Kennedy bulbospinal amyotrophy. Spinal and Bulbar Kennedy Amyotrophy Essential Drugs

Kennedy's spinal bulbar amyotrophy is a hereditary neurodegenerative disease. The first symptoms usually occur after 40 years, mostly men get sick. Disease...

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Kennedy's spinal bulbar amyotrophy is a hereditary neurodegenerative disease. The first symptoms usually occur after 40 years, mostly men get sick. The disease is characterized by progressive weakness, atrophy of the muscles of the extremities, and atrophy of the muscles controlled by the medulla oblongata (bulbus medulae spinalis): the soft palate, larynx, pharynx, and tongue. Sometimes a violation of sensitivity develops. In addition to neuromuscular symptoms, in some cases there are also endocrine symptoms: gynecomastia and reduced fertility.

The cause of the disease is a mutation in the androgen receptor gene. In the genome of patients with spinal bulbar amyotrophy, the number of repeats of the three-nucleotide CAG sequence is increased in the first exon of this gene (accordingly, several extra glutamine amino acids appear in the protein). In a healthy person, there are from 11 to 33 such repeats, in patients - more than 40. The more repeats are contained in the mutant gene, the more severe the disease. Such a receptor not only loses its function, but has a toxic effect on cells. This toxic effect is especially strong in some nerve cells, which leads to the development of the disease.

The gene encoding the androgen receptor is located on the X chromosome. This means that in men it is present in a single copy, and a mutation in this single copy will cause disease. In women, even when the mutation is present in both copies of the gene on both X chromosomes, the disease manifests itself in a very mild form. If there is only one mutant copy of the gene, women do not develop the disease. This type of inheritance is called X-linked recessive inheritance.

Method

The polymerase chain reaction is used to determine the number of repeats. With its help, you can get many copies of the desired gene region, and then compare the size of this gene region in the test sample with standard samples and similar products of the polymerase chain reaction carried out with DNA with a known number of repeats.

Reference values ​​- norm
(AR gene (Kennedy spinal bulbar amyotrophy), identification of frequent mutations)

Information regarding the reference values ​​of the indicators, as well as the very composition of the indicators included in the analysis, may differ slightly depending on the laboratory!

Norm:

For men:

More than 40 repetitions lead to the development of the disease. The more repetitions, the more severe the disease. The son of such a person will not inherit the mutations, and will certainly be healthy. The daughter with a probability of 100% will be the carrier of the mutation.

Less than 33 repetitions is the norm.

For women:

The presence of more than 40 repeats in both copies of the gene can cause a very mild form of the disease. All the sons of such a woman will be sick, and all the daughters will be carriers.

The presence of more than 40 repeats in only one copy of the gene does not cause disease in women, but leads to the fact that her son will inherit the disease with a 50% probability, and her daughter will be a carrier of the mutant gene with a 50% probability.

Less than 33 repetitions is the norm.

Indications

A genetic study will help clarify the diagnosis and distinguish Kennedy's spinal bulbar amyotrophy from diseases that occur in a similar way.

Women who have male relatives with Kennedy's spinal bulbar amyotrophy will be able to find out if they are carriers of the mutation.

An adult form of spinal muscular atrophy, the hallmark of which is a slow and relatively favorable course. It is manifested by a combination of flaccid paresis of the proximal muscle groups of the limbs, bulbar syndrome and endocrine disorders. Diagnostic search is carried out using electroneuromyography, muscle biopsy, genealogical analysis, DNA diagnostics, androgenic profile assessment. Symptomatic therapy: anticholinesterase agents, nootropics, L-carnitine, vitamins, therapeutic exercises, massage.

Kennedy's bulbospinal amyotrophy is a genetically determined rare pathology of the nervous system, accompanied by endocrine disorders. It owes its name to the American neurologist W. Kennedy, who first described it in detail in 1968. It is inherited recessively linked to the X chromosome. Along with scapuloperoneal, distal, monomelic, oculopharyngeal muscle atrophy, in clinical neurology, Kennedy's amyotrophy refers to adult forms of spinal amyotrophies. Her debut occurs after the age of 40.

According to world statistics, the prevalence is at the level of 25 cases per 1 million people. At the end of the 20th century, only 10 verified family cases of bulbospinal amyotrophy were registered in Russia. This rarity may be due to insufficiently accurate diagnosis, as a result of which the disease is interpreted as amyotrophic lateral sclerosis.

Causes of amyotrophy Kennedy

The genetic substrate of the disease is the expansion (increase in the number of repeats) of the CAG triplet (cytosine-adenine-guanine) in the androgen receptor gene, located on the Xq21-22 site of the long arm of the X chromosome. The core of pathogenesis is degenerative changes in the nuclei of the brain stem and anterior horns of the spinal cord. Damage to the trunk leads to the development of bulbar syndrome and occurs 10-20 years after the appearance of peripheral paresis associated with damage to the spinal motor neurons of the anterior horns.

X-linked inheritance of bulbospinal amyotrophy causes morbidity predominantly in males. A woman can get sick if she inherits one defective X chromosome from her mother and the other from her father. However, in women, Kennedy's amyotrophy has a milder course, severe cases are rare, and a subclinical form is possible.

Symptoms of amyotrophy Kennedy

The manifestation of the disease, as a rule, occurs in the period from 40 to 50 years. The onset is characteristic with slowly progressive weakness in the proximal limbs: in the shoulders and hips. Paresis is accompanied by fascicular twitches, muscle hypotension, atrophy of muscle tissue, extinction of tendon reflexes; gradually spread more distally. The sensitive area remains intact. Pathological pyramidal signs are absent.

After 10-20 years from the debut, perioral fasciculations, bulbar manifestations (dysphagia, dysphonia, dysarthria), fasciculations and atrophic changes in the tongue occur. Joint contractures may form. Fasciculations of the perioral muscles are a marker of bulbospinal amyotrophy. They are rapid, involuntary contractions of the muscles around the mouth, resulting in twitching of the corners of the mouth or puckering of the lips.

Often, Kennedy's amyotrophy is accompanied by endocrine pathology. In sick men, gynecomastia, decreased libido, impotence, testicular atrophy are observed. Approximately one third are diagnosed with male infertility associated with azoospermia. In 30% of cases, diabetes mellitus is noted. Symptoms of hypogonadism and signs of feminization appear against the background of normal blood testosterone levels and are most likely due to a defect in androgen receptors, which consists in their insensitivity to male hormones.

Kennedy Amyotrophy Diagnosis

Diagnosis is carried out by neurologists according to the neurological status, ENMG, histological examination of the skeletal muscle preparation, the conclusions of the endocrinologist and geneticist. Neurological examination determines the peripheral nature of paresis. Assumptions about the topic of the lesion (anterior horns of the spinal cord) are confirmed by the data of electroneuromyography (ENMG). In addition, ENMG reveals a polyneuropathic complex and other typical features that distinguish bulbospinal amyotrophy from other similar diseases. A muscle biopsy reveals a picture of alternation of atrophic muscle fibers with hypertrophic ones, characteristic of spinal amyotrophies.

Additionally, a study of total testosterone and blood sugar is carried out, an analysis of the androgenic profile, and a spermogram is performed according to indications. Mandatory is the consultation of a geneticist with the compilation and evaluation of the family tree, the performance of DNA studies. Diagnostic search provides for a differential diagnosis with amyotrophic lateral sclerosis, tick-borne encephalitis, progressive Becker muscular dystrophy, myopathy, Werdnig-Hoffman amyotrophy, Kugelberg-Welander amyotrophy.

Treatment and prognosis of amyotrophy Kennedy

Symptomatic treatment is carried out, mainly aimed at maintaining the metabolism of nerve and muscle tissues. As a rule, patients are prescribed nootropics (gamma-aminobutyric acid, piracetam), B vitamins, L-carnitine, a preparation from the brain of pigs, anticholinesterase agents (ambenonium chloride, galantamine). For the same purpose, massage and physiotherapy exercises are shown, which increase the blood supply, and hence the metabolism, of the affected muscle groups. In addition, massage and exercise therapy help prevent the formation of joint contractures. Some researchers note the positive effect of a long-term course of taking testosterone preparations. However, the large number of negative effects of testosterone limits its widespread use.

The prognosis of Kennedy amyotrophy is relatively favorable. Due to the slow flow, patients retain the ability to move and self-service. Life expectancy is not less than the general population. However, due to hormonal disorders, there is an increased likelihood of developing malignant neoplasms, in particular, breast cancer in men.

SA is a heterogeneous group of hereditary diseases of the peripheral nervous system, which are characterized by pronounced clinical polymorphism.

Spinal muscular atrophy (or SA) is a heterogeneous group of hereditary diseases that occur with damage and loss of motor neurons of the anterior horns of the spinal cord.

Amyotrophy is a violation of muscle trophism, accompanied by thinning of muscle fibers and a decrease in their contractility, due to damage to the nervous system: motor neurons (at various levels of the central nervous system - neurons of the motor cortex, nuclei of the brain stem, anterior horns of the spinal cord) or peripheral nerve fibers. The disease is considered hereditary as a result of gene mutations, although if we look at the case history, many patients do not have a family history.

There are hereditary and symptomatic amyotrophies. Neurogenic hereditary amyotrophies are divided into two large groups - spinal and neural amyotrophies. In most cases, spinal forms are more severe. These include: spinal amyotrophy (Werdnig-Hoffmann disease), Kugelberg-Welander pseudomyopathic progressive spinal amyotrophy, rare forms of spinal amyotrophy and undifferentiated forms. Neural amyotrophies: Charcot-Marie-Tooth disease, Dejerine-Sotta hypertrophic neuropathy, Roussy-Levi syndrome, atactic polyneuropathy or Refsum disease, as well as undifferentiated forms.

SA are also divided into adults and children. Proximal SA of childhood include: acute malignant infantile SA of Werdnig-Hoffmann (type 1 spinal amyotrophy), chronic infantile SA (type 2 spinal amyotrophy), juvenile SA (Kugelberg-Welander disease), rare forms of SA in childhood : infantile neuronal degeneration, congenital form of Peliceus-Merzbacher disease, congenital cervical SA, atypical variant of GM-gangliosidosis, progressive bulbar palsy (Fazio-Londe syndrome), pontobulbar palsy with deafness (Vialetto-Van Lare syndrome).

Adult SA: Kennedy's bulbospinal amyotrophy, distal SA, segmental SA, monomyelic SA, Stark-Kaiser scapulo-peroneal SA, Fenichel's facial humeral SA, oculopharyngeal SA. There are also undifferentiated forms of SA with rapidly progressive, slowly progressive and non-progressive course.

According to the recommendation of the European Consortium for the Study of Neuromuscular Diseases, the clinical criteria for spinal muscular amyotrophy are: [ 1 ] symmetrical muscular hypotension and hypotrophy, [ 2 ] fasciculations of various muscle groups, [ 3 ] hypo- or areflexia of limb muscles, [ 4 ] lack of sensory, cerebellar and intellectual disorders.

note! There are no pathognomonic changes in spinal muscular amyotrophy. However, it is important to determine the activity of serum creatine kinase: it is believed that exceeding its norm by more than 10 times is characteristic of myodystrophy and contradicts the diagnosis of spinal muscular amyotrophy.

read also the post: Creatine Kinase (Neurologist's Handbook)(to the website)

Electroneuromyography (ENMG) reveals symptoms of damage to peripheral motor neurons: spontaneous muscle activity, an increase in the duration and amplitude of action potentials of motor units at a normal speed of impulse conduction along afferent and efferent fibers of peripheral nerves. Histological examination of muscle biopsies reveals signs of denervation muscle atrophy.

Classical proximal SA in adults begins in the 3rd decade of life and is inherited in an autosomal recessive manner. SA usually debuts at age 40 - 50 however, there are cases with onset in adolescence. The distribution of muscle weakness in the autosomal dominant type is in some cases much wider than in the autosomal recessive type. The proximal muscles are also more severely affected than the distal ones. Symptoms progress slowly, motor functions and the ability to walk in the vast majority of patients are preserved in adulthood and even in old age. Weakness of the bulbar muscles is not typical. The oculomotor muscles are not affected. Tendon reflexes are depressed or absent. Joint contractures are rare. The level of CPK is normal or slightly elevated. The following forms of SA in adults will be considered:

1. Kenedy's bulbospinal amyotrophy;
2. distal SA;
3. segmental SA;
4. monomyelic SA;
5. scapuloperonial SA of Stark-Kaiser;
6. Fenichel's facial scapulohumeral SA;
7. oculopharyngeal spinal amyotrophy.

bulbospinal Kennedy amyotrophy. A rare X-linked form of spinal amyotorfia; debuts in the 4th decade of life, although occasionally there are cases of the first manifestations at 12-15 years of age. Ken is mapped on the long arm of the X chromosome in the Xq21-22 segment. The mutation affects the androgen receptor gene and is an expansion of the nucleotide triplet (cytosine - adenine - guanine). The core of the clinical picture of the disease is weakness, atrophy and fasciculations in the proximal muscle groups of the limbs, tendon areflexia, weakness of facial muscles, atrophy and fasciculations in the tongue, perioral fasciculations, dysarthria and dysphagia (the latter is not a prognostically unfavorable sign), postural tremor and cramps. Rarely, axonal neuropathy develops. Bulbar disorders usually occur 10 years after the onset of the disease. Typical endocrine disorders: gynecomastia (!), testicular atrophy, decreased potency and libido, diabetes mellitus. A third of patients suffer from infertility due to azoospermia. Manifestations of feminization and hypogonadism are probably associated with the insensitivity of defective androgen receptors to male sex hormones (their level in patients remains normal). The prognosis of the disease is generally favorable. Walking and the possibility of self-service are preserved. Life expectancy is not shortened. However, there is an increased risk of malignant tumors due to hormonal imbalance (breast cancer), which requires oncological alertness. The disease must be distinguished from ALS. At present, it is possible to conduct direct DNA diagnosis of the disease, establish heterozygous carriage, and carry out prenatal diagnosis.

Distal SA. Autos.-recess. form can begin in early childhood, while autos.-domin. form - at 23 - 25 years. With both types of inheritance, both severe clinical forms and moderate forms can be presented. The disease begins with weakness and atrophy of the anterior leg muscles, which are accompanied by deformities of the feet. Tendon reflexes may be preserved. The clinical picture may resemble HMSN type Ι, however, sensitivity is not impaired in SA. In severe autos.-reces. forms, muscle weakness gradually spreads to the proximal muscles of the legs, and sometimes the arms. The degree of weakness in the arms varies between different families, but is almost the same in representatives of the same family. Approximately 25% of patients have scoliosis. In some families, the affected may show pseudohypertrophy or atrophy of the calf muscles. ENMG data make it possible to distinguish the disease from peripheral neuropathy: the speed of conduction along the motor axons is normal, despite signs of total denervation of the small muscles of the foot. Evoked sensory potentials are also normal. The level of CPK is normal, sometimes moderately elevated.

Segmental SA: only the hands or only the feet are affected; the disease is characterized by genetic heterogeneity: autos.-home. inheritance is typical of the adult-onset form; autos.-recess. - for a form that begins in adolescents, mostly boys. Hand atrophy is usually asymmetrical, progresses over 2 to 4 years, and sometimes affects the forearms. Fasciculations and cramps are characteristic. Usually, the growth of artophia stops with time, but in some cases the muscles of the legs are involved.

Monomelic SA: This rare form affects the muscles of the arm or leg. Most cases have been reported in Japan and India. Monomelic AS usually occurs as sporadic cases with a 10:1 male predominance, suggesting an X-linked recessive inheritance pattern. Age of debut varies from 10 to 25 years. Muscle weakness and atrophy increase imperceptibly. The hand is affected more often than the leg. Weakness may be distributed only proximally, only distally, or involve the entire limb. Atrophy is initially unilateral and occurs in muscles innervated by C7, C8, and Th1 spinal segments. Bilateral muscle weakness usually develops within 2 years. Often there is a unilateral or bilateral postural tremor of the hands. Fasciculations in the proximal muscle groups precede the onset of weakness and atrophy. The progression of the disease is slow and after 5 years, as a rule, stabilization occurs. However, after 15 years, another limb may be involved in the pathological process. Other causes of monoplegia must be excluded.

Scapuloperoneal SA Stark-Kaiser. This rare form of SA is genetically heterogeneous. Cases inherited in an autosomal dominant manner make their debut in the 3rd-4th decade of life and are characterized by a relatively benign course, while cases with autosomal recessive inheritance make their debut at 3-5 years of age. Linkage to the 12q24 locus is assumed. In some patients, a mutation in the SMN gene of the 5th chromosome is determined, which casts doubt on the nosological independence of a number of cases of scapuloperoneal CA and indicates a peculiar variant of proximal CA gene expression. Weakness and atrophy of the muscles prevail in the humeroscapular muscle group and the extensors of the foot. Perhaps the slow spread of atrophy to the proximal legs and the muscles of the pelvic girdle. Differential diagnosis is carried out with scapuloperoneal myodystrophy.

Facial-shoulder SA Fenichela. A rare autosomal recessive form of AS that begins in the 2nd decade of life. The gene has not yet been mapped. The disease mimics Landouzy-Dejerine's facial scapulohumeral myodystrophy, but with it, tendon reflexes are usually induced, and muscle strength is slightly reduced. On EMG, a neuronal-axonal type of lesion is recorded. CPK activity is normal. A number of researchers dispute the nosological independence of this form and consider it within the framework of the Landouzy-Dejerine disease.

Oculopharyngeal SA. An autosomal dominant mode of inheritance is assumed. The disease usually begins in the 4th decade of life with external ophthalmoplegia, dysphagia, and dysarthria. In some cases, weakness in the distal extremities and back muscles joins. The course is slow, benign. Sometimes the disease is considered within the framework of mitochondrial myopathies.

source: materials of the guide for doctors "Diseases of the nervous system" ed. N.N. Yakhno, D.R. Shtulman, ed. 2nd, volume 1; Moscow, "Medicine", 2001 (as well as the following articles).

read also:

article "A clinical case of late debut of spinal amyotrophy in an adult patient - a stage in the development of amyotrophic lateral sclerosis?" T.B. Burnasheva; Israeli Medicine Center, Almaty, Kazakhstan (Medicine magazine No. 12, 2014) [read];

article "A clinical case of late onset of undifferentiated spinal amyotrophy" Goncharova Ya.A., Simonyan V.A., Evtushenko S.K., Belyakova M.S., Evtushenko I.S.; State Institution "Institute of Emergency and Reconstructive Surgery named after A.I. VC. Husak of the National Academy of Medical Sciences of Ukraine”, Donetsk National Medical University. M. Gorky (International neurological journal, No. 5, 2012) [read];

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Definition
Spinal amyotrophies are a group of hereditary diseases caused by a primary dystrophic process in the anterior horns of the spinal cord, manifested by flaccid paresis and muscle atrophy.
They make up about 7% of other motor neuron diseases, which also include amyotrophic lateral sclerosis, very rare primary lateral sclerosis, and progressive bulbar palsy. The prevalence of spinal amyotrophy among the population is from 0.65 to 1.6 per 100,000 population.

Classification
Various clinical forms of spinal amyotrophies differ in age of onset, rate of progression, and type of inheritance of the disease.

The most common forms:
I. Spinal amyotrophies of childhood and adolescence:
1) acute malignant infantile spinal amyotrophy (Verdnig-Hoffmann);
2) chronic infantile spinal amyotrophy;
3) juvenile spinal amyotrophy (Kugelberg-Welander).
II. Spinal amyotrophies of adults:
1) bulbospinal amyotrophy (Kennedy);
2) distal spinal amyotrophy (Duchenne-Arana);
3) scapulo-peroneal amyotrophy (Vulpiana).

Clinic and diagnostic criteria
1. General clinical features: symmetrical weakness of the proximal, less often distal muscles. Relatively rare is the asymmetry of the lesion of the muscles of the limbs, the involvement of the bulbar muscle group. There are usually no sensory disturbances, pyramidal insufficiency is not typical, although sometimes it occurs at a late stage of the disease.

2. Diagnostic criteria:
- the hereditary nature of the disease (the type of inheritance is not always easy to establish);
- muscular atrophy with fasciculations, fibrillations;
- EMG - a picture of the defeat of the anterior horns of the spinal cord;
- absence of sensory and pelvic disorders;
- progressive course;
- beam atrophy of muscle fibers during biopsy.

3. Clinical features of individual forms:
1) Verdnig-Hoffmann spinal amyotrophy (malignant infantile spinal amyotrophy) is an autosomal recessive disease, the mutant gene is mapped on the 5th chromosome. Another gene has been identified that provides suppression of apoptosis - the programmed death of neurons. It is this gene that is often absent in severely ill patients. The incidence of the disease is 1: 25,000 newborns. Recently, it has been subdivided into acute (actually the Werdnig-Hoffmann form) and chronic infantile spinal amyotrophy.
The acute form manifests itself in the first 5 months of life and ends fatally by 1.5 years. In the chronic form, early childhood (beginning before 1.5-2 years, death by 4-5 years from respiratory failure, pneumonia) and late form (beginning before 2 years, immobility by 10 years, death at the age of 15-18 years) ). The main symptoms: paresis of the proximal legs, then arms, trunk muscles, respiratory, areflexia, fibrillation, fasciculations of the skeletal muscles and tongue, contractures, bone deformities, bulbar symptoms, general hyperhidrosis. On EMG - spontaneous bioelectrical activity at rest with the presence of fasciculation potentials. With arbitrary contractions, a reduced electrical activity is recorded with a "palisade" rhythm. The activity of enzymes in the blood serum does not change. At pathomorphological examination - a decrease in the number of cells in the anterior horns of the spinal cord, in the motor nuclei of the brain stem, degenerative changes in them. In muscles - beam atrophy of muscle fibers;

2) Kugelberg-Welander spinal amyotrophy (juvenile or pseudomyopathic form) - a disease with an autosomal recessive type of inheritance. The type of flow, the nature of the distribution of muscle atrophies are similar to Erba-Roth muscular dystrophy, but there are common muscle fasciculations. EMG confirms the spinal nature of muscle atrophy. The pathomorphology of muscles during biopsy, along with neurogenic (beam) amyotrophy, reveals signs of primary (diffuse) muscle damage.
The disease begins between the ages of 2 and 15 and progresses very slowly. Muscle weakness and atrophy develop first in the proximal legs, pelvic girdle and gradually spread to the muscles of the shoulder girdle. Some patients have muscle pseudohypertrophy, hyperfermentemia (especially an increase in CPK), which makes this form similar to PMD. Bone deformities and muscle retractions are absent. Bulbar movement disorders occur at a late stage of the disease. Patients retain the possibility of self-service for a long time, and often they are able to work for a number of years;

3) Kennedy's bulbospinal amyotrophy - X-linked recessive disease, usually manifesting after 30 years. It is caused by a specific mutation in the androgen receptor gene mapped on the X chromosome. Only men get sick. Beginning - from the proximal limbs, after 10-20 years (sometimes earlier) bulbar disorders occur in the form of atrophy and weakness of the masticatory muscles, dysphagia, dysarthria. Due to the very slow progression of the disease, bulbar disorders do not lead to severe impairment of vital functions for many years. There is a tremor of the hands, head, reminiscent of essential trembling. A characteristic symptom is fasciculations in the perioral muscles and tongue and endocrine disorders (gynecomastia, decreased potency, testicular atrophy, diabetes mellitus). The course is slow, the social prognosis is mostly favorable;

4) distal spinal Duchenne-Aran amyotrophy. The mode of inheritance is autosomal dominant or autosomal recessive, sporadic cases are very frequent. Beginning after 20 years (more often at 30-50). The classic form of the disease is characterized by the onset from the distal parts of the upper extremities (“clawed hand”), later atrophy spreads to the forearm, shoulder (“skeleton hand”), after many years weakness of the muscles of the peroneal group and other muscles of the lower leg, thighs, torso joins. There is mild pyramidal symptoms. At the beginning of the process, there may be a unilateral lesion, monoparesis (Mozolevsky Yu. V. et al., 1988). A combination with parkinsonism, torsion dystonia and myoclonic hyperkinesis is possible (Makarov A. Yu., 1967). The disease rarely significantly affects the social status of patients due to extremely slow progression (with the exception of cases with comorbidity);

5) Vulpian's scapulo-peroneal form. It begins between the ages of 20-40 with atrophy of the muscles of the shoulder girdle (restriction of movement in the shoulder joints, “pterygoid” shoulder blades), with time, weakness of the extensors of the feet and lower legs joins, although the reverse sequence is also possible. The differential diagnosis should first of all be carried out with Davidenkov's scapulo-perojeal myodystrophy. The progression is slow, often elderly patients with a 30-40-year period of the disease move independently.

4. Data from additional studies:
- EMG, ENMG. With total EMG, there are signs of anterior horn lesion: at rest, spontaneous bioelectrical activity in the form of fissiculation potentials with an amplitude of up to 200 μV, with an voluntary contraction, EMG is reduced with a “palisade” rhythm and sharply discharged with severe muscle damage. On ENMG - a decrease in the amplitude of the M-response and the number of functioning motor units. The speed of the impulse varies depending on the form of spinal amyotrophy and the age of the patient;
- muscle biopsy (typical fascicular atrophy, in contrast to diffuse with PMD);
- MRI. Sometimes allows to reveal atrophy of the spinal cord;
- study of the activity of CPK, LDH, ALT in the blood serum (in contrast to PMD, it is normal or slightly increased);
- medical genetic counseling.
Differential diagnosis: 1. With PMD, phenocopying spinal amyotrophy (Erba-Roth disease, Davidenkov's scapulo-peroneal myodystrophy, etc.).
2. Acute spinal amyotrophy of Werdnig-Hoffman - with other causes of the "sluggish child" syndrome (atonic form of cerebral palsy, congenital myopathy, Marfan's syndrome, etc.).
3. With amyotrophic lateral sclerosis - Kennedy's bulbospinal amyotrophy, other forms of adult spinal amyotrophy (the final diagnosis is often after 1-3 years of observation of the patient).
4. With cervical ischemic myelopathy (spinal amyotrophies of adults).
5. With chronic forms of tick-borne encephalitis, Lyme disease.
6. With post-polio syndrome.

Course and forecast
It depends on the age of onset of the disease. In children's forms, death is even in the case of a chronic course and the onset of the disease up to 2 years. In the case of juvenile Kugelberg-Welander amyotrophy, the possibility of self-care remains for many years. In other forms of spinal amyotrophy in adults, life expectancy does not actually change, however, an increasing motor deficit usually leads to limited life activity and disability (many years after the onset of the disease).

Principles of treatment
Hospitalization for primary diagnosis, repeated courses of maintenance therapy (1-2 times a year), in case of decompensation of the disease after an injury, an infectious disease, etc.
The treatment is based on the same principles as myodystrophy - improving the conduction of a nerve impulse, correcting energy disorders in the muscles, and improving peripheral blood circulation. Also used drugs that stimulate the function of the central nervous system - cerebrolysin, nootropics. Methods of physiotherapy are widely used, in particular, amplipulse - phoresis of benzohexonium, prozerin. In some cases, orthopedic correction of contractures, paresis is necessary.

Medical and social examination Criteria of VUT

An indication for VL in working patients (with Kugelberg-Welander amyotrophy, adult spinal amyotrophy) may be temporary decompensation, a prophylactic course of treatment in a hospital (duration - 1-2 months).
Characteristics of disability
With rapidly progressing early childhood forms (Werdnig-Hoffman disease), the ability to move and self-service is quickly impaired. In other forms, the ability to move and manipulative actions suffers (distal form of adult amyotrophy), to communicate due to dysarthria (Kennedy's bulbospinal amyotrophy). In the final stages of all forms, the leading criterion for assessing the state of vital activity will be the ability to move and self-service due to widespread paresis and contractures.

Contraindicated types and working conditions
1) All types of intensive physical labor, work with a forced position of the body, with prolonged tension of a certain muscle group, at a prescribed pace (on an assembly line, in a team), driving professions; 2) work related to exposure to toxic substances, vibration, radiation, etc.

Indications for referral to BMSE
1. At the age of up to 18 years, when a child, if there are medical indications, can be recognized as disabled.
2. Moderate or severe impairment of motor functions, limiting the ability to move independently, self-service or work.
3. For working patients, it is impossible to continue working in the specialty due to the progressive course of the disease, persistent decompensation, and long-term temporary disability.

Able-bodied patients
With a benign, slowly progressive course (especially with dominant forms of inheritance); with mild paresis of the distal part of only the lower or only the upper limbs (adult spinal amyotrophy); with mild paresis in the proximal lower extremities and pelvic girdle, with education, specialty, work experience, in the absence of factors in their work that adversely affect the course of the disease. When creating the necessary working conditions for such patients, often according to the conclusion of the VC, they can remain able to work for a long time.

Required minimum examination when referring to BMSE
1) Information about the type of inheritance of the disease.
2) EMG, ENMG.
3) The results of the pathomorphological study of the muscle biopsy.
4) The results of determining the activity of CPK in blood serum.

Indications for referral to BMSE
When determined at the age of up to 18 years: a) partial impairment of life and social maladaptation as a manifestation of a hereditary disease (chronic spinal Werdnig-Hoffman amyotrophy, Kugelberg-Welander amyotrophy and other childhood and juvenile forms); b) a pronounced progressive impairment of the motor function of the limbs.

When determined after 18 years:
Group I: determined in the later stages, with an extended generalization of the atrophic process that has ended: lower or upper paraplegia, pronounced tetraparesis; severe damage to the muscles of the trunk, widespread contractures in large joints of the limbs, since these disorders lead to a violation of the ability to move and self-service of the third degree (more often in the Werdnig-Hoffman form);

Group II: slow progression, but in the stage of the beginning generalization of the atrophic process, in the presence of a pronounced distal lower paraparesis, its combination with moderate paraparesis of the upper limbs, especially if the process captures the forearms; in the presence of a pronounced proximal lower paraparesis and paresis of the muscles of the pelvic girdle, which leads to a sharp violation of the ability to walk and stand; with pronounced upper paraparesis - both distal and proximal; in case of accession to a significantly pronounced (2-3 points) paresis of the legs, even mild bulbar disorders (according to the criteria for impaired mobility, labor activity of the second degree);

Group III: slowly progressive amyotrophies with moderately pronounced paraparesis of the upper or lower extremities, moderately pronounced paresis of the proximal lower extremities and pelvic girdle, if these disorders lead to the inability to work in the main profession, and rational employment is impossible, or for the period of vocational training of persons who do not have profession, as well as those forced to acquire a new one (more often in the Kugelberg-Welander form) - according to the criteria for limiting the ability to move independently of the first degree and (or) to work at the first degree.

With a pronounced violation of motor functions, the futility of rehabilitation measures, disability is established indefinitely (after no more than 4 years of observation of the patient).

Reasons for disability: 1) disability since childhood (in the form of Kugelberg-Welander); 2) a general disease or a disease acquired during military service (with adult spinal amyotrophies).
Corresponds to that carried out in relation to patients with PMD. In forms with a known gene locus, prenatal diagnosis is possible in the initial period of pregnancy. In the case of Kugelberg-Welander amyotrophy, early career guidance and training of patients often contributes to the prevention of disability, while in adults with spinal amyotrophy, rational employment, sometimes after acquiring a new profession.

Rehabilitation
An individual program is compiled for patients with Kugelberg-Welander disease and adult spinal amyotrophies.
1. Medical rehabilitation consists of repeated courses of drug therapy, massage, physiotherapy exercises, spa treatment, supply of orthopedic shoes, fixing devices, a bed and a mattress of a special design. Its psychological aspect includes the organization of training for disabled children at home, the orientation of the patient and his parents to an adequate employment arrangement, and the organization of the child's life in the family.
2.Vocational rehabilitation:
a) vocational training in technical schools (lyceums, colleges), vocational rehabilitation centers for patients with Kugelberg-Welander amyotrophies and adult spinal amyotrophies. Recommended specialties: accounting, office work organization, marketing, jurisprudence and accounting in the social security system, rate technologist, radio mechanic for the repair of stationary radio and television equipment, shoemaker for shoe repair, watchmaker, bookbinder, etc .;
b) employment of disabled people of group III. Depending on the predominant localization and severity of muscle atrophy, they may be recommended to work:
- mental work: economist, planner, engineer, technologist, lawyer, translator, statistician, bibliographer, librarian;
- Accounting, clerical and administrative work: an accountant, a rater, an accountant, a merchandiser, an inspector of the personnel department, a hostel commandant, etc.;
- light and moderate physical labor (for patients with paresis of the legs): fitter-assembler of small-sized products, radio and television equipment repairman in the workshop, bookbinder;
- work in mass household professions (in case of damage to the upper or lower extremities): watchman, timekeeper, dispatcher at a stationary workplace, kiosk.

Labor recommendations should provide for the optimal nature of labor, requiring light physical and neuropsychic stress in comfortable or close to comfortable conditions (I category of severity - a one-time weight lift of not more than 2 kt, physical activity per shift - 900 kcal).

c) disabled people of group II (adult amyotrophy and Kugelberg-Welander disease) can be employed at home in their main specialty (highly qualified mental workers), as well as a bookbinder, gluer, assembler of small parts, knitter.

3. Social rehabilitation: supplying patients with special devices for using the bathroom, toilet, as well as a wheelchair. Due to the progressive course of the disease, driving is contraindicated for the patient.

It is extremely important for each person to maintain their independence and activity. However, there are diseases in which patients gradually become incapacitated and can only move around with assistance or in wheelchairs. These types of diseases include spinal muscular atrophy, in which a person can not only stop walking, but even sometimes is unable to breathe on his own.

Spinal muscular atrophy (SMA, spinal amyotrophy) is a whole group of hereditary diseases characterized by degeneration of motor neurons in the spinal cord.

This is one of the most common pathologies among genetic disorders. The incidence among newborns is one case per 6,000–10,000 children, depending on the country studied. Almost half of those born with SMA cannot even reach the age of two and die.

However, muscle atrophy is not only a childhood disease, people of all ages can suffer from it. Scientists have found that every 50th inhabitant of the Earth is a carrier of the recessive gene SMN1 (survival motor neuron), which leads to SMA. Although all types of this disease come from a mutation in one chromosome region, it has many forms with varying degrees of symptoms at all ages. Despite the loss of motor activity of the muscles, their sensitivity is preserved. The intellect of patients is not affected by the process, it is fully consistent with the norm.

This disease was first described in 1891 by Guido Werding, who not only recorded the symptoms, but also studied morphological changes in the muscles, nerves and spinal cord.

The most common types of proximal SMA occur (approximately 80–90% of all cases), in which muscles located closer to the center of the body (femoral, vertebral, intercostal, etc.) are more affected.

Video of a patient with spinal muscular atrophy

Types of disease and severity of manifestations

Among the proximal species, four forms of the disease are distinguished, which are grouped based on the age of onset of the process, the severity of symptoms, and average life expectancy.

Forms of proximal spinal amyotrophy - table

There are a number of spinal muscular atrophies that involve the distal parts of the body. The upper extremities are most often affected, and the disease itself is usually recorded at a fairly adult age.

With SMA, the muscles significantly lose their mass and volume.

In addition to this classification, there is a division of SMA into isolated (occurring only due to damage to motor neurons in the spinal cord) and combined forms (additional diseases such as heart disease, oligophrenia, congenital fractures, etc. join spinal amyotrophy).

Causes and factors of pathology

Spinal muscular dystrophy occurs due to inherited recessive genes located on the fifth chromosome (SMN, NAIP, H4F5, BTF2p44). As a rule, parents do not have manifestations of SMA, but both are carriers and in 25% of cases pass on a defective gene to their child, which disrupts the synthesis of the SMN protein, which leads to degeneration of motor neurons in the spinal cord.

Violations in the work of just one section of the chromosome lead to different types of SMA

At a certain stage of embryonic development, there is a programmed cell death of the precursors of motor neurons that have formed in excess. Of these, approximately half should remain in the norm, which further differentiates into nerve cells. However, at a certain period, this process is stopped by the functioning of the SMN gene. When mutated, its work is disrupted, cell death continues even after the birth of a child, which leads to spinal muscular atrophy.

The disease affects the motor neurons of the anterior horns of the spinal cord.

Symptoms in children and adults

The main symptom of SMA disease is muscle flaccidity, weakness, and wasting. However, each of the forms of spinal amyotrophy has its own characteristics:

SMA in pregnancy is associated with many complications. Often a woman cannot give birth on her own and she is prescribed a caesarean section.

X-rays show the curvature of the spine and its subsequent correction with the help of surgery

Diagnosis and differential diagnosis

A method that with 100% probability indicates the presence of spinal muscular atrophy is DNA analysis using molecular genetic diagnostics. It aims to identify a defective gene on the fifth chromosome, at the 5q11-q13 locus.

DNA analysis will help to accurately establish the diagnosis

Biochemical analysis is carried out to identify the content of creatine kinase (CPK), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). If their level is normal, then this makes it possible to exclude progressive muscular dystrophy similar in symptoms.

With the help of EFI (electrophysiological research), impulses of the bioelectrical activity of the brain and nerve trunks are recorded. In SMA, there is a “palisade” rhythm characteristic of damage to the neurons of the anterior horns.

MRI (magnetic resonance imaging) and CT (computed tomography) do not always help to identify the characteristic changes for MCA on images.

Differential diagnosis is necessary in order to distinguish spinal muscular atrophy from muscular dystrophy, cerebral palsy, amyotrophic lateral sclerosis, Marfan's syndrome, tick-borne encephalitis and other diseases of the central nervous system.

Tandem mass spectrometry, which allows to determine the decrease in the level of various amino acids in the body, reveals a lack of SMN protein.

Treatment

At the moment, there is no effective treatment for spinal muscular atrophy. At the initial detection of the disease, mandatory hospitalization with various studies is indicated.

Medical therapy

Drug therapy is aimed at improving the conduction of nerve impulses, normalizing blood circulation and slowing down the destruction of motor neurons. Use the following drugs:

anticholinesterase drugs are aimed at reducing the activity of an enzyme that breaks down acetylcholine, which, in turn, transmits excitation along nerve fibers. These include Sangviritrin, Oksazil, Prozerin;
Prozerin improves the passage of an impulse from a neuron to a muscle

preparations for stimulating metabolism in muscle and nerve fibers - Potassium orotate, Actovegin, Nicotinic acid.
Actovegin improves metabolism in nervous tissue

Diet

It should be understood that the basis of nutrition for a patient with SMA should be food that can provide the muscles with the necessary substances as much as possible.

It is worth enriching the patient's diet with foods high in protein. However, there are currently no reliable data that indicate an improvement in the condition of patients with a certain diet. In some cases, an excess intake of amino acids in the body can be harmful, since there is not enough muscle tissue to process them.

Legumes - a source of protein

It is necessary to reduce the calorie content of food, because due to insufficient physical activity, some patients tend to gain excess weight.

Physiotherapy methods, including massage

Patients need to conduct sessions of therapeutic massage aimed at maintaining muscle functions. UHF (ultra-high-frequency therapy), electrophoresis, manual practices will also be useful. There are special breathing exercises to stimulate the lungs.

Massage is a treatment for spinal amyotrophy

With the help of normalized physical activity, joint stiffness can be prevented and muscles can be kept in good shape. Very useful classes in the pool, where there is a minimum load on the spine. It is important to choose the right orthopedic devices that will support the chest and limbs.

Patients with SMA are forced to use special walkers that support them while walking

Folk remedies

Folk remedies for the treatment of spinal muscular atrophy do not exist. It is very important to immediately consult a doctor after the first symptoms are detected. In no case should you self-medicate, as this can lead to death.

Treatment prognosis and possible complications

The treatment prognosis is highly dependent on the type of spinal muscular atrophy. With the most malignant first variant, the most common outcome is the early death of the patient, and in other cases it is sometimes possible to maintain the ability to move independently until old age.

Complications of SMA include: scoliosis, acute pulmonary insufficiency, paralysis, chest deformities, loss of chewing and swallowing functions.

Prevention

There is no cure for spinal muscular atrophy. The only thing that can be done is to consult a geneticist during pregnancy planning.