$Unique_ID{BRK04087} $Pretitle{} $Title{Parkinson's Disease} $Subject{Parkinson's Disease Parkinsonism (Paralysis Agitans; Shaking Palsy; Secondary Parkinsonism; Symptomatic Parkinsonism; Postencephalitic Parkinsonism; Drug-Induced Parkinsonism) Parkinsonism Dementia Complex Juvenile Parkinsonism of Hunt (Hunt Corpus Striatum Syndrome; Pallidopyramidal Syndrome) Hallervorden-Spatz Disease Benign Familial Tremor Benign Essential Tremor Progressive Supranuclear Palsy Olivopontocerebellar Atrophy} $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1990, 1991, 1992, 1993 National Organization for Rare Disorders, Inc. 4: Parkinson's Disease ** IMPORTANT ** It is possible the main title of the article (Parkinson's Disease) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names and disorder subdivisions covered by this article. Synonyms Parkinsonism (Paralysis Agitans; Shaking Palsy; Secondary Parkinsonism; Symptomatic Parkinsonism; Postencephalitic Parkinsonism; Drug-Induced Parkinsonism) Information on the following diseases can be found in the Related Disorders section of this report: Parkinsonism Dementia Complex Juvenile Parkinsonism of Hunt (Hunt Corpus Striatum Syndrome; Pallidopyramidal Syndrome) Hallervorden-Spatz Disease Benign Familial Tremor Benign Essential Tremor Progressive Supranuclear Palsy Olivopontocerebellar Atrophy General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Parkinson's disease is a slowly progressive neurologic condition characterized by involuntary trembling (tremor), muscular stiffness or inflexibility (rigidity), slowness of movement and difficulty carrying out voluntary movements. Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented regions of the brain), causing a decrease in dopamine levels in the brain. Dopamine is a neurotransmitter, which is a chemical that sends a signal in the brain. Parkinsonian symptoms can also develop secondary to hydrocephalus (a condition in which the head is enlarged and areas of the brain accumulate excessive fluids, resulting in an increase in pressure on the brain), head trauma, inflammation of the brain (encephalitis), obstructions (infarcts) or tumors deep within the cerebral hemispheres and the upper brain stem (basal ganglia), or exposure to certain drugs and toxins. Parkinson's disease is slowly progressive and may not become incapacitating for many years. Symptoms Parkinson's disease generally begins with a subtle slight tremor, especially in the hands. At first, the tremor occurs at rest, then becomes more pronounced with fatigue and emotional stress, lessening during voluntary movements. The tremor may be limited to the arms or extend to the neck, jaws and legs. Voluntary movements such as walking become increasingly difficult. Walking becomes slow, stiff and shuffling. Perception, thinking processes and sensation generally remain normal, although some patients may experience a reduction of intellectual abilities (dementia). The depression that sometimes develops in Parkinson's disease may be part of the disease or a reaction to it. As the disease advances, a stooped posture and an immobile, unblinking facial expression with frequent drooling develops. Oily skin (seborrhea) may be present on the face and scalp. A feeling of being "frozen" in a position, unable to make a voluntary movement, is a repeated symptom of Parkinson's disease. Causes The cause of Parkinson's disease is unknown in most cases. A few cases have resulted from carbon monoxide or manganese poisoning. Drug-induced parkinsonian symptoms can develop from drugs used to treat psychiatric disorders (dopamine-receptor antagonistic drugs). These symptoms usually disappear when the drugs are withdrawn or the dosage is decreased, or with time during treatment. A few families with multiple cases of Parkinson's disease have been identified but a genetic basis has not been established. Affected Population Although 10 to 20 percent of all cases of Parkinson's disease are diagnosed in individuals under the age of 40 years, this disorder occurs primarily in the middle-aged and elderly population. Between 300,000 and 500,000 cases of classic Parkinson's disease are found in the United States. As the National Institute of Neurological Disorders and Stroke reported in a study of major neurologic disorders in biracial populations, the occurrence of Parkinson's disease shows no gender (male to female) or racial differences. Related Disorders Symptoms of the following disorders can be similar to those of Parkinson's Disease. Comparisons may be useful for a differential diagnosis. Juvenile Parkinsonism of Hunt is an extremely rare hereditary syndrome with onset during the teens, 20's or early 30's. Parkinsonism Dementia Complex is associated with motor neuron disease such as amyotrophic lateral sclerosis (ALS). A rare form of Parkinson's-like syndrome has been found in western Pacific Islands and has been determined to be caused by eating a locally grown toxic bean. A drug-induced Parkinsonism was identified in young heroin addicts who abused a "designer drug" originally in a fairly localized community in California. Primates (i.e., monkeys) given the same toxic substance are considered a study model for this disorder because parkinsonism can be induced by the heroin substitute. Benign Essential Tremor Syndrome is a disorder of the nervous system that has no known cause. It is characterized by a fine or coarse tremor, primarily in the hands and head. This disorder is similar to Benign Familial Tremor, which tends to run in families. Benign essential tremor syndrome may be slowly progressive, eventually affecting other parts of the body. When the affected area of the body is in movement or voluntarily moved or held in one position, the tremor is rhythmic and occurs at the rate of about 4 to 12 times per second. This is in contrast to Parkinson's tremors, which usually diminish or disappear entirely with purposeful movement. The tremors mainly affect the upper extremities and are aggravated by stress, anxiety, fatigue and cold. (For more information on this disorder, choose "Benign Essential Tremor Syndrome" as your search term in the Rare Disease Database). Hallorvorden-Spatz Disease affects movement. It is associated with degeneration of the nervous system. A variety of symptoms can develop, including muscular rigidity, stiffness, uncontrolled movement, contractions (spasticity) and dementia. Onset typically occurs during childhood, although occasionally the disease appears in adulthood. Imperfect articulation of speech, mental retardation and facial grimacing are reported less frequently. The clinical syndrome may resemble parkinsonism in some cases. (For more information on this disorder choose "Hallervorden-Spatz Disease" as your search term in the Rare Disease Database). Olivopontocerebellar Atrophy is a group of inherited forms of Ataxia (impaired ability to coordinate movement). It is characterized by progressive neurologic degeneration (gradual deterioration) affecting certain areas of the brain. The loss of these brain cells (neurons) results in impaired muscle coordination (ataxia), tremor, involuntary movement and speech disturbance (dysarthria). A wide variety in severity and age of onset may be found in all types of Olivopontocerebellar atrophy. (For more information on this disorder, choose "Olivopontocerebellar Atrophy" as your search term in the Rare Disease Database). Progressive Supranuclear Palsy (PSP) is a neurologic disorder associated with spastic weakness of muscles affected by the cranial nerves; i.e., muscles of the face, throat and tongue. Onset of the disorder usually occurs in middle age. The first noticeable symptom of this disorder is usually loss of balance while walking. Patients may have unexplained falls or a stiff awkwardness in the walk. New symptoms can develop during the course of PSP, and previously mild problems may become more severe with time. (For more information on this disorder, choose "Progressive Supranuclear Palsy" as your search term in the Rare Disease Database). Therapies: Standard With proper treatment, many Parkinson's disease patients may enjoy a normal life span. A number of drugs provide degrees of symptomatic relief. These include levodopa, anticholinergics and amantadine, a dopamine releasing agent that acts in coordination with levodopa. Anticholinergic agents such as trihexyphenidyl, benztropine mesylate, biperiden and diphenhydramine help control tremors and rigidity. Amantadine hydrochloride helps reduce tremors and rigidity and improves spontaneous movements. Bromocriptine (Parlodel) and/or pergolide (Permax) may be useful in some cases, particularly in conjunction with other drugs such as the combination of levodopa and carbidopa (Sinemet). The treatment of choice is a combination of levodopa (the precursor of an amino acid) and carbidopa (an enzyme inhibitor). This drug (Sinemet) tends to become less effective over time. Some doctors have suggested that patients try to prevent the "on-off" phenomenon by taking Sinemet an hour before meals since protein is found in almost all foods composed of amino acids which compete with levodopa for access to the brain. However, since many Parkinson's patients are debilitated due to the combined effects of the disease and aging, and may also have difficulty eating regularly due to tightened throat muscles, good nutrition is often difficult to maintain. Therefore, depleting protein in the diet of Parkinson's patients could be harmful or dangerous. Proper diet will permit absorption of the drug by the brain's receptor cells so that the protein in the meal will have much less effect on the drug's usefulness. If patients experience nausea with this method, they can take the drug with soda crackers or a similar non-protein snack. The orphan drug deprenyl (Eldepryl) was approved for marketing by the FDA in 1989. This drug is a monoamine oxidase inhibitor which can be used in late stage Parkinson's disease in combination with levodopa and carbidopa. More recent research suggests that Eldepryl given to people with early stage Parkinson's disease may significantly delay progression of more advanced symptoms. Physical therapy for Parkinson's patients may include exercises for speaking, swallowing and overall muscle tone. Exercises will not stop the disease's progression, but may reduce disability. Exercise can also improve the emotional well-being of a patient. Therapies: Investigational Additional dopamine agonist drugs are under investigation for Parkinson's disease. In the very early stages of experimentation is the implantation of cells from the patient's own adrenal gland or from fetal tissue into the brain to increase the amount of dopamine available to the affected structures. Animal studies continue to examine whether this procedure may become more effective in humans with time. Three studies published in the November 26th, 1992 issue of the New England Journal of Medicine indicate that fetal cell transplants into brains of people with Parkinson's Disease have resulted in moderate improvement of symptoms. Dosages of Parkinson's drugs were able to be reduced in most patients. However, more research is needed to determine the long-term effectiveness and reduction of brain damage from the surgery. Worldwide interest in drugs to treat Parkinson's disease is evident in the various new therapies being developed. In Italy, Farmitlalia Carlo Erba is investigating the drug cabergoline to treat Parkinson's symptoms. In Japan, Thomai researchers are studying the Dopamin D-2 agonist talipexole. In Israel, Teva Pharmaceuticals is developing TVP101 as a possible treatment. Merrell-Dow is testing MDL72974A. Hoffmann-LaRoche is studying the RO and N-(2 aminoethyl)-5-chloro-2-pyridine carboxamide. Ropinerole is being developed by SmithKline Beecham. Many of the trials are in early Phase I and II stages. The orphan product Apomorphine HCL injection is being tested for the treatment of the on-off fluctuations associated with late-stage Parkinson's Disease. The product is manufactured by: Britannia Pharmaceuticals Ltd. Forum House, Brighton Rd. Redhill, Surrey, UK This disease entry is based upon medical information available through May 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Parkinson's disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Parkinson's Disease Foundation Columbia Presbyterian Hospital Neurologic Institute 710 W. 168th St. New York, NY 10032 (212) 923-4700 United Parkinson Foundation 360 W. Superior St. Chicago, IL 60610 (312) 664-2344 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 International Tremor Foundation 360 W. Superior St. Chicago, IL 60610 (312) 664-2344 References THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. P. 1421. CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W.B. Saunders Co., 1988. Pp. 2143-7. MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 707, 710-1, 1409, 1703. PRINCIPLES OF NEUROLOGY, 4th ed.: Raymond D. Adams, and Maurice Victor: McGraw Hill, Inc., 1989. Pp. 940-1. UNILATERAL TRANSPLANTATION OF HUMAN FETAL MESENCEPHALIC TISSUE INTO THE CAUDATE NUCLEUS OF PATIENTS WITH PARKINSON'S DISEASE: D.D. Spencerr, et al.; The New England Journal of Medicine; (November 26, 1992, issue 327 (22)). Pp. 1541-47. SURVIVAL OF IMPLANTED FETAL DOPAMINE CELLS AND NEUROLOGIC IMPROVEMENT 12 TO 42 MONTHS AFTER TRANSPLANTATION FOR PARKINSON'S DISEASE C.R. Freed, M.D., et al.; The New England Journal of Medicine; (November 26, 1992, issue 327 (22)). Pp. 1549-55. BILATERAL FETAL MESENCEPHALIC GRAFTING IN TWO PATIENTS WITH PARKINSONISM INDUCED BY 1-METHYL-4PHENYL-1,2,3,6-TETRAHYDROPYRIDINE: Hakan Widner, M.D., et al.; The New England Journal of Medicine; (November 26, 1992, issue 327 (22)).