Neuromuscular scoliosis: clinical guidelines

List of Abbreviations

ALT – alanine aminotransferase

AST – aspartate aminotransferase

BiPAP – Biphasic Positive Airway Pressure, BPAP, BiPAP

CPAP – Constant Positive Airway Pressure, CPAP

VAS – Borg visual analogue scale

DAG – dystrophin-glycoprotein complex

RF – respiratory failure

DNA – deoxyribonucleic acid

CP – cerebral palsy

FVC – forced vital capacity

ACE inhibitor – angiotensin-converting enzyme inhibitor (ATX C09AA ACE inhibitors)

MV – invasive mechanical ventilation

kDa – kilodalton

CT – computed tomography

CK – creatine phosphokinase (synonym – creatine kinase)

ABG – arterial blood gas composition

LDH – lactate dehydrogenase

INR – international normalized ratio

MRI – magnetic resonance imaging

NIV – non-invasive ventilation

NMD – neuromuscular diseases

FEV1 – forced expiratory volume in the first second of the forced expiration maneuver

MUAP – motor unit action potentials

BMD – Becker muscular dystrophy

DMD – Duchenne muscular dystrophy

PEF – peak expiratory flow

PCF – peak cough flow

RNA – ribonucleic acid

SMA – spinal muscular atrophy

SMA I – spinal muscular atrophy, type I

ATD – assistive technology devices

FSI FSBSI «Research Centre for Medical Genetics» of the Ministry of Science and Higher Education of the Russian Federation

FVC – functional vital capacity

CP – cerebral palsy

ECG – electrocardiography

EMG – electromyography

ENMG – electroneuromyography

EchoCG – echocardiography

GMFCS – Gross Motor Function Classification System, Scale of global motor impairments

CFCS – Communication Function Classification System

MACS – Manual Ability Classification System

MFM – Motor Function Measure, scale for assessing motor function in patients with neuromuscular diseases

HFMSE – Hammersmith Functional Motor Scale Expanded, expanded Hammersmith functional motor scale for SMA patients

RULM – Revised Upper Limb Module in SMA

Terms and Definitions

Amyotrophy (Friedreich's ataxia, Charcot-Marie-Tooth disease, Roussy-Levy syndrome): equinus foot deformity (clubfoot), kyphoscoliosis; gait and handwriting disturbance, dysarthria, leg weakness; hearing impairment and loss, impaired deep sensation, progressive muscle atrophy, optic atrophy, cataract, pelvic organ dysfunction, dementia, diabetes mellitus, hypogonadism, rhythm disorders, atrioventricular and intraventricular conduction abnormalities. Population frequency: 2.7:100,000. Sex ratio: unknown. Inheritance type: autosomal recessive [113].

Congenital structural myopathies are a heterogeneous group of genetically determined diseases with various inheritance types and a variety of clinical courses. Muscle function is impaired. Common features of congenital structural myopathies include early onset (from birth or the first months of life), generalized muscle hypotonia, decreased or absent tendon reflexes, muscle atrophy, and skeletal structural anomalies. As a rule, a non-progressive course.

Hyperkyphosis – exceeding the limits of normal parameters of the thoracic spine in the sagittal plane (>40°).

Hypokyphosis – flattening of the thoracic kyphosis beyond the lower limit of its normal parameters (<20°), but without the formation of a thoracic lordosis.

Gibbus – sharp-peaked angular kyphosis.

Kyphosis – change in the shape of a spinal segment in the sagittal plane with the formation of a deformity, with a posteriorly facing convexity; abnormal kyphosis.

Kyphoscoliosis – a combination of scoliotic deformity with true hyperkyphosis. Rotational deformity combined with apparent kyphosis should not be designated by this term.

Spinal correction and instrumental fixation – a surgical intervention during which correction and stabilization of spinal segments are performed using fixation devices.

Muscular dystrophy – Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive disorders characterized by progressive proximal muscle weakness caused by degeneration of muscle fibers. Becker dystrophy has a later onset and causes milder symptoms.

Muscular dystrophies are a clinically heterogeneous group of disorders that all share the clinical characteristics of progressive muscle weakness. The term "dystrophy", used in its strictest pathological sense, refers to chronic and severe myopathic changes in muscles. Most muscular dystrophies share common pathological features of fibrosis and fatty tissue replacement, especially in the later stages of the disease. A clinically and genetically diverse group of hereditary disorders of the structure of striated muscle, including cardiac muscle, characterized by progressive muscle weakness and wasting. Progressive motor deficit.

Neuromuscular diseases (NMD) are a vast group of genetic heterogeneous diseases whose main clinical manifestations are weakness and atrophy of various muscle groups.

Proximal 5q spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disease characterized by progressive symptoms of flaccid paralysis and muscle atrophy due to degeneration of anterior horn α-motor neurons of the spinal cord [1].

Spinal muscular dystrophies (SMA) are a group of hereditary childhood diseases first described by Werdnig in 1891. The disease manifests as symmetric atrophy of the lower motor neurons of the anterior horns and roots of the spinal cord, which causes progressive paralysis against the background of neuromuscular transmission disorders.

GMFCS is an international classification system of motor functions for patients with cerebral palsy older than two years, which assesses the patient's general functional activity in their usual environment and the degree of its limitation. Crucially, it evaluates the everyday level of activity, rather than the maximum possible level demonstrated only during examination.

The Risser sign is a quantitative test that determines the stage of ossification of the iliac apophysis, which begins at the anterior superior iliac spine and proceeds dorsally toward the posterior superior iliac spine. The process indicates skeletal maturation stages and takes an average of two years. According to Risser, the iliac crest is divided into 4 parts, and the staging is as follows: Risser-0 (absence of the apophyseal shadow), Risser-1 (ossification involving up to 25% of the crest), Risser-2 (ossification involving up to 50% of the crest), Risser-3 (ossification involving up to 75% of the crest), Risser-4 (complete ossification of the crest), Risser-5 (fusion of the apophysis and the iliac body). Risser-4 corresponds to the cessation of spinal growth.

Spina bifida is a failure of closure of the vertebral canal resulting from defective fusion of the vertebral arches (spina bifida posterior) or bodies (spina bifida anterior).

Spina bifida aperta (open spinal dysraphism) is a synonym commonly used for congenital neural tube defects—combined malformations of the spinal canal, spinal cord, and its membranes, including meningomyeloceles, lipomyelomeningoceles, and rachischisis.

Spina bifida occulta (hidden spinal dysraphism) is a failure of fusion of the vertebral arches not accompanied by the formation of a spinal hernia.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Neuromuscular scoliosis is a three-dimensional spinal deformity and an orthopedic complication of a group of neuromuscular disorders characterized by "impaired nerve impulse conduction along the nerve fiber or associated with impaired neuromuscular transmission" [2].

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

Depending on the level of the lesion, neuropathic and myopathic spinal deformities are distinguished [3].

The former are subdivided into disorders affecting the upper motor neuron and the lower motor neuron (Fig. 1). Neuropathic deformities associated with upper motor neuron lesions include scoliosis in patients with cerebral palsy (CP), syringomyelia, and central nervous system tumors. Spinal deformities caused by lower motor neuron lesions may result from poliomyelitis and other viral myelitides, spinal muscular atrophies, and other conditions. As a rule, spinal deformity in these pathologies is progressive in nature [4, 5].

Myopathic spinal deformities can occur in muscular dystrophies (Duchenne muscular dystrophy, merosin-deficient congenital muscular dystrophy) and myasthenia gravis.

Additionally, neuromuscular scoliosis (kyphoscoliosis) can develop both secondary to a spinal cord tumor and following its resection without adequate spinal stabilization [6]. In such states, it is appropriate to refer to it as denervating or paralytic (kyphoscoliosis). Following surgical treatment of spinal tumors, a deformity similar in character to post-laminectomy or post-traumatic deformity may develop [7, 8].

1.3 Epidemiology of the Disease or Condition

The incidence of spinal deformity depends on the underlying neuromuscular disease and the severity of its manifestations [9].

Table 1. Prevalence of spinal deformities in neuromuscular diseases

The total prevalence of neuromuscular diseases is approximately 1 in 3,000–3,500 of the population across various global populations [10, 11, 12]. Currently, the federal register of the Russian Federation contains over 1,300 patients; however, extrapolating these statistics to the population of the Russian Federation suggests there are approximately 48,000 patients with neuromuscular diseases in the country. Progressive muscular dystrophies and spinal amyotrophies are the most common disorders in this group (13–33 patients per 100,000 population and 10 patients per 100,000 population, respectively [12]).

The prevalence of proximal spinal muscular atrophy is 1 in 6,000–10,000 newborns [13]. Data on the prevalence of this disease in the Russian Federation are lacking. The carrier frequency in the general population is 1/40–1/50 [14, 15]. According to the Research Centre for Medical Genetics (Ministry of Science and Higher Education of the Russian Federation), the carrier frequency of spinal muscular atrophy in Russia is 1 in 36 individuals, with an estimated incidence of 1 in 5,184 newborns [16].

Scoliosis is highly prevalent in children with type 1 and type 2 spinal muscular atrophy, with an incidence of 60–90% and onset in early childhood [17, 18].

The overall incidence of scoliosis in the cerebral palsy population ranges from 21% to 76%, depending on the case series and the severity of cerebral palsy [11, 12, 19, 20, 21, 22]. Curves are typically under 40°, but the magnitude of scoliosis depends on the severity of cerebral palsy [11]. The incidence of scoliosis increases with age and decreased mobility. Persson-Bunke M. et al. found that the risk of developing scoliosis increases with advancing age in patients with cerebral palsy and higher GMFCS levels (patients with cerebral palsy and GMFCS levels IV–V have a 50% risk of clinically moderate or severe scoliosis by age 18) [20]. Hägglund G. et al. showed that 8% of patients with GMFCS level V had clinical signs of scoliosis by age 5, and 75% of patients with GMFCS level V developed a spinal deformity with a Cobb angle ≥40° by age 20 [23].

Lumbar hyperlordosis or thoracic kyphoscoliosis are also frequently observed in cerebral palsy [22]. The natural history of scoliosis progression in patients with cerebral palsy indicates that flexible spinal deformity begins between 3 and 10 years of age, with rapid progression to rigid scoliosis [19]. Gu Y. et al. determined that patients with quadriplegic cerebral palsy and a deformity >40° by 12 years of age had a higher probability of progression compared to those with a curve ≤40° at the same age [24].

The prevalence of Friedreich ataxia in Caucasians is estimated at 1/20,000 to 1/50,000, and scoliosis develops in 60–79% of patients [25].

In patients with Duchenne muscular dystrophy who do not receive glucocorticoids, the probability of developing severe progressive scoliosis is approximately 90% [26, 27], whereas the probability of osteoporosis-induced vertebral compression fractures is low. Daily glucocorticoid therapy has been shown to reduce the risk of scoliosis [28, 29], although the risk of vertebral fractures increases [30, 31].

1.4 Features of Coding the Disease or Condition

M41.4 – Neuromuscular scoliosis. Scoliosis due to cerebral palsy, Friedreich ataxia, poliomyelitis, and other neuromuscular disorders.

In these clinical guidelines, aspects of the course of various neuromuscular diseases are considered solely within the framework of risk assessment, preoperative evaluation, and intra- and postoperative patient management.

1.5 Classification of the disease or condition

The most comprehensive etiological classification of scoliosis, kyphosis, and lordosis was presented by Lonstein E.J. et al. (1995) [32]:

I. Idiopathic

A. Infantile (0 to 3 years):

1. resolving;

2. progressive.

B. Juvenile (3 to 10 years).

C. Adolescent (older than 10 years).

II. Neuromuscular

A. Neuropathic:

1. Upper motor neuron lesions:

a. cerebral palsy;

b. spinocerebellar degeneration:

1) Friedreich disease;

2) Charcot-Marie-Tooth disease;

3) Roussy-Levy syndrome;

c. syringomyelia;

d. spinal cord tumor;

e. spinal cord injury;

f. other causes.

2. Lower motor neuron lesions:

a. poliomyelitis;

b. other viral myelitides;

c. trauma;

d. spinal muscular atrophies:

1) Werdnig-Hoffmann disease;

2) Kugelberg-Welander disease;

3) myelomeningocele (paralytic).

3. Dysautonomia (Riley-Day syndrome).

4. Other.

B. Myopathic.

1. Arthrogryposis.

2. Muscular dystrophy.

3. Congenital hypotonia.

4. Myotonic dystrophy.

5. Other.

III. Congenital

A. Disorders of formation.

1. Wedge vertebra.

2. Hemivertebra.

B. Segmentation defects.

1. Unilateral.

2. Bilateral.

C. Mixed anomalies.

IV. Neurofibromatosis

V. Mesenchymal disorders

A. Marfan syndrome.

B. Ehlers-Danlos syndrome.

C. Other.

VI. Rheumatoid diseases

A. Juvenile rheumatoid arthritis.

B. Other.

VII. Post-traumatic deformities

A. Post-fracture.

B. Post-surgical.

1. Post-laminectomy.

2. Post-thoracoplasty.

VIII. Due to extra-spinal contractures

A. Post-empyema.

B. Post-burn.

IX. Osteochondrodystrophic

A. Diastrophic dwarfism.

B. Mucopolysaccharidosis (e.g., Morquio disease).

C. Spondyloepiphyseal dysplasia.

D. Multiple epiphyseal dysplasia.

E. Achondroplasia.

F. Other.

X. Due to osteomyelitis.

XI. Metabolic disorders.

A. Rickets.

B. Osteogenesis imperfecta.

C. Homocystinuria.

D. Other.

XII. Due to lumbosacral junction pathology.

A. Spondylolysis and spondylolisthesis.

B. Congenital lumbosacral anomalies.

XIII. Due to tumors.

A. Of the spinal column.

1. Osteoid osteoma.

2. Histiocytosis X.

3. Other.

B. Of the spinal cord (see neuromuscular scoliosis).

1.6 Clinical presentation of the disease or condition

Clinical manifestations of spinal deformity in NMD are characterized by the development of:

1) scoliosis;

2) kyphosis;

3) kyphoscoliosis;

4) lumbar hyperlordosis;

5) pelvic obliquity;

6) torsional chest deformity.

The main features of the course of NMD are presented in Table 2 [33, 34].

Table 2. Main features of neuromuscular diseases [116]

AD – autosomal dominant; AR – autosomal recessive; XL – X-linked;

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition based on:

1. Anamnestic data – established or suspected neuromuscular disease;

2. Physical examination data – signs of spinal deformity in the frontal or sagittal planes;

3. Laboratory tests – confirmed neuromuscular disease based on genetic testing;

4. Instrumental examination – spinal deformity confirmed by instrumental diagnostic methods.

2.1 Complaints and Anamnesis

• In patients with neuromuscular diseases, for a comprehensive assessment of the patient's status and its dynamics, it is recommended to evaluate:

  – the severity of complaints reported by the patient and their parents (for children);

  – the onset time of spinal deformity and the rate of its progression;

  – the rate of onset and progression of complaints;

  – history of prior treatment;

  – level of physical activity, its conditions and limitations;

  – presence of comorbid conditions;

  – ongoing pharmacotherapy or device dependency and their duration;

  – presence of allergies or drug intolerance [32].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: the first stage of diagnosis is taking the medical history. It is necessary to find out at what age and by whom the spinal deformity was first noticed, whether the patient's parents sought medical attention, whether treatment was carried out, what specific treatment was given, and what the effect was. The child's activity and age-appropriate development are assessed. Available medical documentation, previous treatments, and specialist opinions are evaluated. At this stage, it is already possible to suspect a hereditary genetic syndrome or disease. When dysmorphic stigmata, various external signs of deviation from normal development—such as impaired organ formation, growth abnormalities, changes in hair growth, skin color and moisture, developmental anomalies, and gross deviations from the norm based on general clinical and paraclinical examination results—are identified, the patient is primarily referred for a consultation with a geneticist. If a specific hereditary genetic syndrome or disease is identified, additional diagnostic methods are prescribed to determine the state and function of various organs and systems that may be involved in the pathological process of this disease. If a genetic pathology is already known, the focus in preoperative evaluation is on target organs and systems that may be involved in the underlying disease. Otherwise, the management tactics for syndromic scoliosis, in the absence of gross deviations from the norm, do not differ from those for congenital and idiopathic scoliosis.

The next stage is eliciting the patient's complaints. In spinal deformity surgery, this element of examination takes on special significance. There are usually two main complaints: a cosmetic defect associated with spinal and chest deformity, and pain syndrome, although it is not necessary for the patient to present with both complaints. During the initial conversation with the patient, they may be absent altogether. It should be taken into account that the patient's self-assessment of their appearance is extremely variable. Complaints not immediately related to spinal deformity, such as sleep, appetite, nutrition, fatigue, activity, shortness of breath, mobility and range of motion in joints, and frequency of colds, which may also suggest the need for further examination, are also evaluated.

It is necessary to find out if the patient is bothered by shortness of breath, when it was first noted, under what exertion it occurs, and whether it worsens over the years.

2.2 Physical Examination

• To assess the orthopedic status in all patients with neurogenic spinal deformities, it is recommended to evaluate:

  – frontal and sagittal spinal balance;

  – spinal mobility using the traction test;

  – compensation of pelvic obliquity;

  – postural control independently or using assistive devices (AD);

  – presence and severity of limb contractures;

  – muscle strength using a muscle strength grading scale (Appendix G1);

  – pain using the visual analogue scale (VAS) (if present) (Appendix G2);

  – BMI [3, 12, 13, 22, 33, 58].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Universal functional scales include: Gross Motor Function Classification System – GMFCS (Appendix G3), as well as CFCS (Appendix G4), MACS (Appendix G5), MFM (Appendix G6), and nosology-specific scales: Revised Upper Limb Module – RULM (Appendix G7), Hammersmith Functional Motor Scale Expanded – HFMSE (Appendix G8), which can be optionally applied by neurologists and physical and rehabilitation medicine physicians depending on the underlying disease.

• All patients with suspected or confirmed neuromuscular disease are recommended an initial examination (evaluation, consultation) by a neurologist to assess and document neurological status [3, 12, 13, 22, 23].

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

• All patients with suspected or confirmed neuromuscular disease are recommended an initial examination (evaluation, consultation) by an orthopedic traumatologist to assess and describe orthopedic status [3, 12, 13, 22, 23].

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

Comment: All patients with suspected or confirmed neuromuscular disease should undergo a joint examination by a neurologist and an orthopedic traumatologist for the purpose of diagnosis and coordination of treatment tactics.

• All patients with suspected neuromuscular disease or hereditary genetic pathology are recommended an initial examination (evaluation, consultation) by a geneticist to conduct genetic testing, verify or rule out genetic pathology [3, 12, 13, 22, 23].

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

• Patients with neuromuscular diseases who have comorbid respiratory, cardiovascular, metabolic disorders, etc., are recommended a consultation with a relevant specialist [36, 98, 99, 100, 101].

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

Comment: Consultants' recommendations are implemented solely in agreement with the attending physician, except in situations requiring emergency medical care.

2.3 Laboratory Diagnostics

• Patients with NMD are recommended to undergo clinical, biochemical, and other tests to assess the patient's condition in accordance with the existing clinical manifestations of vertebral and extravertebral pathology [32].

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

• In the outpatient setting, patients with NMD are recommended to undergo the following laboratory tests:

  – blood sodium level test,

  – blood potassium level test,

  – blood chloride level test,

  – determination of ABO blood groups,

  – determination of Rh factor (Rhesus D antigen),

  – determination of hepatitis B virus surface antigen (HBsAg) in the blood,

  – determination of antibodies to hepatitis C virus in the blood,

  – determination of IgM and IgG antibodies to human immunodeficiency virus HIV-1 in the blood,

  – determination of IgM and IgG antibodies to human immunodeficiency virus HIV-2 in the blood,

  – determination of antibodies to Treponema pallidum in non-treponemal tests (RPR, RPR/USR) (qualitative and semi-quantitative test) in blood serum,

  – coagulogram (screening hemostasis test),

  – complete blood count (CBC),

  – general general-medical blood biochemistry test,

  – urinalysis [32].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• In the outpatient setting, patients with NMD are recommended specialist consultations to predict disease progression:

  – pediatric patients require an initial examination (evaluation, consultation) by a pediatrician, while adult patients require an initial examination (evaluation, consultation) by a general practitioner (therapist).

  – initial examination (evaluation, consultation) by a neurologist;

  – initial examination (evaluation, consultation) by a geneticist (if diagnosis is unverified) [205, 206];

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• In the inpatient setting, patients with NMD are recommended to undergo laboratory tests:

  – coagulogram (screening hemostasis test),

  – complete blood count (CBC),

  – general general-medical blood biochemistry test,

  – urinalysis [32, 202].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: other laboratory tests are prescribed by the attending physician based on recommendations from other medical specialists.

• In the inpatient setting, patients with NMD are recommended specialist consultations to assess somatic status and intervention risks:

  – pediatric patients require an initial examination (evaluation, consultation) by a pediatrician, while adult patients require an initial examination (evaluation, consultation) by a general practitioner (therapist).

  – initial examination (consultation) by an anesthesiologist-resuscitologist,

  – initial examination (evaluation, consultation) by a neurologist;

  – consultations with other medical specialists as prescribed by the attending physician [32].

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

2.4 Instrumental Diagnostics

• To determine the tactics of conservative and surgical treatment, all patients with spinal deformity are recommended to undergo:

  – radiography of the cervical spine,

  – radiography of the thoracic and lumbar spine in anteroposterior and lateral projections while standing (if verticalization is possible in ambulatory-stage patients), sitting (if verticalization is possible in early non-ambulatory stage patients), or supine (in late non-ambulatory stage patients),

  – radiography of the pelvis in the anteroposterior projection while supine [3].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: anteroposterior radiographs are recommended to be performed annually for spinal curvature of less than 15-20°, and every 6 months for curvature greater than 20° until skeletal maturity. An interval of more than 1 year between radiographs increases the likelihood that scoliosis progression will go unnoticed. After skeletal maturity, the decision on the need for radiography is re-evaluated based on clinical assessment.

• To determine the tactics of surgical treatment, all patients with spinal deformity are recommended to undergo computed tomography of the spine (prior to surgical intervention) [3]

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: computed tomography provides information on damage to the bone structure of the vertebrae, making it possible to assess the shape and size of the structures of the vertebrae and the spinal canal, which is especially important when planning surgical interventions. Great attention is paid to studying the structural features and torsion of the vertebrae at the apex of the deformity, as well as osteopenia of the caudal lumbosacral spine and pelvis, which determine the scope and planning of the surgical intervention.

• To determine the tactics of surgical treatment, all patients with spinal deformity are recommended to undergo magnetic resonance imaging of the spine (if necessary, prior to surgical intervention) [3].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: MRI provides accurate information on the condition of the spinal cord. The morphology of vertebral syndrome, the presence of myelopathy, and vertebromedullary conflict are identified quite clearly.

• To assess respiratory lung function during the preparation stage for surgical treatment, it is recommended to study unforced respiratory volumes and flows using a peak flow meter, perform remote monitoring of pulmonary function parameters, and undergo spiral CT of the lungs [35, 36].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• It is recommended to perform whole-body and lumbar spine dual-energy X-ray absorptiometry (DEXA) to rule out osteoporosis when preparing for surgical intervention [35, 118].

• with a frequency of 1 time per year

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: given the extremely limited motor activity of patients with NMD, it is important to focus on "bone density". Pronounced osteoporosis (Z-score <-2.5 SD) is a limitation to surgical correction of scoliosis due to the high risk of implant-related complications [122, 123].

Patients with SMA are characterized by a high frequency of fractures and osteopenia. These risks are caused not only by muscle weakness and low mobility of patients, but also by the fact that the SMN gene plays a role in bone tissue metabolism [38].

• For patients with type I 5q SMA, as well as patients with type II SMA, it is recommended to determine the partial pressure of oxygen in soft tissues (oximetry) during night sleep at the slightest suspicion to detect nocturnal hypoventilation and obstructive sleep apnea [39].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: the use of pulse oximetry as the sole method for monitoring nocturnal hypoventilation is considered acceptable when capnography is not available. Normally, saturation levels are within 95-100%. If SpO2 is below 90%, urgent measures must be taken. Saturation between 94-90% is considered borderline. Patients with hypoventilation are recommended to have a pulse oximeter at home.

• Patients with proximal muscle hypotonia and muscle weakness who do not have genetic confirmation of the diagnosis are recommended to undergo magnetic resonance imaging of the muscular system for the purpose of differential diagnosis between 5q SMA and other neuromuscular disorders [40].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: muscle MRI reveals fatty replacement of muscle tissue. A characteristic lesion pattern is visualized—hypertrophy and relative sparing of the adductor longus muscle, which is quite specific for spinal muscular atrophy. However, this specific lesion pattern manifests at a late stage of the disease; at the very onset of the disease and in young children, it is quite difficult to detect.

• All patients with SMA type I and SMA type II older than 5 years with a decrease in forced expiration by 45% or more are recommended to undergo cardiorespiratory monitoring once every 6 months to monitor the progression of respiratory disorders [114].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• Pediatric patients with 5q SMA are recommended to undergo polysomnography if hypoventilation is suspected, to clarify its nature and rule out sleep apneas [41].

GCR ALoE 2Grade of Recommendation A (Level of Evidence – 2).

Comments: patients with SMA are prone to sleep-related breathing disorders, most commonly hypoventilation due to reduced tidal volume, impaired diaphragm function, and decreased function of the intercostal and accessory muscles. There is also obstructive syndrome due to weakness of the laryngeal and pharyngeal muscles, predisposing to upper airway collapse [114].

Patients with NMD are recommended a preoperative respiratory function assessment to determine the risk of respiratory complications (risks of decreased respiratory muscle strength, worsening hypoventilation, impaired airway secretion clearance, aspiration, obstructive and central apneas. These conditions can lead to nosocomial infections, prolonged mechanical ventilation, tracheostomy, and in some cases, death.) [35].

Respiratory function assessment should include a detailed medical history and physical examination, targeted chest radiography, evaluation of respiratory function and cough efficacy, as well as screening for sleep-disordered breathing [35, 36]. Respiratory function assessment includes measurement of vital capacity (study of unforced respiratory volumes and flows (spirometry)) and daytime pulse oximetry (SpO2). An SpO2 of less than 95% on room air is defined as a clinically significant pathological value requiring additional assessment of carbon dioxide partial pressure.

Assessment of the severity of hypoventilation to clarify its nature and rule out sleep apnea in adults has not been described; however, we consider it appropriate to extend the recommendation "to perform polysomnography if hypoventilation is suspected to clarify its nature and rule out sleep apnea" to adult patients with 5q SMA.

Respiratory failure is a frequent cause of death, especially in DMD [45].

• All patients with NMD, for the purpose of preventing and dynamically monitoring cardiac insufficiency, are recommended to undergo invasive blood pressure monitoring [113, 114, 119].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

2.5 Other Procedures

Comments: morphological examination of muscle biopsies in patients with spinal muscular atrophy reveals non-specific signs of fascicular atrophy and grouping of muscle fibers. Most of the enlarged muscle fibers belong to type I. All immunohistochemical markers will be normal. Ultrastructural changes will also be non-specific.

Data on the necessity of evaluation and results of muscle tissue biopsy (surgical) material in adult patients with atypical forms of 5q SMA are absent. It is advisable to address this issue within a multidisciplinary medical board [Consensus of the authors of the clinical guideline].

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

3.1. Conservative management

Comments: there is no inter-expert consensus on the type of braces to be used in such patients. Most experts recommend rigid thoracolumbar spinal orthoses (functionally corrective braces) with support on the pelvis, the lower thoracic aperture, and with an "abdominal window".

• Patients with NMD are recommended any options of custom-made rigid thoracolumbar spinal orthoses that allow maintaining a sitting position, provided they do not impair pulmonary function [49].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• Conservative treatment methods are recommended as a leading component in the following situations:

  – in the absence of indications for surgical treatment;

  – in the presence of limitations for surgical correction of scoliosis: low BMI <12; severe osteoporosis (Z-score < -2.5 SD) [50, 118, 119].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: orthotic management is a palliative method which, as a standalone method, is capable of influencing the progression of spinal deformity [48, 51].

Braces commonly used in the treatment of idiopathic scoliosis are often ineffective in patients with cerebral palsy (CP) [52, 53, 54, 118, 119].

In addition, patients do not always adhere to brace-wearing rules. Seizure activity in epileptic forms, limitation of chest wall movements associated with brace wearing can exacerbate existing pulmonary problems and lead to pressure ulcers. Olafsson Y. et al. showed some limitations on curve progression in ambulatory patients with small lumbar curves [55]. Nakamura N. et al. demonstrated improvements in scoliosis, sitting stability, and caregiver satisfaction in a group of patients using TSLO functionally corrective braces [56]. Pettersson K. and Rodby-Bousquet E., having studied 251 patients with 2800 CP who used a brace, concluded that most children use them for functional improvement (stability, head control, and arm/hand function) rather than deformity prevention [57].

In patients with CP, it is recommended to use wheelchairs with lateral trunk support or custom seating inserts as a means to control spinal deformity [57].

Comments: Nuzzo R.M. et al. [155] reported that injection of botulinum toxin type A** into the muscles on the concave side of the scoliotic deformity helped slow down scoliosis progression and increase the effectiveness of bracing treatment. However, the short-term efficacy of botulinum toxin type A** and the fact that it cannot be used in later stages due to mechanical collapse of the spinal deformity should be taken into account.

3.2. Surgical treatment

• Surgical intervention for correction and fixation of spinal segments for patients with NMD is recommended in cases of:

  – scoliosis greater than 40° Cobb (for SMA greater than 50°),

  – hyperkyphosis or hyperlordosis greater than 50° Cobb,

  – global trunk imbalance in the frontal and (or) sagittal plane,

  – rapid progression of scoliotic deformity (more than 5° per year, for SMA ≥10° annually),

  – the need for verticalization and improvement of quality of life [22, 61-67].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: in DMD patients receiving glucocorticoids, surgical correction and fixation is justified if the frontal plane curvature or sagittal plane deviation is ≥30° Cobb, with a progression rate of ≥10° annually, as well as in case of osteoporotic vertebral fractures and persistent pain unresponsive to pharmacotherapy of these syndromes, regardless of skeletal maturity.

Comments: when making a decision on surgical intervention, it is recommended to take into account decreased respiratory function, rib cage deformity, hyperkyphosis, impact on patient mobility and functioning, pelvic obliquity, and trunk imbalance. It is recommended to postpone surgical intervention in children under 4 years of age [65].

In children aged 8 to 12 years, the surgical approach depends on clinical data, particularly regarding skeletal maturity and spinal growth.

• In cases where pelvic obliquity is 15° or more, it is recommended to perform correction and posterior instrumented fixation of the thoracic and lumbar spine involving the pelvis [68-71].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: in DMD, posterior spinal stabilization is justified only in non-ambulatory patients with spinal curvature greater than 20° who are not receiving glucocorticoids and have already reached spinal maturity [26, 74, 75].

For children, the Recommendation Strength Level is C (level of evidence – 4); for all patients, the Recommendation Strength Level is C (level of evidence – 5).

3.3. Other treatment

3.3.1 Anesthetic management of patients with neuromuscular diseases.

3.3.1.1 Preoperative management of patients with NMD

• Preoperative preparation is recommended for all patients, even in the "asymptomatic" course [202].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments:

• to assess respiratory reserve comprehensively: chest radiography or chest CT; CPET with peak cough flow assessment; pulmonologist consultation; overnight pulse oximetry or cardiorespiratory monitoring. In case of limited respiratory reserve, perioperative non-invasive ventilation and the use of manual and instrumental techniques to stimulate and facilitate coughing are mandatory. Especially in non-ambulatory patients, preoperative preparation must be supplemented by non-invasive ventilation (NIV) for at least 1 month prior to surgery [91, 92, 93, 94].

• Cardiac assessment must be performed at least 2 months prior to surgery. If function is decreased, controlled therapy should be administered until surgical intervention. Cardiologist evaluation is recommended starting from 10 years of age [36].

• Initial pediatric endocrinologist consultation with nutritional status optimization [95, 36].

• Initial pediatric endocrinologist consultation with X-ray densitometry, and correction of osteopenia if detected [96].

• Avoid premedicant medications that can cause respiratory depression and hypoventilation up to respiratory arrest [97].

• Consider the administration of a stress dose of methylprednisolone** during surgery in patients receiving long-term steroid therapy (for the prevention of acute adrenal insufficiency) [98, 99, 100].

• Tracheal intubation in patients with NMD should be performed according to existing and clinically relevant difficult airway protocols [97].

• Central venous access should preferably be established under ultrasound guidance [101, 102].

• Maintenance of normal body temperature [103].

• Consider acquiring a new wheelchair or modifying the existing one (seat, backrest, armrests, headrest, etc.) prior to surgical treatment.

General principles of intraoperative management of patients with neuromuscular diseases

Comments: minimizing blood loss volume and surgical time plays an important role, especially during extensive surgical interventions.

This aspect is detailed in the draft clinical guidelines by the National Public Association "Federation of Anesthesiologists and Reanimatologists" of Russia entitled "Perioperative management of patients with neuromuscular diseases (draft)" [176].

3.3.2 Surgical antibiotic prophylaxis

• In the surgical treatment of patients with idiopathic scoliosis, it is recommended to perform surgical antibiotic prophylaxis (SAP) of surgical site infection with a single preoperative administration of an antibacterial drug to reduce the risk of infectious complications [177]. The use of these medications should take into account the age restrictions specified in the instructions for medical use.

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

Comments. For patients with an unremarkable allergic history and without significant risk factors for methicillin-resistant Staphylococcus aureus carriage, first- and second-generation (I and II generation) cephalosporins (cefazolin**, cefuroxime**) are used for SAP, administered intravenously 30 to 60 minutes before the skin incision. In case of intolerance to beta-lactam antibacterials (penicillins), vancomycin** should be used, administered over a minimum of 60 minutes with the start of intravenous infusion 2 hours before the incision, or #clindamycin**. In the presence of significant risk factors for methicillin-resistant Staphylococcus aureus (MRS) carriage, the SAP regimen should include systemic antibacterial drugs (ATC: J01) with anti-MRS activity (vancomycin**). In most cases, a single preoperative dose of a systemic antibacterial drug is sufficient for effective prophylaxis. For prolonged procedures (more than 3 hours) or massive blood loss, an additional intraoperative dose of a systemic antibacterial drug (ATC: J01) should be administered (the approximate timing of intraoperative administration is two half-lives after the preoperative dose). Administration of systemic antibacterial drugs (ATC: J01) after wound closure in the operating room is inappropriate, even in the presence of established drains.

Single doses of basic antibacterial drugs for SAP in trauma and orthopedic surgical interventions in adults: #cefazolin** 2 g (for patients weighing ≥120 kg – 3 g), cefuroxime** 1.5 g, #clindamycin** 900 mg, vancomycin** 15 mg/kg as a slow IV infusion, #ciprofloxacin** 400 mg (10 mg/kg in children), #levofloxacin** 500 mg (10 mg/kg in children) [177].

Single doses for children should be calculated based on actual weight: cefazolin** 30 mg/kg, cefuroxime** 50 mg/kg, #clindamycin** 10 mg/kg, vancomycin** 15 mg/kg [177, 192, 193].

3.3.3 Postoperative analgesia

• For adequate pain management in patients with neuromuscular diseases, it is recommended to use multimodal analgesia for adults and children, taking into account age restrictions, which may include NSAIDs (from group M01A Anti-inflammatory and antirheumatic products, non-steroids), paracetamol**, gabapentinoids (ATC group code N02BF), and immediate-release opioids (ATC group code N02A) considering the age restrictions in the instructions for medical use; if multimodal analgesia cannot be prescribed, monomodal analgesia should be used [180, 181, 182, 194].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Among pharmacological strategies, the current consensus is the use of multimodal analgesia (MMA), which involves the combination of several analgesics (opioid and non-opioid) from group N02 Analgesics with different mechanisms of action and non-pharmacological interventions aimed at targeting the peripheral and/or central parts of the nervous system [206]. This combination allows for more effective pain relief by enhancing the effects of various drugs, which in most cases leads to a reduction in the frequency of prescriptions and/or doses of opioid analgesics. Thus, MMA improves the risk profile of each drug while providing synergistic pain control using different drug classes. Postoperative MMA may include psychotherapy, physical therapy, NSAIDs, paracetamol**, gabapentinoids (ATC group code N02BF), regional analgesia (single injection or placement of peripheral nerve catheters), local injections, and opioids [181, 196].

In modern scientific literature, authors emphasize the use of the lowest effective doses of opioids for the shortest possible duration, avoiding extended-release opioids. As an adjuvant during MMA in adult patients, a single intravenous administration of #dexamethasone** 1.25–20 mg can be used before surgery (60 minutes prior to incision), which provides a significant reduction in pain [180].

It must be kept in mind that the duration of parenteral administration of most NSAIDs from the ATC group M01A "Anti-inflammatory and antirheumatic products, non-steroids" (ketorolac**, ketoprofen**, diclofenac**) is limited to two days in accordance with the instructions for medical use, which requires timely switching of the patient to oral administration, changing the drug, or approving further use with the medical commission. The specific choice of local anesthesia method and medicinal products is made by the attending physician individually, in accordance with the patient's characteristics, local protocols, and the equipment of the medical organization.

When prescribing analgesic therapy for children, a single dose should be chosen taking into account the child's weight and age. Preference should be given to analgesics with oral or rectal administration routes, avoiding intramuscular injections.

Recommended analgesics from group N02 Analgesics are listed in Appendices A3.3 and A3.4.

3.3.4 Postoperative management of patients with NMD

Comments: transfer to the ICU after surgery should be considered for any patient at risk of respiratory complications. ICU capabilities allow for comprehensive cardiovascular and respiratory monitoring, as well as multi-component therapy, including non-invasive ventilation (NIV), use of cough assist devices, or airway secretion aspiration.

• – Adequate analgesia is a critical component of postoperative management in patients with neuromuscular diseases. The depth of analgesia should be tailored to minimize respiratory center depression. Opioid analgesics carry an additional risk of respiratory depression. A safe and effective method of pain relief in this scenario is epidural analgesia as part of multimodal analgesia [105, 178, 179, 202].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: timely prevention and relief of pain syndrome prevent the development of secondary hypoventilation due to muscle rigidity following thoracic, upper abdominal, or spinal surgeries. The dose of administered opioids must provide adequate analgesia without suppressing the cough reflex and spontaneous breathing.

• – For adequate analgesia in patients with spinal deformities following surgical treatment, it is recommended to use multimodal analgesia, which may include non-steroidal anti-inflammatory and antirheumatic drugs (ATC group code: M01A), paracetamol**, gabapentinoids (ATC group code: N02BF), and immediate-release opioids, taking into account age restrictions in the instructions for medical use; if its prescription is not possible, monomodal analgesia should be used [180, 181, 182].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: it is necessary to ensure adequate pain relief for the patient prior to any manipulations and throughout the entire treatment period, the duration of which varies significantly depending on the chosen patient management strategy. When providing pain management in an inpatient setting, prescriptions made during the emergency medical care stage must be taken into account.

– Among pharmacological strategies, the current consensus is the use of multimodal analgesia (MMA), which involves the combination of several analgesic drugs (opioid and non-opioid) with different mechanisms of action and non-pharmacological interventions aimed at targeting the peripheral and/or central parts of the nervous system [183]. This combination allows for more effective pain relief by enhancing the effects of various drugs, which in most cases leads to a reduction in the frequency of prescriptions and/or doses of opioid analgesics. Thus, MMA improves the risk profile of each drug while providing synergistic pain control using different drug classes. Postoperative MMA may include psychotherapy, physical therapy, NSAIDs, paracetamol**, gabapentinoids, regional anesthesia (single injection or placement of peripheral nerve catheters), local injections, and opioids [184].

– When prescribing analgesic therapy in children, a single dose should be chosen taking into account the child's weight and age. Preference should be given to analgesics with oral or rectal administration routes, avoiding intramuscular injections. When choosing analgesics for multimodal analgesia, it should be taken into account that perioperative use of #pregabalin 2 mg/kg twice daily** in children with posterior instrumented spinal fusion does not reduce postoperative opioid consumption [185].

3.3.5 Prophylaxis of venous thromboembolic complications

Comments: to assess the individual risk of VTE development, it is advisable to use the Caprini scale (Appendix G9).

• In adult patients at high risk of bleeding, it is recommended to use mechanical thromboprophylaxis before surgery, and the first administration of a low-molecular-weight heparin from the heparin group (ATC code B01AB) should be delayed until hemostasis is achieved (12–24 hours after surgery) [194, 195, 188].

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

• If a patient is admitted with restricted mobility, including due to hemi- and tetraparesis/-paralysis, it is recommended to initiate pharmacological VTE prophylaxis in the preoperative period [189].

GGR CLeE 5Grade of Recommendation C (Level of Evidence – 5)

• When performing pharmacological VTE prophylaxis in children, it is recommended to consider the use of #enoxaparin sodium** (for age under 2 months: 0.75 mg/kg every 12 h, older than 2 months: 0.5 mg/kg every 12 h) or heparin sodium** [191, 184].

GGR CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: In pediatric practice, there is no standardized and validated risk assessment tool for thromboprophylaxis [190].

• Children are recommended to undergo mechanical thromboprophylaxis [204].

GGR CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: tracheal extubation in patients with neuromuscular diseases is recommended to be performed with full control over bronchial secretion and achievement of normal or borderline SpO2 values in ambient air or against the background of NIV. When there is a high risk of respiratory complications, the use of a protocol based on a combination of non-invasive pulmonary ventilation with active cough augmentation methods is recommended.

Comments: CPAP therapy (Continuous Positive Airway Pressure) is a method for correcting sleep-related breathing pauses by creating a constant positive pressure in the airways.

Comments: it is recommended in children older than 1 year to use epidural anesthesia with ropivacaine hydrochloride solution** 2 mg/1 ml injection solution administered via an infusion pump (infusion pump) (consensus of the clinical guideline authors). The main aspects of perioperative management of patients with neuromuscular diseases are detailed in the draft clinical guidelines of the All-Russian Public Organization «Federation of Anesthesiologists and Reanimatologists» of Russia «Perioperative Management of Patients with Neuromuscular Diseases (Draft)» and in Appendix B2 [176].

Comments: custom-made seating inserts (molded seating systems) with the ability to be attached to a wheelchair base can be used as an alternative to custom modular wheelchairs.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Patients with neuromuscular scoliosis are recommended a comprehensive set of medical rehabilitation methods for patients with musculoskeletal disorders, aimed at improving motor functions (especially maintaining trunk posture and mobility in a wheelchair), improving respiratory function and exercise tolerance, preventing pain caused by spasticity and/or rib impingement on the iliac crest, improving self-care, and other daily living functions [121, 122].

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

bracing (only in conservative treatment) [32, 47, 48, 49, 53, 56, 57].

GCR CLEL 4Grade of Recommendation C (Level of Evidence – 4)

(see section "Conservative Treatment"), hydrokinesitherapy, massage, physiotherapy, and reflexology [49, 131].

GGR CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: Bracing is recommended only in the absence of indications for surgical treatment and/or in the presence of limitations for surgical correction of scoliosis in children: BMI <12; osteopenia (Z-score <-3 SD) (see section "Conservative Treatment") [52, 53, 48, 56, 51, 55]. Bracing is not recommended in patients who have undergone surgical correction for neuromuscular scoliosis. With modern treatment methods, the use of braces is excessive and can negatively affect respiratory function, especially in the early postoperative period [122].

Comment: establishing a rehabilitation diagnosis using the ICF is central to rehabilitation planning [135-139].

• Bracing is recommended only in the absence of indications for surgical treatment and/or in the presence of contraindications to surgical correction of scoliosis in children: BMI <12; osteopenia (Z-score <-3 SD) (see section "Conservative treatment") [52, 53, 48, 56, 51, 55].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

Comments: with modern treatment methods, the use of braces is redundant and can negatively affect respiratory function, especially in the early postoperative period [122].

Comments: Physical exercise is beneficial for maintaining and improving exercise tolerance in patients with neuromuscular disorders. Physical exercise includes cardiovascular exercises, which can increase endurance and limit the likelihood of cardiopulmonary complications [145]. Exercises for training and strengthening the muscles involved in maintaining trunk balance and upper extremity manipulation also lead to a marked improvement in exercise tolerance and functional independence in some patients with neuromuscular diseases [147, 150, 151]. Physical rehabilitation does not have a significant impact on the progression of spinal deformity in patients with neuromuscular diseases, but it is effective in improving or maintaining active functioning. Therefore, during the non-surgical treatment period, continuous monitoring and assessment of progressive spinal deformity are important [125].

Comments: the use of wheelchair seating inserts can be effective in preventing scoliosis progression, preventing pressure ulcer formation, and enhancing comfort while sitting [122, 58]. Wheelchair accessories may include various inserts, lateral chest supports, shoulder or lap safety belts, foot and neck supports, as well as pommels between the thighs [122]. A study by Holmes K.J. et al. [58] showed that the use of a 3-point lateral support pad system provided a more symmetrical trunk position and reduced the severity of spinal deformity in patients with cerebral palsy.

Comments: due to the change in sitting posture, the wheelchair requires adaptation. Care should be taken to ensure that wheelchair adaptation procedures are initiated in a timely manner under the supervision of an occupational therapist. The wheelchair must be adapted in such a way as to ensure maximum comfort and balance of the trunk and head in the sitting position [122].

Comments: due to the fact that bone fusion healing after surgery takes from 3 to 9 months, trunk flexion and rotation, as well as hip flexion greater than 90°, are not permitted during this period [122].

Comments: home-based medical rehabilitation is organized by the medical organization to which the patient is attached for primary health care. During home-based medical rehabilitation, video demonstrations of correct physical exercises at home may be provided [122].

Comments: data on the efficacy of botulinum toxin type A are mixed. Nuzzo RM. et al. [155] reported that botulinum toxin type A** injections in patients with neuromuscular scoliosis due to cerebral palsy who needed to delay surgery increased the efficacy of subsequent surgical treatment and halted scoliosis progression. Kotwicki T. et al. [121] noted the efficacy of botulinum toxin type A** in reducing pain severity developing secondary to spasticity.

Conversely, a prospective, randomized, triple-blind study did not demonstrate the efficacy of botulinum toxin type A** in reducing radiological and clinical manifestations of scoliosis in children with cerebral palsy, apart from an initial subjective yet positive evaluation of the effect by the patients' parents [158]. Su YC et al. [159] in a systematic review with meta-analysis were unable to draw a definitive conclusion regarding the efficacy of botulinum toxin type A** in patients with neuromuscular scoliosis due to high heterogeneity of results among studies and a small sample size. More randomized controlled trials with appropriate target muscle selection and standardized outcome assessment should be conducted to study the efficacy of botulinum toxin type A** in the treatment of scoliosis [159].

Comments: some studies recommend hydrokinesiotherapy, which includes various types of exercises, aerobics (stretching, strength exercises, and stability training), in warm (above 30 °C) shallow water (chest-deep) [165, 166].

Comments: a study by M.R. Shaimurzhin et al. [168] demonstrated the effectiveness of manual therapy (mobilization and post-isometric relaxation techniques) in slowing the progression of motor impairments and the severity of scoliotic spinal deformity in children with SMA.

For children – Grade of recommendation C (Level of evidence – 5)

For adults – Grade of recommendation B (Level of evidence – 3)

Comments: according to a meta-analysis of randomized controlled trials evaluating the efficacy of acupuncture in patients with cerebral palsy, acupuncture combined with physical rehabilitation had a positive effect on gross motor skills, reduced spasticity, and improved daily activities [174].

• Sanatorium-resort treatment is recommended for pediatric patients with neuromuscular scoliosis and may include physical exercises, massage, balneotherapy, and various physiotherapy methods [161, 175].

GRL CLEL 4Recommendation Grade C (Level of Evidence – 4).

5. Prevention and Dispensary Observation

• All patients with orthopedic pathology and NMD are recommended to undergo dispensary follow-up by an orthopedic traumatologist [32].

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

Methods for preventing the development of neuromuscular scoliosis include the use of orthosis/bracing therapy and assistive rehabilitation devices (ARDs), as well as informing risk groups (patients with NMD) about measures to prevent secondary orthopedic complications.

The period of dispensary follow-up for patients with orthopedic complications of NMD is indefinite. The main monitoring methods are clinical examination, laboratory tests, and imaging studies. The criterion for effective treatment of neuromuscular scoliosis is an improvement in the clinical and imaging manifestations of the disease. Imaging criteria for deformity control during conservative treatment include: no progression of deformity within 20° Cobb, no increase in pelvic obliquity, and improvement in bone mineral density according to X-ray densitometry, which usually becomes apparent 6–8 months after the start of treatment. For patients who have undergone surgical treatment, the imaging signs of efficacy include preservation of deformity correction, absence of signs of spinal deformity progression and hardware instability, absence of peri-implant resorption, and the presence of signs of bone block formation (vertebrae) in the fixation zone.

During the first 6 months after surgery, patients are evaluated by an orthopedic traumatologist and a neurologist every 3 months. In the absence of clinical and imaging signs of disease progression or complications, radiography of the thoracic and lumbar spine is performed at 3 and 6 months, and spinal CT at 12 months.

Follow-up MRI or additional CT is performed in patients with signs of neurological impairment, persistent clinical activity, and to address the issue of subsequent targeted therapy with the possibility of intrathecal administration.

If complications are present, the patient continues follow-up/treatment with relevant specialists:

– with an orthopedic traumatologist, surgeon, or neurosurgeon – in the presence of fistulas, instability, and spinal deformity. If these complications can be eliminated, surgical treatment is performed in specialized departments/centers of spinal surgery with the patient's consent and after informing them of the relevant surgical risks;

– with a neurologist, urologist, or physical medicine and rehabilitation physician – in case of manifestations of myelo-/radiculopathy;

– with an endocrinologist – in the presence of osteoporosis;

– with a surgeon, plastic surgeon, or social workers – in case of irreversible neurological and neurotrophic disorders.

Patients with NMD remain under dispensary register (DR) with a neurologist and an orthopedic traumatologist for three years after surgery.

6. Organization of Medical Care

Surgical care for patients with neuromuscular scoliosis is provided as part of high-tech medical care in an inpatient setting. Conservative treatment, depending on the severity of clinical manifestations and the complexity of the devices, can be carried out either on an outpatient basis or in a specialized inpatient facility (neurological or rehabilitation bed profile).

Indications for hospitalization in a medical organization are:

1. presence of indications for surgical treatment of NMS;

2. development of neurological complications of NMS;

3. vertebrogenic pain syndrome refractory to conservative methods;

4. development of spinal hardware instability with the risk of soft tissue damage, including cases accompanied by pain syndrome and spinal deformity impairing the patient's quality of life;

5. chronically functioning fistula (present for more than 3 months).

Indications for patient discharge from the inpatient medical facility are:

1. radiological evidence of maintained neuromuscular scoliosis correction;

2. absence of signs of hardware instability;

3. normalization of general laboratory parameters – Hb, ESR, leukocyte differential count;

4. absence of signs of infectious and inflammatory changes in the surgical site;

5. relief of vertebrogenic pain syndrome to levels that do not require prescription of injectable analgesics or are subjectively rated by the patient as no higher than 3 points on the VAS.

Further treatment of the patient with resolution or improvement of clinical manifestations of the underlying disease may be continued, taking into account indications, in an inpatient or outpatient setting, including specialized (neurological, rehabilitation) departments/centers, under the supervision of a surgeon and/or trauma surgeon / orthopedic surgeon.

7. Additional Information

Patient-oriented factors having a negative impact on treatment outcomes:

1. somatic status of the patient, including the presence of acute and chronic diseases – obesity, respiratory failure; comorbid chronic inflammatory diseases of the urinary and respiratory systems, oral cavity, skin, and subcutaneous adipose tissue; diseases accompanied by neurotrophic disorders;

2. osteoporosis;

3. immunodeficiency states, including those caused by prior therapy (glucocorticoids, immunosuppression).

Disease-oriented factors having an adverse effect on the disease outcome:

1. unfavorable course of the underlying disease with progressive muscle damage;

2. development of secondary chest deformities.

Potentially adverse factors associated with disease treatment:

1. in conservative treatment – development of severe soft tissue neurotrophic manifestations;

2. in surgical treatment – unstable instrumental fixation and wound infection.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

¹ – Russian Association of Spine Surgeons (RASS);

² – Association of Traumatologists and Orthopedists of Russia (ATOR);

³ – AOSpine Global Association for Spine Science;

⁴ – Union of Rehabilitologists of Russia.

Conflict of interest:

The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. Orthopedic trauma surgeons.

2. Neurosurgeons.

3. Neurologists.

4. Surgeons.

Stages of assessing levels of evidence and grades of recommendation:

1. Definition of search and selection criteria for publications on clinical trials (CT) regarding the efficacy and/or safety of the medical intervention described in the recommendation statement.

2. Systematic search and selection of CT publications in accordance with the previously defined criteria.

Systematic search and selection of clinical trial publications:

The evidence base for the recommendations consisted of publications retrieved via information retrieval in the following databases: Central Scientific Medical Library (CSML) "Russian Medicine", MEDLINE (US NLM), and COCHRANE Library; scientific electronic libraries eLibrary.ru and "CyberLeninka"; as well as on the Internet using Yandex, Google, and Google Scholar search engines, by reviewing leading specialized peer-reviewed domestic medical journals on the subject and treatment guidelines for fractures from the international Association for Osteosynthesis AO/ASIF.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table 3. Scale for assessing grades of recommendation (GR) for prevention, diagnosis, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Appendix A3.1 Assessment of rehabilitation potential and procedures [118, 119]

ROM – range of motion;

CHOP-INTEND – Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders;

HINE – Hammersmith Infant Neurological Examination;

AFOs – Ankle Foot Orthosis;

KAFOs – Knee Ankle Foot Orthosis;

HKAFOs – Hip Knee Ankle Foot Orthosis;

TLSOs – Thoracolumbosacral Orthosis;

WHFO – Wrist Hand Finger Orthosis;

HFMSE – Hammersmith Functional Motor Scale Expanded (for SMA patients);

RULM – Revised Upper Limb Module (for SMA);

MFM – Motor Function Measure (for patients with neuromuscular diseases);

6MWT – 6-Minute Walk Test;

ADL – Activities of Daily Living.

Appendix A3.3. Pain management recommendations for major musculoskeletal trauma in adults

The table presents analgesic medications and their dosing regimens in accordance with the Clinical Guideline for the Management of Acute Musculoskeletal Pain [183].

Appendix A3.4 Pain medication dosing regimen for children

¹ In children under 12 years of age, morphine** is preferred if opioid analgesics are required, as the use of tramadol** is associated with a higher risk of adverse reactions [198, 199].

² Not recommended for use in children, as its metabolite accumulates in the body and provokes seizures upon repeated administration [200].

Key scales/tests recommended for the evaluation of 5q SMA patients with various motor abilities

CHOP-INTEND – The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders;

HINE – Hammersmith Infant Neurological Examination – Assessment of neurological status in infants;

HFMSE – Hammersmith Functional Motor Scale-Expanded – Assessment of motor functions in 5q SMA;

RULM – Revised Upper Limb Module – Assessment of upper limb motor function;

MSM – Motor Function Measure – Assessment of motor function;

6-MWT – The 6 Minute Walk Test

Appendix B. Physician Action Algorithms

Appendix B1. Physician's algorithm of actions in suspected acute inflammatory spinal disease

Appendix C. Patient Information

1. Postoperative rehabilitation. The early rehabilitation period continues until the wound is completely healed and the pre-surgical level of verticalization is restored. The pace and characteristics of the rehabilitation period are individual for each person.

2. Postoperative sutures. In most cases, the patient is discharged after the sutures have healed by primary intention. This means that a "crust" forms on the surface of the suture, beneath which a narrow linear scar develops. Daily suture care is performed according to the attending physician's prescriptions. Once the "crust" detaches, the scar requires no further treatment. Scar maturation typically occurs within 1 month. It is recommended to wear cotton or knit clothing that does not irritate the skin in the area of the postoperative suture. It is extremely undesirable to touch the suture with hands (cleaning is done with cotton swabs); expose the suture to water or moisture. Visiting saunas and steam rooms is not recommended until complete healing. For showering, a waterproof dressing can be independently applied over the suture; do not peel off the "crusts" before the scar forms;

3. Psycho-emotional changes. In some cases, the following phenomena may be observed after discharge: emotional lability, irritability, tearfulness; lowered mood, apathy, fatigue; sleep disturbances. These manifestations are a natural bodily reaction to "surgical stress" and resolve as the general condition improves, without any treatment. In rare cases (when the condition causes significant distress), consulting a psychotherapist, neurologist, or the attending physician is recommended. To help stabilize emotional well-being, maintaining a balance between active periods and rest, and listening to or viewing relaxation music programs is beneficial. If falling asleep is difficult, it is advisable to switch to another activity (listen to music, read, change body position), and air out the room. The body needs some time to restore normal sleep patterns. In case of prolonged sleep disturbance, consultation with a neurologist is recommended.

4. Pain. Pain in the cervical, thoracic, or lumbar spine is possible. This pain may occur or intensify after physical exertion. This is a common phenomenon and should not cause alarm. Medications prescribed by the attending physician, relaxation exercises, and light massage may be used. If the pain becomes pronounced, persistent, and radiates to the arms or legs, it is recommended to consult a local neurologist, making sure to consult the attending physician first.

5. The journey home. You can travel home by car, bus, train, or plane. As a rule, transportation is carried out in a prone or side-lying position. In a car, you can ride in the back seat or on a fully reclined front passenger seat. On a train, transportation is carried out on the lower bunk of a compartment (the necessary certificate can be obtained from the head nurse of the department). On a bus or plane, it is best to recline the seat back or occupy several vacant seats. At the airport, you must have your discharge summary and X-ray with you.

6. Orthopedic regimen. Prolonged standing should be avoided. Heavy lifting and carrying (not more than 3 kg), seasonal agricultural work, and general physical education are strictly prohibited. Sitting is not recommended until fatigue sets in during the first 6 months after surgery; avoid trunk flexion and rotation, as well as bending and lifting the legs. Assistance is recommended for comfortably putting on shoes. Sleeping on a semi-firm bed with a small pillow is advised. To go to bed or use the restroom, conditions similar to those in the hospital must be set up (handrails, stands, supports).

7. Stair climbing. If walking is possible, going up and down stairs requires significantly more effort than walking on a flat surface. You should ascend and descend stairs step-by-step (using the trailing-leg method) with rest stops, holding onto the handrails.

8. Studies. Individualized education is recommended after surgery. The school or university administration must be notified of the surgery. For home schooling, proper organization of the workstation is required: the desk height must be correctly adjusted, and the light source must be sufficiently bright. Classes can be conducted while lying down, standing, or kneeling. Take a break if fatigue occurs. At school or university, classes should be conducted in similar body positions. If fatigue appears, it is best to be excused from class and rest in a lying position.

9. Profession. It is undesirable to choose a profession associated with prolonged standing.

10. Nutrition. A proper dietary regimen is important during the recovery period. It is advisable to avoid fried and fatty foods, as well as to reduce the intake of salty foods, sweets, and organ meats. Body weight should correspond to height. Mealtimes should be consistent. Excessive food intake should be avoided. Nutrition should be diverse, wholesome, and vitamin-rich.

11. Physical activity. Any physical activity, except for walking, may be permitted only after consulting the attending physician. Physical loads should be increased gradually, moving from light exercises to more complex ones. Swimming in a pool is recommended no earlier than 3 months after surgery (at least 2 times a week). Sports involving the risk of falls and trauma are not recommended.

12. Follow-up care and control examinations. After discharge, you should make an appointment with an orthopedic trauma surgeon, general practitioner/primary care physician, and neurologist. You must bring your discharge summary to the appointment.

    Physiotherapy is not recommended during the first 6 months after surgery. A follow-up examination to assess treatment efficacy is performed at 6 months, 1 year, and 2 years postoperatively. To do this, you need to book an appointment in advance at the outpatient clinic reception desk using the phone number listed in your discharge summary!

13. Disability status. For issues regarding obtaining (extending) disability status, please consult your attending physician (hardware is implanted permanently and removed only for specific clinical indications). If you have any questions related to your surgery, please do not hesitate to contact your attending physician directly. Every patient returns to their usual activity level at their own individual pace. Do not compare yourself to other patients. Alternate between an upright position and rest. Avoid walking to the point of fatigue. For some time, pain in the area of the postoperative sutures may be bothersome. Listen to the radio or music to distract yourself, or get up and take a short walk before trying to fall asleep again. Mood swings are common during recovery and will resolve over time. It is recommended to wear cotton or knit clothing that does not irritate the skin around the postoperative incision. It is important to inform every healthcare provider you visit that you have undergone spine surgery. Any recommendations or treatment modalities proposed in an outpatient setting must be coordinated with your attending physician.

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

Appendix G1. Muscle strength scoring

Russian name: Muscle Strength Grading Scale

Source (official developer website, validation publication) [110]:

Type (underline): rating scale

Purpose: assessment of muscle strength

Content (template):

Appendix G2. Visual analogue scale for pain

Russian name: Visual Analog Scale for Pain (Numerical) (VAS)

Original name (if applicable): Visual Analog Scale (VAS)

Source (official developer website, validation publication): [111]

Type (underline): rating scale

Purpose: assessment of pain severity

Content (template):

Appendix G3. Functional scale for assessing global motor impairments

Russian name: Gross Motor Function Classification System – GMFCS

Original name: Gross Motor Function Classification System (GMFCS)

Source (official developer website, validation publication): [120]

Type: rating scale

Purpose: assessment of upper extremity motor function

Content (template): This is a descriptive system that accounts for the degree of motor development and movement limitations in daily life for 5 age groups of patients with cerebral palsy: under 2 years, 2 to 4 years, 4 to 6 years, 6 to 12 years, and 12 to 18 years. According to GMFCS, there are 5 levels of gross motor function development:

Level I – walks without limitations

• Under 2 years – onset of independent walking

• 2 to 4 years – independent walking without running and jumping

• 4 to 6 years – independent walking, climbing stairs, running, and jumping

• 6 to 12 years, 12 to 18 years – independent walking over obstacles, running, and jumping, participation in sports activities

Level II – walks with limitations

• Under 2 years – crawls on stomach and hands-and-knees, cruises along furniture

• 2 to 4 years – crawls on hands-and-knees, cruises, independent walking by 4 years of age

• 4 to 6 years – independent walking for short distances, climbs stairs using a handrail, unable to run or jump

• 6 to 12 years, 12 to 18 years – independent walking for long distances in familiar settings, uses mobility aids outdoors, runs and jumps poorly

Differences between Level I and Level II: children at level II have limitations in freedom of movement, walking outdoors, and in peer groups; assistive devices are required to master walking. Movement quality is impaired – the child cannot run or jump

Level III – walks using assistive mobility devices

• Under 2 years – rolls over and crawls on stomach

• 2 to 4 years – creeps on belly or crawls on hands-and-knees (reciprocally), walks with handheld mobility devices for short distances

• 4 to 6 years – can stand up from a chair without support, but walks only with assistive devices

• 6 to 12 years, 12 to 18 years – walks only with assistive devices, can ascend and descend stairs with a handrail, moves outdoors exclusively in a wheelchair

The difference between Level II and Level III lies in the degree of functional activity. Level III children require assistive devices and orthoses for walking. Level II children do not require walking aids after 4 years of age.

Level IV – moves with limitations; powered mobility devices may be used

• Under 2 years – rolls over, but does not maintain sitting posture

• 2 to 4 years – sits in adapted equipment, but creeps on belly

• 4 to 6 years – can sit down and stand up from a chair with adult assistance, at best can move short distances using assistive devices

• 6 to 12 years, 12 to 18 years – moves around the room by rolling or crawling on the stomach, can move in walkers supporting the pelvic girdle and trunk

The difference between Level III and Level IV is evident in the ability to sit, even with the use of assistive devices. Level III children sit independently, move across the floor independently, and walk using assistive devices. Level IV children can sit, but independent mobility is very limited. Level IV children are more frequently transported in a wheelchair.

Level V – mobility is restricted to a manual wheelchair

• Under 2 years – require adult assistance to roll over

• 2 to 4 years – some children achieve independent mobility using a motorized high-tech wheelchair

• 4 to 6 years, 6 to 12 years, 12 to 18 years – some children achieve independent mobility using a high-tech power wheelchair. Level V children cannot independently control movements and maintain posture against gravity (do not maintain head and trunk control). Independent mobility is possible only with the use of advanced power wheelchairs.

Appendix G4. Classification of communication functions and skills

Russian name: Communication Function Classification System

Original name (if applicable): Communication Function Classification System (CFCS)

Source (official developer website, validation publication): http://cfcs.us/

Type (underline): rating scale

Purpose: assessment of communication functions and skills

Content (template):

CFCS includes five levels:

1. Effective communication with familiar and unfamiliar communication partners.

The child easily comprehends incoming messages, transmits their own messages, and successfully acts in both roles. Communication occurs effortlessly and at a comfortable pace for all participants (both familiar and unfamiliar). Communication breakdowns are quickly resolved and do not affect communicative productivity.

2. Effective but slower-paced communication with familiar and unfamiliar communication partners.

The child acts as both a sender and a receiver of messages, communicating with both acquaintances and strangers, although they may require additional time to understand a message or to formulate and express their own. Communication misunderstandings are usually resolved without outside help and do not affect communication productivity. The overall pace of communication is reduced.

3. Simple communication only with familiar people.

The child easily understands and sends messages, but only during communication with familiar people. Communication with strangers is often ineffective.

4. Delayed simple communication only with familiar people.

Possible communication options: 1) sometimes successful sender and receiver; 2) successfully sends messages, but poor understanding; 3) good understanding of messages, but poor output.

5. Rare simple communication even with familiar people.

The child is limited as a sender and receiver. The child's communication is incomprehensible to most people. The child poorly understands speech addressed to them. Sometimes communication is successful with familiar people.

Appendix G5. Classification of manual skills

Russian title: Manual Ability Classification System

Original title (if applicable): Manual Ability Classification System (MACS)

Source (official developer website, validation publication): https://www.macs.nu/

Type (underline): rating scale

Purpose: assessment of hand functions and manual abilities

Content (template):

The MACS classification includes 5 levels by analogy with the Gross Motor Function Classification System (GMFCS).

Level I – the child handles objects easily and successfully.

Level II – the child handles most objects, but with somewhat reduced quality and/or speed of achievement.

Level III – the child handles objects with difficulty; needs help in preparation and/or modification of activities.

Level IV – the child handles a limited selection of easily managed objects in adapted situations.

Level V – the child does not handle objects and has severely limited ability to perform even simple actions.

Appendix G6. Motor function rating scale

Russian title: Motor function rating scale

Original title (if applicable): Motor Function Measure (MFM)

Source (official developer website, validation publication): https://mfm-nmd.org

[Berarda C., Payan C., Hodgkinsona I., Fermanian J. The MFM Collaborative Study Group A motor function measure scale for neuromuscular diseases. Construction and validation study. Neuromuscular Disord. 2005; 15: 463–470] [117]

Type (underline): rating scale

Purpose: assessment of motor function in patients with neuromuscular diseases

Content (template):

List of 32 motor function measurement items with starting position and required exercises

Appendix G7. Upper limb motor function assessment module

Russian title: Revised Upper Limb Module

Original title (if available): REVISED UPPER LIMB MODULE

Source (official developer website, validation publication): [115]

Type (underline): rating scale

Purpose: assessment of upper extremity motor function

Content (template):

Appendix G8. HFMSE functional motor scale

Russian title: Functional Motor Scale

Original title (if available): The Hammersmith Functional Motor Scale Expanded (HFMSE)

Source (official developer website, validation publication): [116]

Type (underline): rating scale

Purpose: assessment of upper extremity motor function

Content (template):

Appendix G9. Caprini Scale for Individual Assessment of Risk of Venous Thromboembolic Complications

Russian title: Scale for Individual Assessment of Risk of Venous Thromboembolic Complications according to Caprini.

Original title: Caprini Score for Venous Thromboembolism

Source: Lobastov K.V., Barinov V.E., Schastlivtsev I.V., Laberko L.A. Caprini scale as a tool for individual risk stratification of postoperative venous thromboembolism in the high-risk group. Pirogov Russian Journal of Surgery. 2014; (12):16-23.

Type: scale

Purpose: assessment of venous thromboembolism risk

Contents:

1 point

Age 41-60 years

Lower extremity edema

Varicose veins

Body mass index > 25 kg/m²

Minor surgery

Sepsis (< 1 month)

Severe pulmonary disease (including pneumonia < 1 month)

Systemic hormonal contraceptive use (oral contraceptives), hormone replacement therapy

Pregnancy and postpartum period (< 1 month)

History of unexplained stillbirths, spontaneous abortions (≥3),

Premature birth with preeclampsia or intrauterine growth restriction

Acute myocardial infarction

Chronic heart failure (< 1 month)

Bed rest in a non-surgical patient

History of inflammatory bowel disease

History of major surgery (< 1 month)

Chronic obstructive pulmonary disease

2 points

Age 61-74 years

Arthroscopic surgery

Malignant neoplasm105

Laparoscopic surgery (duration > 45 min)

Bed rest > 72 h

Limb immobilization (< 1 month)

Central venous catheterization

Major surgery (duration > 45 min)

3 points

Age > 75 years

Personal history of VTE

Family history of VTE

Factor V Leiden mutation

Prothrombin G20210A mutation

Hyperhomocysteinemia

Heparin-induced thrombocytopenia

Elevated anticardiolipin antibodies

Lupus anticoagulant

5 points

Stroke (< 1 month)

Multiple trauma (< 1 month)

Major joint arthroplasty

Femur and lower leg fractures (< 1 month)

Spinal cord injury/paralysis (< 1 month)

Interpretation: Depending on the score obtained during history taking and patient examination, the patient is stratified into one of the risk groups:

• low risk: 0–1 point;

• moderate risk: 2 points;

• high risk: 3–4 points;

• very high risk: 5 points or more.