Polyneuropathy - Diagnosis

Diagnosis of polyneuropathy

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Anamnesis

When slowly progressing sensorimotor polyneuropathy is detected, which debuted in the peroneal muscle group, it is necessary to clarify the hereditary anamnesis, especially the presence of fatigue and weakness of the leg muscles, changes in gait, and foot deformities (high instep) in relatives.

If symmetrical weakness of the wrist extensors develops, lead intoxication must be ruled out. As a rule, toxic polyneuropathies are characterized, in addition to neurological symptoms, by general weakness, increased fatigue, and sometimes abdominal complaints. It is also necessary to find out what medications the patient is taking to rule out drug-induced polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy is characterized by a relatively slow development of the disease (over several months), with alternating exacerbations and temporary improvements typical. Unlike Guillain-Barré syndrome, a connection with a previous viral infection is rarely detected (20%). In 16% of cases, acute development of symptoms resembling Guillain-Barré syndrome is observed. In this case, the diagnosis of chronic inflammatory demyelinating polyneuropathy is established during dynamic observation (the occurrence of an exacerbation 3-4 months after the onset of the disease allows for the correct diagnosis).

Slowly progressive development of asymmetric muscle weakness suggests multifocal motor neuropathy.

Diabetic polyneuropathy is characterized by slowly progressing hypoesthesia of the lower extremities, combined with a burning sensation and other painful manifestations in the feet.

Uremic polyneuropathy usually occurs against the background of chronic kidney disease, accompanied by renal failure.

In the development of sensory-vegetative polyneuropathy, characterized by burning, dysesthesia, against the background of 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 a systemic process (lung damage, gastrointestinal tract, cardiovascular system, general weakness, weight loss, fever) is characteristic of systemic vasculitis and collagenoses.

Diphtheritic polyneuropathy develops 2-4 weeks after diphtheritic pharyngitis. After 8-12 weeks, the process becomes generalized with damage to the muscles of the extremities, then the condition of the patients quickly improves, and after several weeks or months, complete (sometimes incomplete) restoration of nerve function occurs.

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Physical examination

Hereditary polyneuropathies are characterized by the predominance of weakness of the extensor muscles of the feet, steppage, absence of Achilles tendon reflexes. In some cases, high arches of the feet or their deformation of the "horse" type are noted. At a later stage, knee and carporadial tendon reflexes are absent, atrophy of the muscles of the feet and shins develops. 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".

Muscle weakness in chronic inflammatory demyelinating polyneuropathy, as in Guillain-Barré syndrome, is often more pronounced in the lower extremities, with relatively symmetrical damage to both proximal and distal muscles. With a long-term course of the disease, muscle atrophy may gradually develop. Sensory disturbances most often predominate in the distal parts of the lower extremities, with damage to both thin (decreased pain and temperature sensitivity) and thick fibers (impaired vibration and joint-muscle sensitivity) possible. Pain syndrome in CIDP is observed less frequently than in Guillain-Barré syndrome (20%). Tendon reflexes are absent in 90% of patients. Facial muscle weakness and mild bulbar disturbances are possible, but severe swallowing and speech disturbances and damage to the respiratory muscles are not typical of chronic inflammatory demyelinating polyneuropathy.

Muscle damage corresponding to the innervation of individual nerves, without sensory disturbances, is characteristic of multiple motor neuropathy. In most cases, upper limbs are predominantly affected. Sensorimotor disorders corresponding to the area of the nerves of the limbs, with pronounced pain syndrome, are characteristic of vasculitis. The lower limbs are most often affected.

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 usually disappear early.

Sensorimotor axonal neuropathies (most toxic and metabolic) are characterized by distal hypoesthesia and distal muscle weakness.

In case of vegetative polyneuropathies, both loss and irritation of vegetative nerve fibers are possible. Hyperhidrosis, vascular tone disorders of the hands (irritation symptoms) are typical for vibration polyneuropathy, while diabetic polyneuropathy, on the contrary, is characterized by dry skin, trophic disorders, vegetative dysfunction of internal organs (reduced heart rate variability, gastrointestinal disorders) (loss symptoms).

Laboratory research

Study of antibodies to gangliosides

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

An increase in the titer of antibodies to ganglioside GD _1b is detected in sensory neuropathies (sensory chronic polyneuropathy, Guillain-Barré 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 gammopathies) and in some cases with other autoimmune polyneuropathies.

_{Vitamin B 12} concentration in the blood. In vitamin B ₁₂ -deficiency polyneuropathy, the concentration of vitamin B ₁₂ in the blood may decrease (below 0.2 ng/mg), but in some cases it may be normal, so this study is rarely used.

General blood analysis. In systemic diseases, an increase in ESR and leukocytosis are noted, in vitamin B ₁₂ -deficiency polyneuropathy - hyperchromic anemia.

Blood and urine tests for heavy metals are performed if there is a suspicion of polyneuropathy associated with intoxication with lead, aluminum, mercury, etc.

Urine tests. If porphyria is suspected, a simple test is performed - a jar of the patient's urine is exposed to sunlight. With porphyria, the urine turns red (pink). If the test is positive, the diagnosis can be confirmed using the Watson-Schwartz test.

Cerebrospinal fluid studies

The protein content in the cerebrospinal fluid increases in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and paraproteinemic polyneuropathies. Protein-cell dissociation is also typical (no more than 10 mononuclear leukocytes/μl). In motor multifocal neuropathy, a slight increase in protein concentration is possible. In diphtheritic polyneuropathy, lymphocytic pleocytosis with increased protein content is often detected. HIV-associated polyneuropathies are characterized by mild mononuclear pleocytosis (above 10 cells in 1 μl), increased protein content.

DNA diagnostics

It is possible to conduct molecular genetic analysis for all main forms of NMSN types I, IIA, IVA, IVB.

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Instrumental research

Stimulation electromyography

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

The scope of the study is determined based on the clinical picture. In case of motor function impairment, it is necessary to study the motor nerves of the lower and upper extremities to assess the symmetry and extent of the process. The most frequently examined nerves are the peroneal, tibial, median and ulnar nerves. In the presence of sensory impairment, it is advisable to study the sural, median and ulnar nerves. To diagnose polyneuropathy, it is necessary to examine at least 3-4 nerves. If multiple mononeuropathy is suspected, a study of clinically affected and intact nerves is carried out, as well as the identification of conduction blocks using the "inching" method - a step-by-step study of the nerve. To diagnose motor multifocal neuropathy, it is necessary to identify partial conduction blocks outside the sites of typical compression in at least two nerves.

When detecting 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 speed of conduction of excitation along the motor and sensory axons of peripheral nerves;
  • the presence of excitation conducting blocks;
  • 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 demyelination process:
  • decreased speed of conduction of excitation along the motor and sensory axons of peripheral nerves (less than 50 m/s in the arms, less than 40 m/s in the legs);
  • increase in duration and polyphasy of the M-response;
  • increase in residual latency (more than 2.5-3 m/s);
  • presence of excitation conduction blocks;
  • expansion of the F-wave latency range.

Needle electromyography

The purpose of needle EMG in polyneuropathy is to identify signs of the current denervation-reinnervation process. Most often, the distal muscles of the upper and lower extremities are examined (e.g., the anterior tibialis muscle, the common extensor of the fingers), and, if necessary, the proximal muscles (e.g., the quadriceps muscle of the thigh).

It is important to remember that the first signs of the denervation process appear no 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 Guillain-Barré syndrome, needle EMG does not reveal pathological changes. At the same time, its implementation is justified, since the detection of a hidden ongoing denervation-reinnervation process helps in the differential diagnosis of chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome in controversial cases.

Nerve biopsy

Nerve biopsy (usually sural) is rarely performed in the diagnosis of polyneuropathy. The study is justified in case of suspicion of amyloid polyneuropathy (detection of amyloid deposits), vasculitis (necrosis of the walls of the vessels feeding the nerve).

A complete set of diagnostic criteria for any polyneuropathy includes:

Clinical manifestations (the main ones are: pain, paresthesia, muscle weakness, hypotrophy, hypotension, decreased reflexes, autonomic disorders, “glove” and “sock” type sensitivity disorders).

Nerve and muscle biopsy (the nature of morphological changes such as axonopathy or myelinopathy is important).

Electrophysiological studies. Stimulation and surface electromyography are used. To determine the nature and level of damage to the peripheral nerve, it is important to study the speed of excitation conduction along the motor and sensory fibers of the peripheral nerves, as well as to analyze the clinical features of the polyneuropathic syndrome.

Biochemical studies of cerebrospinal fluid, blood and urine.

Manifestations of polyneuropathies may also include sensory ataxia, neuropathic tremor, as well as fasciculations, myokymia, cramps, and even generalized muscle tension (stiffness). In the latter case, as a rule, a delay in muscle relaxation after voluntary contraction ("pseudomyotonia") is detected and is observed in some axonopathies. These forms should be differentiated from damage to the cells of the anterior horn of the spinal cord and Schwartz-Jampel syndrome.

Any polyneuropathic syndrome is subject to certain principles of clinical description. In particular, polyneuropathy is always clinically classified into three clinical categories: by predominant clinical signs (which nerve fibers are predominantly or selectively affected), by the distribution of the lesion, and by the nature of the course. Attention is paid to the age of the onset of the disease, family history, and the presence of current somatic diseases.

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Differential diagnostics

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Hereditary polyneuropathies

Charcot-Marie-Tooth disease is characterized by slowly progressive weakness of the peroneal muscles with loss of Achilles tendon reflexes. At early onset of the disease (at 10-20 years), it is easy to suspect hereditary genesis: the detection of a sharply increased threshold of evoked M-responses during stimulation EMG, a marked decrease in nerve conduction velocity (less than 38 m/s along the median nerve), is most likely associated with NMSN type I. The diagnosis is confirmed using molecular genetic methods. If predominantly axonal changes are detected (conduction velocity along the median nerve is more than 45 m/s), it is advisable to conduct a genetic analysis for NMSN type II. The detection of a marked decrease in nerve conduction velocity (less than 10 m/s) in combination with a marked delay in motor development is characteristic of NMSN type III (Dejerine-Sottas syndrome), which is also characterized by thickening of the nerve trunks. The combination of an equally marked decrease in nerve conduction velocity with sensorineural hearing loss, ichthyosis, pigmentary degeneration of the retina, and cataracts may be associated with Refsum disease (NMSN type IV).

In the axonal type of Charcot-Marie-Tooth disease, the study of the conduction function of the nerves reveals a decrease in the amplitude of M-responses with virtually intact SR; needle EMG reveals a denervation-reinnervation syndrome, often combined with fasciculation potentials, which in some cases leads to an erroneous interpretation of the pathology as spinal muscular atrophy. Unlike spinal muscular atrophy, Charcot-Marie-Tooth disease is characterized by a distal distribution of muscle weakness and atrophy. An additional criterion may be the detection of sensory impairment (clinically or by EMG). In Kennedy's spinal amyotrophy, a violation of the conduction function of the sensory nerves is also revealed, but it can be distinguished by other signs: bulbar impairment, gynecomastia, etc. Genetic analysis is of decisive importance.

If hereditary polyneuropathy is suspected and there is no clear family history, examination of relatives of patients helps to identify subclinical forms of NMSN. Many of them do not present active complaints, but when questioned, they indicate that it is difficult for them to choose shoes because of the high arch of the foot, and their legs get tired in the evening. Achilles reflexes are often absent or reduced, but muscle strength, including the peroneal group, may be sufficient. A study of the CRV often reveals demyelinating changes in the absence of axonal ones, while the CRV can be significantly reduced. With needle EMG, signs of reinnervation of varying degrees are usually revealed without pronounced denervation, that is, the reinnervation process completely compensates for the slightly pronounced denervation of muscle fibers, which leads to a long-term subclinical course of the disease.

Porphyritic polyneuropathy

Porphyric polyneuropathy can imitate polymyositis. Differential diagnosis is based on the results of needle EMG, which reveals a primary muscular type of changes in polymyositis. In polymyositis, a sharp increase in CPK activity in the blood is observed. Porphyric polyneuropathy differs from Guillain-Barré syndrome by the presence of abdominal disorders, CNS damage (insomnia, depression, confusion, cognitive impairment), and frequent preservation of Achilles reflexes. In some cases, porphyric polyneuropathy can resemble lead intoxication (general weakness, abdominal symptoms, and predominant weakness in the arm muscles). Botulism is excluded based on anamnesis data and by studying neuromuscular transmission.

Autoimmune polyneuropathies

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Chronic inflammatory demyelinating polyneuropathy

The combination of distal and proximal muscle weakness with distal hypoesthesia that developed over 2-4 months suggests chronic inflammatory demyelinating polyneuropathy. Episodes of spontaneous remissions and exacerbations are typical. Stimulation EMG reveals axonal-demyelinating sensorimotor changes. Detection of a moderate increase in antibodies to gangliosides GM ₁, GM ₂, and increased protein content in the cerebrospinal fluid confirms the immune nature of polyneuropathy. With rapid development of polyneuropathy and its severe course, it is necessary to exclude Guillain-Barré syndrome. A marked increase in the parameters of the MUAP during examination with a needle electrode suggests a longer course of the disease than indicated by the patient.

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Paraproteinemyges polyneuropathy

Predominance of sensory disturbances, progressive course without remissions, demyelinating changes in EMG allow us to suspect paraproteinemic polyneuropathy. The diagnosis is confirmed by detection of monoclonal gammopathy in electrophoresis/immunoelectrophoresis of blood plasma and antibodies to myelin-associated glycoprotein. In addition, detection of Ben-Jones protein in urine, increased protein concentration and detection of monoclonal IgM in cerebrospinal fluid are important.

Multifocal motor mononeuropathy

The development of pronounced atrophy, asymmetric muscle weakness, fasciculations and the absence of sensory disturbances in multifocal motor mononeuropathy are often the cause of erroneous diagnosis of motor neuron disease. In differential diagnosis, the detection of conduction blocks in two or more motor nerves by the "inching" method (a step-by-step study of the conduction function of nerves) helps. Lesions in multifocal motor mononeuropathy fit into the innervation zones of individual nerves, and at the neuronal level of damage, this dependence is disrupted. In addition, motor neuron diseases are characterized by the presence of pronounced fasciculation potentials, including in clinically unaffected muscles.