Deep Brain Stimulation Surgery for Movement Disorders
Deep Brain Stimulation Surgery for Movement Disorders
Background:

 - Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like
 Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered
 device called a neurostimulator (like a pacemaker) that is placed under the skin in the
 chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these
 areas helps to block the nerve signals that cause abnormal movements. Researchers also want
 to record the brain function of people with movement disorders during the surgery.

 Objectives:

 -  To study how DBS surgery affects Parkinson s disease, dystonia, and tremor.

 -  To obtain information on brain and nerve cell function during DBS surgery.

 Eligibility:

 - People at least 18 years of age who have movement disorders, like Parkinson's disease,
 essential tremor, and dystonia.

 Design:

 -  Researchers will screen patients with physical and neurological exams to decide whether
 they can have the surgery. Patients will also have a medical history, blood tests,
 imaging studies, and other tests. Before the surgery, participants will practice
 movement and memory tests.

 -  During surgery, the stimulator will be placed to provide the right amount of stimulation
 for the brain. Patients will perform the movement and memory tests that they practiced
 earlier.

 -  After surgery, participants will recover in the hospital. They will have a followup
 visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be
 programmed and adjusted over weeks to months to find the best settings.

 -  Participants will return for followup visits at 1, 2, and 3 months after surgery.
 Researchers will test their movement, memory, and general quality of life. Each visit
 will last about 2 hours.
Objective:

 The objective of this protocol is to provide DBS surgery and to collect physiology and
 efficacy data related to DBS therapy and motor and cognitive function in people with
 medically refractory Parkinson s disease (PD), dystonia, and essential tremor (ET). All
 treatment under this protocol will be based on the current standard of care for DBS surgery.

 Study Population:

 Patients 18 years and older with medically refractory PD, dystonia and/or ET may participate
 in this study.

 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. The
 therapeutic goal of this procedure is to implant chronically stimulating macroelectrodes in
 the basal ganglia or thalamic nuclei in order to alleviate the symptoms of PD, dystonia or
 ET. Pre- and post-operative imaging will be used to precisely localize electrode locations
 within the brain and will be correlated with measures of clinical efficacy and recorded
 intra-operative neural activity. Intra-operative microelectrode recordings, as well as micro-
 and macroelectrode electrical stimulation, will be used to confirm positioning of electrode
 leads. Intra-operative electrode recordings will also be used to investigate the
 neurophysiological mechanisms of deep brain stimulation and to explore the neural circuits
 underlying motor and cognitive processing in the basal ganglia. Intraoperative physiology
 will be used for clinical and research purposes. Patients will be followed for 3 months after
 the surgical procedure to determine effectiveness of DBS treatment.

 Outcome Measures:

 The primary goal of this protocol is to determine the physiology and efficacy of DBS surgery
 for movement disorders. Efficacy outcome measures include the change in motor symptoms, as
 measured by the UPDRS III scale, the Burke-Fahn-Marsden (BFM) dystonia rating scale, and the
 Tremor Rating Scale before and 3 months after treatment. Secondary measures include 1) levels
 of effective drug therapy before and after surgery; 2) change in behavior and performance of
 activities of daily living; 3) complications of therapy as measured by the UPDRS I, II, and
 IV scales before and after surgery and the SF-12 score; 4) radiographic correlation of DBS
 electrode position and clinical changes; and 5) neurophysiological mechanisms of DBS and
 motor and cognitive function in the basal ganglia.
-  INCLUSION CRITERIA:

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

 Be 18 years of age or older.

 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:

 -  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

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

 Agree to undergo DBS if indicated to treat medically refractory movement disorder.

 EXCLUSION CRITERIA:

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

 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; active heart disease needing immediate
 intervention; active respiratory disease needing immediate intervention; uncorrected
 coagulation abnormalities or need for therapeutic anticoagulation which cannot be
 interrupted; current or pre-existing life-threatening respiratory disease, such as
 respiratory failure or ARDS.

 Unable to complete cognitive assessments and testing necessary to adequately evaluate risks
 and benefits of surgery

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

 -  History of CVA, 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 tumor, or stroke,
 which could cause the movement disorder.

 -  Features atypical of idiopathic Parkinson s disease.

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

 Depression or evidenced by self-report on the Beck Depression Inventory-2 (score above 20).

 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.

 Patients with tremor-dominant PD with Scans Without Evidence of Dopaminergic Effect (SWEDD)
 will be excluded based on clinical and historic information, including DaT functional
 imaging obtained during routine clinical evaluation of PD as needed.