The causes and pathogenesis of polyneuropathy

The pathogenesis of polyneuropathic syndromes is a very complex problem. Specific mechanisms of development of polyneuropathic disorders in various forms of pathology are not fully understood. These difficulties are associated primarily with the variety of nosological forms that can cause damage to the peripheral nervous system; from these forms it is necessary to single out the only way by excluding all the others. The difficulty is also in the need to determine to what extent this pathology contributes to the development of neuropathy. Proceeding from this, for each disease it is necessary to assume the mechanisms by means of which the polyneuropathic syndromes are formed.

The mechanisms of reaction of the peripheral nervous system are of several types:

1. Wallerian degeneration (reaction to the intersection of the nerve);
2. atrophy and degeneration of the axon;
3. segmental demyelination;
4. primary lesion of the bodies of nerve cells. The last three processes are designated as axonopathy, myelinopathy and neuronopathy.

The Wallerian rebirth is caused by mechanical damage. In the zone of innervation of the trunk, paralysis and loss of sensation immediately arise. Distal from the site of damage, there is degeneration of axons and myelin sheaths. The quality of recovery depends on the degree of destruction of lemmocytes (Schwann cells), the nerve shell and surrounding soft tissues. Other factors can play an important role: focal and multifocal ischemia of the trunk can cause distal degeneration at a large extent, if the blood flow decreases sharply, which is observed in systemic vasculitis.

Myelinopathy means damage to the myelin sheaths with preservation of axons. The most significant functional manifestation of demyelination is the blockade of conductivity. Demyelination and remyelination can proceed quickly and often within a few days and weeks result in complete recovery. The forecast for this type is more favorable and recovery is faster.

At the base of axonopathy are metabolic disturbances in neurons, leading to distal decay of axons. Clinically, this is manifested by a distal symmetrical polyneuropathy. Usually the development of axonal degeneration of the peripheral nerve is observed in systemic metabolic diseases and the effects of exogenous toxins, however the exact sequence of changes in the nervous tissue resulting in axonopathy remains unclear.

Neuronopathy means the primary destruction of the body of a nerve cell. If the cells of the anterior horns become the target, motor neuronopathy arises. Sensory neuronopathy affects the ganglion cells of the posterior roots, which often causes marked sensitivity disorders. An example is acute sensory neuronopathy, inflammatory diseases of the ganglia of the posterior roots and cranial ganglia in carcinomatosis, surrounding herpes, as well as toxic conditions. Clinically, neuronopathies are characterized by poor recovery.

In a number of forms of peripheral neuropathies, changes in peripheral vegetative formations are simultaneously found. In the pathological process, mainly the main vegetative ganglia, unmyelinated visceral fibers, the vagus nerve and smooth muscles are involved. In sympathetic ganglia, pathologically altered neurons are found, which are much larger in size than normal ones. Lymphocytic infiltrates, macrophages and plasma cells are found along the clumps of vegetative nerves and ganglia. Sometimes, in lemmocytes in the perivascular regions or in the abdominal organs, the wreaths of unmyelinated axons are revealed. These plexuses closely border on the nerve nodes, histologically resembling neuromas, and can reproduce the pattern of atypical axonal degeneration. The expressed demyelination of the vagus nerve can be observed in patients with diabetic and alcoholic neuropathy.

Pathogenesis of polyneuropathy

Regardless of the etiological factor in polyneuropathies, two types of pathological processes are identified: axon damage and demyelination of nerve fibers. Both processes are closely interrelated: in the axonal type of lesion, secondary demyelination occurs, with the demyelinating lesion the axonal component is secondarily attached. Primarily axonal is the majority of toxic polyneuropathies, axonal type of Guillain-Barre syndrome, type II NMSH. The primary demyelinating polyneuropathies include the classical variant of Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, paraproteinemic polyneuropathies, and type I NMSH.

In axonal polyneuropathies, the transport function of the axial cylinder suffers mainly from the axoplasmatic current carrying in the direction from the motoneuron to the muscle and back a number of biological substances necessary for the normal functioning of the nerve and muscle cells. In the process, the nerves containing the longest axons are primarily involved. The change in the trophic function of the axon and axonal transport leads to the appearance of denervation changes in the muscle. Denervation of muscle fibers stimulates the development of terminal and then collateral scoring, the growth of new terminals and the re-reinforcement of muscle fibers, which leads to a change in muscle structure.

With stimulation EMG, the axonal type of changes is characterized by a decrease in the amplitude of the M-response at a relatively safe rate of excitation. The process of reinnervation leads to the enlargement of the muscles, which indirectly affects the amplitude of the F waves, reveals an increased number of F waves with an amplitude exceeding 5% of the amplitude of the M-response in this muscle. In the study of PDE with the help of a needle electrode, signs of denervation of muscle fibers (fibrillation potentials), necrosis of muscle fibers (positive acute waves) and reinnervation (increase in the duration and amplitude of PDE) are revealed.

Clinically, the defeat of the axon of motor fibers causes muscle weakness in the distal parts of the limbs and muscle atrophy.

When demyelination occurs a disturbance of the saltatory conduction of the nerve impulse, as a result of which the rate of conduction along the nerve decreases. Normally, the speed of the nerve impulse along the peripheral motor and sensory nerves is 40-70 m / s on the lower extremities and 50-80 m / s on the upper limbs. The most pronounced demyelination is observed in hereditary polyneuropathies, in which the rate of conduction can be 5-20 m / s (Russi-Levy syndrome, NMSNIII, IV types); with NMSNIA type of speed on the lower limbs is 25-35 m / s, on the hands - 30-38 m / s. The acquired demyelinating polyneuropathies, as a rule, are characterized by a slight decrease in the speed of the exercise (30-40 m / s on the lower extremities and 40-50 m / s on the upper extremities).

Demyelinating nerve damage clinically manifests the development of muscle weakness (often with a non-typical "classical" polyneuropathy proximal distribution), early prolapse of tendon reflexes, without the development of muscle atrophy. The presence of atrophy indicates an additional axonal component.

Demyelination of nerves can be caused by autoimmune aggression with the formation of antibodies to various components of the peripheral myelin protein (acquired demyelinating polyneuropathies, paraproteinemic, paraneoplastic polyneuropathies), genetic disorders (type I NMSH), exotoxins (diphtheria polyneuropathy). Damage to the axon of the nerve can be caused by the impact on the nerves of exogenous or endogenous toxins (uremic, alcoholic, drug polyneuropathy, polyneuropathy in poisoning with heavy metals and organic compounds), genetic factors (NMSH type II).

Some important clinical markers of individual etiological types of polyneuropathy

Cranial polyneuropathy:

OVDP (Miller Fisher variant), diphtheria, trichlorethylene, hereditary amyloidosis, idiopathic cranial polyneuropathy.

Heavy tetraplegia with sensitive disorders, bulbar and other stem disorders, paralysis of the respiratory muscles (Landry type):

Acute inflammatory demyelinating polyneuropathy (OBDP) Guillain-Barre, post- and parainfection polyneuropathy, postvaccinal polyneuropathy, diphtheria, hyperthyroidism, porphyria, paraneoplastic polyneuropathy.

Mainly motor asymmetric forms:

Post and parainfectious polyneuropathies, lead, gold, penicillin, diabetes, vascular forms.

Polineuropathy with predominantly proximal accentuation of paralysis:

OVDP, gold, winecrestine, hyperthyroidism, giant cell arteritis, porphyria.

Polyneuropathy with a preferred upper limb injury:

Lead, with skin contact with mercury, acrylamide, hypoglycemia.

Polineuropathy with the muscle of the eyeball:

The Miller Fisher syndrome, alcohol, Beriberi, Wernicke's encephalopathy, hyperthyroidism, Fridreich's disease, Nonne-Mariesche disease, a hypertrophic form of neural muscle atrophy of the Dejerine-Sott type (Dejerine- Sottas).

Polineuropathy with pupillary disorders:

Pandisavtonomy, Miller Fisher syndrome, alcohol, diabetes, hypertrophic form of neural muscle atrophy of the Dejerine-Sotta type.

Polyneuropathy involving the trigeminal nerve: trichlorethylene, diamidine.

Polyneuropathy involving the facial nerve:

OVDP, post- and para-infectious polyneuropathy, diphtheria, amyloidosis, sarcaidosis, Melkerson-Rosenthal disease, Sjogren's syndrome, Guillain-Barre syndrome, Lyme disease, HIV infection, Tangier disease.

Polyneuropathy involving nervus stato-acusticus:

Dinitrobenzene; streptomycin; gentamicin; the Strachan-Scott syndrome, described among the inhabitants of Liberia, the Nigerian "atactic neuropathy", Jamaican neuropathy, Refsum disease, Waldenstrom disease, sarcoidosis.

Polyneuropathy with loss of pain and temperature sensitivity:

Leprosy, Tanger disease, hereditary sensory polyneuropathy type I - III, amyloidosis, scleroderma.

Polyneuropathy with spontaneous pain:

Talium, arsenic, gold, carbon disulfide, dinitrophenol, DDT, thalidomide, vincristine, beriberi, diabetes mellitus, Fabry disease, hereditary sensory polyneuropathy type I-II, porphyria, paraneoplastic sensory neuronopathy, nodular periarteritis, polyneuropathy Guillain Barre , amyloidosis, polyneuropathy in HIV infection, alcoholic polyneuropathy

Polineuropathy with the syndrome of "hot feet":

Isoniazid, thalidomide, alcohol, beriberi, pellagra, Stron-Scott syndrome, Nigerian "atactic neuropathy", uremic polyneuropathy, diabetes.

Polyneuropathy with pronounced vegetative-trophic disorders:

Pandisavtonomia, arsenic, carbon disulfide, hexacarbon, acrylamide, arylphosphate, isoniazid, thalidomide, diabetes, Fabry's disease, Dejerine-Sotta muscular atrophy, I-II hereditary sensory polyneuropathy, amyloidosis

Polineuropathy with ulcerative-mutation disorders:

Leprosy, arsenic, hereditary sensory polyneuropathy of types I and II.

Polineuropathy with palpable thickening of the nerves:

Leprosy, acromegaly, Refsum's disease, hypertrophic form of neural muscular atrophy.

Polyneuropathy with a marked decrease in the rate of excitation along the nerve:

OVDP, chronic inflammatory demyelinating polyneuropathy (CVD), post-and parainfection polyneuropathy, postvaccinal polyneuropathy, diphtheria, globoid cell leukodystrophy Krabbe, metochromatic leukodystrophy, Refsum's disease, hypertrophic forms of neural muscular atrophy, Roussy-Levi syndrome ), Pelecius-Merzbacher's disease (Pellizaeus-Merzbacher), lead, hexochlorophene, tellurium, acetyl ethyl tetramethyltetralin (AETT), diabetes, and disproteinemia.

Polyneuropathy with pleocytosis:

Post or parainfection polyneuropathy, meningo-polyradiculopathy Garin-Bujadoux-Bannwarth, paraneoplastic polyneuropathy, sarcoidosis.

Polyneuropathy with additional mononeuropathy:

Leprosy, hypothyroidism, acromegaly, amyloidosis, scleroderma, Sicca-komplex ("dry syndrome").

Polyneuropathy with impaired bladder function:

OVDP, post- or parainfection polyneuropathy, postvaccinal polyneuropathy, pandisavtonomia, acrylamide, arylphosphate, diabetes, hydroxyquinoline.

Polyneuropathy with concomitant meningeal syndrome:

Parainfection polyneuropathy, meningopolyradiculopathy Garin-Vujadoux-strongannwarth, paraneoplastic polyneuropathy, leukemic polyneuropathy, sarcoidosis.

Polyneuropathy with concomitant spasticity:

Mercury, Arylphosphate, Pellagra, Jamaica Polyneuropathy, Folic Acid Deficiency Syndrome, B12 beriberi, disorders of absorption and nutrition, hypoglycemia, Crabbe globoid cell leukodystrophy, metochromatic leukodystrophy, Bassen-Kornzweig syndrome (Bassen-Kornzweig), Friedreich disease, Nonna-Miries disease, OPCA , Russi-Levy syndrome, porphyria, paraneoplastic polyneuropathy, vascular forms, Behcet's disease (Vehcet).

Polyneuropathy with concomitant atrophy of the optic nerve:

Parainfection polyneuropathy, thallium, mercury, carbon disulfide, acrylamide, isoniazid, streptomycin, Stron-Scott syndrome, Nigerian "atactic neuropathy", Jamaica neuropathy, diabetes, Friedreich disease, Nonna-Mariesh disease, OPCA, hypertrophic neuronal amyotrophy of Dejerine-Sotta.

Polyneuropathy with edema of the nipple of the optic nerve:

OVDP, post- and parainfection polyneuropathy, post-vaccination polyneuropathy.

Polyneuropathy with concomitant retinopathy:

Chlorokine, diabetes, Refsum's disease, Bassen-Kornzweig syndrome.

Polyneuropathy with concomitant ataxia:

The syndrome of Miller Fisher, mercury, carbon disulfide, diphenin, alcohol, pellagra, Nigeria "ataxia-neuropathy", Jamaica neuropathy, strongi2 avitaminosis, absorption and nutrition disorders, diabetes, metachromatic leukodystrophy, Refsum's disease, Bassen-Cornzweig syndrome, Friedreich disease, Nonne's disease -Maryesha, OPCA, ataxia-telangiectasia of Louis-Bar, Marinesco-Sjogren's syndrome, Russi-Levy syndrome, paraneoplastic polyneuropathy, Machado-Joseph disease.

Polyneuropathy with concomitant extrapyramidal symptoms:

Lead, carbon disulfide, disulphuram, pellagra, globoid cell leukodystrophy, Nonne-Maries disease, OPCA, Louis-Bar syndrome.

Polyneuropathy with concomitant myoclonus:

Lead, carbon disulfide, gold, methyl bromide, DDT, globoid cell leukodystrophy.

Polyneuropathy with concomitant tremor:

Lead, acrylamide, DDT, psychotropic drugs, alcohol, Russi-Levy syndrome.

Polineuropathy with concomitant epileptic seizures:

Lead, waist, isoniazid, alcohol, pellagra, Friedreich disease, porphyria, nodular periarteritis, lupus erythematosus.

Polyneuropathy with concomitant somatic conditioned psychosis:

Chronic intoxication with inorganic and organic poisons, isoniazid, psychotropic drugs, disulfuram, malnutrition and absorption, endocrine disorders, globoid cell leukodystrophy, Crabbe's methochromatic leukodystrophy, Fabry's disease, Friedreich's disease, Nonne-Mariesh disease, OPCA, Marinesco-Sjogren's syndrome, hereditary sensory neuropathy III and IV types.

Polyneuropathy with concomitant myopathy:

Chloroquine, emitin, alcohol, hypothyroidism, hyperthyroidism, sarcoidosis, nodular periarteritis, lupus erythematosus, scleroderma, giant cell arteritis, Sicca-komplex.

Polyneuropathy with concomitant involvement of joints:

Nodular periarteritis, hypersensitive angiitis, rheumatoid arthritis, lupus erythematosus, Wegener's disease, Sicca-komplex (dry syndrome), Whipple's disease, Behcet's disease.

Polyneuropathy with concomitant changes in the skin and mucous membranes:

Postin or parainfectious polyneuropathy, meningopolyradiculopathy Garin-Vujadoux-Vannwarth, leprosy, waist, mercury, arsenic, gold, penicillin, diphenine, disulphuram, Strona-Scott syndrome, malabsorption and nutrition, Fabry's disease, Refsum disease, ataxia-telangiectasia, familial dysautonomy of Riley-Day, porphyria, cryoglobulinemia, Merkelson-Rosenthal syndrome, lupus erythematosus, scleroderma, Wegener's granulomatosis, atrophic acrodermatitis, Behcet's disease.

Polyneuropathy with symptoms of autonomic neuropathy (peripheral autonomic failure):

Acute vegetative neuropathy (paraneoplastic, Guillain-Barre syndrome, porphyria polyneuropathy, toxic (vincristine), autonomic neuropathy in diabetes mellitus, amyloid polyneuropathy, autonomic neuropathy in HIV infection, hereditary sensory and vegetative neuropathy (Riley-Dey's syndrome).

There are various classifications of polyneuropathy (and neuropathy in general), but there is no generally accepted classification. The above data we want to supplement one of the generalized classifications, built primarily on clinical principles.

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.

Hereditary polyneuropathies:

• hereditary motor-sensory neuropathy (NMSN) I type (synonyms - neural amyotrophy Sharko-Mari-Tus, demyelinating type of NMSN);
• Russi-Levi syndrome (phenotypic variant of NMSN IA);
• NMSH type II (axonal type NMSN);
• NMSH III type (Dejerine-Sott syndrome, hypertrophic type of NMSN);
• NMSN IV type (Refsum's disease);
• Neuropathy with a tendency to paralysis from compression;
• porphyria polyneuropathy;
• hereditary sensory-vegetative polyneuropathies.

Acquired polyneuropathies:

• Autoimmune polyneuropathies:
  • acute inflammatory demyelinating polyneuropathies (Guillain-Barre syndrome, Miller-Fisher syndrome);
  • acute inflammatory axonal polyneuropathy (axonal type of Guillain-Barre syndrome);
  • chronic inflammatory demyelinating polyneuropathy;
  • paraproteinemic polyneuropathies;
  • paraneoplastic polyneuropathies;
  • multiple mononeuropathies: motor multifocal neuropathy with conduction blocks, sensorimotor multifocal neuropathy with conduction blocks (Sumner-Lewis syndrome);
• Metabolic polyneuropathies:
  • diabetic polyneuropathy;
  • polyneuropathy with other endocrine diseases;
  • uremic polyneuropathy;
  • hepatic polyneuropathy;
  • polyneuropathy with primary systemic amyloidosis;
• Polyneuropathy associated with a deficiency of vitamins:
  • vitamin B _1- deficient polyneuropathy;
  • vitamin B _6- deficient polyneuropathy;
  • vitamin B _12- deficiency polyneuropathy;
  • vitamin E-deficiency polyneuropathy;
• Toxic polyneuropathies:
  • alcoholic polyneuropathy;
  • medicinal polyneuropathies;
  • polyneuropathy in case of poisoning with heavy metals, organic solvents and other toxic substances;
  • polyneuropathy in systemic diseases (systemic lupus erythematosus, scleroderma, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, vasculitis);
• Infectious-toxic polyneuropathies:
  • diphtheria infectious-toxic polyneuropathy;
  • polyneuropathy after influenza, measles, mumps, infectious mononucleosis;
  • postvaccinal polyneuropathies;
  • polyneuropathy in tick-borne borreliosis;
  • polyneuropathy in HIV infection;
  • polyneuropathy with leprosy.

Multifocal motor and sensorimotor mononeuropathies, strictly speaking, do not belong to polyneuropathies, but also are systemic autoimmune diseases of the peripheral nerves, and are therefore considered in this section.

[1], [2]

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.

The prevalence of multifocal motor neuropathy is approximately 1 per 100 000 population, men are sick three times more often than women. The median age at onset of the disease is 40 years.

Signs of diabetic polyneuropathy are revealed in 10-60% of patients with diabetes mellitus (up to 66% with type 1 diabetes mellitus and up to 59% in type 2 diabetes mellitus). When diagnosing diabetes, symptoms of polyneuropathy are detected in 7.5%, and 25 years after the onset of the disease - in 50%.

Uremic polyneuropathy is found in 10-83% of patients with chronic renal failure. The probability of its development is associated not so much with the age of the patient as with the duration and severity of renal failure.

Diphtheria polyneuropathy develops in 20% of patients who have suffered diphtheria.

[3], [4], [5], [6], [7], [8], [9]