Movement Disorders

Brain cells

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

The field of movement disorders refers to conditions such as Parkinson's disease (PD), tremor, dystonia, tics, and other involuntary movements. These are complex disorders with genetic and environmental factors contributing to their cause. Movement disorders can be divided into two groups: those that result in too much movement and those that result in slowness or too little movement. One of the most common movement disorders is essential tremor, which is commonly familial and results in shaking of the hands, head, and voice. Another very common disorder is Parkinson’s disease, which is characterized by tremor, slowness of movement, and trouble walking. There are many other neurological disorders that resemble Parkinson's disease and are grouped under the term parkinsonism. While there are some clinical differences, often the only way to make a definitive diagnosis is by autopsy of the brain. Examples of other types of parkinsonism include Progressive Supranuclear Palsy, Multiple System Atrophy, and Cortical Basal Ganglionic Degeneration. Treatment of these syndromes generally consists of the same medications used for Parkinson's disease, although the response is often less satisfactory.

Mayo Clinic neurologists in Arizona, Jacksonville, and Rochester are conducting research investigating many movement disorders. Research is aimed at determining the cause for these disorders as well as finding new treatments that will improve symptoms and eventually slow or stop the progression of these disorders.

Parkinson's Disease

Mayo Clinic neurologists are pursuing complex, multiple, and interconnecting investigations with an overall goal of understanding the natural history of Parkinson's disease (as well as other movement disorders), finding its cause(s), and developing better treatments. The continual interaction of individuals and research teams and labs reflects the rapid and constant evolution of research in the field of neuroscience and constitutes an extraordinary strength that we believe is a model for medical research on any disease. Our research is a reflection of the unique collaboration and multidisciplinary work done at Mayo Clinic.

Below is a sampling of some of the current projects and achievements.

Epidemiology and Genetics of Parkinson's Disease

Walter A. Rocca, M.D., is working to clarify the etiology of Parkinson's disease and to identify means to prevent it in independent but related studies based on different sampling and measurement strategies. The studies will use current work and preliminary findings, along with a control group of 800 cases of PD referred to the Mayo Clinic from a 120-mile radius or from a five-state region and 800 controls free of PD and parkinsonism.

The first is a historical cohort study to test the association between unilateral and bilateral oophorectomy before menopause and PD in an established population-based cohort. The study will include over 2,000 women who underwent oophorectomy and a corresponding group of women of the same age and residence who did not undergo oophorectomy.

A second historical cohort study will test the association between personality traits measured by the Minnesota Multiphasic Personality Inventory (MMPI) and PD in an established research cohort. The study will include nearly 9,000 persons who underwent MMPI testing while residing in Minnesota. The proposed case-control study is strong because it has adequate statistical power to confirm preliminary findings on the role of estrogen in PD and to explore the link between substance use and novelty seeking behaviors in PD. These studies will contribute greatly to understanding the causes and possible prevention of PD by exploring novel hypotheses and by using innovative methods.

E2007 as Adjunct Treatment to Levodopa in Patients with Parkinson's Disease

Charles Adler, M.D., Ph.D., Virgilio Evidente, M.D., and Erika Driver-Dunckley, M.D., will conduct a randomized, double-blind, placebo-controlled, parallel group study of the efficacy and safety of 2 of E2007 (an investigational drug) and placebo in levodopa treated Parkinson's Disease (PD) patients with motor fluctuations. Treatment will be given orally for twenty weeks with follow-up lasting up to twenty-four weeks (there is a two- to three-week screening period before treatment begins). Safety and efficacy will be monitored at multiple scheduled visits. This is a phase 3 study sponsored by Eisai Medical Research, Inc. The primary objective of this study is to compare the efficacy of certain doses of E2007 and a placebo in patients with PD who experience end-of-dose "wearing off" fluctuations in their motor function. Patient diaries will serve as the primary efficacy measure.

Fluorodopa Positron Emission Tomography in the Early Detection of Parkinson's Disease

Demetrius Maraganore, M.D., is working toward demonstrating that early PD can be discriminated from normal aging. This feasibility study is an indispensable step toward the development of fluorodopa positron emission tomography (PET) as a screening tool for preclinical detection in at risk family members.

The Molecular Epidemiology of Parkinson's Disease

The Molecular Epidemiology of Parkinson's Disease (MEPD) study is funded by the National Institutes of Health. Demetrius Maraganore, M.D., Ph.D., is leading this effort to study the pathogenesis of Parkinson's disease. The study will have three major goals:

  1. to refine the association between linkage-derived susceptibility genes and PD using a family-based Mayo sample of 1,500 matched pairs of PD cases and unaffected siblings or unrelated population controls;
  2. to study interactions of these genes and their interactions with environmental and gender-related factors; and
  3. to determine how these genes interact with environmental risk factors including pesticides, tobacco, coffee, and alcohol.

The Global Genetics Consortium

The Genetic Epidemiology of Parkinson's Disease Consortium (GEO-PD) was created with funding from the Michael J. Fox Foundation (Edmond J. Safra Global Genetics Consortia Program). The Consortium originally included twenty-four investigators from eighteen sites, eleven countries, and four continents who agreed to share biospecimens and available data for a collaborative-pooled analysis of alpha-synuclein gene promoter variability and Parkinson's disease. The consortium has since increased in size to represent multiple investigators from thirty-one sites, twenty countries, and six continents. By October 31, 2010, it is projected that the sites will have data and DNA available for more than 20,000 cases and 20,000 controls.

New members are actively sought for these and future projects, which will focus on genetic association studies of PD. Investigators are required to have data and DNA available for a minimum of 100 PD cases and 100 unrelated controls, and to be willing to share small aliquots of DNA from a small sub-sample for genotyping reliability studies.

The Arizona Parkinson's Disease Consortium

The Arizona Parkinson's Disease Consortium (APDC) includes investigators from multiple institutions throughout Arizona: Mayo Clinic Scottsdale, Sun Health Research Institute, Barrow Neurologic Institute, Banner Good Samaritan Medical Center, Arizona State University, and the Translational Genomics Research Institute. The APDC focuses on investigation into the causes and diagnosis of PD and dementia in PD, as well as formulation of cures and new treatments, including drug discovery and development that may ultimately lead to prevention, better treatments, and a cure for the disease.

Prescott Family Initiative with the Arizona Parkinson's Disease Consortium

Parkinson's disease is currently diagnosed clinically by finding slowness of movement along with either rest tremor or rigidity. However, the only way to definitively diagnose PD is by autopsy. In addition to being a disorder of movement, thirty to seventy-five percent of patients with PD develop dementia which can be very disabling. While there are treatments (medications and surgical procedures) that improve the motor symptoms, there are no treatments that slow or halt disease progression or prevent dementia in PD patients. Unfortunately, the underlying cause of PD and of dementia in PD is unknown. Charles H. Adler, M.D., Ph.D., of Mayo Clinic Arizona, and Thomas G. Beach, M.D., Ph.D., of Sun Health Research Institute, jointly lead the Arizona Parkinson Disease Consortium. This group of clinicians and scientists from five institutions in Arizona are working with the Brain and Body Donation Program at Sun Health Research Institute to enroll healthy elderly individuals and people with Parkinson's disease, Alzheimer's disease, and other neurologic disorders who are willing to donate their brain and other organs for research purposes. Currently there are 800 living subjects enrolled, and over 950 brains have been collected. Participants are evaluated annually by a movement disorders specialist, a behavioral neurologist, and a neuropsychologist looking for signs of PD and dementia. The major goal is to find the earliest clinical markers for the onset of PD and for the onset of dementia in people with PD so that studies of treatments to slow or stop these disorders can be started earlier. One of the critical features of the program is the confirmation of the clinical diagnosis by autopsy.

A Developing Database

Ryan Uitti, M.D., is conducting research on the delineation of the longitudinal progression of all movement disorders. A comprehensive longitudinal database has been established employing validated examination ratings in more that 4,000 patient visits over ten years. In particular, work with Parkinson's disease focuses on asymmetry of motor findings and identifying factors predictive for specific long-term outcomes. He and his research team are actively comparing phenotypes between genetic and sporadic forms of parkinsonism. Research topics also include surgical treatment and outcome measures for Parkinson's disease, essential tremor, and dystonia. Clinical therapeutic trials are also being carried out for PD in conjunction with multi-center trials of the Parkinson Study Group (PSG), NIH (NET-PD), and industry.

Additional areas of research focus

Charles Adler, M.D., Ph.D., also is leading investigations of normal and abnormal movement in various disorders. This includes studying handwriting and other movements in patients with Parkinson's disease and the effect of medication and deep brain stimulation on the movements. Another area of research is Dr. Adler's investigations of new treatments for multiple movement disorders, including pharmaceutical trials as well as single site studies performed only at Mayo Clinic.

Yips: A Focal Task-Specific Dystonia

Dr. Adler and John N. Caviness, M.D., are conducting a study investigating joint position of the fingers and wrist and muscle contractions in the forearm and upper arm while putting. This study is in collaboration with researchers at Arizona State University. Some golfers complain of an involuntary movement while making a putt, and this is known as the yips. The research is comparing golfers who complain of the yips with golfers that do not complain of this. The goal of the research is to determine if some of the subjects with the yips have an involuntary movement disorder such as tremor or dystonia. This research may have implications to not only golf but other task-specific movement disorders such as writer's cramp and musician's cramp.