Deep Brain Stimulation Surgery for Focal Hand Dystonia

Objectives

To confirm the safety and efficacy of thalamic deep brain stimulation (DBS) targeting the
ventralis oralis anterior/ventralis oralis posterior (VOA/VOP) nuclear complex in the
treatment of subjects with focal hand dystonia (FHD); and to study the electrophysiologic
properties of neurons in the VOA/VOP complex. Deep brain stimulation DBS is FDA approved for
Parkinson s disease, Essential tremor, Dystonia (humanitarian exemption), Obsessive-
Compulsive disorder (humanitarian exemption) but not for focal hand dystonia.

Study population

Five adults with focal hand dystonia will be studied.

Design

This is a pilot study of 5 subjects with severe intractable FHD whose activities of daily
living and quality of life are severely impaired. They will be recruited from our clinic and
referring practices. The subjects will undergo unilateral VOA/VOP DBS implantation, followed
by programming to optimal parameters. The subjects will be followed at monthly intervals for
3 months, then every 3 months for 2 years, and then every 6 months until 5 years from the
start. The safety of the procedure will be the primary outcome of the study. Efficacy will be
assessed in several secondary outcomes, the most important ones being the change in dystonia
severity and a quality of life scores. The electrophysiologic features of the motor ventral
thalamic neurons will be recorded intraoperatively.

Outcome measures

Primary

-Number and severity of adverse events in the 5-year follow-up period.

Secondary

- Upper extremity sub-score of the Burke-Fahn-Marsden (BFM) scale and Arm Dystonia
Disability Scale (ADDS) at baseline and every follow up visit

- For subjects with FHD type musician s dystonia: Tubiana and Chamagne scale at every
follow up visit

- For subjects with FHD type Writer s cramp: Writer's Cramp Impairment Scale

- Improvement on patient reported outcomes evaluated by the SF-12 Health Status Survey at
baseline and at every follow up visit

- Neuropsychological evaluation at baseline, 3 and 12 months post DBS surgery

- Dose of botulinum toxin injection required at baseline, 1 and 5 years.

Exploratory

-Intraoperatory electrophysiologic characteristics of the motor ventral thalamic neurons.

- INCLUSION CRITERIA:

- FHD diagnosed by a neurologist

- BFM upper extremity subscore of 3 or more (score range 0 to 4) or ADDS difficulty of
performing score equal to or more than 3.

- Patients must score 3 or below on the Tubiana and Chamagne scale or inability to
perform at the concert level or patients must score a rating of "severe" on at least
one item, impacting the patient s employment or essential activities on the Writer s
Cramp Impairment scale.

- Symptoms causing significant impairment in quality of life and daily activities by
patient self-assessment and SF12 scale, as reported by subjects. The subjects should
be severely impaired in at least one of the following domains: handwriting, typing or
playing an instrument. The impairment needs to have affected employment, manifested by
substantive change in, or loss of, employment or career of choice.

- All patients must have failed or achieved inadequate benefit (continuing functional
impairment) with at least two trials of botulinum toxin treatments.

- Women of childbearing age will have to agree to use contraception methods for the
first 3 post operative months.

EXCLUSION CRITERIA:

- Subjects younger than 22 years old.

- MRI findings that would make participation and surgery unsafe (such as tumor or other
space occupying lesion, stroke, hemorrhage or hematoma, edema, hydrocephalus, abscess)
and MRI findings that would confound study outcomes (such as iron deposits in the
basal ganglia, demyelinating disease, traumatic brain injury, structural or
developmental abnormality, moderate or severe white matter hyperintensities).

- Subjects with prior brain surgery

- Pregnant or nursing women as safety of DBS has not been established in this group.

- Presence of a more widespread neurologic syndrome with the dystonia being part of it,
and/or dystonia caused by an ongoing etiology, such as tardive dystonia associated
with ongoing psychotropic treatment or an inherited neurodegenerative syndrome
associated with intractable dystonia

- Intellectual disability as measured by the estimated General Ability Index (GAI) of
the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), which would render the
participant not able to provide informed consent or to comply with the study
procedures (estimated GAI less than 70)

- Dementia as evidenced by formal neuropsychological evaluation and Mattis Dementia
Rating Scale-2 (DRS-2) score below 128.

- Depressed subjects as determined by the neuropsychology screen, including Beck
Depression Inventory (BDI). Subjects scoring above 20 on the BDI will be excluded

- Subjects with uncontrolled co-existing medical conditions: uncontrolled systemic
hypertension with values above 170/100; active heart disease needing immediate
intervention; active respiratory disease needing immediate intervention; uncorrected
coagulation abnormalities; any condition that would render thepatient unable to safely
cooperate with the surgery and study tests as judged by the screening physician

- Presence of a contraindication to undergo a brain MRI

- Metal in the body which would make having anMRI scan unsafe, such as pacemakers,
medication pumps, aneurysm clips, metallic prostheses (including metal pins and
rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner
or small metal fragments in the eye that welders and other metal workers may
have;

- Uncomfortable in small closed spaces (have claustrophobia) such that the
participant will be uncomfortable in the MRI machine;

- Unable to lay comfortably flat on their back for up to one hour in the MRI
scanner;

- Subjects who require diathermy

- Subjects who require post-op MRIs with full body coil

-- Subjects with an active systematic infection

- Subjects who are immune-compromised

- Subjects who are on anticoagulation therapy that would preclude their ability to
undergo the implant procedure

- Subjects who are allergic or have shown hypersensitivity to any materials of the
neurostimulation system which may come in contact with the body

- Subjects that cannot appoint a Durable power of attorney (DPA)