
contains no tunneled neck connector wire and no chest pacemaker deice. This will help to
lessen infection, and will assist in limiting device-related fractures due to tics involving
neck region. Also, the system can record electro-encephalograph data from the area of the
electrodes, which will assist us in gathering information about what specific physiological
changes are correlated with tics.

Inclusion Criteria:

- diagnosis of TS must be made by both a neurologist and a psychiatrist and must meet
standardized criteria

- must have a minimum score on the primary tic rating scale

- symptoms must be causing significant impairment in functioning, making it impossible
or almost impossible to do daily activities, including work or school and interactions
with friends and family, causing severe distress and a poor quality of life

- symptoms have not responded well enough to medications prescribed by a neurologist or
psychiatrist experienced in treating TS. Must have had trials of drugs from three
different classes of drugs that have not worked.

- must have received stable and effective treatment of any other existing medical or
psychological problems for the past 6 months.

- current TS related-medication(s) must be stable for at least a month without a dose
change prior to surgery and must be willing to keep these medications stable and
unchanged throughout the study or must be off of TS-related medications for at least
three months prior to surgery

- If tics involve only one group of muscles or might be controllable by botulinum toxin
treatment, must try botulinum treatment before considering surgery.

- must have a negative urine drug screen

- must give informed consent

Exclusion Criteria:

- have a simple motor tic or movement disorder other than TS, or medication-related
movement disorders from TS medications

- have had any previous brain surgery including deep brain stimulation, ablative
capsulotomy or cingulotomy

- have another psychiatric condition (including body dysmorphic disorder, a delusional
disorder or a biological brain disorder), dementia or cognitive dysfunction that would
place subject at risk for worsening cognition and/or may impact ability to comply with
study procedures. Also included is any other psychiatric disorder that requires
medications or treatments that would interfere with the functioning of the DBS device.

- have any significant substance abuse or dependence (e.g., stimulants, alcohol,
opiates, benzodiazepines) within the past six months

- have a severe medical disease including cardiovascular disorder, lung disorder, kidney
disease, chronic neurological disease, hematological disease, or frailty that impacts
tolerability of the surgery as judged by the screening physicians

- pre-surgery MRI is considered abnormal. You may also be excluded if your brain is
considered very small.

- have a history of serious suicidal behavior, are unable to control suicide attempts,
or are currently at risk of suicide, in the judgement of the investigator

- have head-banging tics or tics that have the potential to damage the RNS System

- are currently pregnant or breast-feeding, plan to become pregnant during the study, or
are not using effective contraception

- are currently enrolled in another investigational study

- have an implant such as a pacemaker or neurostimulator containing electrical circuitry
or that generates electrical signals

- have any metal orthopedic pins or plates, metal orthodontics, or non-removable body
jewelry

- require diathermy treatments during physical or occupational therapy

- have a problem that will require repeat Magnetic Resonance Imaging (MRI) scans