Dystonia: Clinical Guidelines

List of Abbreviations

BS — blepharospasm

BT — botulinum therapy

BoNT-A – Botulinum toxin type A**

VAS – visual analogue scale

HIV – human immunodeficiency virus

WHO – World Health Organization

GABA – gamma-aminobutyric acid

DOPA — L-3,4-dihydroxyphenylalanine

UNITS — botulinum toxin unit

CT – computed tomography

LD – laryngeal dystonia

PT – physical therapy

mg – milligram

day – 24 hours

Russian Ministry of Health – Ministry of Health of the Russian Federation

ICD-10 – International Classification of Diseases 10th Revision

ICF – International Classification of Functioning, Disability and Health

MSDSBT – Interregional public organization of botulinum therapy specialists

MRI – magnetic resonance imaging

OMD – oromandibular dystonia

synd. – syndrome

US – ultrasound examination

Federal Law No. 323 – Federal Law No. 323-FZ "On the Fundamentals of Healthcare Protection in the Russian Federation"

fMRI – functional magnetic resonance imaging

CD – cervical dystonia

CNS – central nervous system

EMG – electromyography

EMG machine – electromyography device

AAN – American Academy of Neurology

COST – European Dystonia Cooperation in Science and Technology

DBS – Deep Brain Stimulation

TWSTRS – Toronto Western Spasmodic Torticollis Rating Scale

** – vital and essential drugs

Terms and Definitions

Blepharospasm – a focal form of muscle dystonia characterized by increased blinking and involuntary forceful closure of the eyes.

Dystonia – a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, oft-repeated movements and/or postures, which are frequently patterned or stereotyped, and that may be associated with tremor and other involuntary movements.

Levels of evidence confidence – reflect the degree of certainty that the estimated effect of a medical technology is true. According to epidemiological principles, the certainty of evidence is determined by 3 main criteria: qualitative and quantitative characteristics, and consistency of the evidence.

Grades of recommendation – unlike levels of evidence, they reflect the degree of certainty not only in the reliability of the intervention effect, but also in that following the recommendations in a specific situation will bring more benefit than negative consequences.

Cervical dystonia (spasmodic torticollis) – a focal form of muscle dystonia characterized by involuntary contractions of neck muscles resulting in abnormal head and neck postures and head tremor.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, typically repetitive movements and/or postures that interfere with specific actions in the involved body areas. Dystonic movements are generally stereotyped and rotational in nature, and may also manifest with tremor. Dystonia typically appears or worsens during voluntary movements and is accompanied by excessive muscle activation [1, 2, 3, 4].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The cause of dystonic syndromes may be attributed to congenital and hereditary factors, and may also result from various nervous system disorders. Inheritance can occur in both an autosomal dominant and autosomal recessive manner. In the vast majority of cases, the etiology of the disease remains undetermined [1, 2, 3, 4].

1.3 Epidemiology of the Disease or Condition

Dystonia ranks 3rd among various forms of movement disorders. According to estimates, the prevalence of dystonia may range from 3 to 11 cases per 100,000 population for generalized forms (usually beginning in the 1st-2nd decades of life and often of hereditary origin) and 30 to 60 cases per 100,000 for focal forms, which typically manifest at an older age [1, 2, 3, 4, 5, 6, 7].

1.4 Features of Coding the Disease or Condition

These clinical guidelines discuss the diagnosis and treatment of dystonia in the following conditions (according to ICD-10):

Dystonia (G24):

G24.0 – Drug-induced dystonia

G24.1 – Idiopathic familial dystonia

G24.2 – Idiopathic non-familial dystonia

G24.3 – Spasmodic torticollis

G24.4 – Idiopathic orofacial dystonia

G24.5 – Blepharospasm

G24.8 – Other dystonia

G24.9 – Dystonia, unspecified

1.5 Classification of the disease or condition

Under the auspices of the Dystonia Medical Research Foundation, the Dystonia Coalition, and the European Dystonia Cooperation in Science and Technology (COST), a Consensus Committee was formed, which presented a new classification of dystonias in 2013 [1]. This classification is based on 2 axes: clinical characteristics and etiology (Table 1). The combination of these two descriptive categories allows for capturing all relevant information about any patient suffering from dystonia and can serve as the basis for developing strategies for further research and treatment [1].

Table 1. Classification of dystonia [1]

Clinical significance of the classification of dystonias and characteristics of individual forms

Classification direction I: clinical characteristics of dystonia

Age-at-onset classification. In childhood-onset dystonia, there is a higher probability of identifying the cause, and this type of dystonia is also characterized by a greater likelihood of progression from focal to generalized. When dystonia appears during the first year of life, there is a very high probability of an underlying inborn error of metabolism. Dystonia presenting between 2 and 6 years of age may lean more towards dystonic cerebral palsy, especially if preceded by motor developmental delay. Other dystonia syndromes, such as dopa-responsive dystonia, tend to manifest between 6 and 14 years of age. Finally, sporadic focal dystonia typically presents after the age of 50. [1, 2, 3, 4]

Body distribution classification. The treatment of choice for focal and segmental dystonia involves the use of other peripheral muscle relaxants – botulinum toxin, whereas systemic medications or surgical treatment (deep brain stimulation [DBS] or intrathecal baclofen pump) are more commonly used for generalized dystonia. The distribution of affected body parts can change over time, typically involving previously unaffected areas. The spread of dystonia can be observed during repeated periodic evaluations.

The following forms of dystonia are distinguished depending on the body regions involved.

• Focal. Only one body region is involved (blepharospasm, oromandibular dystonia, cervical dystonia, laryngeal dystonia, and writer's cramp). Cervical dystonia is considered a form of focal dystonia even though not only the neck but also the shoulder may be involved in this pathology.

• Segmental. Two or more contiguous body regions are affected (cranial dystonia, bibrachial dystonia).

• Multifocal. Two or more non-contiguous body regions are affected (dystonia of an upper and lower limb, or cranial and lower limb).

• Generalized. The trunk and at least 2 other regions are involved. Generalized forms involving the legs are considered separately from dystonia forms where the legs are spared.

• Hemidystonia. Multiple body regions on one side are affected. Usually secondary to a contralateral brain lesion [1, 2, 3, 4].

Temporal pattern

There are 4 types of temporal variability.

• Persistent: dystonic manifestations remain stable throughout the day.

• Action-specific: dystonia manifests only during the performance of specific actions or tasks.

• Diurnal fluctuations: dystonia manifestations with marked daily fluctuations in triggering conditions, severity, and phenomenology.

• Paroxysmal: sudden, self-limiting episodes of dystonia, usually triggered by a specific factor, followed by return to baseline neurological status [1, 2, 3, 4].

Associated features

• Isolated dystonia: dystonia is the sole motor manifestation (though tremor may be present).

• Combined dystonia: combined with other movement disorders (such as myoclonus, parkinsonism, etc.) [1, 2, 3, 4].

Classification direction II: etiology

Signs of degeneration identified at the macroscopic, microscopic, or molecular level are an important way of subdividing various forms of dystonia into degenerative and non-degenerative categories.

• Degeneration (progressive structural abnormality, such as neuronal loss).

• Static lesion (non-progressive neurodevelopmental abnormality or acquired lesion).

• No evidence of degeneration or structural abnormalities [1, 2, 3, 4].

Congenital or acquired form

Congenital forms of dystonia include those with a proven genetic etiology.

• Autosomal dominant form. This category includes several autosomal dominant forms, such as DYT1 (OMIM #128100), DYT5 (#128230), DYT6 (#602629), DYT11 (#159900), rapid-onset dystonia-parkinsonism (DYT12, #128235), neuroferritinopathy (NBIA3, #606159), dentatorubral-pallidoluysian atrophy (#125370), and Huntington's disease (#143100).

• Autosomal recessive form. The list of autosomal recessive forms of congenital dystonia is continuously expanding. Among these forms are Wilson's disease (OMIM #277900), PKAN (NBIA1, #234200), PLAN (NBIA2, #256600), and juvenile parkinsonism type 2 (PARK2, #600116), along with a number of metabolic disorders.

• X-linked recessive form. Congenital dystonia with X-linked inheritance includes forms such as X-linked dystonia-parkinsonism (Lubag) (DYT3, OMIM #314250), Lesch-Nyhan syndrome (#300322), and Mohr-Tranebjærg syndrome (#304700).

• Mitochondrial form. Mitochondrial forms, such as Leigh syndrome (OMIM #256000) or Leber hereditary optic neuropathy with dystonia (#500001), also represent inherited forms of dystonia.

The DYT classification is presented in this article as a list to help distinguish disease subtypes, rather than as part of a formal classification system.

Acquired forms of dystonia are caused by known specific etiologies.

• Perinatal brain injury: dystonic cerebral palsy, late-onset dystonia.

• Infection: viral encephalitis, encephalitis lethargica, subacute sclerosing panencephalitis, human immunodeficiency virus (HIV), others (tuberculosis, syphilis, etc.).

• Drug-induced: dopamine receptor agonists, L-DOPA and its derivatives, antipsychotics, antiepileptic drugs, and calcium channel blockers.

• Toxic: manganese, cobalt, carbon disulfide, cyanides, methanol, disulfiram, and 3-nitropropionic acid.

• Vascular disorders: ischemia, hemorrhage, arteriovenous malformations (including aneurysms).

• Neoplastic disorders: brain tumor and paraneoplastic encephalitis.

• Brain injury: head trauma, brain surgery (including stereotactic ablation), and electrical injury.

• Psychogenic disorders (functional).

If the cause of dystonia is not identified, it is classified as idiopathic.

Idiopathic dystonia, in turn, can be classified as:

• A sporadic form.

• A familial form.

This category includes many cases of focal or segmental isolated dystonia with adult onset. The most common forms of focal dystonia may be sporadic or familial in nature. As research progresses and new genes responsible for the development of dystonia are discovered, idiopathic forms may be reclassified as inherited [1, 2, 3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. The classification of dystonia is important for adequate patient management, predicting the course of the disease, genetic counseling, and treatment.

1.6 Clinical presentation of the disease or condition

The clinical presentation is characterized by a combination of motor and non-motor manifestations. Motor manifestations associated with dystonia present as a specific unnatural dystonic posture with or without distal tremor, specific excessive movements at the peak of dystonic movements, mirror movements on the affected side when performing movements with the contralateral side, and the presence of sensory tricks (gestures or antagonistic movements) to eliminate or reduce the abnormal posture or movement. Non-motor symptoms of dystonia—pain, depression, anxiety, social phobias—are characteristic clinical manifestations that, along with motor symptoms, constitute the clinical picture of the disease and significantly affect patients' quality of life [1, 2, 3, 4, 5, 6, 10, 11].

Dystonia syndrome exhibits a significant degree of phenotypic variability with frequent overlap between different syndromes. There is no pathognomonic presentation that allows for reliable clinical-etiological correlations for either genetic or environmental forms. Some typical and more common syndromes encountered in clinical practice are briefly described here as examples. Consideration of these dystonia syndrome types is recommended as a general clinical approach used to assist in the etiological diagnosis of dystonia. The use of phenomenological classification (Table 1) helps to recognize dystonia syndromes into diagnostically useful phenomenological categories [1].

Clinical features of individual forms of dystonia

Cervical dystonia, blepharospasm, and writer's cramp are the most common forms of focal dystonia. Rarer forms include oromandibular, laryngeal, pharyngeal, and focal foot dystonia. Focal dystonias affect individuals of working age, with a high degree of social maladaptation and disability due to the development of marked functional deficits (keeping the head straight in cervical dystonia, functional "blindness" in blepharospasm, impaired writing in writer's cramp, impaired speech, chewing, and swallowing in oromandibular and pharyngeal dystonia, and vocalization disorders in laryngeal dystonia) [1, 3, 22].

Cervical dystonia (CD), or spasmodic torticollis, is the most common form of muscular dystonia. CD is characterized by involuntary contractions of the neck and shoulder muscles, leading to abnormal postures and/or movements of the neck, shoulders, and head [23]. CD is characterized by the involvement of a limited group of neck and occipital muscles in hyperkinesia. The involvement of neck muscles (manifesting to varying degrees) leads to the development of abnormal positions of the head, neck, and shoulders, most often accompanied by rotation around the horizontal axis (torticollis) and dystonic head tremor, where antagonistic muscles also contract. Pain in the cervical, occipital, and shoulder regions is observed in 75% of cases. Myofascial syndromes with typical radiation develop in the affected muscles, which is one of the leading causes of pain. Pain can also be caused by compression of nerve trunks by spastic muscles and irritation of pain receptors in periarticular structures. The onset of the disease in most cases is subacute or gradual (over several weeks or months). In the early stages of CD, many patients manage to reduce its severity with sensory tricks (touching the chin or cheek). The dynamic nature of CD is manifested in its close connection with movement and posture. Thus, it increases with voluntary movements and verticalization, and decreases significantly in the supine position. Dystonia is exacerbated by fatigue and psycho-emotional stress. The diurnal fluctuation phenomenon is characteristic: a decrease in the severity of CD after sleep. Alcohol intake transiently reduces symptoms in the first months after disease onset. CD usually progresses during the first 2–5 years of the disease, after which (without treatment) symptoms reach a plateau. As a rule, this disease is not only a cause of disability but also significantly limits patients' daily activities. Depression, anxiety disorders, and social phobias are the most common conditions associated with CD, which further deepens its social significance and justifies the development of careful treatment approaches for this disease. In 75% of cases, patients with CD exhibit the hyperekplexia phenomenon (jumping or startling in response to unexpected stimuli).

Spontaneous remissions during the first 5 years develop in no more than 20% of patients. The average duration of remissions is 6 months. For a long time, many patients retain voluntary control over involuntary head movements. In 1/3 of patients, dystonia subsequently involves other body parts. There is a regular combination of CD with writer's cramp (45%), blepharospasm (35%), oromandibular dystonia (10%), and dystonic hand tremor (27%).

The head can move in the horizontal, frontal, and sagittal planes, as well as undergo lateral displacement ("shift"). Professor G. Reichel (Germany) distinguished movements in the neck relative to the trunk and movements of the head relative to the neck ("torticollis, torticaput, laterocollis, laterocaput, anterocollis, anterocaput, retrocollis, retrocaput").

The most typical manifestation of CD is rotation of the head (chin)—torticollis. As the disease progresses, new muscles become involved in the pathological process, which may be accompanied by a change in head position in not just one or two, but all three planes. As a rule, there is a combination of abnormal postures (e.g., turning the head to the side and tilting the head toward the shoulder). The direction of head displacement is evaluated by the direction of chin displacement. [3]

Blepharospasm (BSP) is caused by dystonic contractions of the *orbicularis oculi* muscle, which is also often accompanied by contractions of the *procerus* and *corrugator* muscles. The development of the disease is usually gradual, starting with eye irritation or dryness, followed by pronounced blinking, especially in bright light. BSP is characterized by a polymorphism of motor manifestations. In clinical practice, the following variants of BSP are observed: 1) increased blinking in 10% of patients; 2) episodes of forceful eye closure in the form of frequent, short-lived, rhythmic spasms of the orbicularis oculi muscles in 17%; 3) episodes of prolonged eye closure in 46%; 4) episodes of frequent rhythmic spasms of the orbicularis oculi muscles combined with isolated eyelid twitches in 7%; 5) eye closure referred to by patients as "drooping eyelids" in 20% [3].

All patients demonstrate a dynamic nature of clinical manifestations. The greatest severity of BSP is observed during activities requiring specific use vision, as well as when standing and walking, outdoors, during emotional stress, fatigue, in crowded rooms, while talking, in the afternoon, and in bright lighting. Alcohol intake transiently improves the condition in some patients. In the early stages of the disease, partial voluntary control over involuntary movements is preserved. The most common sensory tricks used by patients to weaken or temporarily eliminate BSP can be divided into three groups: 1) maneuvers leading to a change in visual afferentation (closing one eye, squinting, wearing tinted glasses, removing and putting on glasses, looking down); 2) various manipulations in the upper half of the face (touching or pressing fingers on the temples, eyebrows, forehead, bridge of the nose, upper eyelid); 3) various manipulations in the lower half of the face (touching the chin, smoking and manipulating a cigarette in the mouth, having a foreign object in the mouth—chewing gum, seeds, pits, candy; coughing, performing various voluntary movements with the muscles of the lower half of the face).

A characteristic feature is the reduction or disappearance of involuntary movements in an unusual environment, particularly during a doctor's appointment. For diagnostic purposes, a provocative maneuver can be used: upon the physician's command, the patient is asked to close their eyes as tightly as possible for 5 seconds, and then open them as wide as possible for 5 seconds. After 4–6 repetitions of these movements, the symptoms of benign essential blepharospasm (BEB) become obvious. Spontaneous remissions are less typical for patients with BEB than for those with cervical dystonia. In 75% of cases, sensory symptoms mark the onset of the disease, including a sensation of eye irritation accompanied by lacrimation, eye pain, a gritty («sand in the eyes») sensation and burning, eye discomfort, and dry eyes (ranging up to dry eye syndrome) [3].

Isolated BEB is observed in approximately 40% of patients [3, 4]. In remaining cases, BEB is combined with manifestations of dystonia in the lower half of the face, collectively termed cranial dystonia. In patients with BEB, even in the early stages, involuntary movements in the lower half of the face may be observed; however, these movements are usually ignored by the patient or perceived as compensatory for opening the eyes [4].

Oromandibular dystonia (OMD) manifests as: involuntary opening and/etal closing of the mouth, jaw clenching (dystonic trismus), deviation of the lips, cheeks, or tongue, involuntary tongue protrusion and other tongue movements, lateral jaw movements, jaw clenching, and a forced smile, especially during speech and chewing. Patients use sensory tricks (gestures) such as: various hand manipulations in the lower half of the face (touching, pressing, etc.), biting the lip, tongue movements inside the oral cavity, chewing or sucking on various objects—fruit pits, seeds, hard candies, or performing other voluntary movements with the muscles of the lower facial region. Voluntary control is rarely observed. Knowledge of OMD symptoms is essential for dentists of various specialties, particularly prosthodontists and orthodontists. OMD typically begins in middle and older age, which is usually when extensive dental treatment and subsequent dental prosthetics are performed; this may act as a trigger for OMD in predisposed patients or in those who already have other manifestations of dystonia that went unnoticed by the dentist (for example, frequent blinking, mildly abnormal head posture, or writer's cramp). One of the markers for the development of OMD is patients' persistent complaint of «difficulty chewing» or «an uncomfortable position of the lower jaw and dentures» [3, 4].

Laryngeal dystonia (LD) is a borderline issue between otolaryngology (phoniatrics) and neurology. The main manifestations of LD are hoarseness, voice breaks during speech, a strained voice, and a «barking» voice. Many patients retain normal whisper speech, and dysphonia may be completely absent during singing (paradoxical kinesia). Dystonic spasms worsen during normal speech under the influence of speech load, emotional stress, and general fatigue. LD is one of the most severe voice disorders, manifesting as strained, strangled, and interrupted phonation. The adductor form is the most typical, observed in 90% of cases. In this form, dystonic hyperactivity is observed in the adductor muscles of the vocal cords (mm. cricothyroideus, cricoarytenoideus lateralis, interarytenoideus). The abductor form is much rarer (less than 10%), in which hyperactivity is observed in the m. cricoarytenoideus posterior. Mixed forms are even rarer. In LD, along with voice disorders, a characteristic symptom is impaired breathing (due to obstructed airflow through the larynx)—interrupted and strained. Sometimes this symptom is mistakenly diagnosed as bronchial asthma. During speech and singing, breathing usually improves (paradoxical kinesia) [3, 4].

Pharyngeal dystonia manifests as difficulty swallowing (more frequently with solid food), and a recurrent sensation of a «lump in the throat» during swallowing and/or at rest. Pharyngeal dystonia is often combined with LD or OMD [3, 5].

Cranial dystonia. This term encompasses manifestations of focal dystonia affecting the face and head in various combinations. Most commonly, there is a combination of generalized blepharospasm (involving the midface) and oromandibular dystonia. This is often referred to by the terms «facial paraspasm, median facial spasm, Meige syndrome, Brueghel syndrome» [3, 5].

Writer's cramp is a task-specific dystonia (manifesting during writing, and in exceptional cases, when working on a computer), occurring at a younger age than cervical dystonia and BEB. The main clinical manifestations of writer's cramp include: hand/arm tension during writing, alteration of hand/arm posture during writing, changes in and slowing of handwriting, loss of fluid handwriting, increased letter size, hand tremor during writing, and handwriting inconsistency. Patients experiment with pens of various shapes and diameters, alter their hand and finger posture while writing, and use their other hand to assist with the writing process. As writer's cramp progresses, other manual tasks—both domestic and professional—may also become impaired. In such cases, it is referred to as progressive writer's cramp [3, 24].

Generalized dystonia is characterized by slow, forced, predominantly rotational movements of the head, trunk, and limbs. It creates the impression that the muscle groups involved in the hyperkinesia are constantly and painfully overcoming the resistance of antagonist muscles. The resulting unusual, uncomfortable postures can persist for prolonged periods. Generalized dystonia is exacerbated by voluntary movements and emotional stress, and disappears during sleep. Gradually, a persistent dystonic posture develops, such as increased lumbar lordosis (lumbar hyperlordosis) with flexion of the hips and internal rotation of the arms and legs. In cases where a persistent pathological dystonic posture occurs due to a marked increase in muscle tone, but hyperkinesia is absent or no longer detectable, it is referred to as fixed (rigid) dystonia [15].

Depending on the age of onset and other characteristics, two forms of the disease are distinguished: an early-onset form associated with a mutation on the long arm of chromosome 9 (9q34), and a late-onset form associated with a mutation on the long arm of chromosome 8 or the short arm of chromosome 18. Dystonia associated with the DYT1 gene, which encodes the TorsinA protein, is the best-known and most thoroughly described etiology-wise pathology; it is inherited in an autosomal dominant manner with a penetrance of approximately 30%. The second identified gene, THAP1, causes DYT6-type dystonia, an autosomal dominant isolated dystonia syndrome with a penetrance of approximately 60%. Similar manifestations can also be observed in sporadic or familial cases of undetermined etiology [15, 18, 20].

Clinical manifestations typically develop in the 1st or 2nd decade of life, and in 1/3 of cases before the age of 15. When onset occurs in early childhood, gait disturbances appear first, which can initially be difficult to interpret correctly. Conversely, when onset occurs in adulthood, involuntary movements first appear in the trunk and upper extremities, and only in 1/3 of cases progress to a generalized form [20].

Myoclonus-dystonia (myoclonic dystonia) features myoclonus-like manifestations during rapid dystonic movements. The myoclonus in myoclonus-dystonia is non-epileptic. Patients with «myoclonic dystonia» (DYT11) exhibit a combination of dystonia and myoclonus; this phenomenon may essentially represent «essential myoclonus,» as many of these patients exhibit only subtle concomitant dystonia, or some patients have pure myoclonus while other members of the same family exhibit both myoclonus and dystonia simultaneously. In many cases, myoclonic jerks can be distinguished from rapid «shock-like» dystonic movements based on clinical and electrophysiological assessment [16].

Dystonia-parkinsonism includes a range of disorders, most of which are inherited, combining features of both dystonia and parkinsonism, sometimes with signs of pyramidal tract involvement or other neurological disorders. Non-motor disorders, including cognitive impairment, also frequently occur. Of particular interest are the following: DOPA-responsive dystonia (DRD, Segawa disease), Wilson's disease, Parkin-, PINK1-, and DJ-1-associated parkinsonism (PARK2, 6, and 7), X-linked dystonia-parkinsonism / Lubag syndrome (DYT3), rapidly progressive dystonia-parkinsonism (DYT12), and neurodegeneration with brain iron accumulation (NBIA, including PANK2- and PLA2G6-associated neurodegeneration, neuroferritinopathy, and other forms). Various new dominant, recessive, and X-linked genes underlying the development of dystonia-parkinsonism continue to be identified and are assigned DYTn or PARKn designations. DOPA-responsive dystonia, formerly referred to as progressive dystonia with marked diurnal fluctuation (Segawa disease), begins in childhood. The disease is caused by a mutation in the GTP cyclohydrolase I gene on the long arm of chromosome 14 (14q22.3). The inheritance pattern is autosomal dominant with low penetrance. The severity of dystonic movements fluctuates throughout the day, but over many years tends to increase as the disease progresses [15, 18, 20].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the disease or condition

Diagnostic criteria for dystonia based on pathognomonic findings:

1. Anamnestic data — presence of involuntary movements at rest and during physical exertion, presence of non-motor symptoms (pain, emotional disturbances, sleep disorders);

2. Physical examination — dystonic posture (with or without tremor), specific features (overflow and mirror movements, sensory tricks);

3. Laboratory and diagnostic examination following a clinical diagnosis (molecular genetic testing if hereditary dystonia is suspected);

4. Other diagnostic examinations.

2.1 Complaints and Anamnesis

Comments: Involuntary movements of various body parts can be triggered by emotional stress. Pain in the affected body part (muscle/muscle group) is characteristic.

Comments: Non-motor symptoms of dystonia—pain, depression, anxiety, social phobias, and sleep disturbances—are characteristic clinical manifestations that, alongside motor symptoms, form the clinical picture of the disease and significantly affect patients' quality of life [1, 2, 3, 5, 6, 23, 26]. Non-motor manifestations of dystonia are part of the primary pathophysiological features of the disease and can be partially explained by the same pathophysiological model from which motor symptoms are presumed to arise. From a clinical perspective, non-motor symptoms significantly impact the quality of life of patients with dystonia and, in combination with pharmacological or surgical methods, can represent therapeutic targets for alleviating dystonia. These symptoms require the same level of attention as the motor features of the disease. Non-motor manifestations of dystonia can variously affect a patient's daily activities and functioning.

2.2 Physical Examination

Comments: Motor manifestations associated with dystonia [1] are presented in Table 2. The severity of dystonia may vary depending on the position of the body or its individual parts and voluntary movements in the affected body part [1, 3, 4, 5, 6, 7, 8]. It is necessary to take into account the significant degree of phenotypic variability of dystonia motor syndromes and the lack of reliable pathognomonic signs determining the clinical and etiological relationship with genetic or external factors [1, 3]. It is proposed to use specially developed clinical scales (which should be listed in the comments) that allow measuring the features of clinical manifestations, severity, disability, the fluctuating nature of dystonia, and the impact of dystonia on the patient's functioning and daily activities [1, 9, 27].

Table 2. Motor manifestations associated with dystonia [1]

Comments: According to a study of 148 patients with cervical dystonia (CD), the purpose of which was to study hypothetical sources of error in the quantitative assessment of the sensory trick effect in CD using the TWSTRS (Toronto Western Spasmodic Torticollis Rating Scale), video recording was used. This made it possible to clarify the necessary duration of testing to identify the sensory trick and showed that the efficacy of the sensory trick can be a criterion for measuring CD severity, the assessment of which using a special video protocol avoids errors in evaluation [28]. Conducting a standardized videocassette clinical examination using a series of scales and questionnaires, including the TWSTRS scale in 48 patients with Huntington's disease, made it possible to study the prevalence, distribution, severity, and impact of dystonia on the patient's functional capabilities. Statistically significant positive correlations (P < 0.05) were observed between dystonia severity, disease stage, and the duration of movement disorders. Recognizing dystonia with a videocassette clinical examination helps manage dystonic symptoms in routine clinical practice, general symptomatic treatment, and functional improvement [29].

Video recording of a patient with dystonia is an important stage of diagnosis, further planning of botulinum toxin type A**, Botulinum toxin type A-hemagglutinin complex** injections and other treatment methods, as well as subsequent evaluation of treatment outcomes [1, 3]. Scales for assessing CD and blepharospasm and video registration protocols are posted on the website www.botulin.ru in the Specialist Library section and in the Medical Technology for the Treatment of Focal Dystonias [23].

2.3 Laboratory Diagnostics

Comments: Genetic testing alone is insufficient to diagnose dystonia in the absence of clinical signs [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. Genetic testing should only be performed after a clinical diagnosis has been established [9].

Comments: In familial dystonia, DYT-1 testing is not recommended in asymptomatic cases. Diagnostic DYT-6 testing is recommended for patients with early-onset dystonia, familial dystonia with a craniocervical phenotype [14, 15], or after ruling out DYT-1. Patients with early-onset myoclonus involving the limbs or neck, especially if autosomal dominant inheritance is possible, should be tested for the DYT-11 gene [7]. Diagnostic testing for the DYT-8 gene is suggested for patients presenting with paroxysmal non-kinesigenic dyskinesia [14]. Genetic testing for GLUT1 mutations is suggested for patients with exercise-induced paroxysmal dyskinesia, especially if GLUT1 involvement is suspected due to the presence of epileptic seizures or hemolytic anemia [16, 18]. Genetic testing to detect heterozygous GTP cyclohydrolase mutations in the DYT-5 gene is suggested for patients with a clinical presentation resembling spastic diplegia in cerebral palsy, characterized by severe motor impairment, hypokinesia, rigidity, and diurnal fluctuations in motor symptoms [30]

Comments: Various neurophysiological tests can confirm functional impairment in patients with dystonia. In most cases, neurophysiological abnormalities are non-specific, may not correlate with the clinical picture, and are clinically insignificant; therefore, they are not recommended for routine use in the diagnosis or classification of dystonia. However, needle electromyography of various muscles can enhance clinical assessment by revealing characteristic features of dystonia. Multi-channel needle EMG of various muscles can be used to assess the characteristics of dystonia [33]. There is no evidence supporting the diagnostic or classification value of more advanced imaging techniques (diffusion-weighted imaging, functional MRI) [31, 32].

Comments: A diagnostic test with #levodopa+[carbidopa]** is indicated for all patients with dystonic gait disorder, diplegia, sporadic spastic paraplegia, ataxic syndrome, or diurnal fluctuations of dystonia presenting at an early age without an alternative diagnosis [18, 30, 34]. This can identify dopa-responsive dystonia (Segawa disease). The drug #levodopa+[carbidopa]** is taken orally at a therapeutic dose appropriate for age and body weight; a pronounced clinical effect should occur within 25–60 minutes and persist for several hours [18, 30, 34].

2.4 Instrumental Diagnostics

Comments: Neuroimaging methods of the brain (magnetic resonance imaging of the brain; functional magnetic resonance imaging of the brain; computed tomography of the brain, etc.) are not routinely recommended when there is a clear clinical diagnosis of primary dystonia in adult patients, as normal results are expected in these cases [31, 32]. Brain structure assessment using brain MRI is necessary when screening for secondary forms of dystonia [31, 32]. Brain computed tomography may be needed to differentiate calcium and iron accumulations [32]. Presynaptic dopaminergic imaging (dopamine transporter or 18F-DOPA PET/SPECT) is an effective method for differentiating dopa-responsive dystonia from juvenile Parkinson's disease presenting with dystonia. It can also be useful for differentiating dystonic tremor from parkinsonian tremor [31, 32].

2.5 Other Procedures

Risk factors for the development of dystonia

Comments: The International Parkinson and Movement Disorder Society evaluated clinical manifestations and predictors in individuals with various types of isolated dystonia in a multicenter, international cross-sectional cohort study of 2,362 people with all types of isolated dystonia (focal, segmental, multifocal, and generalized). It is recommended to consider the following peripheral factors as risk factors for the development of dystonia: prolonged excessive muscle use, pain syndrome, prolonged postural loads in the affected area, and local trauma 0.5–2 years before disease onset, as well as to recognize the early appearance of sensory symptoms as a manifestation of excessive afferent input [35]. A case-control study of 67 patients with cervical dystonia and 67 of their healthy siblings, assessing environmental exposure using a detailed standardized 124-question questionnaire, showed that patients with cervical dystonia, compared to their healthy siblings, had an increased frequency of car accidents (10.1, 95% CI 2.1 to 47.4, p = 0.004) and surgical episodes (6.5, 95% CI 1.76 to 23.61, p = 0.005). Multivariate analysis showed that car accidents and surgical episodes are significantly associated with cervical dystonia status. Soft tissue trauma increases the risk of developing cervical dystonia in genetically predisposed individuals [36]. A study of the Taiwan National Health Insurance Research Database involving 65,704 individuals with peripheral trauma identified 189 patients with dystonia (0.28%) in the trauma group and 52 patients with dystonia (0.08%) in the non-trauma group. The incidence density of dystonia was 2.27 per 10,000 individuals in the trauma group and 0.71 per 10,000 individuals in the non-trauma group; other variables associated with dystonia incidence included female sex aged 40 years and older, depression, and sleep disorders [37].

Comments: The study of peripheral mechanisms of CD pathogenesis and symptom formation was performed using orthopedic diagnostics and motor stereotype analysis, history of trauma, and pain syndrome assessment. In 40 out of 95 examined patients with CD, a "short leg" was found on the side opposite to head rotation, along with pain and other sensory symptoms in the same region. ENMG and sympathetic skin response data indicated pathological changes in sympathetic autonomic fibers as well as in nerve axons on both sides, predominantly on the CD side. The correlations observed between the side of head rotation and the side of the peripheral factor suggest that peripheral factors (primarily the "short leg" factor) often determine the side of head rotation. Thus, CD therapy should also target peripheral mechanisms rather than central ones alone [38]. Therefore, correction of the "short leg" serves as an additional therapeutic intervention in patients with cervical dystonia.

Differential diagnosis

Comments: Differential diagnosis of cervical dystonia is carried out with the following diseases and syndromes: congenital muscular torticollis, myopathic syndromes, orthopedic and rheumatic disorders (atlantoaxial subluxation, shoulder subluxation, spinal curvature, etc.), lesions of the 11th cranial nerve or root, upper cervical roots, congenital anomalies of the cervical vertebrae, vertebral pathology (pathological fractures, spondylitis), space-occupying lesions in the soft tissues of the neck, compensatory head positioning and movements in abducens and other extraocular nerve palsies, nystagmus, strabismus, corneal scars, head tilt in syringomyelia or high spinal cord tumor, acute torticollis in cervical disc pathology, benign paroxysmal torticollis in infants, Sandifer syndrome (gastroesophageal reflux), tics, psychogenic torticollis

Comments: Ruling out myasthenia gravis is of fundamental importance, as myasthenia gravis is a contraindication for treatment with botulinum toxin type A**, botulinum toxin type A-hemagglutinin complex**. In hemifacial spasm, the eyebrow is elevated (due to frontalis muscle spasm), whereas in blepharospasm, it is drawn into the orbit.

Comments: to perform an accurate differential diagnosis of laryngeal dystonia from other laryngeal disorders, phoniatric and phonioscopic examination with visualization of all laryngeal structures is recommended [3]. The differential diagnosis of writer's cramp includes parkinsonian and spastic hemisyndromes, neuropathies, plexopathies, overuse syndromes, and essential tremor [3, 24].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Formulated based on the optimal selection of characteristics: nosological unit, ICD-10 code, age category, disease stage, disease phase, complications, stratification risk, type of medical care, conditions of medical care, form of medical care that have the greatest impact on patient management tactics (Tab. 3).

Table 3. Patient models with dystonia

3.1 Conservative Treatment

Introduction: the goals of treatment are to achieve sustained disease remission while maintaining patients' ability to work and social activity, as well as to prevent the recurrence of dystonia symptoms [25]. This can only be achieved through regular repeated injections of drugs (peripherally acting muscle relaxants, ATC code M03AX01) with the active substance Botulinum toxin type A** or Botulinum toxin type A-hemagglutinin complex** into the spastic muscles.

Comments:this method eliminates pathological muscle contractions while preserving their function. To achieve sustained remission and maintain patients' quality of life, botulinum toxin type A** or botulinum toxin type A-hemagglutinin complex** preparations must be prescribed to patients with idiopathic cervical dystonia (predominantly rotational form) aged 18 years and older immediately after the diagnosis of focal dystonia is established, as they are first-line treatments. Injections should be performed regularly, on average every 3 to 4 months. However, the interval between injections may vary depending on the severity of the main clinical manifestations and the patient's well-being, but should not be less than 12 weeks. A flexible injection interval strategy ("on demand" when the effect of the previous injection begins to wear off) is advisable. The safety and high efficacy of botulinum toxin therapy have been proven by numerous controlled studies and 30 years of clinical practice [25, 49]. The clinical effect after the injection appears on days 7 to 21 and manifests as a pronounced reduction in muscle tension, spasms, and pain. The therapeutic effect of drugs containing the active substance botulinum toxin type A** or botulinum toxin type A-hemagglutinin complex** is associated not only with its symptomatic action as a local muscle relaxant, but also with its effect on afferent pathways at the segmental-peripheral and suprasegmental levels, which suggests a pathogenetic role of botulinum toxin therapy in the treatment of focal dystonias [3, 23, 32, 43, 46, 50]. In recent years, data have emerged on the long-term efficacy and safety of botulinum toxin type A**, botulinum toxin type A–hemagglutinin complex** preparations. Clinical doses of all botulinum toxin type A** and botulinum toxin type A–hemagglutinin complex** preparations are expressed in units of activity (U) and are not interchangeable. It is recommended to carry out 3 to 4 injection courses per year depending on the severity of the disease symptoms and the specific botulinum toxin type A** or botulinum toxin type A–hemagglutinin complex** preparation used. The approved package inserts for botulinum toxin type A** and botulinum toxin type A–hemagglutinin complex** preparations describe the doses and routes of administration. There are also medical technologies detailing the methods of administration and injection techniques for various forms of focal dystonia [23, 40]. Drugs of this class may only be administered by specialists with special training and experience in handling botulinum toxin. When choosing the injection site, one should be guided by the standard muscle layout; the exact injection site is determined according to anatomical landmarks and palpation data, as well as using additional methods: needle electromyography, electrical stimulation, ultrasound, and CT. Most muscles are selected and injected in accordance with the analysis of dystonic movements, topographical anatomy, and muscle palpation [40, 41, 42]. Written informed consent for treatment with botulinum toxin must be obtained. It is recommended to actively contract the injected muscles for 20 minutes after the botulinum toxin therapy procedure; the patient must remain under observation in the medical facility for one hour to monitor for the development of immediate allergic reactions [3, 49]. In case of an insufficient effect noted during follow-up examination of the patient, subsequent injections involve the selection and replacement of treatment regimens, changing the dose of botulinum toxin type A** or botulinum toxin type A–hemagglutinin complex**, using additional injection guidance methods, and consulting with a more experienced botulinum toxin therapist. The technique of botulinum toxin therapy for other forms of focal dystonias is described in detail in the medical technology [23, 51, 52]; the recommended dose of the drug must not be exceeded [3, 4, 14, 15, 16, 17, 18, 19, 20, 26, 31, 32].

Comments: Both types registered in the Russian Federation, botulinum toxin type A-hemagglutinin complex** and botulinum toxin type A-hemagglutinin complex**, have similar efficacy and can remain effective for a long time [43].

Comments: both types registered in the Russian Federation, botulinum toxin type A**, botulinum toxin type A–hemagglutinin complex**, have similar efficacy and can remain effective for a long time. To ensure the best efficacy and safety of botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** injections, the highest possible injection accuracy is required [40, 41, 42, 43].

Comments: Treatment of adductor spasmodic dysphonia using #botulinum toxin type A** was performed in 13 patients as part of a double-blind, placebo-controlled study. Patients were diagnosed by an interdisciplinary team consisting of a speech-language pathologist, an otolaryngologist, and a neurologist. #Botulinum toxin type A** or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance. #botulinum toxin type A** markedly reduced hypertonus, decreased the range of dystonic frequencies, and improved spectrographic voice characteristics. Patients, following the administration of #botulinum toxin type A**, noted a significant improvement in voice compared to the placebo group. #Botulinum toxin type A** proved to be an effective and safe method for treating adductor-type laryngeal dystonia [67]. A comparison of the effects of unilateral (50 IU of botulinum toxin type A**) and bilateral thyroarytenoid muscle injections (25 IU of #botulinum toxin type A** on each side) in 50 patients with adductor-type laryngeal dystonia showed that standard unilateral and bilateral injections of #botulinum toxin type A** provide an equivalent degree of improvement in laryngeal dystonia symptoms. The control group included 15 healthy subjects [67]. However, there is insufficient data to confirm efficacy in abductor-type laryngeal dystonia and muscle tension dysphonia. Another study [68] evaluated the effects of unilateral (15 IU of botulinum toxin) and bilateral (2.5 IU of botulinum toxin each) injections of the cricothyroid muscle. At 6 weeks post-injection, maximum phonation time was significantly lower with unilateral botulinum toxin administration.

Comments: A search of the Cochrane Library, MEDLINE, and EMBASE databases for randomized studies comparing botulinum toxin type A** with placebo in hemifacial spasm revealed one small randomized, placebo-controlled crossover study involving 11 individuals, in which patients underwent four injection sessions comparing placebo with three different doses of botulinum toxin type A**—low dose: half of the intermediate dose; intermediate dose; and high dose: double the intermediate dose, and one placebo. The effect of botulinum toxin type A** was superior to placebo. Despite the scarcity of high-quality controlled data, all available studies indicate that botulinum toxin type A** is effective and safe for the treatment of hemifacial spasm. Future trials should investigate technical factors such as optimal treatment intervals, various injection techniques, doses, types of botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex**, quality of life, long-term efficacy, safety, and immunogenicity. Botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** should be compared with surgical microvascular decompression [69].

Comments:A placebo-controlled study evaluated 25 patients with hand tremor. Subjects were randomized to receive 50 units of botulinum toxin or placebo injections into the wrist flexors and extensors of the upper extremity. If patients did not respond to the initial injection, they were eligible for a repeat injection of 100 units at 4 weeks [25]. Botulinum toxin type A** may be and botulinum toxin type A-hemagglutinin complex** are effective in other types of upper limb dystonia, but more careful dose adjustment is required due to frequently occurring muscle weakness. Botulinum toxin type A preparations are safe and effective for long-term repeated injections, but physicians and patients should be aware that high cumulative doses can be hazardous, especially in children [25]. Given the complexity and individual need for therapeutic intervention with botulinum toxin injections in writer's cramp, it is difficult to standardize a generalized injection regimen and specific recommendations. The overall efficacy from the selected study shows that 76% of all patients included in the study responded to symptoms such as writer's cramp, as well as various task-specific dystonias, including musician's dystonia. Data from 11 years concerning 420 patients with dystonia (50 with hand cramps and 10 with arm dystonia) were analyzed. A total of 1,831 botulinum toxin injections into 39 target muscles were analyzed for dystonia. Botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** were used. An average of 70.3 IU of toxin was applied to the affected target muscles (an average of 2.5 muscles), most commonly the flexor digitorum superficialis (48%), flexor carpi ulnaris (42%), extensor carpi ulnaris (34%), extensor carpi radialis (30%), flexor digitorum profundus (30%), flexor pollicis longus (28%), flexor carpi radialis (12%), pronator (8%), extensor indicis (8%), and epicondylar extensors (6%). Ultrasound or EMG was used as accuracy control, noting that the dose range was strictly individual and varied from 9.3 IU for small muscles such as the index finger to 35.4 IU for larger muscles such as the extensor carpi ulnaris [70]. Injections of 50 IU of #botulinum toxin type A** into the flexor and extensor muscles of the wrist of the upper extremity are recommended; if there is no therapeutic effect after 4 weeks, a repeat injection is administered at a dose of 100 IU of #botulinum toxin type A** [25].

Comments: Currently, the prevalence of intrathecal #baclofen** administration is decreasing due to adverse events associated with the drug and equipment operation features, as well as the greater availability and efficacy of deep brain stimulation. Bilateral stereotactic radiofrequency thalamotomy, intradural rhizotomy, and microvascular decompression are currently not recommended for use (GPP). There is no evidence base for using this method in primary dystonia. Intrathecal #baclofen** infusions are a well-established treatment for spasticity. There is also evidence supporting the treatment of secondary generalized dystonia with intrathecal #baclofen**. The benefits of the method include tone reduction, improved positioning, and a decrease in pressure ulcer formation. Despite these benefits, significant complications can occur with this therapy, including drug withdrawal, catheter infections, overdoses, and baclofen pump failure. To improve patient selection and outcomes, many centers offering intrathecal #baclofen** therapy utilize a multidisciplinary team consisting of physicians, surgeons, and physical therapists [69]. It is recommended to start #baclofen** infusions at a rate of 200 mcg/day. The dose should be increased by 50 mcg every 8 hours until one of three endpoints is reached: (1) a clinically significant response (a reduction in the mean BAD score by 25% or more), (2) undesirable side effects, or (3) no clinically significant response at an infusion rate of 900 mcg/day [72].

3.1.1. Conservative treatment of dystonia in children

For patients under 18 years of age, treatment recommendations are based on "mixed" pediatric-adult studies and expert opinions [73].

• As a first-line drug for children with dystonia, the central anticholinergic #trihexyphenidyl** is recommended (initial dose 1–2 mg daily divided into 3 doses, then the dose is increased weekly by 1–2 mg divided into 3 doses; target dose: 1–2 mg/kg/day divided into 3 doses) to improve abnormal movements, posture, and gait in children [73, 74, 75].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Anticholinergic drugs, such as #Trihexyphenidyl**, are among the most effective treatments for generalized dystonia in children. A prospective, double-blind, crossover study [76] demonstrated a significant clinical benefit of #Trihexyphenidyl** at a dose of 30 mg compared to placebo in children and young adults with segmental and generalized dystonia. Fahn et al. [74] conducted an open-label study demonstrating moderate to marked improvement with #Trihexyphenidyl** in 61-71% of children (mean daily dose 41 mg) compared to 19-38% of adults (mean daily dose 24 mg). #Trihexyphenidyl** is better tolerated by children than by adults; adverse events during therapy include constipation (43%), decreased urination frequency (19%), irritability/behavioral changes (13%), and dry mouth [77]. Less common adverse events include blurred vision, chorea, rash, and somnolence [78]. #Trihexyphenidyl** usually requires long-term treatment (from several weeks to several months) before a clinical response occurs [79].

Comments: Baclofen** acts as a gamma-aminobutyric acid (GABA) agonist, targeting GABA-B receptors. It reduces the excitability of motor neurons, primarily at the spinal cord level. Oral baclofen has very limited penetration across the blood-brain barrier (BBB), therefore high doses of oral baclofen** are required to achieve clinical benefit [83]. Oral baclofen** is frequently used in clinical practice for pediatric dystonia, although therapeutic data are extremely limited and most data are based on expert opinion [84]. Greene et al. [80] found moderate improvement with baclofen in 7 of 16 children with idiopathic dystonia. Baclofen** is generally well tolerated by children. The most common adverse events include fatigue, nausea, constipation, somnolence, and dizziness. High doses of baclofen** may exacerbate axial hypotonia [85, 86]. Given its poor BBB penetration when taken orally, intrathecally administered baclofen via a pump has a greater effect on spasticity and dystonia.

Comments: Greene et al. found that 16% of patients (children and adults) responded to clonazepam**. The response to therapy was higher in children than in adults. Chuang et al. [88] evaluated 33 patients (children and adults) with hemidystonia and found a 50% response to clonazepam** and diazepam**. Clonazepam** has also been reported to be useful in the treatment of myoclonus-dystonia in children [89, 90]. The most common adverse event of benzodiazepines in children is sedation. Less frequent side effects include behavioral changes, disinhibition, confusion, and respiratory depression [88]. Sudden discontinuation of benzodiazepines can cause exacerbation of dystonia and withdrawal symptoms.

Comments: #Levodopa** is the main treatment for dopa-responsive dystonia and produces a significant clinical effect in these conditions [91, 92]. A trial of #Levodopa** should be conducted with a starting dose for children of 1 mg/kg/day with gradual titration to a target dose of 5–10 mg/kg/day. The drug should be taken for at least 3 months up to a maximum dose of 600 mg/day (if necessary, 10 mg/kg/day) in every child with an unknown cause of dystonia [92, 93]. One randomized crossover study evaluated the efficacy of levodopa in CP and dystonia [94]. The side effect profile in children is generally favorable. The most common side effects include nausea, dizziness, behavioral changes, insomnia, and orthostatic hypotension. Not all children with dopa-responsive dystonia respond well to #Levodopa**: up to 36% of children with tyrosine hydroxylase deficiency do not respond to this treatment [95]. #Levodopa** should be prescribed in combination with a dopa decarboxylase inhibitor (carbidopa), usually in a 4:1 ratio. In addition, depending on the genetic cause of dopa-responsive dystonia, additional treatment with monoamine oxidase B inhibitors, antidepressants, tryptophan, and carbidopa may be required. This is particularly typical for autosomal recessive forms of dopa-responsive dystonia [96, 97].

Comments:  #Tetrabenazine**is mainly used to treat chorea and other hyperkinetic movement disorders in adults and children [98]. Most adverse events of#Tetrabenazine**are dose-dependent: sedation, behavioral changes, depression, movement difficulties, nausea, and parkinsonism [99]. Notably,#Tetrabenazine**has never been associated with tardive dystonia, making it a good option for pediatric patients.

Comments: Botulinum toxin type A preparations (botulinum therapy) in children with dystonia are approved for patients aged 12 years and older with blepharospasm [100] and for patients aged 2 years and older for the treatment of sialorrhea and upper and lower limb spasticity [101]. The dosage of botulinum toxin type A** depends on body weight and the muscle group into which the drug is injected. Currently, there are no standard dosage recommendations for botulinum toxin in children with dystonia. The injection dose is often determined based on data obtained from adults with focal dystonia and children with spasticity [102, 103, 104, 105, 106]. The average interval between injections is 3–6 months. Two to four treatment cycles may be required to fully optimize the response.

3.2 Surgical Treatment

Comments: The primary anatomical target for stimulation (DBS – Deep Brain Stimulation, neuromodulation) is the internal globus pallidus, although stimulation of the ventrolateral thalamus and subthalamic nucleus is also considered. It has been noted that the course of dystonia following implantation of the stimulation system has certain features: dystonic movements (including phasic, myoclonic, and tremulous movements) regress immediately within hours or days postoperatively, whereas the severity of dystonic postures (tonic components of the disorder) decreases more slowly over weeks or months [107, 108, 109, 110]. The efficacy of treatment for primary dystonia is 40–90%, while for secondary dystonia the results are less predictable [109, 111]. Long-term evaluation of postoperative outcomes in cervical dystonia (including head tremor and myoclonus, prominent phasic dystonic movements, sagittal and lateral head tilts) at 1–2 years demonstrated a 50–70% reduction in disease severity, a 60–70% reduction in patients' disability, and a 50–60% reduction in pain [111, 112]. DBS is a good therapeutic option for primary generalized and segmental dystonia when adequate improvement has not been achieved with pharmacotherapy or botulinum toxin treatment. DBS is a good therapeutic option for cervical dystonia when adequate improvement has not been achieved with pharmacotherapy or botulinum toxin treatment. DBS is generally less effective in secondary dystonias, with the exception of delayed-onset dystonia. DBS requires specialized expertise and a multidisciplinary team. This procedure may have side effects.

3.2.1. Surgical treatment of dystonia in children

Comments: Data regarding deep brain stimulation in children are rapidly accumulating in the scientific literature. Over the past few years, several systematic reviews have been published summarizing the existing literature on deep brain stimulation in pediatric dystonia and status dystonicus. To date, deep brain stimulation (DBS) is a targeted therapy that continues to evolve as a treatment option for children with medically refractory dystonia of various etiologies [115, 116, 117, 118].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: according to several studies, patients with writer's cramp and other forms of focal dystonia show improved motor function after physical therapy, sensory retraining, and motor learning.

Treatment strategies for dystonia depend on the focal, segmental, or generalized distribution of symptoms. Chemodenervation with #botulinum toxin type A** remains the treatment of choice for focal, multifocal, and segmental dystonia. Electromyography improves injection accuracy and can reduce the number of injections, frequency, side effects, and costs by precisely identifying dystonic muscle activity. The characterization of dystonia as a sensory disorder has prompted the use of non-invasive neuromodulation procedures. These methods require further study, but the simultaneous use of rehabilitation techniques improves treatment outcomes. Pallidal deep brain stimulation is useful for medically refractory primary generalized and, potentially, focal dystonia, such as cervical dystonia [120].

Comments: according to the results of a randomized study involving 32 patients with dystonia who received a multidisciplinary 1-week inpatient rehabilitation program with daily physical exercise, occupational retraining, speech therapy, and psychotherapy interventions, an improvement in symptoms according to the CGI scale (Appendix G3) was noted in 86.7% of patients, with these parameters maintained in 69.2% after 6 months of follow-up.

Comments: cautious interpretation of physical therapy efficacy as an adjuvant treatment is required. Further high-quality studies are needed before conclusions can be drawn. Studies report improvements in head posture, pain reduction, increased cervical range of motion, and enhanced quality of life.

Comments: Based on a systematic review published in Movement Disorders Clinical Practice in 2018, an analysis of scientific data on the use of various rehabilitation methods for patients with focal dystonia was performed, grouped into 6 categories: (1) motor practice, (2) constraint-induced movement therapy, (3) sensory reorganization, (4) normalization of muscle activity using external methods, (5) neuromodulation with training, and (6) compensatory strategies. It was concluded that goal-directed motor practices and neuromodulation methods combined with intensive motor training are the priority rehabilitation methods for patients with focal forms of dystonia.

4.1. Medical rehabilitation of pediatric dystonia

In children, the course of dystonia may be influenced by ongoing brain maturation and plasticity; dystonia impedes motor development and the consolidation of correct motor skills; at the same time, children's limited cognitive and social skills can complicate rehabilitation tasks [125]. All children with dystonia require comprehensive rehabilitation by a multidisciplinary therapeutic team, including a physical therapist, a physical and rehabilitation medicine physician, an exercise therapy physician, a medical massage and rehabilitation nurse, an occupational therapist, and, in many cases, speech therapists (with the development of an individual speech therapy rehabilitation program) and psychologists. Specific treatment modalities should be tailored to the individual needs of the child and their family [126].

Comments: Two recent studies investigated the efficacy of visual hand muscle biofeedback in children with dystonia [127, 128]. In children with dystonia, biofeedback training significantly reduced synkinesis and task-unrelated muscle overactivity. A recently published study of 10 children with dystonia reported significant improvement in hand function after using EMG biofeedback for 5 hours a day for 1 month [129].

5. Prevention and Dispensary Observation

There is no effective prevention for dystonia.

6. Organization of Medical Care

Medical care, with the exception of medical care provided as part of clinical trials, in accordance with Federal Law No. 323-FZ dated November 21, 2011, "On the Basics of Protecting the Health of Citizens in the Russian Federation," is organized and provided:

1. in accordance with the regulations on the organization of medical care by types of medical care, which is approved by the authorized federal executive body;

2. in accordance with the regulations on the provision of medical care in the specialty "neurology", mandatory for application across the Russian Federation by all medical organizations; based on these clinical guidelines;

3. taking into account the standards of medical care approved by the authorized federal executive body.

Indications for hospitalization in a medical organization in an emergency or urgent form are:

1. presence of complications of dystonia requiring specialized medical care in emergency and urgent forms;

2. presence of complications of dystonia treatment (surgical intervention, pharmacotherapy).

Indications for hospitalization in a medical organization in a planned form are:

1. the need for surgical intervention (deep brain stimulation for patients with various types of dystonia, microvascular decompression of the 7th cranial nerve root in case of neurovascular conflict in hemifacial spasm, etc.);

2. the need for botulinum therapy in severe forms of dystonia requiring monitoring in an inpatient or day-care setting;

3. the presence of indications for combined treatment (surgical methods, botulinum therapy) requiring monitoring in an inpatient or day-care setting.

Indications for discharging a patient from a medical organization are:

1. completion of the course of treatment or one of the stages of specialized medical care in an inpatient or day-care setting, provided there are no treatment complications requiring drug correction and/or medical interventions;

2. refusal of the patient or their legal representative from specialized medical care in an inpatient or day-care setting established by a medical panel of the healthcare organization providing medical care, provided there are no complications of the underlying disease and/or treatment requiring drug correction and/or medical interventions in an inpatient setting;

3. the need to transfer the patient to another medical organization of the appropriate profile for medical care. The conclusion on the feasibility of transferring the patient to a specialized medical organization is made after a preliminary consultation based on the provided medical documents and/or a preliminary examination of the patient by medical specialists of the planned receiving medical organization.

7. Additional Information

The International Classification of Functioning, Disability and Health (ICF) can be used as an optimal tool for practical patient management and evaluation of the outcomes of the chosen therapeutic strategy [130]. The application of the ICF approaches to classifying impaired body functions and structures, activity, and participation (functioning) allows describing the patient's health and environment with a high degree of individualized detail from biological, psychological, and social perspectives, as well as determining their need for medical and social assistance. The structure of the ICF is represented by two parts: "functioning and disability" and "contextual factors". The "functioning and disability" part in turn includes 4 domains: body functions and structures, activity, and participation (Tab. 4).

Table 4. Structure of the International Classification of Functioning

Example of ICF application in clinical practice for CD therapy

Patient F. - age 63

Diagnosis: CD, laterocollis

Main problems:

• Pain

• Dystonia symptoms

• After the specified time interval, the specified parameter is evaluated. In this case, the patient shows positive dynamics in pain reduction, thanks to the appropriate choice of therapy (injections of botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex**.);

• Based on the degree of success in achieving the goal, the chosen therapy method can be evaluated and a further treatment plan can be drawn up.

The ICF is a fundamental tool for assessing the quality of medical care, allowing the evaluation of the quality and effectiveness of the chosen therapy strategy [21].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Orlova Olga Ratmirovna, Head of the Working Group, MD, Professor, Department of Nervous Diseases, Institute of Professional Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University); President of the Interregional Public Organization of Botulinum Therapy Specialists (MIOBTS)

2. Vera V. Alferova, MD, DSc, Leading Researcher at the Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Member of the Presidium of the All-Russian Society of Neurologists.

3. Artemiev Dmitry Valerievich, PhD, Associate Professor, Department of Neurology with a Course of Reflexology and Manual Therapy, Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation

4. Batysheva Tatiana Timofeevna, MD, Professor, Chief freelance pediatric specialist in rehabilitation of the Ministry of Health of the Russian Federation, Chief freelance pediatric neurologist of the Moscow Healthcare Department, Honored Doctor of Russia, Director of the Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Healthcare Department, Head of the Department of Neurology, Rehabilitation and Child Psychology, FSMO MI RUDN.

5. Bykova Olga Vladimirovna, MD, Head of the Research Department, Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Healthcare Department, Professor of the Department of Neurology, Physical and Rehabilitation Medicine and Child Psychology, FSMO MI RUDN.

6. Gekht Alla Borisovna, MD, Professor, Director of the Z.P. Solovyov Psychoneurological Clinical Center of the Moscow Healthcare Department, Professor of the Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Member of the Presidium of the National Stroke Association, Scientific Secretary of the All-Russian Society of Neurologists.

7. Guzeva Valentina Ivanovna, MD, Professor, Corresponding Member of the Russian Academy of Natural Sciences, Head of the Department of Neurology, Neurosurgery and Medical Genetics, Saint Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation. Chief freelance pediatric neurologist of the Ministry of Health of the Russian Federation.

8. Viktoria V. Guzeva, MD, DSc, Professor, Professor at the Department of Neurology, Neurosurgery and Medical Genetics, Saint Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation.

9. Guzeva Oksana Valentinovna, MD, Professor, Professor of the Department of Neurology, Neurosurgery and Medical Genetics, Saint Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation.

10. Dmitriev Alexander Borisovich, PhD, Head of the Department of Functional Neurosurgery, Federal Center of Neurosurgery of the Ministry of Health of the RF (Novosibirsk)

11. Zalyalova Zuleikha Abdullazyanovna, MD, Professor of the Department of Neurology and Rehabilitation, Kazan State Medical University of the Ministry of Health of the Russian Federation, Head of the Republican Clinical Diagnostic Center for Extrapiramidal Pathology and Botulinum Therapy

12. Zakharov Denis Valerievich, MD, Leading Researcher, Head of the Department of Rehabilitation of Psychoneurological Patients, V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology

13. Ivanova Galina Evgenievna, MD, Professor, Chairperson of the Union of Rehabilitologists of Russia, Chief Freelance Rehabilitation Specialist of the Ministry of Health of the RF

14. Klimov Yury Andreevich, PhD, Dean of the Faculty of Medicine, MVSh RGSU

15. Konovalova Zagidat Narimanovna, PhD, Neurologist, Central Institute of Botulinum Therapy and Actual Neurology (CIBAN), Honored Doctor of the Republic of Dagestan.

16. Kostenko Elena Vladimirovna, Deputy Chair of the Working Group, MD, Professor, Department of Neurology, Neurosurgery and Medical Genetics, Department of Public Health and Healthcare named after Acad. Yu.P. Lisitsyn, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Deputy Director for Scientific Work, Moscow Scientific and Practical Center for Medical Rehabilitation, Restorative and Sports Medicine named after S.I. Spasokukotsky of the Moscow Healthcare Department

17. Kotlyarov Valery Viktorovich, PhD, Head of the Medical Methodology Department, NMF "Neurotech", Neurologist at the Pyatigorsk Medical Center "Polyclinika"

18. Krasavina Diana Alexandrovna, MD, Professor, Head of the Department of Traumatology, Orthopedics, ITU, Prosthetics and Rehabilitation, Saint Petersburg Institute of Advanced Training for Expert Physicians of the Ministry of Labor of Russia

19. Nezdorovina Victoria Gennadievna, PhD, Head of Neurosurgical Department No. 2, A.L. Polenov Russian Neurosurgical Institute – branch of the V.A. Almazov National Medical Research Center (Saint Petersburg).

20. Pavlov Nikolay Alexandrovich, PhD, Leading Researcher, Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Member of the Presidium of the All-Russian Society of Neurologists.

21. Pokhabov Dmitry Vladimirovich, MD, Professor of the Department of Nervous Diseases with a Postgraduate Training Course, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Ministry of Health of the Russian Federation, Director of the Center for Innovative Neurology, Extracapsular Disorders and Botulinum Therapy, FSCC FMBA of Russia

22. Timerbaeva Sofia Leonidovna, MD, Neurologist, National Medical Research Center "Rehabilitation Center" of the Ministry of Health of the Russian Federation, Vice-President of the MIOBTS

23. Alexey A. Tomskiy, PhD in Medicine, Senior Researcher, Head of the Functional Neurosurgery Group, National Medical Research Center for Neurosurgery named after Academician N.N. Burdenko of the Russian Ministry of Health

24. Anatoly D. Fesyun – MD, PhD, Acting Director, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health

25. Dina R. Khasanova, MD, PhD, Professor, Chief Angioneurologist of the Ministry of Health of the Republic of Tatarstan, Professor at the Department of Neurology and Neurosurgery of the Faculty of Advanced Training and Professional Retraining of Specialists, Kazan State Medical University of the Russian Ministry of Health, Board Member of the National Stroke Association.

26. Svetlana E. Khatkova, MD, PhD, Professor, Head of the Department of Rehabilitation for Central and Peripheral Nervous System Disorders, Chief Freelance Neurologist, National Medical Research Center «Lechebno-Reabilitatsionny Tsentr» of the Russian Ministry of Health

27. Rafiz K. Shikhkerimov, MD, PhD, Neurologist, City Polyclinic No. 166 of the Moscow Healthcare Department, Chief Neurologist of the Southern Administrative Okrug of Moscow

28. Nikolay N. Yakhno, MD, PhD, Academician of the RAS, Department of Nervous Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Conflict of interest

The members of the working group declared no financial or non-financial conflicts of interest regarding the topic of these clinical guidelines. Working group member(s) who reported circumstances that could potentially lead to a conflict of interest were excluded from the discussion of sections related to the conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Neurologists

2. Neurosurgeons

3. Ophthalmologists

4. Medical rehabilitation physicians

5. Internists

6. General practitioners (family physicians)

7. Otolaryngologists

8. Pediatricians

9. Trauma and orthopedic surgeons

10. Dentists

11. Related specialists

Table P1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table P2. Scale for assessing levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table P3. Scale for assessing grades of recommendation (GR) for methods of prevention, diagnostics, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Appendix A3. Reference Materials

Treatment of dystonia is a set of medical and psychological measures aimed at achieving complete or partial remission of dystonia symptoms, which should include early and timely diagnosis of the disease, correction of possible functional impairments, prevention and reduction of potential disability, improvement of quality of life, preservation of the patient's working capacity, and social adaptation into society.

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Order of the Ministry of Health of the Russian Federation No. 926n dated November 15, 2012, «On Approval of the Procedure for Providing Medical Care to Adult Patients with Nervous System Diseases»;

2. Order of the Ministry of Health of the Russian Federation No. 1047n dated December 14, 2012, «On Approval of the Procedure for Providing Medical Care to Children in the Profile "Neurology»;

3. Order of the Ministry of Health of the Russian Federation No. 788n dated July 31, 2020, «On Approval of the Procedure for Organizing Medical Rehabilitation for Adults».

4. Order of the Ministry of Health of the Russian Federation No. 878n dated October 23, 2019, «On Approval of the Procedure for Organizing Medical Rehabilitation for Children»

Current instructions for medicinal products mentioned in these clinical guidelines can be found on the website http://grls.rosminzdrav.ru.

Appendix B. Physician Action Algorithms

Algorithms of the physician's actions in managing a patient with dystonia

Appendix C. Patient Information

Dystonia is a neurological disorder with a likely genetic predisposition and low penetrance. Involuntary movements, abnormal postures, muscle spasms, and pain syndrome—the main manifestations of dystonia—are treatable with botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex**. The goal of therapy is to achieve sustained remission and restore (maintain) social activity. Botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** are reversible blockers of synaptic transmission in cholinergic and other synapses, local intramuscular injection of which leads to prolonged relaxation of the injected muscles and reduction of pain syndrome. Following intradermal administration of botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex**, a decrease in sweating is observed in the injection area. The safety and efficacy of botulinum toxin therapy are confirmed by international evidence-based studies. The duration of the effective action of an injection can be 2 to 4 months (in some cases up to 6 months), after which repeat treatment courses are possible/necessary (2 to 6 botulinum toxin procedures per year). A positive effect is observed on days 7 to 14 (up to 21 days) after the injection. Within 1 to 30 days after the injections, temporary non-serious adverse events are possible (their manifestations depend on the injection site): injection site pain, headache, general weakness, weakness of the injected muscles, swallowing difficulties, upper eyelid weakness, microhematomas, dry eye, blurred vision, allergic reactions (edema, rash, flu-like symptoms), and other symptoms specified in the package inserts for botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** preparations. According to international studies, in a small proportion of cases, low sensitivity (insensitivity) to botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** preparations, as well as reduced efficacy after repeated injections, is observed. Medical contraindications (restrictions) to botulinum toxin therapy include: known hypersensitivity to any of the components of the drug; neuromuscular transmission disorders (myasthenia gravis, myasthenic and myasthenoid syndromes); treatment with aminoglycoside antibiotics 1 week before and 2 weeks after the injection; blood clotting disorders; pregnancy, breastfeeding; acute illness and the exacerbation phase of chronic diseases; local inflammatory process at the injection site.

Additional recommendations after the procedure and measures to improve the outcomes of botulinum therapy: perform active movements with the injected muscles during the first hours after injection; lying down is not recommended for 3–4 hours after the procedure; do not heat the injection area and limit alcohol intake for 7 days after injection; do not cool the injection area. In case of adverse events, report them to the physician who performed the injection or the physician providing follow-up care. Upon recurrence of dystonia symptoms and/or appearance of new symptoms, consult the attending physician to address the administration of the next dose of type A botulinum toxin** or type A botulinum toxin-hemagglutinin complex**. All recommendations of the attending physician regarding rehabilitation and prevention of dystonia, as well as additional recommendations, should be followed [1, 3, 32].

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Toronto Western Spasmodic Torticollis Rating Scale

Russian title: Toronto Western Spasmodic Torticollis Rating Scale

Original title: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Source: Consky E.S, Basinski A., Belle L. et al. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): assessment of validity and inter-rater reliability // Neurology. – 1994. – N 40. – P. 445. [27].

Not validated in the Russian Federation.

Type: rating scale.

Purpose: assessment of the severity of spasmodic torticollis symptoms

Content (Template)

Key (interpretation): The scale includes 3 subscales allowing the assessment of separate aspects of cervical dystonia: severity (0–35 points), disability (0–30 points), and pain (0–20 points). Each subscale of the TWSTRS is assessed independently, and then the scores are summed up so that the final total score can range from 0 to 85, reflecting the sum of the scores across the 3 subscales [25, 131]

Notes. Use of the scale requires specialized training. Scoring on the scale before and after botulinum toxin therapy allows evaluation of treatment efficacy

Appendix G2. Visual Analog Scale for Pain Assessment

Russian title: Visual Analog Scale for Pain VAS

Original title: Visual Analog Scale for Pain (VAS Pain)

Source: J Clin Nurs. 2005 Aug;14(7):798-804. doi: 10.1111/j.1365-

2702.2005.01121.x. Pain: a review of three commonly used pain rating scales Amelia Williamson 1, Barbara Hoggart. [132].

Affiliations expand DOI: 10.1111/j.1365-2702.2005.01121.x

Official developer website: The Visual Analog Scale (as a graphical rating scale) was first published in 1921 by Hayes & Patterson as a new method for supervisors to evaluate workers; two years later, Freud presented a more detailed list of pros and cons of visual analog scales. - https://deru.xcv.wiki/wiki/Visuelle_Analogskala

The scale is validated in the Russian Federation; specialized training is required for its use.

Source: Methodological recommendations for the Pilot Project "Development of the Medical Rehabilitation System in the Russian Federation" "Practical Application of Rating Scales in Medical Rehabilitation", 2015-2016, p. 91

Type: rating scale.

Purpose: assessment of pain intensity

Content (template): The VAS is a 10 cm straight line. Its beginning corresponds to the absence of pain sensation – "no pain" – and the endpoint reflects excruciating, unbearable pain – "worst imaginable pain". The line can be either horizontal or vertical. The patient is asked to make a mark on it corresponding to the intensity of pain they are currently experiencing. The distance between the beginning of the line ("no pain") and the mark made is measured in centimeters and rounded to the nearest whole number. Each centimeter on the line corresponds to 1 point.

Key (interpretation): The VAS for pain is used to assess pain intensity without regard to its causes and localization. It is a subjective tool for pain assessment and is primarily used for managing patients with pain.

If the patient has a pain syndrome, they should be encouraged to keep a pain diary (twice a day, morning and evening, assess pain intensity using the VAS and record it). Using a pain diary helps the patient better understand their pain problem and thus accelerates the process of relief from it. In other words, using a diary not only objectifies the patient's pain and distress but also has a therapeutic effect.

Notes. It should be noted by the neurologist that when assessing pain with the VAS, it is necessary to clearly explain what constitutes maximum pain intensity and what constitutes its complete absence. Thus, 0 points are given when the patient has no unpleasant sensations and distress related to pain and is in a good mood. 10 points represent very severe pain that is impossible to tolerate. It is so severe that it prevents the patient from moving or speaking.

At a mark up to 2 cm, pain is classified as mild, from 2 to 4 cm as moderate, from 4 to 6 cm as severe, from 6 to 8 cm as very severe, and up to 10 cm as unbearable. As a rule, all patients, including children over 5 years old, easily learn the VAS, but patients sometimes find it difficult to represent their pain level as a point on a straight line. In this situation, it is better to use the Numerical Rating Scale for pain

Appendix G3. Clinical Global Impression Scale

Russian title: Clinical Global Impressions scale

Original title: Clinical Global Impression Scale

Sources: Spearing M.K., Post R.M., Leverich G.S. et al. Modification of the Clinical Global Impression (CGI) scale for use in bipolar illness (BP): the CGI-BP // Psychiatr. Res., 1997; Zaider TI, Heimberg RG, Fresco DM, Schneier FR, Liebowitz MR. Evaluation of the clinical global impression scale among individuals with social anxiety disorder. Psychol Med 2003; 33(4):611–22. [133].

Not validated in the Russian Federation

Type: rating scale

Purpose: serves as a measure of symptom severity, treatment response, and treatment efficacy in clinical practice and research. It is intended to assess patient functioning before and after the initiation of pharmacotherapy. The scale includes 3 assessment items: 1) Severity of Illness (CGI-S), 2) Global Improvement (CGI-I), and 3) Efficacy Index (CGI-E, which is a measure of the therapeutic effect and side effects characteristic of the administered drugs [73].

Content (template):

1. Considering your general clinical experience with this specific category of patients, how severe would you rate the current psychiatric disorder of this patient?

   Scores Disorder Severity Degree

   0. Not assessed

   2. Borderline mentally ill

   3. Mildly ill

   4. Moderately ill

   5. Markedly ill

   6. Severely ill

   7. Among the most extremely ill patients

2. Rate total improvement, whether or not you believe it is entirely due to drug treatment. Assess how much the patient's condition has changed compared to their baseline state.

   Scores Global Improvement Rating

   0. Not assessed

   1. Very much improved

   2. Much improved

   3. Minimally improved

   4. No change

   5. Minimally worse

   6. Much worse

   7. Very much worse

3. Efficacy Index: rate this item based solely on the effect of the medication. Select the conditions that best describe the degree of therapeutic effect and side effects, and record the number in the box where these two metrics intersect.

Example: therapeutic effect is rated as "moderate", and side effects are rated as "do not significantly affect the patient's functional status".

Therapeutic effect

Side effects

None Do not affect

Affect

Significant Significant 1 2 3 4 improvement.

Complete or near-complete remission of all symptoms Moderate Moderate 5 6 7 8 improvement.

Partial remission of symptoms Minimal

Minimal 9 10 11 12 improvement that does not alter patient care status

Unchanged or worse 13 14 15 16 Note: 0 – no assessment

Key (interpretation): The CGI is rated on a 7-point scale, with the severity of illness scale using a response range from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients).

CGI-C (Clinical Global Improvement or Change) ratings range from 1 (Very much improved) to 7 (Very much worse).

Notes. Assessment of treatment response should take into account both therapeutic efficacy and treatment-related adverse events, and ranges from 0 (Significant improvement and no side effects) to 4 (Unchanged or worse and side effects outweigh the therapeutic effect). Each CGI item is assessed separately; the scale does not calculate a total score.

Complexity of botulinum toxin injection procedures in the treatment of dystonias

The procedure of treating various types of dystonia using botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** is a complex, high-tech medical care method that requires special conditions and equipment, as well as highly qualified specialists. The physician performing the injection of botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** must possess high-level knowledge and practical skills, and undergo specialized training in injection administration and related techniques. Preparation for the injection must include the use of modern clinical assessment methods for dystonia (using specialized rating scales), the ability to select target muscles for injections and determine the dosage regimen of the drug, and identifying the need for concomitant treatment modalities. The preparation process for the injection should take a sufficient amount of time due to its direct correlation with the success of the procedure. A particularly important component of the procedure is the use of injection guidance methods. The medical institution must be equipped with special devices that allow for high-precision injections (EMG machine, ultrasound machine). The physician must be proficient in operating visualization equipment to ensure injection accuracy. Thus, the procedure of administering botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** for the treatment of various types of dystonia is a manipulation that requires significant time expenditure, necessary technical equipment, and a qualified specialist [23, 51, 52, 134, 135].