Dystonia - An Overview

Introduction

Movement disorders are classified based on fewer movements (hypokinetic) or excess movements (hyperkinetic). Dystonia, a hyperkinetic movement disorder, is an abnormal posturing of a muscle or the whole body. Clinically, the movements are continuous or intermittent muscle contractions causing abnormal repetitive movements. The condition can mostly affect a body part (focal dystonia), two or more adjoining body parts (segmental dystonia), or the whole body (generalized dystonia). The most frequent clinical presentation of dystonia in adults is cervical (neck) dystonia and focal hand dystonia. On the other hand, in children, generalized dystonia is found more frequently.

Dystonia is the third most frequent movement disorder after Parkinson’s disease (PD, a brain disorder that causes uncontrollable movements) and essential tremors (causes uncontrolled shaking in hands and arms during action and rest).

What Are the Clinical Features of Dystonia?

Four features can illustrate dystonia, they are age at onset, body distribution, progression, and associated aspects.

1. Age At Onset: The age at onset is crucial for a specific form of dystonia. It also helps in patient counseling and care due to its prognostic (outcome) value. Children with dystonia are more likely to have a detectable cause and generalized dystonia, whereas dystonic signs in adulthood are more focal. When grouping focal dystonia, the median age at onset ranges from six to 38 years. On the contrary, the combined forms range from zero to 40 years. These observations highlight the importance of relating the clinical description to age at onset. Further, age at onset can identify patterns or characteristics that can establish a specific diagnosis or treatment.

2. Body Distribution: Dystonia can present in any body region. However, it is most frequently seen in the cranial (head) and cervical (neck) region, larynx, trunk, and limbs. A combination of the areas can also be seen. Diagnosis and therapy depend on the classification of the involved body regions. Apart from focal, segmental, and generalized dystonia, multifocal (involving two nonadjacent or more body parts) and hemidystonia (body regions restricted to one side are involved) are also found in individuals.

3.Temporal Pattern (Progression of Dystonia): Signs and severity can vary in individuals. For example, dystonia can spread, which allows for a distinction between static and progressive forms. There is also diurnal variability (daytime occurrence) and fluctuation. Clinically, the temporal pattern is pertinent to define a specific diagnosis and treatment options. The temporal pattern of dystonia is divided into four groups:

• Persistent: Dystonia is present throughout the day with almost the same intensity.

• Paroxysmal: Episodes of dystonia are self-limited and induced by a trigger. After the episode, the patient returns to the previous state.

• Diurnal Fluctuations: The signs and severity vary following a circadian rhythm.

• Action-Specific: Dystonic movements present during a specific task.

4. Associated Aspects: Dystonia can occur alone or in conjunction with other movement disorders. It forms combined with myoclonus (sudden, brief involuntary twitching or jerking of a muscle or group of muscles), PD, essential tremors, or other movement disorders and are denoted as defined syndromes.

Complex dystonia describes syndromes involving dystonia combined with other brain disorders or systemic presentations. These syndromes include a range of neurodegenerative diseases, heavy metal disorders, fat storage disorders, genetic disorders, and disorders of vitamin metabolism. In Wilson’s disease (a genetic disorder that leads to copper accumulation in organs), dystonia is present along with psychiatric features and a dysfunctional liver.

What Are the Investigative Approaches to Dystonia?

Basic Investigations:

• Specific blood tests include copper and ceruloplasmin (a protein that binds copper) levels, lactate, pyruvate (metabolic enzymes), and antinuclear antibody (ANA; raised in autoimmune movement disorders) screening to look for findings causing the nervous system disorder. They should be individualized based on the clinical picture and the associated features.

• Positive clinical findings or laboratory abnormalities lead to further investigations, including electrophysiological (EP) studies, to assess for associated heart or nerve disorders.

• Lumbar puncture is used to study the dopamine pathway metabolites (implicated in PD) and can serve as a guide for further genetic testing.

• Muscle or skin biopsy and blood or urine tests may help investigate rarer causes, such as genetic and metabolic disorders.

• Brain magnetic resonance imaging (MRI) is not always recommended. However, it is done in Wilson's disease and may show radiological signs of Wilson's disease.

Genetic Testing: DYT1 dystonia (associated with the gene DYT 1) presents in childhood or adolescence. It is recommended that DYT1 testing should be done in dystonia patients before and after the age of 30 for a better outcome.

What Are the Effective Treatment Options for Dystonia?

Treatment of dystonia is done with drugs, botulinum toxin injections, and deep brain stimulation surgery.

Drugs:

• Trihexyphenidyl (an anticholinergic drug; that stops involuntary muscle movements) is given in generalized and focal dystonias. The side effects are the dryness of mouth and eyes, nausea, confusion, memory loss, hallucinations, and urinary retention.

• Tetrabenazine is a dopamine-depleting drug used in the symptomatic treatment of hyperkinetic movement disorders. One must note that there is insufficient evidence to support the use of Tetrabenazine for focal dystonia. However, it is commonly used for generalized dystonia. Tetrabenazine should be avoided in depression patients as it can increase the chances of suicide.

• Clonazepam is a benzodiazepine drug acting as a muscle relaxant used in generalized dystonia. Clonazepam can cause sleepiness, and there is a risk of an accident in professions involving heavy machine operation and prolonged driving. Hence, a patient must avoid these activities during the intake of this medication.

Botulinum Toxin: Botulinum toxin (BT) is used to treat many muscle hyperactivity syndromes, gland disorders, and pain conditions. Dystonia is one of the most important indications of BT. However, the safety and efficacy of BT are unclear in patients less than 16 years for the treatment of cervical dystonia. Further, there is insufficient data to allow its use in pregnancy and lactation. The main side effects are excessive weakness in the injected muscles and medication spread to the adjacent muscles causing their weakness. Other side effects are fatigue, flu-like symptoms, dry mouth and eyes, and dizziness.

Deep Brain Stimulation Surgery: Deep brain stimulation (DBS) is one of the most important advances in clinical neuroscience. DBS can directly measure pathological brain activity and deliver stimulation for therapeutic effects in brain and psychiatric disorders. The DBS device comprises a lead with four electrodes and a programmable pulse generator (delivers the current). DBS is used for the treatment of generalized and segmental dystonia.

Conclusion

Dystonia is a brain disorder characterized by involuntary and abnormal muscle contractions. It arises from a dysfunction within the central nervous system. However, it is a lifelong disorder in which patients have a normal expectancy. Still, some patients may have complete disease remission. The severity of symptoms is unpredictable, as they may fluctuate, disappear, or stabilize for some time.