What is dystonia?
Dystonia is a brain disorder that impairs normal control of movement due to a combination of muscle over- and under-activity that leads to involuntary movements, postures, or both. It is the basis of golfers’ yips, leads to musicians giving up their careers and is a major component of cerebral palsy, as depicted by Daniel Day Lewis in his Academy Award winning performance in My Left Foot, a biopic of the Irish artist Christy Brown.
The involuntary muscle activity in dystonia is usually most prominent when a person is performing an action. It may be present only during action or even only during a specific task e.g. writing but not typing on a keyboard.
The involuntary muscle activity in dystonia is usually most prominent when a person is performing an action.
Abnormal muscle contractions result in involuntary twisting or turning of the affected body part, which may be stable and manifest primarily as an abnormal posture, or unstable and manifest primarily as an involuntary movement, although there is usually still an underling subtle abnormality of posture.
Cervical (neck) dystonia will cause a person’s head to turn at an angle and make it difficult to look straight. The abnormal posture in an individual will always be similar, but can be very different from one affected individual to another.
Blepharospasm (eyelid dystonia) causes the eyelids to clamp shut when the person is trying to open them. In musician’s dystonia, the fingers or wrist cannot be controlled skilfully because of superimposed muscle spasms.
Dystonia can occur as an isolated problem, or combined with other neurological problems in a disease affecting multiple parts of the nervous system. The most common type of dystonia occurs as an isolated problem that develops in adulthood and is limited to one part of the body.
Prevalence of the disorder
Estimates of the prevalence of this type of dystonia vary greatly, from 0.01-1% of the population. The cause is unknown in the vast majority of such cases, however it is probably a disorder of neuronal function rather than a degenerative disease.
When dystonia is combined with other neurological problems, the cause is often an underlying brain injury or neurodegenerative disorder, of which there are many examples, some common and some rare.
Rational treatment of dystonia is hampered by limited understanding of its pathophysiology.
Rational treatment of dystonia is hampered by limited understanding of its pathophysiology. Oral medications are beneficial in only a minority of patients, and in a limited fashion. In many but by no means all forms of dystonia limited to one part of the body, botulinum toxin injections are the treatment of choice.
The toxin is injected into and temporarily weakens muscles that are overactive in the dystonia, rather than targeting the brain which is where dystonia originates, and can be likened to treating engine problems by adjusting tyre pressures!
Fortunately, however, this treatment strategy is often highly effective. For people with severely disabling isolated dystonia, especially if it is generalized to multiple parts of the body, deep brain stimulation via electrodes inserted into the basal ganglia, deep structures in the middle of the brain that are involved in movement control, can be beneficial.
Monogenetic forms of dystonia are rare. Currently, mutations in 13 genes have been identified which can cause isolated or predominant dystonia, as well as a number of genes required for the biosynthesis of dopamine (of note, degeneration of neurons that produce dopamine is the cause of Parkinson’s disease).
The likelihood of detecting a specific genetic mutation in a person with dystonia in the absence of a family history is extremely low
Some have only been reported in a handful of families from around the world. The likelihood of detecting a specific genetic mutation in a person with dystonia in the absence of a family history is extremely low, and even in established families with dystonia, genetic testing will often be negative.
However, each gene which is discovered provides insights into the neuronal and cellular mechanisms that are involved in the pathogenesis of dystonia, and a new potential therapeutic target. For example, the genes that are currently known to cause dystonia are important in either calcium homeostasis/signalling or neurodevelopment.
Clues from the changes caused by dystonia
In parallel with genetic research, studies in people with dystonia using neurophysiological tools including transcranial magnetic stimulation, as well as brain imaging tools such as functional MRI, are providing clues on how the nervous system and brain activity are altered in dystonia.
These studies also offer the hope of a better understanding of the pathophysiology of dystonia, thereby allowing rational design of medical, surgical and neurorehabilitation therapies.
For example, a study of people with apparently sporadic (non-familial) isolated dystonia and their families using a neurophysiological test of the ability to sense electrical impulses separated by a short interval of time, has offered the tantalising suggestion that sporadic dystonia may have an underlying genetic underpinning.
Dystonia is a complex and often disabling disorder for which there are still only very limited treatment options.
Dystonia is a complex and often disabling disorder for which there are still only very limited treatment options. At our Movement Disorders Unit at Westmead Hospital in Sydney, Australia, we, like many other centers around the world, combine a clinical and research interest in dystonia to try to gain knowledge and establish therapies for dystonia.
Local and international collaborations between clinicians from multiple disciplines, patients and experts in neurophysiological, imaging and genetic techniques underpin this approach.