Dystonia

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

Isolate the primary and secondary forms of dystonia, while their clinical manifestations depend on the etiology. Dystonia is a syndrome manifested by deforming movements and postures that result from simultaneous involuntary contraction of agonist muscles and antagonists.

[1],

Causes of dystonia

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

Primary dystonia combines diseases in which dystonia is the only neurological manifestation. They are subdivided in turn into sporadic and hereditary. Most forms of primary dystonia are sporadic, with onset in adulthood; and most of them - focal or segmental (blepharospasm, oromandibular dystonia, spastic torticollis, spastic dysphonia, writing spasm, dystonia of the foot). But this includes hereditary generalized torsion dystonia.

In primary forms of dystonia in the brain, patients do not find pathomorphological changes and associate its pathogenesis with neurochemical and neurophysiologic disorders mainly at the level of stem-subcortical formations.

"Dystonia-plus" unites a group of diseases that differ both from primary dystonia and from geredodegenerative forms of dystonia. Like primary dystonia, dystonia plus is based on neurochemical disorders and is not accompanied by structural changes in the brain. But, if the primary dystonia is manifested by "pure" dystonia, then dystonia plus, in addition to the dystonic syndrome, includes all other neurological syndromes. We are talking about two options for dystonia plus: dystonia with Parkinsonism and dystonia with myoclonus. Dystonia with Parkinson's disease includes several inherited diseases, among which the main form is the so-called dopa-sensitive dystonia, which includes several separate genetic variants (DYT5, tyrosine hydroxylase deficiency, bioptner insufficiency, dystonia sensitive to dopamine agonists). The second variant of dystonia-plus is called myoclonic dystonia or hereditary dystonia with fulminant jerking (jerks), sensitive to alcohol. The name "dystonia-myoclonus" is also proposed. Her gene is not mapped. The disease was first described by SNDavidenkov in 1926.

Secondary dystonia is defined as a dystonia that develops mainly as a result of exposure to external factors that cause damage to the brain tissue. In recent years, it has been shown that damage to the spinal cord and peripheral nerves (often subclinical) can contribute to the development of dystonia. Secondary dystonia includes a wide range of diseases: perinatal lesions of the central nervous system, encephalitis, craniocerebral trauma, thalamotomy, pontinus myelinolysis, antiphospholipid syndrome, other cerebrovascular diseases, brain tumor, multiple sclerosis, side effects of some drugs (most often levodopa), 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 "geredo-degeneration" is applicable to this category. But some diseases, attributed to this group, have an unknown etiology and so far the role of genetic factors in their genesis is unclear. With these diseases, dystonia can act as a leading manifestation, but is usually combined with other neurologic syndromes, especially with parkinsonism. This group includes quite a few different, but quite rare, diseases: dystonia-parkinsonism, linked to the X-chromosome (Lubag); dystonia-Parkinsonism with a rapid onset; juvenile parkinsonism (in the presence of dystonia); Huntington's chorea; Machado-Joseph disease (variant of spin-cerebellar degeneration); Wilson-Konovalov's disease; Gallerwolden-Spatz disease; progressive supranuclear palsy; corticobasal degeneration; some leukodystrophies, metabolic disorders and other diseases.

Diagnosis of many of these diseases requires a genetic examination; a number of diseases involve the use of biochemical studies, cytological and biochemical analysis of tissue biopsy and other paraclinical methods of diagnosis. A detailed description of this wide range of diseases can be found in the relevant neurological reference books and manuals (especially devoted to pediatric neurology). The very same dystonic syndrome is diagnosed exclusively clinically.

Unlike the diagnosis of other hyperkinesia, the recognition of dystonia requires the consideration of not only the motor pattern of hyperkinesia, but also a careful analysis of its dynamism. The fact that the motor pattern of dystonia in certain regions of the body can be so different, polymorphic or atypical, that the analysis of its dynamism (that is, the ability to transform, strengthen, relax or stop hyperkinesis under the influence of various exogenous or endogenous influences). We are talking about the phenomenon of daily fluctuations, the stopping effect of alcohol, emotional changes in clinical manifestations, corrective gestures, paradoxical kinesia, phased metamorphoses of some dystonic syndromes and other dynamic features that can not be described in detail and well covered in recent 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 requires an appropriate questioning by the doctor, which increases the chances of adequate clinical diagnosis of dystonia. All other, neurological syndromes similar in appearance or resembling dystonia, (for example, non-dystonic blepharospasm, vertebrogenic or myogenic torticollis, many psychogenic syndromes, etc.) do not possess this dynamism. Consequently, clinical recognition of the latter can be of fundamental importance in the process of diagnosing dystonia.

Pseudodystonia includes a range of diseases that can resemble dystonia (most often due to the presence of pathological postures), but do not refer to true dystonia: Sandyfer's syndrome (due to gastroesophageal reflux), sometimes Isaac's syndrome (armadillo syndrome), some orthopedic and vertebrogenic diseases, rarely epileptic seizures. Some diseases accompanied by a pathological position of the head can sometimes serve as an excuse for the exclusion of dystonia. This can include psychogenic dystonia.

The diagnosis of primary dystonia is established only clinically.

[2]

Forms of dystonia

Dystonia of the foot can be manifested by extension and turning of the foot, as well as by pronounced flexion of the fingers, dystonia of the hand - by flexion of the fingers, dystonia of the neck and trunk - by their rotational movements. Dystonia in the face area manifests itself in a variety of movements, including forced closing or opening of the mouth, closing eyes, stretching the lips, protruding the tongue. Dystonic postures often have a quirky character and disability patients. They always disappear during sleep and sometimes during relaxation.

Dystonia can involve any part of the body. In the prevalence of focal dystonia (it is denoted 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 arise for various reasons - in hereditary metabolic diseases (for example, aminoaciduria or lipidosis), carbon monoxide poisoning, trauma, stroke or subdural hematoma. 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 hereditary diseases. At some of them the genetic defect is now established. These diseases can be transmitted by autosomal dominant, autosomal recessive or X-linked types and combined with other extrapyramidal syndromes - myoclonia, tremor or parkinsonism. In many families, variable penetrance is noted, while in some cases the disease manifests itself in childhood, and in others - in mature.

Although each of the variants of hereditary dystonia has its own peculiarities, there are general patterns. As a rule, dystonia starting in childhood initially involves the lower limbs, then the trunk, neck and upper limbs. Usually, it tends to generalize and causes a significant physical defect, but leaves cognitive functions intact. In contrast, dystonia starting at adulthood is rarely generalized and usually remains focal or segmental, involving the trunk, neck, upper limbs, or cranial musculature (eye or mouth muscle). Cervical or axial forms of dystonia usually manifest at the age of 20-50 years, whereas cranial dystonia is usually between 50 and 70 years.

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

Classification of dystonia

The etiological classification of dystonia is currently being improved and, apparently, has not yet acquired its final form. It includes 4 sections (primary dystonia, dystonia plus, secondary dystonia, hereditary degenerative forms of dystonia). Some singled out another form - the so-called pseudodistony. Diagnosis of almost all forms of dystonia is exclusively clinical.

• Primary dystonia.
• "Dystonia plus."
  • Dystonia with Parkinsonism (dystonia, sensitive to levodopa, dystonia, sensitive to dopamine agonists).
  • Dystonia with myoclonic twitching, sensitive to alcohol.
• Secondary dystonia.
  • Cerebral palsy with dystonic (athetoid) manifestations.
  • Delayed dystonia against cerebral palsy.
  • Encephalitis (including with HIV infection).
  • IMT.
  • After thalamotomy.
  • Damage to the brain stem (including Pontinus myelinolysis).
  • Primary antiphospholipid syndrome.
  • Disorders of cerebral circulation.
  • Arterio-venous malformation.
  • Hypoxic encephalopathy.
  • Brain tumor.
  • Multiple sclerosis.
  • Intoxications (carbon monoxide, cyanides, methanol, disulfiram, etc.).
  • Metabolic disorders (hypoparathyroidism).
  • Iatrogenic (levodopa, neuroleptics, ergot preparations, anticonvulsants).
• Hereditary neurodegenerative diseases.
  • X-linked recessive diseases (dystonia-parkinsonism, linked to the X-chromosome, Merzbacher-Pelitseus disease).
  • Autosomal dominant diseases (dystonia-Parkinsonism with a rapid onset, juvenile Parkinsonism, Huntington's disease, Machado-Joseph, dentato-rubro-pallid-Lewis atrophy, other spinocerebellar degenerations).
  • Autosomal recessive diseases (Wilson-Konovalov, Nyman-Pick disease, GM ₁ and CM _2- gangliosidoses, metachromatic leukodystrophy, Lesch-Naikhan disease, homocystinuria, glutaric acidemia, Hartnap's disease, ataxia-telangiectasia, Gallervorden-Spatz disease, juvenile ceroid lipofuscinosis, neuroacanthosis, etc.).
  • Probably, autosomal recessive diseases (familial calcification of the basal ganglia, Rett's disease).
  • Mitochondrial diseases (diseases of Lee, Leber, other mitochondrial encephalopathies).
  • Diseases that occur with Parkinson's syndrome (Parkinson's disease, progressive supranuclear palsy, multiple systemic atrophy, cortico-basal degeneration).
• Pseudodystonia.

Classification of dystonia according to the peculiarities of its distribution provides for five possible options:

1. focal,
2. segmented,
3. multifocal.
4. generalized and
5. hemidistonia.

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

Multifocal dystonia reflects this 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 writing spasm, etc.). Hemidistonia is a syndrome consisting of brachial and dystonic dystonia on one half of the body (the same half of the face is rarely involved). Hemidistonia is an important sign in practice because it always indicates the symptomatic (secondary) nature of dystonia and indicates the primary organic lesion of the contralateral hemisphere, the nature of which is subject to mandatory clarification. Generalized dystonia is a term used to refer to dystonia in the muscles of the trunk, limbs, and face. Only to this syndrome form of dystonia is the term "torsion" and "deforming muscular dystonia" applicable. The focal forms predominant in the population are designated by the term "dystonia".

Between the focal and generalized forms of dystonia, there are very peculiar relationships. Six relatively independent forms of focal dystonia are known: blepharospasm, oromandibular dystonia (cranial dystonia), spastic torticollis (cervical dystonia), writing spasm (brachial dystonia), spastic dysphonia (laryngeal dystonia), dystonia of the foot (dystonia). A rare form is a syndrome called "belly dancing". 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 is never generalized, or as a first stage of the disease, followed by the stage of the spread of dystonia to other parts of the body until complete generalization. Thus focal dystonia can be either an independent syndrome, when no other dystonic syndromes are attached to it at all stages of the disease, or the first manifestation of generalized dystonia. The relationship between the focal and generalized forms of dystonia is mediated by age: the more older a dystonia debuts, the less likely its subsequent generalization. For example, the appearance of spasmodic torticollis in a child inevitably portends the formation of a generalized torsion dystonia. Spastic 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 its final form. It includes four sections: primary dystonia, "dystonia plus", secondary dystonia and geredodegenerative forms of dystonia. We believe that it should be supplemented by another form - the so-called pseudodistony. The diagnosis of almost all forms of dystonia is carried out exclusively clinically.

[7], [8], [9], [10], [11],

Diagnosis of dystonia

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

[12], [13]

Neurochemical changes

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

The most important exception is Segawa's disease, an autosomal recessive disorder in which dystonia is prone to diurnal fluctuations (decreases in the morning and is intensified by day and evening) and is significantly improved under the influence of small doses of levodopa. The gene of Segawa disease, which encodes GTP cyclohydrolase I, is an enzyme involved in the synthesis of bioptin, an obligate co-factor of tyrosine hydroxylase. In patients with Segawa's disease, the activity of tyrosine hydroxylase and the synaptic level of dopamine are reduced. It is assumed that during sleep, the synaptic level of dopamine is partially restored, but after waking quickly decreases, accompanied by increased dystonia in the afternoon.

Ljubeg disease is an X-linked disease observed in Filipinos and manifested by a combination of dystonia and Parkinsonism. With the help of PET in patients, a decrease in the uptake of 11C-fluorodopa is revealed, which indicates a violation of dopamine metabolism in the brain.

The loss of the GAG codon in the DYT-1 gene underlies most cases of childhood dystonia inherited in an autosomal dominant type. This mutation is especially common among Ashkenazi Jews and first appeared in one of their ancestors, who lived about 300 years ago in Lithuania. This gene encodes a protein called torsin A, which is detected in the dopaminergic neurons of the black substance, the granular cells of the cerebellum, the cells of the dentate nucleus and the pyramidal cells of the gigocampus. The function of this protein remains unknown, as well as its effect on the functioning of the dopaminergic system. However, the ineffectiveness of levodopa preparations in this disease indicates that the activity of the dopaminergic system does not suffer.

Treatment of dystonia

When starting to treat dystonia, first of all it is necessary to determine whether it reacts to levodopa or a dopamine receptor agonist. If not, then antagonists of muscarinic cholinergic receptors (cholinolytics), baclofen, carbamazepine, benzodiazepines with long-term action should be tested. Trial treatment with various drugs should be carried out systematically, in order to clearly determine whether this or that remedy has a therapeutic effect or not. In many patients, pharmacotherapy has only a very mild effect. In dystonia beginning in childhood, there is sometimes a significant improvement in long-term treatment with high doses of antagonists of muscarinic cholinergic receptors. In these patients, trial treatment should last at least 6 months, because the therapeutic effect may not appear immediately.

In dystonia, resort to surgical treatment, in particular stereotaxic thalamotomy or pallidotomy. Despite the significant risk of severe dysarthria and other complications that are possible with a bilateral operation that is necessary for generalized dystonia or spastic krivoshe thanks to modern neurovisualization and neurophysiological techniques, stereotactic operations have become an indispensable method in the most severe cases. In recent years, not only destructive, but also stimulating methods of interfering with deep structures of the brain have been increasingly used. As one possibility, a combination of microstimulation of the pale balloon or thalamus on one side and pallidotomy or thalamotomy on the other hand is suggested. Local injections of botulinum toxin every 2-4 months are an effective method of treating focal dystonia. Injections are performed in the muscles involved in hyperkinesis and cause their partial weakening, which, however, is sufficient to reduce the severity of dystonic contractions. Injections have to be repeated on a regular basis. Adverse events are minimal. In some patients, shortly after the injection, excessive muscle weakness develops, which lasts for 1-2 weeks. To avoid recurrence of this complication, the dose in subsequent administrations is reduced. In some patients, with excessive administration of botulinum toxin, antibodies to toxins are formed, which reduce its long-term effectiveness.