Stimulation electromyography. Hereditary motor sensory neuropathy (Charcot-Marie-Tooth)

Method of determination Sequencing. The conclusion of a geneticist is issued!

Material under study Whole blood(with EDTA)

Study of mutations in the LMNA gene.

type of inheritance.

Autosomal recessive.

Genes responsible for the development of the disease.

The LMNA A/C (LAMIN A/C) gene encodes the lamin protein. It is located on chromosome 1 in the 1q22 region. Consists of 12 exons.

Mutations in the lamin gene also lead to the development of dilated cardiomyopathy with rhythm and conduction disturbances (DCM), muscular dystrophy Emery-Dreyfus, Slovenian-type hand-heart syndrome, Hutchinson-Gilford progeria, familial partial lipodystrophy, Maloof syndrome, congenital muscular dystrophy, limb-girdle type 1B muscular dystrophy, mandibuloacral dysplasia, lethal restrictive dermopathy.

To date, more than 40 loci responsible for hereditary motor-sensory neuropathies have been mapped, more than twenty genes have been identified, mutations in which lead to the development of the clinical phenotype of HMSN.

Definition of disease.

Charcot-Marie-Tooth disease (CMT), or Charcot-Marie neural amyotrophy, also known as hereditary motor and sensory neuropathy (HMSN), is a large group of genetically heterogeneous peripheral nerve diseases characterized by symptoms of progressive polyneuropathy with predominant lesion muscles of the distal limbs. HMSN is not only the most common hereditary disease of the peripheral nervous system, but also one of the most common hereditary human diseases.

Pathogenesis and clinical picture.

The disease manifests at the age of 20-40 years and its clinical manifestations largely resemble those of hereditary sensory neuropathies. The first signs of the disease are ulcers on the skin of the feet and legs, which often become infected. Characterized by the occurrence of spontaneous amputations of the toes and severe disorders of sensitivity. Weakness and atrophy occur mainly in the muscles of the distal legs, involvement of the distal arms in the process was noted only in half of the patients. The appearance of pain and autonomic disorders is not typical. There is significant intrafamilial variability in the severity of clinical manifestations.

Variant B1 was described in 9 siblings from the same family with consanguineous parents. The disease manifests itself in the second decade of life and is characterized by typical clinical manifestations. motor-sensory severe polyneuropathy. In 80% of patients, there is a deformity of the feet of the horse type. Decrease or disappearance of tendon reflexes from the legs is characteristic. In 60% of patients in the described family, as the disease progressed, involvement of the proximal muscle groups in the pathological process was noted. lower extremities. Kyphoscoliosis was detected in 30% of cases. The electromyogram reveals signs of axonal damage, a decrease in the amplitude of the M-response and sensory potential in the legs. The speed of impulse conduction along the peripheral nerves, as a rule, is not changed.

Only at B2, a number of patients showed a decrease in the speed of impulse conduction along the motor and sensory fibers of peripheral nerves (up to 30-40 m/sec). At morphological study a biopsy of peripheral nerves reveals a decrease in the number of myelin fibers, both small and large in diameter, processes of degeneration and regeneration of axons, as well as single bulbous thickenings of the nerves.

Frequency of occurrence:

For all forms, HMSN varies from 10 to 40:100,000 in different populations.

A list of mutations under study can be provided upon request.

Literature

1. Milovidova T.B., Shchagina O.A., Dadali E.L., Polyakov A.V. , Classification and diagnostic algorithms for various genetic variants of hereditary motor-sensory polyneuropathy // Medical genetics. 2011 v. 10. N 4. p. 10-16.
2. Shchagina O.A., Dadali E.L., Tiburkova T.B., Ivanova E.A., Polyakov A.V., Features of clinical manifestations and algorithms for molecular genetic diagnosis of genetically heterogeneous variants of hereditary motor-sensory polyneuropathies. // Molecular biological technologies in medical practice, "Alfa Vista N", Novosibirsk, 2009 p.183-193.
3. Shchagina O.A., Mersiyanova I.V., Dadali E.L., Fedotov V.P., Polyakov A.V. Mapping and identification of genes for Charcot-Marie-Tooth disease of the second type.// Medical Genetics, 2005, vol. 4, No. 8, pp. 378-382.
4. Bouhouche, A., Benomar, A., Birouk, N., Mularoni, A., Meggouh, F., Tassin, J., Grid, D., Vandenberghe, A., Yahyaoui, M., Chkili, T., Brice, A., LeGuern, E. A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3. Am. J. Hum. Genet. 65: 722-727, 1999.
5. OMIM.

Most hereditary sensorimotor neuropathies are demyelinating (eg, Charcot-Marie-Tooth type 1 disease). The pattern of inheritance can be autosomal dominant (most common), X-linked dominant, autosomal recessive, and X-linked recessive; sporadic cases are not uncommon.

In childhood or adolescence, foot deformity appears (hollow foot with hammer-shaped toes, which makes it difficult to choose shoes), hanging feet, progressive atrophy of the distal muscles of the legs, and later of the hands. Due to atrophy of the muscles of the lower third of the thigh and lower leg, the legs take on the shape of inverted bottles. Tendon reflexes in the legs are lost early, in the hands - much later. A moderate decrease in tactile, vibrational and proprioceptive sensitivity also joins later.

Some patients have concomitant symptoms: atrophy optic nerves, pigmentary degeneration retina, coordination disorders, extrapyramidal disorders, symptoms of damage to cortical motor neurons, scoliosis, dysraphia, autonomic disorders. As a rule, there is Raynaud's syndrome, thickened nerves are sometimes visible or palpable. A hollow foot is observed in a third of cases; this is a characteristic, but not pathognomonic symptom, and is not uncommon in healthy people.

Most cases are familial, although this is not always obvious (there are asymptomatic cases, some relatives consider their illness to be "arthritis", etc.). In general, the disease progresses slowly, but can proceed in different ways: if some patients lose their ability to work quite early, others work until retirement age.

The rate of propagation of excitation along the motor nerves is significantly reduced, the action potentials of sensory nerves are reduced or absent. Nerve biopsy often shows nerve hypertrophy with "bulbous" Schwann cell thickenings resulting from alternating demyelination and remyelination.

Treatment is symptomatic, exercise therapy is important for the prevention of contractures and facilitation of movements. Most patients need orthopedic shoes, some need ankle braces, sometimes resort to surgical treatment contractures and paralysis.

Other hereditary sensorimotor polyneuropathies

Other forms of hereditary sensorimotor neuropathies include Charcot-Marie-Tooth type 2 disease, Dejerine-Sotte syndrome, and Refsum disease. Dejerine-Sott syndrome is characterized by early start, severe course, pronounced thickening of the nerves, ataxia, nystagmus, hyperkinesis, kyphoscoliosis, increased protein levels in the CSF.

Chronic demyelinating polyneuropathy with nerve hypertrophy is seen in some leukodystrophies. childhood, combined in this case with atrophy of the optic nerves, mental retardation or dementia, epileptic seizures and various movement disorders.

Sensory motor neuropathy is part of clinical picture a number of hereditary metabolic disorders.

Among them, autosomal recessive ones predominate, but there are X-linked recessive ones (Fabry disease and adrenomyeloneuropathy). These diseases are rare but treatable, so it is important to diagnose them.

Prof. D. Nobel

Stimulation EMG includes various techniques studies of peripheral nerves, autonomic nervous system and neuromuscular transmission:

• SRV on motor fibers;
• NRT for sensitive fibers;
• F-wave;
• H-reflex;
• blink reflex;
• bulbocavernosus reflex;
• evoked skin-sympathetic potential (VKSP);
• decrement test.

Stimulation methods for studying the conductive function of motor fibers, sensory fibers and VCSP make it possible to identify the pathology of each type of nerve fiber in the nerve and determine the localization of the lesion (the distal type of nerve damage is typical for polyneuropathies, local impairment of the conduction function - for tunnel syndromes, etc.) .

The options for the reaction of the peripheral nerve to damage are rather limited.

Any pathological factor, disturbing nerve function, ultimately leads to damage to the axons, or the myelin sheath, or both of these formations.

Objectives of the study: to determine the functional state and degree of damage to the motor, sensory and autonomic structures of the nerves; local violations function of myelinated nerves, as well as recovery motor functions; diagnosis and differential diagnosis of lesions of sensorimotor formations at the segmental, suprasegmental, peripheral and neuromuscular levels; identification and assessment of the degree of neuromuscular transmission disorders in myasthenia gravis and myasthenic syndromes; perspective assessment various methods treatment and the results of the use of certain medicines, as well as the degree of rehabilitation of patients and restoration of the function of the affected motor and sensory nerves.

INDICATIONS

Suspicion of diseases associated with impaired function of motor and sensory fibers of peripheral nerves or neuromuscular transmission:

• various polyneuropathies;
• mononeuropathies;
• motor, sensory and sensorimotor neuropathies;
• multifocal motor neuropathy;
• tunnel syndromes;
• traumatic nerve damage;
• neural amyotrophy, including hereditary forms;
• root lesions spinal cord, cervical-brachial and lumbosacral plexus;
• endocrine disorders (especially hypothyroidism, diabetes 2 types) ;
• sexual dysfunction, sphincter disorders;
• myasthenia gravis and myasthenic syndromes;
• botulism.

CONTRAINDICATIONS

There are no special contraindications (including the presence of implants, pacemakers, epilepsy) for stimulation EMG. If necessary, the study can be carried out in patients in a coma.

PREPARATION FOR THE STUDY

Special training is not required. Before the start of the study, the patient takes off his watch, bracelets. Usually the patient is in a semi-sitting position in a special chair, the muscles should be as relaxed as possible. The limb under study is immobilized to exclude distortion of the shape of the potentials.

The extremity during the study should be warm (skin temperature 26-32 ° C), since with a decrease in skin temperature by 1 ° C, a decrease in NRV occurs by 1.1-2.1 m/s. If the limb is cold, before examination it is well warmed up with a special lamp or any heat source.

METHODOLOGY AND INTERPRETATION OF THE RESULTS

Stimulation EMG is based on the registration of the total response of a muscle (M-response) or nerve to stimulation with an electric current pulse. Examine the conductive function of motor, sensory and autonomic axons of peripheral nerves or functional state neuromuscular transmission.

Dysfunction of the axon (axonal process) leads to the development of the denervation-reinnervation process (DRP) in the muscle, the severity of which is determined using needle EMG. Stimulation EMG reveals a decrease in the amplitude of the M-response.

Dysfunction of the myelin sheath (demyelinating process) is manifested by a decrease in NRV along the nerve, an increase in the threshold for evoking an M-response, and an increase in residual latency.

It should be taken into account that the primary axonal process often causes secondary demyelination, and during the demyelinating process, at a certain stage, secondary lesion axon. The task of EMG is to determine the type of nerve lesion: axonal, demyelinating, or mixed (axonal demyelinating).

Stimulation and recording of the muscle response is carried out using surface electrodes. Standard dermal silver chloride (AgCl) disk or cup electrodes are used as lead electrodes, which are attached with an adhesive plaster. To reduce the impedance, conductive gel or paste is used, the skin is thoroughly wiped with ethyl alcohol.

M-answer

M-response - the total action potential that occurs in the muscle with electrical stimulation of its motor nerve. The M-response has the maximum amplitude and area in the zone of distribution of the end plates (at the motor point). The motor point is the projection onto the skin of the zone of the end plates of the nerve. The motor point is usually located on the most convex section (abdomen) of the muscle.

In the study of the M-response, a bipolar method of assignment is used: one electrode is active, the second is a reference. An active recording electrode is placed in the region of the motor point of the muscle innervated by the nerve under study; reference electrode - in the area of ​​the tendon of this muscle or in the place where the tendon is attached to the bone protrusion (Fig. 8-1).

Figure 8-1. Investigation of the conductive function ulnar nerve. Applying electrodes: an active abducting electrode is located at the motor point of the muscle that abducts the little finger; reference - on the proximal phalanx of the fifth finger; stimulating - at the distal point of stimulation on the wrist; grounding - just above the wrist.

In the study of the conductive function of the nerves, stimuli of supramaximal intensity are used. Usually, the M-response from the nerves of the hands begins to be recorded at a stimulus value of 6-8 mA, from the nerves of the legs - 10-15 mA. As the intensity of the stimulus increases, the amplitude of the M-response increases due to the inclusion of new MUs in the M-response.

A smooth increase in the amplitude of the M-response is associated with different excitability of nerve fibers: first, low-threshold fast-conducting thick fibers are excited, then thin, slow-conducting fibers. When all muscle fibers of the studied muscle are included in the M-response, with a further increase in the intensity of the stimulus, the amplitude of the M-response ceases to increase.

For the reliability of the study, the amplitude of the stimulus is increased by another 20-30%.

This value of the stimulus is called supramaximal.

Stimulation is carried out at several points along the course of the nerve (Fig. 8-2). It is desirable that the distance between the stimulation points be at least 10 cm. The M-response is recorded at each stimulation point. The difference in the latency of M-responses and the distance between the stimulation points make it possible to calculate the NPV for the nerve.

Rice. 8-2. Scheme for studying the conduction function of the ulnar nerve. Schematically shows the location of the outlet electrodes and the stimulation points of the ulnar nerve. At the distal point of stimulation, the M-response has the shortest terminal latency. The difference in latencies between the distal and more proximal points of stimulation determines the SRV.

When examining the conductive function of motor nerves, the following parameters are analyzed:

• the amplitude of the M-response;
• shape, area, duration of the negative phase of the M-response;
• the presence of conduction blocks, the decrement of the amplitude and area of ​​the M-response;
• M-response evoking threshold;
• NRV for motor (motor) fibers, M-response latency;
• residual latency.

The main diagnostically significant parameters are the amplitude of the M-response and CRV. The amplitude, area, shape, and duration of the M-response reflect the amount and timing of muscle fiber contraction in response to nerve stimulation.

M-response amplitude

The amplitude of the M-response is estimated from the negative phase, since its shape is more constant, and is measured in millivolts (mV). A decrease in the amplitude of the M-response is an electrophysiological reflection of a decrease in the number of contracting muscle fibers in a muscle.

Reasons for the decrease in the amplitude of the M-response:

Violation of the excitability of nerve fibers, when part of the nerve fibers does not generate an impulse in response to stimulation electric shock(axonal type of nerve damage - axonal polyneuropathies);

Demyelination of nerve fibers, when muscle fibers do not respond to nerve impulse, which leads to a decrease in the amplitude of the M-response, however, the trophic function of the nerve remains intact;

Various myopathies (PMD, polymyositis, etc.). The M-response is absent in muscle atrophy, nerve rupture, or its complete degeneration.

The neural level of the lesion is characterized by an increase in the threshold for evoking an M-response and a violation of the SRV, an increase in residual latency, and "scattered" F-waves.

For the neuronal level of damage (ALS, spinal amyotrophies, spinal cord tumor, myelopathy, etc.), when the number of motoneurons and, accordingly, axons and muscle fibers decreases, the normal threshold for evoking the M-response, normal SRV, "giant", large and repeated F-waves and their complete loss.

The muscle level of the lesion is characterized by normal SRV and the threshold for inducing an M-response, the absence of F-waves or the presence of low-amplitude F-waves.

Stimulation EMG data do not allow an unambiguous assessment of the level of damage to the peripheral neuromotor apparatus - this requires needle EMG.

Shape, area and duration of the M-response

Normally, the M-response is a negative-positive signal fluctuation. The duration of the M-response is measured by the duration of the negative phase, the area

The M-response is also measured by the area of ​​the negative phase. Self-reliant diagnostic value indicators of the area and duration of the M-response do not have, but in conjunction with the analysis of its amplitude and shape, one can judge the processes of formation of the M-response.

With demyelination of nerve fibers, the M-response is desynchronized with an increase in its duration and a decrease in amplitude, and at the proximal points, desynchronization increases.

Excitation block

The excitation conduction block is the decrement of the amplitude of the M-response during stimulation at two adjacent points of more than 25% (calculated as the ratio of the amplitude A1:A2, expressed as a percentage, where A1 is the amplitude of the M-response at one point of stimulation, A2 is the amplitude of the M-response at the next, more proximal stimulation point). In this case, the increase in the duration of the negative phase of the M-response should not exceed 15%.

At the heart of the pathogenesis of the block of the conduction of excitation is a persistent local focus of demyelination (no more than 1 cm), causing a violation of the conduction of the impulse. Tunnel syndromes are a classic example of blocks in the conduction of excitation.

Two diseases with multiple persistent blocks of excitation conduction are known - motor-sensory multifocal polyneuropathy (Sumner-Lewis) and multifocal motor neuropathy with blocks of excitation conduction.

Correct diagnosis of multifocal motor neuropathy is extremely important, as the disease clinically mimics ALS, which often leads to serious diagnostic errors.

An adequate method for identifying blocks of excitation conduction in multifocal motor neuropathy is the method of stepwise examination of the nerve - "inching", which consists in stimulating the nerve at several points with a step of 1-2 cm. The location of the blocks of excitation conduction in multifocal motor neuropathy should not coincide with places of nerve compression in typical carpal tunnel syndromes.

M-response threshold

The threshold for evoking an M-response is the intensity of the stimulus at which the minimum M-response appears. Usually, the M-response from the nerves of the arms begins to be recorded at a stimulus amplitude of 15 mA and a duration of 200 μs, from the legs - 20 mA and 200 μs, respectively.

For demyelinating polyneuropathies, especially for hereditary forms, in which the initial M-response can appear at a stimulus intensity of 100 mA and 200 μs, an increase in the threshold for evoking M-responses is characteristic. Low stimulation thresholds are observed in children, in thin patients (3-4 mA). Changes in the thresholds for evoking M-responses should not be considered as an independent diagnostic criterion- they must be evaluated in conjunction with other changes.

The speed of propagation of excitation along the motor fibers and the latency of the M-response

CVD is defined as the distance that an impulse travels along a nerve fiber per unit of time and is expressed in meters per second (m/s). The time between the delivery of an electrical stimulus and the onset of the M-response is called the latency of the M-response.

CRV decreases during demyelination (for example, with demyelinating polyneuropathies), since in the areas of destruction of the myelin sheath, the impulse does not propagate in a saltatory manner, but sequentially, as in unmyelinated fibers, which causes an increase in the latency of the M-response.

The latency of the M-response depends on the distance between the stimulating and retracting electrode, therefore, when stimulating at standard points, the latency depends on the patient's height. Calculation of RTS avoids the dependence of the results of the study on the height of the patient.

NRV in the area of ​​the nerve is calculated by dividing the distance between stimulation points by the difference in M-response latencies at these points: V = (D 2 - D 1)/ (L 2 - L 1), where V is the speed of conduction along the motor fibers; D 2 - distance for the second point of stimulation (distance between the cathode of the stimulating electrode and the active discharge electrode); D 1 - distance for the second point of stimulation (distance between the cathode of the stimulating electrode and the active discharge electrode); D 2 - D 1 reflects the distance between stimulation points; L 1 - latency at the first point of stimulation; L 2 - latency at the second point of stimulation.

A decrease in CRV is a marker of the process of complete or segmental demyelination of nerve fibers in neuritis, polyneuropathy, such as acute and chronic demyelinating polyneuropathies, hereditary polyneuropathy (Charcot-Marie-Tooth disease, except for its axonal forms), diabetic polyneuropathy, nerve compression (tunnel syndromes, injuries ) . Determination of SRV allows you to find out on which part of the nerve (distal, middle or proximal) pathological changes.

Residual latency

Residual latency is the calculated time of passage of an impulse along axon terminals. In the distal segment, the axons of the motor fibers branch into terminals. Since the terminal does not have a myelin sheath, the CRF for them is significantly lower than for myelinated fibers. The time between the stimulus and the onset of the M-response upon stimulation at the distal point is the sum of the transit time along the myelinated fibers and the transit time along the axon terminals.

To calculate the time of impulse passage through the terminals, it is necessary to subtract the time of impulse passage through the myelinated part from the distal latency at the first stimulation point. This time can be calculated by assuming that the CRV at the distal site is approximately equal to the CRV at the segment between the first and second stimulation points.

Formula for calculating residual latency: R = L - (D:V l-2), where R - residual latency; L - distal latency (time from stimulus to the beginning of the M-response upon stimulation at the distal point); D - distance (distance between the active discharge electrode and the cathode of the stimulating electrode); V l-2 - SRV on the segment between the first and second points of stimulation.

An isolated increase in residual latency on one of the nerves is considered a sign of tunnel syndromes. The most common carpal tunnel syndrome for the median nerve is carpal tunnel syndrome; for the elbow - Guyon's canal syndrome; for the tibial - tarsal tunnel syndrome; for the peroneal - compression at the level of the rear of the foot.

An increase in residual latencies on all studied nerves is characteristic of demyelinating type neuropathies.

Criteria for normal values

IN clinical practice it is convenient to use the lower limits of the norm for the amplitude of the M-response and SRV and the upper limits of the norm for the residual latency and the threshold for inducing the M-response (Table 8-1).

Table 8-1. Normal values parameters for studying the conduction function of motor nerves

Normally, the amplitude of the M-response is slightly higher at the distal points of stimulation; at the proximal points, the M-response is somewhat stretched and desynchronized, which leads to some increase in its duration and a decrease in amplitude (by no more than 15%). NRV along the nerves is slightly higher at the proximal stimulation points

A decrease in CRV, amplitude and desynchronization (increase in duration) of the M-response indicate nerve damage. The study of NRV on motor fibers allows you to confirm or refute the diagnosis and conduct differential diagnosis in diseases such as tunnel syndromes, axonal and demyelinating polyneuropathies, mononeuropathies, hereditary polyneuropathies.

Electromyographic criteria for demyelinating nerve damage

Classical examples of demyelinating neuropathies are acute and chronic inflammatory demyelinating polyneuropathies (CIDP), dysproteinemic neuropathies, hereditary motor sensory neuropathy (HMSN) type 1.

The main criteria for demyelinating polyneuropathies:

• an increase in the duration and polyphasia of the M-response with normal amplitude
• decrease in NRV along motor and sensory axons of peripheral nerves;
• "loose" character of F-waves;
• the presence of excitation blocks.

Electromyographic "clear criteria for nerve damage of an axonal nature. Most toxic (including medicinal) neuropathies are considered classic examples of axonal neuropathies. HMSN type 11 (axonal type of Charcot-Marie-Tous disease).

The main criteria for axonal polyneuropathies:

• decrease in the amplitude of the M-response;
• normal NRV values ​​for motor and sensory axons of peripheral nerves;

With a combination of demyelinating and axonal signs, an axonal-demyelinating type of lesion is ascertained. Most a sharp decline SRV along peripheral nerves is observed in hereditary polyneuropathies.

In Russi-Levi syndrome, CVD can decrease to 7-10 m/s. with Charcot-Marie-Tus disease - up to 15-20 m / s. With acquired polyneuropathies, the degree of decrease in CRV is different depending on the nature of the disease and the degree of pathology of the nerves. The most pronounced decrease in velocities (up to 40 m/s on the nerves upper limbs and up to 30 m/s on the nerves of the lower extremities) are observed in demyelinating polyneuropathies. in which the processes of demyelination of the nerve fiber prevail over the damage to the axon: in chronic demyelinating and acute demyelinating polyneuropathy (GBS, Miller-Fisher syndrome).

Predominantly axonal polyneuropathy (for example, toxic: uremic, alcoholic, diabetic, drug, etc.) is characterized by a normal or slightly reduced CRV with a pronounced decrease in the amplitude of the M-response. To establish the diagnosis of polyneuropathy. at least three nerves must be examined. However, in practice it is often necessary to investigate large quantity(six or more) nerves.

An increase in the duration of the M-response serves as additional evidence of demyelinating processes in the nerve under study. The presence of blocks of conduction of excitation is characteristic of tunnel syndromes. and also for multifocal motor neuropathy with conduction blocks.

An isolated lesion of one nerve suggests mononeuropathy. including carpal tunnel syndrome. With radiculopathy in the initial stages, the conductive function of the motor nerves often remains intact. With absence adequate treatment within 2-3 months, the amplitude of the M-response gradually decreases. the threshold for its evoking may increase with intact SRV.

A decrease in the amplitude of the M-response with other absolutely normal requires expanding the diagnostic search and considering the possibility of a muscle disease or a disease of the motor neurons of the spinal cord. which can be confirmed by needle EMG.

Study of the conductive function of sensory nerves

NRV on sensory fibers is determined by recording the action potential of the afferent (sensory) nerve in response to its transcutaneous electrical stimulation. Methods of registration of SRV on sensory and motor fibers have much in common. at the same time, there is an important pathophysiological difference between them: in the study of motor fibers, the reflex response of the muscle is recorded. and in the study of sensory fibers - the excitation potential of the sensory nerve.

There are two ways to conduct research: orthodromic. in which the distal parts of the nerve are stimulated. and signals are recorded at proximal points. and antidromic. at which registration is carried out distal to the point of stimulation. In clinical practice, the antidromic method is more often used as a simpler one. although less accurate.

Methodology

The position of the patient, the temperature regime, the electrodes used are similar to those in the study of the function of motor fibers. You can also use special finger electrodes for the study of sensory fibers. When registering from the nerves of the hands, the active electrode is applied to the proximal phalanx II or III (for the median nerve) or the fifth finger (for the ulnar nerve), the reference electrode is located on the distal phalanx of the same finger (Fig. 8-3).

The position of the grounding and stimulating electrodes is similar to that in the study of motor fibers. When registering the sensory response of the sural nerve, the active electrode is placed 2 cm below and 1 cm posterior to the lateral malleolus, the reference electrode is 3-5 cm distal, the stimulating electrode is placed along the sural nerve on the posterolateral surface of the leg. At correct location stimulating electrode, the patient feels the irradiation of an electrical impulse along the lateral surface of the foot.

The ground electrode is located on the lower leg distal to the stimulating one. The sensory response is much lower in amplitude (for the ulnar nerve - 6-30 mV, while the motor response is 6-16 mV). The excitation threshold of thick sensory fibers is lower than that of thinner motor fibers; therefore, stimuli of subthreshold (in relation to motor fibers) intensity are used.

Most often, the median, ulnar, gastrocnemius, and less commonly, the radial nerve are examined.

The most significant parameters for clinical practice:

• sensory response amplitude;
• NRT on sensory fibers, latency.

Sensory response amplitude

The amplitude of the sensory response is measured by the "peak-peak" method (maximum negative - minimum positive phase). Violation of the axon function is characterized by a decrease in the amplitude of the sensory response or its complete loss.

Speed ​​of propagation of excitation and latency

As with motor fiber testing, latency is measured from stimulus artifact to the onset of response. CRV is calculated in the same way as in the study of motor fibers. A decrease in CRV indicates demyelination.

Normal values

In clinical practice, it is convenient to analyze the results relative to the lower limit of normal values ​​(Table 8-2).

Table 8-2. Lower bounds normal values ​​of the amplitude and CRV of the sensory response

Clinical significance of the analyzed parameters

As in the study of motor fibers, a decrease in CRF is characteristic of demyelinating processes, and a decrease in amplitude is characteristic of axonal processes. With severe hypesthesia, the sensory response is sometimes not possible to register.

Sensory disorders are detected in tunnel syndromes, mono- and polyneuropathies, radiculopathies, etc. For example, for carpal tunnel syndrome characteristic is an isolated decrease in the distal SRV along the median sensory nerve at normal speed at the level of the forearm and along the ulnar nerve. At the same time, in the initial stages, the SRV decreases, but the amplitude remains within the normal range. In the absence of adequate treatment, the amplitude of the sensory response also begins to decrease. Compression of the ulnar nerve in the Guyon canal is characterized by an isolated decrease in distal velocity along the sensory fibers of the ulnar nerve. A generalized decrease in CRV along sensory nerves is characteristic of sensory polyneuropathy. Often it is combined with a decrease in the amplitude of the sensory response. A uniform decrease in CRV below 30 m/s is characteristic of hereditary polyneuropathies.

The presence of anesthesia/hypesthesia in the presence of normal conductive function of sensory fibers makes it possible to suspect a higher level of damage (radicular or central genesis). In this case, the level of sensory disturbances can be clarified using somatosensory evoked potentials (SSEPs).

F-wave research

F-wave (F-response) - the total action potential of the DE muscle that occurs during electrical stimulation mixed nerve. Most often, F-waves are analyzed in the study of the median, ulnar, peroneal, tibial nerves.

Methodology

In many ways, the registration technique is similar to that in the study of the conductive function of motor fibers. In the process of studying motor fibers, after recording the M-response at the distal stimulation point, the researcher switches to the F-wave recording application, records F-waves with the same stimulus parameters, and then continues to study motor fibers at other stimulation points.

The F-wave has a small amplitude (usually up to 500 µV). When a peripheral nerve is stimulated at a distal point, an M-response with a latency of 3-7 ms appears on the monitor screen, an F-response has a latency of about 26-30 ms for the nerves of the arms and about 48-55 ms for the nerves of the legs (Fig. 8-4) . Standard research includes registration of 20 F-waves.

Diagnostically significant indicators of the F-wave:

• latency (minimum, maximum and average);
• speed range F-wave propagation;
• the phenomenon of "scattered" F-waves;
• F-wave amplitude (minimum and maximum) ;
• the ratio of the average amplitude of the F-wave to the amplitude of the M-response, the phenomenon of "giant F-waves";
• blocks (percentage of falling out) of F-waves, that is, the number of stimuli left without an F-response;
• repeated F-waves.

Latency, F-wave velocity range, "scattered" F-waves

Latency is measured from stimulus artifact to the onset of the F-wave. since the latency depends on the length of the limb, it is convenient to use the range of F-wave propagation velocities. The expansion of the velocity range towards low values ​​indicates a slowdown in conduction along individual nerve fibers, which may be an early sign of a demyelinating process.

In this case, a part of the F-waves may have a normal latency.

Calculation of RTS from the F-wave: V = 2 x D: (LF - LM - 1 ms), where V - RTS determined using the F-wave; D is the distance measured from the point under the cathode of the stimulating electrode to the spinous process of the corresponding vertebra; LF - F-wave latency; LM - latency of the M-response; 1 ms - the time of the central delay of the pulse.

With a pronounced demyelinating process, the phenomenon of "scattered" F-waves is often detected (Fig. 8-5), and in the most advanced stages their complete loss is possible. The reason for "scattered" F-waves is considered to be the presence of multiple foci demyelination along the nerve, which can become a kind of "reflector" of the impulse.

Reaching the focus of demyelination, the impulse does not propagate further antidromic, but is reflected and orthodromic propagates to the muscle, causing contraction of muscle fibers. The phenomenon of "scattered" F-waves is a marker of the neuritic level of damage and practically does not occur in neuronal or primary muscle diseases.

Rice. 8-4. Registration of the F-wave from the ulnar nerve healthy person. The M-response was recorded at a gain of 2 mV/D, its amplitude was 10.2 mV, the latency was 2.0 ms; F-waves were recorded at an amplification of 500 μV/d, the average latency is 29.5 ms (28.1 -32.0 ms), the amplitude is 297 μV (67-729 μV), the CRP determined by the F-wave method is 46 .9 m/s, speed range - 42.8-49.4 m/s.

Rice. 8-5. The phenomenon of "scattered" F-waves. Study of the conduction function of the peroneal nerve in a 54-year-old patient with diabetic polyneuropathy. The resolution of the M-response region is 1 mV / D, the F-wave region is 500 μV / d, the sweep is 10 ms / d. Determine the range of RTS in this case does not seem possible.

F-wave amplitude, "giant" F-wave phenomenon

Normally, the amplitude of the F-wave is less than 5% of the amplitude of the M-response in this muscle. Typically, the amplitude of the F-wave does not exceed 500 μV. F-wave amplitude is measured "peak to peak". During reinnervation, the F-waves become larger. Diagnostically significant is the ratio of the average amplitude of the F-wave to the amplitude of the M-response. An increase in the amplitude of the F-wave by more than 5% of the amplitude of the M-response (large F-waves) indicates the process of reinnervation in the muscle.

The appearance of the so-called giant F-waves with an amplitude of more than 1000 μV, reflecting the degree of pronounced reinnervation in the muscle, is also of diagnostic significance. "Giant" F-waves are most often observed in diseases of the motor neurons of the spinal cord (Fig. 8-6), although they can also appear in neural pathology that occurs with severe reinnervation.

F-wave dropout

The fallout of the F-wave is called its absence on the registration line. The cause of the loss of the F-wave can be a lesion of both the nerve and the motor neuron. Normally, 5-10% F-waves are acceptable. Complete loss of F-waves indicates the presence of a pronounced pathology (in particular, it is possible in the later stages of diseases with severe muscle atrophy).

Rice. 8-6. "Giant" F-waves. Examination of the ulnar nerve of a patient (48 years old) with ALS. The resolution of the M-response region is 2 mV / d, the F-wave region is 500 μV / d, the sweep is 1 ms / d. The average amplitude of the F-waves is 1084 µV (43-2606 µV). The speed range is normal (71 -77 m/s).

Repeated F-waves

Normally, the probability of a response from the same motor neuron is extremely small. With a decrease in the number of motor neurons and a change in their excitability (some motor neurons become hyperexcitable, others, on the contrary, respond only to strong stimuli), there is a possibility that the same neuron will respond many times, so F-waves of the same latency, shape and amplitude appear, called repeated. The second reason for the appearance of repeated F-waves is an increase in muscle tone.

Normal values

in a healthy person, it is considered acceptable if up to 10% of fallouts, "giant" AND repeated F-waves appear. When determining the speed range, the minimum speed should not be lower than 40 m/s for the nerves of the arms and 30 m/s for the nerves of the legs (Table 8-3). "Scattered" F-waves and complete loss F-waves are not normally observed.

Table 8-3. Normal values ​​of the amplitude and propagation velocity of F-waves

Normal values ​​of the minimum F-wave latencies depending on the growth are presented in Table. 8-4.

Table 8-4. Normal latency values ​​of F-waves, MS

Clinical relevance

The expansion of the range of erv, determined by the F-wave method, and, accordingly, the lengthening of the F-wave latencies, the phenomenon of "scattered" F-waves, suggest the presence of a demyelinating process.

In acute demyelinating polyneuropathy, as a rule, only a violation of the conduction of F-waves is detected, in chronic - F-waves may be absent (blocks of F-waves). Frequent repeated F-waves are observed with damage to the motor neurons of the spinal cord. Especially characteristic of diseases of motor neurons is the combination of "giant" repeated F-waves and their loss.

Another sign of damage to motor neurons is the appearance a large number"giant" F-waves. The presence of large F-waves indicates the presence of a reinnervation process in the muscle.

Despite high sensitivity F-waves, this method can only be used as an additional method (in conjunction with the data from the study of the conductive function of peripheral nerves and needle EMG).

Study of the H-reflex

H-reflex (H-response) - the total action potential of the DE muscle, which occurs when a weak electric current stimulates the afferent nerve fibers coming from this muscle.

Excitation is transmitted along the afferent fibers of the nerve through back roots From the spinal cord to the intercalary neuron and to the motor neuron, and then through the anterior roots along the efferent nerve fibers to the muscle.

Analyzed indicators of H-response: trigger threshold, shape, ratio of H-reflex amplitude to M-response, latent period or speed of its reflex response.

Clinical relevance. When pyramidal neurons are damaged, the threshold for evoking an H-response decreases, and the amplitude of the reflex response increases sharply.

The reason for the absence or decrease in the amplitude of the H-response may be pathological changes in the anterior horn structures of the spinal cord, afferent or efferent nerve fibers, posterior or anterior spinal nerve roots.

Study of the blink reflex

Blinking (orbicular, trigeminofacial) reflex - the total action potential that occurs in the examined facial muscle (for example, t. Orbicularis ocu li) with electrical stimulation of the afferent nerve fibers of one of the branches n. trigem eni - I, II or III. As a rule, two evoked reflex responses are recorded: the first - with latent period about 12 ms (monosynaptic, an analogue of the H-reflex), the second - with a latent period of about 34 ms (exteroceptive, with polysynaptic spread of excitation in response to irritation).

In the case of normal SRV along the facial nerve, an increase in the time of the reflex blinking response along one of the branches of the nerve indicates its damage, and its increase along all three branches of the nerve indicates damage to its node or nucleus. With the help of the study, it is possible to conduct a differential diagnosis between damage facial nerve in the bone canal (in this case, there will be no reflex blinking response) and its defeat after leaving the stylomastoid foramen.

Study of the bulbocavernosus reflex

Bulbocavernous reflex - the total action potential that occurs in the examined muscle of the perineum during electrical stimulation of the afferent nerve fibers n. pudendus.

The reflex arc of the bulbocavernosal reflex passes through the sacral segments of the spinal cord at the level of S 1 -S 4 , afferent and efferent fibers are located in the trunk of the pudendal nerve. When examining the function of the reflex arc, one can get an idea of ​​the spinal level of innervation of the sphincters, muscles of the perineum, as well as identify disorders in the regulation of sexual function in men. The bulbocavernosus reflex study is used in patients suffering from sexual dysfunction and pelvic disorders.

The study of evoked cutaneous sympathetic potential

The study of VKSP is carried out from any part of the body on which there are sweat glands. As a rule, VKSP registration is carried out from the palmar surface of the hand, the plantar surface of the foot, or the urogenital region. An electrical stimulus is used as a stimulus. Assess the SRV on the vegetative fibers and the amplitude of the VKSP. The study of VKSP allows you to determine the degree of damage to the vegetative fibers. Analyze myelinated and unmyelinated vegetative fibers.

Indications. Autonomic disorders associated with impaired heart rate, sweating, blood pressure as well as sphincter disorders, erectile dysfunction and ejaculation.

Normal indicators of VKSP. Palmar surface: latency - 1.3-1.65 ms; amplitude - 228-900 μV; plantar surface - latency 1.7-2.21 ms; amplitude 60-800 μV.

Interpretation of results. NRV and VCSP amplitude are reduced in sympathetic fiber lesions. Some neuropathies develop symptoms associated with damage to myelinated and unmyelinated autonomic fibers. These disorders are based on damage to the autonomic ganglia (for example, in diabetic polyneuropathy), the death of unmyelinated axons of peripheral nerves, as well as fibers vagus nerve. Sweating disorders, heart rhythm disorders, blood pressure, genitourinary system- the most frequent autonomic disorders with various polyneuropathies.

Study of neuromuscular transmission (decrement test)

Disturbances in synaptic transmission may be due to presynaptic and postsynaptic processes (damage to the mechanisms of mediator synthesis and release, disruption of its action on the postsynaptic membrane, etc.). The decrement test is an electrophysiological method by which the state of neuromuscular transmission is assessed, based on the fact that, in response to rhythmic nerve stimulation, the phenomenon of a decrease in the amplitude of the M-response (its decrement) is revealed.

The study allows you to determine the type of neuromuscular transmission disorder, assess the severity of the lesion and its reversibility in the process of pharmacological tests [test with neostigmine methyl sulfate (prozerin)], as well as the effectiveness of treatment.

Indications: suspicion of myasthenia gravis and myasthenic syndromes.

The variety of clinical forms of myasthenia gravis, its frequent association with thyroiditis, tumors, polymyositis and other autoimmune processes, wide variations in the effectiveness of the same interventions in different patients make this method of examination extremely important in the system of functional diagnostics.

Methodology

The position of the patient, the temperature regime and the principles of applying electrodes are similar to those in the study of the conductive function of the motor nerves.

The study of neuromuscular transmission is carried out in a clinically more weak muscle, since in an intact muscle, a violation of neuromuscular transmission is either absent or minimally expressed. If necessary, the decrement test can be performed in various muscles of the upper and lower extremities, face and trunk, however, in practice, the study is most often carried out in the deltoid muscle (stimulation of the axillary nerve at Erb's point). If strength in the deltoid muscle is preserved (5 points), but weakness of facial muscles is present, the orbicularis oculi muscle should be tested. If necessary, a decrement test is performed in the muscle that removes the little finger of the hand, the triceps muscle of the shoulder, the digastric muscle, etc.

At the beginning of the study, in order to establish the optimal stimulation parameters, the M-response of the selected muscle is recorded in a standard way. Then, indirect electrical low-frequency stimulation of the nerve innervating the studied muscle is performed at a frequency of 3 Hz. Five stimuli are used and subsequently the presence of a decrement in the amplitude of the last M-response relative to the first is assessed.

After performing the standard decrement test, post-activation relief and post-activation exhaustion tests are performed.

Interpretation of results

During an EMG examination in a healthy person, stimulation with a frequency of 3 Hz does not reveal a decrement of the amplitude (area) of the M-response of the muscle due to the large margin of reliability of neuromuscular transmission, that is, the amplitude of the total potential remains stable throughout the entire period of stimulation.

Rice. 8-7. Decrement test: study of neuromuscular transmission in a patient (27 years old) with myasthenia gravis (generalized form). Rhythmic stimulation of the axillary nerve with a frequency of 3 Hz, registration from the deltoid muscle (muscle strength 3 points). Resolution - 1 mV / d, sweep - 1 ms / d. The initial amplitude of the M-response is 6.2 mV (the norm is more than 4.5 mV).

If the reliability of neuromuscular transmission decreases, the exclusion of muscle fibers from the total M-response is manifested by a decrease in the amplitude (area) of subsequent M-responses in a series of impulses in relation to the first, that is, the M-response decrement (Fig. 8-7). Myasthenia gravis is characterized by a decrement of the M-response amplitude of more than 10% with its normal initial amplitude. The decrement usually corresponds to the degree of reduction muscle strength: with a strength of 4 points, it is 15-20%, 3 points - 50%, 1 point - up to 90%. If, with a muscle strength of 2 points, the decrement is insignificant (12-15%), the diagnosis of myasthenia gravis should be questioned.

For myasthenia, the reversibility of neuromuscular transmission disorders is also typical: after the administration of neostigmine methyl sulfate (prozerin), an increase in the amplitude of the M-response and / or a decrease in the block of neuromuscular transmission is noted.

A pronounced increase in the amplitude of the M-response during the period of post-activation relief makes it possible to suspect the presynaptic level of the lesion, in this case, a test with tetanization (stimulation with a series of 200 stimuli at a frequency of 40-50 Hz) is performed in the muscle that abducts the little finger of the hand, which reveals an increment in the amplitude of the M-response . The amplitude increment of the M-response of more than +30% is pathognomonic for the presynaptic level of the lesion.

First Description NMSN, known in the world literature, was made by the French neurologists Charcot and Marie in 1886, in the article "Regarding a specific form of progressive muscular atrophy, often familial, starting with lesions of the feet and legs, and late lesions of the hands." Simultaneously with them, the disease was described by Howard Tut in his dissertation "Peroneal type of progressive muscular atrophy", who for the first time made the correct assumption about the relationship of the disease with defects in the peripheral nerves. In Russia, a neuropathologist, Davidenkov Sergey Nikolaevich, for the first time in 1934 described a variant of neural amyotrophy with increased muscle weakness when cooling.

Charcot-Marie-Tooth disease ( CMT), or Charcot-Marie neural amyotrophy, also known as hereditary motor-sensory neuropathy (HMSN), is an extensive group of genetically heterogeneous diseases of peripheral nerves, characterized by symptoms of progressive polyneuropathy with a predominant lesion of the muscles of the distal extremities. HMSN is not only the most common hereditary disease of the peripheral nervous system, but also one of the most common hereditary human diseases. The frequency of all forms of HMSN varies from 10 to 40:100,000 in different populations.

Clinical and genetic heterogeneity of Charcot-Marie neural amyotrophy was the basis for the search for loci linked to these diseases. To date, more than 40 loci responsible for hereditary motor-sensory neuropathies have been mapped, more than twenty genes have been identified, mutations in which lead to the development of the clinical phenotype of HMSN. All types of HMSN inheritance have been described: autosomal dominant, autosomal recessive, and X-linked. The most common is autosomal dominant inheritance.

Primary nerve damage leads to secondary muscle weakness and atrophy. IN most suffer fat "fast" nerve fibers covered with myelin sheath ("pulp" fibers) - such fibers innervate skeletal muscles. Long fibers are damaged more strongly, therefore, first of all, the innervation of the most distal (remote) muscles, which experience greater physical activity- these are the muscles of the feet and legs, to a lesser extent - the muscles of the hands and forearms. The defeat of sensory nerves leads to a violation of pain, tactile and temperature sensitivity in the feet, legs and hands. On average, the disease begins at the age of 10-20 years. The first symptoms are weakness in the legs, a change in gait (stamping, "cock" gait, or "steppage"), tucking of the legs, sometimes there are mild transient pains in the lower part of the legs. In the future, muscle weakness progresses, atrophy of the muscles of the legs occurs, the legs take on the appearance of “inverted bottles”, deformity of the feet often occurs (the feet acquire a high arch, then the so-called “hollow” foot is formed), the muscles of the hands and forearms are involved in the process. When examined by a neuropathologist, a decrease or loss of tendon reflexes (Achilles, carporadial, less often knee), sensory disturbances are revealed.

All motor-sensory neuropathies are currently divided into three main types according to electroneuromyographic (ENMG) and morphological features: 1) demyelinating (HMSHI), characterized by a decrease in the speed of impulse conduction (SPI) along the median nerve, 2) axonal variant (HMSHII), characterized by normal or slightly reduced SPI along the median nerve, 3) an intermediate variant (intermedia) with SPI along the median nerve from 25 to 45 m/s. The value of SPI equal to 38 m/s, determined by the motor component of the median nerve, is considered a conditional boundary between HMSHI (SPI<38м/с) и НМСНII (СПИ>38m/s). Thus, the ENMG study acquires special meaning for DNA diagnostics, since it allows you to select the most optimal algorithm genetic testing for every family.

Age of onset, severity, and progression depend on the type of neuropathy, but can vary greatly even within the same family. The most common form of the disease HMSHIA - from 50% to 70% of all cases of HMSH type 1 in various populations. In 10% of cases, X-linked forms of HMSN are detected, among which the form with a dominant type of inheritance - HMCNIX, which makes up 90% of all X-linked polyneuropathies, predominates. Among type II HMSN, the dominant form, HMSHIIA, is most common in 33% of all cases (Table 1).

Hereditary motor sensory neuropathies with an autosomal recessive pattern of inheritance are relatively rare, but clinically indistinguishable from HMSN with an autosomal dominant pattern of inheritance. HMSN 4D(Lom), 4C, 4H and 4J are some of these diseases. It is noteworthy that the NDRG1 and SH3TC2 genes contain frequent mutations characteristic of gypsies.

The Center for Molecular Genetics LLC has developed and is searching for the most common mutations of gypsy origin responsible for the development of HMSN 4D(Lom) (Arg148X) and 4C (Arg1109X). Also, the Center for Molecular Genetics LLC has developed a system for searching for repeated mutations in the GDAP1 (Leu239Phe), SH3TC2 (Arg954X and Arg659Cys), FIG4 (Ile41Thr) and FGD4 (Met298Arg and Met298Thr) genes responsible for autosomal recessive types of HMSN.

Table 1. Genes responsible for development various forms NMSN. (Genes are highlighted in blue, the analysis of which is carried out at the Center for Molecular Genetics LLC)

The Center for Molecular Genetics LLC has developed and is conducting diagnostics of HMSN I, II and intermediate types with autosomal dominant (AD), autosomal recessive (AR) and X-linked inheritance.

We have developed . The set is intended for use in diagnostic laboratories of the molecular genetic profile.

When conducting prenatal (antenatal) DNA diagnostics for a specific disease, it makes sense to diagnose frequent aneuploidies (Down, Edwards, Shereshevsky-Turner syndromes, etc.) on the already existing fetal material, paragraph 54.1. Relevance this study due to the high total frequency of aneuploidy - about 1 per 300 newborns, and the lack of the need for repeated sampling of fetal material.

The first description of HMSN known in the world literature was made by the French neurologists Charcot and Marie in 1886, in the article "Regarding a specific form of progressive muscular atrophy, often familial, beginning with lesions of the feet and legs, and late involvement of the hands." Simultaneously with them, the disease was described by Howard Tut in his dissertation "Peroneal type of progressive muscular atrophy", who for the first time made the correct assumption about the relationship of the disease with defects in the peripheral nerves. In Russia, a neuropathologist, Davidenkov Sergey Nikolaevich, for the first time in 1934 described a variant of neural amyotrophy with increased muscle weakness during cooling.

Charcot-Marie-Tooth ( CMT), also known as hereditary motor sensory neuropathy (HMSN), is an extensive group of genetically heterogeneous diseases of peripheral nerves, characterized by symptoms of progressive polyneuropathy with a predominant lesion of the muscles of the distal extremities. HMSN is not only the most common hereditary disease of the peripheral nervous system, but also one of the most common hereditary human diseases. The frequency of all forms of HMSN varies from 10 to 40:100,000 in different populations.

Clinical and genetic heterogeneity of hereditary motor-sensory neuropathies was the basis for the search for loci associated with these diseases. To date, more than 40 loci responsible for hereditary motor-sensory neuropathies have been mapped, more than twenty genes have been identified that lead to the development of the clinical phenotype of HMSN. All types of HMSN inheritance have been described: autosomal dominant, autosomal recessive, and X-linked. The most common is autosomal dominant inheritance.

Primary nerve damage leads to secondary muscle weakness and atrophy. Thick “fast” nerve fibers covered with a myelin sheath (“pulp” fibers) suffer the most - such fibers innervate skeletal ones. Long fibers are damaged more strongly, therefore, the innervation of the most distal (remote) muscles, which are under great physical stress, is first of all disturbed - these are the feet and legs, to a lesser extent - the hands and forearms. The defeat of sensory nerves leads to a violation of pain, tactile and temperature sensitivity in the feet, legs and hands. On average, the disease begins at the age of 10-20 years. The first symptoms are weakness in the legs, a change in gait (stamping, "cock" gait, or "steppage"), tucking of the legs, sometimes there are mild transient pains in the lower part of the legs. In the future, muscle weakness progresses, atrophy of the muscles of the legs occurs, the legs take on the appearance of “inverted bottles”, deformity of the feet often occurs (the feet acquire a high arch, then the so-called “hollow” foot is formed), hands and forearms are involved in the process. When examined by a neuropathologist, a decrease or loss of tendon reflexes (Achilles, carporadial, less often knee), sensory disturbances are revealed.

All motor-sensory neuropathies are currently divided into three main types according to electroneuromyographic (ENMG) and morphological features: 1) demyelinating (HMSHI), characterized by a decrease in the speed of impulse conduction (SPI) along the median nerve, 2) axonal variant (HMSHII), characterized by normal or slightly reduced SPI along the median nerve, 3) an intermediate variant (intermedia) with SPI along the median nerve from 25 to 45 m/s. The value of SPI equal to 38 m/s, determined by the motor component of the median nerve, is considered a conditional boundary between HMSHI (SPI<38м/с) и НМСНII (СПИ>38m/s). Thus, the ENMG study acquires a special meaning for -diagnostics, since it allows you to select the most optimal genetic examination algorithm for each family.

Age of onset, severity, and progression depend on the type of neuropathy, but can vary greatly even within the same family. The most common form of the disease is HMCHIA, accounting for 50% to 70% of all cases of HMCH type 1 in various populations. In 10% of cases, X-linked forms of HMSN are detected, among which the form with a dominant type of inheritance, HMCNIX, predominates, accounting for 90% of all X-linked polyneuropathies. Among type II HMSN, the dominant form, HMSHIIA, is most common in 33% of all cases (Table 1).

Table 1. Genes responsible for the development of various forms of HMSN. (Genes are highlighted in blue, the analysis of which is carried out at the Center for Molecular Genetics LLC

The Center for Molecular Genetics LLC has developed and is conducting diagnostics of HMSN I, II and intermediate types with autosomal dominant (AD), autosomal recessive (AR) and X-linked inheritance.

We have developed a kit for registration of duplications in the PMP22 gene locus in HMSN 1A disease using two microsatellite repeats by PCR. The set is intended for use in diagnostic laboratories of the molecular genetic profile.

http://www.dnalab.ru/diagnosticheskie_uslugi/monogennye_zabolevanija-diagnostika/nmsn