Deep Brain Stimulation Therapy in Movement Disorders

Objective:

The purposes of this protocol are:

- To train NINDS Medical Neurology Branch fellows and other trainees in all aspects of
deep brain stimulation (DBS) treatment of medically refractory Parkinson s disease (PD),
dystonia, essential tremor (ET) and other indications, including patient selection,
physiology, and programming and management after DBS placement;

- To maintain a cohort of patients treated with DBS who can participate in other NIH
protocols addressing the efficacy of functional surgery and the relevant physiology.

- To use physiology and efficacy data related to DBS therapy and motor and cognitive
function in these patient populations. All the data collected will be an outcome of
standard of care and all analyses will be retrospective.

All treatment under this protocol will be based on the current standard of care for DBS
therapy. Subjects may be enrolled in the study for the teaching value or to support
participation in other DBS protocols, or for both reasons.

Study Population:

Patients 18 years and older with medically refractory PD, dystonia, ET may participate in
this study. Other indications will be added with subsequent amendments if FDA approval of
deep brain stimulation is extended to other conditions.

Study Design:

The treatment that is rendered in this protocol is standard of care for PD, dystonia, and ET.
Patients confirmed to have medically refractory PD, dystonia or ET will be offered DBS as a
therapeutic option. Patients will be evaluated for their eligibility for the procedure and
the risk/benefit balance for surgical therapy will be assesse. After completing the
evaluation, a decision will be made on recommending the procedure. At that point the patients
will be referred for the surgical intervention to the NIH Surgical Neurology Branch or to
collaborating surgeons in the community. If the surgery is performed at the NIH, the
Neurology DBS team can be involved in surgical planning, target selection, intraoperative
physiology recording and testing, as specified under SNB protocols. After the surgery, the
patients will be followed in the NIH DBS clinic and the DBS programming will be initiated and
performed as outlined below. The patients will be followed up for at least two years, and
then they will have the option to transfer their care back to the neurologists in the
community or continue care with the NIH Neurology team if care in the community is not
available.

In addition, patients can be enrolled in the protocol at various points in relation to DBS
surgery.

Outcome Measures:

The protocol is a teaching protocol and no research questions are addressed prospectively.
The main goals of this protocol are (1) to provide training in DBS management procedures to
trainees in the Medical Neurology Branch and other sections. and (2) to provide care for
patients treated with DBS, whose surgery was performed at NIH or another facility, who could
participate in other research protocols at the NIH, (3) To use clinically-generated data on
outcome measures, including the change in motor symptoms, as measured by the UPDRS III scale,
changes in quality of life for PD patients measured by UPDRS part II and other scales, the
Burke-Fahn-Marsden (BFM) dystonia rating scale and the Tremor Rating Scale before and 1 year
after treatment, levels of effective drug therapy before and after surgery; change in
behavior and performance of activities of daily living; complications of therapy as measured
by the UPDRS I, II, and IV scales before and after surgery and the SF-12 score; radiographic
correlation of DBS electrode position and clinical changes; neurophysiological mechanisms of
DBS and relevant basal ganglia physiology.

All data collected will be done as standard of care and all analysis will be retrospective.

- INCLUSION CRITERIA:

To be eligible for entry into the study, candidates must meet all the following criteria:

- Be 18 years of age or older.

- Can speak and understand sufficient English or Spanish to provide informed consent and
complete study assessments validly.

- Able to provide informed consent.

- Have a clinical diagnosis of idiopathic PD, primary dystonia, or ET:

- The diagnosis of idiopathic PD will be based on the UK Brain Bank Criteria, and
confirmed by the Movement Disorders Neurologists in the NIH Parkinson Clinic.

- The diagnosis of primary (generalized or segmental), hemidystonia, or cervical
dystonia will be confirmed on clinical examination in the NIH Movement Disorders
Clinic.

- The diagnosis of ET will be confirmed on clinical examination in the NIH Movement
Disorders Clinic (the diagnosis of ET will be based on bilateral, largely
symmetric postural or kinetic tremor involving hands and forearms that is visible
and persistent. Additional or isolated tremor in head may be present but there
should be the absence of abnormal posturing).

- History of appropriate response to dopaminergic medication, with at least a 30%
improvement in motor UPDRS with L-DOPA by history or in-clinic testing, for the PD
patients. OR

--Patients with tremor-dominant PD that do not respond to dopaminergic therapy and
that exhibit a tremor score of at least 2 for tremor severity on at least one side of
the body on the motor UPDRS examination.

- Unsatisfactory clinical response to maximal medical management (with trials of both
higher and lower doses of drugs), including:

- For PD patients:

- good benefit from dopaminergic medication but associated with insufficient
duration of action or unacceptable side-effects OR

- intractable disabling motor fluctuations (severe off periods, dyskinesias, or
freezing spells) OR

- For ET and dystonia:

--intractable symptoms of ET or dystonia impacting at least 2 activities of daily
living.

- Interested in being evaluated to undergo DBS, if indicated, to treat medically
refractory movement disorder or Patients already implanted with DBS for continued
management

EXCLUSION CRITERIA:

For those who have not had DBS:

Candidates will be excluded if they meet any of the following criteria:

- under 18 years

- Clinically significant medical disease that would increase the risk of developing pre-
or postoperative complications, including but not limited to uncontrolled systemic
hypertension with values above 170/100; unstable heart disease; unstable respiratory
disease; uncorrected coagulation abnormalities or need for therapeutic anticoagulation
which cannot be interrupted;

- Intellectual impairment as determined by a score of less than 70 on the estimated
General Ability Index (GAI), a composite score of the Wechsler Adult Intelligence test
fourth Edition (WAIS-IV) or equivalent to FSIQ less than 70, which would render the
participant unable to provide informed consent or to comply with the study procedures.

- Evidence of secondary or atypical parkinsonism/dystonia/tremor as suggested by:

- History of stroke, exposure to toxins, neuroleptics, or encephalitis

- Neurologic signs of upper motor neuron or cerebellar involvement, supranuclear gaze
palsy, or orthostatic hypotension.

- MR-imaging with evidence indicative of secondary disease such as iron deposits in
putamen, tumor, or stroke, which could cause the movement disorder.

- Dementia as evidenced by formal neuropsychological evaluation, Mattis Dementia Rating
Scale (DRS-2) score, and clinical evaluations.

- Unable to complete cognitive assessments and testing in English or Spanish.

- Depression or anxiety as evidenced by self-report on the Beck Depression Inventory- 2
(score above 20) and Beck Anxiety Inventory, respectively.

- Unable to undergo MR-imaging because of implanted 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, or if candidates are
uncomfortable in small closed spaces (have claustrophobia), or cannot lie comfortably
on their back for up to one hour.

- Pregnant women.

- Otherwise not eligible for DBS surgery, for example known inability to undergo
anesthesia

For those who have had DBS:

1. Contra-indications for ongoing stimula ide effects of DBS despite stimulation parameter
adjustment