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What is it?
Early-onset generalised dystonia, the most common hereditary form of dystonia, is characterised by the twisting of the limbs, specifically the foot/leg or hand/arm. The spasms may spread to involve twisting contractions of other parts of the body.
Symptoms
Symptoms in early-onset generalised dystonia can range from twisted postures, turning in of the foot or arm, muscle spasms, unusual walking with bending and twisting of the torso, rapid, sometimes rhythmic, jerking movements; and progression of symptoms leading to sustained or fixed postures. Because the legs and trunk are so commonly affected in early-onset generalised dystonia, abnormal gait may be common.
Factors such as age and body site play a significant role in the progression of early-onset generalised dystonia. The younger the age of onset, the more likely the dystonic symptoms will begin in one of the legs, spread upward to other areas, and possibly become generalised.
Symptoms commonly begin with a specific action, that is, the abnormal movements appear with a specific action, and are not present at rest. For example, if it begins in one leg, the symptoms may be present only when walking and disappear when the child runs or walks backwards.
In generalised dystonia that begins in the arm, symptoms may be task-specific, apparent only during the act of writing or playing a musical instrument. If the disorder progresses, the symptoms of arm dystonia may appear when another part of the body is engaged in voluntary motor activity. If the dystonia spreads to involve parts of the body other than the limb of onset, it will first move to adjacent segments of the body, and then more distally.
Dystonia is usually present continually throughout the day whenever the affected body part is in use and may disappear with sleep.
The age of onset varies, but the peak period is between the ages of seven and ten with symptoms progressing, then stabilising within a five-year period.
If early-onset generalised dystonia causes any type of impairment, it is because muscle contractions interfere with normal function. Features such as cognition, strength, and the senses, including vision and hearing, are normal. While dystonia is not fatal, it is a chronic disorder.
Historically, early-onset generalised dystonia has also been referred to as idiopathic torsion dystonia and dystonia musculorum deformans.
Cause
Early-onset generalised dystonia is believed to be due to abnormal functioning of the basal ganglia which are deep brain structures involved with the control of movement. The basal ganglia assist in initiating and regulating movement. What goes wrong in the basal ganglia is still unknown. An imbalance of dopamine, a neurotransmitter in the basal ganglia, may underlie several different forms of dystonia.
In 1997, researchers identified the DYT1 gene responsible for early-onset generalised dystonia. The DYT1 gene contains the genetic code for a previously unknown protein called “TorsinA,” and it has significant similarities to the heat-shock proteins and chaperone proteins. Found in virtually all living organisms, the heat-shock proteins help cells recover from stresses including heat, traumatic injury, and chemical poisoning. Until now, no human disease has been associated with these proteins.
In people with early-onset dystonia, the DYT1 gene has a mutation that causes the deletion of three “letters” or nucleotides called GAG in the genetic code. This GAG deletion results in the loss of an amino acid, called glutamic acid, which is a component of the TorsinA protein. This relatively minute change in the TorsinA blueprint apparently causes critical changes in the function of the protein. The role of the TorsinA protein is currently unknown, but somehow this defective protein disrupts communication among the neurons responsible for movement and muscle control, leading to the symptoms of the dystonia disorder. Individuals who have this mutation are carriers of the DYT1 GAG deletion.
Researchers believe that the same mutation in the DYT1 gene appeared independently in several ethnic populations throughout history and is possibly one of only a few mutations that result in early-onset dystonia. Exactly how the abnormal gene causes the dystonia is presently unknown.
The mode of inheritance for early-onset generalised dystonia is autosomal dominant. Only one copy of the DYT1 gene is needed to cause symptoms. For reasons scientists do not yet understand, only 30 to 40% of those with the abnormal DYT1 gene develop symptoms of dystonia. There is no way yet to predict whether a person with the abnormal gene will develop symptoms of the disorder, and the severity of the illness may differ markedly within a family.
Most cases of early-onset dystonia are not due to new mutations but rather to accurate or "faithful" copying and inheritance of a gene mutation that occurred many generations in the past.
Diagnosis
Diagnosis of early-onset generalised dystonia is based on information from the affected individual and the physical and neurological examination. Since this is a hereditary form of dystonia, a family history may be obtained.
Testing for the DYT1 gene is helpful in confirming diagnosis of early-onset generalised dystonia. However, if the test is negative, this does not mean that the person does not have dystonia, but that he/she does not have this particular genetic subtype of dystonia.
Treatment
Currently there is no cure for dystonia, but treatments are available to help to ease the symptoms related to the disorder including spasms, pain, and disturbed postures. Working with your doctor, an individualized strategy for treatment can be developed.
The approach for treatment of dystonia is usually three-tiered: oral medications, botulinum toxin injections, and surgery. These therapies may be used alone or in combination. Complementary care may also have a role in the treatment management, depending on the form of dystonia, and supportive therapy may provide an important adjunct to medical treatment.
Medications
Treating generalised dystonia is a step-by-step process. Physicians need to be very conscious of how their patients are reacting to prescribed medications and potential side effects. There are many pharmacological options for dystonia, and physicians depend heavily on oral medications to treat this form of dystonia. The most thoroughly studied medications used to treat dystonia are anticholinergics, the most popular of which are Artane (benzhexol) and Cogentin (benztropine). Children can tolerate much higher doses of these medications than adults can, but, as children age, the dose may need to be decreased, usually without a significant loss of effectiveness. Side effects related to Artane may include confusion, forgetfulness, memory loss as well as lesser effects such as dry mouth, blurred vision, and trouble urinating.
A child diagnosed with early-onset generalised dystonia will often receive a trial prescription of levodopa to rule out dopa-responsive dystonia. Levodopa can have remarkable benefit for people with dopa-responsive dystonia, and it can sometimes help the symptoms of generalised dystonia. Side effects may include light-headedness, nausea, constipation, and sometimes fatigue.
Botulinum Toxin
Botulinum toxin injections may be effective in treating generalised dystonia as an adjunct to oral medications for a specific group of muscles. For example, if the neck muscles are profoundly in spasms, injections of botulinum toxin into the neck may give added benefit to relieving symptoms already being obtained with medications.
Botulinum toxin is a therapeutic muscle-relaxing agent that helps reduce the uncontrollable muscular contractions associated with dystonia. It is injected into specific muscles where it acts to weaken muscle activity sufficiently to reduce a spasm but not enough to cause paralysis.
Surgery
Surgical treatment for dystonia is usually reserved for those persons where the potential benefits outweigh the potential risks and for those for whom non-surgical treatment is no longer providing adequate control of the symptoms. Each patient is unique, and the muscles involved vary from one patient to another. It is for this reason that pre-operative evaluation by a movement disorders expert is essential.
Some operations intentionally damage small regions of the thalamus (thalamotomy), globus pallidus (pallidotomy), or other deep centers in the brain. Pallidotomy and thalamotomy target regions of the brain that are involved in movement generation. By destroying one or the other of portions of these small brain regions, these surgeries rebalance movement and posture control. During the past few years, improved technology has allowed precise targeting of select areas in the thalamus or pallidum, reducing risk of complications.
The technique of deep brain stimulation (DBS) has been used in place of the conventional approach of lesioning or ablation. DBS entails placing a permanent radio frequency stimulating the electrode in the brain, which is connected to a pulse generator implanted in the chest wall. Whereas ablation causes permanent destruction of the targeted area, DBS acts reversibly to inactivate the area. It can be adjustable in terms of frequency and amplitude of the current pulses, thus specifying the area influenced.
Complementary Therapy
The use of sensory tricks is also effective in dealing with early-onset generalised dystonia. Some of the common “tricks” used are touching the involved or adjacent body part, elevating one leg when standing in one place, or placing one hand on the back of the head when the trunk is involved. Different sensory tricks work for different people, and if a person finds a sensory trick that works, it usually continues to work.
Physical therapy may also play a treatment role. In some cases stretching can be helpful to preserve a full range of motion. Strengthening exercises can also be beneficial if they are not too strenuous and are specifically suited for each individual case.
Support
Dystonia and its emotional offshoots affect every aspect of a person’s life - how we think, the way we act, and how we cope. By educating yourself with information, you have taken the first step in dealing with dystonia.
Stress is an inevitable part of life, and although it clearly does not cause dystonia, it can aggravate dystonia symptoms. Stress-reduction programmes such as relaxation techniques, meditation, and journal writing may be beneficial.
Sometimes depression can be a byproduct of dystonia. Depression may aggravate symptoms and make them worse, but, often, treating depression can result in an improvement of dystonia. It is important to remember that depression is a disorder; it is treatable and not a reflection of one’s self.
Many people are experiencing similar symptoms. Reassurance from family, friends, and others who have dystonia is beneficial. Dystonia Ireland has a support group in Dublin and it is our intention eventually to set up similar groups throughout Ireland. Sharing experiences at support group meetings offers encouragement, camaraderie, and the latest information about new treatments and medical advances.
With written permission, this information is reproduced from materials published and copyrighted by the Dystonia Medical Research Foundation, Chicago, IL, USA www.dystonia-foundation.org
