Dystonia

Disease/Disorder

Anatomy or system affected: Neuromuscular system

Definition: Dystonia is the term used to describe an array of movement disorders characterized by repetitive muscle spasms, tremor, or excessive muscle activation. Dystonia is generally intermittent in nature, often leading to twisting, abnormal contraction patterns in skeletal muscles. It affects men, women, and children of all ages, and is present in about 300,000 people in the United States alone. It is a chronic, nonfatal condition that in most cases does not affect longevity, cognition, or intelligence.

Key terms:

basal ganglia: an area of the inner brain responsible for integrating sensory and motor activity to insure appropriate levels of muscle activation

co-contraction: the tendency for nontask-specific muscles to contract during the execution of a motor skill, often disrupting or opposing normal motor patterns

dysphonia: abnormal function of the larynx or voice box leading to thin, airy speech (abduction dysphonia) or difficulty in having the vocal cords initiate sound (adduction dysphonia)

focal dystonia: a form of dystonia where only specific, localized muscles are susceptible to dystonic symptoms

task-specific focal dystonia: a form of dystonia whereby localized dystonic contractions are present only during the execution of very specific actions

motor neuron: a nerve cell that is responsible for initiating skeletal muscle activity

motor activity or patterns: the characteristics of muscle contraction that result from motor neuron stimulation

motor cortex: that part of the cerebral cortex of the brain responsible for the activation of specific motor neurons to create movement

primary dystonia: forms of dystonia that occur without the presence of other neurologic or metabolic disease

secondary dystonia: forms of dystonia that occur in response to the presence of another neurologic or metabolic disease, to specific trauma, or to exposure to specific medication

sensory neuron: a nerve cell that is responsible for conveying sensory information from various parts of the body back to the brain and spinal cord

somatosensory cortex: that part of the cerebral cortex that is responsible for receiving and interpreting sensory information from various parts of the body

Types of Dystonia

Early-onset generalized dystonia (DYT 1 and Non-DYT 1). This nonfatal, chronic form of dystonia begins in childhood. Difficulties in the limbs are often the initial signs, but it often spreads to other body parts in such a way as to lead to twisting types of contractions. It may be due to a mutation of the DYT 1 gene (also known as the TOR1A gene), although mutation of the DYT 1 gene is not always a prerequisite (non-DYT 1). It is often referred to by different names including Oppenheim’s dystonia, early onset dystonia, idiopathic torsion dystonia, or child-onset dystonia.

Myoclonic dystonia. This is a hereditary form of dystonia, and it includes jerking muscular contractions in combination with more sustained postural abnormalities. Depression, anxiety, obsessive-compulsive disorders, and panic attacks may accompany its expression.

Paroxysmal dystonia (dyskinesia). This is an episodic form of dystonia where abnormal movements are only present during attacks. The movements may be jerky and ballistic, or in other cases, may involve quick motions of the hands and feet (referred to as choreic movements). Between episodes, victims experience normal movement.

Rapid-onset dystonia parkinsonism. This term has recently been used to describe a wide-ranging set of disorders having sudden onset where Parkinson-like movements are accompanied by dystonic symptoms. It is thought to be hereditary, with numerous forms including autosomal-dominant, recessive, and x-linked varieties. Symptoms may develop over hours or a few days, and will usually stabilize in four weeks without further deterioration. It is also hereditary.

Focal dystonia. This category includes several adult-onset forms that affect various parts of the body. These include the eyes (blepherospasm characterized by excessive squinting and blinking), the neck and shoulders (cervical dystonia, otherwise known as spasmodic torticollis, characterized by a twisted torso posture), the face, mouth, or jaw (oromandibular dystonia), the vocal chords (laryngeal dystonia or spasmodic dysphonia), or the hands (writer's cramp). These all may have primary or secondary origins.

Task-specific focal dystonia. Task-specific dystonia describes forms of dystonia where dystonic symptoms occur only during selective motor activities that often involve highly skilled, repetitive movements. The same muscles that show dystonic activity under such conditions are very often normal when used for other activities.

Musician’s dystonia. Musician’s dystonia is a subcategory of task-specific dystonia in which key muscle functions required to play a given instrument are subjected to dystonic symptoms, but only during the use of the instrument. The symptoms typically appear in the hands or fingers of pianists or plucked instrument players (guitar and harp, for example), in the facial muscles of brass players (particularly muscles controlling the lips), but may affect muscles of the jaw as well, typically leading to a clamping effect due to overactivation of the masseter muscle. Co-contraction of nontask-specific muscles is common as well.

Psychogenic dystonia. This occurs when dystonic symptoms are secondary to some preexisting psychological disorder. The type of disorder may vary from patient to patient, and the unwanted movements that result are not under conscious control.

Causes and Symptoms

The symptoms of the various forms of dystonia have been addressed above. With respect to the causes of this disorder, several varieties of dystonia have clear genetic origins, as has been previously noted in the cases of early-onset generalized dystonia, myoclonic dystonia, X-linked dystonia Parkinsonism, and rapid-onset dystonia Parkinsonism. However, genetic causes are not always the case. Many forms of dystonia are idiopathic, with no known specific cause. Precise biochemical mechanisms for developing this organic disorder remain elusive to scientists. Nonetheless, numerous factors have been implicated. Among these are physical trauma to the affected body part, secondary responses to medication, and various toxins that specifically can affect the basal ganglia. Whatever the cause, it appears that alterations in sensory-motor processing occurring at various levels within the brain (particularly in the basal ganglia) are involved. These alterations result in the loss of appropriate inhibition of nontask-specific muscles which, in turn, leads to an overactivation of motor activity, including co-contractions of nontask-specific muscles. In the task-specific varieties in particular, personality traits such as anxiety and perfectionism have been suggested as possible co-factors, along with overuse through repetitive activities, particularly those requiring very rapid and fine movements. Most likely, the cause is multifactorial.

Treatment and Therapy

To date, there is no cure for dystonia that restores function to 100 percent of normal capacity. Because of the wide variety of types of dystonia, treatment and therapy is highly specialized. For some forms of secondary dystonia, oral medications may be helpful. Among the drugs often used with varied success are levodopa, trihexyphenidyl, clonazepam, and baclofen. In focal dystonia where the offending muscles can be isolated, botulinum toxin (BOTOX) is frequently injected with fairly good success, although chronic use can lead to atrophy (wasting and weakness) of the injected muscles. BOTOX essentially blocks transmission of motor neurons in the sites where it is injected. Other approaches, particularly in task-specific focal dystonia such as writer's cramp and the varied forms of musician’s dystonia, sensory-motor retraining or splinting techniques may be employed to attempt to reestablish a level of control, though these efforts are typically unable to restore function completely.

In some drastic cases where oral medications, BOTOX injections, or other treatments are ineffective (usually severe generalized dystonia), surgical techniques have been employed. Among these are very precisely targeted ablation surgeries where areas of the brain are physically disrupted or removed. Careful identification of target tissues is imperative. Modern three-dimensional imaging techniques as well as microelectrode brain mapping make these procedures much more precise than in previous years, and the outcomes have been modestly favorable. Target areas that have shown some success in severe cases include the globus pallidus or the thalamus, both substructures of the basal ganglia. These procedures are not without risk, however, including a one to two percent chance of stroke or hemorrhage. In procedures targeting the globus pallidus, a risk is that vision may be adversely affected. Additionally, deep brain stimulation techniques have shown some promise. In these procedures, electrodes are implanted deep within the brain in very precise locations and a pulse generator is implanted under the collarbone. Through careful testing, a correct amount of electrical pulse stimulation can be identified that helps to ameliorate symptoms.

Perspective and Prospects

Dystonia, and particularly task-specific focal dystonia (like musician's dystonia) is a relative newcomer to medicine and research. In the past 15–20 years, there has been an exponential rise in the number of peer-reviewed publications that have been investigating the causes and treatment of this movement disorder. Numerous national and international organizations exist that are devoted to helping understand and treat dystonia. The Dystonia Medical Research Foundation (DMRF), founded in 1976, supports a wide array of research efforts, providing seed money for initiatives aimed at ameliorating the far-reaching effects of this disorder. In many cases, this seed money has led to more widely-funded projects supported by the National Institutes of Health. The major areas where emphasis has most recently been placed have been (1) research that has identified dystonia as a disorder primarily brought on by aberrant brain circuitry; (2) studies identifying various triggers for dystonia; (3) studies identifying and isolating no fewer than nineteen genes and gene markers thought to be implicated in dystonia; and (4) papers that have an examined and evaluated various treatment strategies. The DMRF joined forces with two other organizations, the Dystonia Coalition and the European Dystonia Federation, to sponsor the Fifth International Dystonia Symposium in Barcelona, Spain, held in the fall of 2011. Additionally, the International Parkinson and Movement Disorders Society as well as the Performing Arts Medical Association have dedicated many of their resources into publicizing dystonia research. The ongoing efforts of these organizations, coupled with the work of neurologists and physicians who are dedicated to working with dystonia, provide much hope for future.

Bibliography

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