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.