Deep Brain Stimulation Surgery for Focal Hand Dystonia
Deep Brain Stimulation Surgery for Focal Hand Dystonia
Researchers want to test a procedure called deep brain simulation (DBS) to treat focal hand
 dystonia (FHD). A device called a neurostimulator is placed in the chest. It is attached to
 wires placed in brain areas that affect movement. Stimulating these areas can help block
 nerve signals that cause abnormal movements.

 Objectives:

 To test DBS as treatment for FHD. To learn about brain and nerve cell function in people with
 dystonia.

 Eligibility:

 People ages 18 and older with severe FHD who have tried botulinum toxin treatment at least
 twice

 Design:

 Participation lasts 5 years.

 Participants will be screened with:

 Medical history

 Physical exam

 Videotape of their dystonia

 Blood, urine, and heart tests

 Brain MRI scan

 Chest X-ray

 Neuropsychological tests: answering questions, doing simple actions, and taking memory and
 thinking tests.

 Hand movement tests

 Participants will have surgery: A frame fixes their head to the operating table. A small hole
 is made in the skull. Wires are inserted to record brain activity and stimulate the brain
 while they do simple tasks. The wires are removed and the DBS electrode is inserted into the
 hole. The neurostimulator is placed under the skin of the chest, with wires running to the
 electrode in the brain. They will have CT and MRI scans during surgery.

 Participants will recover in the hospital for about 1 week.

 The neurostimulator will be turned on 1 4 weeks after discharge. Participants will have
 regular visits until the study ends. Visits include:

 Checking symptoms and side effects

 MRI

 Movement, thinking, and memory tests

 If the neurostimulator s battery runs out, participants will have surgery to replace it.

 ...
Objectives

 To confirm the safety and possible trends toward 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. Trends toward
 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

 -  Intraoperatory electrophysiologic characteristics of the motor ventral thalamic neurons

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

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

 Exploratory

 - Local field potentials and their response to stimulation (in participants with inclusion
 implanted pulse generator capable of sensing capabilities)
-  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 or psychiatry screen,
 including Beck Depression Inventory (BDI) and psychiatric evaluation. Subjects scoring
 above 20 on the BDI or exhibiting moderate or severe active depression 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)