Polyneuropathy: an overview of information

Polineuropathy is a diffuse lesion of the peripheral nerves, not limited to the involvement of any one nerve or one limb. Electrodiagnostic tests are needed to identify the affected nerves, the distribution and severity of the lesion. The treatment of polyneuropathy is aimed at weakening or eliminating the cause of neuropathy.

Polyneuropathies are a heterogeneous group of diseases, characterized by systemic damage to the peripheral nerves (Greek poly - many, peiro - nerve, pathos - disease).

Polyneuropathy is a phenomenon of multiple damage to the peripheral nerves, in which autonomic disorders in the limbs are one of the permanent symptoms of the disease. At present, about 100 causes of this form of pathology are known. However, a fairly clear idea of the mechanisms through which any of the exogenous or endogenous pathological conditions affects the nervous system, causing symptoms of neuropathy, does not exist.

ICD-10:

• G60. Hereditary and idiopathic neuropathy;
• G61. Inflammatory polyneuropathy;
• G62. Other polyneuropathies;
• G63. Polyneuropathy in diseases classified elsewhere,

[1], [2], [3], [4], [5], [6], [7], [8]

Epidemiology of polyneuropathy

Polyneuropathy is a very common group of diseases. They are detected in approximately 2.4%, and in the older age groups - in almost 8% of the population. The most common polyneuropathies include diabetic and other metabolic, toxic, and also some hereditary polyneuropathies. In clinical practice, the wording of "polyneuropathy of an unclear genesis" is very common, which in reality in most cases have an autoimmune or hereditary genesis. 10% of all polyneuropathies of unknown origin are paraproteinemic, about 25% - toxic polyneuropathies.

The incidence of hereditary polyneuropathies is 10-30 per 100 000 population. The most common types of NMSH IA type (60-80% of hereditary neuropathies) and NMSM type II (axonal type) (22%). X-linked HMSN and IBMS type IB are rarely detected. IA type IAH are detected equally among men and women; in 75% of cases, the disease begins before 10 years, in 10% - up to 20 years. NMSH type II begins most often in the second decade of life, but there may be a later debut (up to 70 years).

The prevalence of chronic inflammatory demyelinating polyneuropathy is 1.0-7.7 per 100 000 population, the disease most often begins in the 5-6th decade of life, although it can debut at any age, including in children. Men are sick twice as often as women. The incidence of Guillain-Barre syndrome is 1-3 cases per 100 000 population per year, men suffer more often than women. The disease can occur at any age (from 2 to 95 years), the peak falls on 15-35 and 50-75 years.

[9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]

Causes of polyneuropathy

Some polyneuropathies (for example, in case of lead intoxication, dapsone application, tick bite, porphyria or Guillain-Barre syndrome) affect mainly motor fibers; others (for example, with ganglionitis of the dorsal root, cancer, leprosy, AIDS, diabetes mellitus or chronic intoxication with pyridoxine) are sensitive. In a number of diseases (for example, Guillain-Barre syndrome, Lyme disease, diabetes, diphtheria), cranial nerves may also be involved. Some drugs and toxins can affect sensitive and / or motor fibers.

Toxic causes of neuropathy

A type	Causes
Axonal motor	Gangliosides; prolonged exposure to lead, mercury, misoprostol, tetanus, tick paralysis
Axonal sensorimotor	Acrylamide, ethanol, allyl chloride, arsenic, cadmium, carbon disulphide, chlorphenoxyl compounds, ciguatoxin, dapsone, colchicine, cyanide, DMAPN, disulfiram, ethylene oxide, lithium, methyl bromide, nitrofurantoin, organophosphorus compounds, podophiline, polychlorinated biphenyls, saxitoxin, Spanish toxic oil , taxol, tetrodotoxin, thallium, trichlorethylene, tri-O-tolyl phosphate, rat venom poison (PNU), vinca alkaloids
Axonal touch	Althritin, bortezomib, chloramphenicol, dioxin, doxorubicin, ethambutol, ethionamide, etoposide, gemcitabine, glutetimide, hydralazine, ifosfamide, interferon alfa, isoniazid, lead, metronidazole, misonidazole, nitric oxide, dicarboxylic acid, derivatives of platinum, propafenone, pyridoxine, statins, thalidomide
Demyelinating	Buktorn, chlorokine, diphtheria, hexachlorophen, muzolimine, perhexylin, procarnamide, tacrolimus, tellurium, zymeldin
Mixed	Amiodarone, ethylene glycol, gold, hexacarbon, n-hexane, sodium cyanate, suramine

DMAPN-dimethylaminopropionitrile; TOCR - triorthocresil phosphate; PNU = N-3-pyridylmethyl-N-nitrophenyl urea.

Polyneuropathy - Causes and pathogenesis

[25], [26], [27], [28], [29], [30], [31], [32]

Symptoms of polyneuropathy

Complaints determine pathophysiology, so polyneuropathy is classified on the substrate lesions: demyelinating (myelin), vascular ( vasa nervorum) and axonal (axonal damage).

Myelin dysfunction. Polyneuropathies based on demyelination often develop as a result of a parainfection immune response, which is triggered by encapsulated bacteria (eg, Campylobacter spp. ), Viruses (eg, enterovirus or influenza virus, HIV) or vaccination (eg against influenza). It is assumed that the antigens of these agents give cross-reactions with antigens of the peripheral nervous system, eliciting an immune response that to some extent destroys myelin. In acute cases (for example, with Guillain-Barre syndrome), rapidly progressive weakness may develop until the respiratory arrest.

Myelin dysfunction disrupts the function of thick sensitive fibers (paresthesia), the degree of muscle weakness outstrips the severity of atrophy, reflexes are greatly reduced, it is possible to involve the muscles of the trunk and cranial nerves. Nerves are affected along the entire length, which manifests itself in the proximal and distal parts of the extremities. The asymmetry of lesions is possible, and the upper parts of the body can be involved earlier than the distal parts of the limbs. Muscle mass and muscle tone are usually quite safe.

Lesions of vasa nervorum. Blood supply of nerves can disrupt chronic arteriosclerotic ischemia, vasculitis and hypercoagulable conditions.

First, dysfunction of the delicate sensory and motor nerves develops, which is manifested by pain and burning sensation. Initially, the disorders are asymmetric and rarely affect the muscles of the proximal 1/3 limb or trunk. Cranial nerves are rarely involved, except in cases of diabetes, when the third pair of cranial nerves is affected. Later violations can become symmetrical. Sometimes vegetative dysfunction and skin changes (for example, atrophic, shiny skin) develops. Muscle weakness corresponds to atrophy, and complete loss of reflexes is rare.

Axonopathy. Axonopathies are usually distal, both symmetrical and asymmetric.

Common causes: diabetes, chronic renal failure and side effects of chemotherapy (for example, vinca alkaloids). Axonopathy can be the result of malnutrition (most often by group B vitamins), as well as excess intake of vitamin B ₆ or alcohol. Less common are metabolic causes: hypothyroidism, porphyria, sarcoidosis and amyloidosis, finally some infections (eg, lime disease), medication (nitric oxide) and the effects of a number of chemicals (eg n-hexane) and heavy metals (lead, arsenic, mercury). In paraneoplastic syndrome against the background of small cell lung cancer, the death of ganglia of the dorsal roots and their sensitive axons results in subacute sensory neuropathy.

Primary axonal dysfunction can begin with symptoms of damage to thick or thin fibers or a combination of these. Usually, neuropathy has a distal symmetrical distribution as a stocking - a glove; it affects first the lower limbs, then the upper limbs and symmetrically spreads to the proximal parts.

Asymmetric axonopathy can result from parainfection or vascular disorders.

Polyneuropathy - Symptoms

Classification of polyneuropathy

At present, there is no generally accepted classification of polyneuropathies. According to the pathogenetic sign, polyneuropathies are divided into axonal, in which the axial cylinder is primarily affected, and demyelinating, which is based on myelin pathology.

By the nature of the clinical picture, motor, sensory and vegetative polyneuropathies are isolated. In a pure form, these forms are rarely observed, the combined damage of two or all three kinds of nerve fibers, for example, motor-sensory, sensory-vegetative forms, is more often revealed.

By the etiological factor of polyneuropathy can be divided into hereditary, autoimmune, metabolic, alimentary, toxic and infectious-toxic.

[33], [34], [35], [36], [37]

Diagnosis of polyneuropathy

Clinical data, especially the rate of development, help in diagnosing and identifying the cause. Asymmetric neuropathies suggest defeat of the myelin sheath or vasa nervorum, and symmetrical, distal neuropathies - toxic or metabolic disorders. Slowly progressing chronic neuropathies can be hereditary, associated with prolonged exposure to toxic substances or with metabolic disorders. Acute neuropathies suggest an autoimmune disorder, vasculitis or a post-infectious cause. Rash, skin ulcers and Raynaud's syndrome in combination with asymmetric axonal neuropathy suggest a hypercoagulable state, parainfection or autoimmune vasculitis. Decreased body weight, fever, lymphadenopathy and massive lesions suggest a tumor or paraneoplastic syndrome.

Electrodiagnostic studies. To determine the type of neuropathy, it is necessary to make EMG and determine the speed of neural conduction. To assess the asymmetry and degree of axon lesion, EMG is performed at a minimum of both legs. Since EMG and the definition of nerve conduction are more closely associated with thick myelinated fibers in the distal segments of the limb, with proximal myelin dysfunction (for example, in the onset of Guillain-Barre syndrome) and with the primary lesion of fine fibers, EMG can be normal. In such cases, the sensitivity and function of the autonomic nervous system should be quantified.

Laboratory tests. Among the main laboratory tests: general blood test, electrolyte level, kidney function, rapid test for responding, fasting blood sugar measurement, hemoglobin A _{1 s}, vitamin B ₁₂, folate and thyroid stimulating hormone. The need for other tests is determined by the specific type of polyneuropathy.

The approach to patients with neuropathy due to acute demyelination is the same as in Guillain-Barre syndrome; To determine the beginning of respiratory failure measure the forced vital capacity of the lungs. In acute or chronic demyelination, tests for infectious diseases and immune dysfunction are performed, including tests for hepatitis and HIV and serum-protein electrophoresis. In addition, antibodies to the myelin-associated glycoprotein are determined. If motor dysfunction predominates, antisulfatide antibodies are determined, with primary sensory dysfunction, a lumbar puncture should be performed. Demyelination due to an autoimmune response often causes protein-cell dissociation: an elevated protein level in the CSF (> 45 mg / dl) at a normal number of leukocytes (<5 / μl).

In asymmetric axonal neuropathies, tests should be performed to identify hypercoagulable conditions and parainfection or autoimmune vasculitis (especially if there are clinical suspicions). At a minimum, determine ESR, rheumatoid factor, antinuclear antibodies, creatine phosphokinase (CKF) in serum. CK can increase when rapid development of the disease leads to a heart attack. When anamnestic indications of the corresponding disorders determine the factors of blood clotting (for example, proteins C and S, antithrombin III, anticardiolipin antibodies, homocysteine levels), and even tests for sarcoidosis, hepatitis C or Wegener's granulomatosis. If the cause is not determined, a biopsy of the muscles and nerves should be performed. Usually take the affected calf nerve. You can take and adjacent to the nerve a piece of muscle tissue, from the gastrocnemius muscle or quadriceps muscle of the thigh, biceps or triceps muscles of the shoulder, deltoid muscle. The muscle should have moderate weakness, and the biopsy site should not contain traces of previous needle introductions (including EMG). Biopsy of nerves with asymmetric axonopathies is more informative than with other types of polyneuropathies.

If the examination did not reveal the cause of the distal symmetrical axonopathies, the heavy metals in the daily urine are determined and the urine protein is electrophoresed. If suspicion of chronic poisoning with heavy metals is carried out, the analysis of hair from the pubic region or the axillary region. Anamnesis and physical examination dictate the need for additional tests to identify other causes.

Polyneuropathy - Diagnosis

[38], [39], [40], [41], [42], [43], [44], [45]

Treatment of polyneuropathy

The treatment of polyneuropathy, if possible, is aimed at eliminating the cause of the disease. It is necessary to cancel the drug and eliminate the toxic effect that led to the development of the disease, to correct the deficiencies of nutrition. These actions eliminate or reduce complaints, but recovery is slow and may be incomplete. If the cause can not be eliminated, treatment is reduced to minimizing disability and pain, in which orthopedic adaptations can help. Amitriptyline, gabapentin, mexiletine and lidocaine applications can alleviate neuropathic pain (for example, a burning sensation in the soles of the feet with diabetes).

When demyelinating polyneuropathies usually use immunomodulatory treatment: plasmapheresis or immunoglobulin intravenously for acute demyelination and glucocorticoids or antimetabolic drugs - for chronic.

Polyneuropathy - Treatment and prognosis