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Last updated:
4/12/2024
Years published: 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1998, 1999, 2000, 2001, 2002, 2003, 2008, 2015, 2020, 2024
NORD gratefully acknowledges Giulietta M. Riboldi, MD PhD, The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders, NYU Langone Health and Steven J. Frucht, MD, Professor of Neurology; Director, The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders, NYU Langone Health, for the preparation of this report.
Summary
Dystonia is a general term for a large group of movement disorders that vary in their symptoms, causes, progression and treatments. This group of neurological conditions is generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). The muscular contractions may be sustained or come and go (intermittent). Movements may be patterned and twisting and/or in some cases shaking or quivering (tremulous) resembling a tremor. Dystonia may occur or be worsened when an individual attempts a voluntary action. There are many different causes for dystonia. Genetic as well as non-genetic factors can contribute to the development of these disorders. In some cases, the exact, underlying cause is unknown (idiopathic). The most characteristic finding associated with most forms of dystonia is twisting, repetitive movements that affect the neck, torso, limbs, eyes, face, vocal chords and/or a combination of these muscle groups. Certain forms such as laryngeal dystonia are not associated with abnormal postures. Dystonia causes varying degrees of disability that range from mild symptoms that come and go to severe, debilitating symptoms that can significantly affect a person’s quality of life. Some patients have pain. Usually there is no weakness in the affected muscle groups. In some people, dystonia can become progressively worse, while in others it remains unchanged or no longer worsens (plateaus). Dystonia may even spontaneously remit in rare cases. The onset of dystonia can be very early in life or during adulthood, depending on the cause. Treatment for dystonia depends upon several factors including the specific subtype present and can include medications, botulinum toxin injections, physical therapy and surgery.
Introduction
Dystonia was first described in the medical literature as far back as the 1800s. The classification of dystonia has always been complicated and controversial, resulting in confusion, not only for patients, but within the medical community as well. A basis for classifying the dystonias has been proposed based on a consensus achieved by an international expert group of physicians (Albanese A, et al. 2013). This group has proposed to classify dystonia based on clinical features and etiology.
Classifying dystonia by clinical features includes age of onset, body distribution, temporal pattern and associated features. Age of onset is broken down into infancy (birth to 2 years), childhood (3-12 years), adolescence (13-20), early adulthood (21-40) and late adulthood (greater than 40 years). Dystonia that develops during infancy or childhood is more likely to have a known cause and to progress to become widespread.
Classifying dystonia by the specific body part(s) affected is common to many classification systems. Generally, dystonia may be focal (affecting an isolated body part), segmental (affecting adjacent body areas), multifocal (two or more noncontiguous areas), generalized (affecting the trunk and two other body regions) and affecting one side of the body (hemidystonia).
Temporal pattern helps to distinguish between dystonia that becomes progressively worse in terms of intensity and/or involvement of other muscles groups or remains unchanged (static). It also refers to the variability in disease expression in relation to other factors such as external triggers or voluntary actions. Temporal patterns can be broken down into four types: persistent, in which dystonia persists throughout the day without fluctuation; task-specific, in which dystonia occurs only during a specific action or task (e.g. writer’s cramp); diurnal fluctuations, in which dystonia fluctuates in severity at certain points throughout the day and often lessens during the night; and paroxysmal in which a sudden, temporary episode of dystonia occurs often as the result of a specific trigger.
Dystonia can also be classified by whether it occurs along with another movement disorder. Isolated dystonia is when dystonia is the only motor feature except for tremor. Combined dystonia is used when another movement disorder such as Parkinsonism or myoclonus is also present.
The etiology axis refers to whether degenerative changes or structural damage is present in the nervous system (nervous system pathology) and whether the disorder is inherited or acquired, or whether the underlying cause is unknown or unproven (idiopathic).
Previous terminology used to categorize dystonia includes primary dystonia, secondary dystonia, dystonia plus syndromes and heredodegenerative dystonia. Primary dystonia referred to cases in which dystonia was the only clinical feature (isolated dystonia), there was no evidence of brain degeneration and without an acquired cause. Primary dystonia may be inherited or occur for unknown reasons (idiopathic). Secondary dystonia referred to cases in which dystonia resulted from a broad range of causes including genetic variants, birth injury, stroke, brain tumors, certain infections and as a reaction to certain drugs. Dystonia plus syndromes referred to disorders in which dystonia occurred in conjunction with another neurological disorder such as myoclonus or Parkinsonism. Heredodegenerative dystonia referred to hereditary cases that were associated with neurodegeneration and occur with other neurological symptoms.
Until a consistent, straightforward classification system is adopted by the medical community confusion regarding terminology in describing dystonia will persist. In addition, dystonia is a rapidly growing disease family and information about these disorders is constantly changing.
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. The most frequent cases of hereditary form of dystonia are changes (pathogenic variants) in the TOR1A gene (especially in the Ashkenazy Jewish population), previously called DYT1-dystonia, and in the KMT2B gene (previously called DYT28 dystonia).
Specific symptoms can vary from one person to another even among individuals with the same subtype. Specific symptoms may occur based upon the specific part of the body involved, age of onset and the underlying cause. Dystonias with an earlier age of onset are more likely to progress from a focal presentation to a generalized one and are usually more severe. Adult-onset forms of dystonia tend to have a focal presentation and usually do not progress.
Some affected individuals can temporarily interrupt dystonic movements or postures by performing a specific action or maneuver. This is known as ‘gestes antagoniste’ or a sensory trick. Usually, the action involves a body part not affected by dystonia, but often nearby the affected area. For example, some individuals can temporarily alleviate cervical dystonia by touching their chins. Changing the pattern of muscle activation can also improve certain dystonic postures. For example, in patients with foot dystonia causing an abnormal turning of one foot when walking, when asked to run or to walk backwards they can present a reduction of this abnormal posturing.
Some of the better-known forms of dystonia are briefly discussed below. NORD has individual reports on many of the specific dystonia subtypes. For more information, choose the specific disorder name as your search term in the Rare Disease Database.
ISOLATED FOCAL DYSTONIA
Isolated focal dystonias are the most common dystonias and can include benign essential blepharospasm, cervical dystonia, oromandibular dystonia and laryngeal dystonia. These dystonias often have adult onset. NORD has individual reports on these forms of dystonia.
Isolated limb dystonia may occur in adults and often affects the arms and/or hands. Many are occupational or task specific. Occupational or task-specific dystonia are general terms that refer to focal dystonia associated with a specific, often repetitive, activity. Initially, affected individuals may exhibit a lack of dexterity when performing the activity. Eventually, the condition progresses to cause repetitive movements and abnormal postures or, in some people, affect other activities involving the same body part. The most common form may be writer’s cramp, in which abnormal flexion, extension or rotation of the fingers and wrist occurs when an affected individual writes. In some people, writing with the unaffected hand (contralateral) can induce dystonic posturing in the affected hand. This phenomenon is called “mirror movements”.
Musician’s dystonia is a form of task-specific dystonia that involves muscles that are involved with performance. Symptoms occur when musicians attempt to play an instrument. Focal hand dystonia and embouchure dystonia are the most common forms. Focal hand dystonia is characterized by painless loss of muscular control in relation to highly practiced movements (as seen with pianists, guitarists, etc.).
Embouchure dystonia is a specific form of musician’s dystonia that affects individuals who play brass and woodwind instruments. This form of dystonia can affect the muscles of the mouth, face, jaw and tongue. The muscular contractions that characterize embouchure dystonia may only occur when the musician is playing or blowing into the mouthpiece of the instrument.
INHERITED DYSTONIA
A genetic classification for dystonia was established that sub-classified dystonia is based upon the specific genetic variant associated with the subtype. Initially, disorders were given the official abbreviation DYT and a number (e.g. DYT1). The subtypes are numbered in the order they were identified in the medical literature. However, this classification has several problems. Designations were assigned without a known gene so that individuals with one form of dystonia were eventually found to have an existing form. For example, individuals with DYT14 were eventually determined to have DYT5. A more recent nomenclature proposes that different forms of dystonia are designated by the prefix DYT- followed by the name of causal gene (Marras et al., 2016). For example, instead of DYT1 dystonia, this form is now called DYT-TOR1A. Another issue is that some disorders included in this classification system do not have dystonia as the primary symptom, but rather another neurological finding such as myoclonus or parkinsonism. These forms are designated with a prefix describing both phenotypes followed by the causative gene name. For example, the X-linked dystonia-parkinsonism (also known as “Lubag disease”) previously called DYT3 is now referred to as DYT/PARK-TAF1. Furthermore, many genetically determined disorders with dystonia as a feature are not included in the classification such as Lesch-Nyhan syndrome, Wilson’s disease and deafness-dystonia-optic neuronopathy syndrome.
Some of the better-known forms of inherited dystonia are described below.
DYT-TOR1A-related dystonia (previously called DYT1) usually begins in childhood or adolescence. However, the disorder may also develop later during life. Symptoms usually 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. Severity can vary greatly from one person to another, even among members of the same family. The disorder can potentially cause significant disability in childhood while, in other cases it can remain undiagnosed until adulthood with only mild symptoms. DYT1-related dystonia is the most common hereditary form of dystonia and is caused by variants in the DYT1 (also known as TOR1A) gene. This form of dystonia is inherited in an autosomal dominant manner.
DYT-KMT2B (previously called DYT28) dystonia is a genetic form of early onset generalized dystonia that was identified in 2016. Although rare, this form of dystonia seems to account for almost 10% of genetic cases of generalized pediatric dystonia. Dystonia is associated with several features (such as small stature, elongated face, broad nasal base and bulbous nasal tip) as well as intellectual disability and developmental delay, microcephaly, renal and respiratory involvement, skin and eye symptoms which can help guide the diagnosis in these patients. This disorder is caused by variants in the KMT2B gene. Most patients have a de novo gene variant, which are genetic changes that spontaneously arose in patients and are not inherited from a parent. The disease is transmitted in an autosomal dominant manner. Several studies have reported a very positive response to treatment with DBS in these patients (Rajan et al., 2021). Therefore, genetic diagnosis can be crucial in these cases to guide therapeutical approaches.
X-linked dystonia-parkinsonism (or “Lubag disease”, DYT/PARK-TAF1 or DYT3) is a form of dystonia found almost exclusively among men from the Philippine Island of Panay. Most female carriers do not develop symptoms (asymptomatic). The symptoms and clinical course are highly variable. Affected individuals may develop symptoms associated with Parkinsonism including abnormal slowness of movement (bradykinesia), resting tremor and an inability to remain in a stable or balanced position (postural instability). Eventually, dystonia develops that usually is focal, most commonly affecting the jaw, neck, trunk or eyes. Some individuals only develop Parkinsonism, which tends to be slowly progressive. Parkinsonism can be more severe, eventually resulting in an unstable gait and recurrent falls. Dystonia tends to be progressive and can become generalized or multifocal. Individuals with a combination of dystonia and Parkinsonism can develop severe, life-threatening complications. The mean age of onset of X-linked dystonia-parkinsonism is 39 years of age. This disorder is caused by variants in the TAF1 gene.
Dopa-responsive dystonia (DRD) is a general term for a few disorders in which generalized dystonia and Parkinsonism are present and often dramatically respond to treatment with levodopa. Levodopa is an amino acid that is converted to dopamine. Dopamine is a brain chemical that serves as a neurotransmitter and is deficient in individuals with DRD. Affected individuals may be misdiagnosed as having cerebral palsy or Parkinson’s disease. Two main forms have been identified and are known as Segawa syndrome, due to variants of the GTP cyclohydrolase 1 (GCH1) gene (called DYT/PARK-GCH1), and tyrosine hydroxylase (TH) deficiency (called DYT/PARK-TH), although many other disorders may mimic dopa-responsive dystonia, including juvenile Parkinsonism. Segawa syndrome is inherited in an autosomal dominant manner; tyrosine hydroxylase deficiency is inherited in an autosomal recessive manner. NORD has individual reports on both disorders. These disorders are also known as DYT5A and DYT5B. Recessive forms of dopa-responsive dystonia can also be caused by sepiapterin reductase (SPR) deficiency.
DYT-THAP1 dystonia (previously called DYT6) is characterized by dystonia affecting the cranial, cervical and laryngeal areas. Dystonia tends to worsen and spread to other areas (generalized dystonia). Some individuals initially exhibit dystonia affecting the arms and later develop cranial and cervical dystonia symptoms. Most often, this disorder has a juvenile onset. DYT-THAP1 is caused by variants in the THAP1 gene and is inherited in an autosomal dominant manner.
Paroxysmal nonkinesigenic dyskinesia (PKND) is a disorder characterized by episodes of dystonia and choreoathetosis. Choreoathetosis is characterized by irregular, rapid, jerky movements that may occur in association with slow, writhing motions. Episodes may last from minutes to hours and can recur multiple times per day or per month. Episodes are often triggered by alcohol, caffeine, hunger, fatigue, stress and nicotine. Movement does not trigger an episode. The onset of the disorder can vary from early childhood to early adulthood. The disorder can potentially be disabling because it can interfere with basic activities such as chewing, swallowing, speaking, walking and coordinating movements of the arms and hands. PNKD is caused by variants in the MR1 gene (also called PNKD gene) and is inherited in an autosomal dominant manner. In some cases, the disorder occurs randomly, for unknown reasons (sporadically). The disorder is also known as PxMD-PNKD (previously called DYT8), paroxysmal dystonic choreoathetosis, or Mount-Reback syndrome.
Paroxysmal kinesigenic dyskinesia (PKD), also known as PxMD-PRRT2 (previously named DYT10), is characterized by episodes of dystonia and choreoathetosis that are triggered by sudden movements or when startled. Episodes usually last seconds or minutes. In some cases, as many as 100 episodes can occur in a single day; in others as few as one a month may occur. In rare cases, jerky, flailing or swinging movements (ballism) may also be seen. Some affected individuals may experience abnormal sensations (aura) in the affected area just before an attack occurs. Age of onset is usually in childhood or adolescence, but the disorder has been reported in individuals ranging from 4 to 57 years of age. PKD is caused by variants in the PRRT2 gene and is inherited in an autosomal dominant manner. These symptoms respond extremely well to a low dose of an antiepileptic medication called carbamazepine.
Myoclonic dystonia, previously known as DTY11, myoclonus-dystonia, or according to the updated nomenclature DYT-SGCE, is characterized by rapid, involuntary, jerking movements (myoclonus) with or without sustained dystonic postures. Myoclonus most often affects the neck, trunk and upper arms. Less commonly, the legs are involved. Myoclonus is caused by muscle contractions or muscle relaxation and cannot be controlled by the affected individual. Affected individuals may also develop focal or segmental dystonia (e.g. writer’s cramp or cervical dystonia). Generally, dystonia does not worsen or progress to other areas. Additional symptoms that have been reported include panic attacks, anxiety, depression and obsessive-compulsive disorder. Onset is usually during childhood or adolescence. Most cases of myoclonus-dystonia are caused by variants in the SGCE gene. The disorder is inherited in an autosomal dominant manner.
Rapid-onset dystonia-parkinsonism (RDP), also known as DYT12 or DYT/PARK-ATP1A3, is characterized by dystonic features and additional symptoms that resemble those seen in Parkinson’s disease (Parkinsonism). Classic features include involuntary dystonic muscle spasms in the arms more often than the legs and prominent involvement of speech and swallowing muscles. Parkinsonian symptoms include involuntary, rhythmic, quivering movements (tremors), bradykinesia and postural instability. Seizures have been reported in some patients. As the name suggests, symptoms usually develop rapidly over a period of a few hours or days, and often after a triggering event such as emotional stress, alcoholic binge drinking, childbirth or certain forms of exercise such as running. RDP is caused by variants in the ATP1A3 gene and is inherited in an autosomal dominant manner. RDP usually begins in adolescence or young adulthood and stabilizes within approximately 4 weeks, with little progression of the disorder thereafter, however the availability of genetic testing has revealed that the clinical spectrum of the disorder is wider than initially appreciated, including alternating hemiplegia of childhood (For more information on this condition, choose “alternating hemiplegia of childhood” in the Rare Disease Database.)
Paroxysmal exertion-induced dyskinesia, also known as PxMD-SLC2A1 or DYT18, is characterized by the combination of chorea, athetosis and dystonia that primarily affects excessively exercised areas of the body. The legs are most commonly affected. An episode may last from a few minutes to more than an hour and occurs after prolonged physical activity or exercise. In some people, additional symptoms have been reported including seizures, hemolytic anemia and migraines. Paroxysmal exertion-induced dyskinesia is caused by variants in the SCL2A1 gene and is inherited in an autosomal dominant manner.
ACQUIRED DYSTONIA
Acquired dystonia may be the result of environmental or disease-related damage to a part of the brain or central nervous system (See Causes section below). Acquired dystonia often presents with other neurological findings such as Parkinsonism. The specific symptoms and severity of these disorders vary based upon the underlying causes, specific body areas involved and other factors.
A specific form of acquired dystonia is tardive dyskinesia, which encompasses forms of dystonia that are induced using certain drugs. Tardive dyskinesia causes 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. NORD has an individual report on tardive dyskinesia.
In some people, dystonia occurs due to a known specific cause (acquired dystonia). Other cases are genetic and occur due to specific genetic variants. Other cases occur randomly for no apparent reason, without a family history of the disorder (sporadically). In many cases, the exact underlying cause of dystonia is unknown or unproven (idiopathic). Most likely, many cases of dystonia develop due to multiple factors including genetic and environmental ones.
Conditions associated with acquired dystonia include brain injury (particularly due to lack of oxygen) during or around the time of birth (perinatal period), certain infections, reactions to certain drugs, brain trauma, or various vascular abnormalities such as stroke, arteriovenous malformations or profuse, excessive bleeding (hemorrhaging). Dystonia can also result from other illnesses affecting the central nervous system.
Multiple genes have been associated with inherited dystonia. Researchers are actively seeking to locate additional genes and gene markers. Genetic factors are also believed to play a role in idiopathic and acquired dystonia, especially in individuals who have a relative with another form of dystonia. These individuals may have a genetic susceptibility to developing the disorder. A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or activated by other genetic modifiers or environmental factors.
Gene variants that have been identified to cause inherited forms of dystonia may be inherited in an autosomal recessive, autosomal dominant X-linked or mitochondrial manner.
Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Dominant genetic disorders may be marked by incomplete penetrance, which means that some individuals who inherit the gene for a dominant disorder will not be affected by the disorder. Variable expressivity can also occur, which means that widely varying signs and symptoms can occur among affected individuals with the same gene variant.
X-linked genetic disorders are conditions caused by a disease-causing gene variant on the X chromosome and mostly affect males. Females who have a disease-causing gene variant on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the gene variant. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease-causing gene variant, he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with an X-linked disorder can reproduce, he will pass the gene variant to all his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male children.
Some forms of dystonia are also classified as mitochondrial diseases. These disorders are caused by variants in the DNA of the mitochondria. Mitochondria are the cell structures that carry the body’s instructions for regulating energy production. Genes for mitochondria (mtDNA) are inherited from the mother. This is because the mtDNA in sperm cells is usually lost during fertilization. A mother with a gene variant in mtDNA will pass the variant to all her children, and her daughters will pass the variant to their children.
Normal mitochondrial genes and gene variants can exist in the same cell, a situation known as heteroplasmy. The number of mitochondria with the gene variant may be outnumbered by the number of mitochondria with a normal gene. Symptoms may not appear until a significant proportion of mitochondria have mtDNA with the gene variant. The uneven distribution of normal genes and gene variants in mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of different symptoms in affected family members.
Several theories attempt to explain the underlying mechanism of dystonia including abnormal functioning of or subtle abnormalities affecting certain areas of the brain including the basal ganglia, cerebellum, cortex, brainstem and thalamus. Imbalances in neurotransmitters have also been studied. Neurotransmitters are chemicals that modify, amplify, or transmit nerve impulses from one nerve cell (neuron) to another, enabling nerve cells to communicate. Although the underlying mechanisms and causes of dystonia are not well understood, research is ongoing to determine the specific roles that genetic, environmental and other factors ultimately play in the development of the disorder.
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. However, because many cases of dystonia go misdiagnosed or undiagnosed, determining the true frequency of dystonia in the general population is difficult. Focal forms of dystonia are approximately 10 times more common than generalized forms.
A diagnosis of dystonia is based upon identification of characteristic symptoms, a detailed patient and family history and a thorough clinical evaluation. Evaluation by a movement disorder specialist may help to confirm a diagnosis of dystonia. Various, specialized tests may be recommended to rule out other conditions. Laboratory testing is essential in acquired dystonia to determine the underlying cause.
Molecular genetic testing can confirm a diagnosis of certain inherited forms of dystonia. Molecular genetic testing can detect variants in the specific genes known to cause inherited dystonia.
Treatment
Currently, no curative therapies are available for dystonia. Current treatments target specific symptoms and are intended to relieve muscle spasms, pain and discomfort, and unnatural postures. No single treatment program is appropriate for every patient.
There are 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 some patients.
There are no oral medications approved by the U.S. Food and Drug Administration (FDA) for dystonia. Sometimes oral medications that affect the activity of neurotransmitters are prescribed. Anticholinergic agents such as benztropine and trihexyphenidyl block the neurotransmitter acetylcholine, and benzodiazepines such as clonazepam, diazepam or lorazepam block the neurotransmitter gamma-aminobutyric acid (GABA). These drugs are most effective in children with generalized dystonia.
Some individuals with dystonia, particularly those with dopa-responsive dystonia (DRD) respond to treatment with very low doses of levodopa, a synthetic version of the neurotransmitter dopamine. Levodopa increases dopamine levels. People with certain different forms of dystonia may respond to medications that block the activity of dopamine (antidopaminergic agents).
A muscle relaxant known as 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. Baclofen can stimulate the body’s ability to process the neurotransmitter GABA.
There is no standard treatment for rapid-onset dystonia-parkinsonism (RDP), although levodopa/carbidopa medications and dopamine agonists (drugs that stimulate dopamine receptors in the absence of dopamine) may provide mild improvement for some affected individuals.
In complex syndromes caused by metabolic conditions where dystonia represents one of their manifestations, such as Wilson’s disease, different treatments specific for each condition can be attempted (summarized in table 5.5 in Jinnah et al., 2019 and Mohammad et al., 2019).
Botulinum toxin therapy is often used for certain forms of dystonia, particularly certain focal dystonias such as cervical dystonia and laryngeal dystonia. Botulinum toxin is a neurotoxin that is injected into muscles in very small doses. After injection into a muscle, the action of botulinum toxin is to interrupt nerve messages to the muscle, preventing the release of the neurotransmitter acetylcholine, which stimulates muscular contractions, and causes weakness of that muscle. The effect of botulinum toxin on the muscle begins approximately 2-3 days following injection, peaks at around 4 weeks and provides relief for approximately 3-6 months. When the effect of botulinum toxin wears off, the symptoms of dystonia recur. The degree of effectiveness of botulinum toxin will differ in each individual. Using ultrasound to guide the injection in the target muscles can significantly increase the benefit of the treatment for certain types of dystonia (such as task specific dystonias or truncal dystonia).
Botulinum toxin is approved by the FDA for cervical dystonia and blepharospasm and is widely used off label to treat all forms of dystonia. The FDA has a “black box” warning concerning the use of any of these toxins. A black box warning denotes that a drug known to be effective for some individuals may cause serious side effects in others.
Surgery is generally reserved for those patients with severe dystonia who do not respond to drug therapy or cannot tolerate side effects as well as those with severe dystonia who become non-responsive to drug treatment. Deep brain stimulation (DBS) with an implantable pulse generator may be performed for some types of dystonia. DBS involves the surgical placement of very thin electrodes into certain areas of the brain such as the globus pallidus. The leads from these electrodes are then connected to a small device called a neurostimulator that is surgically implanted usually near the collarbone. These stimulators send small electrical pulses to the brain. After the DBS is placed, the stimulators are programmed for the optimal outcome. The electrical pulses block or interfere with the nerve signals that cause the symptoms of dystonia.
DBS has become the mainstay for surgical treatment of individuals with dystonia. Older surgical procedures such as thalamotomy or pallidotomy are rarely used anymore for the treatment of dystonia. These procedures involved the precise destruction of a tiny area of the brain to interrupt the nerve pathways responsible for the symptoms of dystonia.
Selective peripheral denervation in which the nerves to the dystonic muscles are severed has been reported to benefit patients with cervical dystonia who do not benefit from other therapies. However, this surgery requires a surgeon who is extensively trained both in the evaluation cervical dystonia and in the surgical procedure. Side effects from the surgery are not uncommon and following surgery, there is a long period of rehabilitation.
Information on current clinical trials is posted on the Internet at https://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
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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DeLong MR. Rapid-Onset Dystonia-Parkinsonism. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:617-618.
JOURNAL ARTICLES
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Jinnah HA. The Dystonias. Continuum (Minneap Minn). 2019;25(4):976–1000. https://pubmed.ncbi.nlm.nih.gov/31356290/
Mohammad SS, Paget SP, Dale RC. Current therapies and therapeutic decision making for childhood-onset movement disorders. Mov Disord. 2019;34(5):637–656. https://pubmed.ncbi.nlm.nih.gov/30919519
Lohmann K, Klein C. Update on the Genetics of Dystonia. Curr Neurol Neurosci Rep. 2017;17(3):26. https://pubmed.ncbi.nlm.nih.gov/28283962
Meyer E, Carss KJ, Rankin J, et al. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet. 2017;49(2):223–237. https://pubmed.ncbi.nlm.nih.gov/27992417/
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Defazio G, Conte A, Gigante AF, Fabbrini G, Berardelli A. Is tremor in dystonia a phenotypic feature of dystonia? Neurology. 2015;84:1053-1059. http://www.ncbi.nlm.nih.gov/pubmed/25663232
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INTERNET
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