Background:

• In transcranial magnetic stimulation (TMS), a device creates a short-lasting magnetic field which induces an electric current in the brain leading to a change in the activity of brain cells. There are different effects on the brain with different rates of stimulation. In a previous study in people with Parkinson's disease, repetitive TMS (rTMS) given at a particular rate temporarily improved their ability to walk. A faster rate of rTMS may be more effective in treating symptoms than the rate originally used.
• This study will compare active rTMS to inactive (sham or Placebo) rTMS. Half of the people in this study will have active rTMS; the other half will have no brain stimulation with rTMS.

Objectives:

- To see if a faster rate of transcranial magnetic stimulation is a more effective treatment for the symptoms of Parkinson's disease than the slower rates that have been studied.

Eligibility:

• Individuals between 40 and 80 years of age who have been diagnosed with mild or moderate Parkinson's disease.
• Participants must currently be taking Sinemet or dopamine agonists drugs (e.g., bromocriptine, cabergoline, pergolide, pramipexole, ropinirole, apomorophine, and rotigotine), and are willing to continue their same treatments for the duration of the study.

Design:

• This study requires 11 outpatient visits to the NIH Clinical Center over 6 weeks. Participants can also be admitted and stay as an inpatient in the NIH Clinical Center for the entire study period (for the 10 visits during the first weeks and the follow-up visit a month later).
• Initial visit will consist of a physical examination; a test of participants' time to walk 10 meters; and questions about memory, mood, and quality of life. Participants should not take Parkinson's disease medications for 12 hours before this visit; once the examinations and tests are complete, participants will be able to take the medications. Researchers will repeat the tests 1 hour after participants take the medication.
• TMS sessions: 8 TMS sessions (4 sessions per week) over 2 weeks. Each stimulation session will last half an hour. Half of the participants will receive active TMS; the other half will receive sham TMS.
• The first 10 participants will have additional tests to study the safety of rapid TMS in patients with Parkinson's disease.
• A day after completing the last TMS session, participants will repeat the same tests as the first visit before and after taking their medication as in the first assessment and respond to questions about mood, memory, and quality of life.
• One month after completing the last TMS session, participants will repeat the same tests as the first visit before and after taking their medication.

Objective:

To demonstrate cumulative and long-lasting improvement of parkinsonian symptoms by 50 Hz rTMS (repetitive transcranial magnetic stimulation) and its safety in Parkinson's Disease (PD) patients.

Study population:

Up to 30 PD patients in Hoehn and Yahr disease stage 2-4 while off medication will be enrolled. Patients must be receiving more than 300 mg of levodopa (including dopamine agonists) and have gait problems.

Design:

This is a randomized, double-blind, placebo (sham)-controlled study of 26 patients with PD in 2 groups (real versus sham stimulation). The study involves performance (8 interventions) of 50 Hz rTMS with large circular coil over the motor cortex on both sides of the brain. Assessment of PD symptoms with standard tests of motor function will be performed over a one-month period.

Outcome measure:

The primary endpoint include the changes in gait speed as assessed by the time it takes to walk 10 meters and the changes in bradykinesia as assessed by measuring the time it takes to do 10 combined hand and arm movements.

Secondary endpoints include the changes in the total, motor and activities of daily living Unified Parkinson's Disease Rating Scale (UPDRS) score.

• INCLUSION CRITERIA:

Men and women aged 40 to 80 years with DOPA-responsive PD

Hoehn and Yahr grade of 2 to 4 while off

Must be on a regimen including levodopa

Total dose of levodopa and dopamine agonists (using dopamine equivalents) has to be equal to or more than 300 milligrams per day

problems with walking and gait time for a 10-meter distance greater than six seconds or more

EXCLUSION CRITERIA:

Any active psychiatric disease

History of seizures and epilepsy

Concurrent use of tricyclic antidepressants, neuroleptic agents, or any other licit or illicit drugs other than anti-parkinsonian agents that could lower the seizure threshold except for SSRI

Pallidotomy, implanted electrodes and generator for deep brain stimulation

Pregnancy

Surgically or traumatically implanted foreign bodies such as a pacemaker, implanted medical pump, implanted hearing aids, metal plate in the skull, or metal implant in the skull or eyes (other than dental appliances or fillings) that may pose a physical hazard during TEP.

Study would cause undue risk or stress for reasons such as tendency to fall, excessive fatigue, general frailty, or excessive apprehensiveness.

Dementia as assessed by the Folstein's Mini-Mental Test Examination (MMSE less than or equal to 24/30) or mentally impaired patients having no capacity to provide their own consent (the physician establishing the diagnosis and applying UPDRS will evaluate patient's mental capacity using conventional clinical interview)

Unable to walk a 10-meter distance.

More than occasional falls, i.e. daily falls (corresponding to a score greater than or equal to 3 and more in UPDRS item 13), history of fall(s) with significant injuries, absence of postural response in the on and/or spontaneous loss of balance in the off condition (corresponding to a score of greater than or equal to 2 and greater than or equal to 3 in on/off condition, respectively, in UPDRS item 30)

Pregnancy is unusual in patients with PD, grade 2-4. Urine sample for the pregnancy test will be obtained in patients of childbearing potential prior to starting the 50 Hz rTMS and also at the initial interview after signing the consent form. Women of childbearing potential will be asked to take appropriate measures to prevent a pregnancy during the study.