Information on the following diseases can be found in the Related Disorders section of this report:

• Marie's Ataxia
• Glutaricaciduria I
• Tardive Dyskinesia
• Parkinson’s Disease
• Hemifacial Spasm

Early onset childhood dystonia (generalized dystonia) is a neurologic movement disorder that usually begins in childhood or adolescence. Symptoms start in one part of the body (usually an arm or leg) and may eventually spread to other parts of the body, causing contractions and spasms of muscles that twist the body into unnatural positions. This is the most common hereditary form of dystonia, in most cases caused by the DYT1 gene.

Dopa-responsive dystonia (DRD), formerly called Segawa's disease, usually begins in childhood or adolescence with difficulty in walking. Symptoms may mimic those of cerebral palsy or Parkinson's disease and it may often be misdiagnosed. DRD is a genetic disorder caused by a deficiency of the brain chemical dopamine.

Paroxysmal dystonia and dyskinesias refer to relatively brief attacks of involuntary movements and a return to normal posture between episodes of symptoms.

Focal dystonias may begin between the ages of 30 and 80, with an average age of onset at 48 years. Symptoms tend to remain localized (focal), meaning they remain isolated to a specific part of the body. Specific common forms of focal dystonias affect the eyelids (blepherospasm), the neck muscles (spasmodic torticollis or cervical dystonia), the face and jaw (oromandibular dystonia), the vocal cords (spasmodic dysphonia), or the hands and arms (writer's camp). Segmental dystonia affects parts of the body that are next to each other (e.g., the shoulder and arm).

X-linked dystonia-parkinsonism (Lubag) is a form of dystonia found almost exclusively among men from the Philippine island of Panay. The symptoms may develop features similar to those of Parkinson's disease.

Myoclonic dystonia is characterized by rapid, jerking movements with or without sustained dystonic postures.

Rapid-onset dystonia-parkinsonism (RDP) is characterized by an abrupt onset of slowed movement (parkinsonism) and the muscle spasms associated with dystonia. Classic features include involuntary dystonic muscle spasms in the arms more often than the legs, prominent involvement of speech and swallowing muscles, slowness of movement, and poor balance. RDP usually begins in adolescence or young adulthood with little progression after symptoms first appear.

Secondary dystonia may be the result of environmental or disease-related damage to a part of the brain called the basal ganglia. Birth injury (particularly due to lack of oxygen), certain infections, reactions to certain drugs, trauma, or stroke can cause the symptoms of secondary dystonia symptoms. Dystonia can also be secondary to other illnesses affecting the central nervous system.

Tardive dystonia and tardive dyskinesia are common forms of secondary dystonia that are induced by the use of certain drugs. Tardive dyskinesia causes generally quick repetitive movements without sustained postures. Tardive dystonia is generally considered a severe form of tardive dyskinesia characterized by muscle contractions resulting in slower, writhing movements. (For more information on this disorder, choose "Tardive Dyskinesia" as your search term in the Rare Disease Database.)
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Multiple genes have been associated with as many forms of dystonia. Researchers are actively seeking to locate additional genes and gene markers. It is generally believed that a combination of genetics and environmental factors are responsible for the onset of symptoms. Non-genetic or secondary forms of dystonia are caused by trauma, exposure to certain medications, stroke and other conditions.

Dystonia can affect individuals of any age, gender, race, or ethnic background. It is estimated that as many as 300,000 people in North America may be affected by the various forms of Dystonia.
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Symptoms of the following disorders can be similar to those of dystonia. Comparisons may be useful for a differential diagnosis:

Marie's Ataxia is a rare inherited disorder of the brain that affects muscle coordination. Usually the first symptom of this disorder is an unsteady manner of walking (gait) and the increasing inability to walk up and down stairs. The lack of coordination and muscle tremors may eventually involve the arms and the legs. Progressive spinal nerve degeneration leads to the wasting away (atrophy) of muscles in the arms, legs, head and neck. This disorder may begin in early adulthood or in middle age. (For more information on this disorder, choose "Ataxia, Marie" as your search term in the Rare Disease Database.)

Glutaricaciduria I is a rare hereditary metabolic disorder characterized by involuntary muscle contortions and an impairment in the ability to carry out voluntary movements. Affected individuals usually appear normal at birth. During the first year of life the symptoms may include vomiting, high levels of different acids in the blood (metabolic acidosis), and decreased muscle tone (hypotonia). These symptoms may progress to dystonia and choreic movements in some patients. (For more information on this disorder, choose "Glutaricaciduria " as your search term in the Rare Disease Database.)

Tardive dyskinesias are rare neurologic syndromes associated with the long-term use of neuroleptic drugs. These drugs may produce symptoms that mimic other movement disorders but are actually side effects of the drug. The major symptoms include involuntary and abnormal facial movements such as grimacing, sticking out the tongue, and the smacking of lips. Involuntary, rapid movements of the arms and legs (chorea) may also occur. (For more information on this disorder, choose "Tardive Dyskinesia" as your search term in the Rare Disease Database.)

Parkinson's disease (PD) is a slowly progressive neurologic movement disorder characterized by involuntary , resting tremor (trembling), muscular stiffness or lack of flexibility (rigidity), slowness of movement (bradykinesia) and difficulty controlling voluntary movements. Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented regions of the brain), resulting in decreasing levels of the neurotransmitter dopamine in the brain. Dopamine is a highly specialized brain chemical that sends a signal to other nerve cells, and participates in the regulation of body movements. Symptoms similiar to those of PD (parkinsonian symptoms) may also develop secondary to hydrocephalus (a condition in which excessive cerebrospinal fluid accumulates the spaces in the brain [ventricles]. As a result, the fluid increases pressure in the brain, and the skull may become enlarged or bulge). Parkinsonian symptoms may also occur as a result of head trauma, inflammation of the brain (encephalitis), obstructions (infarcts), or tumors deep within the cerebral hemispheres (cerebrum) and base of the brain (i.e., basal ganglia), or exposure to certain drugs and toxins. Parkinson's disease usually begins in late adulthood. It is slowly progressive; however, it may not become incapacitating for many years. (For more information on this disorder, choose "Parkinson's disease" as your search term in the Rare Disease Database.)

Hemifacial spasm, which is characterized by contractions on one side of the face, is technically not a form of dystonia. Hemifacial spasm may be caused by inflammation of irritation to a facial nerve. (For more information on this disorder, choose "Hemifacial Spasm" as your search term in the Rare Disease Database.)
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At this time, there is no cure for the various types of dystonia. Current treatments are symptomatic and intended to relieve muscle spasms, pain and discomfort, and unnatural postures. No single treatment program is appropriate for every patient.

There are essentially three treatment options: oral medications, botulinum toxin injections, and surgery. These treatments may be used alone or in combination. In addition, physical and speech therapy may provide a helpful complement to medical treatment.

In addition, in April 2003, the U.S. Food and Drug Administration (FDA) granted a Humanitarian Device Exemption (HDE) for people with the most disabling forms of dystonia to have access to a device sometimes called a "brain pacemaker". Known as Activa Therapy, it is a product of Medtronic, Inc., of Minneapolis and has already been approved for treating symptoms of advanced Parkinson's Disease and essential tremor, the two most common movement disorders.

Activa Therapy uses brain stimulation technology to deliver carefully controlled electrical pulses to precisely targeted areas of the brain involved in movement control. The stimulation appears to block the brain signals that cause the motor symptoms of Parkinson's disease and essential tremor, and scientists believe it works the same way for dystonia. The surgically implanted device that delivers electrical stimulation is similar to a cardiac pacemaker.

Medtronic estimates that about 10 percent of dystonia patients are candidates for treatment with Activa Therapy. For information, call (800) 494-4104 or go to http://www.brainpacemaker.com.

Some medications used to treat various types of dystonia include: Artane (trihexyphenidyl); Cogentin (benztropine), drugs known as benzodiazepines such as Valium (diazepam) or Klonopin (clonazepam); Lioresal (baclofen); Tegretol (carbamazepine), Sinemet or Madopar (carbidopa/levodopa); for specific forms of dystonia Parlodel (bromocriptine), Symmetrel (amantadine), and others.

Injections with botulinum toxin may be very helpful in relieving dystonic muscle spasms. The botulinum toxin is injected directly into the muscle(s) to relax the muscle and reduce or eliminate spasms. The therapeutic effects of the injections may not become obvious before five to 10 days. Injections usually need to be repeated after three to four months when symptoms return.

There are two versions of botulinum toxin now available: They are botulinum toxin type A (Botox) from Allergan Inc. and botulinum toxin type B (Myobloc), from Elan Pharmaceuticals.

Baclofen, which may help periodically to reduce muscle spasms may be prescribed and delivered by means of an implantable pump that releases the drug directly into the area around the spinal cord.

Surgery may be considered in patients with the most severe dystonia whose symptoms do not respond to other forms of treatments. Surgery is undertaken to interrupt, at various levels of the nervous system, the pathways responsible for abnormal movements. This may be done by intentionally damaging small regions of the brain (as in unilateral thalamotomy).

Deep brain stimulation (DBS) (see above) with an implantable pulse generator is another possible treatment used for some types of dystonia. Surgery is generally reserved for those patients with severe dystonia who do not respond to drug therapy or to those with severe dystonia who become non-responsive to drug treatment. During this surgical procedure, electrodes are implanted into a specific are deep within the brain (e.g., thalamus). The leads from these electrodes are then connected to a pulse generator that is surgically implanted near the collarbone. Continuous delivery of electrical stimulation to a specific area of the thalamus may help to "reorder" the movement control center in the brain. The pulses may be adjusted by the patient through the use of magnet placed over the generator.

Dopa-responsive dystonia (DRD) symptoms are treated with very low doses of levodopa, a synthetic version of dopamine.

There is no standard treatment for Rapid-onset dystonia-parkinsonism (RDP), although levodopa/carbidopa medications and dopamine agonists may provide mild improvement for some affected individuals.
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Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

The number of entries under dystonia (see below) in the online genetic database maintained by Dr. V. A. McCusick and the Johns Hopkins University suggests the complexity of this disorder.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University;
Entry No: 128100; OMIM Name: Torsion Dystonia 1, Autosomal Dom; Last Update: 12/16/99. Entry No: 128101; OMIM Name: Dystonia Musculorum Deformans 4; Last Update: 9/9/98.
Entry No: 128230; OMIM Name: Dystonia, Progressive, Diurnal Var; Last Update: 2/5/99.
Entry No: 128235; OMIM Name: Dystonia 12; Last Update: 10/24/00. Entry No: 159900; OMIM Name: Myoclonic Dystonia; Last Update: 8/23/01. Entry No: 224500; OMIM Name: Dystonia Musculorum Deformans 2; Last Update: 3/2/00. Entry No: 224550; OMIM Name: Dystonia with Ringbinden; Last Update: 2/19/94. Entry No: 224570; OMIM Name: Dystonia Famil, Vis. Fail. Striat. Luc.; Last Update: 6/11/99. Entry No: 224600; OMIM Name: Dystonia, Periodic Kenesigenic; Last Update: 2/19/94. Entry No: 305050; OMIM Name: Dystonia-Deafness Syndrome; Last Update: 6/12/98. Entry No: 314250; OMIM Name: Dystonia 3, Torsion, X-Linked; Last Update: 12/27/01. Entry No: 602124; OMIM Name: Dystonia 7, Torsion; Last Update: 5/5/98. Entry No: 602629; OMIM Name: Dystonia 6, Torsion; Last Update: 7/2/98.
Entry No: 605204; OMIM Name: Torsion Dystonia 1 Gene; Last Update: 7/2/98.

TEXTBOOKS
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1465-66, 1577.

Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:314-15.

Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:74, 77, 491, 1077-80.

REVIEW ARTICLES
Friedman J, Standaert DG. Dystonia and its disorders. Neurol Clin. 2001;19:681-705, vii.

GoetzCG, Horn SS. Treatment of tremor and dystonia. Neurol Clin. 2001;19:129-44, vi-vii.

Misbahuddin a, Warner TT. Dystonia: an update on genetics and treatment. Curr Opin Neurol. 2001;14:471-75.

Bressman SB. Dystonia Update. Clin Neuropharmacol. 2000;23:239-51.

Adler CH. Strategies for controlling dystonia. Overview of therapies that may alleviate symptoms. Postgrad Med. 2000;108:151-52, 155-56, 159-60.

Scott BL. Evaluation and treatment of dystonia. South Med J. 200;93:746-51.