Dystonia: classification, symptoms and treatment

Muscular dystonia, also known as torsion dystonia, is actually a generic term for a large group of movement disorders that differ in their symptoms, causes, progression, and treatment methods. These neurological conditions are usually characterized by involuntary muscle contractions, which cause the body to perform abnormal, sometimes painful movements and take unusual positions (postures).

Muscle contractions can be steady or occur occasionally (with more or less interruptions). The movements are of the twisting type or in some cases the affected part of the body trembles, resembling a tremor.

Dystonia can occur or be aggravated when a person takes any action or performs a strictly defined work. There are many different causes of dystonia. Genetic and non-genetic factors may contribute to the development of these disorders. In some cases, the exact cause is unknown, then talk about idiopathic dystonia.

Video: Dystonia

Subtypes of dystonia

Dystonia was first described in the medical literature as early as the 1800s. It is characterized by characteristic signs associated with most subtypes of dystonia. They are twisting, repetitive movements that affect the neck, torso, limbs, eyes, face, vocal cords and / or a combination of these muscle groups. Some forms of the disease, such as laryngeal dystonia, are not associated with changes in normal body positions.

Dystonia causes varying degrees of pain and disability, ranging from mild symptoms, quickly coming, to severe and even debilitating manifestations. They can significantly affect the quality of human life. In some cases, dystonia may gradually progress, while in others it remains unchanged for a long time.

Dystonia can even spontaneously spread to other parts of the body. Treatment of the disease depends on several factors, including the specifically diagnosed subtype.

The main subspecies of dystonia:

• Blepharospasm (benign essential blepharospasm [BEB])
• Cervical Dystonia (Spastic Torticollis [ST])
• Acquired dystonia
• Dopa-sensitive dystonia (DRD)
• DYT1-related dystonia
• Focal dystonia
• Generalized dystonia
• DYT6-related dystonia
• Myoclonic dystonia
• Oromandibular dystonia
• Embouchure dystonia
• Paroxysmal dystonia, choreoathetosis
• Paroxysmal kinesogenic dystonia (PKD)
• Primary dystonia
• Rapidly beginning dystonia-parkinsonism (RDP)
• Paroxysmal non-kinesitic dyskinesia (PKND)
• Segmental dystonia
• Spastic Dysphonia (SD)
• Spastic Torticollis (Cervical Dystonia)
• Tardive dyskinesia
• Late dystonia
• Writing cramp
• X-linked dystonia-parkinsonism
• Dyskinesia caused by paroxysmal load

There are several theories that try to explain the main mechanism of development of dystonia. In particular, abnormal functioning or subtle disorders affecting certain areas of the brain, including the basal ganglia, the cerebellum, the cerebral cortex and the thalamus, occur. An imbalance involving neurotransmitters is also under study.

Neurotransmitters are chemicals that modify, amplify or transmit nerve impulses from one nerve cell (neuron) to another, allowing nerve cells to bind.

Although the underlying mechanisms and causes of dystonia are not well understood, research continues to determine the specific role that genetic, environmental, and other factors ultimately play in the development of the disorder.

Dystonia: classification

Dystonia classification has always been complex and controversial, which led to confusion not only among patients, but also among the medical community. A new basis for the classification of dystonias was proposed in the form of a consensus reached by an international group of experts (Albanese A, et al. 2013). This group proposed to classify dystonia in two directions: clinical features and etiology (causes of the disease).

Clinical signs of dystonia include:

• Age of onset of the disease.
• Localization of the affected part of the body.
• Temporary characteristics and related features.

The age of onset of the disease is divided into infancy (from birth to 2 years), childhood (3–12 years), adolescence (13–20 years), early adulthood (21–40 years), and late adulthood (over 40 years).

Dystonia, which develops in infancy or childhood, is more likely to have a known cause. It often progresses, taking a widespread form.

Dystonia classification by individual affected parts of the body is common to many classification systems. As a rule, dystonia can be:

• Focal (affecting an isolated part of the body).
• Segmental (affecting the adjacent areas of the body).
• Multifocal (two or more non-adjacent areas).
• Generalized (affecting the trunk and two other areas of the body).
• Hemidistonia (affects one side of the body).

Temporary symptoms that progressively worsen or remain unchanged (static) help to distinguish dystonia. This also applies to the variability of the severity of the disease in relation to other factors, such as external triggers or voluntary actions.

Temporary patterns (forms) can be divided into four types:

1. Permanent, in which dystonia persists throughout the day without hesitation.
2. Specific to the task in which dystonia occurs only during a specific action or task (for example, the writer's convulsion).
3. Daily fluctuations in which the severity of dystonia varies during the day and often decreases overnight.
4. Hot flashes, in which a sudden, temporary episode of dystonia often occurs as a result of exposure to a specific trigger.

Dystonia can also be classified according to whether it occurs together with another movement disorder.

• Isolated dystonia is when dystonia is the only sign of impaired movement, with the exception of tremor.
• Combined dystonia is used when another movement disorder is also present, such as parkinsonism or myoclonus.

The etiology of the disease refers to whether degenerative changes or structural damage are present in the nervous system (pathology of the nervous system). There is also a hereditary or acquired disease, or the cause is unknown or not proven (idiopathic).

Modern terminology used to classify dystonia includes:

• Primary dystonia.
• Secondary dystonia.
• Muscular dystonia plus syndromes.
• Hereditary dystrophic dystonia.

Primary dystonia is characterized by the presence of a single clinical feature (isolated dystonia), with no signs of brain degeneration and any acquired cause. Primary dystonia can be hereditary or occur for unknown reasons (idiopathic).

Secondary dystonia results from a wide range of causes, including:

• Genetic mutations.
• Birth injuries.
• Stroke.
• Brain tumors.
• Some infections.
• The reaction of the body to certain drugs.

Muscular dystonia, along with syndromes, refers to disorders in which there is a combination of the disease with another neurological disorder, such as myoclonus or parkinsonism.

Hereditary dystrophic dystonia refers to hereditary cases that have been associated with neurodegeneration. Other neurological symptoms may also be observed.

Signs of dystonia

Early childhood dystonia (generalized form) is a neurological movement disorder that usually begins in childhood or adolescence.

• Symptoms begin in one part of the body (usually on the arm or leg) and can eventually spread to others, causing contractions and muscle spasms that twist the body into unnatural positions. This is the most common hereditary form of dystonia, in most cases triggered by the DYT1 gene.
• Specific symptoms can vary from person to person, even among people with the same subtype. Specific symptoms may occur depending on the specific part of the body, the age of onset and the root cause.

Dystonias developing at an early age are more likely to move from focal to generalized manifestations and usually proceed more difficult. Dystonia in adults is most often manifested by focal manifestations and usually does not progress.

Some victims may temporarily interrupt dystonic movements or postures by performing a specific action or maneuver. In particular, a touch technique can be used. Usually, a part of the body not affected by dystonia is involved in the action, but often near the affected area. For example, some people may temporarily relieve cervical dystonia by touching their chin.

Some of the most well-known forms of dystonia are briefly described below.

Isolated focal (focal) dystonia

Isolated focal dystonias are the most common movement disorders. They often include benign essential blepharospasm, cervical dystonia, oromandibular dystonia and laryngeal dystonia. These disorders are more common in adults.

Isolated dystonia of the limbs can occur in adults and often affects the hands and / or legs. Many of them are occupational diseases or specific ones that occur when performing a specific task.

• Occupational or task-specific dystonia is a generic term that includes focal dystonias associated with a specific, often repetitive activity. Initially, patients may have a lack of dexterity in performing a particular job. Eventually, the condition progresses, causing repetitive movements and abnormal postures. The most common form can be a writer's convulsion, in which abnormal flexion, extension or twisting of the fingers and wrist occurs, especially when the patient writes.
• A dystonia of a musician is a form of dystonia that is specific to a particular activity, during which certain muscle groups are involved. Symptoms occur when musicians try to play an instrument. Focal dystonia and cushion dystonia are the most common forms. For focal dystonia of the hand is characterized by a painless loss of muscle control in connection with the often practiced movements (for example, like pianists, guitarists, etc.).
• Ambushury dystonia is a special form of movement disorder among musicians, which affects people who often play brass and woodwind instruments. This form of dystonia can affect the muscles of the mouth, face, jaw and tongue.Muscle contractions, which characterize ambushural dystonia, can occur only when the musician plays or blows into the mouthpiece of the instrument.

Hereditary dystonia

The development of dystonia may be associated with a specific genetic mutation / locus associated with subtypes.Violations received a formal abbreviation DYT and a number (for example, DYT1). Subtypes are numbered in the order of their identification in the medical literature. It was revealed about 25 forms.

The created classification of hereditary dystonia has several problems. Designations were identified without a known gene, so that people with a single form of dystonia eventually found different subtypes. For example, in patients with DYT14, the subtype DYT5 was ultimately determined.

Another problem is that some disorders included in this classification system do not have the main symptom of dystonia.Other neurological signs, such as myoclonus or parkinsonism, are determined instead. In addition, many genetically determined disorders with dystonia and the presence of the necessary trait are not included in the classification. In particular, we are talking about Lesch-Nyhan syndrome, Wilson's disease, deafness syndrome and optical neuronopathy.

Description of the most famous forms of hereditary dystonia

• DYT1-related dystonia is inherited in an autosomal dominant manner. Usually develops in childhood or adolescence.However, the disorder may also develop later in life. Symptoms are usually localized in one part of the body (usually in the area of ​​the arm or leg). Ultimately, they can spread to other parts of the body, causing contractions and muscle spasms that twist the body into unnatural positions. The severity can vary considerably from one person to another, even among members of one family. The disease can lead to significant disability in childhood, while in other cases it remains undiagnosed until adulthood and is manifested only by mild symptoms.
• Dopa-sensitive dystonia (DRD) is a general term for several disorders that determine generalized dystonia and parkinsonism, and often there is a strong reaction to treatment with levodopa. Levodopa is an amino acid that turns into dopamine. Dopamine is a brain chemical that serves as a neurotransmitter and is not enough in people with DRD. Victims may be misdiagnosed as having cerebral palsy or Parkinson’s disease. Two main forms have been identified - Segawa syndrome and tyrosine hydroxylase deficiency, although many other disorders can mimic dystonia associated with dopa, including juvenile parkinsonism. Segava syndrome is inherited in an autosomal dominant manner; Tyrosine hydroxylase deficiency is inherited in an autosomal recessive manner.
• DYT6-associated dystonia is characterized by lesions of the skull, neck and larynx. Dystonia tends to worsen and spread to other areas (generalized dystonia). Some people initially have dystonia, which affects the hands, and then develop symptoms of cranial and cervical dystonia. Most often this disorder has a juvenile onset. DYT6-related dystonia is caused by mutations in the THAP1 gene and is inherited in an autosomal dominant manner.
• Dyskinesia caused by paroxysmal stress , also known as DYT18, is characterized by a combination of chorea, athetosis and dystonia, which primarily affects excessively trained areas of the body. Most often affected legs. An episode can last from a few minutes to an hour or more. It occurs mainly after prolonged physical activity or increased exercise. In some cases, there are additional signs, including convulsions, hemolytic anemia and migraine.Dyskinesia caused by paroxysmal load is associated with mutations in the SCL2A1 gene and is inherited in an autosomal dominant manner.
• Myoclonic dystonia , better known as DTY11 or myoclonus dystonia, is characterized by fast, involuntary jerky movements (myoclonus) with stable dystonic positions or without them. Myoclonus most often affects the neck, torso and shoulders. Less involved legs. Myoclonus is caused by muscle contraction or relaxation and cannot be controlled by the affected person. Patients may also develop focal or segmental dystonia (for example, writer's convulsion or neck dystonia). As a rule, the course of the disease does not worsen and does not spread to other areas. Additional symptoms that may occur include panic attacks, anxiety, depression, and obsessive-compulsive disorder. The first attacks are usually determined in childhood or adolescence. Most cases of myoclonus dystonia are caused by mutations in the SGCE gene. The disorder is inherited in an autosomal dominant manner.

Acquired dystonia

Acquired dystonia can be the result of environmental or disease-related damage to a part of the brain or the central nervous system. Acquired dystonia is often accompanied by other neurological manifestations, such as parkinsonism.The specific symptoms and severity of these disorders vary depending on the underlying causes, specific areas of the body, and other factors.

One form of acquired dystonia is tardive dyskinesia, which encompasses the forms of dystonia induced by the use of certain drugs. Tardive dyskinesia causes fast repetitive movements without sustained irregular postures. Late dystonia is usually considered a severe form of tardive dyskinesia, characterized by muscle contraction, resulting in slower writhing movements.

Video: Demystifying Dystonia

Standard treatments

Currently, there are no effective treatments for dystonia. Most often, the effect is directed to specific symptoms, that is, symptomatic treatment is carried out. First of all, muscle spasms, pain and discomfort are removed, efforts are also made to restore the natural postures.

There are three main treatment options:

• Oral medications.
• Use of botulinum toxin injections.
• Surgical intervention.

These treatments can be used alone or in combination. In addition, physical and speech therapy can be, in certain cases, a useful addition to medical treatment.

Drug treatment of dystonia is considered ineffective. While there are no oral medications approved by the Office of the Food and Drug Administration (FDA) for use in dystonia. Among the tablet means most often used are those that affect the activity of neurotransmitters.

Anticholinergics , such as benztropine and trihexyphenidyl, block the neurotransmitter acetylocholine, and benzodiazepines, such as clonazepam, diazepam or lorazepam, block the neurotransmitter of gamma-aminobutyric acid (GABA).

These drugs are most effective in children with generalized dystonia. Adults due to side effects are often prescribed a more limited dose.

Some people, especially those who suffer from dopa-sensitive dystonia (DRD), respond to treatment with very low doses of levodopa, the synthetic version of the neurotransmitter dopamine. Levodopa increases dopamine levels. In other cases, with some different forms of dystonia, patients may respond to medications that block dopamine activity (anti-dopaminergic agents).

A muscle relaxant, known as baclofen , can help to periodically reduce muscle spasms. In particular, a baclofen pump can be implanted, which delivers the medicine directly to the area around the spinal cord. Baclofen can stimulate the body’s ability to generate the neurotransmitter GABA.

There is no standard treatment for rapidly developing dystonia-parkinsonism (RDP), although levodopa / carbidopa drugs and dopamine agonists (drugs that stimulate dopamine receptors in the absence of dopamine) can provide a slight improvement for some sick people.

Botulinum toxin therapy is often used for certain forms of dystonia, especially for certain focal lesions, such as neck dystonia and laryngeal dystonia.

Botulinum toxin is a neurotoxin that is injected into the muscles in very small doses. After injection into the muscle, the action of botulinum toxin is aimed at interrupting the nerve messages in the muscle. As a result, the release of the neurotransmitter acetylcholine, which stimulates muscle contractions and causes weakness of this muscle, is prevented.

The effect of botulinum toxin on the muscles begins approximately 2-3 days after the injection. Peak concentration occurs after about 4 weeks and provides relief for about 3-6 months. When the action of botulinum toxin passes, the symptoms of dystonia develop anew. The degree of effectiveness of botulinum toxin depends on each case separately.

Botulinum toxin approved by the FDA for the treatment of neck dystonia and blepharospasm. It is widely used for purposes other than treatment for all forms of dystonia. Botulinum toxin is produced:

• Allergan Pharmaceuticals (as BOTOX®).
• Elan Pharmaceuticals (as MYOBLOC®).
• Ipsen Pharmaceuticals (as DYSPORT®).
• Merz Pharmaceuticals (as XEOMIN®).

These brands are not interchangeable, and each must be administered as a unique drug. The FDA has a black box warning regarding the use of any of these toxins. The warning is that a drug that is effective for some can cause serious side effects in others.

The operation , as a rule, is indicated for patients with severe dystonia, who are not helped by drug therapy, or the person cannot tolerate its side effects. Also, sometimes patients with severe dystonia stop responding to drug treatment, and then surgery is also recommended.

Deep brain stimulation (DBS) with an implantable neurostimulator may be indicated for some types of dystonia.DBS involves the surgical placement of very thin electrodes in certain areas of the brain, such as the pale ball. The leads from these electrodes are then connected to a small device called a neurostimulator, which is surgically implanted, usually near the collarbone. These stimulants send small electrical impulses to the brain. They, in turn, block or interfere with the nerve signals that cause dystonia symptoms.

DBS has become the basis for the surgical treatment of people with dystonia. Older surgical procedures, such as thalamotomy or pallidotomy, are rarely used to treat dystonia. These procedures included the pinpoint destruction of a tiny area of ​​the brain in order to interrupt the nerve pathways responsible for signs of the disease.

Selective peripheral denervation , in which the nerves of the dystonic muscles are separated, can also benefit patients with cervical dystonia, especially if other types of therapy are not indicated. However, this operation requires the participation of an experienced surgeon who has been thoroughly trained both in assessing the condition of the muscles of the neck and in performing the surgery. The side effects of the operation are not uncommon, and after it is completed, a long rehabilitation period is necessary.

Conclusion

The group of diseases called dystonia is diverse, both in its characteristics and course. The disease can practically not manifest in any way, but in severe cases it can lead to disability.

There is no general method of treatment for all dystonias, therefore, depending on the severity of symptoms, the patient's age and other indicators, drug therapy, botulinum-toxic treatment or surgery can be used.

Video: What is Dystonia and What Does it Feel Like?