Polyneuropathy: diagnosis

Diagnosis of polyneuropathy

[1], [2], [3]

Anamnesis

When detecting slowly progressive sensorimotor polyneuropathy, which debuted from the peroneal group of muscles, it is necessary to clarify the hereditary history, especially the presence of fatigue and weakness of the leg muscles, changes in gait, and deformities of the feet (high rise).

With the development of symmetrical weakness of the extensors of the hand, it is necessary to exclude intoxication with lead. As a rule, toxic polyneuropathies are characterized, in addition to neurologic symptoms, by general weakness, increased fatigue, sometimes by abdominal complaints. It is also necessary to find out what preparations the patient takes to exclude drug polyneuropathy.

For chronic inflammatory demyelinating polyneuropathy is characterized by a relatively slow development of the disease (for several months), with a typical alternation of exacerbations and temporary improvements. Unlike Guillain-Barre syndrome, the association with a viral infection is rarely detected (20%). In 16% of cases observed acute development of symptoms, reminiscent of Guillain-Barre syndrome. In this case, the diagnosis of chronic inflammatory demyelinating polyneuropathy is established with dynamic observation (the onset of exacerbation after 3-4 months after the onset of the disease allows us to establish the correct diagnosis).

Slowly progressive development of asymmetric muscle weakness allows to suspect multifocal motor neuropathy.

For diabetic polyneuropathy is characterized by slowly progressing hypoesthesia of the lower extremities in combination with a burning sensation and other painful manifestations in the feet.

Ureemic polyneuropathy usually occurs against a background of chronic kidney disease, accompanied by renal failure.

With the development of sensory-vegetative polyneuropathy, characterized by burning, dysesthesia, amid a sharp decrease in body weight, it is necessary to exclude amyloid polyneuropathy.

The development of mononeuropathy with severe pain syndrome in a patient with signs of the systemic process (lung, GI, cardiovascular, general weakness, weight loss, fever) is characteristic of systemic vasculitis and collagenosis.

Diphtheria polyneuropathy develops 2-4 weeks after diphtheria pharyngitis. After 8-12 weeks, the process is generalized to the limb muscles, then the condition of the patients quickly improves, and in a few weeks or months a complete (sometimes incomplete) recovery of the nerve function occurs.

[4], [5], [6], [7], [8], [9],

Physical examination

For hereditary polyneuropathies, the weakness of the extensor muscles of the feet, the steppe, the absence of Achilles tendon reflexes are predominant. In a number of cases, high ceilings of the feet or their deformation by the "horse" type are noted. At a later stage, there are no knee and carporadial tendon reflexes, atrophies of the muscles of the feet and legs develop. 15-20 years after the onset of the disease, weakness and atrophy of the muscles of the hands develop with the formation of a "clawed paw".

Muscular weakness in chronic inflammatory demyelinating polyneuropathy, as well as in Guillain-Barre syndrome, is more often expressed in the lower limbs, revealing a relatively symmetrical lesion of both proximal and distal muscles. With a long course of the disease, muscle atrophies can gradually develop. Sensory disorders most often predominate in the distal parts of the lower limbs, and it is possible to defeat both thin (decrease in pain and temperature sensitivity) and thick fibers (violation of vibration and joint-muscle sensitivity). Pain syndrome in CVD is observed less frequently than with Guillain-Barre syndrome (20%). Tendon reflexes are absent in 90% of patients. There may be weakness of the facial muscles, slight bulbar disorders, however, severe disturbances in swallowing and speech and defeat of the respiratory muscles for chronic inflammatory demyelinating polyneuropathy are not characteristic.

The defeat of the muscles, corresponding to the innervation of individual nerves, without sensory disorders is characteristic of multiple motor neuropathy. In most cases, upper limbs predominate. Sensory motor disorders, the corresponding region of the nerves of the extremities, with a pronounced pain syndrome are characteristic of vasculitis. Most often suffer from lower limbs.

Sensory polyneuropathies are characterized by distal distribution of hypoesthesia (like "socks and gloves"). In the initial stages of the disease, hyperesthesia is possible. Distal tendon reflexes, as a rule, drop out early.

Sensomotor axonal neuropathies (most toxic and metabolic) are characterized by distal hypodeses and distal muscular weakness.

With vegetative polyneuropathies, both fallout phenomena and irritation of vegetative nerve fibers are possible. For the vibration polyneuropathy, hyperhidrosis is typical, disturbances of the vascular tone of the hands (irritation symptoms), for diabetic polyneuropathy, on the contrary, dry skin, trophic disorders, autonomic dysfunction of the internal organs (decreased heart rate variability, gastrointestinal disturbances) (symptoms of fallout).

Laboratory research

Investigation of antibodies to gangliosides

Investigation of antibodies to GM ₂ -gangliosides is recommended to be carried out in patients with motor neuropathies. High titers (more than 1: 6400) are specific for motor multifocal neuropathy. Low titers (1: 400-1: 800) are possible with CVD, Guillain-Barre syndrome and other autoimmune neuropathies, as well as with ALS. It should be remembered that an elevated titer of antibodies to GM _1- gangliosides is detected in 5% of healthy individuals, especially the elderly.

An increase in the titer of antibodies to ganglioside GD _{1b is} revealed in sensory neuropathies (sensory chronic polyneuropathy, Guillain-Barre syndrome and sometimes chronic inflammatory demyelinating polyneuropathy).

An increase in the titer of antibodies to ganglioside GQ _1b is typical for polyneuropathies with ophthalmoparesis (in Miller-Fisher syndrome they are detected in 90% of cases).

Antibodies to myelin-associated glycoprotein (anti-MAG antibodies) are detected in 50% of patients with paraproteinemic polyneuropathy (with monoclonal IgM-gamma-pathologies) and in some cases with other autoimmune polyneuropathies.

The concentration of vitamin B ₁₂ in the blood. With vitamin B _12- deficiency polyneuropathy, it is possible to reduce the concentration of vitamin B ₁₂ in the blood (below 0.2 ng / mg), but in some cases it can be normal, so this study is rarely used.

General blood analysis. In systemic diseases, an increase in ESR and leukocytosis is noted, with vitamin B _12- deficient polyneuropathy - hyperchromic anemia.

The analysis of blood, urine for the content of heavy metals is carried out with suspicion of polyneuropathy associated with intoxication with lead, aluminum, mercury, etc.

Research of urine. If there is a suspicion of porphyria, a simple test is carried out - the jar with the urine of the patient is exposed to sunlight. With porphyria, the color of urine is reddish (pink). With a positive sample, you can confirm the diagnosis with the Watson-Schwarz test.

Studies of cerebrospinal fluid

The protein content in the cerebrospinal fluid rises with Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, paraproteinemic polyneuropathies. Also typical is protein-cell dissociation (no more than 10 mononuclear leukocytes / μl). With motor multifocal neuropathy, a slight increase in protein concentration is possible. In diphtheritic polyneuropathy, lymphocytic pleocytosis with a high protein content is often detected. For HIV-associated polyneuropathies, mild mononuclear pleyocytosis (above 10 cells per 1 μl), increased protein content is characteristic.

DNA Diagnostics

It is possible to carry out molecular genetic analysis for all the main forms of NMSA I, IIA, IVA, IVB types.

[10], [11]

Instrumental research

Stimulation electromyography

The study of the conductive function of motor and sensory fibers allows to confirm the diagnosis of polyneuropathy, to determine its character (axonal, demyelinating), to identify the blocks of conduction along the nerves.

The scope of the study is determined based on the clinical picture. When the motor functions are disturbed, it is necessary to study the motor nerves of the lower and upper extremities to assess the symmetry and prevalence of the process. The most frequently examined are the peroneal, tibial, median and ulnar nerves. In the presence of sensory disorders, it is advisable to study the gastrocnemius, median, ulnar nerves. For the diagnosis of polyneuropathy, a test of at least 3-4 nerves is necessary. If there is a suspicion of multiple mononeuropathy, the clinically affected and intact nerves are examined, as well as the detection of the blocks of the induction method - a step-by-step investigation of the nerve. To diagnose motor multifocal neuropathy, it is necessary to identify partial blocks of conduction outside of the sites of typical compression by not less than two nerves.

When revealing systemic damage to peripheral nerves, it is necessary to clarify the type of pathological process (axonal or demyelinating).

• o The main criteria of the axonal process:
  • decrease in the amplitude of the M-response;
  • normal or slightly reduced rate of excitation on the motor and sensory axons of peripheral nerves;
  • presence of blocks conducting excitation;
  • an increase in the amplitude of F waves, the appearance of large F waves with an amplitude exceeding 5% of the amplitude of the M-response.
• The main criteria of the demyelinating process:
  • decrease in the rate of excitation on the motor and sensory axons of peripheral nerves (in hands less than 50 m / s, on the legs less than 40 m / s);
  • an increase in the duration and polyphase of the M-response;
  • increase in residual latency (more than 2.5-3 m / s);
  • presence of excitation blocks;
  • expansion of the range of F-wave latency.

Needle electromyography

The purpose of needle EMG in polyneuropathy is to reveal the signs of the current denervation-re-reinvation process. The distal muscles of the upper and lower extremities (for example, the anterior tibialis muscle, the common extensor of the fingers), and, if necessary, the proximal muscles (for example, the quadriceps muscle of the thigh) are most often studied.

It must be remembered that the first signs of the denervation process appear not earlier than 2-3 weeks after the onset of the disease, and signs of the reinnervation process - no earlier than 4-6 weeks. Therefore, in the early stages of the Guillain-Barre syndrome, needle-like EMG does not reveal pathological changes. At the same time, it is justified, since the detection of the latent current denervation-re-reinversion process helps in the differential diagnosis of chronic inflammatory demyelinating polyneuropathy and Guillain-Barre syndrome in controversial cases.

Nerve biopsy

A biopsy of the nerves (often gastrocnemius) is rarely performed in the diagnosis of polyneuropathies. The study is justified for suspected amyloid polyneuropathy (detection of amyloid deposits), vasculitis (necrosis of the walls of vessels feeding the nerve).

A complete set of diagnostic criteria for any polyneuropathy includes:

Clinical manifestations (the main of them: pain, paresthesia, muscle weakness, hypotrophy, hypotension, decreased reflexes, vegetative disorders, sensitivity disorders by the type of "gloves" and "socks").

A biopsy of the nerve and muscle (the character of morphological changes is important by the type of axonopathy or myelinopathy).

Electrophysiological studies. Use stimulation and surface electromyography. To determine the nature and level of peripheral nerve damage, it is important to study the rate of excitation on motor and sensitive peripheral nerve fibers, as well as the analysis of the clinical features of the polyneuropathic syndrome.

Biochemical studies of cerebrospinal fluid, blood and urine.

The manifestations of polyneuropathy can also include sensory ataxia, neuropathic tremor, as well as fasciculations, myocciia, krampi and even generalized muscle tension (stiffness). In the latter case, as a rule, a delay in muscle relaxation after an arbitrary contraction ("pseudomotonium") is detected and is observed in certain axonopathies. These forms should be differentiated with damage to the cells of the anterior horns of the spinal cord and Schwarz-Jampel syndrome.

Any polyneuropathic syndrome obeys certain principles of clinical description. In particular, polyneuropathy is always clinically classified according to three clinical categories: by prevailing clinical signs (which nerve fibers predominantly or selectively suffer), by the distribution of the lesion and by the nature of the course. Pay attention to the age of debut of the disease, family history and the presence of current somatic diseases.

[12], [13], [14], [15], [16],

Differential diagnostics

[17], [18], [19], [20], [21]

Hereditary polyneuropathies

Sharko-Mari-Tus disease is characterized by the slowly progressing weakness of the peroneal muscles with prolapse of Achilles tendon reflexes. At the early onset of the disease (10-20 years), it is not difficult to suspect a hereditary genesis: detection of a sharply increased threshold of M-responses induced by stimulation EMG, a marked decrease in nerve conduction velocity (less than 38 m / s along the median nerve) is most likely due to NMSN I type. The diagnosis is confirmed with the help of molecular genetic methods. When detecting predominantly axonal changes (the velocity of the median nerve is more than 45 m / s), it is advisable to carry out a genetic analysis on NMSH type II. A pronounced decrease in the speed of the nerve conduction (less than 10 m / s) in combination with a pronounced delay in motor development is characteristic of type III NMSH (Dejerine-Sotta syndrome), which is also characterized by a thickening of the nerve trunks. The combination of an equally pronounced reduction in the speed of the nerve conduction with neurosensory hearing loss, ichthyosis, retinal pigmentary degeneration, cataracts may be associated with Refsum disease (type IV HMS).

In the axonal type of the Charcot-Marie-Tous disease, an investigation of the conductive function of the nerves reveals a decrease in the amplitude of the M-responses for practically conserved SRV; needle EMG reveals the denervation-re-reinversion syndrome, often combined with the potentials of fasciculations, which in some cases leads to erroneous treatment of pathology as spinal muscular atrophy. In contrast to spinal muscular atrophy, Charcot-Marie-Toce's disease is characterized by a distal distribution of muscle weakness and atrophy. An additional criterion can be the detection of sensory disorders (clinically or with EMG). With Kennedy's spinal amyotrophy, there is also a disturbance in the conductive function of sensory nerves, but it can be distinguished by other signs: bulbar disorders, gynecomastia, and others. Genetic analysis plays a decisive role.

If there is a suspicion of hereditary polyneuropathy and a lack of a clear family history, an examination of the relatives of patients helps to identify subclinical forms of NMSM. Many of them do not make active complaints, but when questioning they indicate that it is difficult for them to pick up their shoes because of the high arch of the foot, their legs are tired by the evening. Achilles reflexes are often absent or reduced, but the strength of the muscles, including the peroneal group, may be sufficient. The study of SRV often reveals demyelinating changes in the absence of axonal changes, while SRV can be significantly reduced. With needle EMG, there are usually signs of reinnervation of various degrees without pronounced denervation, that is, the reinnervation process completely compensates for the negligible denervation of muscle fibers, which leads to a prolonged subclinical course of the disease.

Porphyria polyneuropathy

Porphyria polyneuropathy can mimic polymyositis. Differential diagnosis is based on the results of needle EMG, revealing the primary-muscle type of changes in polymyositis. With polymyositis, a sharp increase in the activity of CK in the blood is observed. From Guillain-Barre syndrome porphyria polyneuropathy is characterized by the presence of abdominal disorders, CNS damage (insomnia, depression, confusion, congested disorders), as well as frequent preservation of achilles reflexes. In some cases, porphyria polyneuropathy can resemble lead intoxication (general weakness, abdominal symptoms and predominance of weakness in the muscles of the hands). Botulism is excluded by history and by the study of neuromuscular transmission.

Autoimmune polyneuropathies

[22], [23], [24], [25], [26], [27]

Chronic inflammatory demyelinating polyneuropathy

The combination of distal and proximal muscle weakness with distal hypoesthesia, developed within 2-4 months, allows to suspect chronic inflammatory demyelinating polyneuropathy. There are episodes of spontaneous remissions and exacerbations. With stimulation EMG, axonal-demyelinating sensomotor changes are revealed. The detection of a moderate increase in antibodies to gangliosides GM ₁, GM ₂, an increased protein content in the CSF allows us to confirm the immune nature of polyneuropathy. With the rapid development of polyneuropathy and severe course it is necessary to exclude the Guillain-Barre syndrome. The pronounced enlargement of the parameters of the PDE when examined with a needle electrode allows one to suspect a longer course of the disease than indicated by the patient.

[28], [29], [30], [31], [32], [33],

Paraproteinemigene polyneuropathy

The predominance of sensory disturbances, a progredient course without remissions, demyelinating changes with EMG allow one to suspect paraproteinemic polyneuropathy. The diagnosis is confirmed by the detection of monoclonal gammopathy in electrophoresis / immunoelectrophoresis of blood plasma and antibodies to myelin-associated glycoprotein. In addition, the detection of the Ben-Jones protein in the urine, the increase in protein concentration and the detection of monoclonal IgM in the liquor are important.

Multifocal motor mononeuropathy

The development of severe atrophy, asymmetric muscle weakness, fasciculations and the absence of sensory disturbances in multifocal motor mononeuropathy often lead to erroneous diagnosis of motor neuron disease. In differential diagnostics, the detection of blocks of conduction on two or more motor nerves is helped by the "inciting" method (a step-by-step study of the conductive function of the nerves). Lesions with multifocal motor mononeuropathy fit into the zones of innervation of individual nerves, and with a neuronal lesion this dependence is disrupted. In addition, for the diseases of motoneuron characterized by the presence of pronounced facies potentials, including in clinically unaffected muscles.