Dystonia

OVERVIEW

Dystonia is a very complex, highly variable neurological movement disorder characterized by involuntary muscle contractions. As many as 250,000 people in the United States have dystonia, making it the third most common movement disorder behind essential tremor and Parkinson’s disease. It is a condition that knows no age, ethnic or racial boundaries – it can affect young children to older adults of all races and ethnicities.

Dystonia results from abnormal functioning of the basal ganglia, a deep part of the brain which helps control coordination of movement. These regions of the brain control the speed and fluidity of movement and prevent unwanted movements. Patients with dystonia may experience uncontrollable twisting, repetitive movements or abnormal postures and positions. These can affect any part of the body, including the arms, legs, trunk, face and vocal cords.

Causes

The exact cause of dystonia is not yet known but may involve alteration in several regions of the brain or the communication between them. Dystonia may be inherited, acquired, or idiopathic (no known cause). Inherited disorders are transmitted genetically. In acquired forms, dystonia is caused by damage or degeneration of the brain (e.g. after a brain injury or stroke) or exposure to particular drugs. In idiopathic dystonia there is no identifiable cause and no structural damage or degeneration to the brain.

Dystonia Classification

Dystonia is classified by three main factors: the age at which symptoms develop; the areas of the body affected; and the underlying cause.

The chance that dystonia will affect multiple body parts is generally linked to the age of onset. The younger one is at onset, the greater the chance that symptoms will spread. Conversely, the older one is at onset, the more likely that the disorder will remain more moderate.

Dystonia Classification by Age

• Childhood onset – 0 to age 12
• Adolescent onset – age 13 to 20
• Adult onset – older than age 20

Dystonia Classification by Body Part

Focal Dystonia

Focal dystonia is limited to one area of the body and can affect the neck (cervical dystonia or spasmodic torticollis), eyes (blepharospasm), jaw/mouth/lower face (oromandibular dystonia), vocal cords (laryngeal dystonia) or arms/legs (limb dystonia). Other less common types of focal dystonias can cause unusual stretching, bending or twisting of the trunk (truncal dystonia) or sustained contractions and involuntary, writhing movements of the abdominal wall (abdominal wall dystonia).

Focal dystonia more commonly affects people in their 40s and 50s and is frequently referred to as adult-onset dystonia. Women are affected about three times more frequently than men. In general, focal dystonias are classified as primary (idiopathic) and are not hereditary.

Segmental Dystonia

Segmental dystonia affects two or more parts of the body that are adjacent or close to one another. Up to 30 percent of people with focal dystonia have spasms in areas adjacent to the primary site. A common form of segmental dystonia affects the eyelids, jaw, mouth and lower face.

Other types of dystonia include multifocal, which involves two or more body parts distant from one another; hemidystonia, which affects half of the body; and generalized, which begins with leg involvement, but generally spreads to one or more additional regions of the body.

Dystonia Classification by Cause

Primary (idiopathic)

Primary (idiopathic) dystonia is the only sign, and secondary causes have been ruled out. Most primary dystonias are variable, have adult onse, and are focal or segmental in nature. However, there are specific primary dystonias with childhood or adolescent onset that have been linked to genetic mutations.

The majority of early-onset primary dystonias, which may appear during childhood or early adulthood, are due to mutations of a gene known as DYT1. This gene has been mapped to the long arm of chromosome 9 at 9q34.1. In about 90 to 95 percent of cases, symptoms begin in a limb and then spread to other regions of the body. This form of dystonia has an average age of onset of 12 and seldom develops after age 29.

DYT6 dystonia is an autosomal dominant primary dystonia that has been mapped to chromosome 8 (8p21q22). It is rarer than DYT1 dystonia and has been studied in two Mennonite families in the United States. In nearly all individuals with this form of dystonia, the disorder begins at an initial site but spreads to multiple body regions, most commonly the limbs, head or neck. Severe difficulties with speech articulation have been noted.

Other familial primary dystonias identified are DYT7, DYT2, and DYT4, all of which have been noted in specific ethnic groups, primarily of European descent.

Secondary (symptomatic)

Secondary (symptomatic) results primarily from secondary causes. These include environmental, such as exposure to carbon monoxide, cyanide, manganese or methanol; underlying conditions and diseases such as brain tumors, cerebral palsy, Parkinson’s disease, stroke, multiple sclerosis, hypoparathyroidism or vascular malformations; brain/spinal cord injuries; inflammatory, infectious or postinfectious brain conditions; and specific medications.

Dystonia-plus Syndromes

Dystonia-plus syndromes results from nondegenerative, neurochemical disorders associated with other neurological conditions. Dystonia-plus syndromes include dopa-responsive dystonia (DRD) or Segawa syndrome, rapid-onset dystonia-parkinsonism (RDP) and myoclonus-dystonia.

Heredodegenerative Dystonia

Heredodegenerative dystonia generally results from neurodegenerative disorders in which other neurological symptoms are present and in which heredity plays a role. These include numerous disorders such as certain X-linked recessive, autosomal dominant, autosomal recessive and/or parkinsonian syndromes. Included in this category: X-linked dystonia-parkinsonism (Lubag), Huntington’s disease, Wilson’s disease, neuroacanthocytosis, Rett’s syndrome, Parkinson’s disease and juvenile parkinsonism.

Symptoms

Dystonia is sometimes misdiagnosed as stress, a stiff neck or a psychological disorder. The intermittent character of the disorder may lead medical practitioners to conclude that a psychological disorder is either the primary cause or a contributing factor. Diagnosis is difficult because dystonia symptoms are similar to those of many other conditions and are so variable in nature.

Dystonia initially arises after specific movements or tasks but, in advanced stages, it may occur at rest. It usually affects the same group of muscles, thus causing a repetitive pattern of movements over time. It generally develops gradually, with localized symptoms suggesting the presence of the disorder. Eye irritation, excessive sensitivity to bright light and increased blinking may be an indication of blepharospasm. Subtle facial spasms, difficulty chewing or changes in speech cadence may indicate oromandibular dystonia. Cramping of the hand during writing or fatigue during walking or other manual activities may indicate limb dystonia.

Dystonia is also variable in its progression. For some patients, the disease steadily worsens; for others, it plateaus. For some, dystonia stabilizes at a relatively minor stage and progresses no further. The advanced stage is marked by rapid and involuntary rhythmic movements, twisting postures, contortions of the torso, abnormal gait and ultimately, fixed postural deformities.

The disorder is usually not associated with pain, but it certainly may lead to pain in affected areas. Cervical dystonia can be particularly painful due to degeneration of the spine, irritation of nerve roots or frequent headaches. Limb dystonia may not cause pain initially but may become painful over time. Uncontrolled muscle movements may cause the joints to deteriorate, possibly leading to the onset of arthritis.

When & How to Seek Medical Care

Early signs of dystonia often are mild, infrequent and linked to a specific activity. See your doctor if you are experiencing involuntary muscle contractions.

Testing & Diagnosis

There is no definitive test for dystonia but doctors can make the diagnosis by learning about the symptoms and performing a neurological exam. Sometimes doctors use other tests such as a brain MRI to make sure something else is not causing the symptoms. For patients with early-onset dystonia or those with an affected relative, doctors may suggest genetic testing.

Treatment

There is no cure for dystonia and treatment is therefore directed at relieving symptoms. There is a three-tiered approach to treating dystonia: botulinum toxin (botox) injections, several types of medication and surgery. These may be used alone or in combination. Medications and botox can both help block the communication between the nerve and the muscle and may lessen abnormal movements and postures.

Botulinum toxin type A was developed in the 1980s. In 2001, the U.S. Food and Drug Administration approved botulinum toxin type B for treatment of cervical dystonia. Researchers created the new drug after some patients began developing resistance to the type A form. The type B drug has mild to moderate side effects such as dry mouth, dysphagia (difficulty swallowing) and indigestion.

Surgical treatment may be considered if medications and other treatments are not providing adequate relief, and if the symptoms negatively affect quality of life. The mainstay of surgical treatment for dystonia is deep brain stimulation (DBS). During DBS surgery, a battery-powered stimulator similar to a pacemaker is implanted in the body and delivers electrical stimulation to the areas of the brain responsible for causing dystonia symptoms. The stimulation to the brain is adjusted by remote control to achieve the appropriate settings for each individual patient.

DBS has replaced other surgical techniques such as stereotactic thalamotomy, pallidotomy, and cervical rhizotomy because of its success and lower risk for side effects. The benefits of any surgery though should always be weighed carefully against its risks. Although some dystonia patients report significant symptom reduction after surgery, there is no guarantee that surgery will help every individual.

Latest Research

Novel approaches to the treatment of dystonia include gene therapy and transcranial magnetic stimulation. Gene therapy may be a future option for patients with inherited forms of dystonia in which a specific gene is thought to be involved. Gene therapy for dystonia, though, has not yet been tested in patients. Transcranial magnetic stimulation is also being investigated as a non-invasive stimulation to treat dystonia. So far it has been studied in only small controlled trials for focal hand or cervical dystonia. Additional investigation is needed.

Resources for More Information

For more information on patient stories visit the Dystonia.uk patient stories section. There are also number of local, national and international support groups addressing some of issues and questions that patients and their families may face after a diagnosis of dystonia is made.

• Dystonia Foundation
• Rare Disease Network
• The Dystonia Society
• The Brain Charity