dystonia

Dystonia is a postural movement disorder characterized by pathological (dystonic) postures and violent, often rotational movements in one or another part of the body.

Primary and secondary forms of dystonia are distinguished, and their clinical manifestations depend on the etiology. Dystonia is a syndrome manifested by deforming movements and postures that arise as a result of simultaneous involuntary contraction of agonist and antagonist muscles.

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Causes of dystonia

1. Primary dystonia.
2. "Dystonia plus"
3. Secondary dystonia
4. Neurodegenerative diseases.
5. Pseudodystonia.

Primary dystonia includes diseases in which dystonia is the only neurological manifestation. They are further subdivided into sporadic and hereditary. Most forms of primary dystonia are sporadic, with onset in adulthood; most of them are focal or segmental (blepharospasm, oromandibular dystonia, spasmodic torticollis, spasmodic dysphonia, writer's cramp, foot dystonia). But hereditary generalized torsion dystonia also belongs here.

In primary forms of dystonia, no pathomorphological changes are found in the brain of patients and its pathogenesis is associated with neurochemical and neurophysiological disorders, mainly at the level of the brainstem-subcortical formations.

"Dystonia plus" unites a group of diseases that differ from both primary dystonia and heredodegenerative forms of dystonia. Like primary dystonia, dystonia plus is based on neurochemical disorders and is not accompanied by structural changes in the brain. However, if primary dystonia is manifested by "pure" dystonia, then dystonia plus, in addition to the dystonic syndrome, includes other neurological syndromes. We are talking about two variants of dystonia plus: dystonia with parkinsonism and dystonia with myoclonus. Dystonia with parkinsonism includes several hereditary diseases, among which the main form is the so-called dopa-sensitive dystonia, which includes several individual genetic variants (DYT5; tyrosine hydroxylase deficiency; biopterin deficiency; dystonia sensitive to dopamine agonists). The second variant of dystonia-plus is called myoclonic dystonia or hereditary dystonia with lightning-fast twitching (jerks), sensitive to alcohol. The name "dystonia-myoclonus" has also been proposed. Its gene has not been mapped. The disease was first described by S.N.Davidenkov in 1926.

Secondary dystonia is defined as dystonia that develops primarily as a result of environmental factors that cause damage to brain tissue. In recent years, it has been shown that spinal cord and peripheral nerve damage (often subclinical) can contribute to the development of dystonia. Secondary dystonia includes a wide range of diseases: perinatal CNS lesions, encephalitis, craniocerebral trauma, thalamotomy, pontine myelinolysis, antiphospholipid syndrome, other cerebrovascular diseases, brain tumors, multiple sclerosis, side effects of certain drugs (most often levodopa), and intoxication. Many cases of secondary dystonia are clinically manifested not as pure dystonia, but as a mix of dystonia with other neurological syndromes.

Neurodegenerative diseases. Since many of these neurodegenerations are caused by genetic disorders, the term heredegenerations is applicable to this category. However, some diseases included in this group have unknown etiology and the role of genetic factors in their genesis remains unclear. In these diseases, dystonia may be the leading manifestation, but is usually combined with other neurological syndromes, especially parkinsonism. This group includes quite a lot of different, but rather rare, diseases: X-linked dystonia-parkinsonism (Lubag); rapid-onset dystonia-parkinsonism; juvenile parkinsonism (in the presence of dystonia); Huntington's chorea; Machado-Joseph disease (a variant of spinocerebellar degeneration); Wilson-Konovalov disease; Hallervorden-Spatz disease; progressive supranuclear palsy; corticobasal degeneration; some leukodystrophies, metabolic disorders and other diseases.

The diagnosis of many of the listed diseases requires genetic testing; a number of diseases require the use of biochemical studies, cytological and biochemical analysis of tissue biopsy and other paraclinical diagnostic methods. A detailed description of this wide range of diseases can be found in the relevant neurological reference books and manuals (especially those devoted to pediatric neurology). Dystonic syndrome itself is diagnosed exclusively clinically.

Unlike the diagnosis of other hyperkinesis, the recognition of dystonia requires taking into account not only the motor pattern of hyperkinesis, but also a thorough analysis of its dynamism. The fact is that the motor pattern of dystonia in individual regions of the body can be so different, polymorphic or atypical that the analysis of its dynamism (i.e. the ability to transform, strengthen, weaken or stop hyperkinesis under the influence of various exogenous or endogenous influences) often acquires a decisive significance in the diagnosis of dystonia. We are talking about the phenomenon of daily fluctuation, the stopping effect of alcohol, emotiogenic changes in clinical manifestations, corrective gestures, paradoxical kinesias, stage-by-stage metamorphoses of some dystonic syndromes and other dynamic features that cannot be described in detail here and are well covered in the latest domestic publications.

It should also be emphasized that the patient, as a rule, does not actively talk about the above-mentioned manifestations of dynamism and a corresponding survey by the doctor is required, which increases the chances of adequate clinical diagnosis of dystonia. All other neurological syndromes that are outwardly similar or reminiscent of dystonia (for example, non-dystonic blepharospasm, vertebrogenic or myogenic torticollis, many psychogenic syndromes, etc.) do not have such dynamism. Therefore, clinical recognition of the latter can be of fundamental importance in the process of diagnosing dystonia.

Pseudodystonia includes a range of diseases that may resemble dystonia (most often due to the presence of pathological postures), but do not belong to true dystonia: Sandifer syndrome (caused by gastroesophageal reflux), sometimes Isaacs syndrome (armadillo syndrome), some orthopedic and vertebrogenic diseases, rarely - epileptic seizures. Some diseases accompanied by pathological head position can sometimes serve as a reason for excluding dystonia. Psychogenic dystonia can also be included here.

The diagnosis of primary dystonia is established only clinically.

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Forms of dystonia

Foot dystonia may manifest itself by extension and inversion of the foot, as well as pronounced flexion of the fingers, hand dystonia - by its flexion with hyperextension of the fingers, dystonia of the neck and trunk - by their rotational movements. Dystonia in the facial area manifests itself in various movements, including forced closing or opening of the mouth, squinting, stretching of the lips, sticking out the tongue. Dystonic postures are often bizarre in nature and disable patients. They always disappear during sleep and sometimes during relaxation.

Dystonia can involve any part of the body. According to prevalence, there are focal dystonia (it is designated by the affected part of the body - for example, cranial, cervical, axial), segmental dystonia, involving two adjacent parts of the body, and generalized dystonia. Patients can weaken involuntary movements with the help of corrective gestures, for example, touching the chin, some patients reduce the severity of torticollis.

Secondary forms of dystonia occur due to various causes - hereditary metabolic diseases (for example, aminoaciduria or lipidosis), carbon monoxide poisoning, trauma, stroke or subdural hematoma. The age of onset and clinical manifestations of secondary dystonia are variable and depend on the etiology of the disease.

Primary dystonia is a group of inherited disorders. In some of them, a genetic defect has now been identified. These disorders can be transmitted in an autosomal dominant, autosomal recessive, or X-linked pattern and may be associated with other extrapyramidal syndromes, such as myoclonus, tremor, or parkinsonism. Variable penetrance is observed in many families, with some individuals developing the disorder in childhood and others in adulthood.

Although each type of hereditary dystonia has its own characteristics, there are common patterns. Typically, childhood-onset dystonia initially involves the lower extremities, then the trunk, neck, and upper extremities. It usually tends to generalize and causes significant physical impairment but leaves cognitive function intact. In contrast, adult-onset dystonia rarely generalizes and usually remains focal or segmental, involving the trunk, neck, upper extremities, or cranial musculature (muscles of the eyes or mouth). Cervical or axial dystonia usually appears between the ages of 20 and 50, while cranial dystonia usually appears between the ages of 50 and 70.

[ 3 ], [ 4 ], [ 5 ], [ 6 ]

Classification of dystonia

The etiological classification of dystonia is currently being improved and, apparently, has not yet acquired a final form. It includes 4 sections (primary dystonia, "dystonia plus", secondary dystonia, hereditary-degenerative forms of dystonia). Some people distinguish another form - the so-called pseudo-dystonia. The diagnosis of almost all forms of dystonia is exclusively clinical.

• Primary dystonia.
• "Dystonia plus"
  • Dystonia with parkinsonism (levodopa-responsive dystonia, dopamine agonist-responsive dystonia).
  • Dystonia with myoclonic jerks, sensitive to alcohol.
• Secondary dystonia.
  • Cerebral palsy with dystonic (athetoid) manifestations.
  • Delayed dystonia against the background of cerebral palsy.
  • Encephalitis (including HIV infection).
  • TBI.
  • After thalamotomy.
  • Brainstem lesions (including pontine myelinolysis).
  • Primary antiphospholipid syndrome.
  • Cerebral circulatory disorders.
  • Arteriovenous malformation.
  • Hypoxic encephalopathy.
  • Brain tumor.
  • Multiple sclerosis.
  • Intoxication (carbon monoxide, cyanides, methanol, disulfiram, etc.).
  • Metabolic disorders (hypoparathyroidism).
  • Iatrogenic (levodopa, neuroleptics, ergot preparations, anticonvulsants).
• Hereditary neurodegenerative diseases.
  • X-linked recessive diseases (dystonia-parkinsonism, X-linked, Merzbacher-Pelizaeus disease).
  • Autosomal dominant diseases (rapid-onset dystonia-parkinsonism, juvenile parkinsonism, Huntington's disease, Machado-Joseph disease, dentato-rubro-pallido-Lewis atrophy, other spinocerebellar degenerations).
  • Autosomal recessive diseases (Wilson-Konovalov disease, Niemann-Pick disease, GM ₁ and CM ₂ gangliosidosis, metachromatic leukodystrophy, Lesch-Nyhan disease, homocystinuria, glutaric acidemia, Hartnup disease, ataxia-telangiectasia, Hallervorden-Spatz disease, juvenile ceroid lipofuscinosis, neuroacancytosis, etc.).
  • Probably autosomal recessive diseases (familial calcification of the basal ganglia, Rett disease).
  • Mitochondrial diseases (Lee's disease, Leber's disease, other mitochondrial encephalopathies).
  • Diseases occurring with parkinsonism syndrome (Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration).
• Pseudodystonia.

The classification of dystonia according to the characteristics of its distribution provides for five possible options:

1. focal,
2. segmental,
3. multifocal.
4. generalized and
5. hemidystonia.

Focal dystonia is a dystonia observed in one region of the body: the face (blepharospasm), neck muscles (spasmodic torticollis), arm (writer's cramp), leg (foot dystonia), etc. Segmental dystonia is a syndrome observed in two adjacent (contiguous) areas of the body (blepharospasm and oromandibular dystonia; torticollis and torsion spasm of the shoulder muscles; tortipelvis and crural dystonia, etc.).

Multifocal dystonia reflects such a distribution of dystonic syndromes when they are observed in two or more areas of the body that are not adjacent to each other (for example, blepharospasm and dystonia of the foot, oromandibular dystonia and writer's cramp, etc.). Hemidystonia is a syndrome consisting of brachial and crural dystonia on one half of the body (the same half of the face is rarely involved). Hemidystonia is an important sign in practical terms, since it always indicates the symptomatic (secondary) nature of dystonia and indicates a primary organic lesion of the contralateral hemisphere, the nature of which must be clarified. Generalized dystonia is a term used to designate dystonia in the muscles of the trunk, limbs and face. Only to this syndromic form of dystonia can the terms "torsion" and "deforming muscular dystonia" be applied. Focal forms that are significantly predominant in the population are designated by the term "dystonia".

There are very specific relationships between focal and generalized forms of dystonia. There are six relatively independent forms of focal dystonia: blepharospasm, oromandibular dystonia (cranial dystonia), spasmodic torticollis (cervical dystonia), writer's cramp (brachial dystonia), spasmodic dysphonia (laryngeal dystonia), and foot dystonia (crural dystonia). A rare form is the syndrome called "belly dance". The relative independence of these forms should be understood as the ability of these syndromes to act either as a single isolated dystonic syndrome that never generalizes, or as the first stage of the disease, followed by a stage of dystonia spreading to other parts of the body up to complete generalization. Thus, focal dystonia can be either an independent syndrome, when no other dystonic syndromes join it at all stages of the disease, or the first manifestation of generalized dystonia. The connection between focal and generalized forms of dystonia is mediated by age: the older the age at which dystonia debuts, the less likely its subsequent generalization. For example, the appearance of spasmodic torticollis in a child inevitably foreshadows the formation of generalized torsion dystonia. Spasmodic torticollis in adulthood, as a rule, does not develop into a generalized form.

The etiological classification of dystonia is currently being improved and apparently has not yet acquired a final form. It includes four sections: primary dystonia, "dystonia plus", secondary dystonia and heredodegenerative forms of dystonia. We believe that it should be supplemented by one more form - the so-called pseudodystonia. The diagnosis of almost all forms of dystonia is carried out exclusively clinically.

[ 7 ], [ 8 ], [ 9 ], [ 10 ]

Diagnosis of dystonia

Diagnostic studies may require a wide range of studies, the choice of which is made in each case according to indications (see above for a list of a large number of acquired and hereditary diseases that may be accompanied by dystonia).

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Neurochemical changes

Neurochemical changes in various forms of dystonia remain poorly understood. None of the forms of primary dystonia reveal focal degenerative changes in the brain. Studies of monoaminergic systems usually do not reveal changes. However, studies of individual families with dystonia are rare. Patients usually die not from dystonia, but from concomitant diseases, so there is a lack of sufficient pathomorphological material.

The most important exception is Segawa disease, an autosomal recessive disorder in which dystonia fluctuates daily (reduces in the morning and increases in the afternoon and evening) and is significantly improved by low doses of levodopa. The Segawa disease gene has been identified, which codes for GTP-cyclohydrolase I, an enzyme involved in the synthesis of biopterin, an obligate cofactor of tyrosine hydroxylase. Patients with Segawa disease have reduced tyrosine hydroxylase activity and synaptic dopamine levels. It is believed that synaptic dopamine levels are partially restored during sleep, but rapidly decrease after awakening, accompanied by an increase in dystonia in the afternoon.

Lubeg disease is an X-linked disorder seen in Filipinos that involves dystonia and parkinsonism. PET scans show decreased 11C-fluorodopa uptake, indicating abnormal dopamine metabolism in the brain.

The loss of a GAG codon in the DYT-1 gene underlies most cases of childhood dystonia, inherited in an autosomal dominant manner. This mutation is particularly common among Ashkenazi Jews and first appeared in one of their ancestors who lived about 300 years ago in Lithuania. This gene codes for the protein torsin A, which is found in dopaminergic neurons of the substantia nigra, granule cells of the cerebellum, cells of the dentate nucleus, and pyramidal cells of the hyoscamp. The function of this protein remains unknown, as well as its effect on the functioning of the dopaminergic system. However, the ineffectiveness of levodopa drugs in this disease indicates that the activity of the dopaminergic system is not affected.

Treatment of dystonia

When starting treatment for dystonia, it is first necessary to determine whether it responds to levodopa or a dopamine agonist. If not, muscarinic cholinergic receptor antagonists (anticholinergics), baclofen, carbamazepine, and long-acting benzodiazepines should be tried. Trial treatment with various drugs should be carried out systematically in order to clearly determine whether a particular drug has a therapeutic effect or not. In many patients, drug therapy produces only a very moderate effect. In dystonia that begins in childhood, significant improvement is sometimes observed with long-term treatment with high doses of muscarinic cholinergic receptor antagonists. In these patients, trial treatment should be continued for at least 6 months, since the therapeutic effect may not be apparent immediately.

Dystonia may also be treated surgically, in particular stereotactic thalamotomy or pallidotomy. Despite the significant risk of severe dysarthria and other complications that may occur with bilateral surgery, which is necessary for generalized dystonia or spasmodic torticollis, modern neuroimaging and neurophysiological techniques have made stereotactic surgery an indispensable method in the most severe cases. In recent years, not only destructive but also stimulating methods of intervention on deep brain structures have been increasingly used. One possibility is a combination of microstimulation of the globus pallidus or thalamus on one side and pallidotomy or thalamotomy on the other side. Local botulinum toxin injections every 2-4 months are an effective treatment for focal dystonia. Injections are given into the muscles involved in hyperkinesis and cause their partial weakening, which is, however, sufficient to reduce the severity of dystonic contractions. Injections must be repeated regularly. Side effects are minimal. Some patients develop excessive muscle weakness shortly after the injection, which resolves within 1-2 weeks. To avoid recurrence of this complication, the dose is reduced for subsequent injections. In some patients, excessively frequent injections of botulinum toxin result in the formation of antibodies to the toxin, which reduce its long-term effectiveness.