Polyneuropathy - Information Review

Polyneuropathy is a diffuse lesion of the peripheral nerves that is not limited to any one nerve or limb. Electrodiagnostic tests are needed to identify the affected nerves, distribution, and severity of the lesion. Treatment of polyneuropathy is aimed at reducing or eliminating the cause of the neuropathy.

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

Polyneuropathies are a phenomenon of multiple lesions of peripheral nerves, in which autonomic disorders in the limbs are one of the constant symptoms of the disease. Currently, about 100 causes of this form of pathology are known. However, there is no sufficiently clear understanding of the mechanisms by which any of the exogenous or endogenous pathological conditions affects the nervous system, causing symptoms of neuropathy.

ICD-10:

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

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Epidemiology of polyneuropathy

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

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

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

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Causes of polyneuropathy

Some polyneuropathies (eg, lead intoxication, dapsone use, tick bite, porphyria, or Guillain-Barré syndrome) affect predominantly motor fibers; others (eg, dorsal root ganglionitis, cancer, leprosy, AIDS, diabetes, or chronic pyridoxine intoxication) affect sensory fibers. A number of diseases (eg, Guillain-Barré syndrome, Lyme disease, diabetes, diphtheria) may also involve the cranial nerves. Some drugs and toxins may affect sensory and/or motor fibers.

Toxic Causes of Neuropathy

Type	Reasons
Axonal motor	Gangliosides; long-term exposure to lead, mercury, misoprostol, tetanus, tick paralysis
Axonal sensorimotor	Acrylamide, ethanol, allyl chloride, arsenic, cadmium, carbon disulfide, chlorophenoxyl compounds, ciguatoxin, dapsone, colchicine, cyanide, DMAPN, disulfiram, ethylene oxide, lithium, methyl bromine, nitrofurantoin, organophosphorus compounds, podophyllin, polychlorinated biphenyls, saxitoxin, Spanish toxic oil, taxol, tetrodotoxin, thallium, trichloroethylene, tri-O-tolyl phosphate, vacor rat poison (PNU), vinca alkaloids
Axonal sensory	Almitrine, bortezomib, chloramphenicol, dioxin, doxorubicin, ethambutol, ethionamide, etoposide, gemcitabine, glutethimide, hydralazine, ifosfamide, alpha interferon, isoniazid, lead, metronidazole, misonidazole, nitric oxide, nucleosides (didanosine, stavudine, zalcitabine), phenytoin, platinum derivatives, propafenone, pyridoxine, statins, thalidomide
Demyelinating	Buckthorn, chloroquine, diphtheria, hexachlorophene, muzolimine, perhexiline, procanamide, tacrolimus, tellurium, zimeldine
Mixed	Amiodarone, ethylene glycol, gold, hexacarbonates, n-hexane, sodium cyanate, suramin

DMAPN - dimethylaminopropionitrile; TOCP - triorthocresyl phosphate; PNU=N-3 - pyridyl-methyl-N-nitrophenyl urea.

Polyneuropathy - Causes and pathogenesis

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Symptoms of polyneuropathy

Complaints are determined by pathophysiology, therefore polyneuropathies are classified according to the substrate of damage: demyelinating (damage to myelin), vascular (damage to vasa nervorum) and axonal (damage to axons).

Myelin dysfunction. Demyelination-based polyneuropathies most often develop as a result of a parainfectious immune response triggered by encapsulated bacteria (eg, Campylobacter spp. ), viruses (eg, enteroviruses or influenza virus, HIV), or vaccination (eg, against influenza). It is assumed that the antigens of these agents cross-react with antigens of the peripheral nervous system, causing an immune response that destroys myelin to varying degrees. In acute cases (eg, Guillain-Barré syndrome), rapidly progressive weakness up to respiratory arrest may develop.

Myelin dysfunction impairs the function of thick sensory fibers (paresthesia), the degree of muscle weakness outpaces the severity of atrophy, reflexes are greatly reduced, and trunk muscles and cranial nerves may be involved. Nerves are affected along their entire length, which is manifested by symptoms in the proximal and distal parts of the limbs. Asymmetry of lesions is possible, and the upper parts of the body may be involved earlier than the distal parts of the limbs. Muscle mass and muscle tone are usually quite preserved.

Vasa nervorum lesions. The blood supply to the nerves can be impaired by chronic arteriosclerotic ischemia, vasculitis, and hypercoagulable states.

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

Axonopathies. Axonopathies are usually distal, both symmetrical and asymmetrical.

Common causes include diabetes mellitus, chronic renal failure, and side effects of chemotherapy (eg, vinca alkaloids). Axonopathy may result from nutritional deficiencies (most often of B vitamins), as well as excess vitamin B6 or alcohol intake _. Less common metabolic causes include hypothyroidism, porphyria, sarcoidosis, and amyloidosis, as well as certain infections (eg, Lyme disease), medications (nitric oxide), and exposure to certain chemicals (eg, n-hexane) and heavy metals (lead, arsenic, mercury). In paraneoplastic syndrome due to small cell lung cancer, loss of dorsal root ganglia and their sensory axons leads to subacute sensory neuropathy.

Primary axonal dysfunction may begin with symptoms of thick-fiber or thin-fiber involvement, or a combination of both. Typically, the neuropathy has a distal, symmetrical, stocking-glove distribution; it affects the lower extremities first, then the upper extremities, and spreads symmetrically to the proximal regions.

Asymmetric axonopathy may result from parainfectious or vascular disorders.

Polyneuropathy - Symptoms

Classification of polyneuropathy

Currently, there is no generally accepted classification of polyneuropathies. According to the pathogenetic feature, polyneuropathies are divided into axonal, in which the primary damage is to the axial cylinder, and demyelinating, which are based on myelin pathology.

According to the nature of the clinical picture, motor, sensory and vegetative polyneuropathies are distinguished. In their pure form, these forms are rarely observed; more often, a combined lesion of two or all three types of nerve fibers is detected, for example, motor-sensory, sensory-vegetative forms.

According to the etiological factor, polyneuropathies can be divided into hereditary, autoimmune, metabolic, alimentary, toxic and infectious-toxic.

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Diagnosis of polyneuropathy

Clinical findings, particularly the rate of progression, aid in diagnosis and identification of the cause. Asymmetric neuropathies suggest myelin sheath or vasa nervorum involvement, whereas symmetric, distal neuropathies suggest toxic or metabolic disorders. Slowly progressive chronic neuropathies may be inherited, related to long-term toxic exposure, or related to metabolic disorders. Acute neuropathies suggest an autoimmune disorder, vasculitis, or postinfectious cause. Rash, skin ulcers, and Raynaud's phenomenon with an asymmetric axonal neuropathy suggest a hypercoagulable state, parainfectious vasculitis, or autoimmune vasculitis. Weight loss, fever, lymphadenopathy, and mass lesions suggest a neoplasm or paraneoplastic syndrome.

Electrodiagnostic studies. To determine the type of neuropathy, it is necessary to perform EMG and determine the speed of nerve conduction. To assess asymmetry and the degree of axon damage, EMG is performed on at least both legs. Since EMG and determination of nerve conduction are largely associated with thick myelinated fibers in the distal segments of the limb, in case of proximal myelin dysfunction (for example, at the onset of Guillain-Barré syndrome) and against the background of primary damage to thin fibers, EMG may be normal. In such cases, sensitivity and functions of the autonomic nervous system should be quantitatively assessed.

Laboratory tests. Basic laboratory tests include a complete blood count, electrolyte levels, renal function tests, rapid reagin test, fasting blood sugar, hemoglobin A1c _{, vitamin B12,} 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 that for Guillain-Barré syndrome; forced vital capacity is measured to detect incipient respiratory failure. In acute or chronic demyelination, tests for infectious diseases and immune dysfunction are performed, including hepatitis and HIV tests and serum protein electrophoresis. In addition, antibodies to myelin-associated glycoprotein are measured. If motor dysfunction predominates, antisulfatide antibodies are measured; if primarily sensory dysfunction, lumbar puncture should be performed. Demyelination due to an autoimmune response often causes albuminocytosis: elevated CSF protein (>45 mg/dL) with a normal white blood cell count (<5/μL).

In asymmetric axonal neuropathies, tests should be performed to detect hypercoagulable states and parainfectious or autoimmune vasculitis (especially if clinically suspected). At a minimum, ESR, rheumatoid factor, antinuclear antibodies, and serum creatine phosphokinase (CPK) should be measured. CPK may be elevated when rapid disease progression leads to muscle infarction. If the history suggests appropriate abnormalities, coagulation factors (eg, proteins C and S, antithrombin III, anticardiolipin antibodies, homocysteine levels) should be measured, and tests for sarcoidosis, hepatitis C, or Wegener's granulomatosis should be performed. If the cause is not identified, muscle and nerve biopsy should be performed. The affected sural nerve is usually sampled. A piece of muscle tissue adjacent to the nerve can also be taken, from the gastrocnemius or quadriceps femoris, biceps or triceps brachii, or deltoid muscle. The muscle should have moderate weakness, and the biopsy site should not contain traces of previous needle insertions (including for EMG). Nerve biopsy in asymmetric axonopathies is more informative than in other types of polyneuropathies.

If the examination does not reveal the cause of distal symmetric axonopathies, heavy metals are determined in 24-hour urine and urine protein electrophoresis is performed. If chronic heavy metal poisoning is suspected, pubic or axillary hair is analyzed. The anamnesis and physical examination dictate the need for other additional tests to identify other causes.

Polyneuropathy - Diagnosis

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Treatment of polyneuropathy

Treatment of polyneuropathy is aimed, if possible, at eliminating the cause of the disease. It is necessary to stop the drug and eliminate the toxic effects that led to the development of the disease, and correct nutritional deficiencies. These actions eliminate or reduce complaints, but recovery is slow and may be incomplete. If the cause cannot be eliminated, treatment is reduced to minimizing disability and pain, which can be done with orthopedic devices. Amitriptyline, gabapentin, mexiletine, and lidocaine applications can relieve neuropathic pain (for example, a burning sensation in the feet in diabetes).

In demyelinating polyneuropathies, immunomodulatory treatment is usually used: plasmapheresis or intravenous immunoglobulin for acute demyelination and glucocorticoids or antimetabolite drugs for chronic demyelination.

Polyneuropathy - Treatment and prognosis